KR20160020261A - Composition for improving digestive functions comprising glabridin from Liquorice - Google Patents
Composition for improving digestive functions comprising glabridin from Liquorice Download PDFInfo
- Publication number
- KR20160020261A KR20160020261A KR1020140105358A KR20140105358A KR20160020261A KR 20160020261 A KR20160020261 A KR 20160020261A KR 1020140105358 A KR1020140105358 A KR 1020140105358A KR 20140105358 A KR20140105358 A KR 20140105358A KR 20160020261 A KR20160020261 A KR 20160020261A
- Authority
- KR
- South Korea
- Prior art keywords
- glabridin
- licorice
- present
- derived
- improving
- Prior art date
Links
- LBQIJVLKGVZRIW-UHFFFAOYSA-N glabridine Natural products C1OC2=C3C=CC(C)(C)OC3=CC=C2CC1C1=CC=C(O)C=C1O LBQIJVLKGVZRIW-UHFFFAOYSA-N 0.000 title claims abstract description 60
- LBQIJVLKGVZRIW-ZDUSSCGKSA-N glabridin Chemical compound C1([C@H]2CC3=CC=C4OC(C=CC4=C3OC2)(C)C)=CC=C(O)C=C1O LBQIJVLKGVZRIW-ZDUSSCGKSA-N 0.000 title claims abstract description 57
- 229940093767 glabridin Drugs 0.000 title claims abstract description 57
- PMPYOYXFIHXBJI-ZDUSSCGKSA-N glabridin Natural products C1([C@H]2CC=3C=CC4=C(C=3OC2)CCC(O4)(C)C)=CC=C(O)C=C1O PMPYOYXFIHXBJI-ZDUSSCGKSA-N 0.000 title claims abstract description 57
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 title claims abstract description 50
- 239000000203 mixture Substances 0.000 title claims abstract description 30
- 230000006870 function Effects 0.000 title claims description 30
- 230000001079 digestive effect Effects 0.000 title claims description 21
- 244000303040 Glycyrrhiza glabra Species 0.000 title abstract description 45
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 title abstract description 13
- 235000011477 liquorice Nutrition 0.000 title abstract description 8
- 230000029087 digestion Effects 0.000 claims abstract description 18
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- 210000000941 bile Anatomy 0.000 claims abstract description 14
- 230000028327 secretion Effects 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 10
- 230000005176 gastrointestinal motility Effects 0.000 claims abstract description 9
- 230000001737 promoting effect Effects 0.000 claims abstract description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 45
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 claims description 37
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 claims description 37
- 229940010454 licorice Drugs 0.000 claims description 37
- 235000013376 functional food Nutrition 0.000 claims description 14
- 230000036541 health Effects 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 229940069445 licorice extract Drugs 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 10
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 10
- 201000006549 dyspepsia Diseases 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 230000006872 improvement Effects 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 239000012141 concentrate Substances 0.000 claims description 5
- 230000030136 gastric emptying Effects 0.000 claims description 5
- 238000000227 grinding Methods 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 208000000718 duodenal ulcer Diseases 0.000 claims description 4
- 238000001291 vacuum drying Methods 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 3
- 206010003591 Ataxia Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000007882 Gastritis Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 230000030135 gastric motility Effects 0.000 claims description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 241000202807 Glycyrrhiza Species 0.000 claims 5
- 206010033645 Pancreatitis Diseases 0.000 claims 1
- 201000001352 cholecystitis Diseases 0.000 claims 1
- 208000023652 chronic gastritis Diseases 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 10
- 230000007774 longterm Effects 0.000 abstract description 3
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 abstract 1
- 230000002411 adverse Effects 0.000 abstract 1
- 239000003613 bile acid Substances 0.000 abstract 1
- 239000000284 extract Substances 0.000 description 15
- 239000003814 drug Substances 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- 229940079593 drug Drugs 0.000 description 8
- 235000013305 food Nutrition 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 235000003599 food sweetener Nutrition 0.000 description 6
- 230000002496 gastric effect Effects 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 5
- 239000004378 Glycyrrhizin Substances 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 239000000469 ethanolic extract Substances 0.000 description 5
- 229960003699 evans blue Drugs 0.000 description 5
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 5
- 229960004949 glycyrrhizic acid Drugs 0.000 description 5
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 5
- 235000019410 glycyrrhizin Nutrition 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000012453 sprague-dawley rat model Methods 0.000 description 5
- YPELFRMCRYSPKZ-UHFFFAOYSA-N 4-amino-5-chloro-2-ethoxy-N-({4-[(4-fluorophenyl)methyl]morpholin-2-yl}methyl)benzamide Chemical compound CCOC1=CC(N)=C(Cl)C=C1C(=O)NCC1OCCN(CC=2C=CC(F)=CC=2)C1 YPELFRMCRYSPKZ-UHFFFAOYSA-N 0.000 description 4
- 235000017443 Hedysarum boreale Nutrition 0.000 description 4
- 235000007858 Hedysarum occidentale Nutrition 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 235000008504 concentrate Nutrition 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 239000001947 glycyrrhiza glabra rhizome/root Substances 0.000 description 4
- 235000013402 health food Nutrition 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229960004085 mosapride Drugs 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000007107 Stomach Ulcer Diseases 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000003308 immunostimulating effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229940124595 oriental medicine Drugs 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 210000001187 pylorus Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 230000002087 whitening effect Effects 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
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 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 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 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
- 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
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 239000003674 animal food additive Substances 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- 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 2
- 230000010234 biliary secretion Effects 0.000 description 2
- 238000010876 biochemical test Methods 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 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 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 235000013365 dairy product Nutrition 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229960001031 glucose Drugs 0.000 description 2
- 239000001649 glycyrrhiza glabra l. absolute Substances 0.000 description 2
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 239000003022 immunostimulating agent Substances 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229940051810 licorice root extract Drugs 0.000 description 2
- 235000020725 licorice root extract Nutrition 0.000 description 2
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 230000001272 neurogenic effect Effects 0.000 description 2
- -1 olive oil Chemical compound 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 239000012646 vaccine adjuvant Substances 0.000 description 2
- 229940124931 vaccine adjuvant Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 230000037303 wrinkles Effects 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- 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
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000008279 Dumping Syndrome Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 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
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000017228 Gastrointestinal motility disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 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
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000032395 Post gastric surgery syndrome Diseases 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 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
- 230000008901 benefit Effects 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
- 235000013361 beverage Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000008242 dietary patterns Nutrition 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 238000013110 gastrectomy Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 208000003243 intestinal obstruction Diseases 0.000 description 1
- 229960001375 lactose Drugs 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
- 230000003902 lesion Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 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
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 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
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 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 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
- 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
- 238000007789 sealing Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 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
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 229960005486 vaccine Drugs 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
- 230000008673 vomiting Effects 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- 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
- A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Mycology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
본 발명은 감초 유래 글라블리딘을 유효성분으로 하는 소화기능 개선용 조성물에 관한 것으로, 구체적으로는 담즙산 분비를 촉진하고 소화기능 개선 효과가 있는 감초 유래 글라블리딘을 유효성분으로 포함하는 소화기능 개선용 조성물 및 감초로부터 글라블리딘을 추출하는 방법에 관한 것이다.
