KR100948332B1 - Composition Comprising the Extracts of Lysimachia clethroides for Prevention and Treatment of Cardiovascular Diseases - Google Patents
Composition Comprising the Extracts of Lysimachia clethroides for Prevention and Treatment of Cardiovascular Diseases Download PDFInfo
- Publication number
- KR100948332B1 KR100948332B1 KR1020080005782A KR20080005782A KR100948332B1 KR 100948332 B1 KR100948332 B1 KR 100948332B1 KR 1020080005782 A KR1020080005782 A KR 1020080005782A KR 20080005782 A KR20080005782 A KR 20080005782A KR 100948332 B1 KR100948332 B1 KR 100948332B1
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- butanol
- vascular
- swimming
- prevention
- Prior art date
Links
- 239000000284 extract Substances 0.000 title claims abstract description 92
- 239000000203 mixture Substances 0.000 title claims abstract description 36
- 238000011282 treatment Methods 0.000 title claims abstract description 16
- 230000002265 prevention Effects 0.000 title claims abstract description 13
- 208000024172 Cardiovascular disease Diseases 0.000 title abstract description 22
- 244000261422 Lysimachia clethroides Species 0.000 title description 2
- 235000009773 Lysimachia clethroides Nutrition 0.000 title description 2
- 230000009182 swimming Effects 0.000 claims abstract description 95
- 230000000694 effects Effects 0.000 claims abstract description 46
- 230000002792 vascular Effects 0.000 claims abstract description 33
- 108010002998 NADPH Oxidases Proteins 0.000 claims abstract description 20
- 102000004722 NADPH Oxidases Human genes 0.000 claims abstract description 20
- 230000036541 health Effects 0.000 claims abstract description 12
- 206010048554 Endothelial dysfunction Diseases 0.000 claims abstract description 10
- 230000008694 endothelial dysfunction Effects 0.000 claims abstract description 10
- 239000004480 active ingredient Substances 0.000 claims abstract description 9
- 235000013376 functional food Nutrition 0.000 claims abstract description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 46
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 25
- 239000000287 crude extract Substances 0.000 claims description 23
- 240000001890 Ribes hudsonianum Species 0.000 claims description 15
- 235000016954 Ribes hudsonianum Nutrition 0.000 claims description 15
- 235000001466 Ribes nigrum Nutrition 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- 206010020772 Hypertension Diseases 0.000 claims description 9
- 102000008052 Nitric Oxide Synthase Type III Human genes 0.000 claims description 9
- 108010075520 Nitric Oxide Synthase Type III Proteins 0.000 claims description 9
- 150000001298 alcohols Chemical class 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 8
- 210000003556 vascular endothelial cell Anatomy 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 208000037803 restenosis Diseases 0.000 claims description 7
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 5
- 108010007843 NADH oxidase Proteins 0.000 claims description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims description 2
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims 3
- 239000012141 concentrate Substances 0.000 claims 2
- 241001137251 Corvidae Species 0.000 abstract description 78
- 230000036772 blood pressure Effects 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 6
- 230000008602 contraction Effects 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 210000000748 cardiovascular system Anatomy 0.000 abstract description 2
- 230000001747 exhibiting effect Effects 0.000 abstract description 2
- 230000033904 relaxation of vascular smooth muscle Effects 0.000 abstract description 2
- 235000013402 health food Nutrition 0.000 abstract 1
- 210000002464 muscle smooth vascular Anatomy 0.000 abstract 1
- 208000019553 vascular disease Diseases 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 238000012360 testing method Methods 0.000 description 17
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- 239000000843 powder Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 241000700159 Rattus Species 0.000 description 9
- 210000002889 endothelial cell Anatomy 0.000 description 9
- 210000002216 heart Anatomy 0.000 description 9
- 101800000733 Angiotensin-2 Proteins 0.000 description 8
- 102400000345 Angiotensin-2 Human genes 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 8
- 235000013361 beverage Nutrition 0.000 description 8
- 210000004204 blood vessel Anatomy 0.000 description 8
- 239000012091 fetal bovine serum Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 230000036542 oxidative stress Effects 0.000 description 8
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 7
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 7
- 239000002034 butanolic fraction Substances 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 230000002883 vasorelaxation effect Effects 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 210000000709 aorta Anatomy 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 210000004351 coronary vessel Anatomy 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000007758 minimum essential medium Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000003642 reactive oxygen metabolite Substances 0.000 description 6
- -1 butanol or the like Chemical class 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000002038 ethyl acetate fraction Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 206010019280 Heart failures Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- 208000029078 coronary artery disease Diseases 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 239000002044 hexane fraction Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000012454 non-polar solvent Substances 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 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 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- 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 3
- 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 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- 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 3
- 229930195725 Mannitol Natural products 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 3
- 229960004373 acetylcholine Drugs 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 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 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
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- PFTAWBLQPZVEMU-UKRRQHHQSA-N (-)-epicatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-UKRRQHHQSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- MQVRGDZCYDEQML-UHFFFAOYSA-N Astragalin Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(CO)O2)O)C(=O)C2=C(O)C=C(O)C=C2O1 MQVRGDZCYDEQML-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000034656 Contusions Diseases 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
- 206010012289 Dementia Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- OVSQVDMCBVZWGM-IDRAQACASA-N Hirsutrin Natural products O([C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1)C1=C(c2cc(O)c(O)cc2)Oc2c(c(O)cc(O)c2)C1=O OVSQVDMCBVZWGM-IDRAQACASA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- FVQOMEDMFUMIMO-UHFFFAOYSA-N Hyperosid Natural products OC1C(O)C(O)C(CO)OC1OC1C(=O)C2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 FVQOMEDMFUMIMO-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 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
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 239000002021 butanolic extract Substances 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 208000001848 dysentery Diseases 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- GXMWXESSGGEWEM-UHFFFAOYSA-N isoquercitrin Natural products OCC(O)C1OC(OC2C(Oc3cc(O)cc(O)c3C2=O)c4ccc(O)c(O)c4)C(O)C1O GXMWXESSGGEWEM-UHFFFAOYSA-N 0.000 description 2
- JPUKWEQWGBDDQB-QSOFNFLRSA-N kaempferol 3-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=CC(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O JPUKWEQWGBDDQB-QSOFNFLRSA-N 0.000 description 2
- 229940041476 lactose 100 mg Drugs 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
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- OVSQVDMCBVZWGM-QSOFNFLRSA-N quercetin 3-O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OVSQVDMCBVZWGM-QSOFNFLRSA-N 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 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
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-3',4',5,7-Tetrahydroxy-2,3-trans-flavan-3-ol Natural products C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- PFTAWBLQPZVEMU-ZFWWWQNUSA-N (+)-epicatechin Natural products C1([C@@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-ZFWWWQNUSA-N 0.000 description 1
- 229930013783 (-)-epicatechin Natural products 0.000 description 1
- 235000007355 (-)-epicatechin Nutrition 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- YNVZDODIHZTHOZ-UHFFFAOYSA-K 2-hydroxypropanoate;iron(3+) Chemical compound [Fe+3].CC(O)C([O-])=O.CC(O)C([O-])=O.CC(O)C([O-])=O YNVZDODIHZTHOZ-UHFFFAOYSA-K 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 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
- 241000397426 Centroberyx lineatus Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 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
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- RTATXGUCZHCSNG-TYSPDFDMSA-N Kaempferol-3-O-rutinoside Natural products OC1[C@H](O)[C@@H](O)C(C)O[C@H]1OCC1[C@@H](O)[C@@H](O)C(O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1 RTATXGUCZHCSNG-TYSPDFDMSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 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
- 208000037093 Menstruation Disturbances Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000021908 Myocardial disease Diseases 0.000 description 1
- RTATXGUCZHCSNG-QHWHWDPRSA-N Nicotiflorin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1 RTATXGUCZHCSNG-QHWHWDPRSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- YPWHZCPMOQGCDQ-UHFFFAOYSA-N Populnin Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=C2C(=O)C(O)=C(C=3C=CC(O)=CC=3)OC2=C1 YPWHZCPMOQGCDQ-UHFFFAOYSA-N 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 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
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000003975 animal breeding Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 210000002403 aortic endothelial cell Anatomy 0.000 description 1
- 210000003433 aortic smooth muscle cell 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
- YEESUBCSWGVPCE-UHFFFAOYSA-N azanylidyneoxidanium iron(2+) pentacyanide Chemical compound [Fe++].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.N#[O+] YEESUBCSWGVPCE-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- IFVTZJHWGZSXFD-UHFFFAOYSA-N biphenylene Chemical group C1=CC=C2C3=CC=CC=C3C2=C1 IFVTZJHWGZSXFD-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 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
- 244000309466 calf Species 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- LPTRNLNOHUVQMS-UHFFFAOYSA-N epicatechin Natural products Cc1cc(O)cc2OC(C(O)Cc12)c1ccc(O)c(O)c1 LPTRNLNOHUVQMS-UHFFFAOYSA-N 0.000 description 1
- 235000012734 epicatechin Nutrition 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 239000004744 fabric Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 235000020510 functional beverage Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin 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
- 238000010438 heat treatment Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- MSBHOJSEFZPTET-UHFFFAOYSA-N isorhamnetin 3-O-galactoside Natural products OCC1OC(OC2=C(Oc3c(O)ccc(O)c3C2=O)c4ccc(O)c(O)c4)C(O)C(O)C1O MSBHOJSEFZPTET-UHFFFAOYSA-N 0.000 description 1
- JDEHKSHYQXNASH-UHFFFAOYSA-N kaempferol-3-O-beta-D-glucopyranoside Natural products OCC1OC(COC2=C(Oc3cc(O)cc(O)c3C2=O)c4ccc(O)cc4)C(O)C(O)C1O JDEHKSHYQXNASH-UHFFFAOYSA-N 0.000 description 1
- ZZZILDYSXRHUNY-UHFFFAOYSA-N kaempferol-3-O-glucoside Natural products OC1OC(COC2=C(Oc3cc(O)cc(O)c3C2=O)c4ccc(O)cc4)C(O)C(O)C1O ZZZILDYSXRHUNY-UHFFFAOYSA-N 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
- 150000002632 lipids Chemical class 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- KNJDBYZZKAZQNG-UHFFFAOYSA-N lucigenin Chemical compound [O-][N+]([O-])=O.[O-][N+]([O-])=O.C12=CC=CC=C2[N+](C)=C(C=CC=C2)C2=C1C1=C(C=CC=C2)C2=[N+](C)C2=CC=CC=C12 KNJDBYZZKAZQNG-UHFFFAOYSA-N 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 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
- 239000012528 membrane Substances 0.000 description 1
- 231100000544 menstrual irregularity Toxicity 0.000 description 1
- 208000030159 metabolic disease Diseases 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
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- RTATXGUCZHCSNG-ZFDPGQBLSA-N nicotiflorin Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC2=C(c3ccc(O)cc3)Oc3c(c(O)cc(O)c3)C2=O)O1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1 RTATXGUCZHCSNG-ZFDPGQBLSA-N 0.000 description 1
- RTATXGUCZHCSNG-UHFFFAOYSA-N nicotiflorine Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=CC(O)=CC=2)=O)O1 RTATXGUCZHCSNG-UHFFFAOYSA-N 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229960002460 nitroprusside Drugs 0.000 description 1
- 235000015097 nutrients 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
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000036407 pain Effects 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
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 235000017807 phytochemicals Nutrition 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004069 plant analysis Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 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
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- KRXANNXAPJODKJ-UHFFFAOYSA-N quercetin 3-O-beta-D-glucopyranoside Natural products OCC1OC(COC2=C(Oc3cc(O)cc(O)c3C2=O)c4ccc(O)c(O)c4)C(O)C(O)C1O KRXANNXAPJODKJ-UHFFFAOYSA-N 0.000 description 1
- BBFYUPYFXSSMNV-UHFFFAOYSA-N quercetin-7-o-galactoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=C2C(=O)C(O)=C(C=3C=C(O)C(O)=CC=3)OC2=C1 BBFYUPYFXSSMNV-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000001991 scapula 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
- 210000003491 skin Anatomy 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000003595 thromboxanes Chemical class 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
- 210000005167 vascular cell Anatomy 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 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
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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)
-
- A—HUMAN NECESSITIES
- A47—FURNITURE; DOMESTIC ARTICLES OR APPLIANCES; COFFEE MILLS; SPICE MILLS; SUCTION CLEANERS IN GENERAL
- A47K—SANITARY EQUIPMENT NOT OTHERWISE PROVIDED FOR; TOILET ACCESSORIES
- A47K1/00—Wash-stands; Appurtenances therefor
- A47K1/08—Accessories for toilet tables, e.g. glass plates, supports therefor
- A47K1/09—Holders for drinking glasses, tooth brushes, hair brushes, or the like
-
- A—HUMAN NECESSITIES
- A46—BRUSHWARE
- A46B—BRUSHES
- A46B17/00—Accessories for brushes
- A46B17/06—Devices for cleaning brushes after use
- A46B17/065—Sterilising brushes; products integral with the brush for sterilising, e.g. tablets, rinse, disinfectant
-
- A—HUMAN NECESSITIES
- A47—FURNITURE; DOMESTIC ARTICLES OR APPLIANCES; COFFEE MILLS; SPICE MILLS; SUCTION CLEANERS IN GENERAL
- A47K—SANITARY EQUIPMENT NOT OTHERWISE PROVIDED FOR; TOILET ACCESSORIES
- A47K5/00—Holders or dispensers for soap, toothpaste, or the like
- A47K5/18—Holders or dispensers for soap, toothpaste, or the like for both soap and toothpaste or the like; in combination with holders for drinking glasses, toothbrushes, or the like ; Toothpaste dispensers; Dental care centers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/08—Radiation
- A61L2/10—Ultraviolet radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Dentistry (AREA)
- Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
본 발명은 큰까치수영 추출물을 포함하는 심혈관계 질환의 치료 및 예방을 위한 조성물에 관한 것으로서, 구체적으로 큰까치수영 추출물은 혈관질환의 주요원인인 NAD(P)H 옥시다제(oxidase)를 강력하게 저해하는 동시에, 혈관평활근 (vascular smooth muscle)의 수축과 이완을 조절하여 강력한 혈관이완 효과를 나타내어 혈압조절 및 혈관내피세포기능장애 (endothelial dysfunction)를 개선시키므로, 이를 유효성분으로 함유하는 조성물은 심혈관계 질환의 예방 및 치료를 위한 의약품 또는 건강기능식품으로 유용하게 이용될 수 있다.The present invention relates to a composition for the treatment and prevention of cardiovascular diseases, including a magpie swimming extract, specifically, a magpie swimming extract strongly inhibits NAD (P) H oxidase, which is a major cause of vascular disease. At the same time, it suppresses the contraction and relaxation of vascular smooth muscle, thereby exhibiting a strong vascular relaxation effect, thereby improving blood pressure control and endothelial dysfunction, and thus the composition containing it as an active ingredient has a cardiovascular system. It can be usefully used as a medicine or health functional food for the prevention and treatment of diseases.
큰까치수영, 심혈관계 질환, 혈관평활근, 의약품, 건강기능식품 Large magpie swimming, cardiovascular disease, vascular smooth muscle, medicine, health food
Description
본 발명은 큰까치수영 추출물을 포함하는 심혈관 질환의 예방 및 치료용 조성물 및 건강기능식품에 관한 것으로, 상세하게는 NAD(P)H 옥시다제(oxidase)를 직접적으로 저해하여 산화스트레스를 저해하고, 동시에 혈관내피형 산화질소 합성효소를 활성화시켜 혈관평활근의 수축과 이완을 조절함으로써 심혈관계 질환을 치료 및 예방하는 효과를 가진 큰까치수영 추출물을 유효성분으로 함유하는 것을 특징으로 한다.The present invention relates to a composition and a health functional food for preventing and treating cardiovascular disease, including a magpie swimming extract, specifically inhibiting oxidative stress by directly inhibiting NAD (P) H oxidase. At the same time, by activating the vascular endothelial nitric oxide synthase by controlling the contraction and relaxation of vascular smooth muscle, it characterized in that it contains a large magpie swimming extract having the effect of treating and preventing cardiovascular diseases as an active ingredient.
세계보건기구(WHO)의 통계에 의하면 1999 년 심혈관질환에 의한 세계 인구의 사망률이 30 % 이상이며 2010 년에는 선진국의 사망률 1 위의 질병이 될 것이고, 특히 일본, 한국 등 아시아의 증가율이 높다고 보고하고 있다. 이는 고령화 사회로의 접근, 식사 습관 등의 변화로 인한 관상동맥 질환 위험 인자 등의 증가로 인한 것으로 추정된다.According to the World Health Organization (WHO) statistics, the mortality rate of the world's population due to cardiovascular disease in 1999 is more than 30%, and in 2010, it will become the
내피세포 기능장애 (endothelial dysfunction)은 1990 년 고혈압 환자에서 비이상적인 혈관의 이완이 발견 (Panza JA et al ., New England Journal of Medecine, 323:22-27, 1990)된 이래 고혈압, 동맥경화, 고지혈증, 당뇨, 비만 등 매우 포괄적인 심혈관계 질환을 유발하는 주된 메커니즘이다 (Brunner H. et al ., J. Hypertens, 2005, 23:233-246). 내피세포는 심장, 혈관 및 림프관의 공동을 따라 줄지어 있는 상피세포로서, 주기능은 혈관확장신경 및 혈관수축신경 매개체를 생산하여 혈관긴장도 및 구조 모두를 조절한다.Endothelial dysfunction was found in 1990 for the release of abnormal blood vessels in hypertensive patients (Panza JA)et al ., New England Journal of Medecine, 323: 22-27, 1990.et al ., J. Hypertens, 2005, 23: 233-246). Endothelial cells are epithelial cells lining the cavity of the heart, blood vessels and lymphatic vessels. The main function is to produce vasodilator and vasoconstrictor mediators that regulate both vascular tone and structure.
심혈관계 질환은 초기 내피세포 기능장애를 시작으로 종래에는 심장 및 혈관계의 이상이 온 것으로서, 동맥경화, 고혈압, 고지혈, 관상동맥질환 (심장마비), 뇌혈관계 질환 (뇌졸증, 치매), 말초혈관질환, 부정맥, 심부전, 울혈성 심장질환, 심근질환 등을 포함하는 심장, 혈관의 이상의 그룹에 대한 명칭이나, 이에 제한되는 것은 아니다.Cardiovascular diseases, including early endothelial dysfunction, have conventionally caused abnormalities of the heart and vascular system, arteriosclerosis, hypertension, hyperlipidemia, coronary artery disease (heart failure), cerebrovascular diseases (stroke, dementia), peripheral vascular disease The names of the abnormal groups of the heart, blood vessels, including, but not limited to, arrhythmia, heart failure, congestive heart disease, myocardial disease, and the like.
심혈관계 질환 발현의 주요 인자로서는 유전적 요인, 생활습관, 당뇨의 합병증 등 매우 다양하게 알려져 있으나 현대의학에 관점에서 NAD(P)H 옥시다제 (NADH 또는 NADPH 옥시다제. 이하, 'NAD(P)H 옥시다제'라 함)의 활성 증가에 따른 활성산소종 (Reactive Oxygen Species, ROS)과 혈관내 산화성 스트레스의 증가 및 내피 세포형 산화질소 합성효소 (endothelial type Nitric Oxide Synthase, eNOS)의 활성감소로 인한 산화질소의 감소에 의한다고 알려져 있다. 내피 세포형 산화질소 합성효소에 의해 생성되는 산화질소는 강력한 혈관이완 인자인 동시에 혈소판 응집, 혈관근육세포 증식, 단핵구 세포의 혈관침착, 동맥경화 관련 단백질 발현을 저해하여 전체적인 심혈관계의 항상성 조절에 매우 중요한 역할을 한다 (Forstermann et al., Circulation, 113:1708-1714, 2006). 그러나 여러 가지 요인으로 인한 혈관내 활성산소종의 생성을 담당하는 NADPH 옥시다제의 활성증가로 인하여 산화질소의 생성은 감소하게 되고 [Gryglewski et al., Nature, 320:454-456, 1986; Paravicini et al., Circulation Research, 91:54-61, 2002; Dusting et al., Clinical and Experimental Pharmacology and Physiology, 25:S34-41, 1998], 또한 만들어진 활성산소종은 접착 분자 발현의 조절 [Lo et al., Am. J. Physiol., 264:L406-412, 1993], 혈관평활근세포 (VSMC, vascular smooth muscle cells)의 증식과 이동 자극 [Griendling and Ushio-Fukai, J. Lab. Clin. Med., 132:9-15, 1998], 산화력이 있는 지단백질(lipoprotein) 조절 등을 야기하여 심혈관계 질환을 발생시킨다 [Lynch and Frei, J. Lipid Res., 34:1745-1753, 1993]. 또한 NAD(P)H 옥시다제에 의하여 증가된 혈관의 활성산소종의 생성은 아테롬성 동맥경화의 임상적 위험 요소와 관상동맥 질환을 가진 환자의 손상된 내피세포의 산화질소(nitric oxide, NO) 기능과 관련이 있으며, 근원적으로 혈관의 수축을 야기한다 [Guzik et al., Cir. Res., 86:E85-90, 2000].Genetic factors, lifestyle, complications of diabetes mellitus, etc. are widely known as major factors in cardiovascular disease expression, but from the viewpoint of modern medicine, NAD (P) H oxidase (NADH or NADPH oxidase. Reactive Oxygen Species (ROS), Intravascular Oxidative Stress and Endothelial Nitric Oxide Synthase (eNOS) It is known to be due to the reduction of nitrogen oxides. Nitric oxide, produced by endothelial nitric oxide synthase, is a potent vasorelaxant and inhibits platelet aggregation, vascular muscle cell proliferation, monocyte deposition, and atherosclerosis-related protein expression, thereby regulating the overall homeostasis of cardiovascular system. Plays an important role (Forstermann et al. , Circulation, 113: 1708-1714, 2006). However, the increased production of NADPH oxidase, which is responsible for the generation of free radical species in blood vessels due to various factors, leads to a decrease in the production of nitric oxide [Gryglewski et al. , Nature, 320: 454-456, 1986; Paravicini et al. , Circulation Research, 91: 54-61, 2002; Dusting et al. , Clinical and Experimental Pharmacology and Physiology, 25: S 34-41, 1998], In addition, the produced reactive oxygen species regulate the expression of adhesion molecules [Lo et al. , Am. J. Physiol., 264: L406-412, 1993], stimulation of proliferation and migration of vascular smooth muscle cells [Vriendling and Ushio-Fukai, J. Lab. Clin. Med., 132: 9-15, 1998], causing oxidative lipoprotein regulation, resulting in cardiovascular disease (Lynch and Frei, J. Lipid Res., 34: 1745-1753, 1993). In addition, the generation of reactive oxygen species in blood vessels increased by NAD (P) H oxidase may be associated with the clinical risk factors of atherosclerosis and the nitric oxide (NO) function of damaged endothelial cells in patients with coronary artery disease. Related, causing root vessel contraction [Guzik et al. , Cir. Res., 86: E85-90, 2000].
종합적으로, NAD(P)H 옥시다제의 직접적인 저해를 통해 활성산소종을 감소, 활성산소종의 하류 발생 억제 및 내피세포형 산화질소 합성효소의 활성유도는 심혈관질환 예방 치료에 있어서 매주 중요한 타겟으로 인식되고 있다 [Forstermann et al ., Circulation, 113:1708-1714, 2006; Boggrell SA et al ., Drug News Perspect., 17(9)615-632, 2005; Inoguchi T., Curr. Drug Targets, 6(4):495-501, 2005; Muzaffar S. et al ., Trends Cardiovasc Med., 15(8):278-282].Overall, the reduction of reactive oxygen species through the direct inhibition of NAD (P) H oxidase, the inhibition of downstream generation of reactive oxygen species, and the induction of endothelial cell type nitric oxide synthase are important targets for the treatment of cardiovascular diseases every week. Recognized [Forstermann et al . , Circulation, 113: 1708-1714, 2006; Boggrell SA et al . , Drug News Perspect., 17 (9) 615-632, 2005; Inoguchi T., Curr. Drug Targets, 6 (4): 495-501, 2005; Muzaffar S. et al . , Trends Cardiovasc Med., 15 (8): 278-282].
현재까지 NAD(P)H 옥시다제를 저해하는 물질로는 디페닐렌 이오노듐 (diphenylene ionodium, DPI)와 호황련에서 추출된 4-히드록시-3-메톡시아세토포에논(4-hyroxy-3-methoxyacetopoenone, Apocyin) [Holland J., et al ., US609051] 이 있으나, 독성 및 특이성의 문제로 인하여 상업화 및 임상에 사용되고 있지는 않다. 또한 산화질소 조절제로서 니트로프루시드(nitroprusside), 니트로글리세린(nitroglycerine)이 존재하고 있으나 임상적 사용에서 내성 및 독성의 문제로 심장마비 등의 응급시에만 사용하고 있다.To date, substances that inhibit NAD (P) H oxidase include diphenylene ionodium (DPI) and 4-hydroxy-3-methoxyacetopoenone (4-hyroxy- 3-methoxyacetopoenone, Apocyin) [Holland J., et al . , US609051, but are not used in commercialization and clinical practice due to issues of toxicity and specificity. In addition, nitroprusside and nitroglycerine are present as nitric oxide regulators, but they are used only in emergencies such as heart attack due to resistance and toxicity in clinical use.
한편, 큰까치수영 (Lysimachia clethroides)는 앵초과에 속하는 여러해살이 풀이포서 양지에서 흔히 자라는 다년초이고 높이는 50-100 cm이며, 전국 각지에 야생하고, 일본, 만주, 중국에도 분포한다. 진주채라고도 불리며 여자의 월경불순, 백대, 소아의 감적, 수종, 이질, 타박상, 이후통 등을 치료한다고 알려져 있다. 민간에서는 월경불순, 이질, 타박상 치료에 오래전부터 사용되고 있으며 신맛이 강하므로 요리에 사용시 신맛을 살리는 음식에 쓰인다 [대한식물도감, 이창복 1980; 한국민간약도감, 박종희 2005; 향약대사전; 한국약용식물도감, 육창수, 1989, 자연초건강초, 권영한 2006).Meanwhile, magpie swimming ( Lysimachia clethroides ) is a perennial plant belonging to the perennial herbaceous genus, 50-100 cm high, wild throughout the country, and distributed in Japan, Manchuria, and China. Also known as nacre, it is known to treat women's menstrual irregularities, white bands, children's markers, edema, dysentery, bruises, and later pains. In the private sector, it has been used for a long time for the treatment of dysmenorrhea, dysentery, and bruises, and it is used for foods that make it sour when used in cooking. Korean Civil Guidebook, Park, Jong-Hee 2005; Fragrance dictionary; Korea Medicinal Plant Book, Chang-Soo Yuk, 1989, Nachochocho, Kwon Younghan 2006).
큰까치수영의 성분에 대한 연구로서는 아스트라갈린 (astragalin), 이소퀘르시트린 (isoquercitrin), 캠페롤-3-오-루티노시드 (kaempferol-3-O-rutinoside), 캠페롤-3-오-(2,6 - 디-오-람노피라노실글루코피라노시드 (kaempferol-3-O-(2,6-di-O-rhamnopyranosylglucopyranoside)), 캠페롤-3-오-(람노피라노실글루코피라노시드) (kaempferol-3-O-(rhamnopyranosylglucopyranoside)) 와 3-오-메틸-퀘르세틴-7-오-[알파-엘-람노피라노실(1-2)-베타-디-글루코피라노시드 ((3-O-methyl- quercetin-7-O-[alpha-L-rhamnopyranosyl(1-2)-beta-D-glucopyranoside)), (-)에피카테친 (epicatechin), 퀘르세틴-3-오-베타-디-글루코피라노시드 (quercetin-3-O-beta-D-glucopyranoside), 캠페롤-3-오-베타-디-글루코피라노시드 (kaempferol-3-O-beta-D-glucopyranoside), 캠페롤-3-오-[알파-엘-람노피라노실(1-6)-베타-디-글루코피라노시드 (kaempferol-3-O-[alpha-L-rhamnopyranosyl(1-6)-beta-D-glucopyranoside])가 분리 보고되었다 (Yasukawa K. et al., Yakugaku Zasshi, 106, 939, 1986; 김진숙등, 약학회지 4, 325-330, 1993). 큰까치수영 추출물, 분리성분들의 약리효과는 식중독 미생물에 대한 항균활성, 항암활성, 항산화 효과 등이 보고되었다 (한지숙 등, 한국식품과학회지, 33, 772-783, 2001; 배기환 등, 생약학회지, 27, 173-177, 1996; 이승은 등, 대한응용생화학회지, 47, 265-269, 2004). Studies on the components of magpie swimming include astragalin, isoquercitrin, kaempferol-3-O-rutinoside, and camphorol-3-o- ( Kaempferol-3-O- (2,6-di-O-rhamnopyranosylglucopyranoside), camphorol-3-o- (ramnopyranosylglucopyranoside) ) (kaempferol-3-O- (rhamnopyranosylglucopyranoside)) and 3-O-methyl-Quercetin-7-O- [alpha-L-ramnopyranosyl (1-2) -beta-di-glucopyranoside ((3 -O-methyl- quercetin-7-O- [alpha-L-rhamnopyranosyl (1-2) -beta-D-glucopyranoside)), (-) epicatechin (epicatechin), quercetin-3-o-beta-di- Glucopyranoside (quercetin-3-O-beta-D-glucopyranoside), camperol-3-O-beta-di-glucopyranoside (kaempferol-3-O-beta-D-glucopyranoside), camphorol- 3-O- [alpha-L-rhamnopyranosyl (1-6) -beta-di-glucopyranoside (kaempferol-3-O- [alpha-L-rhamnopyranosyl (1-6) -beta-D-glucopyranoside ]) Has been reported separately (Yasukawa K. et al., Yakugaku Zasshi, 106, 939, 1986; Kim, Jin-Sook, et al., Korean Journal of Pharmacy 4, 325-330, 1993). Antimicrobial activity, anticancer activity and antioxidant activity have been reported (Han Ji Sook et al., Korean Society of Food Science and Technology, 33, 772-783, 2001; Korean Journal of Pharmacognosy, 27, 173-177, 1996; Biochemical Journal, 47, 265-269, 2004).
상기 문헌 중 큰까치수영 추출물에 대한 NADPH 옥시다제 저해를 통한 혈관내 산화스트레스 억제, 직접적인 혈관 이완효과, 내피 세포형 산화질소 합성효소 활성증가 및 혈압조절 효과에 대해서는 어떠한 개시나 교시도 이루어진 바 없다. 다만, 이승은 등의 보고 (대한응용생화학회지, 47, 265-269, 2004)에 따르면 큰까치수영 추출물에 대해 안지오텐신 전환효소 활성 저해시험을 진행한 결과, 4000 ㎍/㎖의 고농도에서 조추출물이 약간의 활성을 나타내었고, 더욱이 n-부탄올 분획물이 안지오텐신 전환효소의 활성에 전혀 영향을 미치지 않고 오히려 활성을 증가 (34 % 증가)하는 것으로 결론지은 바 있다.No disclosure or teaching has been made about the inhibition of vascular oxidative stress, direct vascular relaxation effect, endothelial cell type nitric oxide synthase activity, and blood pressure regulating effect through inhibition of NADPH oxidase against the extracts of the magpies. However, according to the report of Lee Seung-eun et al. (Korean Journal of Applied Biological Chemistry, 47, 265-269, 2004), crude extracts were slightly inhibited at high concentrations of 4000 ㎍ / ㎖ after the angiotensin converting enzyme activity was tested on the magpie swimming extract. It was concluded that the n-butanol fraction had no effect on the activity of angiotensin converting enzyme but rather increased the activity (34% increase).
본 발명자들은 다수의 식물 추출물을 대상으로 NAD(P)H 옥시다제 활성저해 및 혈관이완 효과를 검색하던 중 큰까치수영 추출물의 강력한 NAD(P)H 옥시다제 활성저해, 혈관내 산화스트레스 감소, 직접적인 내피세포형 산화질소 합성효소 활성증강, 혈관이완 및 혈압조절 효과를 확인하여 본 발명을 완성하였다.We searched for a number of plant extracts to detect NAD (P) H oxidase inhibitory activity and vasorelaxant effect. Endothelial cell type nitric oxide synthase activity enhancement, confirming the effect of vascular relaxation and blood pressure to complete the present invention.
특히, 상기 이승은 등의 보고와는 상이하게 10 ㎍/㎖ 미만의 저농도에서 안지오텐신 저해효소와 관계없이 직접적으로 큰까치수영의 조추출물이 혈관이완 등의 효과를 지님을 확인하였고, 상기 효과는 n-부탄올 분획물에서 더욱 높아진다는 사실을 발견했다.In particular, Lee Seung-eun, unlike the report of et al. Confirmed that the crude extract of large magpie swimming directly at low concentrations of less than 10 ㎍ / ㎖ irrespective of angiotensin inhibitors, such as vascular relaxation, the effect is n- It was found to be higher in the butanol fraction.
본 발명은 상기와 같은 발견을 기초로 안출된 것으로서, 큰까치수영 추출물을 유효성분으로 함유하는 심혈관계 질환의 예방 및 치료용 조성물을 제공하는 것을 그 목적으로 한다.The present invention has been made on the basis of the above findings, and an object of the present invention is to provide a composition for the prevention and treatment of cardiovascular diseases containing the magpie swimming extract as an active ingredient.
본 발명은 또한 큰까치수영 추출물을 유효성분으로 함유하는 심혈관계 질환의 예방용 건강기능식품을 제공하는 것을 또 다른 목적으로 한다.It is another object of the present invention to provide a dietary supplement for the prevention of cardiovascular diseases, which contains a magpie swimming extract as an active ingredient.
본 발명의 심혈관계 질환의 예방 및 치료용 조성물은 상술한 바와 같은 목적을 달성하기 위하여 큰까치수영 추출물을 유효성분으로 함유하는 것을 특징으로 한다.The composition for the prevention and treatment of cardiovascular diseases of the present invention is characterized by containing a magpie swimming extract as an active ingredient in order to achieve the object as described above.
또한, 상기 큰까치수영 추출물은 잎 또는 전초를 사용하여 추출한 것이 바람 직하다.In addition, the magpie swimming extract is preferably extracted using leaves or outposts.
또한, 상기 큰까치수영 추출물은 물, C1 내지 C5의 저급알콜 및 그 혼합물로 이루어진 군에서 선택된 용매로 추출한 것이 바람직하다.In addition, the magpie swimming extract is preferably extracted with a solvent selected from the group consisting of water, C 1 to C 5 lower alcohols and mixtures thereof.
또한, 상기 C1 내지 C5의 저급알콜은 메탄올, 에탄올 또는 부탄올인 것이 바람직하다.In addition, the lower alcohol of C 1 to C 5 is preferably methanol, ethanol or butanol.
또한, 상기 큰까치수영 추출물은 30 내지 95 중량%의 에탄올 수용액으로 추출한 것이 바람직하다.In addition, the magpie swimming extract is preferably extracted with an aqueous ethanol solution of 30 to 95% by weight.
또한, 상기 큰까치수영 추출물은 물, C1 내지 C3의 저급알콜 및 그 혼합물로 이루어진 군에서 선택된 용매로 추출하고, 이를 부탄올로 재추출한 것이 바람직하다.In addition, the magpie swimming extract is extracted with a solvent selected from the group consisting of water, lower alcohols of C 1 to C 3 and mixtures thereof, and it is preferably extracted again with butanol.
또한, 상기 큰까치수영 추출물은 물, C1 내지 C3의 저급알콜 및 그 혼합물로 이루어진 군에서 선택된 용매로 추출 및 농축하여 조추출물을 수득하고, 상기 조추출물을 물에 현탁하고, 헥산, 에틸아세테이트, 및 부탄올 순으로 재추출한 것이 바람직하다.In addition, the magpie swimming extract is extracted with a solvent selected from the group consisting of water, C 1 to C 3 lower alcohols and mixtures thereof to obtain a crude extract, the crude extract is suspended in water, hexane, ethyl Preference is given to re-extracting in the order of acetate and butanol.
또한, 상기 큰까치수영 조추출물은 30 내지 95 ℃에서 수득되는 것이 바람직하다.In addition, the large magpie swimming crude extract is preferably obtained at 30 to 95 ℃.
또한, 상기 조추출물 : 물은 1 : 5 내지 25의 부피 비율로 혼합 현탁되는 것이 바람직하다.In addition, the crude extract: water is preferably mixed and suspended in a volume ratio of 1: 5 to 25.
또한, 상기 헥산, 에틸아세테이트 또는 부탄올 : 현탁액은 1 : 0.1 내지 2.0 의 부피 비율로 혼합 추출되는 것이 바람직하다.In addition, the hexane, ethyl acetate or butanol: suspension is preferably mixed and extracted in a volume ratio of 1: 0.1 to 2.0.
또한, 상기 부탄올은 n-부탄올인 것이 바람직하다.In addition, the butanol is preferably n-butanol.
또한, 상기 큰까치수영 추출물은 NAD(P)H 옥시다제 저해 활성을 갖는 것을 특징으로 한다.In addition, the magpie swimming extract is characterized by having NAD (P) H oxidase inhibitory activity.
또한, 상기 큰까치수영 추출물은 혈관이완 효과를 갖는 것을 특징으로 한다.In addition, the magpie swimming extract is characterized in that it has a vascular relaxation effect.
또한, 상기 큰까치수영 추출물은 내피세포형 산화질소 합성효소의 활성증가 효과를 갖는 것을 특징으로 한다In addition, the magpie swimming extract is characterized in that it has an effect of increasing the activity of endothelial cell type nitric oxide synthase
또한, 상기 큰까치수영 추출물은 혈압의 강하와 혈관내 산화스트레스의 감소 효과를 갖는 것을 특징으로 한다.In addition, the magpie swimming extract is characterized in that it has a effect of lowering blood pressure and vascular oxidation stress.
또한, 상기 심혈관계 질환은 울혈성 심장병, 관상동맥질환 (심장마비), 허혈성심장병(심근허혈), 고지혈증, 동맥경화, 고혈압, 저혈압, 부정맥, 심부전증, 혈관재협착, 뇌혈관질환 (뇌졸중, 치매), 말초혈관질환 및 대사성 질환으로 이루어진 군에서 선택된 것일 수 있다.In addition, the cardiovascular diseases include congestive heart disease, coronary artery disease (heart failure), ischemic heart disease (myocardial ischemia), hyperlipidemia, arteriosclerosis, hypertension, hypotension, arrhythmia, heart failure, vascular restenosis, cerebrovascular disease (stroke, dementia) ), Peripheral vascular disease and metabolic disease.
한편, 본 발명의 심혈관계 질환의 예방용 건강기능식품은 큰까치수영 추출물 을 유효성분으로 함유하는 것을 특징으로 한다.On the other hand, the health functional food for the prevention of cardiovascular diseases of the present invention is characterized by containing the magpie swimming extract as an active ingredient.
상술한 바와 같이, 본 발명의 큰까치수영 추출물은 NAD(P)H 옥시다제의 활성을 강하게 저해하는 동시에 혈관 이완효과를 나타내므로, 심혈관계 질환의 예방 및 치료를 위한 약학조성물 또는 건강기능식품으로써 유용하게 이용될 수 있다.As described above, the magpie swimming extract of the present invention strongly inhibits the activity of NAD (P) H oxidase and at the same time exhibits a vascular relaxation effect, so as a pharmaceutical composition or health functional food for the prevention and treatment of cardiovascular diseases. It can be usefully used.
이하, 본 발명의 바람직한 구현예에 대하여 상세히 설명한다. 또한, 하기의 설명에서는 구체적인 구성요소 등과 같은 많은 특정사항들이 도시되어 있는데, 이는 본 발명의 보다 전반적인 이해를 돕기 위해서 제공된 것일 뿐 이러한 특정 사항들 없이도 본 발명이 실시될 수 있음은 이 기술분야에서 통상의 지식을 가진 자에게는 자명하다 할 것이다. 그리고, 본 발명을 설명함에 있어서, 관련된 공지 기능 혹은 구성에 대한 구체적인 설명이 본 발명의 요지를 불필요하게 흐릴 수 있다고 판단되는 경우 그 상세한 설명을 생략한다.Hereinafter, preferred embodiments of the present invention will be described in detail. In addition, in the following description there are shown a number of specific details such as specific components, which are provided only to help a more comprehensive understanding of the present invention, it is common in the art that the present invention may be practiced without these specific details. It is self-evident to those who have knowledge of the world. In describing the present invention, when it is determined that a detailed description of a related known function or configuration may unnecessarily obscure the subject matter of the present invention, the detailed description thereof will be omitted.
본 발명의 큰까치수영 추출물은 하기와 같이 수득될 수 있다.The magpie swimming extract of the present invention can be obtained as follows.
상기 큰까치수영의 뿌리 및 지상부를 포함하는 전초를 채취한 것, 양식한 것 또는 시판되는 것 등 제한 없이 사용할 수 있으며, 추출을 위한 용매는 물, C1 내지 C5의 저급알콜 및 그 혼합물로 이루어진 군에서 선택된다. 본 발명자들은 큰까치수영 가지와 잎을 물로 씻어 이물질 및 염분을 제거하고 건조한 후, 큰까치수영 시료 중량의 약 5 내지 50 배, 바람직하게는 10 내지 30 배에 달하는 부피의 물 및 메탄올, 에탄올, 부탄올 등과 같은 C1 내지 C5의 저급알콜의 극성 용매 또는 이들의 약 1:0.1 내지 1:10의 혼합비를 갖는 혼합용매로, 바람직하게는 30 내지 95 중량%의 에탄올 수용액으로 50 내지 95 ℃에서 1 시간 내지 7 일 동안 추출하는 과정을 2 내지 5 회 반복 수행한다. 또는, 이러한 물 또는 저급알콜 수용액으로 추출한 후 부탄올로 재추출하는 것이 더욱 바람직하다. 이어서 상기 추출물을 감압농축 및/또는 동결건조하여 큰까치수영 조추출물을 수득할 수 있다.It can be used without limitation, such as harvested, cultured or commercially available, including the root and the ground portion of the large magpie swimming, the solvent for extraction is water, lower alcohol of C 1 to C 5 and mixtures thereof It is selected from the group consisting of. The present inventors wash the magpie swimming branches and leaves with water to remove foreign substances and salts, and after drying, the volume of water and methanol, ethanol, about 5 to 50 times the weight of the magpie swimming sample, preferably 10 to 30 times A polar solvent of C 1 to C 5 lower alcohols such as butanol or the like, or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably at 50 to 95 ° C. with an aqueous 30 to 95% by weight ethanol solution. Extraction for 1 hour to 7 days is repeated 2 to 5 times. Alternatively, it is more preferable to extract with water or a lower alcohol aqueous solution and re-extract with butanol. Subsequently, the extract may be concentrated under reduced pressure and / or lyophilized to obtain a magpie swimming crude extract.
또한, 본 발명의 추출물 중 비극성용매 가용 추출물은 상기 조추출물을 증류 수에 현탁한 후, 이를 현탁액의 약 0.1 내지 100 배, 바람직하게는 약 1 내지 5 배 부피의 헥산, 에틸아세테이트, 클로로포름과 같은 비극성 용매를 가하여 1 회 내지 10 회, 바람직하게는 2 회 내지 5 회 비극성용매로 추출, 분리함으로써 수득할 수 있다. 또한 추가로 통상의 분획 공정을 수행할 수도 있다 (Harborne. J.B., Phytochemical medthods : A guide to modern techniques of plant analysis, 3rd Ed., pp.6-7, 1998). In addition, the non-polar solvent soluble extract of the extract of the present invention, after suspending the crude extract in distilled water, it is about 0.1 to 100 times, preferably about 1 to 5 times the volume of hexane, ethyl acetate, chloroform It can be obtained by adding and separating a nonpolar solvent 1 to 10 times, preferably 2 to 5 times by adding a nonpolar solvent. It is also possible to further carry out conventional fractionation processes (Harborne. J. B., Phytochemical medthods: A guide to modern techniques of plant analysis, 3rd Ed., Pp. 6-7, 1998).
더욱 바람직하게는 상기 공정으로 수득된 큰까치수영 조추출물, 바람직하게는 큰까치수영 에탄올 수용액 추출물에 n-부탄올, 헥산, 에틸아세테이트 등의 유기용매를 극성이 낮은 용매부터 극성이 높은 용매 순으로, 바람직하게는 헥산, 에틸아세테이트, 및 n-부탄올의 순으로 순차적으로 용매분획, 감압농축하여 큰까치수영 헥산, 에틸아세테이트, n-부탄올 분획물을 수득할 수 있다.More preferably, the macromolecular swimming crude extract obtained by the above process, preferably organic solvents such as n-butanol, hexane, ethyl acetate, and the like, are extracted from the lower polarized solvent to the higher polarized solvent, Preferably, hexane, ethyl acetate, and n-butanol may be sequentially solvent fractionated and concentrated under reduced pressure in order to obtain a large-sized swimming hexane, ethyl acetate, and n-butanol fractions.
본 발명은 상기의 제법으로 얻어진 큰까치수영 조추출물 또는 비극성용매 가용 추출물을 유효성분으로 함유하는 심혈관계 질환의 예방 및 치료용 조성물을 제공한다.The present invention provides a composition for the prophylaxis and treatment of cardiovascular diseases, which comprises a large magpie swimming crude extract or a non-polar solvent soluble extract obtained by the above-mentioned method as an active ingredient.
본 발명에 따른 심혈관계 질환의 예방 및 치료용 조성물은, 조성물 총 중량에 대하여 상기 추출물 0.1 내지 99 중량%를 포함한다.The composition for preventing and treating cardiovascular diseases according to the present invention comprises 0.1 to 99% by weight of the extract based on the total weight of the composition.
본 발명의 큰까치수영 추출물을 포함하는 조성물은 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The composition comprising the magpie swimming extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the preparation of the composition.
본 발명의 추출물의 약학적 투여 형태는 이들의 약학적으로 허용가능한 염의 형태로 사용될 수도 있고, 또한 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수도 있다.Pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, or may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.
본 발명에 따른 추출물을 포함하는 약학 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. Pharmaceutical compositions comprising extracts according to the invention, respectively, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, external preparations, suppositories and sterile injectable solutions according to conventional methods. Can be formulated and used.
추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에이스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 및 광물유를 들 수 있다. Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, aceitol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 상기 추출물에 적어도 하나 이상의 부형제, 예를 들면 전분, 칼슘카보네이트(calcium carbonate), 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may comprise at least one excipient in the extract, for example starch, calcium carbonate, sucrose. Or lactose, gelatin, or the like is mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
경구 투여를 위한 액상 제제로는 현탁액, 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.Liquid preparations for oral administration 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. have.
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수용제, 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), 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.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 oils such as olive oil, injectable esters such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 추출물의 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 추출물은 1 일 0.0001 내지 100 ㎎/㎏, 바람직하게는 0.001 내지 100 ㎎/㎏으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the preferred effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. 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 발명은 심혈관계 질환의 예방 효과를 나타내는 상기 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강기능식품을 제공한다.The present invention provides a health functional food comprising the extract and a food acceptable food supplement additive exhibiting a prophylactic effect of a cardiovascular disease.
큰까치수영 추출물을 첨가할 수 있는 건강기능식품으로는 예를 들어, 각종 일반식품류, 음료, 껌, 차, 비타민 복합제 등이 있다.Health functional foods to which the blackcurrant swimming extract can be added include, for example, various general foods, beverages, gums, teas, vitamin complexes, and the like.
또한, 상기 큰까치수영 추출물은 심혈관계 질환의 예방 효과를 목적으로 식품 또는 음료에 첨가될 수 있다. 이때, 식품 또는 음료 중의 상기 추출물의 양은 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 g을 기준으로 0.02 내지 5 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다.In addition, the magpie swimming extract may be added to food or beverage for the purpose of preventing cardiovascular diseases. At this time, the amount of the extract in the food or beverage may be added to 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 g. have.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 외에 다른 성분에는 특별한 제한이 없으며, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등의 추가 성분을 함유할 수 있다. 상술한 천연탄수화물의 예로는 모노사카라이드, 예를 들어 포도당, 과당 등; 디사카라이드, 예를 들어 말토오스, 수크로오스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 솔비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제인 타우마틴, 스테비아 추출물, 예를 들어 레바우디오시드 A, 글리시르히진 등; 및 합성 향미제, 예를 들어 사카린, 아스파르탐 등을 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 g당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health functional beverage composition of the present invention is not particularly limited to other ingredients in addition to containing the extract as an essential ingredient in the indicated ratio, and may contain additional ingredients such as various flavoring agents or natural carbohydrates as in general beverages. . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a flavoring agent other than the above-mentioned, a natural flavoring agent, taumartin, a stevia extract, for example, rebaudioside A, glycyrrhizin, etc .; And synthetic flavoring agents such as saccharin, aspartame and the like. The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 g of the composition of the present invention.
상기 외에 본 발명의 추출물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 및 천연 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 추출물들은 천연 과일 쥬스, 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이때, 첨가제의 비율은 그다지 중요하지는 않지만 본 발명의 추출물 100 중량부당 0.01 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the extract of the present invention has various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, coloring and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective properties Colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extracts of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. At this time, the ratio of the additive is not very important, but is generally selected from the range of 0.01 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.
이하, 본 발명을 하기 실시예 및 시험예에 의거하여 보다 구체적으로 설명한 다.Hereinafter, the present invention will be described in more detail based on the following Examples and Test Examples.
실시예Example
실시예 1: 큰까치수영 조추출물의 제조Example 1 Preparation of Large Magpie Swimming Crude Extracts
강원도 지역에서 채취한 큰까치수영을 물로 씻어 이물질을 제거한 후 건조하여 분쇄하고 추출용기에 큰까치수영 25 g과 70 중량%의 에탄올 수용액 총 500 ㎖를 가하여 환류 냉각하면서 70 ℃에서 3 시간씩 3 회 반복하여 가열추출한 다음, 거름종이로 여과하고, 그 여액을 40 ℃의 수욕 상에서 감압 농축 및 동결건조하여 큰까치수영 조추출물 5.3 g 을 수득하였다.The large magpie swimming collected in Gangwon-do area was washed with water to remove foreign substances, dried and crushed. 25 g of large magpie swimming and 500 ml of 70 wt% ethanol aqueous solution were added to the extraction vessel and refluxed three times at 70 ℃ for 3 hours. The mixture was repeatedly extracted by heating, filtered through a filter paper, and the filtrate was concentrated under reduced pressure and lyophilized on a water bath at 40 ° C. to obtain 5.3 g of a large magpie swimming crude extract.
실시예 2: 큰까치수영 조추출물의 분획물 제조Example 2: Preparation of Fractions of Blackcurrant Swimming Crude Extracts
실시예 1에서 수득한 큰까치수영 조추출물 5 g을 정제수 50 ㎖에 현탁한 후 50 ㎖의 헥산, 에틸아세테이트, n-부탄올의 순으로 순차적으로 용매분획을 각 3 회 실시하여 각 용매 분획을 얻었으며, 이를 감압농축하여 큰까치수영의 헥산, 에틸아세테이트, n-부탄올 분획물을 수득하였다.5 g of the magpie swimming crude extract obtained in Example 1 was suspended in 50 ml of purified water, and then 50 ml of hexane, ethyl acetate, and n-butanol were sequentially subjected to three solvent fractions, thereby obtaining each solvent fraction. The resultant was concentrated under reduced pressure to obtain hexane, ethyl acetate, and n-butanol fractions.
시험예 1: 큰까치수영 추출물의 NAD(P)H 옥시다제 활성 저해 효과 측정Test Example 1: Determination of NAD (P) H oxidase activity inhibitory effect
상기 실시예 1 내지 실시예 2에 의해 제조된 큰까치수영 조추출물 및 분획물의 심혈관계 질환 발전 지표효소인 NAD(P)H 옥시다제 활성저해 효과를 측정하기 위하여, 흰쥐의 혈관동맥평활근세포 (Rat aortic smooth muscle cells, RASMC) 및 송아지 혈관내피세포 (Bovine aortic endothelial cells, BAECs)를 대상으로 NADPH 옥시다제 활성의 변화를 비교하였고, 그 결과는 다음 표 1과 같다. 먼저 혈관동맥평활근세포와 혈관내피세포를 각각 MEM (minimum essential medium)과 DMEM (Dubleco's minimum essential medium) 및 10 % FBS (Fetal bovine serum) 용액과 혼합하여 96 웰플레이트(well plate)에서 24 시간 동안 5 % CO2/37 ℃의 조건에서 배양 후 FBS가 제외된 배양액으로 다시 24 시간 동안 배양하였다. 세포가 안정화된 후에 HBSS (Hank's balanced salt solution)으로 세포를 씻어내고 상기 실시예 1에서 수득한 큰까치수영의 추출물을 진탕시킨 후 15 분 동안 반응시켰다. 이후 HBSS로 다시 씻어내고 100 mM의 NAD(P)H 와 5 μM의 루시제닌(Lucigenin)을 반응액에 첨가하여 1 시간 동안 NAD(P)H 옥시다제의 활성을 발광판독기(Luminescence Reader. Victor Light, PerkineElmer)를 이용하여 측정하였다. 시험은 3 회 가동시키고 2 내지 7 회 반복하였다. 그 이후 대조군의 활성과 시료처리 군의 활성을 비교하여 IC50 값을 계산하였다. IC50 값은 NADPH 옥시다제의 활성의 50 %를 저해하는 시험물질의 ㎍/㎖ 단위의 농도이다.In order to measure the inhibitory effect of NAD (P) H oxidase activity, a cardiovascular disease development index enzyme of the magpie swimming crude extract and fractions prepared by Examples 1 to 2, rat vascular smooth muscle cells (Rat Changes in NADPH oxidase activity were compared in aortic smooth muscle cells (RASMC) and bovine aortic endothelial cells (BAECs), and the results are shown in Table 1 below. First, vascular artery smooth muscle cells and vascular endothelial cells were mixed with MEM (minimum essential medium), DMEM (Dubleco's minimum essential medium) and 10% Fetal bovine serum (FBS) solution for 5 hours in a 96 well plate. while% CO 2/24 time again under the condition of 37 ℃ to the culture medium after the culture, except the FBS was cultured. After the cells were stabilized, the cells were washed with HBSS (Hank's balanced salt solution) and shaken with an extract of the magpie swimming obtained in Example 1, followed by reaction for 15 minutes. After rinsing again with HBSS and adding 100 mM NAD (P) H and 5 μM lucigenin to the reaction solution, the activity of NAD (P) H oxidase for 1 hour was measured by Luminescence Reader. Victor Light , PerkineElmer). The test was run three times and repeated 2-7 times. After that, the IC50 value was calculated by comparing the activity of the control group with that of the sample treatment group. The IC50 value is the concentration in μg / ml of the test substance that inhibits 50% of NADPH oxidase activity.
상기 표 1에서 보는 바와 같이 본 발명의 큰까치수영 추출물은 혈관세포의 NADPH 옥시다제 활성을 저해하는 정도가 매우 우수한 것을 알 수 있다. 또한 분획물 중에서는 n-부탄올 추출물의 효과가 뛰어남을 알 수 있다.As shown in Table 1, the magpie swimming extract of the present invention can be seen that the degree of inhibiting the NADPH oxidase activity of vascular cells is very excellent. In addition, it can be seen that the effect of the n-butanol extract in the fraction.
시험예Test Example 2: 2: 큰까치수영Magpie swimming 추출물의 Of extract 혈관이완효과Vasorelaxant effect 측정 (관상동맥 및 대동맥) Measurement (Coronary and Aorta)
상기 실시예 1 및 실시에 2에 의해 제조된 큰까치수영 조추출물 및 분획물의 혈관이완 효과를 확인하기 위하여 돼지 심장의 관상동맥 및 쥐의 대동맥의 이완효과를 비교하였고, 그 결과는 도 1, 표 2 (관상동맥), 및 표 3 (대동맥)에 나타난 바와 같다. 관상동맥은 도축장에서 도살 직후의 돼지심장을 구입한 후 적출하였으며, 대동맥은 웅성 SD (Sparague-Dawley)계 흰쥐로부터 적출하여 18 mM NaCl, 4.7 mM KCl, 1.1 mM MgSO4, 1.2 mM KH2PO4, 1.5 mM CaCl2, 25 mM NaHCO3, 10 mM 글루코스가 들어있는 크렙스(Krebs) 용액 (pH 7.4)에 넣고 연결 조직과 지방을 제거한 후 약 3 ㎜의 길이의 절편으로 만들었다. The relaxation effects of the coronary artery of the porcine heart and the aortic artery of the rat were compared to confirm the vasorelaxant effect of the magpie swimming crude extract and fractions prepared by Examples 1 and 2, and the results are shown in FIG. 2 (coronary artery), and Table 3 (aortic artery). Coronary arteries were isolated from the slaughterhouse after the purchase of pig heart immediately after slaughter, and the aorta was extracted from male SD (Sparague-Dawley) rats. 18 mM NaCl, 4.7 mM KCl, 1.1 mM MgSO 4 , 1.2 mM KH 2 PO 4 , 1.5 mM CaCl 2 , 25 mM NaHCO 3 , and 10 mM glucose (Krebs) solution (pH 7.4) was added to remove the connective tissue and fat was made into sections of about 3 mm in length.
준비한 관상동맥 및 대동맥 절편을 95 % O2 및 5 % CO2 기체로 포화시킨 37 ℃의 크렙스 용액에서 고정시킨 후, 등척성 장력 (isometric tension)을 힘-변위 변환기 (force-displacement transducer, HugoSachs, Germany)가 장착된 생리기록계(Grass physiograph, HugoSachs, Germany)를 이용하여 측정하였다. 관상동맥의 경우 먼저 트롬복산 유도체인 U46619 (1-60 nM)로 혈관최고수축의 80 %로 수축시키고 10 분 후, 300 nM의 브레드키닌(Bradykinin)으로 이완 반응시켜 혈관 내피 세포의 안전성을 측정한 다음, 크렙스 용액으로 3 회 세척하고 실험을 수행하였다. 혈관이완 효과 변화 측정은 먼저 약물을 U46619로 수축하였으며, 이어서 큰까치수영 추출물에 의한 이완 반응을 농도 의존적으로 시험하였다.After the prepared coronary and aortic sections were fixed in a 37 ° C. Krebs solution saturated with 95% O 2 and 5% CO 2 gas, the isometric tension was applied to a force-displacement transducer, HugoSachs, Germany. ) Was measured using a physiological recorder (Grass physiograph, HugoSachs, Germany). Coronary artery was first contracted with 80% of vascular maximal contraction with thromboxane derivative U46619 (1-60 nM), and after 10 minutes, it was relaxed with 300 nM Bradykinin to measure the safety of vascular endothelial cells. Next, it was washed three times with Krebs solution and the experiment was performed. Vasorelaxant effect change measurements were first contracted to U46619, followed by concentration dependent testing of the relaxation response by the magpie swimming extract.
흰쥐의 대동맥의 경우 페닐에프린(phenylephrine)으로 혈관최고수축의 80 %로 수축시키고 15 분 후, 10 μM의 아세틸콜린(acetylcholine)으로 이완 반응시켜 혈관 내피 세포의 안전성을 측정한 다음, 크렙스 용액으로 3 회 세척하고 실험을 수행하였다. 혈관 이완 효과 변화 측정은 먼저 약물을 페닐에프린으로 수축하였으며, 이어서 큰까치수영 조추출물 및 분획물 추출물에 의한 이완 반응을 농도 의존적으로 시험하였다. 이 시험은 5 내지 10의 서로 다른 개체에서 적출한 혈관을 가지고 반복시험하였으며, ED50 값은 수축된 혈관이 시료처리에 의해 50 %의 혈관이완을 나타내는 시료의 농도(㎍/㎖)를 가리킨다.In the case of rat aorta, phenylephrine contracted to 80% of vascular contraction, and after 15 minutes, it was relaxed by 10 μM of acetylcholine to measure the safety of vascular endothelial cells. Wash three times and perform the experiment. The measurement of vascular relaxation effect change was first contracted with phenylephrine, followed by a concentration-dependent relaxation test by the magpie swimming crude extract and fraction extract. This test was repeated with blood vessels taken from 5 to 10 different individuals, and the ED 50 value indicates the concentration of the sample (μg / ml) in which the contracted vessel showed 50% vascular relaxation by sample treatment.
그 결과 도 1에 나타난 바와 같이 본 발명의 큰까치수영 추출물은 1 내지 10 ㎍/㎖의 농도에서부터 유의하게 이완하기 시작하여 30 ㎍/㎖ 농도에서는 96 ± 2 %이완을 하였다. 표 2 및 표 3에 나타난 바와 같이 큰까치수영 추출물은 관상동맥 및 대동맥에서 혈관을 이완시키는 정도가 매우 우수한 것을 알 수 있다. 또한 분획물 중에서는 n-부탄올 추출물의 효과가 뛰어남을 알 수 있다.As a result, as shown in Figure 1, the magpie swimming extract of the present invention began to relax significantly from the concentration of 1 to 10 ㎍ / ㎖ and relaxed 96 ± 2% at 30 ㎍ / ㎖ concentration. As shown in Table 2 and Table 3 it can be seen that the magpie swimming extract has a very good degree of relaxation of blood vessels in the coronary and aorta. In addition, it can be seen that the effect of the n-butanol extract in the fraction.
시험예Test Example 3: 3: 큰까치수영Magpie swimming 추출물의 Of extract 내피세포형Endothelial cell type 산화질소 합성효소 활성 테스트 Nitric Oxide Synthase Activity Test
상기 실시예 1 및 실시예 2에 의해 제조된 큰까치수영 조추출물의 내피세포형 산화질소 합성효소의 활성 증강에 대한 효과를 송아지 혈관내피세포 (Bovine aortic endothelial cells)의 내피세포형 산화질소 합성효소 (eNOS)의 1177 번 세린 잔기 (serine residue)와 에이케이티(Akt)의 473 세린 잔기 (serine residue) 인산화 정도로서 비교하였고, 그 결과는 도 3에 나타낸 바와 같다.The endothelial nitric oxide synthase of calf vascular endothelial cells has an effect on the enhancement of the activity of endothelial nitric oxide synthase of the magpie swimming crude extract prepared by Examples 1 and 2 The 1177 serine residue (eNOS) and 473 serine residue phosphorylation degree of Akt were compared as shown in FIG. 3.
먼저 혈관내피세포를 DMEM (Dubleco's minimum essential medium) 및 10 % FBS (Fetal bovine serum) 용액과 혼합하여 배양 후 FBS가 제외된 배양액으로 다시 24 시간 동안 배양하였다. 세포가 안정화된 후에 시료를 각 농도별로 처리한 후 30 분 동안 반응시켰다. 이후 단백질을 추출하고 원심분리하고 상등액을 취하여 세포의 파편들을 제거하였다. 추출한 단백질은 SDS-폴리아크릴아미드 겔(polyacrylamide gel)에 전기영동시킨 후 니트로셀룰로오스 막 (nitrocellulose membrane)으로 겔의 단백질을 블롯시켰다. 3 % BSA로 1 시간 동안 차단(blocking)한 후에 1:1,000의 비율로 phospho-eNOS, phospho-Akt 항체 (Cell Signaling, 미국)를 하루 밤 동안 4 ℃에서 배양하였다. 다음으로, 1:2000의 비율로 희석한 2 차 항체를 처리하여 1 시간 상온에서 배양한 후 화학발광법(chemiluminescence)로 현상하였다.First, vascular endothelial cells were mixed with DMEM (Dubleco's minimum essential medium) and 10% FBS (Fetal bovine serum) solution, followed by incubation for 24 hours in a culture medium without FBS. After the cells stabilized, the samples were treated at each concentration and allowed to react for 30 minutes. The protein was then extracted, centrifuged and the supernatant removed to remove debris from the cells. The extracted protein was electrophoresed on SDS-polyacrylamide gel and blot the protein of the gel with a nitrocellulose membrane. After blocking for 1 hour with 3% BSA, phospho-eNOS and phospho-Akt antibodies (Cell Signaling, USA) were incubated at 4 ° C. overnight at a ratio of 1: 1,000. Next, the secondary antibody diluted at a ratio of 1: 2000 was treated, incubated at room temperature for 1 hour, and then developed by chemiluminescence.
그 결과 도 3에서 보는 바와 같이, 큰까치수영 추출물은 산화질소를 생성시키는 내피 세포형 산화질소 합성효소의 활성화(phospho-eNOS) 증가 효과 및 그 상위 조절 인자인 에이케이티의 활성화(phospho-Akt) 증가 정도가 큰 것을 알 수 있다.As a result, as shown in Figure 3, the magpie swimming extract has an effect of increasing the activation of endothelial cell type nitric oxide synthase (phospho-eNOS) that produces nitric oxide and its higher regulatory factor (phospho-Akt) It can be seen that the increase is large.
시험예Test Example 4 : 4 : 큰까치수영Magpie swimming 추출물의 심혈관계 질병 동물모델에서의 효과 테스트 Effect Test of Extract on Cardiovascular Disease Animal Model
실시예 2에서 수득한 큰까치수영 추출물의 질병동물에서 혈압강하 효과, 혈관내 산화스트레스 개선, 내피세포 기능장애 개선의 효과를 확인하고자 안지오텐신2에 의해 야기된 질병모델에서 그 정도를 비교하였고, 그 결과는 도 4, 도 5, 도 6 및 표 4와 같다.To determine the effect of blood pressure lowering effect, vascular oxidative stress, and endothelial dysfunction in the diseased animal of the magpie swimming extract obtained in Example 2, the degree was compared in the disease model caused by
웅성 SD(Sparague-Dawley, 6주령)계 흰쥐를 오리엔트바이오로부터 구입하여, 명암주기 12 시간 단위로 조절되는 소동물 사육실에서 고형사료와 물을 자유롭게 공급하여 1 주간 순화한 다음 임의적으로 대조군과 안지오텐신2를 처리할 군으로 각각 6 마리씩 분류하였다. 안지오텐신2를 처리하기 3 일 전부터 실시예2에서 수득한 큰까치수영 추출물을 0.5 % CMC(carboxymethylcellulose)에 100 mg/kg로 현탁하여 1 일 2 회 경구투여하였다. 대조군은 0.5 % CMC만 투여하였다. 안지오텐신2 처리는 삼투성 미니펌프(mini-osmotic pump, alzet model 2002)에 안지오텐신2를 65 ng/min/kg으로 생리식염수에 녹여 넣은 후 상기 흰쥐를 마취시킨 다음 피부를 절개하여 견갑간 영역에 삽입함으로 실시하였다. 혈압측정은 경구투여 시작과 동시에 실시하였으며, 2 일에 1 회, 2 주간, 오전 경구투여 1 시간 후 측정하였다. 혈압측정은 검체를 미리 45 내지 50 ℃에서 약 10 분간 가온한 후, 자동혈압 기록계를 사용하여 테일-커프 플레티스모그래프(tail-cuff plethysmography)법에 의해 꼬리 동맥의 최고혈압(수축기 혈압)을 비관혈적으로 측정하였고 동시에 심박수를 측정하였다.A male SD (Sparague-Dawley, 6-week-old) rat was purchased from Orient Bio, and was freely supplied with solid feed and water in a small animal breeding room controlled by a 12-hour contrast cycle. 6 animals were divided into groups to be treated. Three days before the
혈관내 산화스트레스와 혈관내피세포 기능장애 정도는 시험예 2에서와 같이 대동맥을 적출하여 DHE (dihydroetidium)의 염색정도 및 아세틸콜린에 의한 이완정도를 특정하여 대조군과 비교하였다. Intravascular oxidative stress and vascular endothelial dysfunction were compared with the control group by specifying the degree of staining of DHE (dihydroetidium) and the relaxation by acetylcholine, as in
시험 결과는 표 4와 같이 안지오텐신2에 의한 시험동물의 혈압상승은 큰까치수영 추출물의 투여에 의하여 유의성 있게 저해됨을 알 수 있다.As shown in Table 4, it can be seen that the blood pressure increase of the test animal by
또한 심박수의 증가분을 측정한 결과 도 4에서와 같이, 큰까치수영 추출물은 빈맥 등 심장에 대하여 바람직하지 않은 부작용을 미치지 않는 것을 확인하였다.In addition, as a result of measuring the increase in heart rate, as shown in Figure 4, the magpie swimming extract did not have an adverse side effect on the heart, such as tachycardia.
또한 혈관내 산화스트레스는 도 5와 같이 안지오텐신2에 의한 산화스트레스의 증가가 큰까치수영 추출물의 투여에 의해 강력하게 저해됨을 알 수 있다.In addition, the vascular oxidative stress can be seen that the increase in the oxidative stress by
또한 안지오텐신2를 처리한 동물에서의 아세틸콜린 0.01 μM에 의한 이완을 대조군과 비교했을 때 이완이 원활하게 일어나지 않는 (대조군 - 27 %, 아세틸콜린 - 8 %) 혈관내피세포 기능장애가 일어났으며, 이러한 혈관내피세포 기능장애는 큰까치수영 추출물 (31 %)의 투여에 의해 개선됨을 알 수 있다.In addition, when angiotensin2 treated animals were relaxed by 0.01 μM of acetylcholine, vascular endothelial dysfunction occurred that did not occur smoothly (control-27%, acetylcholine-8%). It can be seen that vascular endothelial dysfunction is improved by administration of magpie swimming extract (31%).
시험예Test Example 5 : 5: 큰까치수영Magpie swimming 추출물의 세포독성 테스트 Cytotoxicity Test of Extracts
상기 실시예 1 및 실시예 2에 의해 제조된 큰까치수영 조추출물의 세포독성정도를 비교하였으며 그 결과는 도 6과 같다. The cytotoxicity of the large magpie swimming crude extracts prepared by Examples 1 and 2 was compared and the results are shown in FIG. 6.
혈관동맥평활근세포를 MEM (minimum essential medium)과 10 % FBS (Fetal bovine serum) 용액과 혼합하여 24 시간 동안 5 % CO2/37 ℃의 조건에서 배양하였다. 세포가 안정화된 후에 상기 실시예 2에서 수득한 큰까치수영의 추출물을 처리하여 진탕시킨 후 24 시간 동안 반응시켰다. 이후 MTS 용액 (cellTiter 96 Aqueous One Solution, promega)을 넣어 1 시간 동안 배양한 후 490 nm에서 흡광도를 측정하였다.The arterial blood vessel smooth muscle cells were mixed with MEM (minimum essential medium) and (Fetal bovine serum) solution, 10% FBS and cultured for 24 hours under the conditions of 5% CO 2/37 ℃. After the cells were stabilized, the extract of the magpie swimming obtained in Example 2 was treated and shaken to react for 24 hours. Thereafter, MTS solution (cellTiter 96 Aqueous One Solution, promega) was added and incubated for 1 hour, and then absorbance was measured at 490 nm.
상기 도 6에서 나타난 바와 같이 본 발명의 큰까치수영 추출물은 세포의 생존에 어떠한 영향도 관찰할 수 없었으며 매우 안전한 약물임을 알 수 있다.As shown in FIG. 6, the magpie swimming extract of the present invention could not observe any effect on the survival of the cells and can be seen as a very safe drug.
시험예Test Example 6: 통계처리 6: Statistical processing
시험결과의 유의성은 실험결과를 스투던트 t-테스트 및 일원본산 분석 (one-way ANOVA test)를 통하여 p가 0.05 이하인 경우 유의한 차이로 판정하였다.The significance of the test results was determined to be a significant difference when the p was less than 0.05 through the Student's t-test and one-way ANOVA test.
아래에 본 발명의 추출물을 포함하는 약학조성물 및 건강기능식품의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, an example of the pharmaceutical composition and the health functional food containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto but is intended to be described in detail.
제제예Formulation example 1: One: 산제의Powder 제조 Produce
큰까치수영 추출물 분말 20 ㎎Blackcurrant Swimming Extract Powder 20mg
유당 100 ㎎
탈크 10 ㎎
상기의 성분들을 혼합하고, 기밀포에 충진하여 산제를 제조하였다.The above ingredients were mixed and filled in airtight cloth to prepare a powder.
제제예Formulation example 2: 정제의 제조 2: preparation of tablets
큰까치수영 추출물 분말 10 ㎎Blackcurrant Swimming Extract Powder 10mg
옥수수 전분 100 ㎎100 mg corn starch
유당 100 ㎎
스테아린산 마그네슘 2 ㎎2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components was prepared by tableting according to the conventional tablet manufacturing method.
제제예Formulation example 3: 캅셀제의 제조 3: Manufacture of capsule
큰까치수영 추출물 분말 10 ㎎Blackcurrant Swimming Extract Powder 10mg
결정성 셀룰로오스 3 ㎎3 mg of crystalline cellulose
락토오스 14.8 ㎎Lactose 14.8 mg
마그네슘 스테아레이트 2 ㎎Magnesium Stearate 2mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.According to a conventional capsule preparation method, the above ingredients were mixed and filled into gelatin capsules to prepare capsules.
제제예Formulation example 4: 주사제의 제조 4: Preparation of Injection
큰까치수영 추출물 분말 10 ㎎Blackcurrant Swimming Extract Powder 10mg
만니톨 180 ㎎Mannitol 180 mg
주사용 멸균 증류수 2794 ㎎Sterile distilled water for injection 2794 mg
Na2HPO412H2O 26 ㎎Na 2 HPO 4 12H 2 O 26 mg
통상의 주사제 제조방법에 따라 1 앰플 (2 ㎖)당 상기의 성분 함량으로 제조하였다.It was prepared in the above ingredient content per ampoule (2 mL) according to a conventional injection method.
제제예Formulation example 5: 5: 액제의Liquid 제조 Produce
큰까치수영 추출물 분말 10 ㎎Blackcurrant Swimming Extract Powder 10mg
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적당량Purified water
통상의 액제 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고, 레몬향을 적당량 가한 다음 상기의 성분을 혼합한 후 정제수를 가하여 전체를 100 ㎖로 조절하고 갈색병에 충진하여 멸균시켜 액제를 제조하였다.According to the conventional liquid preparation method, each component is added and dissolved in purified water, lemon flavor is added, then the above ingredients are mixed, purified water is added, the whole is adjusted to 100 ml and sterilized by filling in a brown bottle. It was.
제제예Formulation example 6: 6: 건강음료의Health drink 제조 Produce
큰까치수영 추출물 분말 10 ㎎Blackcurrant Swimming Extract Powder 10mg
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 g100 g of vitamin E (powder)
젖산철 19.75 gIron lactate 19.75 g
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinamide 3.5 g
비타민 A 0.2 g0.2 g of vitamin A
비타민 B1 0.25 g0.25 g of vitamin B1
비타민 B2 0.3 g0.3 g of vitamin B2
물 적당량Water
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동안 85 ℃에서 교반 가열 후, 만들어진 용액을 여과하고 멸균된 2 ℓ의 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관하여 본 발명에 따른 건강음료 조성물 제조에 사용하였다. 상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층이나 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.After mixing the above components according to a conventional healthy beverage production method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated and stored in the present invention Used to prepare a healthy beverage composition according to. Although the composition ratio is a composition suitable for a preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
도 1은 돼지 관상동맥에 대한 큰까치수영 추출물의 혈관이완 활성을 측정한 도면이다.1 is a view measuring the vasorelaxant activity of the magpie swimming extract for pig coronary arteries.
도 2는 흰쥐 대동맥에 대한 큰까치수영 추출물의 혈관이완 활성을 측정한 도면이다.Figure 2 is a measure of the vasorelaxant activity of the magpie swimming extract on the rat aorta.
도 3은 큰까치수영 추출물에 의한 내피 세포형 산화질소 합성효소 (eNOS) 와 에이케이티 (Akt) 단백질의 활성 정도를 측정한 도면이다.Figure 3 is a measure of the activity of the endothelial cell type nitric oxide synthase (eNOS) and Akt (Akt) protein by the magpie swimming extract.
도 4는 큰까치수영 추출물에 의한 심박수의 영향 정도를 측정한 도면이다.Figure 4 is a measure of the effect of heart rate by the magpie swimming extract.
도 5는 큰까치수영 추출물에 의한 혈관내 산화스트레스 감소 정도를 측정한 도면이다.Figure 5 is a measure of the degree of vascular oxidative stress reduction by the magpie swimming extract.
도 6은 큰까치수영 추출물의 세포독성 정도를 측정한 도면이다.Figure 6 is a measure of the cytotoxicity of the magpie swimming extract.
Claims (10)
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020080005782A KR100948332B1 (en) | 2008-01-18 | 2008-01-18 | Composition Comprising the Extracts of Lysimachia clethroides for Prevention and Treatment of Cardiovascular Diseases |
PCT/KR2008/007485 WO2009091121A2 (en) | 2008-01-18 | 2008-12-17 | Composition comprising the extracts of lysimachia clethroides for prevention and treatment of cardiovascular diseases |
EP08870585A EP2240191A4 (en) | 2008-01-18 | 2008-12-17 | Composition comprising the extracts of lysimachia clethroides for prevention and treatment of cardiovascular diseases |
CN2008801250721A CN101969969A (en) | 2008-01-18 | 2008-12-17 | Composition comprising the extracts of lysimachia clethroides for prevention and treatment of cardiovascular diseases |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020080005782A KR100948332B1 (en) | 2008-01-18 | 2008-01-18 | Composition Comprising the Extracts of Lysimachia clethroides for Prevention and Treatment of Cardiovascular Diseases |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20090079650A KR20090079650A (en) | 2009-07-22 |
KR100948332B1 true KR100948332B1 (en) | 2010-03-17 |
Family
ID=40885751
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020080005782A KR100948332B1 (en) | 2008-01-18 | 2008-01-18 | Composition Comprising the Extracts of Lysimachia clethroides for Prevention and Treatment of Cardiovascular Diseases |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP2240191A4 (en) |
KR (1) | KR100948332B1 (en) |
CN (1) | CN101969969A (en) |
WO (1) | WO2009091121A2 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101168566B1 (en) | 2010-05-20 | 2012-07-27 | 재단법인 제주테크노파크 | Compostion and Method for Controling Plant Disease Occurred by Magnaporthe grisea |
KR102014824B1 (en) | 2018-05-09 | 2019-08-28 | 주식회사 진생바이팜 | Health food composition for vascular relaxation and anti-thrombotic effects comprising Black Ginseng Radix, Salviae Miltiorrhizae Radix, Leonuri Herba and Cnidii Rhizoma |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100989093B1 (en) | 2008-01-18 | 2010-10-25 | 한화제약주식회사 | Composition Comprising the Extracts of Branch of Lindera obtusiloba for Prevention and Treatment of Cardiovascular Diseases |
CN110419740A (en) * | 2018-08-07 | 2019-11-08 | 湖南炎帝生物工程有限公司 | Nostoc composition and its application in improvement cognitive ability |
WO2023128540A1 (en) * | 2021-12-31 | 2023-07-06 | 한국 한의학 연구원 | Composition for preventing, ameliorating, or treating metabolic diseases, containing extract of lysimachia mauritiana as active ingredient |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1173028C (en) * | 1999-04-01 | 2004-10-27 | 宋栋梁 | Chiense herbal medicine wine |
KR100535269B1 (en) * | 2003-08-27 | 2005-12-09 | 학교법인 한림대학교 | Composition comprising extract from lysimachiae herba for preventing and treating arteriosclerosis and enhancement of immunity |
CN1278737C (en) * | 2003-12-17 | 2006-10-11 | 昆明紫健生物技术有限公司 | Compound medicinal formulation with bioactivity |
CN100358530C (en) * | 2004-11-11 | 2008-01-02 | 云南白药集团股份有限公司 | Medicine prepn for treating cerebral apoplexy and its prepn |
CN101199563B (en) * | 2007-12-14 | 2010-06-02 | 苏州大学 | Use of Loosestrife total saponine in preparing medicine for treating liver cancer |
-
2008
- 2008-01-18 KR KR1020080005782A patent/KR100948332B1/en not_active IP Right Cessation
- 2008-12-17 CN CN2008801250721A patent/CN101969969A/en active Pending
- 2008-12-17 EP EP08870585A patent/EP2240191A4/en not_active Withdrawn
- 2008-12-17 WO PCT/KR2008/007485 patent/WO2009091121A2/en active Application Filing
Non-Patent Citations (2)
Title |
---|
논문1 : J.Korea Soc. Appl. Biol. Chem. Vol. 47. No.2. (2004)* |
논문2 : Journal of life Science, Vol. 14, No. 3. (2004)* |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101168566B1 (en) | 2010-05-20 | 2012-07-27 | 재단법인 제주테크노파크 | Compostion and Method for Controling Plant Disease Occurred by Magnaporthe grisea |
KR102014824B1 (en) | 2018-05-09 | 2019-08-28 | 주식회사 진생바이팜 | Health food composition for vascular relaxation and anti-thrombotic effects comprising Black Ginseng Radix, Salviae Miltiorrhizae Radix, Leonuri Herba and Cnidii Rhizoma |
Also Published As
Publication number | Publication date |
---|---|
EP2240191A2 (en) | 2010-10-20 |
WO2009091121A2 (en) | 2009-07-23 |
WO2009091121A3 (en) | 2009-09-03 |
EP2240191A4 (en) | 2011-04-13 |
KR20090079650A (en) | 2009-07-22 |
CN101969969A (en) | 2011-02-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100989093B1 (en) | Composition Comprising the Extracts of Branch of Lindera obtusiloba for Prevention and Treatment of Cardiovascular Diseases | |
KR20090084439A (en) | A composition comprising extract of sophora flavescens or prenylated flavonoids compounds isolated therefrom preventing or treating diabetic complication | |
KR100834348B1 (en) | Composition comprising the extracts of dictyota coriaceum for prevention and treatment of cardiovascular dyscrasia | |
KR101682697B1 (en) | Compositions for prevention or treatment of diabetic complications comprising extract of Aucuba japonica | |
KR100948332B1 (en) | Composition Comprising the Extracts of Lysimachia clethroides for Prevention and Treatment of Cardiovascular Diseases | |
KR20120101743A (en) | Composition for treating and preventing diabetes containing dendropanoxide from leaves of dendropanax morbifera leveille | |
KR101785495B1 (en) | Composition comprising Chrisanthemum indicum extract or fraction for treating, improving or preventing obesity or obesity-related disease | |
KR100587398B1 (en) | Composition comprising the extract of Cucurbita spe. or purified extract isolated therefrom having Anti-adipogenic and Anti-obesity activity | |
KR101692032B1 (en) | Anti-cancer composition containing erythronium japonicum extract | |
KR20160123130A (en) | Composition comprising Chrisanthemum indicum extract or fraction for treating, improving or preventing obesity or obesity-related disease | |
KR20110055771A (en) | Composition comprising extract of cirsium japonicum or compounds isolated therefrom for preventing or treating diabetes and diabetic complications | |
KR20150077794A (en) | Anti-obesity composition comprising herbal extracts as an active ingredient | |
KR100569089B1 (en) | Composition having brain function and congnition enhancing activity | |
KR101681980B1 (en) | Compositions for prevention or treatment of diabetic complications comprising extract of Colona auricaulata | |
KR101596006B1 (en) | Composition for Prevention and Treatment of Cardiovascular Diseases | |
KR101436213B1 (en) | Compositions for prevention and/or treatment of obesity comprising extracts of Boehmeria sieboldiana | |
KR20100002239A (en) | Composition comprising the extracts of leaves of lindera obtusiloba for prevention and treatment of cardiovascular diseases | |
KR100629624B1 (en) | Composition comprising the leaf extract of Rubus Coreanus having anti-inflammatory activity | |
KR20070060306A (en) | Pharmaceutical composition comprising shikonin derivatives from lithospermum erythrorhizon for treating or preventing diabetes mellitus | |
KR20120111653A (en) | Pharmaceutical composition containing prunus yedonesis bark extract or isolated prunetin compound for blood vessel disease | |
KR20140045647A (en) | Compositions for the prevention or treatment of metabolic diseases or complications thereof for containing pheophorbide compounds or pharmaceutically acceptable salts thereof as an active ingredient | |
KR102025572B1 (en) | Composition for preventing, ameliorating or treating metabolic diseases comprising mixture of Diospyros lotus leaf and grape fruit stem extract as effective component | |
KR20130140448A (en) | Pharmaceutical compositions for prevention or treatment of diabetic complications comprising an extract of capsosiphon fulvescens or the compounds isolated from thereof | |
KR100912290B1 (en) | Novel 6,8-di?,?-demethylallyl-3,5,7,2',4',6'-hexahydroxy- flavanone or pharmaceutically acceptable salt thereof, preparation method thereof and composition for removing hangover containing the same as an active ingredient | |
KR101786463B1 (en) | Composition of the metabolic syndrome as an active ingredient the essential oil components of those Litsea japonica and a manufacturing method thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
N231 | Notification of change of applicant | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant | ||
FPAY | Annual fee payment |
Payment date: 20130311 Year of fee payment: 4 |
|
FPAY | Annual fee payment |
Payment date: 20140117 Year of fee payment: 5 |
|
FPAY | Annual fee payment |
Payment date: 20150311 Year of fee payment: 6 |
|
FPAY | Annual fee payment |
Payment date: 20160311 Year of fee payment: 7 |
|
FPAY | Annual fee payment |
Payment date: 20170310 Year of fee payment: 8 |
|
FPAY | Annual fee payment |
Payment date: 20180306 Year of fee payment: 9 |
|
LAPS | Lapse due to unpaid annual fee |