KR101961921B1 - Antihypertensive peptides derived from Paralichthys olivaceus and antihypertensive composition comprising the same - Google Patents
Antihypertensive peptides derived from Paralichthys olivaceus and antihypertensive composition comprising the same Download PDFInfo
- Publication number
- KR101961921B1 KR101961921B1 KR1020170078632A KR20170078632A KR101961921B1 KR 101961921 B1 KR101961921 B1 KR 101961921B1 KR 1020170078632 A KR1020170078632 A KR 1020170078632A KR 20170078632 A KR20170078632 A KR 20170078632A KR 101961921 B1 KR101961921 B1 KR 101961921B1
- Authority
- KR
- South Korea
- Prior art keywords
- flounder
- hydrolyzate
- seq
- present
- peptide
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 57
- 239000000203 mixture Substances 0.000 title claims abstract description 36
- 241000269979 Paralichthys olivaceus Species 0.000 title claims abstract description 18
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 27
- 230000003276 anti-hypertensive effect Effects 0.000 title description 13
- 241000269908 Platichthys flesus Species 0.000 claims abstract description 34
- 206010020772 Hypertension Diseases 0.000 claims abstract description 33
- 235000013305 food Nutrition 0.000 claims abstract description 30
- 210000003205 muscle Anatomy 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 22
- 239000004480 active ingredient Substances 0.000 claims abstract description 12
- 230000036541 health Effects 0.000 claims description 12
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 7
- 235000013376 functional food Nutrition 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 102000005158 Subtilisins Human genes 0.000 claims description 5
- 108010056079 Subtilisins Proteins 0.000 claims description 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 abstract description 45
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 abstract description 45
- 230000002401 inhibitory effect Effects 0.000 abstract description 25
- 230000002265 prevention Effects 0.000 abstract description 9
- 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 31
- 150000001413 amino acids Chemical group 0.000 description 21
- 239000003814 drug Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- XBCWOTOCBXXJDG-BZSNNMDCSA-N Leu-His-Phe Chemical compound C([C@H](NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CN=CN1 XBCWOTOCBXXJDG-BZSNNMDCSA-N 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 102400000345 Angiotensin-2 Human genes 0.000 description 7
- 101800000733 Angiotensin-2 Proteins 0.000 description 7
- 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 7
- 229950006323 angiotensin ii Drugs 0.000 description 7
- 230000036772 blood pressure Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- JGLXHHQUSIULAK-OYDLWJJNSA-N Trp-Pro-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC=3C4=CC=CC=C4NC=3)N)C(O)=O)=CNC2=C1 JGLXHHQUSIULAK-OYDLWJJNSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000000654 additive Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000001631 hypertensive effect Effects 0.000 description 4
- 238000003032 molecular docking Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 241000269982 Paralichthys Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- -1 ethyl oleate Chemical class 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 2
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-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
- 101000984728 Chiropsoides quadrigatus Angiotensin-converting enzyme inhibitory peptide Proteins 0.000 description 2
- 208000007530 Essential hypertension Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- MMFKFJORZBJVNF-UWVGGRQHSA-N His-Leu Chemical group CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 MMFKFJORZBJVNF-UWVGGRQHSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 229960002478 aldosterone Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 108010007119 flavourzyme Proteins 0.000 description 2
- 108010025306 histidylleucine Proteins 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012457 nonaqueous media Substances 0.000 description 2
- 239000003755 preservative agent Substances 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
- 238000011160 research Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 108010011485 Aspartame Proteins 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
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 238000010159 Duncan test Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 241000282326 Felis catus Species 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
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- RCHFYMASWAZQQZ-ZANVPECISA-N Gly-Trp-Ala Chemical compound C1=CC=C2C(C[C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CN)=CNC2=C1 RCHFYMASWAZQQZ-ZANVPECISA-N 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
- 101000877589 Homo sapiens Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha Proteins 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 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 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
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 102100035480 Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha Human genes 0.000 description 1
- 241000700159 Rattus Species 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
- 201000004239 Secondary hypertension Diseases 0.000 description 1
- 241000519995 Stachys sylvatica Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- KISFXYYRKKNLOP-IHRRRGAJSA-N Val-Phe-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)O)N KISFXYYRKKNLOP-IHRRRGAJSA-N 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I 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)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 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
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 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
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 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
- 235000008429 bread Nutrition 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003792 electrolyte Substances 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
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 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
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 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
- 239000003446 ligand Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 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
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 230000001105 regulatory effect Effects 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
- 239000004576 sand Substances 0.000 description 1
- 235000013580 sausages Nutrition 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
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/326—Foods, ingredients or supplements having a functional effect on health having effect on cardiovascular health
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/80—Antihypertensive peptides
Abstract
The present invention relates to a flounder ( Paralichthys olivaceus) relates to a peptide isolated from fractions of less than 5 kDa of the hydrolyzate of the muscles in the pharmaceutical composition or food composition for the prevention or treatment of hypertension comprising as the active ingredient, flounder (Paralichthys olivaceus ) and the peptides isolated from the fractions have inhibitory activity against angiotensin I converting enzyme (ACE). Therefore, the fractions of the hydrolysates of the flounder ( Paralichthys olivaceus ) The isolated peptides can be used in pharmaceutical compositions or food compositions for treating or preventing hypertension.