The present invention relates to a composition for improving digestion function containing glabelin derived from licorice root as an active ingredient, and more particularly to a composition for improving digestive function, which comprises glycyrrhizin-derived glabridin having an effect of improving digestive function, And a method for extracting glabridin from licorice.
산업이 발달하고 빠르게 근대화되어감에 따라 현대인의 식생활은 서구화되어 가고 이러한 식생활 패턴의 변화로 인하여 인체의 신진대사에 부조화를 초래하게 되었다. 또한, 고칼로리 식품, 인스턴트식품 및 고지방 식품 등의 섭취가 증가하고 섬유소 등의 섭취가 감소하며, 편한 생활을 추구하는 생활습관에 의해 운동부족 현상이 일어나, 현대인에게는 기능성 소화 장애가 큰 문제가 되고 있다. 기능성 소화 장애란, 위 자체에 기질성 병변이 발견되지 않는데도 환자가 소화기 계통의 증상을 나타내는 임상 증후군을 말하며, 유형으로는 상부 위장관형과 하부 위장관형이 존재한다. 특히 우리나라에서 압도적으로 많은 상부 위장관형은 속 쓰림, 트림, 구역질, 구토, 소화불량, 식후 상복부 불쾌감, 공복 시 상복부 통증 등이 있으며, 신경성 위장병 및 신경성 위염 등으로 표현 될 수 있다. 하부 위장관 영역 질환으로는 수술 후 장폐색, 위 절제후의 덤핑 증후군과 하부 위장관 영역의 과민성 대장 증후군, 변비, 설사 등이 있다.As the industry has developed and rapidly become modernized, modern people 's diet has become westernized, and this change in diet pattern has caused incompatibility with human metabolism. In addition, intake of high-calorie foods, instant foods, and high-fat foods increases, intake of fibrin and the like decreases, and exercise habits are caused by lifestyle habits that are convenient for living, and functional digestive disorders become a serious problem for modern people . Functional digestive disorder refers to a clinical syndrome in which the patient has symptoms of digestive system even though no gastric lesion is found in the stomach, and there are types of upper gastrointestinal type and lower gastrointestinal type. Especially in Korea, overwhelmingly many upper gastrointestinal types can be described as genital sores, trims, nausea, vomiting, dyspepsia, postprandial discomfort, abdominal pain at fasting, neurogenic gastroenteritis and neurogenic gastritis. Lower gastrointestinal tract diseases include bowel obstruction, post-gastrectomy dumping syndrome, irritable bowel syndrome in the lower gastrointestinal tract, constipation, and diarrhea.
실제적으로 임상에서 다양한 종류의 약제들이 사용되고 있지만, 기능성 소화 불량증에서 약제들의 유용성을 입증하기는 매우 어려운 상태이며, 기능성 소화 불량증의 증상들이 매우 다양하여 객관적으로 평가하고 분석하기 어렵다. 또한 대부분의 연구에서 기능성 소화불량증 환자들에게 위약(placebo) 효과가 30 내지 50%에 이른다는 사실도 고려되어야 한다. 아직까지 모든 기능성 소화불량증 환자에서 효과가 입증되어 있는 약제는 없으며, 현재는 그 증상의 완화에 기준하여 기능성 소화불량증에서 많이 이용되는 약제들은 제산제, H2-수용체 길항제(H2-receptor antagonist), 위장운동 촉진제(prokinetics)등이 있다(Sachs G, Spenney JG, et al; Physiol. Rev.58, pp106-173, 1978). 이들 중 일부는 위산억제 효과뿐만 아니라 위장관 평활근에 이완 효과도 나타내어 노약자들은 이들 복용제에 따른 심한 복부 팽만감을 호소한다. 또한 기능성 소화불량 환자들의 일부는 위장관 운동 장애도 함께 가지고 있다. 이러한 문제를 해결하기 위해 다양한 방법들이 연구되어 오고 있으며, 그 결과로서 다양한 건강기능식품 또는 식품 등이 개발되어 오고 있다. 하지만 현재까지 효과적으로 소화기능을 개선하는 건강기능식품은 없는 실정이다.
Although various kinds of medicines are actually used in clinical practice, it is very difficult to demonstrate the usefulness of medicines in functional dyspepsia, and it is difficult to objectively evaluate and analyze the symptoms of functional dyspepsia. It should also be noted that in most studies, the placebo effect is 30 to 50% in patients with functional dyspepsia. It is not yet proven drug that is effective in all patients with functional dyspepsia up, now, based on relief of the symptoms of drug which is widely used in functional dyspepsia are antacids, H 2 - receptor antagonist (H 2 -receptor antagonist), And prokinetics (Sachs G, Spenney JG, et al., Physiol. Rev. 58, pp. 106-173, 1978). Some of them show not only gastric acid suppression effect but also relaxation effect on gastrointestinal smooth muscle, and elderly people complain of severe abdominal bloating according to these dosing agents. Some patients with functional dyspepsia also have gastrointestinal motility disorders. Various methods have been studied to solve these problems, and as a result, various health functional foods or foods have been developed. However, there are no health functional foods that improve the digestive function effectively until now.
한편, 감초(甘草, Chinese Liquorice)는 콩과에 속하는 여러해살이풀로 중국 북동부와 시베리아, 몽골, 중국 북부 등지에 분포한다. 뿌리와 줄기 밑 부분을 감미제와 위궤양·십이지장궤양의 치료제로 사용한다. 다른 약의 작용을 순하게 하므로, 한방에서 다양한 용도로 쓴다. 특히 감초에 글라블리딘 성분은 피부 미백 활성이 있어 화장품의 원료로 사용되기도 하며 항산화 기능 및 지방대사 생리활성 기능이 보고되어 있다. 하지만 아직 소화작용 개선에 대한 기능은 알려진 바 없다.On the other hand, licorice (Chinese Liquorice) is a perennial herb that belongs to the bean family, and is distributed in northeastern China, Siberia, Mongolia and northern China. Roots and stem bottoms are used for the treatment of sweeteners, stomach ulcers and duodenal ulcers. Because the action of other medicines is made clear, it is used for various purposes in oriental medicine. In particular, the glabridin component of licorice has skin whitening activity and is used as a raw material for cosmetics, and its antioxidant function and lipid metabolism physiological activity have been reported. However, the function of improving digestion is not yet known.
본 발명자들은 이러한 필요성에 따라 새로운 기능성 식품소재 또는 의약품 소재를 개발하고자 연구하였으며, 그 결과 상기한 바와 같은 글라블리딘이 담즙 분비를 촉진하여 지방소화에 도움을 주고, 위장관의 운동에 도움을 주는 효과가 있음을 확인하고 본 발명을 완성하게 되었다.
The present inventors have studied to develop a new functional food material or a pharmaceutical material according to the necessity. As a result, the above-mentioned glabridin promotes bile secretion and thus helps to digest fat, And the present invention has been completed.
이에 본 발명자들은 감초 유래 글라블리딘을 유효성분으로 하는 소화기능 개선용 건강 기능성 식품 조성물 및 소화장애증 치료용 약학 조성물을 개발하여 본 발명을 완성하였다.Accordingly, the inventors of the present invention have developed a health functional food composition for improving digestion function and a pharmaceutical composition for treating digestive discomfort, which comprises licorice derived glabridin as an active ingredient, and completed the present invention.
따라서, 본 발명의 목적은 감초 유래 글라블리딘을 유효성분으로 하는 소화기능 개선용 건강 기능성 식품 조성물을 제공하는 것이다.Accordingly, an object of the present invention is to provide a health functional food composition for improving digestion function, which comprises licorice-derived glabridin as an active ingredient.
본 발명의 또 다른 목적은, 감초 유래 글라블리딘을 유효성분으로 하는 소화장애증 예방 및 치료용 약학 조성물을 제공하는 것이다.It is still another object of the present invention to provide a pharmaceutical composition for preventing and treating digestive disorders caused by licorice derived glabridin as an active ingredient.
본 발명의 또 다른 목적은, 글라블리딘을 포함하는 감초 추출물 제조 방법을 제공하는 것이다.It is another object of the present invention to provide a method for producing licorice extract comprising glabridin.
본 발명의 또 다른 목적은, 담즙 분비 촉진, 지방 소화 개선 및 위장관 운동 활성화 기능으로 이루어진 군에서 선택되는 어느 하나 이상의 기능을 가지는 감초 유래 글라블리딘을 제공하는 것이다.
Another object of the present invention is to provide a licorice-derived glabridin having at least one function selected from the group consisting of biliary secretion promotion, fat digestion improvement, and gastrointestinal motility activation function.
상기의 목적을 달성하기 위해, 본 발명은 담즙 분비를 촉진하여 지방소화에 도움을 주고, 위장관의 운동에 도움을 주는 효과를 가진 감초 유래 글라블리딘을 유효성분으로 하는 소화기능 개선용 조성물에 관한 것이다.In order to achieve the above object, the present invention relates to a composition for improving digestive function, which comprises glycyrrhizin-derived glabridin having an effect of promoting bile secretion and helping digestion of gastrointestinal tract, will be.
본 발명의 또 다른 목적을 달성하기 위해, 본 발명은 감초 유래 글라블리딘을 유효성분으로 하는 소화장애증 예방 및 치료용 약학 조성물을 제공한다.
In order to achieve still another object of the present invention, the present invention provides a pharmaceutical composition for preventing and treating digestive disorders caused by licorice derived glabridin as an active ingredient.
이하 본 발명을 상세히 설명한다. Hereinafter, the present invention will be described in detail.
본 발명은 하기 화학식1로 표시되는 감초 유래 글라블리딘을 유효성분으로 하는 감초추출물을 포함한다.The present invention includes a Licorice root extract containing licorice derived glabridin represented by the following general formula (1) as an active ingredient.
[화학식1][Chemical Formula 1]
본 발명의 글라블리딘은 감초로부터 추출된 것임을 특징으로 한다.The glabridin of the present invention is characterized in that it is extracted from licorice root.
감초는 뿌리와 줄기 밑 부분을 감미제와 위궤양·십이지장궤양의 치료제로 사용한다. 다른 약의 작용을 순하게 하므로, 한방에서 다양한 용도로 쓴다. 감초 추출물에는 글라블리딘이 다량 함유되어 있다. 글라블리딘의 효능으로는 본 발명에서의 소화기능 개선 뿐 아니라 미백 및 주름개선, 항산화 기능을 갖는다.Licorice is used as a treatment for sweeteners, stomach ulcers, duodenal ulcers, and roots and stem bottoms. Because the action of other medicines is made clear, it is used for various purposes in oriental medicine. Licorice extract contains a large amount of glabridine. The efficacy of glabridin has not only the improvement of digestion function but also whitening and wrinkle improvement and antioxidative function in the present invention.
본 발명의 건강 기능성 식품은 분말, 과립, 정제, 캡슐, 시럽제 또는 음료의 형태일 수 있다.The health functional food of the present invention may be in the form of powders, granules, tablets, capsules, syrups or drinks.
상기 “건강 기능성 식품 조성물”은 감초 추출물 유래 글라블리딘을 일반 식품에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가지는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용시 발생할 수 있는 부작용 등이 없는 장점이 있다.The above-mentioned " health functional food composition " is a food prepared by adding glabridin derived from licorice root extract to general food, or by encapsulation, powdering, suspension or the like, and has a health-specific effect when ingested. , There is an advantage that there is no side effect that may occur when a food is used as a raw material for a long period of taking the medicine.
상기 건강 기능성 식품의 형태 및 종류에는 특별한 제한은 없다. 상기 글라블리딘 또는 글라블리딘을 포함하는 감초 추출물을 첨가할 수 있는 건강식품의 형태는 분말, 과립, 정제, 캡슐, 시럽제 또는 음료 등일 수 있고, 건강식품의 종류는 버터, 요구르트, 치즈를 포함한 유제품, 아이스크림류를 포함한 낙농제품, 빵, 초콜릿류, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the form and kind of the health functional food. The form of the health food to which the licorice extract including glabridin or glabridin can be added may be powder, granule, tablet, capsule, syrup or beverage, and the kind of health food may include butter, yogurt, cheese There are usually dairy products, dairy products including ice cream, breads, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, gums, soups, drinks, tea, drinks, alcoholic beverages and vitamins. All of the health foods in the.
본 발명의 건강 기능성 식품 조성물은 통상의 건강식품과 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 수크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리스리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. The health functional food composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient as well as normal health food. The above-mentioned natural carbohydrates are sugar saccharides such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like.
상기 외에 본 발명의 건강 기능성 식품 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 글라블리딘 또는 이를 포함한 추출물은 천연과일 쥬스, 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01~10 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health functional food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, , Alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the glabridin of the present invention or the extract containing it may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 10 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명의 감초 유래 글라블리딘을 유효성분으로 포함하는 소화기능 개선용 건강 기능성 식품은 담즙 분비 촉진, 지방 소화 개선 및 위장관 운동 활성화 기능으로 이루어지는 군에서 선택된 어느 하나 이상의 기능을 가질 수 있다.
The health functional food for improving digestive function comprising the licorice-derived glabridin of the present invention as an active ingredient may have one or more functions selected from the group consisting of promoting bile secretion, improving fat digestion, and activating gastrointestinal motility.
본 발명은 하기 화학식1로 표시되는 감초 유래 글라블리딘을 유효성분으로 포함하는 소화장애증 예방 및 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing and treating digestive disorders caused by licorice derived glabridin represented by the following formula (1) as an active ingredient.
[화학식1][Chemical Formula 1]
본 발명의 의약물의 제조시에는 생약 추출물 그 자체로도 사용할 수 있지만, 약학적으로 허용되는 담체(carrier), 부형제(forming agent), 희석제(diluent) 등과 혼합하여 분말, 과립, 캡슐 또는 주사제 등의 고상 및 액상으로도 제조가 가능하다. 구체적으로 정제, 환제, 과립제, 분말, 새세이(sachet), 엘렉실제, 현탁제, 유제, 액제, 시럽, 에어로졸, 연질 또는 경질 젤라틴 캅셀제, 멸균 분말 등의 형태를 형성할 수 있으며, 특히 경구투여용 제제로 제형화된 형태가 바람직하다.In the preparation of the medicament of the present invention, the herbal extract may be used as such, but it may be mixed with a pharmaceutically acceptable carrier, a forming agent, a diluent or the like to prepare a powder, a granule, a capsule, It can be manufactured in solid or liquid phase. The composition may be in the form of tablets, pills, granules, powders, sachets, elctronic agents, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, sterilized powders, A formulation formulated as a drag formulation is preferred.
본 발명의 약학 조성물의 당해 기술 분야에 알려진 적합한 제제는 문헌 (Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA, 2013)에 개시되어 있는 것을 사용하는 것이 바람직하다. 포함될 수 있는 담체, 부형제 및 희석제로는 락토오스, 덱스트로오스, 수크로오스, 소르비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시 벤조에이트, 프로필히드록시 벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등이 있다. 상기 조성물을 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘 카보네이트, 수크로오스, 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔, 마크로골, 트윈 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. Suitable formulations known in the art for the pharmaceutical compositions of the present invention are preferably those disclosed in Remington ' s Pharmaceutical Sciences, Mack Publishing Company, Easton PA, 2013. Examples of carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which are prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose, lactose, It is prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of suppository bases include withexol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명의 글라블리딘은 감초로부터 추출된 것임을 특징으로 한다.The glabridin of the present invention is characterized in that it is extracted from licorice root.
감초는 뿌리와 줄기 밑 부분을 감미제와 위궤양·십이지장궤양의 치료제로 사용한다. 다른 약의 작용을 순하게 하므로, 한방에서 다양한 용도로 쓴다. 감초 추출물에는 글라블리딘이 다량 함유되어 있다. 글라블리딘의 효능으로는 본 발명에서의 소화기능 개선 뿐 아니라 미백 및 주름개선, 항산화 기능을 갖는다.Licorice is used as a treatment for sweeteners, stomach ulcers, duodenal ulcers, and roots and stem bottoms. Because the action of other medicines is made clear, it is used for various purposes in oriental medicine. Licorice extract contains a large amount of glabridine. The efficacy of glabridin has not only the improvement of digestion function but also whitening and wrinkle improvement and antioxidative function in the present invention.
본 발명의 소화장애증은 위장관 과운동증, 위 배출 장애, 궤양 대장염, 과민성 대장 증후군(IBS), 염증성 대장 질환(IBD), 위 운동 장애, 담낭염, 췌장염, 십이지장 궤양, 위 궤양, 만성 위염, 위식도 역류 질환 및 기능성 소화불량으로 이루어진 군에서 선택되는 어느 하나인 것을 특징으로 한다.
The present invention relates to the use of a compound of the present invention in the manufacture of a medicament for the treatment or prophylaxis of gastrointestinal disorders such as gastrointestinal tract and ataxia, gastric emptying disorders, ulcerative colitis, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), gastric motility disorder, Gastroesophageal reflux disease, and functional dyspepsia.
본 발명은The present invention
(a) 감초에 알코올, 물과 알코올, 아세톤 또는 물과 아세톤을 넣어 상기 감초를 추출하는 단계;(a) extracting the licorice by adding alcohol, water and alcohol, acetone or water and acetone to licorice;
(b) 감압하에서 고온에서 농축하여 알코올 또는 아세톤을 제거하는 단계; (b) concentrating at a high temperature under reduced pressure to remove alcohol or acetone;
(c) 수득된 농축물을 고온에서 진공 건조하는 단계; 및(c) vacuum drying the obtained concentrate at a high temperature; And
(d) 수득된 분말을 그라인딩 밀을 이용하여 입자를 작고 고르게 분쇄 처리 후 체를 이용하여 균질한 입자를 얻는 단계를 포함하는 하기 화학식1로 표시되는 글라블리딘을 포함하는 감초추출물 제조 방법을 제공한다.(d) a step of grinding the obtained powder using a grinding mill to obtain homogeneous particles by using a sieve after the pulverization of the particles is carried out in a small and uniform manner, to obtain a licorice extract containing glabridin represented by the following formula do.
[화학식1][Chemical Formula 1]
발명의 상기 (b) 단계에서 알코올 또는 아세톤을 제거하기 위한 온도 조건은 40℃ 내지 80℃의 범위이며, 바람직하게는 50℃ 내지 70℃의 범위이다. 또한, 이의 온도 조건을 3시간 내지 9 시간동안 유지하여 알코올 또는 아세톤을 제거한다.The temperature condition for removing the alcohol or acetone in the step (b) of the present invention is in the range of 40 캜 to 80 캜, preferably in the range of 50 캜 to 70 캜. Also, its temperature condition is maintained for 3 hours to 9 hours to remove alcohol or acetone.
발명의 상기 단계 (c)에서 수득된 농축물은 40℃ 내지 80℃의 범위, 바람직하게는 50℃ 내지 70℃의 범위에서 진공 건조를 수행한다.The concentrate obtained in the above step (c) of the present invention undergoes vacuum drying in the range of 40 캜 to 80 캜, preferably in the range of 50 캜 to 70 캜.
상기 “진공 건조”란 1기압 이하로 감압하여 행하는 건조로, 수득된 농축물을 건조기 내에 밀폐하고, 고온 저압 상태로 수분을 제거하는 것을 의미한다. The term " vacuum drying " as used herein means a drying furnace which is performed by reducing the pressure to 1 atmospheric pressure or less, sealing the obtained concentrate in a dryer, and removing moisture at a high temperature and a low pressure.
상기 “그라인딩 밀”이란 회전하는 원통형의 동체로 이루어지며, 물질을 잘게 분쇄하는 기계이다.The " grinding mill " means a rotating cylindrical body and is a machine for finely crushing a material.
본 발명의 감초로부터 추출된 글라블리딘 중량은 총 감초추출물 중량의 1% 내지 20%인 것을 특징으로 한다.The weight of the glabridin extracted from licorice of the present invention is 1% to 20% of the total licorice extract weight.
감초추출물 총 중량에 대한 글라블리딘의 중량은 1% 내지 20%, 바람직하게는 2% 내지 10%인 것을 특징으로 한다.The weight of the glabridin based on the total weight of the licorice extract is 1% to 20%, preferably 2% to 10%.
상기 제조 방법으로 추출된 감초 추출물은 면역증강제, 백신의 효능을 향상시킬 수 있는 첨가물로서 사용되는 백신보강제 (adjuvants), 치료 효능을 증강시킬 수 있는 보조치료제, 사료첨가제 등의 용도로 이용될 수 있다.The licorice extract extracted by the above-described method can be used as an immunity enhancer, an adjuvant used as an additive for improving the efficacy of a vaccine, an adjunct therapeutic agent for enhancing therapeutic efficacy, a feed additive and the like .
면역증강제의 경우는 본 발명이 제공하는 감초 열탕추출물을 동결건조형태로 생산하여 사용시 희석액에 부유하여 주사로 사용되게 되며, 백신보좌제인 경우는 백신의 보좌제로 사용하는 오일(oil)이나 알루미늄 겔(aluminium gel)에 흡착시켜 사용하게 된다. 보조치료제의 경우는 면역증강제의 경우와 동일하며, 사료첨가제로 사용되는 경우는 본 발명이 제공하는 감초 열탕추출물을 건조하여 분말형태로 만들어 사료에 첨가하여 사용하게 된다. In the case of an immunostimulant, the liquorice extract of the present invention is produced in a lyophilized form and suspended in a diluent to be used as an injection. In the case of a vaccine adjuvant, the oil or the aluminum gel aluminum gel) to be used. When the adjuvant is used as a feed additive, the liquorice extract of the present invention is dried and powdered to be added to the feed.
면역증강효능을 나타내기 위한 감초 열탕추출물의 사용량은 면역세포 및 동물의 종류에 따라 다르나, 면역증강제, 백신보강제, 보조치료제 또는 사료첨가제 등의 제형내에서 사용시 제형의 부피를 기준으로 10㎍/㎖~1㎎/㎖인 것이 바람직하고, 면역세포 시험은 면역증강물질을 선발하는 과정으로 간주할 때, 실제 적용 농도는 실험동물에서의 유효농도를 기준으로 하여야 할 것이므로 제형의 부피를 기준으로 100㎍/㎖인 것이 더욱 바람직하다.
The amount of the licorice hot-water extract to exhibit the immunostimulating effect depends on the type of the immune cells and the animal, but it is preferably 10 μg / ml based on the volume of the formulation when used in a formulation such as an immunostimulating agent, a vaccine adjuvant, ~ 1 mg / ml, and when the immune cell test is regarded as a process of selecting an immunostimulating substance, the actual application concentration should be based on the effective concentration in an experimental animal. Therefore, 100 μg / Ml.
본 발명은 담즙 분비 촉진, 지방 소화 개선 및 위장관 운동 활성화 기능으로 이루어지는 군에서 선택되는 어느 하나 이상의 기능을 가지는 감초 유래 글라블리딘을 제공한다.
The present invention provides a licorice-derived glabridin having at least one function selected from the group consisting of biliary secretion promotion, fat digestion improvement, and gastrointestinal motility activation function.
따라서 본 발명은 감초 유래 글라블리딘을 유효성분으로 하는 소화기능 개선용 조성물에 관한 것으로 구체적으로는 담즙산 분비를 촉진하고 소화기능 개선 효과가 있는 감초 유래 글라블리딘을 유효성분으로 포함하는 건강 기능성 식품 조성물 및 약학 조성물에 관한 것이다. 본 발명에 따른 감초의 글라블리딘은 담즙 분비 촉진과 위장관 운동 개선에 매우 효과적으로 사용될 수 있다. 또한 장기복용에 따른 부작용의 발생 가능성이 작아 매우 안전하다.
Accordingly, the present invention relates to a composition for improving digestion function using glabridin derived glabridin as an active ingredient, and more particularly, to a composition for improving digestive function, which comprises glycyrrhizin-derived glabridin as an active ingredient, Compositions and pharmaceutical compositions. The glabridin of Licorice according to the present invention can be very effectively used for promoting bile secretion and improving gastrointestinal motility. Also, it is very safe because the possibility of side effects from long-term use is small.
도 1은 각각 물, 아세톤, 에탄올을 용매로 하여 글라블리딘을 추출 후 흰쥐에 경구투여하여 담즙 분비량을 측정한 그래프이다.FIG. 1 is a graph showing the amount of bile secreted by oral administration to rats after extracting glabridin with water, acetone, and ethanol as solvents.
이하 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.
However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.
<< 실시예Example 1> 1>
글라블리딘을Glyburidine 포함하는 감초추출물의 추출방법 Extraction method of licorice extract containing
건조된 감초(Glycyrrhiza glabra) 뿌리를 60℃에서 아세톤으로 여과기에서 환류 추출시켰다. 여과물을 수집하고 감압하에서 50-60℃에서 6-7시간 농축하여 아세톤을 제거했다. 결과적으로 수득된 수용성 농축물을 65-70℃에서 진공건조 하였다. 결과적으로 수득된 분말을 Grind, Mill을 이용하여 입자를 작고 고르게 분쇄 처리 하고, Sieve를 이용하여 균질한 입자를 얻을 수 있었다.
Dried licorice ( Glycyrrhiza glabra ) roots were refluxed in a filter with acetone at 60 ° C. The filtrate was collected and concentrated under reduced pressure at 50-60 < 0 > C for 6-7 h to remove acetone. The resulting aqueous concentrate was vacuum dried at 65-70 < 0 > C. As a result, the obtained powder was pulverized into small and uniform particles using Grind and Mill, and homogeneous particles were obtained using a sieve.
<< 실시예Example 2> 2>
글라블리딘을Glyburidine 포함하는 감초 추출물의 담즙분비 증가 효과 확인 Confirming the effect of licorice extract containing cholesterol
본 발명에 따른 감초 유래 글라블리딘의 담즙분비 증가에 대한 평가방법으로는 7주령 스프라그 도울리(Spraugue-Dawley:SD)계 수컷 흰쥐를 24시간 동안 절식시킨 후 체중을 측정한 다음, 여러 가지 용매를 이용하여 추출한 감초 유래 글라블리딘을 100 mg/kg의 용량으로 물에 녹여 한번 경구 투여 하였고, 투여 후 1시간 간격으로 담즙을 채취하여 담즙 분비량을 측정하였다.As a method for evaluating the bile secretion increase of licorice-derived glabridin according to the present invention, 7-week-old Sprague-Dawley (SD) male rats were fasted for 24 hours and then weighed, Glycyrrhizin-derived glabridin extracted with a solvent was dissolved in water at a dose of 100 mg / kg and then administered orally once. Bile juice was collected every hour after administration to measure bile secretion amount.
그 결과, 도1에 표시된 그래프와 같이 감초 유래 글라블리딘을 흰쥐에 경구투여하면, 0-2시간 사이에 유의성 있게 담즙 분비가 증가됨을 관찰할 수 있었다. 에탄올 추출물과 아세톤 추출물에서 유의적으로 담즙 분비의 증가를 확인할 수 있었다.
As a result, as shown in the graph of FIG. 1, when the licorice-derived glabridin was orally administered to rats, it was observed that bile secretion was significantly increased between 0-2 hours. Ethanol extract and acetone extract significantly increased bile secretion.
<< 실시예Example 3> 3>
장에서 소화관까지의 이동거리 Distance from the intestine to the digestive tract GITGIT (( gastricgastric intestinalintestinal transittransit )의 측정)
본 발명에 따른 감초 유래 글라블리딘에 대한 소화관 이동거리 측정 평가 방법으로는 6주령 ICR계 수컷 흰쥐를 사용하였으며 24시간 동안 절식시키고, 물은 충분한 양을 공급하였다. 체중을 측정한 다음 대조약물인 메토클로프라이드(Metoclopride, Sigma-Aldrich)와 여러 가지 용매를 이용하여 추출한 감초 유래 글라블리딘은 소화관 이동거리 확인 물질인 5% 에반스블루(evans blue) 투여 30분 전에 경구 투여하였다. 5% evans blue 투여 30분 후에 흰쥐를 경추 탈골하여 흰쥐의 복부를 경중선을 따라 절개하고 위의 유문부부터 직장까지 장이 끊어지지 않도록 적출하였다. 적출한 소화관은 측정하기 쉽도록 펼쳐서 유문부에서 5% evans blue 선단부까지의 이동거리를 측정하였으며 유문부에서 직장부까지의 거리(소화관 전체 길이)를 측정하였다. 투여한 5% evans blue의 소화관 이동률(T)을 구하기 위해 소화관 전체 길이(A)와 5% evans blue의 최선단부까지의 거리(B)로부터 식을 이용해 산출하였다. (T=(B/A)*100(%))As a method for evaluating the distance of digestive tract to glabridin derived from licorice root according to the present invention, a 6-week-old ICR male rats were used, fasted for 24 hours, and supplied with a sufficient amount of water. After measuring the body weight, the licorice-derived glabridin, which was extracted with Metoclopride (Sigma-Aldrich) and various solvents, was administered 30 minutes before the 5% evans blue administration Orally. After 30 minutes of administration of 5% evans blue, the rats were excised from the cervical vertebra and the abdomen of the rats was incised along the midline to remove the intestine from the pyloric portion to the rectum. The distance of the digestive tract from the pylorus to the distal end of the 5% evans blue was measured and the distance from the pylorus to the rectum (the length of the digestive tract) was measured. The total length (A) of the digestive tract and the distance (B) to the best end of 5% evans blue were calculated using the equation to determine the gastrointestinal tract migration rate (T) of 5% evans blue. (T = (B / A) * 100 (%))
그 결과 에탄올 추출물과 아세톤 추출물에서 소화관 이동거리가 증가하였으며 대조약물과 비교했을 때 유의적인 차이를 보였다. 따라서 감초 유래 글라블리딘이 소화 위장관 운동 개선에 도움을 주는 것을 확인할 수 있었다. As a result, the distances of gastrointestinal tract movement increased in ethanol extract and acetone extract. Therefore, it was confirmed that licorice - derived glabridine helps to improve digestive gastrointestinal motility.
(Significantly different from control. *p<0.05)
(Significantly different from control. * P < 0.05)
<< 실시예Example 4> 4>
위 top 배출능Emission Capability GEGE (( gastricgastric emptyingemptying )의 측정)
본 발명에 따른 감초 유래 글라블리딘의 위 배출능 측정 평가 방법으로 6주령 스프라그 도울리 (Spraugue-Dawley:SD)계 수컷 흰쥐를 24시간 동안 절식시키고, 물은 충분한 양을 공급하였다. 체중을 측정한 다음 대조약물인 모사프라이드(Mosapride, Sigma-Aldrich)와 실험예 1의 감초 유래 글라블리딘을 위 배출능 확인물질인 0.05% 페놀레드 (phenol red) (w/v) 1.5 ml를 투여 30분 전에 경구투여 하였다. 0.05% phenol red (w/v) 경구 투여 후 20분 후 ether 마취하에 개복하고 유문과 분문을 결찰한 후 위를 적출하였다. 적출한 위는 0.01N NaOH 3 ml내에서 균질화 시킨 후, 균질액 1 ml에 20% trichloroacetic acid (w/v) 0.2 ml를 가하여 단백질을 침전 시키고 1,600 g의 속도로 20분간 원심 분리하였다. 원심 분리 후 상층액 0.6 ml에 0.5N NaOH 0.8 ml를 가한 후 560 nm에서 흡광도를 측정하였다.
Six-week old Sprague-Dawley (SD) male rats were fasted for 24 hours and water was supplied in sufficient quantity to evaluate gastric emptying ability of licorice derived glabridin according to the present invention. After the body weight was measured, 1.5 ml of 0.05% phenol red (w / v), which is a comparative drug, Mosapride (Sigma-Aldrich) and the licorice-derived glabridin of Experimental Example 1, Oral administration was given 30 minutes before administration. Twenty minutes after oral administration of 0.05% phenol red (w / v), the rats were lavaged under ether anesthesia and the stomachs were excised after ligating the pylorus and the trunk. The extracted stomachs were homogenized in 3 ml of 0.01N NaOH, and the proteins were precipitated by adding 0.2 ml of 20% trichloroacetic acid (w / v) to 1 ml of the homogenate and centrifuged at 1,600 g for 20 minutes. After centrifugation, 0.8 ml of 0.5 N NaOH was added to 0.6 ml of the supernatant and the absorbance was measured at 560 nm.
감초 유래 글라블리딘과 Mosapride를 경구투여하고 관찰한 결과, 에탄올 추출물과 아세톤 추출물이 대조군에 비해 배출능이 증가됨을 보였다. 양성대조군인 Mosapride와 동등 또는 그 이상의 우수한 위 배출능 효과가 있음을 확인하였다.The results of oral administration of glabridin and Mosapride derived from licorice showed that the ethanol extract and acetone extract increased the excretion rate of the extract. It was confirmed that there was an excellent gastric emptying effect equivalent to or better than the positive control group Mosapride.
(Significantly different from control. *p<0.05, ***p<0.001)
(Significantly different from control. * P <0.05, *** p <0.001)
<< 실시예Example 5> 5>
랫트에In rats 대한 About 급성경구투여Acute oral administration 독성실험 Toxicity experiment
6주령의 특정병원부재 (SPF) SD계 암수 랫트를 사용하여 실시예 1의 감초 유래 글라블리딘에 대한 급성독성실험을 실시하였다. 실험군의 구성은 군당 암수 각각 5 마리씩의 동물에 대하여 본 발명의 감초 유래 글라블리딘을 1 g/㎏, 2 g/㎏ 및 5 g/㎏의 용량군으로 하였으며, 시험물질은 5% HPMC(hydroxypropylmethyl cellulose) 용액에 현탁하여 1회 경구투여 하였다. 시험물질 투여 후 동물의 폐사여부, 임상증상, 체중변화를 관찰하고 혈액학적 검사와 혈액 생화학적 검사를 실시하였으며, 부검하여 육안으로 복강장기와 흉강장기의 이상여부를 관찰하였다. Acute toxicity test on licorice-derived glabridin of Example 1 was conducted using SD male and female rats at 6 weeks of age with a specific hospital member (SPF). The experimental group was composed of 5 g / kg, 2 g / kg and 5 g / kg of the licorice-derived glabridin of the present invention, and the test substance was 5% HPMC (hydroxypropylmethyl cellulose) solution and then orally administered once. After the administration of the test substance, the mortality, clinical symptoms, and weight changes of the animals were observed, and hematological tests and blood biochemical tests were carried out, and autopsy was performed to observe the abnormalities of the abdominal organs and thoracic organs.
그 결과, 시험물질을 투여한 모든 동물에서 특기할 만한 임상증상이나 폐사된 동물은 없었으며, 체중변화, 혈액검사, 혈액생화학 검사, 부검소견 등에서도 독성변화는 관찰되지 않았다. 또한, 본 발명의 감초 유래 글라블리딘을 투여한 실험군과 투여하지 않은 대조군의 현미경적 소견을 비교한 결과, 간장, 비장, 신장, 뇌, 피부, 생식기계, 위장, 대장, 심장, 폐장 등 실질 장기 등에서 본 발명의 추출물이 독성을 나타내지 않는 것으로 확인되었다. 이상의 결과 실험된 본 발명의 추출물은 모두 랫트에서 5 g/㎏까지 독성변화를 나타내지 않는 안전한 물질로 판단되었다.
As a result, there were no clinically symptomatic or dead animals in all the animals to which the test substance was administered, and no toxic change was observed in weight change, blood test, blood biochemical test, and autopsy findings. In addition, the microscopic findings of the experimental group administered with licorice-derived glabridin of the present invention and the control group of the untreated control group were compared with each other, and as a result, It was confirmed that the extract of the present invention does not show toxicity. As a result, the extract of the present invention was judged to be a safe substance showing no toxicity change to 5 g / kg in rats.
<< 실시예Example 6> 6>
소화기능 임상시험Digestive function clinical trial
평소 소화기능 장애가 있는 환자 50명을 대상으로 테스트를 수행하였다. 구체적으로 실시예1에 따라 추출된 감초 유래 글라블리딘을 환자 25명에게 경구투여 하였고 나머지 25명은 대조군으로 글라블리딘 성분을 제외한 조성물만을 경구투여 하였다. 본 임상시험은 블라인드 테스트로 진행되었으며 소화기능장애와 관련된 설문조사를 통해 소화기능 개선 여부를 확인하였다.Fifty patients with normal digestive dysfunction were tested. Specifically, the licorice-derived glabridin extracted according to Example 1 was orally administered to 25 patients and the remaining 25 patients were orally administered only the composition excluding the glabridin component as a control group. This study was carried out with blind test and the digestive function was confirmed by questionnaire related to digestive dysfunction.
그 결과 감초 유래 글라블리딘을 함유한 조성물을 경구투여한 군에서 유의한 소화기능개선 효과가 나타났으며 대조군에서는 유의한 결과를 확인하기 어려웠다.
As a result, the oral administration of the composition containing the licorice derived glabridin showed significant improvement of the digestive function and it was difficult to confirm the significant results in the control group.
본 발명에 따른 감초 유래 글라블리딘은 담즙 분비 촉진과 위장관 운동 개선에 매우 효과적으로 사용될 수 있다. 또한, 장기복용에 따른 부작용의 발생 가능성이 작아 산업상 이용가능성이 크다.
Glycyrrhizin-derived glabridin according to the present invention can be very effectively used for promoting bile secretion and improving gastrointestinal motility. In addition, the possibility of side effects due to long-term use is low and thus there is a high possibility of industrial use.
Claims (9)
[화학식1]
A health functional food composition for improving digestion function comprising glabridin represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]
The health functional food composition according to claim 1, wherein the glabridin is extracted from licorice.
The health functional food composition according to claim 1, wherein the composition for improving digestion function has at least one function selected from the group consisting of promoting bile secretion, improving fat digestion, and activating gastrointestinal motility.
[화학식1]
Claims 1. A pharmaceutical composition for preventing and treating digestive discomfort comprising glabridin represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]
[Claim 5] The pharmaceutical composition according to claim 4, wherein the glabridin is extracted from licorice.
The method of claim 4, wherein the digestive disorder is selected from the group consisting of gastrointestinal tract and ataxia, gastric emptying disorder, ulcerative colitis, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), gastric motility disorder, cholecystitis, pancreatitis, duodenal ulcer, , Chronic gastritis, gastroesophageal reflux disease, and functional dyspepsia. ≪ Desc / Clms Page number 24 >
(b) 감압하에서 고온에서 농축하여 알코올 또는 아세톤을 제거하는 단계;
(c) 수득된 농축물을 고온에서 진공 건조하는 단계; 및
(d) 수득된 분말을 그라인딩 밀을 이용하여 입자를 작고 고르게 분쇄 처리 후 체를 이용하여 균질한 입자를 얻는 단계를 포함하는 하기 화학식1로 표시되는 글라블리딘을 포함하는 감초추출물 제조 방법.
[화학식1]
(b) concentrating at a high temperature under reduced pressure to remove alcohol or acetone;
(c) vacuum drying the obtained concentrate at a high temperature; And
(d) obtaining a homogeneous particle using a sieve after finely pulverizing the obtained powder using a grinding mill to obtain a granulated licorice extract.
[Chemical Formula 1]
The method according to claim 7, wherein the weight of glabridin extracted from licorice is 1% to 20% of the total weight of licorice extract.
Derived glabridin having at least one function selected from the group consisting of bile secretion promotion, fat digestion improvement and gastrointestinal motility activation function extracted by the method of claim 7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020140105358A KR102014922B1 (en) | 2014-08-13 | 2014-08-13 | Composition for improving digestive functions comprising glabridin from Liquorice |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020140105358A KR102014922B1 (en) | 2014-08-13 | 2014-08-13 | Composition for improving digestive functions comprising glabridin from Liquorice |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20160020261A true KR20160020261A (en) | 2016-02-23 |
| KR102014922B1 KR102014922B1 (en) | 2019-08-27 |
Family
ID=55449186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020140105358A KR102014922B1 (en) | 2014-08-13 | 2014-08-13 | Composition for improving digestive functions comprising glabridin from Liquorice |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR102014922B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210119253A (en) * | 2020-03-24 | 2021-10-05 | (주)에이앤바이오 | Composition for improving cat hairball discharge and gastrointestinal diseases |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20230141995A (en) | 2022-03-30 | 2023-10-11 | 박형범 | Composition for improving digestive functions comprising a mixed plant extract powder as an active ingredient |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100570803B1 (en) * | 2003-01-21 | 2006-04-13 | 학교법인 인하학원 | A process of extracting glabridine from licorice root |
| KR20110123114A (en) * | 2010-05-06 | 2011-11-14 | 씨제이제일제당 (주) | A pharmaceutical composition and a health functional food composition for preventing, treating or improving a gastrointestinal dyskinetic disease |
-
2014
- 2014-08-13 KR KR1020140105358A patent/KR102014922B1/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100570803B1 (en) * | 2003-01-21 | 2006-04-13 | 학교법인 인하학원 | A process of extracting glabridine from licorice root |
| KR20110123114A (en) * | 2010-05-06 | 2011-11-14 | 씨제이제일제당 (주) | A pharmaceutical composition and a health functional food composition for preventing, treating or improving a gastrointestinal dyskinetic disease |
Non-Patent Citations (1)
| Title |
|---|
| Life Sciences.2002, Vol.71, pp.1449-1463 1부* * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210119253A (en) * | 2020-03-24 | 2021-10-05 | (주)에이앤바이오 | Composition for improving cat hairball discharge and gastrointestinal diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| KR102014922B1 (en) | 2019-08-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20110067789A (en) | A composition comprising the extract of crude drug selected from eriobotryae folium and dendropanax morbiferafor treating and preventing neuro-degenerative disease | |
| KR100597235B1 (en) | Composition comprising Schizandrae Fructus extract as an effective component for preventing and treating arthritis | |
| KR101964054B1 (en) | Pharmaceutical composition comprising extract of Lonicera japonica for prevention and treatment of Crohn's disease | |
| KR102014922B1 (en) | Composition for improving digestive functions comprising glabridin from Liquorice | |
| JP5969529B2 (en) | Anti-inflammatory agent | |
| KR101018403B1 (en) | composition comprising the extract of soybean leaves for the prevention?delay or treatment of gout | |
| WO2005094858A1 (en) | Antidiabetic composition | |
| KR101119410B1 (en) | Foeniculum vulgar extracts compositions for treating or preventing inflammatory diseases | |
| KR102410771B1 (en) | Composition for preventing or treating sarcopenia comprising blueberry extract | |
| WO2013141573A1 (en) | Composition comprising ethanol extract of rumex acetosa l. for improving gastrointestinal diseases | |
| WO2013187576A1 (en) | Composition comprising silymarin as active ingredient for preventing and treating peptic ulcers caused by alcohol consumption | |
| KR101181347B1 (en) | Composition for the prevention and treatment of lipid-related cardiovascular disease or obesity containing the extracts of Dictamnus dasycarpus as active ingredient | |
| KR100892180B1 (en) | Composition comprising powder of tangerine peel or the extract thereof for treating and preventing gastrointestinal disease | |
| KR20160059152A (en) | Anti-obesity composition comprising Cirsium japonicum leaf extract as effective component | |
| KR20150106478A (en) | Extract of Black raspberry containing lactic acid bacterium for immunological enhancement and improving climacteric symptoms | |
| KR101531922B1 (en) | Composition containing improvement of gastric disease by using the ethanolic extract of Rumex acetosa L. | |
| KR101241338B1 (en) | Composition for the prevention and treatment of lipid-related cardiovascular disease or obesity containing extracts of Polygonum aviculare as active ingredient | |
| KR102664506B1 (en) | Composition for enhancing intestinal function comprising mixture of Ponciri Fructus Immaturus and bamboo leaf as effective component | |
| KR100533283B1 (en) | Composition comprising extract of herbal mixture for prevention or treatment of osteoporosis | |
| KR102183916B1 (en) | Composition containing complex extracts for preventing, improving or treating dyslipidemia | |
| KR102183915B1 (en) | Composition containing complex extracts for improving blood circulation | |
| KR102019974B1 (en) | A composition for preventing, improving or treating alcoholic gastro-intestinal disease comprising the extracts from licorice and dandelion | |
| WO2013133677A1 (en) | Composition containing reaction mixture of red-ginseng extract and persimmon vinegar for preventing or treating vascular diseases | |
| KR101144232B1 (en) | Blueberry extracts as an effective components for prevention and treatment of Hyperuricemia | |
| KR101552816B1 (en) | Compositions for preventing or treating benign prostatic hyperplasia comprising extracts of Veratrum nigrum |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant |