KR101621842B1 - A composition comprising the compounds(ID-56D2) isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia - Google Patents
A composition comprising the compounds(ID-56D2) isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia Download PDFInfo
- Publication number
- KR101621842B1 KR101621842B1 KR1020160011362A KR20160011362A KR101621842B1 KR 101621842 B1 KR101621842 B1 KR 101621842B1 KR 1020160011362 A KR1020160011362 A KR 1020160011362A KR 20160011362 A KR20160011362 A KR 20160011362A KR 101621842 B1 KR101621842 B1 KR 101621842B1
- Authority
- KR
- South Korea
- Prior art keywords
- treatment
- secretion
- extract
- amylase
- composition
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 50
- 206010013781 dry mouth Diseases 0.000 title claims abstract description 26
- 239000000203 mixture Substances 0.000 title abstract description 46
- 239000000284 extract Substances 0.000 title abstract description 34
- 241001412277 Ixeridium dentatum Species 0.000 title description 4
- 208000005946 Xerostomia Diseases 0.000 title description 2
- 239000004480 active ingredient Substances 0.000 claims abstract description 20
- 230000036541 health Effects 0.000 claims abstract description 11
- 235000013376 functional food Nutrition 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 230000002265 prevention Effects 0.000 claims abstract description 8
- 230000000694 effects Effects 0.000 claims description 29
- 235000013305 food Nutrition 0.000 claims description 14
- PAFVXYXCHDGMRW-NOVFUMPVSA-N Ixerisoside A Chemical compound C=C1C[C@H]([C@@H]2[C@@H]([C@@H]3[C@H]1C[C@@H](C3=C)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O)OC(=O)C2=C)OCC(=O)C5=CC=C(C=C5)O PAFVXYXCHDGMRW-NOVFUMPVSA-N 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 235000013361 beverage Nutrition 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 7
- 239000002775 capsule Substances 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 230000035882 stress Effects 0.000 claims description 6
- 229940088594 vitamin Drugs 0.000 claims description 6
- 229930003231 vitamin Natural products 0.000 claims description 6
- 235000013343 vitamin Nutrition 0.000 claims description 6
- 239000011782 vitamin Substances 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 5
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 5
- 235000015872 dietary supplement Nutrition 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 208000027932 Collagen disease Diseases 0.000 claims description 3
- 208000005647 Mumps Diseases 0.000 claims description 3
- 230000032683 aging Effects 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 208000010805 mumps infectious disease Diseases 0.000 claims description 3
- 238000001959 radiotherapy Methods 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 235000013373 food additive Nutrition 0.000 claims description 2
- 239000002778 food additive Substances 0.000 claims description 2
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 claims 1
- 229960000794 baclofen Drugs 0.000 claims 1
- 230000028327 secretion Effects 0.000 abstract description 63
- 239000004382 Amylase Substances 0.000 abstract description 59
- 102000013142 Amylases Human genes 0.000 abstract description 59
- 108010065511 Amylases Proteins 0.000 abstract description 59
- 235000019418 amylase Nutrition 0.000 abstract description 59
- 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 abstract description 50
- 239000008103 glucose Substances 0.000 abstract description 49
- 210000003079 salivary gland Anatomy 0.000 abstract description 39
- 210000004027 cell Anatomy 0.000 abstract description 34
- 210000002472 endoplasmic reticulum Anatomy 0.000 abstract description 18
- 238000002474 experimental method Methods 0.000 abstract description 12
- 238000001243 protein synthesis Methods 0.000 abstract description 4
- 230000014616 translation Effects 0.000 abstract description 4
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 230000003647 oxidation Effects 0.000 abstract description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 abstract 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 34
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 34
- 229960001052 streptozocin Drugs 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
- 210000003296 saliva Anatomy 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 150000003839 salts Chemical class 0.000 description 17
- HLZBRVYCKXUHSB-UHFFFAOYSA-N ixerin M Natural products CC(C)C(O)C(=O)OC1CC(=C)C2CC(OC3OC(CO)C(O)C(O)C3O)C(=C)C2C4OC(=O)C(=C)C14 HLZBRVYCKXUHSB-UHFFFAOYSA-N 0.000 description 15
- 239000000469 ethanolic extract Substances 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 230000003247 decreasing effect Effects 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
- -1 Sesquiterpene glycosides Chemical class 0.000 description 11
- 238000010171 animal model Methods 0.000 description 11
- 230000036962 time dependent Effects 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 239000000796 flavoring agent Substances 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 206010057190 Respiratory tract infections Diseases 0.000 description 6
- 101710151717 Stress-related protein Proteins 0.000 description 6
- 235000019634 flavors Nutrition 0.000 description 6
- 230000007774 longterm Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 239000000287 crude extract Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000012046 mixed solvent Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 229930009674 sesquiterpene lactone Natural products 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 206010063409 Acarodermatitis Diseases 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
- 241001412304 Ixeris Species 0.000 description 4
- 241000447727 Scabies Species 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 229930182470 glycoside Natural products 0.000 description 4
- 235000013402 health food Nutrition 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000401 methanolic extract Substances 0.000 description 4
- 208000005687 scabies Diseases 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000130993 Scarabaeus <genus> Species 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
- 244000269722 Thea sinensis Species 0.000 description 3
- 206010047623 Vitamin C deficiency Diseases 0.000 description 3
- 241000949975 Xeris Species 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 230000033116 oxidation-reduction process Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 208000010233 scurvy Diseases 0.000 description 3
- 150000002107 sesquiterpene lactone derivatives Chemical class 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 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
- YEDFEBOUHSBQBT-UHFFFAOYSA-N 2,3-dihydroflavon-3-ol Chemical class O1C2=CC=CC=C2C(=O)C(O)C1C1=CC=CC=C1 YEDFEBOUHSBQBT-UHFFFAOYSA-N 0.000 description 2
- 241000529771 Andryala Species 0.000 description 2
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000404507 Crepis blattarioides Species 0.000 description 2
- 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 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108091006081 Inositol-requiring enzyme-1 Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 241001317584 Ixeris chinensis Species 0.000 description 2
- 241001022267 Ixeris repens Species 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 206010039424 Salivary hypersecretion Diseases 0.000 description 2
- 241000239226 Scorpiones Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 241000529664 Urospermum Species 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000000174 gluconic acid Substances 0.000 description 2
- 235000012208 gluconic acid Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229940041476 lactose 100 mg Drugs 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000002200 mouth mucosa Anatomy 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000006318 protein oxidation Effects 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
- 230000009467 reduction Effects 0.000 description 2
- 229940092258 rosemary extract Drugs 0.000 description 2
- 235000020748 rosemary extract Nutrition 0.000 description 2
- 239000001233 rosmarinus officinalis l. extract Substances 0.000 description 2
- 208000026451 salivation Diseases 0.000 description 2
- 229930004725 sesquiterpene Natural products 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000002137 ultrasound extraction Methods 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- OXSUDBCWSPDPMH-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)CC(O)(C(O)=O)CC(O)=O OXSUDBCWSPDPMH-UHFFFAOYSA-N 0.000 description 1
- BNNMDMGPZUOOOE-UHFFFAOYSA-N 4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 BNNMDMGPZUOOOE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- 241000219318 Amaranthus Species 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 239000000120 Artificial Saliva Substances 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000208838 Asteraceae Species 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006326 Breath odour Diseases 0.000 description 1
- 101100317454 Caenorhabditis elegans xbp-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000742 Cotton Polymers 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
- 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
- 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
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 1
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 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
- 241000206602 Eukaryota Species 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
- 108010010803 Gelatin Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 101150112743 HSPA5 gene Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241000510052 Ixeris japonica Species 0.000 description 1
- 241000125411 Ixeris stolonifera Species 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 241000237503 Pectinidae Species 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 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
- 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
- 101100111629 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR2 gene Proteins 0.000 description 1
- 241001049108 Scabiosa columbaria Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 208000025371 Taste disease 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
- YJQCOFNZVFGCAF-UHFFFAOYSA-N Tunicamycin II Natural products O1C(CC(O)C2C(C(O)C(O2)N2C(NC(=O)C=C2)=O)O)C(O)C(O)C(NC(=O)C=CCCCCCCCCC(C)C)C1OC1OC(CO)C(O)C(O)C1NC(C)=O YJQCOFNZVFGCAF-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000009911 Urinary Calculi Diseases 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003779 Vitamin B12 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
- 206010047700 Vomiting Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 241000758405 Zoopagomycotina Species 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 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
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-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
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229940037769 calcium carbonate 100 mg Drugs 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940069647 citric acid 1000 mg Drugs 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 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
- 230000002255 enzymatic effect Effects 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
- 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
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000008717 functional decline Effects 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
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 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
- 239000003102 growth factor Substances 0.000 description 1
- 101150028578 grp78 gene Proteins 0.000 description 1
- 235000001497 healthy food Nutrition 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical class [H]O* 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 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
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000004379 membrane Anatomy 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
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000001590 oxidative effect 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
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- QVLTXCYWHPZMCA-UHFFFAOYSA-N po4-po4 Chemical compound OP(O)(O)=O.OP(O)(O)=O QVLTXCYWHPZMCA-UHFFFAOYSA-N 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
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect 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
- 235000020637 scallop Nutrition 0.000 description 1
- 230000002000 scavenging effect Effects 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
- 230000000580 secretagogue effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 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
- 238000003756 stirring Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 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
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 235000019669 taste disorders Nutrition 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 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
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- RMNIZOOYFMNEJJ-UHFFFAOYSA-K tripotassium;phosphate;hydrate Chemical compound O.[K+].[K+].[K+].[O-]P([O-])([O-])=O RMNIZOOYFMNEJJ-UHFFFAOYSA-K 0.000 description 1
- ZHSGGJXRNHWHRS-VIDYELAYSA-N tunicamycin Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](O)[C@@H](CC(O)[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(NC(=O)C=C2)=O)O)O1)O)NC(=O)/C=C/CC(C)C)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O ZHSGGJXRNHWHRS-VIDYELAYSA-N 0.000 description 1
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 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
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 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
- 229940033203 vitamin b6 0.5 mg Drugs 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 238000001262 western blot Methods 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
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A23L1/30—
-
- A23L1/3002—
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- 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
- A23V2200/312—Foods, ingredients or supplements having a functional effect on health having an effect on dental health
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 씀바귀 추출물로부터 분리된 화합물을 유효성분으로 함유하는 구강건조증의 예방 및 치료용 조성물에 관한 것으로, 본 발명에 따른 씀바귀 추출물이 (1) 침샘세포(human salivary gland cells, HSG cells)를 이용한 실험에서, 씀바귀와 고농도 포도당을 동시 처리시 아밀라아제 분비를 촉진시키며, 소포체 스트레스 관련 단백질의 발현을 감소시킬 뿐만 아니라, (6) 단기간 및 장기간 고농도의 포도당과 동시 처리 시에 단백질 합성과 관련된 소포체 내 산화-환원 환경이 잘 유지됨을 확인함으로서, 구강건조증의 예방 및 치료용 약학 조성물 및 건강기능식품으로 유용하게 이용될 수 있다.The present invention relates to a composition for the prevention and treatment of dry mouth, which comprises a compound isolated from the extract of Zygomycetum koreensis as an active ingredient. The present invention relates to a composition for preventing and treating oral dryness, which comprises (1) human salivary gland cells In the experiment, it was shown that simultaneous treatment of scabbard and high concentration glucose promotes the secretion of amylase, and not only reduces the expression of the endoplasmic reticulum stress protein, but also (6) the oxidation of endoplasmic reticulum associated with protein synthesis during simultaneous treatment with high- - By confirming that the reducing environment is maintained well, it can be usefully used as a pharmaceutical composition for the prevention and treatment of dry mouth, and as a health functional food.
Description
본 발명은 씀바귀 추출물로부터 분리된 화합물(ID-56D2)을 유효성분으로 함유하는 구강건조증의 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention and treatment of dry mouth syndrome containing, as an active ingredient, a compound (ID-56D2) isolated from scarab extract.
[문헌 1] 정보섭외 향약대사전, 영림사, p1057-1058, 1998년[Document 1] Metabolism of Information Extracts, Young Lim, p1057-1058, 1998
[문헌 2] Hwa-Young Lee, Geum-Hwa Lee, Hye-Kyung Kim, Seung Hyun Kim, Kyung pyo Park, Han-Jung Chae, Hyung-Ryong Kim. Ixeris dentata-induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells. Food and Chemical Toxicology. 62 2013. 739-749.[2] Hwa-Young Lee, Geum-Hwa Lee, Hye-Kyung Kim, Seung Hyun Kim, Kyungpyo Park, Han-Jung Chae, Hyung-Ryong Kim. Ixeris dentata- induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells. Food and Chemical Toxicology. 62 2013. 739-749.
[문헌 3] J. Marco, Juan F. Sanz-Cervera, Alberto Yuste, M. Carmen Oriola. Sesquiterpene lactones and dihydroflavonols from Andryala and Urospermum species. Phytochemistry. 36(3) 1994. 725-729.[Literature 3] J. Marco, Juan F. Sanz-Cervera, Alberto Yuste, M. Carmen Oriola. Sesquiterpene lactones and dihydroflavonols from Andryala and Urospermum species. Phytochemistry. 36 (3) 1994. 725-729.
[문헌 4] Tsutomu Warashina, Mie Ishino, Toshio Miyase, Akira Ueno. Sesquiterpene glycosides from Ixeris debilis and Ixeris repens. Phytochemistry. 29(10) 1990. 3217-3224.[Document 4] Tsutomu Warashina, Mie Ishino, Toshio Miyase, Akira Ueno. Sesquiterpene glycosides from Ixeris debilis and Ixeris repens . Phytochemistry. 29 (10) 1990. 3217-3224.
[문헌 5] Keiichi Nishimura, Toshio Miyase, Akira Ueno, Tadataka Noro, Masanori Kuroyanagi, Seigo Fukushima. Sesquiterpene lactones from Ixeris stolonifera A. Gray. Chemical and Pharmaceutical Bulletin. 33(8) 1985. 3361-3368. [Literature 5] Keiichi Nishimura, Toshio Miyase, Akira Ueno, Tadataka Noro, Masanori Kuroyanagi, Seigo Fukushima. Sesquiterpene lactones from Ixeris stolonifera A. Gray. Chemical and Pharmaceutical Bulletin. 33 (8) 1985, 3361-3368.
[문헌 6] W. Kisiel, B. Barszcz. Sesquiterpene lactone glycosides from Crepis pyrenaica . Phytochemistry. 39(6) 1995. 1395-1397.[Literature 6] W. Kisiel, B. Barszcz. Sesquiterpene lactone glycosides from Crepis pyrenaica. Phytochemistry. 39 (6) 1995. 1395-1397.
[문헌 7] Lipson KL, Ghosh R, Urano F. The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells, PLoS One. 3(2) 2008. e1648.[Literature 7] Lipson KL, Ghosh R, Urano F. The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells, PLoS One. 3 (2) 2008. e1648.
[문헌 8] Benjamin P. Tu and Jonathan S. Weissman. Oxidative protein folding in eukaryotes: mechanisms and consequences, The Journal of Cell Biology. 164(3) 2004. 341-346.[Literature 8] Benjamin P. Tu and Jonathan S. Weissman. Oxidative protein folding in eukaryotes: mechanisms and consequences, The Journal of Cell Biology. 164 (3) 2004. 341-346.
구강 건조증(xerostomia)은 여러 가지 원인에 의하여 타액의 분비량이 감소되어 구강 점막이 건조화되는 질환으로 주로 저작기능과 언어기능의 이상을 호소하게 되고, 심한 구취와 충치의 발생이 생기며 정도에 따라 구강 점막의 작열감 또는 구강 점막의 궤양 등으로 심한 고통을 겪게 된다.Xerostomia is a disease in which saliva secretion is reduced due to various causes and causes dry mouth mucosa. It usually complains of dysfunction of chewing function and language function. It causes severe bad breath and tooth decay, Or burning of the mucous membranes or ulcers of the oral mucosa.
타액은 구강 환경 및 구강 기능의 유지에 중요한 역할을 한다. 즉, 타액에는 음식물 섭취 기능과 구강 환경 유지 기능의 두가지 기능이 있다. 타액의 음식물 섭취 기능에 있어서는 타액은 음식 덩어리의 형성 및 소화 효소 작용과 같은 소화 작용, 또는 미각자극물질의 가용화 또는 가스틴(gastin)(카르보네이트 탈수소효소임)의 분비를 통한 미각을 유지하는 작용을 나타낸다. 구강 환경 유지 기능에 있어서는, 타액은 치아나 점막의 자정 효과, 치아의 재석회화 작용, 항균 작용, 면역 작용, 성장 인자 등에 의한 조직 복구 증진 작용, 및 항염증작용을 나타낸다.Saliva plays an important role in maintaining oral environment and oral function. In other words, saliva has two functions: food intake function and oral environment maintenance function. In the food intake function of saliva, the saliva maintains the taste through the formation of the food mass and the digestion such as the digestive enzymatic action, or the solubilization of the taste stimulant substance or the secretion of gastin (which is a carbonate dehydrogenase) Lt; / RTI > In the oral environment maintenance function, the saliva shows a midnight effect of the teeth and mucous membranes, a rejuvenation effect of the teeth, an antibacterial effect, an immune function, a tissue restoration enhancing action by growth factors and the like, and an anti-inflammatory action.
최근, 다양한 요인에 의해서 야기되는 타액분비의 저하를 호소하는 환자가 증가하고 있다. 따라서, 그의 치료에 대한 사회적 요구가 높아지고 있다. 타액분비 저하는 방사선요법이나 이하선염에 의해 유발되는 침샘 자체의 비정상, 및 대사성 질환 (예를 들면, 바세도우씨병, 당뇨병 등), 또는 콜라겐 질환과 같은 기타 질환에 수반되고, 또한 타액분비 저하는 스트레스 요인 또는 다양한 의약품의 부작용에 의해서도 유발된다. 최근 인구의 고령화에 따라, 침샘의 기능이 노화에 의해 저하되고, 고령자에게 병발되는 다양한 복합 질환에 대한 각종 약품 요법의 결과로서 타액분비의 저하를 호소하는 환자의 수가 미래에는 점점 더 증가할 것으로 생각되고 있다.Recently, there are increasing numbers of patients who complain of decreased salivation caused by various factors. Therefore, the social demand for his treatment is increasing. The lowering of saliva secretion is accompanied by abnormality of the salivary gland itself caused by radiotherapy or mumps, and other diseases such as metabolic diseases (for example, bassadoesitic disease, diabetes mellitus) or collagen diseases, Or by side effects of various medicines. As the population ages in recent years, the number of patients who complain of salivary gland function decline due to aging and the decrease of saliva secretion as a result of various medications for various diseases that accompany to the elderly will increase in the future .
타액분비 저하는, 구강 건조의 결과, 혀가 붉게 변하고, 때로 갈라지게 되어 타액분비 저하 환자는 섭식 시에 아픔을 호소하고, 씹거나 삼키는데 곤란을 호소한다. 또한, 타액분비 저하는 구강에 불편한 느낌, 또는 미각 장애 및 발음 장애를 유발하고, 의치 불안정, 충치, 치주염의 발증, 구내염, 폐렴, 및 소화기능 부전을 유발하는 것으로 알려졌다.Decreased saliva secretion, as a result of oral dryness, reddened tongue, sometimes cracked, salty fluid secretion patients suffer pain at the time of appeal, chew or swallow difficulty. In addition, lowering of saliva secretion has been known to cause uncomfortable feeling in the oral cavity, or taste disorder and pronunciation disorder, causing dental instability, cavities, periodontal disease, stomatitis, pneumonia, and digestive dysfunction.
타액분비 저하의 치료로서 인공 타액의 국소적용이 사용되지만, 그 효과는 한시적이고 한정적이다. 타액분비 촉진제로서 무스카린 수용체 효능제로서 알려진 아네톨 트리티온, 및 세비멜린 염산염이 사용되는데, 이들은 그 효과가 불안정하고 오심, 구토, 식욕감퇴, 복부 불쾌감과 같은 소화기계 부작용의 가능성 문제가 있는 등 몇몇 단점이 있다. 이러한 상황에서, 타액분비 저하의 치료를 위한 새로운 치료제의 개발이 요망되고 있다.Topical application of artificial saliva is used as a treatment for saliva secretion reduction, but the effect is temporary and limited. Anitol trithione, known as muscarinic receptor agonists, and sevimeline hydrochloride, are used as salivary secretagogues. They are unstable in their effectiveness and have a possibility of adverse gastrointestinal side effects such as nausea, vomiting, loss of appetite and abdominal discomfort There are some disadvantages. In this situation, the development of a new therapeutic agent for the treatment of salivation deficiency is desired.
상기와 같이 심한 고통을 수반하는 구강 건조증의 예방 및 치료를 위해 이미 타액 분비 촉진 효과가 있다고 알려진 화합물과는 다른 부작용 없는 천연물 성분의 타액분비 촉진용 조성물의 개발이 절실히 필요한 상태이다.For the prevention and treatment of dry mouth accompanied by severe pain as described above, development of a composition for promoting the saliva secretion of a natural ingredient without adverse effect, which is different from a compound already known to have saliva secretion promoting effect, is desperately needed.
씀바귀(Ixeris dentata NAKAI)는 국화과(Compositae)에 속하는 다년생 초본으로서, 전초를 산고매라고 지칭하며, 동속 식물로서는 선씀바귀(Ixeris chinensis NAKAI), 벋은 씀바귀(Ixeris debilis A. GARY) 등이 있으며, 요로결석, 폐렴, 타박상 등의 치료에 사용되어 온 바 있다 (정보섭외 향약대사전, 영림사, p1057-1058, 1998년). Ixeris dentata NAKAI) is a perennial herb that belongs to the Compositae, and refers to the outpost as a mountain stop, and Ixeris chinensis NAKAI), I xeris debilis A. GARY) have been used in the treatment of urinary stone, pneumonia, bruises, and the like.
그러나, 상기 문헌의 어디에도 씀바귀 추출물 또는 이로부터 분리된 화합물의 구강건조증에 대한 치료효과에 대한 어떠한 언급 또는 교시 내용도 없다. However, there is no mention or teaching in the literature of the therapeutic efficacy of dry extract or compounds isolated therefrom on oral dryness.
이에 본 발명자들은 섭취가 용이하고 인체에 안전하며 구강건조증을 치료할 수 있는 물질을 찾고자 연구 노력한 결과, 씀바귀 추출물로부터 분리된 화합물이 (1) 침샘세포(human salivary gland cells, HSG cells)를 이용한 실험에서, 씀바귀와 고농도 포도당을 동시 처리시 아밀라아제 분비를 촉진시키며, 소포체 스트레스 관련 단백질의 발현을 감소시킬 뿐만 아니라, (6) 단기간 및 장기간 고농도의 포도당과 동시 처리 시에 단백질 합성과 관련된 소포체 내 산화-환원 환경이 잘 유지됨을 확인함으로서, 구강건조증 치료 및 예방효과를 나타냄을 확인함으로써 본 발명을 완성하게 되었다.As a result of efforts to find a substance which is easy to ingest, safe for human body and can treat dry mouth, the present inventors have found that a compound isolated from the extract of Zygomycetum is (1) an experiment using human salivary gland cells (HSG cells) (6) the oxidation-reduction of endoplasmic reticulum (ER) associated with protein synthesis during simultaneous treatment with glucose at a high concentration for a short period of time and a long period of time, as well as to reduce amylase secretion during simultaneous treatment of scabies and high- And confirming that the environment is well maintained, it shows the treatment and prevention effect of dry mouth, thereby completing the present invention.
상기 목적을 달성하기 위하여, 본 발명은 씀바귀 추출물로부터 분리된 화합물을 유효성분으로 함유하는 구강건조증의 예방 또는 치료용 약학조성물을 제공한다.In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating dry mouth, which comprises a compound isolated from the extract of Zygomycis koreana as an active ingredient.
또한, 본 발명은 씀바귀 추출물로부터 분리된 화합물을 유효성분으로 함유하는 구강건조증의 예방 또는 개선용 건강기능식품을 제공한다. In addition, the present invention provides a health functional food for preventing or ameliorating dry mouth symptoms containing as an active ingredient, a compound isolated from an extract of Ascarians.
본원에서 정의되는 씀바귀는 씀바귀(Ixeris dentata NAKAI), 선씀바귀(Ixeris chinensis NAKAI), 또는 벋은 씀바귀(Ixeris debilis A. GARY) 로부터 선택된 씀바귀를 포함한다. The conspiracy defined here is the Ixeris dentata NAKAI), Ixeris chinensis NAKAI, or I xeris debilis A. GARY.
본원에서 정의되는 추출물은 물, 탄소수 1 내지 4의 저급알코올 또는 이들의 혼합용매로부터 선택된 용매에 가용한 추출물, 바람직하게는 물 및 에탄올 혼합용매, 보다 바람직하게는 30 내지 100%(v/v) 물 및 에탄올 혼합용매에 가용한 추출물을 포함한다.The extract as defined herein is an extract which is soluble in a solvent selected from water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably a water and ethanol mixed solvent, more preferably 30 to 100% (v / v) And extracts soluble in water and ethanol mixed solvent.
본원에서 정의되는 씀바귀 추출물로부터 분리된 화합물은 11,13-디히드로인테그리폴린(dihydrointegrifolin) 3-O-β-D-글루코시드 (glucopyranoside) (ID-56B2), (2) 익세리소시드(ixerisoside) A, (ID-56D2), (3) 익세린(ixerin) M, (ID-56D1B), 및 (4) 8-에피이소리피디올(epiisolipidiol)-3-β-D-글루코피라노시드(glucopyranoside), (ID-57D)로 구성된 군으로부터 선택된 1개 이상의 화합물이다. The compound isolated from the scabbard extract as defined herein is 11,13-dihydrointegrifolin 3-O- beta -D-glucopyranoside (ID-56B2), (2) ixerisoside A, (ID-56D2), (3) ixerin M, (ID-56D1B), and (4) epiisolipidiol-3-ss-glucopyrano Glucopyranoside, (ID-57D).
본원에서 정의되는 구강건조증은 방사선요법, 이하선염, 바세도우씨병, 당뇨병 등의 대사성 질환, 콜라겐 질환, 스트레스, 노화, 또는 의약품의 부작용에 기인한 구강건조증임을 특징으로 한다.As defined herein, the dry mouth syndrome is characterized by a dry mouth syndrome caused by a metabolic disease such as radiotherapy, mumps, bassedodiosis, diabetes, collagen diseases, stress, aging, or side effects of medicines.
본 발명의 화합물은 당해 기술분야에서 통상적인 방법에 따라 약학적으로 허용 가능한 염 및 용매화물로 제조될 수 있다.The compounds of the present invention may be prepared into pharmaceutically acceptable salts and solvates by methods conventional in the art.
약학적으로 허용 가능한 염으로는 유리산(free acid)에 의해 형성된 산부가염이 유용하다. 산부가염은 통상의 방법, 예를 들면 화합물을 과량의 산 수용액에 용해시키고, 이 염을 메탄올, 에탄올, 아세톤 또는 아세토니트릴과 같은 수혼화성 유기 용매를 사용하여 침전시켜서 제조한다. 동일한 몰량의 화합물 및 물 중의 산 또는 알코올(예, 글리콜 모노메틸에테르)을 가열하고 이어서 상기 혼합물을 증발시켜서 건조시키거나, 또는 석출된 염을 흡인 여과시킬 수 있다.Pharmaceutically acceptable salts include acid addition salts formed by free acids. The acid addition salt is prepared by a conventional method, for example, by dissolving the compound in an excess amount of an acid aqueous solution, and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. The same molar amount of the compound and the acid or alcohol (e.g., glycol monomethyl ether) in water may be heated and then the mixture may be evaporated to dryness, or the precipitated salt may be filtered by suction.
이 때, 유리산으로는 유기산과 무기산을 사용할 수 있으며, 무기산으로는 염산, 인산, 황산, 질산, 주석산 등을 사용할 수 있고 유기산으로는 메탄술폰산, p-톨루엔술폰산, 아세트산, 트리플루오로아 세트산, 시트르산, 말레인산(maleic acid), 숙신산, 옥살산, 벤조산, 타르타르산, 푸마르산, 만데르산, 프로피온산(propionic acid), 구연산(citric acid), 젖산(lactic acid), 글리콜산(glycollic acid), 글루콘산(gluconic acid), 갈락투론산, 글루탐산, 글루타르산(glutaric acid), 글루쿠론산(glucuronic acid), 아스파르트산, 아스코르빈산, 카본산, 바닐릭산 및 히드로 아이오딕산 등을 사용할 수 있다.As the free acid, organic acids and inorganic acids can be used. As the inorganic acids, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid and the like can be used. Examples of the organic acids include methanesulfonic acid, p -toluenesulfonic acid, acetic acid, trifluoroacetic acid Citric acid, lactic acid, glycollic acid, gluconic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid and hydroiodic acid can be used.
또한, 염기를 사용하여 약학적으로 허용 가능한 금속염을 만들 수 있다. 알칼리 금속 또는 알칼리토 금속염은, 예를 들면 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리토 금속 수산화물 용액 중에 용해하고, 비 용해 화합물염을 여과한 후 여액을 증발, 건조시켜 얻는다. 이때, 금속염으로서는 특히 나트륨, 칼륨 또는 칼슘염을 제조하는 것이 제약상 적합하며, 또한 이에 대응하는 은염은 알칼리 금속 또는 알칼리토 금속염을 적당한 은염(예, 질산은)과 반응시켜 얻는다.In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving a compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the non-soluble compound salt, and evaporating and drying the filtrate. At this time, it is preferable for the metal salt to produce sodium, potassium or calcium salt in particular, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).
본 발명의 화합물의 약학적으로 허용 가능한 염은, 달리 지시되지 않는 한, 본 발명의 화합물에 존재할 수 있는 산성 또는 염기성기의 염을 포함한다. 예를 들면, 약학적으로 허용 가능한 염으로는 히드록시기의 나트륨, 칼슘 및 칼륨염이 포함되며, 아미노기의 기타 약학적으로 허용 가능한 염으로는 하이드로브로마이드, 황산염, 수소 황산염, 인산염, 수소 인산염, 이수소 인산염, 아세테이트, 숙시네이트, 시트레이트, 타르트레이트, 락테이트, 만델레이트, 메탄설포 네이트(메실레이트) 및 p-톨루엔설포네이트(토실레이트) 염이 있으며, 당업계에서 알려진 염의 제조 방법이나 제조과정을 통하여 제조될 수 있다. Pharmaceutically acceptable salts of the compounds of the present invention include, unless otherwise indicated, salts of acidic or basic groups that may be present in the compounds of the present invention. For example, pharmaceutically acceptable salts include sodium, calcium and potassium salts of hydroxy groups, and other pharmaceutically acceptable salts of amino groups include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen phosphate phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate rate, methane sulfonate (mesylate) and p - toluene sulfonate (tosylate) and a salt, the salt manufacturing method or manufacturing process known in the art ≪ / RTI >
본 발명의 씀바귀 추출물로부터 분리된 화합물들은 하기와 같은 제조방법으로 수득될 수 있다. Compounds isolated from the scabious extract of the present invention can be obtained by the following production method.
예를 들어, 이하, 본 발명을 상세히 설명한다.For example, the present invention will be described in detail below.
본 발명의 씀바귀 추출물은 하기와 같이 제조될 수 있다. 건조된 씀바귀를 세척 및 세절 후 정제수를 포함한 물, 메탄올, 에탄올, 부탄올 등의 탄소수 1 내지 4의 저급알코올 또는 이들의 혼합용매로부터 선택된 용매, 바람직하게는 물 및 에탄올 혼합용매, 보다 바람직하게는 30~100% 에탄올 을 수회 섞은 다음에 30℃ 내지 150℃, 바람직하게는 50℃ 내지 100℃의 온도에서 30분 내지 48시간, 바람직하게는 1시간 내지 12시간 동안 초음파 추출법, 열수 추출법, 상온 추출법 또는 환류추출법, 바람직하게는 초음파 추출법을 약 1 내지 20회, 바람직하게는 2 내지 10회 반복 수행하여 얻은 추출액을 여과, 감압 농축, 및 건조하여 본 발명의 씀바귀 조추출물을 얻을 수 있다.The scarab extract of the present invention can be prepared as follows. After drying and shredding the dried scabbard, the scabbard is washed with water containing purified water, a solvent selected from lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol and butanol, or a mixed solvent thereof, preferably water and ethanol mixed solvent, more preferably 30 Followed by ultrasonic extraction, hot water extraction, room temperature extraction or the like at a temperature of 30 ° C to 150 ° C, preferably 50 ° C to 100 ° C for 30 minutes to 48 hours, preferably 1 hour to 12 hours, The extract obtained by repeatedly performing the reflux extraction method, preferably the ultrasonic extraction method, about 1 to 20 times, preferably 2 to 10 times, is filtered, concentrated under reduced pressure, and dried to obtain the crude extract of the present invention.
씀바귀 추출물로부터 분리된 화합물은 상기에서 얻은 조추출물, 바람직하게는 10 내지 90% 에탄올 조추출물 중량의 약 0.0005 내지 0.005배, 바람직하게는 0.05 내지 0.5배 부피 (v/w%)의 물을 가한 후, 에틸 아세테이트 및 부탄올을 이용한 통상적인 분획과정을 수행하여 n-헥산, 메틸렌 클로라이드, 에틸 아세테이트 등의 비극성 용매에 가용한 비극성 용매 가용 추출 분획물; 및 부탄올, 물 등의 극성용매에 가용한 극성용매 가용 추출 분획물을 수득하는 제 1단계; 상기에서 얻은 부탄올, 물 등의 극성용매에 가용한 극성용매 가용 추출 분획물, 바람직하게는 물 가용분획물을 플래쉬 컬럼크로마토그래피, RP C18 컬럼크로마토그래피 또는 실리카겔 오픈 컬럼크로마토그래피, Diaion HP-20 컬럼크로마토그래피 등의 이온 크로마토그래피를 이용한 정제방법을 선택적으로 수회 반복 수행하여 본 발명의 화합물인 코릴라진을 각각 정제 및 수득할 수 있다. Compounds isolated from the crude extract are obtained by adding water of about 0.0005 to 0.005 times, preferably 0.05 to 0.5 times the volume (v / w%) of the crude extract, preferably 10 to 90% ethanol crude extract, , Ethyl acetate and butanol to obtain non-polar solvent-soluble extract fractions which are used in non-polar solvents such as n-hexane, methylene chloride and ethyl acetate; And a polar solvent-soluble fraction extracted in a polar solvent such as butanol and water; The polar solvent-extractable fraction, preferably the water-soluble fraction, obtained in the above-mentioned polar solvent such as butanol and water is subjected to flash column chromatography, RP C18 column chromatography or silica gel open column chromatography, Diaion HP-20 column chromatography Or the like can be selectively and repeatedly carried out several times to purify and obtain the compound of the present invention, corrillazine.
본 발명은 상기의 제조방법 및 상기 제조공정으로 얻어진 씀바귀 추출물로부터 분리된 화합물을 유효성분으로 함유하는 구강건조증의 치료 또는 예방을 위한 약학 조성물 및 건강기능식품을 제공한다. The present invention provides a pharmaceutical composition and a health functional food for the treatment or prevention of dry mouth syndrome containing the compound as an active ingredient, the compound being separated from the extract of Zygomycethe sp. Obtained by the above production method and the production process.
본 발명의 씀바귀 추출물로부터 분리된 화합물이 (1) 침샘세포(human salivary gland cells, HSG cells)를 이용한 실험에서, 씀바귀와 고농도 포도당을 동시 처리시 아밀라아제 분비를 촉진시키며, 소포체 스트레스 관련 단백질의 발현을 감소시킬 뿐만 아니라, (6) 단기간 및 장기간 고농도의 포도당과 동시 처리 시에 단백질 합성과 관련된 소포체 내 산화-환원 환경이 잘 유지됨을 확인함으로서, 구강건조증 치료 및 예방효과를 나타냄을 확인하였다.(1) In experiments using human salivary gland cells (HSG cells), it was found that the simultaneous treatment of scabbard and high glucose concentration promotes the secretion of amylase, and the expression of endoplasmic reticulum stress-related proteins (6) It is confirmed that the oxidation-reduction environment in the endoplasmic reticulum associated with protein synthesis is maintained well during the simultaneous treatment with glucose at a high concentration for a short period of time and for a long period of time.
본 발명의 약학조성물은, 조성물 총 중량에 대하여 상기 화합물을 0.01 내지 80 중량%, 바람직하게는 10 내지 50 중량%로 포함한다. The pharmaceutical composition of the present invention contains 0.01 to 80% by weight, preferably 10 to 50% by weight of the above compound, based on the total weight of the composition.
본 발명의 화합물을 포함하는 약학조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The pharmaceutical compositions comprising the compounds of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.
본 발명의 화합물의 약학적 투여 형태는 이들의 약학적 허용가능한 염의 형태로도 사용될 수 있고, 또한 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다.The pharmaceutical dosage forms of the compounds of the present invention may also be used in the form of their pharmaceutically acceptable salts and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable set.
상기 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있으며, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose) 또는 락토오스(Lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The composition may be formulated into various formulations, such as oral or parenteral formulations. When formulating the composition, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant may be 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, Sucrose), lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate talc are also 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, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명에 따른 화합물은 조성물 총 중량에 대하여 0.1~50 중량%로 포함되는 것이 바람직하다. 그러나 상기와 같은 조성은 반드시 이에 한정되는 것은 아니고, 환자의 상태, 질환의 종류 및 진행 정도에 따라 변할 수 있다. The compound according to the present invention is preferably contained in an amount of 0.1 to 50% by weight based on the total weight of the composition. However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.
본 발명에 따른 화합물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 1일 0.01 mg/kg 내지 10 g/kg으로, 바람직하게는 1 mg/kg 내지 1 g/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the compound according to the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, in order to obtain the desired effect, it is preferable to administer it at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. The administration may be carried out once a day or divided into several doses. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.
본 발명에 따른 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 (intracerebroventricular) 주사에 의해 투여될 수 있다.The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
본 발명에 따른 조성물은 목적 질환의 예방 및 치료를 위하여 단독으로, 또는 수술, 호르몬 치료, 약물 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The composition according to the present invention may be used alone or in combination with methods for the treatment and / or treatment of an objective disease or using surgery, hormone therapy, drug therapy and biological response modifiers.
본 발명에 따른 씀바귀 추출물 자체는 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용 시에도 안심하고 사용할 수 있는 약제이다. The herbal extract according to the present invention has little toxicity and side effects, and therefore can be safely used for long-term administration for preventive purposes.
또한 본 발명은 씀바귀 추출물로부터 분리된 화합물을 유효성분으로 함유하는 구강건조증의 개선 및 예방을 위한 건강기능식품을 제공한다. The present invention also provides a health functional food for improving and preventing dry mouth symptoms, which comprises a compound isolated from the extract of Zygomycota as an active ingredient.
본 발명의 화합물을 포함하는 건강기능식품은 구강건조증의 예방 및 개선을 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 발명의 화합물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 침출차, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.The health functional food containing the compound of the present invention can be used variously for medicines, foods and beverages for prevention and improvement of dry mouth symptoms. Examples of the foods to which the compound of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, leach tea, health supplements and the like, and they are in the form of powder, granule, tablet, capsule or beverage Can be used.
따라서 또한, 본 발명은 구강건조증의 예방 및 개선 효과를 갖는 씀바귀 추출물로부터 분리된 화합물을 유효성분으로 함유하는 건강보조식품 또는 식품첨가제를 제공한다.Accordingly, the present invention also provides a health supplement or a food additive containing, as an active ingredient, a compound isolated from an extract of Zygomycetum having an effect of preventing and improving dry mouth.
본 발명의 화합물을 첨가 가능한 식품 형태는 캔디류의 각종 식품류, 음료, 껌, 차, 비타민 복합제, 또는 건강보조 식품류인 식품 등을 포함한다.Food forms to which the compounds of the present invention can be added include various foods of candy, beverages, gums, tea, vitamin complexes, or foods that are health supplement foods.
본 발명의 화합물은 구강건조증의 예방 및 개선을 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 화합물의 양은 일반적으로 본 발명의 건강식품 조성물은 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ml를 기준으로 0.02 내지 10 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다. The compounds of the present invention may be added to foods or beverages for the purpose of preventing and improving oral dryness. At this time, the amount of the compound in the food or beverage may generally be from 0.01 to 15% by weight of the total food weight of the health food composition of the present invention, and the health beverage composition is preferably 0.02 to 10 g based on 100 ml, Can be added at a ratio of 0.3 to 1 g.
본 발명의 건강 음료 조성물은 지시된 비율로 필수 성분으로서 상기 화합물의 혼합물을 함유하는 것 외에 액체성분에는 특별한 제한점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등의 디사카라이드, 예를 들어 말토스, 슈크로스 등의 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ml당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health beverage composition of the present invention may contain various flavoring agents or natural carbohydrates as an additional ingredient, such as ordinary beverages, in addition to containing a mixture of the above-mentioned compounds as essential ingredients in the indicated ratios, have. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 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 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명에 따른 씀바귀 추출물로부터 분리된 화합물이 (1) 침샘세포(human salivary gland cells, HSG cells)와 동물 모델을 이용한 실험에서, 씀바귀 및 씀바귀 유효성분과 고농도 포도당을 동시 처리시 아밀라아제 분비를 촉진시키며, 소포체 스트레스 관련 단백질의 발현을 감소시킬 뿐만 아니라, 단기간 및 장기간 고농도의 포도당과 동시 처리 시에 단백질 합성과 관련된 소포체 내 산화-환원 환경이 잘 유지됨을 확인함으로서, 구강건조증의 예방 및 치료용 조성물 및 건강기능식품으로 유용하게 이용될 수 있다.(1) In experiments using animal models with human salivary gland cells (HSG cells), it was found that the compounds of the present invention inhibit the secretion of amylase during the simultaneous treatment of the high-concentration glucose and the high- It was confirmed that not only the expression of the ER stress related protein was reduced but also the oxidative-reductive environment in the endoplasmic reticulum associated with protein synthesis was maintained well during the simultaneous treatment with glucose at a high concentration of short and long term, Can be usefully used as a functional food.
도 1은 고농도 포도당으로 인한 아밀라아제의 분비능실험 결과이며:
도 2는 씀바귀 추출물의 UPLC 성분분석 실험 결과이며 (도 2A는 8-epiisolipidiol-3-β-D-glucopyranoside 0.1 mg/mL의 chromatogram이며, 도 2B는 8-epiisolipidiol-3-β-D-glucopyranoside과 씀바귀 에탄올 추출물의 chromatogram (파란색: 8-epiisolipidiol-3-β-D-glucopyranoside, 검은색: 씀바귀 추출물)이며, 도 2C는 Ixerin M 0.05 mg/mL의 chromatogram이며; 도2D는 Ixerin M 과 씀바귀 에탄올 추출물의 chromatogram 데이터임);
도 3은 씀바귀 추출물로 인한 아밀라아제의 분비 효과 실험결과이며 (도3A은 침샘세포에서 장기간 고농도 포도당 처리 시 에탄올과 메탄올 씀바귀 추출물로 인한 아밀라아제의 분비 효과 실험 결과이며; 도 3B는 0, 20, 40, 60, 80과 100%의 에탄올 씀바귀 추출물별로 처리시 아밀라아제의 분비를 확인한 실험결과임);
도 4는 침샘세포에서 장기간 고농도 처리 시 100% 에탄올 씀바귀 추출물로 인한 시간 의존적인 아밀라아제의 분비 효과 실험결과이며(도 4A및 4 B는 각각 0, 1, 2, 3, 5, 7 일 별로 40 mM glucose를 단독 처리시와 100% 에탄올 씀바귀 추출물과 고농도의 포도당을 동시 처리시 아밀라아제의 분비를 확인한 결과임)
도 5는 침샘세포에서 장기간 고농도 처리 시 씀바귀 유효성분인 ID-56D1B (Ixerin M) 으로 인한 시간 의존적인 아밀라아제의 분비 효과 실험실과이며 (도 5A 및 5B는 각각 0, 1, 2, 3, 5, 7 일 별로 40 mM glucose를 단독 처리시와 Ixerin M 유효성분 추출물과 고농도의 포도당을 동시 처리시 아밀라아제의 분비를 확인한 결과임);
도 6은 침샘세포에서 단기간 고농도 처리 시 씀바귀 유효성분인 ID-57D로 인한 시간 의존적인 아밀라아제의 분비 효과 실험 결과이며 (도 6A는 0.005, 0.001, 0.002, 0.004 mg/mL의 ID-57D의 씀바귀 유효성분을 농도별를 처리하여 세포 생존도를 측정한 결과이며; 도 6B 및 C에서는 0, 12, 24, 36, 48 시간 대별로 40 mM glucose를 단독 처리시와 ID-57D와 고농도의 포도당을 동시 처리시 아밀라아제의 분비를 확인한 결과이며, 도 6D에서는 고농도의 포도당을 처리시와 ID-57D를 동시 처리시 소포체의 스트레스 관련 단백질의 발현을 확인한 결과임);
도 7은 침샘세포에서 장기간 고농도 처리 시 씀바귀 유효성분인 ID-57D로 인한 시간 의존적인 아밀라아제의 분비 효과 실험결과이며 (도 7A 및 도 7B는 0, 1, 2, 3, 5, 7 일 별로 40 mM glucose를 단독 처리시와 씀바귀 유효성분인 ID-57D와 고농도의 포도당을 동시 처리시 아밀라아제의 분비를 확인한 결과이며, 도 4C에서는 고농도의 포도당을 처리시와 ID-57D를 동시 처리시 소포체의 스트레스관련 단백질의 발현을 확인한 결과이며, 도 7D은 침샘세포에 0, 1, 2, 3, 5, 7 일 별로 고농도의 포도당을 처리시와 ID-57D를 고농도 포도당에 동시 처리 후 Oxydation정도를 확인한 결과임);
도 8은 동물 모델에서 스트렙토조토신(Streptozotocin) 처리시 씀바귀로 인한 혈당 변화 실험결과를 나타낸 도이며;
도 9는 동물 모델에서 스트렙토조토신 처리시 씀바귀로 인한 침샘의 무게, 단백질의 양 및 아밀라아제의 분비 효과 실험 결과이며;
도 10은 동물 모델에서 스트렙토조토신 처리시 씀바귀로 인한 타액과 침샘에서의 아밀라아제의 분비능 실험결과이며;
도 11은 동물 모델에서 스트렙토조토신 처리시 씀바귀로 인한 타액 분비율 실험결과이며;
도 12은 동물 모델에서 스트렙토조토신 처리시 씀바귀로 인한 침샘의 조직학적 분석 실험결과를 나타낸 도이다.Figure 1 shows the results of an assay for the secretion of amylase from high glucose:
FIG. 2 is a graph showing the result of UPLC analysis of the crude extract (FIG. 2A is a chromatogram of 8-epiisolipidiol-3-.beta.-D-glucopyranoside of 0.1 mg / mL and FIG. 2B is of 8-epiisolipidiol-3-.beta.-D-glucopyranoside FIG. 2C is a chromatogram of Ixerin M 0.05 mg / mL; FIG. 2D is a chromatogram of ethanol extract of Ixerin M and Zygomycetum; FIG. 2C is a chromatogram of Ixerin M 0.05 mg / Lt; / RTI >
FIG. 3 is a graph showing the results of experiments on the secretion effect of amylase due to ethanol extract and methanol extract on the high concentration glucose treatment in salivary gland cells; FIG. 3B shows the results of the secretion effects of amylase on 0, 20, 40, 60, 80 and 100% of ethanol extracts of Amaranthus japonicus);
FIG. 4 is a graph showing the results of time-dependent secretion of amylase from 100% ethanol extract of rosemary extract during long-term high-concentration treatment in salivary gland cells (FIGS. 4A and 4B show 40 mM glucose alone and the simultaneous treatment of 100% ethanol extract with high concentration of glucose and amylase secretion)
FIG. 5 is a time-dependent secretion effect study of amylase by ID-56D1B (Ixerin M), which is an effective ingredient for scavenging in high concentration treatment in salivary gland cells (FIGS. 5A and 5B are 0, 1, 2, 3, The result of amylase secretion in the simultaneous treatment of Ixerin M active ingredient extract and high glucose at 40 mg / day for 7 days);
FIG. 6 shows the results of the time-dependent secretion effect of amylase secreted by ID-57D, which is an effective component of the secretion in short-term high-concentration treatment in salivary gland cells (FIG. 6A shows 0.005, 0.001, 0.002, 0.004 mg / mL ID- 6B and C show the results of single cell treatment of 40 mM glucose, and simultaneous treatment of ID-57D and glucose at 0, 12, 24, 36, and 48 hours FIG. 6D shows the expression of stress-related proteins in the endoplasmic reticulum when treating high glucose and ID-57D simultaneously);
FIG. 7 shows the results of time-dependent secretion of amylase in the saline-germ cells treated with ID-57D, which is the active component of the secretion in high concentration treatment (FIGS. 7A and 7B show results of 40 mM glucose and the secretion of amylase in the simultaneous treatment of ID-57D and high concentration glucose in the case of treatment with high glucose and ID-57D at the same time, stress in the endoplasmic reticulum FIG. 7D shows the result of confirming the degree of Oxydation after treating high glucose at 0, 1, 2, 3, 5 and 7 days in salivary gland cells and ID-57D at high glucose concentration simultaneously being);
FIG. 8 is a graph showing the results of blood sugar change experiments due to scurvy during treatment with streptozotocin in an animal model; FIG.
FIG. 9 shows experimental results on the salivary gland weight, amount of protein and secretion effect of amylase in the animal model when treated with streptozotocin;
FIG. 10 shows the results of an assay for the secretion of amylase in saliva and salivary glands due to scurvy during streptozotocin treatment in animal models;
Figure 11 shows the results of saliva fraction ratios due to scurvy during streptozotocin treatment in animal models;
FIG. 12 is a graph showing the results of histological analysis of salivary glands due to scabies during streptozotocin treatment in an animal model. FIG.
이하, 본 발명을 실시예에 의해 상세히 설명한다. Hereinafter, the present invention will be described in detail by way of examples.
단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.
비교예 1. 씀바귀 메탄올 추출물COMPARATIVE EXAMPLE 1 < tb >
문헌(Hwa-Young Lee, Geum-Hwa Lee, Hye-Kyung Kim, Seung Hyun Kim, Kyung pyo Park, Han-Jung Chae, Hyung-Ryong Kim. Ixeris dentata-induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells. Food and Chemical Toxicology, Pages 11, Model 5G, 4, October 2013)에서는 한국생명공학연구원 한국 식물추출물은행(한국식물추출물은행 http://extract.pdre.re.kr, 대전)으로부터 구입한 씀바귀 메탄올 추출물을 사용하였다. 추출용매에 따른 유효성분 함량을 비교하기 위해서 건조된 씀바귀를 100% 메탄올로 추출하여 사용하였다. Literature (Hwa-Young Lee, Geum- Hwa Lee, Hye-Kyung Kim, Seung Hyun Kim, Kyung pyo Park, Han-Jung Chae, Hyung-Ryong Kim. Ixeris dentata- induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells. (Korea Plant Extract Bank, http://extract.pdre.re.kr , Daejeon) from Korea Biotechnology Research Institute in Korea, Food and Chemical Toxicology, Pages 11,
실시예 1. 씀바귀 에탄올 추출물EXAMPLES Example 1. Ethanol extract of horseradish
실험에 사용된 건조 상태의 씀바귀(Ixeris dentata)은 정우당 (정우당 http://www.herbseoul.com/, 서울)으로부터 구입하였다. 분쇄시료 30~40g을 HPLC용 100% 에탄올 용액 200mL으로 50℃에서 초음파분쇄기 (BRAONSON Ultrasonication corporation, ultrasonic cleaner, BRANSON)를 이용하여 추출하였고 이 추출액을 무형광 솜을 사용하여 여과시킨 후, 농축시켰다. 상기 시료를 동결 건조시킨 후 건조물을 하기 실험에 사용하였다. The dried Ixeris dentata used in the experiment was purchased from Jeung Woo ( http://www.herbseoul.com/ , Seoul, Korea). 30 ~ 40g of the pulverized sample was extracted with 200 mL of 100% ethanol solution for HPLC by using an ultrasonic pulverizer (BRAONSON Ultrasonication corporation, ultrasonic cleaner, BRANSON) at 50 ° C, and the extract was filtered using a cotton pad and concentrated. After the sample was lyophilized, the dried material was used in the following experiment.
실시예 2. Example 2. 씀바귀 추출물의 유효 성분 정량 실험Determination of active ingredient of extract
상기 비교예 및 실시예의 추출물들의 성분함량 및 성분상을 확인하기 위하여, 하기 표 1에 기재된 바와 같은 HPLC 분석조건으로 성분분석을 수행하였다.In order to confirm the component content and the component phase of the extracts of the above Comparative Examples and Examples, component analysis was performed under the HPLC analysis conditions as shown in Table 1 below.
씀바귀 추출물내 유효성분 함량 측정은 Waters ACQUITY UPLC H-Class System과 INNOPIA Inno C18 (4.6 x 150 mm, 5 μm) 컬럼을 이용하여 210 nm에서 측정하였다.The active ingredient content in the extract was measured at 210 nm using a Waters ACQUITY UPLC H-Class System and INNOPIA Inno C18 (4.6 x 150 mm, 5 μm) column.
2-1. 분석조건의 선정2-1. Selection of analysis conditions
○ 분석기기: Waters ACQUITY UPLC H-Class System○ Analytical instrument: Waters ACQUITY UPLC H-Class System
○ 컬럼 온도(Column temperature) 및 유속(flow rate): 30°C, 1 mL/min, 10 μL 주사(injection) Column temperature and flow rate: 30 ° C, 1 mL / min, 10 μL injection
○ 고정상, 이동상 및 검출조건: INNOPIA Inno C18 (4.6 x 150 mm, 5 μm), 210 nm○ Fixed phase, mobile phase and detection conditions: INNOPIA Inno C18 (4.6 × 150 mm, 5 μm), 210 nm
2-2. 결과2-2. result
상기 실험 결과, 씀바귀 추출물의 지표성분인 익세린 (Ixerin) M 및 ID-57D (8-epiisolipidiol-3-β-D-glucopyranoside)의 유효성분 함량 면에서, 100% 메탄올 추출물은 0.0507mg/100 mg (익세린 M) 및 0.0mg/100 mg (ID-56D1B)으로 나타난데 반하여, 100% 에탄올 추출물은 0.1266 mg/100 mg (익세린M) 및 0.2675mg/100 mg ((ID-56D1B)으로 나타나, 100% 에탄올추출물에서 Ixeris M과 ID-56D1B가 가장 많은 함량을 가지고 있음을 확인하였고, 0, 20, 40, 60, 80과 100%의 에탄올 씀바귀 추출물에서 씀바귀 지표성분의 함량을 확인한 결과 100% 에탄올추출물에서 Ixeris M과 8-EI-3G가 가장 많은 함량을 가지고 있음을 확인하였다. (도 2 및 표 2참조)As a result of the above experiment, in terms of the active ingredient content of Ixerin M and ID-57D (8-epiisolipidiol-3-β-D-glucopyranoside) which are the index components of scarab, the 100% methanol extract contained 0.0507 mg / 100 mg (ID-56D1B) and 0.1266 mg / 100 mg (Ixerin M) and 0.0675 mg / 100 mg (ID-56D1B), respectively, , And Ixeris M and ID-56D1B were found to be the most abundant in 100% ethanol extracts, and the content of indomethacin in the ethanol extracts of 0, 20, 40, 60, 80 and 100% Ixeris M and 8-EI-3G were the most abundant in the ethanol extracts (see FIG. 2 and Table 2).
(연세대)100% MeOH
(Yonsei University)
실시예 3. 씀바귀 추출물 분리화합물.Example 3. Scutellariae Extract Isolation Compound.
상기 실시예 1의 씀바귀 에탄올추출물로부터 하기와 같은 분리공정으로 (1) 11,13-dihydrointegrifolin 3-O-β-D-glucopyranoside, (이하, ID-56B2이라 함, 참고문헌: J. Marco, Juan F. Sanz-Cervera, Alberto Yuste, M. Carmen Oriola. Sesquiterpene lactones and dihydroflavonols from Andryala and Urospermum species. Phytochemistry, Page 727, Compound 4, 1994), (2) ixerisoside A, (ID-56D2이라 함, 참고문헌: Tsutomu Warashina, Mie Ishino, Toshio Miyase, Akira Ueno. Sesquiterpene glycosides from Ixeris debilis and Ixeris repens. Phytochemistry, Page 3220, Compound 9, 1990), (3) ixerin M, (ID-56D1B이라 함, 참고문헌: Keiichi Nishimura, Toshio Miyase, Akira Ueno, Tadataka Noro, Masanori Kuroyanagi, Seigo Fukushima. Sesquiterpene lactones from Ixeris stolonifera A. Gray. Chemical and Pharmaceutical Bulletin, Page 3363, Compound 1, 1985), (4) 8-epiisolipidiol-3-β-D-glucopyranoside, (ID-57D이라 함, 참고문헌: W. Kisiel, B. Barszcz. Sesquiterpene lactone glycosides from Crepis pyrenaica. Phytochemistry, Page 1396, Compound 4, 1995)을 각각 분리하였고 이들의 물성치를 각각 기존 문헌에 기재된 바와 비교하여 그 화합물 구조를 동정하였다. (1) 11,13-dihydrointegrifolin 3-O-? -D-glucopyranoside (hereinafter referred to as ID-56B2, reference: J. Marco, Juan F. Sanz-Cervera, Alberto Yuste, M. Carmen Oriola, Sesquiterpene lactones and dihydroflavonols from Andryala and Urospermum species. (2) ixerisoside A (referred to as ID-56D2, reference: Tsutomu Warashina, Mie Ishino, Toshio Miyase, Akira Ueno. Sesquiterpene glycosides from I xeris debilis and Ixeris repens . Phytochemistry,
상기 화합물들을 분리하고자 먼저 건조된 씀바귀 5 kg을 100% MeOH로 4시간 동안 3회 반복 초음파추출한 뒤, 추출액을 여과 후 감압 농축하여 MeOH extract 700 g을 얻었다. 이를 물에 분산시켜 chloroform (CHCl3), ethyl acetate (EtOAc), H2O 순으로 분획하여 각각 53.3 g, 17 g, 550 g의 추출물을 얻었다. H2O 분획을 HP-20 resin에 통과시켰으며, 이 때 용매로는 Water:MeOH(0:1 → 1:0)을 사용하여 5개의 fraction으로 나누었다 (3A-3E). 3B fraction에 대하여 silica gel column(30×40 ㎝) chromatography를 반복하였으며 용출 용매로는 CHCl3-MeOH = 4:1을 사용하여 ID-56B2 (15.0 mg) 을 얻었다. 3D fraction에 대하여 15% Acetonitrile in H2O를 용출용매로 하여 prep-LC를 실행하여 ID-56D2 (7.0 mg), ID-56D1B (4.6 mg)와 ID-57D (10.3 mg) 을 얻었다. In order to separate the compounds, 5 kg of dried scallops were ultrasonically extracted with 100% MeOH three times for 4 hours. The extract was filtered and concentrated under reduced pressure to obtain 700 g of MeOH extract. The fractions were fractionated in chloroform (CHCl 3 ), ethyl acetate (EtOAc) and H 2 O in the order of 53.3 g, 17 g and 550 g, respectively. The H 2 O fraction was passed through HP-20 resin, which was divided into five fractions (3A-3E) using Water: MeOH (0: 1 → 1: 0) as the solvent. 3B fraction was purified by silica gel column chromatography (30 × 40 cm). ID-56B2 (15.0 mg) was obtained by eluting with CHCl 3 -MeOH = 4: 1. Running a prep-LC to 15% Acetonitrile in H 2 O as eluent with respect to the 3D fraction to obtain the ID-56D2 (7.0 mg), ID-56D1B (4.6 mg) and ID-57D (10.3 mg).
(a) 11,13-디히드로인테그리폴린(dihydrointegrifolin) 3-O-β-D-글루코시드 (glucopyranoside) (ID-56B2)(a) 11,13-dihydrointegrifolin 3-O-? -D-glucopyranoside (ID-56B2)
- 분자량: C21H30O9 (MW: 426.46)- Molecular weight: C 21 H 30 O 9 ( MW: 426.46)
- 1H- NMR & 13C-NMR (표 3)- 1 H- NMR & C-13 NMR (Table 3)
2.30 (m)1.93 (m)
2.30 (m)
2.60 (m)2.82 (m)
2.60 (m)
5.06 (s)4.89 (s)
5.06 (s)
5.37 (s)5.30 (s)
5.37 (s)
3.85 (d, 11.6)3.64 (dd, 5.4, 11.6)
3.85 (d, 11.6)
(b) 익세리소시드(ixerisoside) A (ID-56D2)(b) ixerisoside A (ID-56D2)
- 분자량: C29H34O11 (MW: 558.57)- Molecular weight: C 29 H 34 O 11 (MW: 558.57)
- 1H- NMR & 13C-NMR (표 4) - 1 H- NMR & 13 C- NMR ( Table 4)
2.33 (m)1.92 (m)
2.33 (m)
6.01 (s)5.41 (s)
6.01 (s)
4.75 (s)5.03 (s)
4.75 (s)
5.46 (s)5.31 (s)
5.46 (s)
3.85 (d, 11.6)3.64 (dd, 4.6, 11.6)
3.85 (d, 11.6)
(c) 익세린(ixerin) M, (ID-56D1B)(c) ixerin M, (ID-56D1B)
- 분자량: C26H38O11 (MW: 526.57)- Molecular weight: C 26 H 38 O 11 (MW: 526.57)
- 1H- NMR & 13C-NMR (표 5) - 1 H- NMR & 13 C- NMR ( Table 5)
2.37 (m)2.00 (m)
2.37 (m)
2.64 (dd, 5.6, 14.1)2.49 (dd, 5.1, 14.1)
2.64 (dd, 5.6, 14.1)
6.19 (d, 3.5)5.58 (d, 3.5)
6.19 (d, 3.5)
5.15 (s)4.91 (s)
5.15 (s)
5.47 (s)5.37 (s)
5.47 (s)
3.86 (d, 11.6)3.64 (dd, 5.4, 11.6)
3.86 (d, 11.6)
(d) 8-에피이소리피디올(epiisolipidiol)-3-β-D-글루코피라노시드(glucopyranoside), (ID-57D)(d) 8-epiisolipidiol-3 -? - D-glucopyranoside, (ID-57D)
- 분자량: C21H32O9 (MW:428.47)- Molecular weight: C 21 H 32 O 9 ( MW: 428.47)
- 1H- NMR & 13C-NMR (표 6) - 1 H- NMR & 13 C- NMR ( Table 6)
2.251.82
2.25
2.58 (dd, 2.8, 13.2)2.26
2.58 (dd, 2.8, 13.2)
5.05 (s)4.91 (s)
5.05 (s)
3.85 (d, 11.6)3.65 (dd, 5.0, 11.6)
3.85 (d, 11.6)
실험예Experimental Example 1. One. 침샘세포에서In salivary gland cells 고농도 포도당 처리시 시간 의존적인 아밀라아제의 분비와 소포체 스트레스 발현 측정 및 산화-환원 환경에 미치는 영향 측정 Measurement of time-dependent secretion of amylase, expression of endoplasmic reticulum stress and effects on oxidative-reductive environment in high glucose treatment
시료들의 침샘세포(human salivary gland cells, HSG cells)에서 고농도 포도당 처리 시 시간 의존적인 아밀라아제의 분비 증가가 소포체 스트레스와 관련 효능을 확인하기 위하여 문헌에 기재된 방법을 응용하여 하기와 같이 실험하였다. (Lipson KL, Ghosh R, Urano F. The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells, PLoS One. 3(2) (2008) e1648.)In order to confirm the time-dependent increase of amylase secretion in human salivary gland cells (HSG cells) of the samples, the method described in the literature was applied as follows to confirm the effect of the stress on the endoplasmic reticulum. (Lipson KL, Ghosh R, Urano F. The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells, PLoS One. 3 (2) (2008) e1648.)
1.1 시약1.1 Reagents
씀바귀 추출물(한국자생식물원), Thapsigargin(sigma, T9033), tunicamycin(sigma, T7765), RPMI Medium 1640 배지 (gibco life technologie, 31800-022)으로 각각 제공 받았다.(Sigma, T9033), tunicamycin (sigma, T7765) and RPMI Medium 1640 medium (gibco life technologie, 31800-022), respectively.
1.2 세포배양1.2 Cell culture
Human salivary gland (HSG) cells는 RPMI 1640(sigma) 배지에 항생제 (antibiotics, 15140, gibco)와 10% fetal bovine serum (FBS, gibco, 10437028)을 첨가하여 배양 하였다. 세포는 일정한 습도를 유지하는 37℃ 항온기에서 공기(95%)와 CO2 (5%)의 혼합기체를 공급하면서 배양하고, 2~3일 마다 계대 배양하였다.Human salivary gland (HSG) cells were cultured in RPMI 1640 medium supplemented with antibiotics (antibiotics, 15140, gibco) and 10% fetal bovine serum (FBS, gibco, 10437028). Cells were cultured in a constant temperature humidified incubator at 37 ° C while supplying a mixed gas of air (95%) and CO 2 (5%) and subcultured every 2 to 3 days.
1.3 아밀라아제 활성 측정1.3 Measurement of amylase activity
아밀라아제 활성은 amylase assay kit (BioVision Co., K711-100)를 사용하여 405nm 파장에서 25℃로 설정한 후 ELISA를 이용하여 측정하였다.Amylase activity was measured using an amylase assay kit (BioVision Co., K711-100) at 25 ° C at a wavelength of 405 nm and then measured by ELISA.
1.4 웨스턴 블롯(Western Blot) 분석1.4 Western Blot Analysis
HSG 세포에 RIPA Buffer 완충액 (20 mM Tris-HCl (pH 7.5), 150 mM NaCl, 1 mM Na2EDTA, 1 mM EGTA, 1% NP-40, 1% sodium deoxycholate, 2.5 mM sodium pyrophosphate, 1 mM β-glycerophosphate, 1 mM Na3VO4)에 단백질 분해효소 억제제(P3100-001, GenDEPOT)를 처리하여 단백질을 추출하였다. 각 시료를 완충액과 섞어 5분간 끓인 후 Sodium dodecyl sulfate-polyacrylamide 겔(0227, AMRESCO)에서 전기영동 하여 단백질은 크기 별로 분리한 후 차단 완충액(blocking buffer(REF232100, BD Difco)으로 차단하고 소포체 스트레스 관련 항체의 발현을 확인하고자 4℃에서 하룻 밤 동안 반응 시킨 후, 이차 항체로 상온에서 1시간 반응시켰다. ECL 용액 (Dae Myung Science Co., Ltd, Korea)를 사용하여 단백질 발현을 확인하였다. Membrane을 actin 항체와 다시 반응시켜 일정한 양의 단백질을 사용하였는지 확인하였다.HSG cells were treated with RIPA Buffer buffer (20 mM Tris-HCl (pH 7.5), 150 mM NaCl, 1 mM Na 2 EDTA, 1 mM EGTA, 1% NP-40, 1% sodium deoxycholate, 2.5 mM sodium pyrophosphate, -Glycerophosphate, 1 mM Na 3 VO 4 ) was treated with a protease inhibitor (P3100-001, GenDEPOT) to extract the protein. Each sample was boiled for 5 minutes and then electrophoresed on sodium dodecyl sulfate-polyacrylamide gel (0227, AMRESCO). Proteins were separated by size, blocked with blocking buffer (REF232100, BD Difco) Was incubated overnight at 4 ° C and reacted with secondary antibody for 1 hour at room temperature to confirm protein expression using ECL solution (Dae Myung Science Co., Ltd., Korea). Re-reacted with antibody to confirm that a certain amount of protein was used.
1.5 Reverse transcription PCR1.5 Reverse transcription PCR
배양한 HSG cell로부터 RNA를 분리하기 위해 1mL의 Trizol(15596-026, life technologies)를 첨가한 후 상온에서 5분간 lysate를 배양(incubation)하였다. 200μL 클로로포름(chloroform)을 첨가하고 15초간 진탕(vortex)한 후 실온에서 10분간 배양(incubation)하였다. 그 후 13000rpm, 4℃에서 15분간 원심 분리한다. 상층액을 튜브에 옮긴 후 500 μL의 이소프로필 알콜(isopropyl alcohol)을 옮겨진 상층액에 넣고 진탕(vortex)하여 섞은 뒤 상온에 10분간 둔다. 13000 rpm으로 4℃, 15분간 원심 분리한다. RNA가 바닥에 침전된다. 미리 준비해둔 60 ℃ water(D5758, sigma-aldrich)에 샘플을 녹여 정량하였다.To separate the RNA from the cultured HSG cells, 1 mL of Trizol (15596-026, life technologies) was added and lysate was incubated at room temperature for 5 minutes. 200 [mu] L of chloroform was added, vortexed for 15 seconds, and incubated at room temperature for 10 minutes. Then centrifuge at 13000 rpm, 4 캜 for 15 minutes. Transfer the supernatant to a tube and add 500 μL of isopropyl alcohol into the transferred supernatant, vortex, mix and incubate at room temperature for 10 minutes. Centrifuge at 13000 rpm at 4 ° C for 15 minutes. RNA is deposited on the bottom. The sample was dissolved in 60 占 폚 water (D5758, Sigma-aldrich) prepared in advance and quantified.
1.6 cDNA 합성과정: Reverse Transcription1.6 cDNA synthesis procedure: Reverse Transcription
PrimeScript TM RT reagent Kit (Perfect Real Time, TaKaRa)를 이용하여 95°°C에서 3분, 95°°C에서 1분 동안 35사이클, 55°°C에서 1분간 72°°C에서 1분간, 72°°C 에서 51분간 진행 후 4℃에 보관한다. PCR (20 μμL)을 위해 cDNA (2.5 μL), double-distilled H2O(10.5 μL), Universal PCR Master Mix (5ΧΧ)(4 μL), reverse primer (0.5 μL), forward primer(0.5 μL)와 DMSO (2 μL)를 첨가한 후 Primus 96 (PeQLab)기기를 이용하여 PCR cDNA를 합성한다.PrimeScript TM RT reaction kit (Perfect Real Time, TaKaRa) for 3 minutes at 95 ° C, 35 cycles for 1 minute at 95 ° C, 1 minute at 72 ° C for 1 minute, 72 ° C C for 51 minutes and then stored at 4 ° C. PCR (20 μL), cDNA (2.5 μL), double-distilled H 2 O (10.5 μL), Universal PCR Master Mix (5 μX), reverse primer (0.5 μL) and forward primer After adding DMSO (2 μL), PCR cDNA is synthesized using Primus 96 (PeQLab) instrument.
1.7 단백질 산화 측정1.7 Protein oxidation measurement
Protein oxidation detection Kit (OxyBlotTM Chemical International, Temecula, CA)를이용하여 단백질 내 카보닐의 양을 측정하였다. 단백질 추출 후 10% SDS-PAGE를 이용하여 단백질을 분리시킨다. Immno-blotTM PVDF transfer membranes(162-0177, bio-rad)에 1차 항체인 디니트로페닐(dinitrophenyl)를 붙인 후 4℃에서 하룻밤 방치(overnight)한 후 다시 2차 항체인 rabbit(sc-2004, santa cruz)을 붙여 실온에서 1시간 동안 반응시켰다. 그 후 SuperDetectTM ECL 용액(Dae Myung Science Co., Ltd, Korea)을 이용하여 단백질의 발현을 확인한다.The amount of carbonyl in the protein was measured using a protein oxidation detection kit (OxyBlot TM Chemical International, Temecula, Calif.). After protein extraction, proteins are separated using 10% SDS-PAGE. Dinitrophenyl, a primary antibody, was added to Immno-blot ™ PVDF transfer membranes (162-0177, bio-rad) and incubated overnight at 4 ° C. The secondary antibody rabbit (sc-2004 , santa cruz) and allowed to react at room temperature for 1 hour. Then SuperDetect TM ECL solution (Dae Myung Science Co., Ltd., Korea).
1.8 통계학적인 처리1.8 Statistical processing
결과들은 평균 ± 표준오차로 표시하고, 변수의 분석들은 Duncan's test를 사용하였다. P 값이 0.05 미만인 경우에 통계적으로 유의 하다는 판정을 하였으며, 모든 실험은 독립적으로 3회 이상 실시하여 통계 처리를 하였다.Results were expressed as mean ± standard error, and Duncan's test was used for analysis of variables. P values less than 0.05 were considered to be statistically significant, and all experiments were performed three times or more independently and statistically.
1.9 실험결과1.9 Experimental Results
1) 장기간 고농도 포도당으로 인한 유효성분에서 아밀라아제의 분비능1) Secretion of amylase from active ingredient due to long-term high glucose concentration
본 실험 결과, 도 1에서 보듯이 침샘세포에서 유효성성분에서 고농도 포도당으로 인한 아밀라아제의 분비능을 연구하고자 장기간 40mM glucose를 함유한 배양액을 유효성분(ID-56B2, ID-56D2, Ixerin M 과 ID-57D를 침샘세포에 처리하였다. 그 후 배양액과 세포 내 아밀라아제의 분비를 확인한 결과, ID-56D1B2와 ID-57D에서 아밀라아제의 분비가 증가하는 것을 확인하였다. 침샘세포에서 유효성성분에서 고농도 포도당으로 인한 아밀라아제의 분비능을 연구하고자 장기간 40mM glucose를 함유한 배양액을 씀바귀 (IXD)추출물과 그 성분(ID-56B2, ID-56D2, Ixerin M 과 ID-57D를 침샘세포에 처리, 그 후 배양액과 세포 내 아밀라아제의 분비를 확인한 결과, ID-56D1B2 (Ixerin M)와 ID-57D에서 아밀라아제의 분비가 증가하는 것을 확인한 결과이다.As shown in FIG. 1, in order to investigate the secretion ability of amylase from high-concentration glucose in the active component of salivary gland cells, a culture medium containing 40 mM glucose for a long period of time was used as the active ingredient (ID-56B2, ID-56D2, Ixerin M and ID- And the amylase secretion was increased in ID-56D1B2 and ID-57D, respectively. The secretion of amylase from the culture medium and intracellular amylase was increased in the salivary gland cells (IXD) extract and its components (ID-56B2, ID-56D2, Ixerin M and ID-57D) were transplanted into salivary gland cells and then secreted in culture medium and intracellular amylase (IDx-56D1B2 (Ixerin M) and ID-57D), and the results showed that the secretion of amylase was increased in ID-56D1B2 (Ixerin M) and ID-57D.
2) 2) 침샘세포에서In salivary gland cells 장기간 고농도 포도당 처리 시 에탄올과 메탄올 씀바귀 추출물로 인한 아밀라아제의 분비 효과 실험 Effects of ethanol and methanol extract on the secretion of amylase during long-term high glucose treatment
본 실험 결과, 도 3A에서 보듯이 100%에탄올과 100%메탄올에서 씀바귀 추출물의 아밀라아제의 분비를 확인한 결과 100% 에탄올 씀바귀 추출물과 고농도의 포도당(G8270, sigma-aldrich)을 동시 처리시 아밀라아제의 분비가 더 많이 증가함을 확인하였고 도 3B에서 보듯이 0, 20, 40, 60, 80과 100%의 에탄올 씀바귀 추출물별로 처리시 아밀라아제의 분비를 확인한 결과, 100% 에탄올 씀바귀 추출물과 고농도의 포도당을 동시 처리시 아밀라아제의 분비가 78% 더 많이 증가하는 것을 확인하였다.As shown in FIG. 3A, the secretion of amylase from the extracts of 100% ethanol and 100% methanol showed that the secretion of amylase during the simultaneous treatment of 100% ethanol extract and high concentration of glucose (G8270, sigma-aldrich) As shown in FIG. 3B, when amylase secretion was observed at 0, 20, 40, 60, 80 and 100% ethanol extracts, the extracts of 100% ethanol and high concentration of glucose were simultaneously treated The secretion of cyamylase was increased by 78%.
3) 3) 침샘세포에서In salivary gland cells 장기간 고농도 처리 시 100% 에탄올 씀바귀 추출물로 인한 시간 의존적인 아밀라아제의 분비 효과 실험 Time-dependent secretion of amylase from 100% ethanol extract of rosemary extract
본 실험 결과, 도 4A, B에서 보듯이 0, 1, 2, 3, 5, 7 일 별로 40mM glucose를 단독 처리시와 100% 에탄올 씀바귀 추출물과 고농도의 포도당을 동시 처리시 아밀라아제의 분비를 확인한 결과 고농도를 단독 처리시 아밀라아제의 분비가 3일 이후부터는 감소되는 반면 100% 에탄올 씀바귀 추출물과 고농도의 포도당을 동시 처리하게 되면 3일 이후에도 아밀라아제의 분비가 95.3% 증가함을 확인하였다. As shown in FIGS. 4A and 4B, the secretion of amylase was observed when 40 mM glucose alone, 0, 1, 2, 3, 5 and 7 days, and 100% Amylase secretion was decreased after 3 days when high concentration was treated alone. However, when 100% ethanol extract and high concentration of glucose were simultaneously treated, the secretion of amylase was increased by 95.3% even after 3 days.
4) 4) 침샘세포에서In salivary gland cells 장기간 고농도 처리 시 씀바귀 유효성분인 ID- At high-concentration treatment for a long time Ingredients ID- 56D1B256D1B2 ( ( IxerinIxerin M) M) 으로to 인한 시간 의존적인 아밀라아제의 분비 효과 실험 Time-dependent secretion effect of amylase
본 실험 결과, 도 5A, B에서 보듯이 0, 1, 2, 3, 5, 7 일 별로 40 mM glucose를 단독 처리시와 Ixrin M 유효성분 추출물과 고농도의 포도당을 동시 처리시 아밀라아제의 분비를 확인한 결과 고농도를 단독 처리시 아밀라아제의 분비가 3일 이후부터는 감소되는 반면 Ixrin M 유효성분 추출물과 고농도의 포도당을 동시 처리하게 되면 3일 이후에도 아밀라아제의 분비가 92.8% 증가함을 확인하였다. As shown in FIGS. 5A and 5B, the secretion of amylase was observed when 40 mM glucose alone was treated at 0, 1, 2, 3, 5 and 7 days and when Ixrin M active ingredient extract and high glucose were simultaneously treated As a result, the secretion of amylase was decreased from 3 days after the high concentration treatment, whereas the secretion of amylase was increased by 92.8% even after 3 days when the extract of Ixrin M and the high concentration of glucose were simultaneously treated.
5) 5) 침샘세포에서In salivary gland cells 단기간 고농도 처리 시 씀바귀 유효성분인 ID-57D로 인한 시간 의존적인 아밀라아제의 분비 효과 실험 Time-dependent secretion effect of amylase in ID-57D
본 실험 결과, 도 6A에서 보듯이 0.005, 0.001, 0.002, 0.004 mg/mL의 ID-57D의 씀바귀 유효성분을 농도별를 처리하여 세포 생존도를 확인하였다. 도 6B, C에서는 0, 12, 24, 36, 48 시간 대별로 40mM glucose를 단독 처리시와 ID-57D와 고농도의 포도당을 동시 처리시 아밀라아제의 분비를 확인한 결과, ID-57D와 고농도의 포도당을 동시 처리시 더 많이 아밀라아제의 분비가 77% 더 많이 증가하는 것을 확인하였다. 도 6D에서는 고농도의 포도당을 처리시와 ID-57D를 동시 처리시 소포체의 스트레스 관련 단백질의 발현을 확인한 결과 단백질의 발현이 증가하지 않음을 확인하였다. 도 6D에서 나타낸 바와 같이, 침샘세포에 0, 12, 24, 36, 48 시간대 별로 고농도(40 mM)의 포도당을 처리시 와 고농도의 포도당에 ID-57D를 동시 처리 시 단백질 합성과 관련된 소포체 내 산화와 환원 반응을 확인하기 위해 Oxyblot의 발현을 확인하였다. 도표에서와 같이 시간 의존적으로 씀바귀를 동시 처리시 세포내 산화-환원 환경이 더 잘 유지됨을 확인하였다.As shown in FIG. 6A, the cell viability of ID-57D was determined by treatment with 0.005, 0.001, 0.002, and 0.004 mg / mL of the active ingredient, In FIG. 6B and FIG. 6C, amylase secretion was observed when 40 mM glucose alone was treated at 0, 12, 24, 36 and 48 hours and when ID-57D and high glucose were simultaneously treated. As a result, ID- At the same time, the secretion of amylase was increased by 77% more. In FIG. 6D, the expression of stress-related proteins in the endoplasmic reticulum was not observed when the high glucose concentration and ID-57D were simultaneously treated. As shown in FIG. 6D, when ID-57D was simultaneously treated with glucose at a high concentration (40 mM) for 0, 12, 24, 36 and 48 hours in salivary gland cells and at high concentration of glucose, And the expression of Oxyblot was confirmed to confirm the reduction reaction. As shown in the chart, it was confirmed that the intracellular oxidation-reduction environment was better maintained at the same time in the time-dependent manner.
6) 6) 침샘세포에서In salivary gland cells 장기간 고농도 처리 시 씀바귀 유효성분인 ID-57D로 인한 시간 의존적인 아밀라아제의 분비 효과 실험 Time-dependent secretion effect of amylase due to ID-57D, an effective ingredient of the scavenger during long-term high-concentration treatment
본 실험 결과, 도 7A,B에서 보듯이 0, 1, 2, 3, 5, 7 일 별로 40mM glucose를 단독 처리시와 씀바귀 유효성분인 ID-57D와 고농도의 포도당을 동시 처리시 아밀라아제의 분비를 확인한 결과 고농도를 단독 처리시 아밀라아제의 분비가 3일 이후부터는 99.5% 감소되는 반면 ID-57D와 고농도의 포도당을 동시 처리하게 되면 3일 이후에도 아밀라아제의 분비가 97.8% 증가함을 확인하였다. 도 4C에서는 고농도의 포도당을 처리시와 ID-57D를 동시 처리시 소포체의 스트레스관련 단백질의 발현을 확인한 결과 고농도의 포도당을 처리하게 되면 소포체 스트레스의 단백질의 발현(GRP78, CHOP, p-eIF2α, XBP-1)이 증가하지만 ID-57D를 동시 처리하게 되면 소포체 스트레스 관련 단백질의 발현이 감소함을 확인하였다. 도 7D에서 나타낸 바와 같이, 침샘세포에 0, 1, 2, 3, 5, 7 일 별로 고농도의 포도당을 처리시와 ID-57D를 고농도 포도당에 동시 처리 후 Oxyblot의 발현을 확인한 결과, 고농도의 포도당을 처리하게 되면 소포체 산화와 환원 환경이 망가진 반면에 ID-57D를 동시처리하게 되면 소포체 내 산환 환원의 환경이 유지됨을 확인하였다.As shown in FIG. 7A and FIG. 7B, when 40 mM glucose alone was treated at 0, 1, 2, 3, 5 and 7 days, the secretion of amylase during the simultaneous treatment of ID-57D and high- As a result, the secretion of amylase was decreased by 99.5% from 3 days after the treatment of high concentration, whereas the secretion of amylase was increased by 97.8% even after 3 days of simultaneous treatment of ID-57D and high glucose. FIG. 4C shows the expression of stress-related proteins in the endoplasmic reticulum when treating high glucose and ID-57D simultaneously. As a result, when high glucose was treated, expression of protein of ER stress (GRP78, CHOP, p-eIF2 ?, XBP -1), but the simultaneous treatment of ID-57D decreased the expression of ER stress-related proteins. As shown in FIG. 7D, the expression of Oxyblot was observed in saline cells treated with glucose at a high concentration of 0, 1, 2, 3, 5, or 7 days and ID-57D at a high glucose concentration, , The endoplasmic reticulum oxidation and reduction environment were destroyed, whereas the simultaneous treatment of ID-57D showed that the environment of the endoplasmic reticulum was maintained.
7) 동물 모델에서 스트렙토조토신 처리시 씀바귀로 인한 혈당 변화 실험7) Experimental study of blood glucose change by streptozotocin treatment in animal model
본 실험 결과, 도 8에서 보듯이 대조군에서는 혈당이 정상적인 범위내서 일정하게 유지됨을 확인하였지만 스트렙토조토신(S0130, sigma-aldrich)을 단독 처리시와 씀바귀와 스트렙토조토신을 동시 처리시 혈당 변화를 측정한 결과 혈당이 300mg/dl 이상으로 고혈당을 유지함을 확인하였다. As shown in FIG. 8, in the control group, it was confirmed that the blood glucose level remained constant within the normal range. However, when the streptozotocin (S0130, sigma-aldrich) was treated alone and the glucose level change As a result, it was confirmed that hyperglycemia was maintained at a blood glucose level of 300 mg / dl or more.
8) 동물 모델에서 8) In animal models 스트렙토조토신Streptozotocin 처리시 씀바귀로 인한 침샘의 무게, 단백질의 양 및 아밀라아제의 분비 효과 실험 Experiments on salivary gland weight, protein amount and secretion effect of amylase due to umbagus during treatment
본 실험 결과, 도 9에서 보듯이 스트렙토조토신(streptozotocin)을 단독 처리시와 씀바귀와 스트렙토조토신을 동시 처리시 침샘 무게와 단백질의 양을 확인한 결과 스트렙토조토신을 단독 처리시 대조군에 비해 침샘 무게는 감소하고 단백질의 양이 증가되는 반면 씀바귀와 스트렙토조토신을 동시 처리하게 되면 침샘 무게는 증가하지만 단백질의 양은 대조군에 비해 증가하지만 스트렙토조토신을 처리한 군에 비해 감소함을 확인하였고 스트렙토조토신을 단독 처리시와 씀바귀와 스트렙토조토신을 동시 처리시 타액과 침샘에서 아밀라아제의 분비를 확인한 결과 스트렙토조토신을 단독 처리시 대조군에 비해 아밀라아제의 분비가 감소하는 반면 씀바귀와 스트렙토조토신을 동시 처리하게 되면 스트렙토조토신을 단독 처리 군에 비해 아밀라아제의 분비가 98% 증가함을 확인하였다. As shown in FIG. 9, when the streptozotocin alone was treated, and the amount of salivary gland and protein was simultaneously measured at the same time, the weight of the salivary glands was reduced compared with the control group In contrast, the amount of protein increased while the weight of the salivary gland was increased by simultaneous treatment of scutellum and streptozotocin. However, the amount of protein was increased compared to the control group, but decreased compared with the group treated with streptozotocin. The secretion of amylase in saliva and salivary glands was measured at the same time. The secretion of amylase was decreased in the single treatment of streptozotocin compared to that of control, whereas the treatment of streptozotocin alone and the treatment of streptozotocin Secretion of amylase compared to Increase of 98% was confirmed that.
9) 동물 모델에서 Streptozotocin 처리시 씀바귀로 인한 타액과 침샘에서의 아밀라아제의 분비능 실험9) Experimental study on secretion of amylase in saliva and salivary glands due to scabies during treatment with Streptozotocin in animal models
본 실험 결과, 도 10에서 보듯이 스트렙토조토신을 단독 처리시와 씀바귀와 스트렙토조토신을 동시 처리시 타액과 침샘에서의 아밀라아제의 분비능을 확인한 결과 스트렙토조토신을 단독 처리시 대조군에 비해 타액과 침샘에서의 아밀라아제의 분비능은 감소되는 반면 씀바귀와 스트렙토조토신을 동시 처리하게 되면 아밀라아제의 분비능은 대조군에 비해 감소하지만 스트렙토조토신을 처리한 군에 비해 97.5% 증가함을 확인하였다. As shown in FIG. 10, when the streptozotocin alone treatment and the secretion of amylase in the saliva and salivary glands were examined at the same time, the treatment of streptozotocin alone showed amylase activity in the saliva and salivary glands While the secretory capacity of amylase was decreased by 97.5% compared with that of the control group compared with that of the control group.
10) 동물 모델에서 스트렙토조토신 처리시 씀바귀로 인한 타액 분비율 실험10) Experiments on the ratio of saliva in the animal model for the treatment of streptozotocin
본 실험 결과, 도 11에서 보듯이 스트렙토조토신을 단독 처리시와 씀바귀와 streptozotocin을 동시 처리시 타액 분비율을 확인한 결과 스트렙토조토신을 단독 처리시 대조군에 비해 타액 분비율이 감소되는 반면 씀바귀와 스트렙토조토신을 동시 처리하게 되면 타액 분비율이 대조군에 비해 감소하지만 스트렙토조토신을 처리한 군에 비해 72% 증가함을 확인하였다. As shown in FIG. 11, when the streptozotocin was treated alone, and the streptozotocin was simultaneously treated with streptozotocin, the salivary ratio was decreased in the case of streptozotocin treatment alone, whereas the ratio of salivary and streptozotocin Simultaneous treatment showed that the saliva fraction was decreased by 72% as compared with the control group, but compared with the group treated with streptozotocin.
11) 동물 모델에서 스트렙토조토신 처리시 씀바귀로 인한 침샘의 조직학적 분석 실험11) Histological analysis of the salivary glands due to scabies during streptozotocin treatment in animal models
본 실험 결과, 도 12에서 보듯이 스트렙토조토신을 단독 처리시와 씀바귀와 스트렙토조토신을 동시 처리시 조직학적 분석을 확인한 결과 스트렙토조토신을 단독 처리시 침샘의 구조가 엉성해지고 망가짐을 확인한 반면 씀바귀와 스트렙토조토신을 동시 처리하게 되면 스트렙토조토신을 단독 처리 군에 비해 침샘의 구조가 잘 유지됨을 확인하였다. 또한 면역염색을 통해 아밀라아제의 발현을 확인한 결과 스트렙토조토신을 단독 처리시 아밀라아제의 발현이 감소함을 확인한 반면 씀바귀와 스트렙토조토신을 동시 처리하게 되면 스트렙토조토신을 단독 처리 군에 비해 아밀라아제의 발현이 증가함을 확인하였다.As shown in FIG. 12, histological analysis of the treatment of streptozotocin alone and simultaneous treatment of scorpion and streptozotocin showed that the structure of the salivary gland was lost and deteriorated upon treatment with streptozotocin alone, while that of scorpion and streptozotocin It was confirmed that the salivary gland structure was maintained better than the single treatment group with streptozotocin. In addition, amylase expression was confirmed by immunohistochemical staining. As a result, amylase expression was decreased when streptozotocin alone was treated, whereas amytase expression of streptozotocin was increased when streptozotocin was co-treated with streptozotocin alone Respectively.
하기에 본 발명의 화합물을 포함하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, formulation examples of the composition containing the compound of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.
<제제예 1> 산제의 제조≪ Formulation Example 1 > Preparation of powders
화합물 ID-56B2 ---------------------------------------- 20 mgCompound ID-56B2 ---------------------------------------- 20 mg
유당 ------------------------------------------------- 100 mgLactose ------------------------------------------------- 100 mg
탈크 -------------------------------------------------- 10 mgTalc ------------------------------------------------- - 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above components are mixed and filled in airtight bags to prepare powders.
<제제예 2> 정제의 제조 ≪ Formulation Example 2 > Preparation of tablet
화합물 ID-56D2 ---------------------------------------- 10 mgCompound ID-56D2 ---------------------------------------- 10 mg
옥수수전분 ------------------------------------------- 100 mgCorn starch ------------------------------------------- 100 mg
유당 ------------------------------------------------- 100 mgLactose ------------------------------------------------- 100 mg
스테아린산 마그네슘 ------------------------------------ 2 mgMagnesium stearate ------------------------------------ 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
<제제예 3> 캡슐제의 제조 ≪ Formulation Example 3 > Preparation of capsules
화합물 ID-56D1B ---------------------------------------- 10 mgCompound ID-56D1B ---------------------------------------- 10 mg
결정성 셀룰로오스 --------------------------------------- 3 mgCrystalline cellulose --------------------------------------- 3 mg
락토오스 --------------------------------------------- 14.8 mgLactose --------------------------------------------- 14.8 mg
마그네슘 스테아레이트 --------------------------------- 0.2 mgMagnesium stearate 0.2 mg < RTI ID = 0.0 >
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.
<제제예 4> 주사제의 제조≪ Formulation Example 4 > Preparation of injection
화합물 ID-ID-57D --------------------------------------- 10 mgCompound ID-ID-57D --------------------------------------- 10 mg
만니톨 ------------------------------------------------ 180 mgMannitol ------------------------------------------------ 180 mg
주사용 멸균 증류수 ----------------------------------- 2974 mgSterile sterile distilled water used - 297 mg
Na2HPO4,12H2O ------------------------------------------- 26 mgNa 2 HPO 4, 12H 2 O ------------------------------------------ - 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당(2㎖) 상기의 성분 함량으로 제조한다.(2 ml) per 1 ampoule according to the usual injection preparation method.
<제제예 5> 액제의 제조≪ Formulation Example 5 > Preparation of liquid agent
화합물 ID-56B2 ---------------------------------------- 20 mgCompound ID-56B2 ---------------------------------------- 20 mg
이성화당 ----------------------------------------------- 10 gIssa Party ----------------------------------------------- 10 g
만니톨 -------------------------------------------------- 5 gMannitol ------------------------------------------------- - 5 g
정제수 ------------------------------------------------- 적량Purified water ------------------------------------------------- Suitable amount
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.
<제제예 6> 건강 식품의 제조≪ Formulation Example 6 > Preparation of health food
화합물 ID-56D2 ------------------------------------- 1000 ㎎Compound ID-56D2 - 1000 mg
비타민 혼합물 ------------------------------------------ 적량Vitamin mixture -------------------------------------------
비타민 A 아세테이트 ----------------------------------- 70 ㎍Vitamin A Acetate ----------------------------------- 70 [mu] g
비타민 E --------------------------------------------- 1.0 ㎎Vitamin E --------------------------------------------- 1.0 mg
비타민 B1 ------------------------------------------- 0.13 ㎎Vitamin B1 ------------------------------------------- 0.13 mg
비타민 B2 ------------------------------------------- 0.15 ㎎Vitamin B2 - 0.15 mg
비타민 B6 -------------------------------------------- 0.5 ㎎Vitamin B6 -------------------------------------------- 0.5 mg
비타민 B12 ------------------------------------------- 0.2 ㎍Vitamin B12 ------------------------------------------- 0.2 g
비타민 C ---------------------------------------------- 10 ㎎Vitamin C ---------------------------------------------- 10 mg
비오틴 ------------------------------------------------ 10 ㎍Biotin ------------------------------------------------ 10 G
니코틴산아미드 --------------------------------------- 1.7 ㎎Nicotinic acid amide 1.7 mg
엽산 -------------------------------------------------- 50 ㎍Folic acid ------------------------------------------------- - 50 [mu] g
판토텐산 칼슘 ---------------------------------------- 0.5 ㎎Calcium pantothenate ---------------------------------------- 0.5 mg
무기질 혼합물 ------------------------------------------ 적량Inorganic mixture --------------------------------------------------------------------------
황산제1철 ------------------------------------------- 1.75 ㎎Ferrous sulfate 1.75 mg < RTI ID = 0.0 >
산화아연 -------------------------------------------- 0.82 ㎎Zinc oxide - 0.82 mg
탄산마그네슘 ---------------------------------------- 25.3 ㎎Magnesium carbonate ---------------------------------------- 25.3 mg
제1인산칼륨 ------------------------------------------- 15 ㎎
제2인산칼슘 ------------------------------------------- 55 ㎎Secondary Calcium Phosphate - 55 mg
구연산칼륨 -------------------------------------------- 90 ㎎Potassium citrate -------------------------------------------- 90 mg
탄산칼슘 --------------------------------------------- 100 ㎎Calcium carbonate - 100 mg
염화마그네슘 ---------------------------------------- 24.8 ㎎Magnesium chloride ---------------------------------------- 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
<제제예 7> 건강 음료의 제조≪ Formulation Example 7 > Preparation of health drink
화합물 ID-ID-57D ------------------------------------ 1000 ㎎Compound ID-ID-57D ------------------------------------ 1000 mg
구연산 ---------------------------------------------- 1000 ㎎Citric acid ---------------------------------------------- 1000 mg
올리고당 ---------------------------------------------- 100 gOligosaccharides ---------------------------------------------- 100 g
매실농축액 ---------------------------------------------- 2 gPlum concentrate ---------------------------------------------- 2 g
타우린 -------------------------------------------------- 1 gTaurine ------------------------------------------------- - 1 g
정제수 ------------------------------------------ 전체 900 ㎖Purified water 900 ml total
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.
Claims (6)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020160011362A KR101621842B1 (en) | 2016-01-29 | 2016-01-29 | A composition comprising the compounds(ID-56D2) isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020160011362A KR101621842B1 (en) | 2016-01-29 | 2016-01-29 | A composition comprising the compounds(ID-56D2) isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020140116792A Division KR101601778B1 (en) | 2014-09-03 | 2014-09-03 | A composition comprising the compounds isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20160028423A KR20160028423A (en) | 2016-03-11 |
KR101621842B1 true KR101621842B1 (en) | 2016-05-18 |
Family
ID=55582998
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020160011362A KR101621842B1 (en) | 2016-01-29 | 2016-01-29 | A composition comprising the compounds(ID-56D2) isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR101621842B1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20200098776A (en) | 2019-02-12 | 2020-08-21 | (주) 바이오에스텍 | Slow-releasing type patch for relieving xerostomia |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102241282B1 (en) * | 2019-07-03 | 2021-04-15 | 전북대학교산학협력단 | Composition for hard tissue formation and, dentin or pulp regeneration containing Ixeris dentata extract and its active compound |
-
2016
- 2016-01-29 KR KR1020160011362A patent/KR101621842B1/en active IP Right Grant
Non-Patent Citations (4)
Title |
---|
Bulletin of the Korean Chemical Society, 2012, 33(1), 337-340 |
Phytochemistry, 1993, 34(6), 1565-1567 |
Planta Medica, 2011, 77(4), 380-382 |
석사학위논문(이화영, 전북대학교, 의학영양치료학 2012.8) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20200098776A (en) | 2019-02-12 | 2020-08-21 | (주) 바이오에스텍 | Slow-releasing type patch for relieving xerostomia |
Also Published As
Publication number | Publication date |
---|---|
KR20160028423A (en) | 2016-03-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100765416B1 (en) | Composition comprising the extract of Siegesbeckiae Herba for preventing and treating arthritis | |
KR101789424B1 (en) | Medicinal-Herb Composition Comprising Chinese matrimony vine Proving Insomniac and the Method of Making the Same | |
KR20210047594A (en) | Compositions for reinforcing skin barrier and improving atopic dermatitis using hydrangenol or phyllodulcin as an active ingredient | |
KR101621842B1 (en) | A composition comprising the compounds(ID-56D2) isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia | |
KR101621838B1 (en) | A composition comprising the compounds(ID-56D1B) isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia | |
KR101829637B1 (en) | A composition for improving, preventing and treating digestion dysfunction, leukocyte reduce, bone marrow suppression by side effects after anti-cancer therapy comprising Rhus verniciflua stoke extract | |
KR101811207B1 (en) | Composition for treatment, improvement or prevention of pulmonary diseases comprising extract of platycarya strobilacea leaf, birch bark or inonotus obliquus as an effective component | |
KR20160141027A (en) | Phamaceutical composition or healthy food comprising water extracts from Pleurotus eryngii var. ferulea (Pf.). for treating or preventing metabolic disorder | |
KR101621847B1 (en) | A composition comprising the compounds (ID-57D) isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia | |
KR20220001315A (en) | A composition comprising an extract of Thymus quinquecostatus Celak for treating and preventing hangover | |
KR101601778B1 (en) | A composition comprising the compounds isolated from an extract of Ixeris dentata NAKAI for treating or preventing xerostomia | |
KR101683344B1 (en) | Composition comprising carnosic acid for preventing or improving menopausal symptoms | |
KR20160028145A (en) | A composition comprising an ethanol extract of Ixeris dentata NAKAI for treating or preventing xerostomia | |
KR20140129492A (en) | Compositions Comprising a Leaf Extract of Cudrania tricuspidata for the Prevention and Treatment of Arthritis disease | |
KR101910013B1 (en) | A composition for improving, preventing and treating of pain comprising herb extract | |
KR100686260B1 (en) | Composition comprising the extract from melandryum firmum for improvement of liver function and treatment of liver diseases | |
KR100826311B1 (en) | Pharmaceutical composition comprising an extract of Prunus persica L preventing from hepatotoxicity and nephrotoxicity induced by anticancer agent | |
KR20150031373A (en) | Phamaceutical and food composition for preventing or treating obesity comprising extract of leaf from Hoppophea rhamnoids as effective component | |
KR101264014B1 (en) | Composition for Preventing or Treating Bone Disease Comprising of Aminocoumarins | |
KR101597187B1 (en) | A composition comprising the extract of Melia azedarach showing anti-cancer activity against stomach tumor | |
KR100895500B1 (en) | Composition for the prevention and treatment of fatty liver diseases containing honokiol as an active ingredient | |
KR20110073801A (en) | Composition comprising the extract of mixed crude drug showing anti-allergic effect | |
KR20140142516A (en) | A composition comprising the extract of Bupleurum falcatum (BF) and Physalis alkekengi var. francheti (PAF) as an active ingredient for preventing and treating inflammatory disease | |
KR100640094B1 (en) | Composition comprising the seed oil of Green Tea having Cholesterol-lowering or antioxidant activity | |
KR20210002954A (en) | Composition for preventing or treating hearing loss comprising extract of leaves or stem of sweet potato |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A107 | Divisional application of patent | ||
A201 | Request for examination | ||
E701 | Decision to grant or registration of patent right | ||
N231 | Notification of change of applicant | ||
GRNT | Written decision to grant | ||
FPAY | Annual fee payment |
Payment date: 20190520 Year of fee payment: 4 |