Description
The present invention relates to a flounder ( Paralichthys The present invention relates to a pharmaceutical composition or food composition for the treatment or prevention of hypertension, which comprises a peptide isolated from fractions of the hydrolyzate of muscle of olivaceus .
The world's hypertensive population has exploded, reaching 1 billion people, and is expected to surpass 1.5 billion by 2025. The proportion of hypertensive patients in the total population is 30% in the United States, 38% in the United Kingdom-Sweden-Italy, 45% in Spain and 55% in Germany, while the developed countries are quite high, but developing countries, especially countries where the economy is changing rapidly in Western style The number of people with hypertension has increased explosively, reaching one in three in India and one out of four in Ghana - South Africa.
The causes of hypertension are almost unknown. Among the factors that raise blood pressure, the renin-angiotensin-aldosterone ring is known to play an important role in regulating blood pressure and body fluid in vivo. Angiotensin II (Angiotensin I), which is present in vivo, is an angiotensin II (angiotensin II) which has a vasoconstrictor activity by the disruption of C-terminal His-Leu by an angiotensin converting enzyme (ACE) The blood vessels are contracted, and the kidney increases the secretion of aldosterone to increase the body fluid level, thereby increasing blood pressure. Therefore, by inhibiting the activity of ACE, blood pressure can be suppressed by lowering angiotensin II production, which is a cause of blood pressure increase.
[Background Art] [0002] In recent years, efforts have been made to obtain a substance having antihypertensive effect from natural substances in hypertension formulations, which have been produced through conventional chemical synthesis methods, due to problems such as side effects. In addition, in order to search for new substances that can be used in diverse applications such as pharmaceuticals and food materials such as enzymes and health supplements, researches on natural living organisms, especially those that are capable of mass culture and breeding, .
On the other hand, marine organisms have a unique metabolic process and a unique environment that are not found in terrestrial organisms, and thus have a variety of novel physiologically active substances. In addition, there has been a lot of research on terrestrial life, but marine life has not been sufficiently studied and it is also a field of high expectation for the development of new useful natural materials.
It is an object of the present invention to provide a pharmaceutical composition for the treatment or prevention of hypertension comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
Another object of the present invention is to provide a food composition for improving or preventing hypertension comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
The present inventors have produced hydrolysates of the muscles of the flounder ( Paralichthys olivaceus ) using the hydrolytic enzymes alcalase, flavourzyme, kojizyme, and protamex , It was confirmed that fractions of the respective hydrolysates with respective molecular weights and peptides having a specific amino acid sequence separated from the fractions had an inhibitory activity against angiotensin I converting enzyme (ACE).
Therefore, the flounder ( Paralichthys olivaceus muscles of the present invention can be used in a pharmaceutical composition or food composition for the treatment or prevention of hypertension using the peptides separated from the fractions of the hydrolyzate of muscle.
In one aspect, the present invention provides a pharmaceutical composition for the treatment or prevention of hypertension, comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 as an active ingredient.
In the present invention, the pharmaceutical composition for treating or preventing hypertension is Val-Phe-Ser-Gly-Trp-Ala (VFSGWAA) -Ala (VFSGWAA) as an active ingredient.
In the present invention, the pharmaceutical composition may further comprise a peptide consisting of the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 3.
In addition, the pharmaceutical composition of the present invention may contain one or more peptides selected from the group consisting of SEQ ID NOS: 1 to 3 as an active ingredient.
In the present invention, the amino acid sequence represented by SEQ ID NO: 2 is Leu-His-Phe (LHF) and the amino acid sequence represented by SEQ ID NO: 3 is Trp-Pro-Trp (WPW).
The peptides were isolated from flounder ( Paralichthys olivaceus muscles, and the hydrolyzate may be an alcalase hydrolyzate, a flavorzyme hydrolyzate, a kojizyme hydrolyzate and a protamex hydrolyzate of flounder, Hydrolysates thereof, and hydrolysates thereof.
In one embodiment of the present invention, the alcalase hydrolyzate, flavorzyme hydrolyzate, kojizyme hydrolyzate and protamex hydrolyzate of the flounder were prepared, and protamex was used The yield of hydrolyzate was the highest at 86.68 ± 1.10%, the protein content was over 70%, and the IC 50 value of ACE (Angiotensin I converting enzyme) inhibition was 68.53 ㎍ / ml. Lt; / RTI >
The ACE (Angiotensin I converting enzyme) is an enzyme that plays a role of converting angiotensin II, which is a decapeptide, into angiotensin II having a vasoconstrictive action by cleaving a dipeptide (His-Leu). An increase in angiotensin II promotes hypertension by promoting strong hypertension and secretion of the antidiuretic hormone aldosterone, inhibiting the excretion of water and sodium, and increasing circulating blood volume. ACE also degrades and inactivates vascular relaxant bradykinin, which in turn results in elevated blood pressure.
In the present invention, the scientific name of the flounder is Paralichthys olivaceus , about 60 cm in length, and a long elliptical shape that is wide up and down. The mouth is large, the teeth are well developed, and the eyes are on the left side of the body. On the side with snow, black and white spots are scattered on a dark yellowish brown background, but the side without snow is white. Inhabits in sand or pearl region of coast 10-200m depth, and spawn in 2-6 months. It appears in all coastal areas of Korea, and is distributed in the Kuril Islands, Japan, and the South China Sea. It is often referred to as a 'bulbous' because of its flat shape, and its eyes are easily distinguished from those on the right, usually because of the snow on the left.
In one embodiment of the present invention, the protamex hydrolysates, which were the most effective, were evaluated in terms of yield, protein content and ACE (Angiotensin I converting enzyme) inhibitory effect in flounder muscle hydrolysates> 10 kDa (over 10 kDa) (5 kDa), and an IC 50 value of inhibiting ACE (Angiotensin I converting enzyme) in the fractions of <5 kDa (<5 kDa) was 35.18 ㎍ / ml, and the fraction with the antihypertensive activity <5 kDa (<5 kDa) was the best.
In one embodiment of the present invention, FPTA (Fast Protein Liquid Chromatography, AKTA START, GE Healthcare) was applied to fractions having the best ACE inhibitory effect of <5 kDa (less than 5 kDa) Peptides consisting of the amino acid sequences shown in SEQ ID NOS: 1 to 3 were isolated from the fractions.
Thus, in the present invention, the peptides are selected from the group consisting of flounder ( Paralichthys olivaceus ) muscle hydrolysates of less than 5 kDa.
Regarding the term "hypertension" of the present invention, the World Health Organization (WHO) defines hypertension as a hypertension when the hypertension exceeds 160 mmHg and the hypertension exceeds 95 mmHg. It is classified as essential hypertension due to unclear underlying cause and secondary hypertension due to causative disease, of which more than 90% is known to belong to essential hypertension.
In one embodiment of the present invention, the flounder ( Paralichthys 1 to 3 isolated from fractions of the hydrolysates of olivaceus muscles were found to have an angiotensin I converting enzyme (ACE) -inhibiting activity, and using these peptides, , A pharmaceutical composition for the treatment or prevention of hypertension.
As used herein, the term "prevention" may refer to any action that inhibits or delays the onset of hypertension by administering the composition of the present invention to a subject. The term "treatment" as used in the present invention means all the actions of causing the hypertensive symptom to be improved or benefited by administering the composition of the present invention to a suspected hypertensive subject.
The pharmaceutical compositions comprising the peptides of the present invention may further comprise suitable carriers, excipients or diluents conventionally used in the manufacture of pharmaceutical compositions. At this time, the peptide included in the composition is not particularly limited, but may include 0.001% by weight to 99% by weight, preferably 0.01% by weight to 50% by weight, based on the total weight of the composition.
The pharmaceutical composition may be any one selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, nonaqueous solutions, suspensions, emulsions, And may be oral or parenteral, various formulations. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.
Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin And the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol,
The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will vary depending on the species and severity, age, sex, The type of drug, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art.
The pharmaceutical composition of the present invention is not particularly limited as long as it is an object for treating hypertension, and any of them can be applied. For example, non-human animals such as monkeys, dogs, cats, rabbits, guinea pigs, rats, mice, cattle, sheep, pigs and goats can be used, , Intraperitoneally, intrapulmonary, and intranasal, and may be administered by a suitable method, including localized administration, if necessary, for localized treatment. The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the individual, the degree of disease, the type of drug, the administration route and the period of time, but can be appropriately selected by those skilled in the art. For example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.
Suitable total daily doses may be determined by the treatment within the scope of sound medical judgment and are generally in the range of 0.001 to 1000 mg / kg, preferably 0.05 to 200 mg / kg, more preferably 0.1 to 100 mg / kg can be administered once or several times a day.
In another aspect, the present invention provides a food composition for improving or preventing hypertension comprising, as an active ingredient, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 1.
In the present invention, the pharmaceutical composition may further comprise a peptide consisting of the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 3.
In addition, the pharmaceutical composition of the present invention may contain one or more peptides selected from the group consisting of SEQ ID NOS: 1 to 3 as an active ingredient.
In the present invention, the amino acid sequence represented by SEQ ID NO: 1 is Val-Phe-Ser-Gly-Trp-Ala-Ala (VFSGWAA), and the food composition for improving or preventing hypertension is Val-Phe-Ser-Gly-Trp- -Ala (VFSGWAA) as an active ingredient.
In the present invention, the food composition may further comprise a peptide consisting of the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 3.
In the present invention, the amino acid sequence represented by SEQ ID NO: 2 is Leu-His-Phe (LHF) and the amino acid sequence represented by SEQ ID NO: 3 is Trp-Pro-Trp (WPW).
In the present invention, the above-mentioned peptides, hypertension, flounder and prevention are as described above.
In the present invention, the term "improvement" means that a suspected disease such as hypertension, which is prevented or treated by using a peptide consisting of the amino acid sequence represented by SEQ ID NOS: 1 to 3, It says.
Specifically, the peptide consisting of the amino acid sequence represented by SEQ ID NOS: 1 to 3 of the present invention may be added to the food composition for the purpose of preventing or improving hypertension.
The food composition of the present invention may be in the form of pills, powders, granules, infusions, tablets, capsules or liquid preparations. The type of food to which the peptides of the present invention can be added is not particularly limited, Various drinks, gum, tea, vitamin complex, and health supplement foods.
In addition to the peptides consisting of the amino acid sequences shown in SEQ ID NOS: 1 to 3, other components may be added to the food composition, and the kind thereof is not particularly limited. For example, it may contain various herbal medicine extracts, food-acceptable food-aid additives or natural carbohydrates such as ordinary food, but is not limited thereto.
The term "food supplementary additive " in the present invention means a component which can be added to foods in a supplementary manner, and is appropriately selected and used by those skilled in the art as added to produce health functional foods of each formulation. Examples of food-aid additives include flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, , a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, and a carbonating agent used in a carbonated beverage. However, the types of the food auxiliary additives of the present invention are not limited by the above examples.
Examples of the natural carbohydrate include monosaccharides such as glucose and fructose; Disaccharides such as maltose, sucrose and the like; And polysaccharides such as dextrin and cyclodextrin and sugar alcohols such as xylitol, sorbitol and erythritol. In addition to the above, natural flavorings (such as tau mart), stevia extracts (rebaudioside A, Etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
The food composition of the present invention may include a health functional food. In the present invention, the food composition may be a health functional food. The term "health functional food " used in the present invention refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids, and circles by using raw materials and components having useful functions in the human body. Here, the term "functionality" means that the structure and function of the human body are controlled to obtain nutritional effects or effects useful for health use such as physiological actions. The health functional food of the present invention can be prepared by a method commonly used in the art and can be prepared by adding raw materials and ingredients that are conventionally added in the art. Also, unlike general medicine, there is an advantage that there is no side effect that can occur when a medicine is used for a long time by using food as a raw material, and it is excellent in portability.
The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). In general, the peptide of the present invention may be added in an amount of 1 to 50% by weight, preferably 5 to 10% by weight, based on the weight of the raw material composition, but is not limited thereto. However, in the case of long-term ingestion intended for health and hygiene purposes or for the purpose of controlling health, the amount can also be used in the above-mentioned range.
There is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health functional foods in a conventional sense.
The flounder ( Paralichthys Since fractions of each molecular weight of the hydrolyzate of olivaceus muscle and peptides isolated from the fractions have inhibitory activity against angiotensin I converting enzyme (ACE), the fractions of the hydrolysates of the flounder ( Paralichthys olivaceus ) The isolated peptides can be used in pharmaceutical compositions or food compositions for treating or preventing hypertension.
Figure 1 shows the results of separating three fractions from the flounder muscle hydrolyzate using FPLC.
Figure 2 shows the peptide and molecular weight of the Val-Phe-Ser-Gly-Trp-Ala-Ala (VFSGWAA) sequence isolated from the fraction of the flounder muscle hydrolysates.
Figure 3 shows peptides and molecular weights of the Leu-His-Phe (LHF) sequence isolated from the fraction of the flounder muscle hydrolysates.
Figure 4 shows peptides and molecular weights of Trp-Pro-Trp (WPW) sequences isolated from fractions of flounder muscle hydrolysates.
FIG. 5 is a graph showing the results of evaluating the ACE inhibitory effect of the peptides isolated from the fraction of the flounder muscle hydrolyzate.
Figure 6 shows the molecular docking analysis of the peptides isolated from the fractions of the flounder muscle hydrolysates.
Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present invention. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.
Example 1. Muscle of flounder Hydrolyzate Produce
Paralichthys olivaceus , purchased from the Fisheries Market of Jeju Island, was used and the bone of the flounder muscle was sprinkled , ground, soaked in water, freeze-dried, and stored at -70 ° C Respectively.
The hydrolysates of the flounder muscles were prepared by using 4 kinds of protein hydrolytic enzymes (Alcalase, Flavourzyme, Kojizyme, Protamex) for 18 hours at a substrate to enzyme ratio of 1000: 1 (weight ratio) Hydrolysis. After the reaction was completed, the mixture was boiled at 100 ° C for 10 minutes to inactivate the enzyme, and the pH was adjusted to 7.0. Centrifuged at 3,500 rpm for 20 minutes, filtered, lyophilized and stored at -70 ° C for use as a sample.
The enzyme hydrolysates using the four hydrolases showed overall high yields. Table 1 shows the yield, protein content and ACE inhibitory activity of the muscle hydrolysates derived from flounder. As shown in Table 1, the yield of the hydrolyzate using protamex was the highest at 86.68 ± 1.10%, the protein content was at least 70%, and the IC 50 value showing the inhibitory effect of ACE (Angiotensin I converting enzyme) was 68.53 ㎍ / ml , Which had ACE inhibitory activity at a relatively low concentration of hydrolysates.
Example 2: Flounder muscle Hydrolyzate Derived molecular weight Fraction ACE inhibitory activity
The protamex hydrolyzate, which had the best effect, was evaluated by collectively evaluating the yield, protein content and ACE (Angiotensin I converting enzyme) inhibitory effect of the flounder muscle hydrolysates prepared in Example 1 to obtain a peptide having an ACE inhibitory effect Containing fractions. The protamex hydrolysates were separated by molecular weight of> 10 kDa (over 10 kDa), 5-10 kDa, <5 kDa (less than 5 kDa) using an ultrafiltration membrane.
Table 2 shows the results of measuring the antihypertensive activity by evaluating the ACE inhibitory effect according to the fraction by molecular weight of the protamex flounder hydrolyzate. As a result, the IC 50 value showing an inhibitory effect of ACE (Angiotensin I converting enzyme) was lowest at <5 kDa (less than 5 kDa) as 35.18 ㎍ / ml, and antithrombotic activity was <5 kDa (less than 5 kDa) And the most excellent ones were confirmed.
Example 3: Peptide Separation and Structural Analysis of Antihypertensive Activity
A total of 3 fractions were obtained by performing FPLC (Fast Protein Liquid Chromatography, AKTA START, GE Healthcare) with a fraction of <5 kDa (less than 5 kDa), which had the best ACE inhibitory effect in Example 2, Respectively.
The molecular weight and amino acid sequence of the peptides were measured using a Q-TOF mass spectrometer (Micromass, Altrincham, UK) electrospray ionization (ESI) to confirm the amino acid sequence of the three fractions, and the results are shown in FIGS. 2 to 4, the amino acid sequence of the peptide is represented by Val-Phe-Ser-Gly-Trp-Ala-Ala (VFSGWAA), Leu-His-Phe (LHF), and Trp-Pro-Trp And the molecular weights were 737.41 Da, 416.23 Da and 488.23 Da, respectively.
Example 4: By Peptide ACE inhibitory efficacy
Angiotensin converting enzyme (ACE) inhibitory effect of the Val-Phe-Ser-Gly-Trp-Ala-Ala (VFSGWAA), Leu-His-Phe (LHF) and Trp- The results are shown in Fig. ACE inhibition activity of the peptides of the VFSGWAA sequence showed the highest antihypertensive activity with the highest ACE inhibitory activity. In the case of VFSGWAA, ACE (Angiotensin I converting Enzyme) inhibits visible IC 50 values are 27.50 ㎍ / ml effect, for LHF 36.63 ㎍ / ml, with 40.42 ㎍ / ml for WPW the peptide of VFSGWAA sequence ACE inhibitory potency Was the highest.
Example 5: Molecular docking analysis of ACE inhibitory peptides
Molecular docking analysis is a program that can predict the binding potential (enzyme active site binding site and ACE inhibitory peptide binding site) and binding energy value of a protein (enzyme) -ligand (ACE inhibiting peptide) complex. (ACE, PDB: 1086) of the protein in the Protein Data Bank (PDB, http://www.rcsb.org) was used and the Flexible Docking program of Accelrys Discovery Studio (DS) .
Figure 6 shows the results of molecular docking analysis of peptides derived from the flounder muscle hydrolysates. The VFSGWAA peptide was found to be hydrogen bonded to the ACE amino acids Glu 384, Arg 522, and His 353, the LHF peptide to Tyr 520, Gln 281 to hydrogen bond, and the WPW peptide to hydrogen bond to Ala 354 and Asp 377. Their binding energies were -216 kcal / mol, -186 kcal / mol and -138 kcal / mol, respectively. The CDOCK interaction energies were -90.70 kcal / mol, -54.62 kcal / mol and -62.67 kcal / Was more effective at inhibiting the ACE enzyme than the other two peptides.
Statistical processing
Experimental results were expressed as the mean ± standard error (SE) value of three or more independent experiments. Duncan test analysis was used for statistical significance between the experimental groups.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, Of the right.
<110> Jeju National University Industry-Academic Cooperation Foundation <120> Antihypertensive peptides derived from Paralichthys olivaceus and antihypertensive composition comprising the same <130> DP20170044 <160> 3 <170> KoPatentin 3.0 <210> 1 <211> 7 <212> PRT <213> Paralichthys olivaceus <400> 1 Val Phe Ser Gly Trp Ala Ala 1 5 <210> 2 <211> 3 <212> PRT <213> Paralichthys olivaceus <400> 2 Leu His Phe One <210> 3 <211> 3 <212> PRT <213> Paralichthys olivaceus <400> 3 Trp Pro Trp One
Claims (8)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020170078632A KR101961921B1 (en) | 2017-06-21 | 2017-06-21 | Antihypertensive peptides derived from Paralichthys olivaceus and antihypertensive composition comprising the same |
| PCT/KR2017/007369 WO2018235981A1 (en) | 2017-06-21 | 2017-07-10 | Paralichthys olivaceus-derived antihypertensive peptide and antihypertensive composition containing same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020170078632A KR101961921B1 (en) | 2017-06-21 | 2017-06-21 | Antihypertensive peptides derived from Paralichthys olivaceus and antihypertensive composition comprising the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20180138433A KR20180138433A (en) | 2018-12-31 |
| KR101961921B1 true KR101961921B1 (en) | 2019-03-26 |
Family
ID=64737658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020170078632A KR101961921B1 (en) | 2017-06-21 | 2017-06-21 | Antihypertensive peptides derived from Paralichthys olivaceus and antihypertensive composition comprising the same |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR101961921B1 (en) |
| WO (1) | WO2018235981A1 (en) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0778076B2 (en) * | 1988-06-10 | 1995-08-23 | 日本水産株式会社 | New peptide |
| KR19990015666A (en) * | 1997-08-08 | 1999-03-05 | 김세권 | Peptide with hypotensive action |
| US7179793B2 (en) * | 2005-02-14 | 2007-02-20 | Ocean Nutrition Canada Limited | Anti-hypertensive dietary supplement |
| KR101150425B1 (en) | 2011-09-26 | 2012-06-01 | 제주대학교 산학협력단 | Composition for controlling blood pressure from styela clava |
| KR101449804B1 (en) * | 2012-09-12 | 2014-10-13 | 부경대학교 산학협력단 | Antihypertensive composition comprising gelatin extract from skate skin and peptide isolated from the extract |
| KR101404850B1 (en) * | 2012-10-09 | 2014-06-09 | 한국기초과학지원연구원 | Antihypersensitive peptide from Chlorella ellipsoidea |
-
2017
- 2017-06-21 KR KR1020170078632A patent/KR101961921B1/en active IP Right Grant
- 2017-07-10 WO PCT/KR2017/007369 patent/WO2018235981A1/en active Application Filing
Non-Patent Citations (2)
| Title |
|---|
| Food and Chemical Toxicology. Vol. 52, pp. 113-120 (2013) |
| 한국수산과학회 양식분과 학술대회, Vol. 2015, No. 5, p. 228 (2015) |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2018235981A1 (en) | 2018-12-27 |
| KR20180138433A (en) | 2018-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9399051B2 (en) | Dipeptidyl peptidase-4 inhibitor | |
| KR101449804B1 (en) | Antihypertensive composition comprising gelatin extract from skate skin and peptide isolated from the extract | |
| KR101734979B1 (en) | Composition for preventing and treating cancer, and enhancing the immune action | |
| JP2004091464A (en) | Obesity inhibitor | |
| KR102003934B1 (en) | Anti-hypertensive composition comprising peptides derived from Paralichthys olivaceus | |
| KR20160141027A (en) | Phamaceutical composition or healthy food comprising water extracts from Pleurotus eryngii var. ferulea (Pf.). for treating or preventing metabolic disorder | |
| KR101991880B1 (en) | Composition for treating or preventing hypertension | |
| KR101961921B1 (en) | Antihypertensive peptides derived from Paralichthys olivaceus and antihypertensive composition comprising the same | |
| KR101847452B1 (en) | Anti-hypertensive composition comprising Scapharca broughtonii extract as effective component | |
| KR101883096B1 (en) | Pharmaceutical composition for preventing or treating acute lung injury or acute respiratory distress syndrome, comprising copper peptide | |
| JP6369951B2 (en) | Dipeptidyl peptidase-IV inhibitor | |
| KR101920117B1 (en) | Manufacturing method of oyster hydrolysate and peptides purified from oyster hydrolysate | |
| KR20200000647A (en) | Anticancer Peptide Isolated from Hydrolysates of larva of Tenebrio molitor, and Anticancer Composition Comprising the Same | |
| KR101404850B1 (en) | Antihypersensitive peptide from Chlorella ellipsoidea | |
| KR102253996B1 (en) | Anti-hypertensive composition comprising peptides derived from hydrolysates of Paralichthys olivaceus | |
| KR20150006971A (en) | A pharmaceutical composition for prevention or treatment of hypertension comprising chayote and allium hookeri as effective components and health functional food comprising the same | |
| JP7144441B2 (en) | Ground flounder having antioxidant and antihypertensive effects and method for producing the same | |
| KR102014413B1 (en) | Composition for anti-obesity comprising extract of Scapharca broughtonii as effective component | |
| KR102045847B1 (en) | Kyung-ok-go having high acceptability and anti-diabetes activity adding the silk of zea mays and pumpkin | |
| KR101629517B1 (en) | Oral composition | |
| KR101921214B1 (en) | Flounder surimi with anti-hypertension effect and manufacturing method thereof | |
| GB2427823A (en) | Inhibition of weight gain with epsilon-polylysine | |
| KR101715996B1 (en) | Composition for antidiabetic activity comprising dichloromethane or ethyl acetate fraction of Hizikia fusiformis extract as effective component | |
| TW200533365A (en) | Composition for inhibiting thrombosis | |
| EP2992890A1 (en) | Pharmaceutical composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant |