JP6494064B2 - リパーゼ活性阻害剤、及び、その抽出製造方法 - Google Patents
リパーゼ活性阻害剤、及び、その抽出製造方法 Download PDFInfo
- Publication number
- JP6494064B2 JP6494064B2 JP2013250309A JP2013250309A JP6494064B2 JP 6494064 B2 JP6494064 B2 JP 6494064B2 JP 2013250309 A JP2013250309 A JP 2013250309A JP 2013250309 A JP2013250309 A JP 2013250309A JP 6494064 B2 JP6494064 B2 JP 6494064B2
- Authority
- JP
- Japan
- Prior art keywords
- inhibitor
- lipase activity
- fat absorption
- lipase
- fat
- 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.)
- Active
Links
- 239000003112 inhibitor Substances 0.000 title claims description 63
- 235000019626 lipase activity Nutrition 0.000 title claims description 47
- 238000004519 manufacturing process Methods 0.000 title description 3
- 238000010521 absorption reaction Methods 0.000 claims description 46
- 239000000284 extract Substances 0.000 claims description 24
- 239000004480 active ingredient Substances 0.000 claims description 23
- 230000037303 wrinkles Effects 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 241000199919 Phaeophyceae Species 0.000 claims description 8
- 238000000638 solvent extraction Methods 0.000 claims description 7
- 244000296825 Amygdalus nana Species 0.000 claims description 2
- 235000003840 Amygdalus nana Nutrition 0.000 claims description 2
- 240000001439 Opuntia Species 0.000 claims description 2
- 235000013389 Opuntia humifusa var. humifusa Nutrition 0.000 claims description 2
- 235000011432 Prunus Nutrition 0.000 claims description 2
- 235000014774 prunus Nutrition 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 108090001060 Lipase Proteins 0.000 description 15
- 102000004882 Lipase Human genes 0.000 description 15
- 239000004367 Lipase Substances 0.000 description 15
- 229940040461 lipase Drugs 0.000 description 15
- 235000019421 lipase Nutrition 0.000 description 15
- 229930014626 natural product Natural products 0.000 description 12
- 235000013305 food Nutrition 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 241001474374 Blennius Species 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 208000008589 Obesity Diseases 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 235000020824 obesity Nutrition 0.000 description 6
- OMOVVBIIQSXZSZ-UHFFFAOYSA-N [6-(4-acetyloxy-5,9a-dimethyl-2,7-dioxo-4,5a,6,9-tetrahydro-3h-pyrano[3,4-b]oxepin-5-yl)-5-formyloxy-3-(furan-3-yl)-3a-methyl-7-methylidene-1a,2,3,4,5,6-hexahydroindeno[1,7a-b]oxiren-4-yl] 2-hydroxy-3-methylpentanoate Chemical compound CC12C(OC(=O)C(O)C(C)CC)C(OC=O)C(C3(C)C(CC(=O)OC4(C)COC(=O)CC43)OC(C)=O)C(=C)C32OC3CC1C=1C=COC=1 OMOVVBIIQSXZSZ-UHFFFAOYSA-N 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 206010003210 Arteriosclerosis Diseases 0.000 description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 244000269722 Thea sinensis Species 0.000 description 3
- ZXQLWSVBDXTOCU-UHFFFAOYSA-N Yahazunol Natural products CC1(O)CCC2C(C)(C)CCCC2(C)C1CC1=CC(O)=CC=C1O ZXQLWSVBDXTOCU-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- -1 indole compound Chemical class 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- ZEAWLOAAKXIHKG-QFUCXCTJSA-N 2-[[(1r,4ar,8ar)-2,5,5,8a-tetramethyl-1,4,4a,6,7,8-hexahydronaphthalen-1-yl]methyl]benzene-1,4-diol Chemical compound C([C@H]1[C@]2(C)CCCC(C)(C)[C@H]2CC=C1C)C1=CC(O)=CC=C1O ZEAWLOAAKXIHKG-QFUCXCTJSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 241001623426 Dictyopteris latiuscula Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 229940086609 Lipase inhibitor Drugs 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 102000019280 Pancreatic lipases Human genes 0.000 description 2
- 108050006759 Pancreatic lipases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000254101 Popillia japonica Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 235000006468 Thea sinensis Nutrition 0.000 description 2
- CPXDKDFWEZFRKT-UHFFFAOYSA-N Zonarol Natural products C=C1CCC2C(C)(C)CCCC2(C)C1CC1=CC(O)=CC=C1O CPXDKDFWEZFRKT-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 235000019577 caloric intake Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000035622 drinking Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- ZEAWLOAAKXIHKG-UHFFFAOYSA-N isozonarol Natural products CC1=CCC2C(C)(C)CCCC2(C)C1CC1=CC(O)=CC=C1O ZEAWLOAAKXIHKG-UHFFFAOYSA-N 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
- 229940116369 pancreatic lipase Drugs 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 239000003826 tablet 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
- 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
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- ZXQLWSVBDXTOCU-IZZBFERCSA-N 2-[[(1r,2r,4as,8as)-2-hydroxy-2,5,5,8a-tetramethyl-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1-yl]methyl]benzene-1,4-diol Chemical compound C([C@@H]1[C@@]2(C)CCCC([C@@H]2CC[C@]1(O)C)(C)C)C1=CC(O)=CC=C1O ZXQLWSVBDXTOCU-IZZBFERCSA-N 0.000 description 1
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- 244000148659 Acanthopanax sieboldianus Species 0.000 description 1
- 235000015559 Acanthopanax sieboldianus Nutrition 0.000 description 1
- 235000000832 Ayote Nutrition 0.000 description 1
- 241000206761 Bacillariophyta Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 240000004160 Capsicum annuum Species 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 241000722731 Carex Species 0.000 description 1
- 241000283153 Cetacea Species 0.000 description 1
- 240000004244 Cucurbita moschata Species 0.000 description 1
- 235000009854 Cucurbita moschata Nutrition 0.000 description 1
- 235000009804 Cucurbita pepo subsp pepo Nutrition 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 241000172189 Dictyopteris Species 0.000 description 1
- 241000024430 Dictyopteris undulata Species 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 229940122601 Esterase inhibitor Drugs 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 240000001080 Grifola frondosa Species 0.000 description 1
- 235000007710 Grifola frondosa Nutrition 0.000 description 1
- 241000143510 Haliotis discus hannai Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 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 1
- 102100023757 Latent-transforming growth factor beta-binding protein 4 Human genes 0.000 description 1
- 101710178977 Latent-transforming growth factor beta-binding protein 4 Proteins 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 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
- 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
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229930194351 Oolonghomobisflavan Natural products 0.000 description 1
- 241000736199 Paeonia Species 0.000 description 1
- 235000006484 Paeonia officinalis Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 240000008154 Piper betle Species 0.000 description 1
- 235000008180 Piper betle Nutrition 0.000 description 1
- 240000001462 Pleurotus ostreatus Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 235000000497 Primula Nutrition 0.000 description 1
- 241000208476 Primulaceae Species 0.000 description 1
- 240000001341 Reynoutria japonica Species 0.000 description 1
- 235000018167 Reynoutria japonica Nutrition 0.000 description 1
- 241000206572 Rhodophyta Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 235000009499 Vanilla fragrans Nutrition 0.000 description 1
- 244000263375 Vanilla tahitensis Species 0.000 description 1
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229940069765 bean extract Drugs 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-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
- 235000020279 black tea Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical class OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000002329 esterase inhibitor Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 235000021332 kidney beans Nutrition 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000008099 melanin synthesis Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 235000020333 oolong tea Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 235000015136 pumpkin Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940119485 safflower extract Drugs 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
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229940079989 star fruit extract Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
したがって、天然物由来の成分で安全性とリパーゼ阻害活性において有効なリパーゼ阻害活性成分の更なる探索が求められているところである。
(1)
で表されるゾナロール、
(2)
で表されるイソゾナロール、
(3)
で表されるヤハズノール、
で表されるエント−ヤハズノール。
[1]上記、式(1)で表されるゾナロール、及び式(2)で表されるイソゾナロールから選択される1又は2の化合物、又はその製剤上許容される塩を有効成分として含有するリパーゼ活性阻害からなる脂肪吸収阻害剤。
[2]ゾナロール、及び、イソゾナロールから選択される1又は2の化合物を含有する有効成分が、褐藻類に属するシワヤハズ又はヤハズグサの溶媒抽出物であることを特徴とする上記[1]に記載の脂肪吸収阻害剤。
[3]褐藻類に属するシワヤハズ又はヤハズグサの溶媒抽出物が、シワヤハズ又はヤハズグサの溶媒抽出物の脂溶性画分であることを特徴とする上記[2]に記載の脂肪吸収阻害剤。
[4]上記[1]に記載のゾナロール、又は、イソゾナロールが、シワヤハズ又はヤハズグサを溶媒抽出し、該溶媒抽出物を更に精製して、分離したゾナロール、又は、イソゾナロールであることを特徴とする上記[1]に記載の脂肪吸収阻害剤。
潮間帯にて採集したシワヤハズ300g(湿重量)の藻体表面を流水で洗い流し、細切して5倍容量のメタノール(MeOH)に1週間浸漬した。抽出液をろ過してエバポレータにて減圧乾固する操作を3回繰り返した。得られた粗抽出物10.0gを酢酸エチルに懸濁させ、等量の蒸留水を加えて液−液分配を行い、水溶性画分を除去した。得られた酢酸エチル層を減圧乾固し、90%MeOHに溶解させ、等量のヘキサンを加えて液−液分配することにより脱脂を行った。得られた90%MeOH層を減圧乾固することで、逆相系シリカゲルに吸着させ、70〜80%MeOHで溶出された成分を集めた。ここで得られた成分の約半分量(0.38g)を用いて、HPLCによる分離を進め、最終的に物質A(72.1mg)と物質B(37.7mg)を得た。
上記分離操作により得られた物質Aと物質Bの一部を各々重メタノールに溶解しプロトンNMR、カーボンNMR、各種二次元NMRをブルカーAV400で測定した。得られたスペクトルを解析して平面構造を推定するとともに、既存の文献と比較することで物質Aをゾナロール、物質Bをイソゾナロールであると同定した。ゾナロール(zonarol)(物質A)及びイソゾナロール(isozonarol)(物質B)の1H−NMR(400 MHz CD3OD)の吸収スペクトルを図1及び図2に示す。
上記実施例で分離同定したサンプル(ゾナロール又はイソゾナロール)の脂肪吸収抑制効果を調べるために以下の実験を行った。すなわち7週齢、雄のddYマウス(n=8)に、サンプルの水懸濁液(33.3mg/kg) 0.5mLとコーン油(8mL/kg)0.2mLの混合液を経口投与して、経時的に尾採血を行った。コントロール群にはサンプルを含まない混合溶液を経口投与し、それぞれの血中中性脂肪濃度(TG)を測定した。その結果を図3に示す。数値は平均値±標準誤差(mg/dl)で表しており、***印は、サンプル投与群のコントロール群に対する有意差を示す。図3の結果から、これらサンプルが脂肪吸収を抑制することが示された。
上記実施例で分離同定したサンプル(ゾナロール又はイソゾナロール)のリパーゼ阻害活性作用を評価するために、Lipase Kit S(大日本住友製薬製)を用いて以下の方法でリパーゼ阻害活性を測定した。サンプルは50%MeOHに溶解して96ウエルプレート上で段階希釈して用いた。コントロールウエルにはサンプルを加えない50%MeOHを用いた。これに市販のブタ膵臓リパーゼ(シグマアルドリッチ製)、Lipase Kit Sに含まれているエステラーゼ阻害剤、発色液を加えて5分間プレインキュベートした後、遮光下30℃で、30分間反応させて、反応停止液を加え405nmで吸光度を測定した。ブランクウエルには、反応の前に停止液を加えた。
Claims (4)
- 下記式(1)
で表されるゾナロール、及び
下記式(2)
で表されるイソゾナロールから選択される1又は2の化合物、又はその製剤上許容される塩を有効成分として含有するリパーゼ活性阻害からなる脂肪吸収阻害剤。 - ゾナロール、及び、イソゾナロールから選択される1又は2の化合物を含有する有効成分が、褐藻類に属するシワヤハズ又はヤハズグサの溶媒抽出物であることを特徴とする請求項1に記載の脂肪吸収阻害剤。
- 褐藻類に属するシワヤハズ又はヤハズグサの溶媒抽出物が、シワヤハズ又はヤハズグサの溶媒抽出物の脂溶性画分であることを特徴とする請求項2に記載の脂肪吸収阻害剤。
- 請求項1に記載のゾナロール、又は、イソゾナロールが、シワヤハズ又はヤハズグサを溶媒抽出し、該溶媒抽出物を更に精製して、分離したゾナロール、又は、イソゾナロールであることを特徴とする請求項1に記載の脂肪吸収阻害剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2013250309A JP6494064B2 (ja) | 2013-12-03 | 2013-12-03 | リパーゼ活性阻害剤、及び、その抽出製造方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2013250309A JP6494064B2 (ja) | 2013-12-03 | 2013-12-03 | リパーゼ活性阻害剤、及び、その抽出製造方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015107922A JP2015107922A (ja) | 2015-06-11 |
JP6494064B2 true JP6494064B2 (ja) | 2019-04-03 |
Family
ID=53438604
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013250309A Active JP6494064B2 (ja) | 2013-12-03 | 2013-12-03 | リパーゼ活性阻害剤、及び、その抽出製造方法 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6494064B2 (ja) |
-
2013
- 2013-12-03 JP JP2013250309A patent/JP6494064B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
JP2015107922A (ja) | 2015-06-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2012516842A (ja) | 代謝症候群の抑制のためのスファランサス・インディクスおよびガルシニア・マンゴスターナ由来の組成物 | |
WO2009093584A1 (ja) | 植物由来の高尿酸血症の予防または改善剤 | |
KR102110040B1 (ko) | 토종보리수 추출물을 포함하는 비만 또는 대사성 질환의 예방 및 치료용 조성물 | |
US20120269913A1 (en) | Crude caffeine complex, improved food products using the crude caffeine complex, and methods of use thereof | |
JP2017210444A (ja) | ウロリチン類を含有するリパーゼ阻害剤 | |
WO2006082743A1 (ja) | 治療剤 | |
JP2004043373A (ja) | リパーゼ阻害剤 | |
JP5305500B2 (ja) | リパーゼ阻害剤及びそれを含有する組成物 | |
JP6494064B2 (ja) | リパーゼ活性阻害剤、及び、その抽出製造方法 | |
KR101927399B1 (ko) | 지방간 치료용 또는 예방용 조성물 | |
JP2017160134A (ja) | ウロリチン類を含有するα−グルコシダーゼ活性阻害剤、およびウロリチン類を含有する血糖値上昇抑制剤 | |
JP4907280B2 (ja) | リパーゼ阻害剤 | |
JP2004238289A (ja) | 血栓形成抑制剤及び機能性食品 | |
JP4843261B2 (ja) | 新規3,4−seco−lupane型トリテルペノイドサポニン化合物 | |
JP6105186B2 (ja) | 膵リパーゼ阻害剤 | |
JP2006016340A (ja) | ザクロ抽出物を有効成分とする、血中尿酸値低下剤 | |
KR101834550B1 (ko) | 3-카페오일-4-디히드로카페오일 퀴닉산을 유효성분으로 함유하는 혈관질환의 예방, 개선 또는 치료용 조성물 | |
JP2011132147A (ja) | 濃縮赤ワインエキスを有効成分とする中性脂肪吸収阻害剤 | |
JP7239135B2 (ja) | α-グルコシダーゼ活性阻害剤および血糖値上昇抑制剤 | |
JP2006008575A (ja) | ヒソップ抽出物の血液流動性改善剤、血流改善剤およびその利用 | |
KR101710276B1 (ko) | 참치 심장 에탄올 추출물을 유효성분으로 포함하는 항당뇨용 조성물 | |
KR20230166571A (ko) | 두룸아마이드 a 화합물을 이용한 지방간 질환 개선용 조성물 | |
US9981895B1 (en) | Compositions and methods of synthesizing arachidin-3 from resveratrol | |
JP2011132173A (ja) | キサンチンオキシダーゼ阻害剤及び尿酸生成阻害剤 | |
KR20160075910A (ko) | 루설라 에센트리카 추출물을 포함하는 고지혈증 치료 또는 예방용 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20161202 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20161202 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20161202 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170731 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170929 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20171207 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181225 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190304 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6494064 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 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |