KR101020245B1 - Composition for improving insomnia containing licorice extract and silk tree extract as effective components and production method thereof - Google Patents
Composition for improving insomnia containing licorice extract and silk tree extract as effective components and production method thereof Download PDFInfo
- Publication number
- KR101020245B1 KR101020245B1 KR1020100079596A KR20100079596A KR101020245B1 KR 101020245 B1 KR101020245 B1 KR 101020245B1 KR 1020100079596 A KR1020100079596 A KR 1020100079596A KR 20100079596 A KR20100079596 A KR 20100079596A KR 101020245 B1 KR101020245 B1 KR 101020245B1
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- sleep
- licorice
- ethanol
- composition
- Prior art date
Links
- 239000000284 extract Substances 0.000 title claims abstract description 79
- 239000000203 mixture Substances 0.000 title claims abstract description 41
- 229940069445 licorice extract Drugs 0.000 title claims description 20
- 240000007185 Albizia julibrissin Species 0.000 title abstract description 9
- 235000011468 Albizia julibrissin Nutrition 0.000 title abstract description 9
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 title description 5
- 206010022437 insomnia Diseases 0.000 title description 5
- 238000004519 manufacturing process Methods 0.000 title description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 87
- 230000004617 sleep duration Effects 0.000 claims abstract description 23
- 230000004620 sleep latency Effects 0.000 claims abstract description 20
- 239000004480 active ingredient Substances 0.000 claims abstract description 16
- 235000013376 functional food Nutrition 0.000 claims abstract description 7
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims description 106
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 claims description 105
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 claims description 105
- 229940010454 licorice Drugs 0.000 claims description 105
- 241000202807 Glycyrrhiza Species 0.000 claims description 82
- 230000007958 sleep Effects 0.000 claims description 82
- 230000000694 effects Effects 0.000 claims description 41
- 239000000469 ethanolic extract Substances 0.000 claims description 39
- 230000006872 improvement Effects 0.000 claims description 15
- 230000001965 increasing effect Effects 0.000 claims description 15
- 230000003247 decreasing effect Effects 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 5
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 111
- 229960001412 pentobarbital Drugs 0.000 description 55
- 229960003529 diazepam Drugs 0.000 description 30
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 30
- 238000000605 extraction Methods 0.000 description 30
- 230000027455 binding Effects 0.000 description 26
- 238000012360 testing method Methods 0.000 description 25
- 244000303040 Glycyrrhiza glabra Species 0.000 description 24
- 230000006698 induction Effects 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 17
- 230000002401 inhibitory effect Effects 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 14
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- 210000003491 skin Anatomy 0.000 description 10
- 230000001419 dependent effect Effects 0.000 description 9
- 230000004044 response Effects 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000007774 longterm Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 6
- 239000007928 intraperitoneal injection Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 5
- 238000009395 breeding Methods 0.000 description 5
- 230000001488 breeding effect Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000000517 effect on sleep Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 235000013361 beverage Nutrition 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 238000002481 ethanol extraction Methods 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 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
- 230000036506 anxiety Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 230000000147 hypnotic effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000037053 non-rapid eye movement Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- WYCMFCPHWDZHMR-UHFFFAOYSA-N 1-(4,7-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-9-yl)-n,n-dimethylmethanesulfonamide Chemical compound C1=CC(C2CC(CN(C)C2C2)CS(=O)(=O)N(C)C)=C3C2=CN(C)C3=C1 WYCMFCPHWDZHMR-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 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
- 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
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 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
- 241000699666 Mus <mouse, genus> Species 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
- 231100000460 acute oral toxicity Toxicity 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 239000003125 aqueous solvent Substances 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
- 230000037396 body weight Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 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
- 238000011156 evaluation Methods 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- OFBIFZUFASYYRE-UHFFFAOYSA-N flumazenil Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C21 OFBIFZUFASYYRE-UHFFFAOYSA-N 0.000 description 2
- 229960004381 flumazenil Drugs 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229960001031 glucose Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000008101 lactose Substances 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
- 229930014626 natural product Natural products 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000004461 rapid eye movement Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- 230000003860 sleep quality Effects 0.000 description 2
- 230000004622 sleep time Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 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
- 239000003826 tablet 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
- 238000012795 verification Methods 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 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
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-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
- 206010002869 Anxiety symptoms Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 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
- 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
- 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
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 1
- 240000008917 Glycyrrhiza uralensis Species 0.000 description 1
- 235000000554 Glycyrrhiza uralensis Nutrition 0.000 description 1
- 241000282412 Homo Species 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
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029216 Nervousness Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010041349 Somnolence 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
- 239000000654 additive Substances 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
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000001367 artery Anatomy 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
- 238000011888 autopsy Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 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
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 230000036996 cardiovascular health Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 239000003479 dental cement Substances 0.000 description 1
- 238000013400 design of experiment Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000002615 epidermis Anatomy 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
- 239000000945 filler Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000020510 functional beverage Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 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 description 1
- 230000037308 hair color Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002372 labelling Methods 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
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 235000011477 liquorice Nutrition 0.000 description 1
- 244000144972 livestock Species 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
- -1 maltose and sucrose Chemical compound 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
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000002503 metabolic effect 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
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 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
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000036385 rapid eye movement (rem) sleep Effects 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
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 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
- 235000013580 sausages Nutrition 0.000 description 1
- 210000004761 scalp Anatomy 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
- 230000001624 sedative effect Effects 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 238000005211 surface analysis Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 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
- 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
- 210000001835 viscera Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Images
Classifications
-
- 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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
-
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Botany (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Food Science & Technology (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Medicines Containing Plant Substances (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Nutrition Science (AREA)
- Neurology (AREA)
- Polymers & Plastics (AREA)
- Anesthesiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
Abstract
Description
본 발명은 유효성분으로 감초 추출물 및 합환피 추출물로 이루어진 군으로부터 선택되는 하나 이상의 추출물을 함유하는 수면개선용 조성물에 관한 것으로, 더욱 상세하게 본 발명은 수면 잠재기(sleep latency)가 감소하고 수면지속기간(sleep duration)을 증가시킬 수 있는 감초 추출물 및 합환피 추출물을 개발함으로써 수면 개선을 위한 기능성 식품산업상 매우 유용한 발명을 제공할 수 있다.The present invention relates to a composition for improving sleep containing at least one extract selected from the group consisting of licorice extract and haphwanpi extract as an active ingredient, more specifically the present invention reduces sleep latency and sleep duration By developing licorice extract and haebhwanpi extract that can increase (sleep duration) can provide a very useful invention in the functional food industry for sleep improvement.
최근 발표에 따르면, 수면은 기억과 학습, 대사조절 및 체중, 안전사고(졸음운전, 근로사고 등), 기분(우울증, 활력 저하), 심혈관 건강, 질환(면역력 저하, 암 저항력 저하, 비만 및 당뇨 유도 등) 등과 밀접하게 관련되어 있어 수면의 중요성을 강조하고 있으며, 따라서 불면증 등의 수면장애 개선 및 수면의 질 향상은 국민건강 및 삶의 질을 높일 수 있는 매우 중요한 요소이다.According to recent announcements, sleep can be associated with memory and learning, metabolic control and weight, safety accidents (drowsiness driving, working accidents, etc.), mood (depression, vitality), cardiovascular health, disease (low immunity, cancer resistance, obesity and diabetes). It is closely related to induction, etc., which emphasizes the importance of sleep. Therefore, improvement of sleep disorders such as insomnia and improvement of sleep quality are very important factors to improve national health and quality of life.
그러나 현대사회에서 많은 사람들은 스트레스와 불안, 초조 때문에 수면장애를 겪고 있다. 통계에 의하면 성인의 약 15%가 불안증상에 의한 불면증 때문에 약물 치료가 필요하다고 알려져 있으며, 나이가 많아질수록 불면증 환자는 더욱 증가한다고 알려져 있다. 불면의 원인으로는 스트레스, 지나친 걱정, 긴장, 공포 등 다양하며, 치료약물로는 벤조디아제핀 계열의 약물과 세로토닌 효능약 등이 사용되고 있으나, 이러한 약물들은 장기간 사용하였을 때 내성 및 의존성이 형성되는 부작용이 심하여, 초기 또는 일시적 불안과 불면을 호소하는 수험생이나 운동선수 및 근로자들이 사용하기에는 부적합하다. However, many people in modern society suffer from sleep disorders due to stress, anxiety and nervousness. According to statistics, about 15% of adults are in need of drug treatment because of insomnia due to anxiety symptoms. There are various causes of insomnia, such as stress, excessive anxiety, tension, and fear.Therapeutic drugs include benzodiazepine-based drugs and serotonin agonists, but these drugs have severe side effects that form resistance and dependence after long-term use. However, it is not suitable for use by candidates, athletes and workers who complain of early or temporary anxiety and insomnia.
따라서, 수면제 장기복용자 및 제한자의 경우 이를 대체할 수 있는 수단으로 천연 수면보조제의 필요성이 높아지고 있다. 선진국에서는 수면제를 대체하거나 줄일 수 있는 수면 증진 건강기능식품의 시장이 확대되고 있으며, LOHAS 트렌드의 확산과 수면에 대한 관심 증가에 따라 수면의 질을 높이고자 하는 욕구가 높아지고 있어 불면증 환자뿐만 아니라 일반인의 수면 증진 건강기능식품에 대한 수요도 더욱 확대될 것으로 전망되고 있다.Accordingly, the necessity of natural sleeping aids is increasing as a means of replacing the sleeping pills long term users and limiters. In developed countries, the market for sleep-enhancing dietary supplements that can replace or reduce sleeping pills is expanding, and the desire to improve sleep quality is increasing due to the spread of LOHAS trends and increased interest in sleep. The demand for health supplements is also expected to expand further.
한국특허공개 제2007-0070307호에는 수면 개선 의약 조성물이 개시되어 있으며, 한국특허공개 제2005-0095930호에는 항우울 또는 항불안 활성을 갖는 합환피 추출물을 함유하는 조성물이 개시되어 있으나, 본 발명의 유효성분으로 감초 추출물 및 합환피 추출물을 함유하는 수면개선 조성물과는 상이하다.Korean Patent Publication No. 2007-0070307 discloses a sleep improving pharmaceutical composition, and Korean Patent Publication No. 2005-0095930 discloses a composition containing a haphwanpi extract having antidepressant or anti-anxiety activity, It is different from the sleep improvement composition containing the licorice extract and Haphwanpi extract as an active ingredient.
본 발명은 상기와 같은 요구에 의해 도출된 것으로서, 본 발명은 수면을 개선시킬 수 있는 기능성 소재의 개발이 요망되고 있으나, 부작용 등 안전성의 문제 때문에 많은 제약을 받고 있는 요즘, 천연물이면서 비교적 안전성이 높은 감초 추출물 및 합환피 추출물로 이루어진 군으로부터 선택되는 하나 이상의 추출물을 유효성분으로 함유하는 수면개선용 조성물을 개발함으로써 본 발명을 완성하였다.The present invention is derived from the above requirements, the present invention has been required to develop a functional material that can improve sleep, but these days are under a lot of restrictions due to safety problems such as side effects, natural products and relatively high safety The present invention was completed by developing a composition for improving sleep containing at least one extract selected from the group consisting of licorice extract and haphwanpi extract as an active ingredient.
상기 과제를 해결하기 위해, 본 발명은 유효성분으로 감초 추출물 및 합환피 추출물로 이루어진 군으로부터 선택되는 하나 이상의 추출물을 함유하는 수면개선용 조성물을 제공한다.In order to solve the above problems, the present invention provides a composition for improving sleep containing at least one extract selected from the group consisting of licorice extract and haphwanpi extract as an active ingredient.
또한, 본 발명은 감초 추출물 및 합환피 추출물로 이루어진 군으로부터 선택되는 하나 이상의 추출물을 유효성분으로 함유하는 수면개선용 기능성 식품을 제공한다.In addition, the present invention provides a functional food for improving sleep containing at least one extract selected from the group consisting of licorice extract and haphwanpi extract as an active ingredient.
또한, 본 발명은 유효성분으로 감초를 26~32% 에탄올로 38~44℃에서 10~14시간 동안 추출하여 제조되는 감초 추출물 및 합환피를 52~62% 에탄올로 18~60℃에서 22~60시간 동안 추출하여 제조되는 합환피 추출물을 중량비 기준으로 2.5~3.5:0.5~1.5로 혼합하는 것을 특징으로 하는 수면개선용 조성물의 제조방법을 제공한다.In addition, the present invention is a licorice extract and haphwanpi prepared by extracting licorice with 26-32% ethanol for 10-14 hours at 38-44 ℃ as an active ingredient 22-60 at 18-60 ℃ with 52-62% ethanol It provides a method for producing a composition for improving sleep, characterized in that the mixture of Hwanhwanpi extract prepared by extracting for a time by mixing 2.5 ~ 3.5: 0.5 ~ 1.5 by weight.
본 발명에 따르면, 본 발명의 수면개선용 조성물은 수면 개선에 효과적이며, 천연물로부터 얻어진 물질을 이용하기 때문에 부작용을 유발하지 않으며, 안전성을 확보할 수 있어, 수면개선을 위한 기능성 식품산업상 매우 유용한 발명이 될 것이다.According to the present invention, the composition for improving sleep of the present invention is effective for improving sleep, and because it uses a material obtained from natural products, does not cause side effects, and can ensure safety, it is very useful in the functional food industry for sleep improvement It will be an invention.
도 1은 감초추출물(GUE), 합환피 추출물(AJE) 및 감초추출물+합환피 추출물(Combination)을 쥐에게 각각 투여하였을 때 수컷과 암컷 그룹 간에 체중 변화를 나타낸 것이다.
도 2는 각각의 샘플을 쥐에게 경구투여하고 45분 후 hyopnotic(45 mg/kg) 농도의 펜토바비탈(pentobarbital)을 쥐에게 복강주사로 투여하고 수면 잠재기(sleep latency)와 수면 지속기간(sleep duration)을 조사한 것이다. *은 대조구와 비교하여 p<0.05에서 유의적 차이가 있고, **은 대조구와 비교하여 p<0.01에서 유의적 차이가 있다(Dunnet's test).
Contr: 대조구(0.5% CMC-saline 10 ml/kg을 경구투여 후 펜토바비탈(pentobarbital) 투여)
DZP: 다이아제팜(diazepam) 2 mg/kg을 경구투여 후 펜토바비탈(pentobarbital) 투여
LE: 감초 에탄올 추출물 경구투여 후 펜토바비탈(pentobarbital) 투여
SE: 합환피 에탄올 추출물 경구투여 후 펜토바비탈(pentobarbital)을 투여
도 3은 유의적으로 효과를 나타내지 않은 250 mg/kg의 감초 및 합환피 에탄올 추출물을 혼합하여 쥐에게 경구투여하고 45분 후 hyopnotic(45 mg/kg) 농도의 펜토바비탈(pentobarbital)을 쥐에게 복강주사로 투여하고 수면 잠재기(sleep latency)와 수면 지속기간(sleep duration)을 조사한 것이다. *은 대조구와 비교하여 p<0.05에서 유의적 차이가 있고, **은 대조구와 비교하여 p<0.01에서 유의적 차이가 있다(Dunnet's test).
DZP: 다이아제팜(diazepam) 0.5 mg/kg을 경구투여 후 펜토바비탈(pentobarbital) 투여
LE: 감초 에탄올 추출물 경구투여 후 펜토바비탈(pentobarbital) 투여
SE: 합환피 에탄올 추출물 경구투여 후 펜토바비탈(pentobarbital)을 투여
도 4는 각각의 샘플을 쥐에게 경구투여하고 45분 후 hyopnotic(45 mg/kg) 농도의 펜토바비탈(pentobarbital)을 쥐에게 복강주사로 투여하고 수면 잠재기(sleep latency)와 수면 지속기간(sleep duration)을 조사한 것이다. *은 대조구와 비교하여 p<0.05에서 유의적 차이가 있고, **은 대조구와 비교하여 p<0.01에서 유의적 차이가 있다(Dunnet's test).
DZP: 다이아제팜(diazepam) 2 mg/kg을 경구투여 후 펜토바비탈(pentobarbital) 투여
LE: 감초 에탄올 추출물 경구투여 후 펜토바비탈(pentobarbital) 투여
SE: 합환피 에탄올 추출물 경구투여 후 펜토바비탈(pentobarbital)을 투여
도 5는 각각의 샘플을 쥐에게 경구투여하고 45분 후 hyopnotic(45 mg/kg) 농도의 펜토바비탈(pentobarbital)을 쥐에게 복강주사로 7일간 연용 투여하고 수면 잠재기(sleep latency)와 수면 지속기간(sleep duration)을 조사한 것이다. *은 대조구와 비교하여 p<0.05에서 유의적 차이가 있고, **은 대조구와 비교하여 p<0.01에서 유의적 차이가 있다(Dunnet's test).
Contr: 대조구(7일 동안 0.5% CMC-saline 10 ml/kg을 경구투여 후 펜토바비탈(pentobarbital) 투여)
DZP: 7일 동안 다이아제팜(diazepam) 0.5 mg/kg을 경구투여 후 펜토바비탈(pentobarbital) 투여
LE: 7일 동안 감초 에탄올 추출물 경구투여 후 펜토바비탈(pentobarbital) 투여
SE: 7일 동안 합환피 에탄올 추출물 경구투여 후 펜토바비탈(pentobarbital)을 투여
도 6은 감초 및 합환피 에탄올 추출물을 혼합하여 각 농도별로 쥐에게 경구투여하고 6시간 동안 수면 뇌파를 측정하여 수면 잠재기(sleep latency)와 측정시간동안의 Wake time, NREM(non-rapid-eye movement) time 및 REM(rapid-eye movement) time을 조사한 것이다. **와 ***은 대조구와 비교하여 각각 p<0.01 및 p<0.005에서 유의적 차이가 있다(Dunnet's test).Figure 1 shows the weight change between male and female groups when the licorice extract (GUE), Haphwanpi extract (AJE) and licorice extract + combined extract (Combination) to the mice, respectively.
Figure 2 is oral administration of each sample to the rat 45 minutes after hyopnotic (45 mg / kg) pentobarbital (pentobarbital) administered to the rat intraperitoneal injection, sleep latency (sleep latency) and sleep duration (sleep) duration). * Has a significant difference at p <0.05 compared to the control, ** has a significant difference at p <0.01 compared to the control (Dunnet's test).
Contr: control (pentobarbital administration after oral administration of 10 ml / kg of 0.5% CMC-saline)
DZP: pentobarbital administration after oral administration of 2 mg / kg of diazepam
LE: Pentobarbital administration after oral administration of licorice ethanol extract
SE: Pentobarbital administered after oral administration of combined ethanol extract
FIG. 3 shows oral administration of 250 mg / kg licorice and mixed skin ethanol extracts, which had no significant effect, orally to rats, and pentobarbital with hyopnotic (45 mg / kg) concentration after 45 minutes. It was administered by intraperitoneal injection and examined the sleep latency and sleep duration. * Has a significant difference at p <0.05 compared to the control, ** has a significant difference at p <0.01 compared to the control (Dunnet's test).
DZP: Pentobarbital administration after oral administration of 0.5 mg / kg of diazepam
LE: Pentobarbital administration after oral administration of licorice ethanol extract
SE: Pentobarbital administered after oral administration of combined ethanol extract
Figure 4 is oral administration of each sample to the rat 45 minutes after hyopnotic (45 mg / kg) pentobarbital (pentobarbital) administered to the rat intraperitoneal injection and sleep latency (sleep latency) and sleep duration (sleep) duration). * Has a significant difference at p <0.05 compared to the control, ** has a significant difference at p <0.01 compared to the control (Dunnet's test).
DZP: pentobarbital administration after oral administration of 2 mg / kg of diazepam
LE: Pentobarbital administration after oral administration of licorice ethanol extract
SE: Pentobarbital administered after oral administration of combined ethanol extract
FIG. 5 is oral administration of each sample to rats, and 45 minutes after the administration of pentobarbital at a concentration of hyopnotic (45 mg / kg) to rats by intraperitoneal injection for 7 days, sleep latency and sleep duration Investigate the sleep duration. * Has a significant difference at p <0.05 compared to the control, ** has a significant difference at p <0.01 compared to the control (Dunnet's test).
Contr: control (pentobarbital administration after oral administration of 10 ml / kg of 0.5% CMC-saline for 7 days)
DZP: pentobarbital administration after oral administration of 0.5 mg / kg of diazepam for 7 days
LE: Pentobarbital administration after oral administration of licorice ethanol extract for 7 days
SE: Pentobarbital administered after oral administration of combined ethanol extract for 7 days
FIG. 6 is a mixture of licorice and mixed ethanol extract and orally administered to rats at different concentrations, and measuring sleep brain waves for 6 hours to measure sleep latency and Wake time and NREM (non-rapid-eye movement). ) time and rapid-eye movement (REM) time. ** and *** were significantly different at p <0.01 and p <0.005, respectively, compared to the control (Dunnet's test).
본 발명의 목적을 달성하기 위해, 본 발명은 유효성분으로 감초 추출물 및 합환피 추출물로 이루어진 군으로부터 선택되는 하나 이상의 추출물을 함유하는 수면개선용 조성물을 제공한다.In order to achieve the object of the present invention, the present invention provides a composition for improving sleep containing at least one extract selected from the group consisting of licorice extract and haphwanpi extract as an active ingredient.
상기 수면개선은 수면 잠재기(sleep latency)가 감소하고 수면지속기간(sleep duration)이 증가하는 효과일 수 있으나, 이에 제한되지 않는다.The sleep improvement may be an effect of decreasing sleep latency and increasing sleep duration, but are not limited thereto.
상기 감초 추출물은 감초 에탄올 추출물일 수 있으나, 이에 제한되지 않는다. 상기 감초 에탄올 추출물은 감초를 26~32% 에탄올로 38~44℃에서 10~14시간 동안 추출하여 제조할 수 있으며, 바람직하게는 감초를 29.3% 에탄올로 41.2℃에서 12시간 동안 추출하여 제조할 수 있다. 상기 추출 범위에서 감초를 추출하는 것은 감초 에탄올 추출물의 방사성 표지된 리간드(GABAA 결합; [3H] flumazenil)에 대한 결합 억제능(1 mg/ml 농도)과 에탄올 추출의 수율을 평가하였을 때 결정된 최적의 조건이기 때문이다.The licorice extract may be, but not limited to, licorice ethanol extract. The licorice ethanol extract may be prepared by extracting licorice with 26 to 32% ethanol at 38 to 44 ° C. for 10 to 14 hours, preferably licorice with 29.3% ethanol for 12 hours at 41.2 ° C. have. Extraction of licorice in the above extraction range is optimal when determined by evaluating the binding inhibitory activity (1 mg / ml concentration) to the radiolabeled ligand (GABA A binding; [ 3 H] flumazenil) and the yield of ethanol extraction of licorice ethanol extract. Because it is a condition of.
또한 상기 합환피 추출물은 합환피 에탄올 추출물일 수 있으나, 이에 제한되지 않는다. 상기 합환피 에탄올 추출물은 합환피를 52~62% 에탄올로 18~60℃에서 22~60시간 동안 추출하여 제조할 수 있으며, 바람직하게는 합환피를 60.3% 에탄올로 20℃에서 57.9시간 동안 추출하거나 또는 55% 에탄올로 58℃에서 24시간 동안 추출하여 제조할 수 있다. 상기 추출 범위에서 합환피를 추출하는 것은 합환피 에탄올 추출물의 방사성 표지된 리간드(5-HT2C 결합; [3H] mesulergine)에 대한 결합 억제능(1 mg/ml 농도)과 에탄올 추출의 수율을 평가하였을 때 결정된 최적의 조건이기 때문이다.In addition, the hwanhwanpi extract may be hwanhwanpi ethanol extract, but is not limited thereto. The hwanhwanpi ethanol extract may be prepared by extracting hwanhwanpi with 52-62% ethanol at 18-60 ° C. for 22-60 hours, preferably extracting hwanhwan-pi with 60.3% ethanol at 20 ° C. for 57.9 hours. Or extracted with 58% ethanol at 58 ° C. for 24 hours. Extracting the mononuclear bark in the extraction range evaluated the binding inhibitory activity (1 mg / ml concentration) and the yield of the ethanol extract against the radiolabeled ligand (5-HT 2C binding; [ 3 H] mesulergine) of the mononuclear bark ethanol extract. This is because it is an optimal condition determined.
상기 수면개선용 조성물에서 감초 추출물과 합환피 추출물의 혼합비율은 중량비 기준으로 2.5~3.5:0.5~1.5인 것을 특징으로 하며, 바람직하게는 감초 추출물과 합환피 추출물의 혼합비율은 중량비 기준으로 3:1인 것을 특징으로 한다. 감초 추출물과 합환피 추출물의 비율이 상기 범위를 벗어나는 경우에는 수면유도효과가 감소할 수 있기 때문이다.The mixing ratio of the licorice extract and haphwanpi extract in the sleep improvement composition is characterized in that 2.5 to 3.5: 0.5 to 1.5 by weight ratio, preferably the mixing ratio of licorice extract and haphwanpi extract 3: It is characterized by one. This is because when the ratio of licorice extract and haphwanpi extract is outside the above range, the sleep induction effect may be reduced.
본 발명의 수면 개선용 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 포함할 수 있다.The sleep improving composition of the present invention may include appropriate carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 수면 개선용 조성물의 약학적 투여 형태는 이들의 약학적 허용 가능한 염의 형태로도 사용될 수 있고, 또한 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다.Pharmaceutical dosage forms of the sleep improving composition of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.
본 발명에 따른 수면 개선용 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 수면 개선용 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함한 다양한 화합물 혹은 혼합물을 들 수 있다. 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 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 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(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The sleep improving composition according to the present invention is formulated in the form of powder, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories, and sterile injectable solutions, respectively, according to a conventional method. Can be used. Carriers, excipients and diluents that may be included in the composition for improving sleep include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Various compounds or mixtures, including cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may include at least one excipient such as starch, calcium carbonate and sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 수면 개선용 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 수면 개선용 조성물은 1일 0.0001 내지 100 mg/kg으로, 바람직하게는 0.001 내지 100 mg/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the sleep improving composition of the present invention depends on the condition and weight of the patient, the extent of the disease, the drug form, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the composition for improving sleep of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably at 0.001 to 100 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
본 발명의 수면 개선용 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관내 (intracerebroventricular) 주사에 의해 투여될 수 있다.The composition for improving sleep of the present invention can be administered to mammals such as mice, mice, livestock, humans by various routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명은 또한, 유효성분으로 감초를 26~32% 에탄올로 38~44℃에서 10~14시간 동안 추출하여 제조되는 감초 추출물 및 합환피를 52~62% 에탄올로 18~60℃에서 22~60시간 동안 추출하여 제조되는 합환피 추출물을 중량비 기준으로 2.5~3.5:0.5~1.5로 혼합하는 것을 특징으로 하는 수면개선용 조성물의 제조방법을 제공한다.The present invention is also a licorice extract prepared by extracting licorice with 26-32% ethanol at 38-44 ° C for 10-14 hours as an active ingredient, and 22-60 at 18-60 ° C with 52-62% ethanol. It provides a method for producing a composition for improving sleep, characterized in that the mixture of Hwanhwanpi extract prepared by extracting for a time by mixing 2.5 ~ 3.5: 0.5 ~ 1.5 by weight.
상기 수면개선용 조성물의 제조방법은 바람직하게는 유효성분으로 감초를 29.3% 에탄올로 41.2℃에서 12시간 동안 추출하여 제조되는 감초 추출물 및 합환피를 60.3% 에탄올로 20℃에서 57.9시간 동안 추출하거나 또는 55% 에탄올로 58℃에서 24시간 동안 추출하여 제조되는 합환피 추출물을 중량비 기준으로 3:1로 혼합하여 제조할 수 있다.Preferably, the method for preparing the composition for improving sleep is used for extracting licorice extract and Hwanhwanpi prepared by extracting licorice with 29.3% ethanol for 12 hours at 41.2 ° C for 57.9 hours at 20 ° C with 60.3% ethanol or The Hwanhwanpi extract prepared by extracting with 55% ethanol at 58 ° C. for 24 hours may be prepared by mixing 3: 1 by weight.
본 발명은 또한, 감초 추출물 및 합환피 추출물로 이루어진 군으로부터 선택되는 하나 이상의 추출물을 유효성분으로 함유하는 수면개선용 기능성 식품을 제공한다.The present invention also provides a functional food for improving sleep containing at least one extract selected from the group consisting of licorice extract and Haphwanpi extract as an active ingredient.
본 발명의 상기 수면개선용 추출물을 식품첨가물로 사용하는 경우, 상기 수면개선용 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 그의 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 추출물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.In the case of using the sleep improvement extract of the present invention as a food additive, the sleep improvement extract may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. The blending amount of the active ingredient can be suitably determined according to the purpose of its use (prevention, health or therapeutic treatment). Generally, in the preparation of food or beverages, the extract of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less with respect to the raw material. However, in the case of long-term intake for health and hygiene or health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. .
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 식품을 모두 포함한다.There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all foods in a conventional sense.
본 발명의 기능성 음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 0.01~0.04 g, 바람직하게는 약 0.02~0.03 g 이다.The functional beverage composition of the present invention may contain various flavors, natural carbohydrates, and the like as additional components, as in general beverages. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as 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. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 수면개선용 조성물은 여러가지 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. 그 밖에 본 발명의 수면개선 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.
In addition to the above, the composition for improving sleep of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, Alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the sleep improvement composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can 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 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.
Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.
실시예Example 1: 감초와 1: licorice 합환피의Bloody 최적 추출 조건의 설정 Setting Optimal Extraction Conditions
1. 실험 디자인(Design of experiment) 1. Design of experiment
(1) 독립변수(Independent variables)의 설정(1) setting of independent variables
(a) 감마아미노부티르산(GABA, gamma-aminobutyric acid) 및 5-HT receptor binding assay에서 결합 능력(binding activity)이 높은 감초(licorice)와 합환피(silk tree)를 대상으로 결합억제능(binding inhibition of competitor(방사성 리간드))이 높은 에탄올 추출 조건을 최적화하기 위해 반응표면분석법을 활용하였다.(a) Gamma-aminobutyric acid (GABA) and binding inhibition of licorice and silk tree with high binding activity in gamma-aminobutyric acid (GABA) and 5-HT receptor binding assays. Response surface analysis was used to optimize the ethanol extraction conditions of the competitor (radioactive ligand).
(b) 영향요인인 독립변수는 에탄올 농도(X 1 , %, v/v), 추출 시간(X 2 , hr) 및 추출 온도(X 3 , ℃)로 설정하였으며, 예비실험을 통해 그 범위를 설정하였다(표 1).(b) Independent variables, which are the influence factors, were set to ethanol concentration ( X 1 ,%, v / v), extraction time ( X 2 , hr) and extraction temperature ( X 3 , ° C). It was set (Table 1).
(2) 종속변수(Dependent variables)의 설정(2) Set up dependent variables
(a) 독립변수들의 변화에 의해 결정되는 종속변수로는 1 mg/ml 농도에서의 방사성 표지된 리간드(GABAA 결합; [3H] flumazenil, 5-HT2C 결합; [3H] mesulergine)에 대한 결합 억제능(Y 1 , %)과 수율(Y 2, %)을 설정하였다(표 2).(a) Dependent variables determined by changes in independent variables include radiolabeled ligands (GABA A binding; [ 3 H] flumazenil, 5-HT 2C binding; [ 3 H] mesulergine) at a concentration of 1 mg / ml. Binding inhibition ( Y 1 , %) and yield ( Y 2 ,%) were set (Table 2).
(b) 최적화 조건의 설정은 결합억제능(Y 1, %)을 대상으로 수행되었으며, 수율(Y 2, %)은 활성변화에 따른 모니터링 자료로 활용하였다.
(b) The optimization condition was set for binding inhibitory activity ( Y 1, %), and the yield ( Y 2 ,%) was used as monitoring data according to activity change.
(3) 실험 디자인 및 통계처리(3) Experiment Design and Statistical Processing
(a) 실험디자인은 중심합성계획법(central composite design)에 의해 이루어졌으며 통계처리시의 오차를 줄이기 위해 실험구를 랜덤하게 선택하여 실험하였다(표 2).(a) The experimental design was made by central composite design, and the experiments were randomly selected to reduce the errors in statistical processing (Table 2).
(b) 통계처리는 MINITAB(Version 13, Minitab Inc., U.S.A.) 프로그램을 이용하여 실시하였다.(b) Statistical processing was performed using MINITAB (Version 13, Minitab Inc., U.S.A.) program.
No.Run
No.
X 1 : 에탄올 농도(%, v/v), X 2 : 추출시간(hr), X 3 : 추출 온도(℃) X 1 : Ethanol concentration (%, v / v), X 2 : Extraction time (hr), X 3 : Extraction temperature (℃)
Y 1 : 1 mg/ml 농도에서의 결합억제능(%), Y 2 : 수율(%)
Y 1 : binding inhibition (%) at 1 mg / ml concentration, Y 2 : yield (%)
2. 반응표면 모델식(Response surface model equation) 확립 및 평가2. Establishment and evaluation of Response surface model equation
(1) 반응표면 모델식의 확립(1) Establishment of response surface model
(a) 반응표면 모델식은 유의성이 없는 항들을 제외하고 종속변수에 대해 영향을 미치는 요인들로만 확립하여 표 3에 나타내었다.(a) The response surface model is shown in Table 3 by establishing only the factors influencing the dependent variables, except for terms that are not significant.
(b) 감초, 합환피의 결합억제능 및 수율이 3개의 독립변수들에 대해 서로 다른 특성으로 영향을 받는 것을 알 수 있었다.
(b) It was found that licorice, binding inhibitory activity, and yield of the combined skin were affected by different characteristics for the three independent variables.
(2) 반응표면 모델식의 평가(2) Evaluation of Response Surface Model
(a) 모델식의 통계적 유의성을 판단할 수 있는 결정계수(R 2) 및 유의수준(P-value)은 각각 0.9 이상 및 0.05 이하로 모델식이 통계적으로 타당하였다(표 3).(a) The coefficient of determination ( R 2 ) and the significance level ( P- value) for determining the statistical significance of the model equation were statistically justified as above 0.9 and below 0.05 (Table 3).
(b) 이는 예비실험을 통해 독립변수의 조건이 설정되었으며, 추출조건의 변화에 따라 결합억제능 및 수율이 일관된 특성을 가지고 반응하기 때문이다.(b) This is because the conditions of independent variables were established through preliminary experiments, and the binding inhibitory ability and yield responded with consistent characteristics according to the change of extraction conditions.
(Quadratic polynomial model)2nd order polynomial model
(Quadratic polynomial model)
감초
licorice
- 4.6947X 3 2 Y 1 = 82.5936 - 9.3057 X 1 - 4.6770
-4.6947 X 3 2
- 4.6000X 1 2 Y 2 = 30.1226-6.6783 X 1 + 2.4016 X 2
-4.6000 X 1 2
합환피
Blood
+ 0.8011X 3 - 1.6929X 1 2 - 0.5088X 2 2 Y 2 = 11.8843-1.2045 X 1 + 1.2494 X 2
+ 0.8011 X 3 -1.6929 X 1 2 0.5088 X 2 2
X 1 : 에탄올 농도(%, v/v), X 2 : 추출시간(hr), X 3 : 추출 온도(℃) X 1 : Ethanol concentration (%, v / v), X 2 : Extraction time (hr), X 3 : Extraction temperature (℃)
Y 1 : 1 mg/ml 농도에서의 결합억제능(%), Y 2 : 수율(%)
Y 1 : binding inhibition (%) at 1 mg / ml concentration, Y 2 : yield (%)
3. 독립변수(에탄올 농도, 시간, 온도)의 종속변수(결합억제능, 수율)에 대한 영향3. Influence of independent variables (ethanol concentration, time, temperature) on dependent variables (binding inhibition capacity, yield)
(1) 감초 (1) licorice
(a) 에탄올 농도(X 1): 결합억제능(Y 1) 및 수율(Y 2) 모두 농도에 가장 크게 영향을 받았으며, 농도가 낮을수록 최대가 되는 경향을 보여 산업적인 대량추출시 가격경쟁력을 확보할 수 있을 것으로 기대되었다.(a) Ethanol concentration ( X 1 ): Both binding inhibitory capacity ( Y 1 ) and yield ( Y 2 ) were most affected by the concentration, and the lower the concentration, the greater the tendency to be. It was expected to be possible.
(b) 추출 시간(X 2): 추출시간이 길어질수록 수율은 증가하는 반면에 결합억제능은 떨어져 추출시간이 길어질 경우 기능성분 외의 성분들이 추출되는 것을 알 수 있었다.(b) Extraction time ( X 2 ): As the extraction time increases, the yield increases, whereas the binding inhibitory activity is decreased, and when the extraction time is long, components other than the functional ingredient were extracted.
(c) 추출 온도(X 3): 결합억제능은 추출 온도가 상승할수록 증가하다가 40℃이상에서는 다시 감소하는 경향을 보였으며, 수율은 온도에 거의 영향을 받지 않았다.
(c) Extraction temperature ( X 3 ): The binding inhibitory activity increased with increasing extraction temperature and decreased again above 40 ℃, and yield was hardly affected by temperature.
(2) 합환피 (2) combined blood
(a) 에탄올 농도(X 1): 결합억제능은 전적으로 에탄올 농도에만 영향을 받는 것으로 나타났으며, 수율과 결합억제능 모두 농도의 변화에 따라 증가하다가 다시 감소하는 유사한 경향을 나타내었다.(a) Ethanol concentration ( X 1 ): The binding inhibitory activity was only affected by ethanol concentration, and both yield and binding inhibitory activity showed similar tendency to increase with decreasing concentration and then decrease again.
(b) 추출 시간(X 2): 결합억제능 및 수율 모두 추출시간이 길어질수록 증가하는 경향을 보였으나 상대적으로 농도에 대한 영향보다는 적게 나타났다.(b) Extraction time ( X 2 ): Both binding inhibition and yield tended to increase as the extraction time increased, but relatively less than the effect on concentration.
(c) 추출 온도(X 3): 추출온도가 높아질수록 결합억제능은 감소한 반면 수율은 증가하는 경향을 나타내었다.
(c) Extraction temperature ( X 3 ): As the extraction temperature increased, the binding inhibitory activity decreased but the yield increased.
4. 최적 추출조건의 설정 및 검증4. Setting and Verification of Optimal Extraction Conditions
(1) 최적 추출조건의 설정 (1) setting of optimum extraction conditions
(a) 각 원료의 에탄올 추출조건의 최적화는 결합억제능(Y 1)이 최대화되는 지점에서 설정되었으며, 수율(Y 2)도 함께 모니터링하여 최적조건에서의 수율을 함께 평가하였다.(a) Optimization of the ethanol extraction conditions of each raw material was set at the point where the binding inhibitory capacity ( Y 1 ) is maximized, and the yield ( Y 2 ) was also monitored to evaluate the yield at the optimum condition.
(b) 추출조건의 최적화는 미니텝(minitab) 프로그램의 response optimizer를 사용하였으며, 표 4에 그 결과를 실제값으로 변환하여 나타내었다.(b) The optimization of the extraction condition was performed using the minitab program's response optimizer, and the results were converted to actual values in Table 4.
(c) 감초의 최적조건은 X 1 = 29.3%, X 2 = 12.0 hr, X 3 = 41.2℃으로 나타났다.(c) The optimum condition of licorice is X 1 = 29.3%, X 2 = 12.0 hr, X 3 = 41.2 ° C.
(d) 합환피의 최적조건은 X 1 = 60.3%, X 2 = 57.9 hr, X 3 = 20℃으로 나타났다.(d) The optimal condition for the combined skin is X 1 = 60.3%, X 2 = 57.9 hr, X 3 = 20 ° C.
(e) 최적조건에서의 결합억제능의 최대값은 감초 92.98%, 합환피 99.36%로 산출되었으며, 이에 따른 수율은 감초 25.95%, 합환피 10.90%로 각각 통계적으로 예상되었다(표 4).
(e) The maximum value of the binding inhibitory activity under the optimum conditions was calculated as 92.98% licorice and 99.36% combined skin, and the yield was statistically expected to be 25.95% licorice and 10.90% combined skin (Table 4).
(2) 검증 (2) verification
(a) 최적조건에서 통계적으로 산출된 종속변수 결합억제능(Y 1)과 수율(Y 2)의 예상값을 최적조건으로 실제 실험을 통해 구한 값과 비교하여 검증하였다.(a) The predicted values of the dependent variable binding inhibitory capacity ( Y 1 ) and the yield ( Y 2 ), which were statistically calculated under the optimum conditions, were verified by comparing them with the values obtained through actual experiments as the optimum conditions.
(b) 결합억제능과 수율의 예상값 모두 실제 최적조건하의 추출물의 값들과 큰 차이를 보이지 않아 본 실험 디자인 및 최적화가 타당한 것으로 나타났다(표 4).(b) Both the expected inhibitory activity and yield were not significantly different from the values of the extracts under the actual optimum conditions, indicating that the experimental design and optimization were justified (Table 4).
감초
licorice
X 2 = 12.0 hr
X 3 = 41.2℃ X 1 = 29.3%
X 2 = 12.0 hr
X 3 = 41.2 ° C
합환피
Blood
X 2 = 57.9 hr
X 3 = 20℃ X 1 = 60.3%
X 2 = 57.9 hr
X 3 = 20 ° C
X 1 : 에탄올 농도(%, v/v), X 2 : 추출시간(hr), X 3 : 추출 온도(℃) X 1 : Ethanol concentration (%, v / v), X 2 : Extraction time (hr), X 3 : Extraction temperature (℃)
Y 1 : 1 mg/ml 농도에서의 결합억제능(%), Y 2 : 수율(%)
Y 1 : binding inhibition (%) at 1 mg / ml concentration, Y 2 : yield (%)
실시예Example 2: 감초 및 2: licorice and 합환피Blood 에탄올 추출물의 급성경구독성시험 Acute Oral Toxicity of Ethanol Extracts
1. 실험방법1. Experimental method
(1) 시험물질(1) Test substance
시험물질인 감초 및 합환피는 상기의 최적조건(감초: 30% 에탄올, 41℃, 12 hr; 합환피: 60% 에탄올, 20℃, 58 hr)에서 추출한 것을 사용하였다.
Licorice and mixed skin of test substance were the optimum conditions (Licorice: 30% ethanol, 41 ℃, 12 hr; Combined skin: 60% Ethanol, 20 ° C., 58 hr) was used.
(2) 시험동물 및 사육환경(2) Test animals and breeding environment
(a) ICR 마우스 수컷 및 암컷을 (주)오리엔트바이오에서 분양받아 실험동물용 사육 상자에 5마리씩 넣어 사육하여 1주일의 순화 사육기간 동안에 일반 증상 관찰을 시행하여 정상적으로 확인된 동물만 시험에 공시하였다.(a) Males and females of ICR mice were distributed in Orient Bio Co., Ltd., and 5 animals were placed in a breeding box for experimental animals. .
(b) 실험기간 동안 온도 23±1℃, 습도 55±5% 및 12시간 주기로 명암 주기(light/dark cycle)를 유지시켰으며, 식이는 자유로이 공급하였다.
(b) The light / dark cycle was maintained at a temperature of 23 ± 1 ° C., a humidity of 55 ± 5%, and a 12 hour period, and the diet was freely supplied.
(3) 시험물질 조제 및 투여 (3) Preparation and administration of test substance
(a) 적응 후 정상으로 판단된 동물에 대하여 체중을 측정하고 수컷 및 암컷으로 나누어 무작위적으로 실험군을 분리하였다. 실험동물의 개체식별은 피모색소표시법 및 사육상자별 태그(tag) 표시법을 이용하여 실시하였다.(a) Body weights were determined for normal animals after adaptation and divided into males and females. Individual identification of experimental animals was carried out using the hair coloring method and tag labeling method by breeding box.
(b) 시험물질의 농도는 1,500 mg/kg을 최대 용량으로 설정하고, 시험물질을 급여하지 않은 대조구와 함께 실험하였다.(b) The concentration of the test substance was set to 1,500 mg / kg at the maximum dose, and the experiment was conducted with the control group not fed the test substance.
(c) 시험물질은 급여 당일 0.5% CMC(carboxymethylcellulose)를 함유한 멸균 식염수에 적정 농도로 용해 및 현탁시킨 후 사용하였으며, 시험물질 현탁액은 시험동물에 경구투여하였다.
(c) The test substance was used after dissolving and suspending it in a suitable concentration in sterile saline containing 0.5% CMC (carboxymethylcellulose) on the day of feeding, and the test substance suspension was orally administered to the test animals.
(4) 관찰항목(4) Observation Items
(a) 모든 시험동물에 대하여 임상증상 관찰 및 사망 동물 수는 투여 직후부터 6시간 동안 매시간 관찰하였으며, 투여 익일부터 7일까지 1일 1회 동물의 일반 상태의 변화, 중독증상 및 사망유무를 관찰하였다.(a) Clinical signs and deaths of all animals were observed every hour for 6 hours immediately after administration, and the change in general condition, poisoning symptoms and death of the animals were observed once a day from the next day to 7 days after administration. It was.
(b) 시험에 사용된 모든 시험동물에 대하여 시험 물질 투여 직전, 투여 후 1일, 2일, 3일, 4일, 5일, 7일, 10일 및 14일에 1회씩 체중을 측정하였다.(b) All test animals used in the test were weighed once immediately prior to administration of the test substance, 1 day, 2 days, 3 days, 4 days, 5 days, 7 days, 10 days and 14 days after administration.
(c) 시험 종료 후 에테르(ether)로 마취하고 설하동맥 및 복부대동맥을 절단하여 치사시킨 다음 외관 및 내부장기의 이상 유무를 육안으로 상세히 관찰하였다.(c) After completion of the test, anesthesia with ether (ether), the sublingual artery and abdominal aorta were cut and lethal, and the appearance and internal organs were observed in detail visually.
2. 감초 및 2. Licorice and 합환피Blood 에탄올 추출물의 Of ethanol extract 급성경구독성Acute Oral Toxicity 시험결과 Test result
(1) 사망동물 및 임상증상 결과(1) Death animals and clinical symptoms
(a) 감초, 합환피 및 감초+합환피 추출물을 4주령의 ICR 마우스 암수 10마리로 구성된 각 시험군에서 1,500 mg/kg의 농도로 경구 투여하여 14일간 관찰하였다.(a) Licorice, Haphwanpi and Licorice + Hapwanpi extract were observed orally for 14 days by oral administration at a concentration of 1,500 mg / kg in each test group consisting of 10 male and female ICR mice at 4 weeks of age.
(b) 14일간 임상증상을 관찰하였을 때 특별한 의심증상 및 비특이적인 중독 증상 또한 나타나지 않았고, 대조구에 비해 진정효과를 나타내었으며, 다음날부터는 대조구와 마찬가지로 정상적인 움직임을 나타내었다.(b) When the clinical symptoms were observed for 14 days, no specific suspicious and nonspecific symptoms of intoxication were observed, and the sedative effect was compared with the control group.
(mg/kg)Dose
(mg / kg)
생존수final
Survival
(saline-CMC)Control
(saline-CMC)
(75:25, w/w)GUE + AJE
(75:25, w / w)
GUE: 감초 에탄올 추출물GUE: Licorice Ethanol Extract
AJE: 합환피 에탄올 추출물
AJE: Hwanhwan Phi Ethanol Extract
(2) 체중 측정(2) weight measurement
시험물질 투여군과 대조구 모두 시험기간 14일 동안 정상적인 체중의 증가를 보였으며, 수컷 및 암컷 그룹 간의 체중 변화율도 차이를 보이지 않았다(도 1).
Both the test substance-treated group and the control group showed normal weight gain during the 14 days of the test period, and there was no difference in the weight change rate between the male and female groups (FIG. 1).
(3) 육안적 해부소견(3) Visual anatomical findings
(a) 시험물질 투여 후 14일 후 시험 종료된 모든 동물을 대상으로 부검을 실시하였으나 특이할 만한 해부소견은 관찰되지 않았다.(a) An autopsy was performed on all animals that were terminated after 14 days of administration of the test substance, but no unusual anatomical findings were observed.
(b) 감초(GUE), 합환피(AJE) 및 감초+합환피 혼합물(GUE+AJE) 그룹들과 대조구를 비교한 결과 특이한 증상은 없었으며, 시험물질 1,500 mg/kg은 사람 체중 60 kg의 경우 90 g에 해당되는 고농도이다.
(b) Comparison of the control group with the licorice (GUE), mixed liquorice (AJE) and licorice + mixed extract (GUE + AJE) groups showed no specific symptoms, and 1,500 mg / kg of the test substance weighed 60 kg of human body weight. In case of high concentrations equivalent to 90 g.
실시예Example 3: 수면유도효과 3: sleep induction effect
1. 실험방법1. Experimental method
(1) 실험재료 (1) Experimental material
실험에 사용한 감초(Glycyrrhiza uralensis Fisher)는 30% 에탄올로 41℃에서 12시간 동안 추출하였고, 합환피(Albizzia julibrissin Durazzini)는 60% 에탄올로 20℃에서 58시간 동안 추출하였다. 추출 후 여과지로 여과한 후 농축기로 감압농축 하였다. 이 농축액을 동결건조 후 분말화하여 실험에 사용하였다.
Licorice Used in Experiments ( Glycyrrhiza uralensis Fisher) extracted with 30% ethanol for 12 hours at 41 ℃, 60% for Albizzia julibrissin Durazzini Extracted with ethanol at 20 ° C. for 58 hours. After extraction, the resultant was filtered with filter paper and concentrated under reduced pressure with a concentrator. The concentrate was lyophilized and then powdered and used in experiments.
(2) 실험동물(2) experimental animals
무게 18-22 g의 수컷 ICR 생쥐를 사육상자에 5마리씩 넣어 실험에 사용되었다. 사육온도는 23±1℃, 습도 55± 5%, 배기 10~18회/hr, 형광등 명암 12 hr cycle(light on at 7:00 am), 조도 300~500 Lux의 조건하에 새로운 환경에 적응시키기 위해 실험 전 1주일간 동물실에 사육되었다. 사료 및 음수는 자유롭게 섭취하게 하였다. 모든 동물들은 KFRI-IACUC (Korea Food Research Institute - Institutional Animal Care and Use Committee)에 의거한 실험동물 사용지침에 의해 사육되었다.
Male ICR mice weighing 18-22 g were placed in breeding boxes and used in experiments. Breeding temperature is 23 ± 1 ℃, humidity 55 ± 5%,
(3) 펜토바비탈(Pentobarbital) 유도 수면효과 분석(3) Analysis of pentobarbital induced sleep effect
모든 실험은 오후 1시에서 5시 사이에 진행되었고, 생쥐들은 실험 전 24시간 동안 절식시켰다. 0.5% carboxymethyl cellulose(Control-0.5% CMC-saline 10 ml/kg)에 희석된 모든 시료는 생쥐에게 펜토바비탈(pentobarbital) 투여 45분 전에 경구투여(p.o.)되었으며, 한 그룹당 15마리의 생쥐를 사용하였다. 잘 알려진 수면제 중 하나인 diazepam은 효과를 가늠하기 위한 대조 약물로서, 펜토바비탈(pentobarbital) 투여 45분 전에 경구투여(p.o.)되었다. 수면을 유도하기 위해 각각 생쥐에게 복강주사(i.p.)되어 수면 잠재기(sleep latency)와 수면 지속기간(sleep duration)을 측정하였다. 펜토바비탈(pentobarbital)을 생쥐에게 복강 내 주사한 뒤부터 등으로 바닥에 기대어 있다가 두위반사를 상실할 때까지의 경과시간을 수면 잠재기(sleep latency)라고 간주하였고, 상자 안의 생쥐 중 펜토바비탈(pentobarbital) 투여 3분 안에 움직임이 멈춘 것, 즉 개체가 3분 이상 움직임이 없을 때에는 잠든 것으로 간주하였다. 동물들은 지속적으로 관찰되었으며, 수면 지속기간(sleep duration)은 생쥐가 상자에 옮겨진 뒤 움직임이 없을 때부터 자율행동을 회복하기까지의 시간으로 간주하였다. sub-hypnotic dosage of pentobarbital-treated 실험에서 수면 개시(sleep onset) 계산 방법은 아래의 식(1)과 같다.All experiments took place between 1 and 5 pm and mice were fasted for 24 hours before the experiment. All samples diluted in 0.5% carboxymethyl cellulose (Control-0.5% CMC-
(1) 수면 개시(sleep onset, %)=No. falling asleep / Total No. × 100
(1) Sleep onset (%) = No. falling asleep / Total No. × 100
(4) 수면구조 분석(4) sleep structure analysis
1주일간 안정화시킨 male SD rat을 마취시킨 후 뇌정위기에 고정하고, 두피를 절개하여 skull에 3개의 뇌파(EEG) 전극과 목 표피 안쪽 근육에 2개의 근전도도(EMG) 전선을 삽입하였다. 치과치료용 cement를 사용하여 수술부위를 고정하고 봉합한 후 항생제를 투여하였다. 수술 후 일주일간 회복 및 5일간 적응을 시킨 후 실험에 사용하였다. 추출물을 경구투여 한 다음 뇌파 측정 챔버에 넣고 6시간 동안 기록하였다. 수면구조의 분석은 SleepSign software(Kissei Comtec Co., Japan)를 사용하였다.
After stabilizing male SD rats for 1 week, anesthesia was fixed to the brain stereotactic region, and the scalp was dissected to insert three electroencephalogram (EEG) electrodes into the skull and two EMG wires into the inner muscles of the neck epidermis. Dental cement was used to fix the surgical site, suture, and then receive antibiotics. One week after surgery and 5 days of adaptation were used for the experiment. The extract was orally administered, and then placed in an EEG chamber and recorded for 6 hours. Sleep structure analysis was performed using SleepSign software (Kissei Comtec Co., Japan).
(5) 통계분석(5) Statistical analysis
모든 실험의 결과는 평균과 표준오차(mean±S.E.M)로 나타내었고, 각 군과 대조구와의 통계적인 비교는 Dunnet's test에 의한 One-way analysis of variance(ANOVA)를 통해 평가하였다. 유의수준의 표시는 P<0.05(*), P<0.01(**) 수준에서 유의성이 보이는 결과를 별표로 표시하였다.
The results of all experiments were expressed as mean and standard error (mean ± SEM), and statistical comparison between each group and control was evaluated by one-way analysis of variance (ANOVA) by Dunnet's test. The significance level was marked with an asterisk for the results showing significance at P <0.05 (*) and P <0.01 (**) levels.
2. 결과 및 고찰2. Results and Discussion
(1) 펜토바비탈(pentobarbital), 다이아제팜(DZP)과 감초 추출물 및 합환피 추출물의 직접적인 수면유도효과 비교(1) Comparison of direct sleep induction effects of pentobarbital, diazepam (DZP), licorice extract, and Hwanhwanpi extract
예비실험으로 펜토바비탈(pentobarbital)의 정확한 hypnotic과 sub-hypnotic 농도를 알아보기 위해 펜토바비탈(pentobarbital)을 25~50 mg/kg(i.p.)의 여러 농도로 수면유도효과를 알아본 결과, 펜토바비탈(pentobarbital)의 hypnotic 농도는 45 mg/kg이였으며, sub-hypnotic 농도는 30 mg/kg 이였다. 펜토바비탈(pentobarbital)을 생쥐에게 hyopnotic(45 mg/kg, i.p.) 농도로 복강주사 하였을 때 생쥐 15마리 모두 펜토바비탈(pentobarbital)에 의한 수면유도 효과를 나타내었으나, 펜토바비탈(pentobarbital)의 sub-hypnotic(30 mg/kg, i.p.) 농도에서는 모두 잠에 들지 않았고, 다이아제팜(2 mg/kg, p.o.) 역시 수면효과가 나타나지 않았다(표 7). 감초(LE)와 합환피(SE) 추출물에서도 높은 농도(1,000 mg/kg, p.o.)임에도 불구하고 수면유도 효과가 나타나지 않았다. 이는 다이아제팜, 감초, 합환피 추출물 단독으로는 아무리 높은 농도에서도 직접적인 수면을 유도하지 못한다는 것을 시사하며, 펜토바비탈(pentobarbital)을 이용하여 수면유도 하였을 때 수면유도 효과가 나타남을 알 수 있었다. As a preliminary experiment, to determine the exact hypnotic and sub-hypnotic concentrations of pentobarbital, pentobarbital was tested for sleep induction at various concentrations of 25-50 mg / kg (ip). The hypnotic concentration of pentobarbital was 45 mg / kg and the sub-hypnotic concentration was 30 mg / kg. When pentobarbital was intraperitoneally injected into mice with hyopnotic (45 mg / kg, ip) concentrations, all 15 mice showed sleep-induced effects by pentobarbital, but the pentobarbital All sub-hypnotic (30 mg / kg, ip) concentrations did not fall asleep, and diazepam (2 mg / kg, po) also showed no sleeping effect (Table 7). Licorice (LE) and Haphwanpi (SE) extracts did not show any sleep induction effect despite the high concentration (1,000 mg / kg, p.o.). This suggests that diazepam, licorice, and Haphwanpi extract alone do not induce direct sleep at high concentrations, and sleep-induced effects are seen when pentobarbital is used.
Pentobarbital: 펜토바비탈Pentobarbital: Pentobarbital
DZP: 다이아제팜(diazepam)DZP: diazepam
LE: 감초 에탄올 추출물LE: Licorice Ethanol Extract
SE: 합환피 에탄올 추출물
SE: Hailhwan ethanol extract
(2) 펜토바비탈의 hypnotic dose에 의해 유도된 쥐에서 감초, 합환피 추출물의 수면유도효과 (2) Sleep-Induced Effects of Licorice and Hawanhwan Extracts in Mice Induced by Hypnotic Dose of Pentobarbital
감초(LE)와 합환피(SE) 추출물을 100, 250, 500, 1,000 mg/kg의 농도로 경구투여 후 펜토바비탈(pentobarbital, 45 mg/kg, 복강주사)에 의한 수면유도 효과를 알아본 결과, 농도 의존적으로 수면 잠재기(sleep latency)는 감소하고 수면 지속기간(sleep duration)은 증가하였다. 감초(LE)와 대조 그룹을 비교하였을 때, 1000 mg/kg의 농도에서 수면 지속기간은 유의적(p<0.05)으로 증가하였으며, 수면 잠재기는 유의적(p<0.01)으로 감소하였다. 합환피(SE)에서는 500(p<0.05)과 1,000 (p<0.01) mg/kg에서 유의적인 수면증진효과가 나타났다. 하지만 낮은 농도(100, 250 mg/kg)에서는 감초(LE)와 합환피(SE) 추출물 모두 유의적으로 수면효과가 나타나지 않았다. 반면, 다이아제팜(2 mg/kg, 경구투여)은 유의적으로 펜토바비탈(pentobarbital)에 의한 수면유도효과가 크게 나타났다(도 2).
The effects of sleep induction by pentobarbital (pentobarbital, 45 mg / kg, intraperitoneal injection) after oral administration of licorice (LE) and Haenghwanpi (SE) extracts at concentrations of 100, 250, 500, and 1,000 mg / kg As a result, the sleep latency decreased and the sleep duration increased in a concentration-dependent manner. When compared with licorice (LE), the sleep duration increased significantly ( p <0.05) and the sleep potential decreased significantly ( p <0.01) at a concentration of 1000 mg / kg. In Hwanhwanpi (SE), 500 ( p <0.05) and 1,000 ( p <0.01) mg / kg showed significant sleep-promoting effects. However, at low concentrations (100, 250 mg / kg), both licorice (LE) and Haphwanpi (SE) extracts showed no significant sleep effect. On the other hand, diazepam (2 mg / kg, oral administration) significantly showed a significant sleep induction effect by pentobarbital (Fig. 2).
(3) 펜토바비탈의 sub-hypnotic dose에 의해 유도된 쥐에서 감초, 합환피 추출물의 수면유도효과(3) Sleep-Induced Effects of Licorice and Hapwanpi Extract in Rats Induced by Sub-hypnotic Dose of Pentobarbital
감초(LE)와 합환피(SE) 추출물이 sub-hypnotic 농도의 펜토바비탈(pentobarbital, 30 mg/kg, 복강주사)에 의한 수면 개시(sleep onset)와 수면유도효과에 미치는 영향을 표 8에 나타내었다. 실험결과, sub-hypnotic 농도의 펜토바비탈(pentobarbital)에서는 대조 그룹의 생쥐 15마리 모두 잠에 들지 않았지만, 다이아제팜(DZP, 2 mg/kg, 경구투여)은 수면 개시(sleep onset)가 93%로 가장 높게 측정되었으며, 15마리 중 14마리가 수면상태에 들었다. 감초(LE)와 합환피(SE) 추출물에서는 농도 의존적으로 수면 개시(sleep onset)의 증가와 수면 지속기간(sleep duration)의 증가가 나타났으며, 특히, 1,000 mg/kg의 농도에서 수면 개시(sleep onset)가 감초와 합환피 추출물 각각 80%와 67%로 측정되었다. The effects of licorice (LE) and hawanpi (SE) extracts on the sleep onset and sleep induction effects of pentobarbital (30 mg / kg, intraperitoneal) at sub-hypnotic concentrations are shown in Table 8. Indicated. As a result, all 15 mice in the control group did not fall asleep in sub-hypnotic pentobarbital, but diazepam (DZP, 2 mg / kg, oral administration) had a 93% sleep onset. Was the highest, and 14 of the 15 were sleeping. Licorice (LE) and Hawanpi (SE) extracts showed a concentration-dependent increase in sleep onset and sleep duration, especially at 1,000 mg / kg. sleep onset) was determined to be 80% and 67%, respectively.
asleep/TotalNo. falling
asleep / Total
Pentobarbital: 펜토바비탈Pentobarbital: Pentobarbital
DZP: 다이아제팜(diazepam)DZP: diazepam
LE: 감초 에탄올 추출물LE: Licorice Ethanol Extract
SE: 합환피 에탄올 추출물
SE: Hailhwan ethanol extract
(4) 감초와 합환피 추출물의 병용경구투여에 대한 펜토바비탈(pentobarbital) 수면유도효과(4) Effects of Pentobarbital Sleep Induction on Concomitant Oral Administration of Licorice and Hawanhwan Extracts
감초(LE)와 합환피(SE) 추출물의 병용경구투여에 대한 수면효과를 알아보기 위해 유의적으로 펜토바비탈(pentobarbital) 수면유도효과에 영향을 주지 않을 만큼의 낮은 농도인 250 mg/kg을 각각 선택하였다. 감초(LE)와 합환피(SE) 추출물을 250 mg/kg의 농도로 수면유도효과를 보았을 때 수면 잠재기(sleep latency)와 수면지속기간(sleep duration)의 효과가 나타나지 않았지만, 감초(LE)와 합환피(SE) 추출물을 병용경구 투여하여 수면유도효과를 보았을 때에는 수면 효과가 유의적으로 증가하였다(p<0.05). 감초(LE) 추출물과 DZP을 병용경구투여 하였거나, 합환피(SE) 추출물과 DZP을 병용경구투여 하였을 때 역시 sleep latency의 유의적인 감소와 sleep duration의 유의적인 증가가 나타났다. 하지만, DZP (0.5 mg/kg, p.o.)을 단독으로 경구투여 하였을 때에는 수면효과가 나타나지 않았다. 5개의 그룹 중 가장 수면증진효과가 뛰어난 그룹은 감초(LE) 추출물(250 mg/kg, p.o.)과 DZP (0.5 mg/kg, p.o.)을 병용경구투여 한 그룹이었다(도 3).
To investigate the sleep effect of the combined administration of licorice (LE) and Hawanhwanpi (SE) extracts, 250 mg / kg, which is low enough to not affect pentobarbital sleep induction effect, Each was selected. When the licorice (LE) and Hapwanpi (SE) extracts had a sleep induction effect of 250 mg / kg, there was no effect of sleep latency and sleep duration. When the combined extract was administered orally, the effect of sleep induction was significantly increased ( p <0.05). Oral administration of licorice (LE) extract and DZP or co-administration of combined extract (SE) extract and DZP also resulted in a significant decrease in sleep latency and a significant increase in sleep duration. However, when oral administration of DZP (0.5 mg / kg, po) alone did not show a sleeping effect. Among the five groups, the most excellent sleep promoting group was a group administered orally with licorice (LE) extract (250 mg / kg, po) and DZP (0.5 mg / kg, po) (FIG. 3).
(5) 감초와 합환피 혼합추출물의 비율에 따른 펜토바비탈(pentobarbital) 수면유도효과(5) Pentobarbital Sleep Induction Effects According to the Ratio of Licorice and Mixed Ring Extracts
감초(LE)와 합환피(SE) 혼합추출물의 비율을 달리한 병용 경구투여의 펜토바비탈(pentobarbital) 수면유도효과를 알아보기 위하여 감초(LE) 500 mg/kg과 합환피(SE) 500 mg/kg을 25:75, 50:50, 75:25의 비율로 혼합하여 혼합추출물을 제조하였다. 비율을 달리한 혼합추출물을 1,000 mg/kg의 농도로 펜토바비탈(pentobarbital)에 의한 수면유도효과를 알아본 결과, 감초(LE) 75: 합환피(SE) 25의 비율인 혼합추출물에서 높은 수면유도 효과를 나타내었다(p<0.01). 수면 잠재기(sleep latency)는 다이아제팜(2 mg/kg, p.o.)만이 유의성 있게 감소하였고(p<0.01), 혼합추출물에서는 큰 차이를 나타내지 않았다. 반면, 수면 지속기간(sleep duration)은 감초(LE)와 합환피(SE)의 비율에 관계없이 3 그룹의 혼합추출물에서 모두 유의성 있는 결과를 나타내었다(p<0.01). 이는 기존 단일 물질보다 물질들을 혼합하였을 때 높은 수면유도 효과가 나타나는 것으로 판단되며, 앞으로 감초(LE)와 합환피(SE) 혼합추출물을 이용한 기능성 식품으로서의 가능성을 시사하였다(도 4).
To investigate the pentobarbital sleep-induced effects of combined oral administration of licorice (LE) and mixed skin (SE) mixed extracts, 500 mg / kg of licorice (LE) and 500 mg of syrup (SE) / kg was mixed at a ratio of 25:75, 50:50, and 75:25 to prepare a mixed extract. As a result of examining the sleep induction effect of pentobarbital at a concentration of 1,000 mg / kg of mixed extracts having different ratios, it was found that high concentration in the mixed extract of licorice (LE) 75: combined skin (SE) 25 Induction effect was shown ( p <0.01). Sleep latency was significantly decreased in diazepam (2 mg / kg, po) only ( p <0.01), and there was no significant difference in the mixed extract. On the other hand, the sleep duration was significant in all three groups of mixed extracts regardless of the ratio of licorice (LE) and combined skin (SE) ( p <0.01). This is judged to have a high sleep induction effect when the substances are mixed than the existing single substance, suggesting the potential as a functional food using a mixture of licorice (LE) and haphwanpi (SE) in the future (Fig. 4).
(6) 감초와 합환피 추출물의 장기간 연용 투여에 대한 펜토바비탈(pentobarbital) 수면유도효과(6) Pentobarbital Sleep Induction Effect on Long-term Continuous Administration of Licorice and Hawanhwan Extracts
감초(LE)와 합환피(SE) 추출물의 장기간 연용 투여에 대한 수면효과를 알아보기 위해 유의적으로 펜토바비탈(pentobarbital) 수면유도효과에 영향을 주지 않을 만큼의 낮은 농도인 250 mg/kg을 각각 선택하였다. 감초(LE)와 합환피(SE) 추출물을 250 mg/kg의 농도로 7 일간 장기간 연용 투여에 대한 수면유도효과를 실험한 결과, 감초(LE)의 유의적인 수면 잠재기(sleep latency)의 감소(p<0.05)와 유의적인 수면 지속기간(sleep duration)이 유의적(p<0.01)으로 증가하였다. 반면에 합환피(SE)에 대한 수면유도효과는 나타나지 않았지만, 대조 그룹보다는 높은 수면 지속기간(sleep duration)과 낮은 수면 잠재기(sleep latency)를 보였다. 다이아제팜(0.5 mg/kg, p.o.) 역시 낮은 농도에서 장기간 연용 투여 하였을 때 감초(LE)와 마찬가지로 유의적인 수면 잠재기(sleep latency)의 감소(p<0.05)와 수면 지속기간(sleep duration)의 유의적인 증가(p<0.01)가 나타났으며, 본 연구에서 단일 물질을 낮은 농도에서 단독으로 경구투여 하였을 때 수면효과가 나타나지 않은 것에 비해 장기간 연용투여 하였을 때 유의적인 결과를 나타낸 것으로 보아 단일물질을 장기간 연용 투여하면 높은 수면증진효과가 나타날 것으로 판단된다(도 5).
To investigate the sleep effects of long-term continuous administration of licorice (LE) and Haphwanpi (SE) extracts, 250 mg / kg, a concentration low enough to not affect the pentobarbital sleep induction effect Each was selected. Experimental study on the sleep induction effect of long-term continuous administration of licorice (LE) and Hwanhwanpi (SE) extract at a concentration of 250 mg / kg showed a significant decrease in sleep latency of licorice (LE) ( p <0.05) and significant sleep duration were significantly increased ( p <0.01). On the other hand, there was no sleep inducing effect on SE, but it showed higher sleep duration and low sleep latency than the control group. Diazepam (0.5 mg / kg, po) also had significant decreases in sleep latency ( p <0.05) and sleep duration, as did licorice (LE) when administered at low concentrations for long-term use. A significant increase ( p <0.01) was observed, and in this study, when a single substance was administered orally at low concentrations alone, there was no significant sleep effect. When administered jointly, it is judged to have high sleep promoting effect (FIG. 5).
(7) 감초와 합환피 추출물의 투여에 따른 수면구조 분석(7) Sleep structure analysis according to the administration of licorice and Hawanhwan extract
감초(LE)와 합환피(SE) 추출물의 혼합물을 250 mg/kg, 500 mg/kg 및 1,000 mg/kg의 농도로 경구투여하고 수면구조를 분석한 결과, 용량의존적으로 수면 잠재기(sleep latency)가 감소하였으며, 총수면시간 및 NREM 수면시간이 증가하였다. 반면에 REM 수면시간은 추출물 투여에 유의적인 영향을 받지 않았다(도 6).The mixture of licorice (LE) and Haphwanpi (SE) extracts was orally administered at concentrations of 250 mg / kg, 500 mg / kg and 1,000 mg / kg, and the sleep structure was analyzed. Decreased and total sleep time and NREM sleep time increased. On the other hand, REM sleep time was not significantly affected by the extract administration (Fig. 6).
Claims (9)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20100051642 | 2010-06-01 | ||
| KR1020100051642 | 2010-06-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR101020245B1 true KR101020245B1 (en) | 2011-03-09 |
Family
ID=43938553
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020100079596A KR101020245B1 (en) | 2010-06-01 | 2010-08-18 | Composition for improving insomnia containing licorice extract and silk tree extract as effective components and production method thereof |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101020245B1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100465898B1 (en) * | 2002-07-10 | 2005-01-13 | 김성도 | Process for preparing beverage from silk tree extract |
-
2010
- 2010-08-18 KR KR1020100079596A patent/KR101020245B1/en active IP Right Grant
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100465898B1 (en) * | 2002-07-10 | 2005-01-13 | 김성도 | Process for preparing beverage from silk tree extract |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101336411B1 (en) | Novel use of rice extract for improving, preventing or treating sleep disorders, anxiety, or depression | |
| KR20120091995A (en) | Composition for invigorating GABAA-benzodiazepine receptor and composition having anxiolitic anti-convulsant anti-depressant and sleep-improving effect containing Brown Seaweed extract | |
| JP6100692B2 (en) | Sleep quality improver | |
| KR101906720B1 (en) | Composition comprising the combination extract of Lycium chinensis, Glycyrrhiza urlaensis FISCH, Foeniculum vulagare MILL, Glycine max MERR, and Pueraria thunbergiana BENTH for preventing and treating menopause-related disease and depression | |
| KR101336502B1 (en) | Novel use of rice bran extract or rice bran powder for improving, preventing or treating sleep disorders, anxiety, or depression | |
| KR101963141B1 (en) | Composition comprising extracts of Opuntia Ficus Indica, Momordica charantia and Passiflora incarnata for preventing or alleviating climacterium | |
| KR101775087B1 (en) | A composition for the prevention or treatment of stress or depression containing mulberrofuran G, sanggenon G and sanggenol A | |
| KR101468551B1 (en) | Composition containing extract of dendropanax morbifera the improvement and remedial of insominia | |
| KR101861784B1 (en) | A composition for improving, preventing and treating pulmonary disease comprising herb extract | |
| KR101690175B1 (en) | Pharmaceutical composition for preventing or treating insomnia comprising Angelica tenuissima extract | |
| JP2016153387A (en) | Sleep-improving agent | |
| CN114269364A (en) | Composition for inhibiting reduction of testosterone and/or dihydrotestosterone | |
| KR101910013B1 (en) | A composition for improving, preventing and treating of pain comprising herb extract | |
| KR101779536B1 (en) | Composition for treating sleep disorder and enhacning sleeping time containing polygonatum extract | |
| KR101020245B1 (en) | Composition for improving insomnia containing licorice extract and silk tree extract as effective components and production method thereof | |
| KR102241762B1 (en) | Composition for improving stress or depression comprising extract of Ishige foliacea | |
| KR20140119236A (en) | Composition for anxiolitic, anti-convulsant, anti-depressant or sleep-improving effect comprising shellfish extract as an effective component | |
| KR102122408B1 (en) | Composition for preventing, ameliorating or treating andropause syndrome comprising roasted Glycyrrhiza uralensis extract as effective component | |
| KR101769972B1 (en) | A composition for improving, preventing and treating pulmonary disease comprising herb extract | |
| KR102245027B1 (en) | Composition for improving sleep disorder containing lettuce and Scutellariae extract as an active ingredient | |
| KR101406529B1 (en) | Composition including an extract from Eurya emarginata for use in treating and preventing an anxiety | |
| KR20150005482A (en) | Composition containing extract of dendropanax morbifera the improvement and remedial of insominia | |
| US20210213081A1 (en) | Composition for preventing, amelioreating, or treating stress or depression comprising medicinal herb extract as effective ingredient | |
| TWI784169B (en) | Prevention or improvement agent for nocturnal frequent urination | |
| KR20120055159A (en) | A composition for reducing sleep induction time and prolonging sleeping time containing chrysanthemum indicum extract, and preparing method for the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| A302 | Request for accelerated examination | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20140808 Year of fee payment: 4 |
|
| FPAY | Annual fee payment |
Payment date: 20150602 Year of fee payment: 5 |
|
| FPAY | Annual fee payment |
Payment date: 20170102 Year of fee payment: 7 |
|
| FPAY | Annual fee payment |
Payment date: 20180220 Year of fee payment: 8 |
|
| FPAY | Annual fee payment |
Payment date: 20190408 Year of fee payment: 9 |
|
| FPAY | Annual fee payment |
Payment date: 20200102 Year of fee payment: 10 |