WO2007043305A1 - インスリン抵抗性改善剤 - Google Patents
インスリン抵抗性改善剤 Download PDFInfo
- Publication number
- WO2007043305A1 WO2007043305A1 PCT/JP2006/318813 JP2006318813W WO2007043305A1 WO 2007043305 A1 WO2007043305 A1 WO 2007043305A1 JP 2006318813 W JP2006318813 W JP 2006318813W WO 2007043305 A1 WO2007043305 A1 WO 2007043305A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- insulin resistance
- hydroxyl group
- compound
- hydrogen atom
- group
- Prior art date
Links
- 206010022489 Insulin Resistance Diseases 0.000 title claims abstract description 152
- 208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 134
- 239000003795 chemical substances by application Substances 0.000 title claims description 51
- 150000001875 compounds Chemical class 0.000 claims abstract description 90
- 235000013305 food Nutrition 0.000 claims abstract description 43
- 239000000284 extract Substances 0.000 claims abstract description 35
- 238000004519 manufacturing process Methods 0.000 claims abstract description 28
- 241000196324 Embryophyta Species 0.000 claims abstract description 26
- 239000004480 active ingredient Substances 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 14
- 241000234280 Liliaceae Species 0.000 claims abstract description 11
- 235000013361 beverage Nutrition 0.000 claims abstract description 9
- 241000209504 Poaceae Species 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 32
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 239000000126 substance Substances 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- RRTBTJPVUGMUNR-UHFFFAOYSA-N Cycloartanol Natural products C12CCC(C(C(O)CC3)(C)C)C3C2(CC)CCC2(C)C1(C)CCC2C(C)CCCC(C)C RRTBTJPVUGMUNR-UHFFFAOYSA-N 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 7
- 101150065749 Churc1 gene Proteins 0.000 claims description 7
- 102100038239 Protein Churchill Human genes 0.000 claims description 7
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 5
- 125000004922 2-methyl-3-pentyl group Chemical group CC(C)C(CC)* 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 238000003809 water extraction Methods 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 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 abstract description 66
- 102000004877 Insulin Human genes 0.000 abstract description 33
- 108090001061 Insulin Proteins 0.000 abstract description 33
- 229940125396 insulin Drugs 0.000 abstract description 33
- 102000014777 Adipokines Human genes 0.000 abstract 2
- 108010078606 Adipokines Proteins 0.000 abstract 2
- 230000002969 morbid Effects 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 41
- 230000000694 effects Effects 0.000 description 29
- 210000001789 adipocyte Anatomy 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 23
- 235000021588 free fatty acids Nutrition 0.000 description 19
- 201000010099 disease Diseases 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 230000009471 action Effects 0.000 description 17
- 235000011399 aloe vera Nutrition 0.000 description 14
- 239000003814 drug Substances 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 12
- 206010012601 diabetes mellitus Diseases 0.000 description 12
- 239000008103 glucose Substances 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 230000036541 health Effects 0.000 description 11
- XZEUYTKSAYNYPK-UHFFFAOYSA-N 3beta-29-Norcycloart-24-en-3-ol Natural products C1CC2(C)C(C(CCC=C(C)C)C)CCC2(C)C2CCC3C(C)C(O)CCC33C21C3 XZEUYTKSAYNYPK-UHFFFAOYSA-N 0.000 description 10
- 244000144927 Aloe barbadensis Species 0.000 description 10
- 235000002961 Aloe barbadensis Nutrition 0.000 description 10
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 10
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- HVXLSFNCWWWDPA-UHFFFAOYSA-N Isocycloartenol Natural products C1CC(O)C(C)(C)C2C31CC13CCC3(C)C(C(CCCC(C)=C)C)CCC3(C)C1CC2 HVXLSFNCWWWDPA-UHFFFAOYSA-N 0.000 description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- HXQRIQXPGMPSRW-UHZRDUGNSA-N Pollinastanol Natural products O[C@@H]1C[C@H]2[C@@]3([C@]4([C@H]([C@@]5(C)[C@@](C)([C@H]([C@H](CCCC(C)C)C)CC5)CC4)CC2)C3)CC1 HXQRIQXPGMPSRW-UHZRDUGNSA-N 0.000 description 10
- ONQRKEUAIJMULO-YBXTVTTCSA-N cycloartenol Chemical compound CC(C)([C@@H](O)CC1)[C@H]2[C@@]31C[C@@]13CC[C@]3(C)[C@@H]([C@@H](CCC=C(C)C)C)CC[C@@]3(C)[C@@H]1CC2 ONQRKEUAIJMULO-YBXTVTTCSA-N 0.000 description 10
- YNBJLDSWFGUFRT-UHFFFAOYSA-N cycloartenol Natural products CC(CCC=C(C)C)C1CCC2(C)C1(C)CCC34CC35CCC(O)C(C)(C)C5CCC24C YNBJLDSWFGUFRT-UHFFFAOYSA-N 0.000 description 10
- FODTZLFLDFKIQH-UHFFFAOYSA-N cycloartenol trans-ferulate Natural products C1=C(O)C(OC)=CC(C=CC(=O)OC2C(C3CCC4C5(C)CCC(C5(C)CCC54CC53CC2)C(C)CCC=C(C)C)(C)C)=C1 FODTZLFLDFKIQH-UHFFFAOYSA-N 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- 206010020772 Hypertension Diseases 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 208000031226 Hyperlipidaemia Diseases 0.000 description 8
- 102100040247 Tumor necrosis factor Human genes 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 210000000577 adipose tissue Anatomy 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000011640 AKR mouse Methods 0.000 description 6
- 102000011690 Adiponectin Human genes 0.000 description 6
- 108010076365 Adiponectin Proteins 0.000 description 6
- 206010003210 Arteriosclerosis Diseases 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 208000011775 arteriosclerosis disease Diseases 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 230000002708 enhancing effect Effects 0.000 description 6
- 235000009200 high fat diet Nutrition 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 238000002372 labelling Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- ZJFQVIALUCQMSK-QFTQTLHLSA-N (1S,3R,6S,8R,11S,12S,15R,16R)-15-[(2R)-5,6-dimethylheptan-2-yl]-7,7,12,16-tetramethylpentacyclo[9.7.0.01,3.03,8.012,16]octadecan-6-ol Chemical compound CC(C)([C@@H](O)CC1)[C@H]2[C@@]31C[C@@]13CC[C@]3(C)[C@@H]([C@H](C)CCC(C)C(C)C)CC[C@@]3(C)[C@@H]1CC2 ZJFQVIALUCQMSK-QFTQTLHLSA-N 0.000 description 5
- 241001116389 Aloe Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- BSLYZLYLUUIFGZ-JRUDBKCSSA-N 4,4,14-trimethyl-9,19-cyclo-5alpha,9beta-cholestane Chemical compound C1CCC(C)(C)[C@H]2[C@@]31C[C@@]13CC[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@@]3(C)[C@@H]1CC2 BSLYZLYLUUIFGZ-JRUDBKCSSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 208000001647 Renal Insufficiency Diseases 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 235000013376 functional food Nutrition 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 208000017169 kidney disease Diseases 0.000 description 4
- 201000006370 kidney failure Diseases 0.000 description 4
- 201000009925 nephrosclerosis Diseases 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000010998 test method Methods 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
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- 102000007156 Resistin Human genes 0.000 description 3
- 108010047909 Resistin Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 206010058339 Splenitis Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000009395 breeding Methods 0.000 description 3
- 230000001488 breeding effect Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 230000004110 gluconeogenesis Effects 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 201000008980 hyperinsulinism Diseases 0.000 description 3
- -1 inorganic acid salts Chemical class 0.000 description 3
- 230000003914 insulin secretion Effects 0.000 description 3
- 230000037356 lipid metabolism Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 150000003548 thiazolidines Chemical class 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- KKSCKZFKHNHGEO-UHFFFAOYSA-N 24-methylenecycloartanol Natural products CC(CCC(=C)C(C)(C)O)C1CCC2C3CCC4C(C)(C)C(O)CCC45CC35CCC12C KKSCKZFKHNHGEO-UHFFFAOYSA-N 0.000 description 2
- 240000007474 Aloe arborescens Species 0.000 description 2
- 235000004509 Aloe arborescens Nutrition 0.000 description 2
- YDQWDHRMZQUTBA-UHFFFAOYSA-N Aloe emodin Chemical compound C1=CC=C2C(=O)C3=CC(CO)=CC(O)=C3C(=O)C2=C1O YDQWDHRMZQUTBA-UHFFFAOYSA-N 0.000 description 2
- 244000101643 Aloe ferox Species 0.000 description 2
- 235000015858 Aloe ferox Nutrition 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 208000037157 Azotemia Diseases 0.000 description 2
- 102100034159 Beta-3 adrenergic receptor Human genes 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- 206010006895 Cachexia Diseases 0.000 description 2
- SGNBVLSWZMBQTH-FGAXOLDCSA-N Campesterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@H](C(C)C)C)C)CC4)CC3)CC=2)CC1 SGNBVLSWZMBQTH-FGAXOLDCSA-N 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 206010012665 Diabetic gangrene Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- 239000004129 EU approved improving agent Substances 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- BTEISVKTSQLKST-UHFFFAOYSA-N Haliclonasterol Natural products CC(C=CC(C)C(C)(C)C)C1CCC2C3=CC=C4CC(O)CCC4(C)C3CCC12C BTEISVKTSQLKST-UHFFFAOYSA-N 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 206010060378 Hyperinsulinaemia Diseases 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
- 102000009433 Insulin Receptor Substrate Proteins Human genes 0.000 description 2
- 108010034219 Insulin Receptor Substrate Proteins Proteins 0.000 description 2
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 2
- 102000043296 Lipoprotein lipases Human genes 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 2
- 102000013566 Plasminogen Human genes 0.000 description 2
- 108010051456 Plasminogen Proteins 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229940076810 beta sitosterol Drugs 0.000 description 2
- 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 description 2
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 2
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 2
- 150000004283 biguanides Chemical class 0.000 description 2
- SGNBVLSWZMBQTH-PODYLUTMSA-N campesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](C)C(C)C)[C@@]1(C)CC2 SGNBVLSWZMBQTH-PODYLUTMSA-N 0.000 description 2
- 235000000431 campesterol Nutrition 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000012156 elution solvent Substances 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 235000008216 herbs Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 2
- 208000006575 hypertriglyceridemia Diseases 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000023185 monocyte chemotactic protein-1 production Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 201000008383 nephritis Diseases 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 201000009104 prediabetes syndrome Diseases 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 2
- 229950005143 sitosterol Drugs 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 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
- 150000003648 triterpenes Chemical class 0.000 description 2
- 208000009852 uremia Diseases 0.000 description 2
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- VFYFMNCKPJDAPV-UHFFFAOYSA-N 2,2'-(5-oxo-1,3-dioxolan-4,4-diyl)diessigs Chemical compound C1N(C2)CN3CN1CN2C3.OC(=O)CC1(CC(O)=O)OCOC1=O VFYFMNCKPJDAPV-UHFFFAOYSA-N 0.000 description 1
- BDHQMRXFDYJGII-UEBIAWITSA-N 24-methylenecycloartanol Chemical compound CC(C)([C@@H](O)CC1)[C@H]2[C@@]31C[C@@]13CC[C@]3(C)[C@@H]([C@H](C)CCC(=C)C(C)C)CC[C@@]3(C)[C@@H]1CC2 BDHQMRXFDYJGII-UEBIAWITSA-N 0.000 description 1
- BJZVHTWNCLKZGN-SPQNPFHSSA-N 24-methylidenecycloartanol Natural products CC(C)C(=C)CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C(C)(C)[C@@H](O)CC[C@@]45C[C@@]35CC[C@]12C BJZVHTWNCLKZGN-SPQNPFHSSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- YPMOAQISONSSNL-UHFFFAOYSA-N 8-hydroxyoctyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCCCCO YPMOAQISONSSNL-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000234282 Allium Species 0.000 description 1
- 235000018185 Betula X alpestris Nutrition 0.000 description 1
- 235000018212 Betula X uliginosa Nutrition 0.000 description 1
- 102100028628 Bombesin receptor subtype-3 Human genes 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- CYJPBOUDPLPYGQ-PJSNPGDSSA-N CC(C)CCC[C@H]([C@H]1CC[C@@]2([C@@]1(CC[C@]34[C@H]2CC[C@@H]5[C@]3(C4)CC[C@@H](C5(C)C)O)C)C)C(O)O Chemical compound CC(C)CCC[C@H]([C@H]1CC[C@@]2([C@@]1(CC[C@]34[C@H]2CC[C@@H]5[C@]3(C4)CC[C@@H](C5(C)C)O)C)C)C(O)O CYJPBOUDPLPYGQ-PJSNPGDSSA-N 0.000 description 1
- 101100504320 Caenorhabditis elegans mcp-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 235000007516 Chrysanthemum Nutrition 0.000 description 1
- 244000189548 Chrysanthemum x morifolium Species 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
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- 108050008832 Fatty acid-binding protein, intestinal Proteins 0.000 description 1
- 102100026748 Fatty acid-binding protein, intestinal Human genes 0.000 description 1
- 206010016807 Fluid retention Diseases 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 201000001431 Hyperuricemia Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 240000001462 Pleurotus ostreatus Species 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
- 206010036790 Productive cough Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 206010038372 Renal arteriosclerosis Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000209056 Secale Species 0.000 description 1
- 235000007238 Secale cereale Nutrition 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241000208292 Solanaceae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 101100122821 Toxoplasma gondii GRA3 gene Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 208000021017 Weight Gain Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229940008102 alloin Drugs 0.000 description 1
- 229940069521 aloe extract Drugs 0.000 description 1
- 235000014104 aloe vera supplement Nutrition 0.000 description 1
- AFHJQYHRLPMKHU-CGISPIQUSA-N aloin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1C2=CC(CO)=CC(O)=C2C(=O)C2=C(O)C=CC=C21 AFHJQYHRLPMKHU-CGISPIQUSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 108010063504 bombesin receptor subtype 3 Proteins 0.000 description 1
- 239000002034 butanolic fraction Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- GGCLNOIGPMGLDB-GYKMGIIDSA-N cholest-5-en-3-one Chemical class C1C=C2CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 GGCLNOIGPMGLDB-GYKMGIIDSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000004146 energy storage Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 208000016253 exhaustion Diseases 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 230000004136 fatty acid synthesis Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- FODTZLFLDFKIQH-FSVGXZBPSA-N gamma-Oryzanol (TN) Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)O[C@@H]2C([C@@H]3CC[C@H]4[C@]5(C)CC[C@@H]([C@@]5(C)CC[C@@]54C[C@@]53CC2)[C@H](C)CCC=C(C)C)(C)C)=C1 FODTZLFLDFKIQH-FSVGXZBPSA-N 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 235000021474 generally recognized As safe (food) Nutrition 0.000 description 1
- 235000021473 generally recognized as safe (food ingredients) Nutrition 0.000 description 1
- 230000010030 glucose lowering effect Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 231100000206 health hazard Toxicity 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 208000006443 lactic acidosis Diseases 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 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
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000003614 peroxisome proliferator Substances 0.000 description 1
- 239000002957 persistent organic pollutant Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 150000003003 phosphines Chemical group 0.000 description 1
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
- 235000017807 phytochemicals Nutrition 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 235000002378 plant sterols Nutrition 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229940096055 prax Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000007727 signaling mechanism Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- 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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
-
- 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
Definitions
- the present invention relates to an insulin resistance improving agent containing a compound having a cyclolanostane skeleton as an active ingredient, and a food or drink containing the same.
- free fatty acids, plasminogen activity ⁇ inhibitory factor, tumor necrosis factor, monosite 'chemoatractant' protein 1 which are factors involved in the onset and seriousness of pathologies related to insulin resistance
- the present invention relates to an insulin resistance improving agent having an effect of regulating the production of adipocyte power in, such as resistin, and a food or drink containing the same.
- Insulin is a type of hormone produced in the spleen of Langerno and Jung Island (La Islet) that produces the power of j8 cells and is present in insulin target tissues such as skeletal muscle, liver, and fat. It acts on not only sugar metabolism but also lipid metabolism and protein metabolism, and plays an important role in the maintenance of homeostasis.
- the action of insulin in each target tissue includes the uptake of glucose in blood into muscle cells and adipocytes, the promotion of glycogen production in the liver and muscle tissue, the suppression of gluconeogenesis in the liver, the glucose in adipocytes Examples include promotion of consumption and fatty acid synthesis, and suppression of lipid degradation.
- Insulin resistance is a state in which more than a normal amount of insulin is required to obtain various actions of insulin at the cellular, organ, and individual levels, that is, an insulin dysfunction state in which sensitivity to insulin is reduced. It is. From the results of previous epidemiological studies, hypertension, diabetes, hyperlipidemia (hypertriglyceridemia, low HDL cholesterolemia), hypertrophy, etc. are considered to be pathologies based on insulin resistance. Insulin resistance leads to a lack of insulin action in glucose metabolism, resulting in compensatory hyperinsulinemia to maintain blood glucose, causing hyperglycemia and impaired glucose tolerance, and exhaustion of spleen
- Hyperinsulinemia is also associated with increased sympathetic nerve activity and sodium absorption in the kidneys to develop hypertension, as well as postprandial hyperlipidemia, hyperuricemia, and plasminogen activation inhibitor (PAI-1). plasminogen activator inhibitor It also induces the rise of -1).
- Non-patent Document 1 insulin resistance induces lipid metabolism abnormality due to insufficient action of insulin, and free fatty acid (FFA) released from fat cells increases in the liver, increasing triglycerides in the liver. (TG) synthesis is promoted, resulting in hyperTGemia. In addition, the activity is usually reduced in insulin-resistant lipoprotein lipase (LPL) 1S insulin resistance state, so that TG degradation is reduced and the worsening of hyperTGemia progresses. In addition, with the progress of diabetes, complications such as retinopathy nephropathy and gangrene due to vascular disorders have occurred, myocardial infarction and cerebral infarction have progressed, and hypertension has progressed with cardiovascular disease. Let Based on the above, it is considered that insulin resistance is greatly involved in the complex pathological deterioration (Non-patent Document 1).
- Adipose tissue is the largest in the body, not just energy storage tissue. Has been recognized as an endocrine organ. These endocrine factors derived from adipose tissue are collectively referred to as adipocyte force-in and play an important role in maintaining homeostasis in metabolism. 'Insulin resistance is thought to be caused by excessive or under-secretion and disruption of lance.
- adipocyte-inducing agents that increase insulin sensitivity and those that induce insulin resistance.
- Typical examples of the former include adiponectin, leptin, and AM PK (AMP-dependent protein kinase). It has been known.
- adiponectin has been reported to release insulin resistance and suppress gluconeogenesis in the liver (Non-patent Document 2).
- adipocyte force-in that induces insulin resistance includes tumor necrosis factor (TNF—) and a kind of inflammatory chemokine.
- TNF— tumor necrosis factor
- MCP-l monocyte c hemoattractant protein-1
- resistin etc.
- TNF— inhibits insulin receptor and IRS1 (insulin receptor substrate 1) tyrosine phosphate in the insulin signaling mechanism, thereby reducing insulin action. It has been reported that the mechanism of action that induces the resistance of a substance.
- MCP-1 is considered to be a causative substance that decreases insulin sensitivity (Non-Patent Documents 3, 4, and 5).
- an insulin resistance ameliorating agent (patent document 1) containing adiponectin or a gene thereof as an active ingredient, a substance having affinity for bombesin receptor subtype 3 (BRS 3) Prevention of diseases caused by insulin resistance as an active ingredient and Z treatment (Patent Document 2), Free fatty acid (FFA) lowering agent containing pyrrole derivative as an active ingredient (Patent Document 3), etc. It is disclosed as an improving agent.
- Sarasuko a food-derived substance as an active ingredient, an insulin resistance-improving composition containing acetic acid and its ions or salts as an active ingredient (Patent Document 4), specific diglycerides and Z or monoglycerides Insulin resistance improving agents (Patent Document 5) and the like comprising oils and fats containing glycerol are disclosed.
- Plant cholesterol such as ⁇ -sitosterol, campesterol, and stigmesterol
- ⁇ -sitosterol has already been known to have an effect of lowering blood cholesterol by inhibiting absorption of cholesterol, and is added to edible oils as an oil and fat composition.
- anti-obesity agents and lipid metabolism improving agents containing cholesterone compounds synthesized from plant sterols such as ⁇ -sitosterol and campesterol as starting materials are disclosed (Patent Documents 6 to 8, Non-Patent Document 6).
- At least one extract of rice bran, shimeji, chrysanthemum, rye, birch and moon cake is extracted, and cycloartol and its derivatives cycloartol and Z or (24S) -24, 25 -An adiponectin secretion promoter containing dihydroxycycloartanol is disclosed (Patent Document 9).
- Aloe vera Aloe barbadenisis Miller
- Patent Document 10 an immunosuppression improving agent characterized by containing a butanol fraction or a mouth-in of an aloe extract, (Patent Document 11 to 14), and prevention of obesity
- Patent Document 15 an improving agent and the like have been disclosed, no effect on improving insulin resistance by Aloe plants has been reported.
- Patent Document 1 International Publication No. 2003Z63894 Pamphlet
- Patent Document 2 JP-A-10-298100
- Patent Document 3 JP-A-8-12573
- Patent Document 4 Japanese Unexamined Patent Application Publication No. 2002-193797
- Patent Document 5 JP 2001-247473 A
- Patent Document 6 Japanese Patent Laid-Open No. 7-165587
- Patent Document 7 JP-A-11-193296
- Patent Document 8 Japanese Patent Laid-Open No. 2001-240544
- Patent Document 9 Japanese Patent Laid-Open No. 2005-68132
- Patent Document 10 JP-A-8-208495
- Patent Document 11 JP 59-214741
- Patent Document 12 Japanese Unexamined Patent Publication No. 2003-286185
- Patent Document 13 U.S. Pat.No. 4598069
- Patent Document 14 US Patent Application Publication No. 2003Z0207818
- Patent Document 15 Japanese Unexamined Patent Publication No. 2000-319190
- Non-patent document 1 Insulin resistance and lifestyle-related diseases, edited by Kazuaki Shimamoto, Diagnosis and Treatment Company, 2003 Year, pages 1-5
- Non-Patent Document 2 Adiposcience, No. 1, No. 3, 2004, pp. 247-257
- Non-Patent Document 3 Proceedings ⁇ National ⁇ Academia ⁇ Ob ⁇ Sciences (Proceedings of the National Academy of Sciences), No. 100, 2003, 7265-72 pages 70
- Non-Patent Document 4 Nature, 389, 1997, 610-614
- Non-Patent Document 5 The 'Netherlands' Journal 'Ob' Medine (The Netherlands Journal of Medicine), Vol. 6, No. 6, 2003, pp. 194-212
- Non-Patent Document 6 Hormone 'Metabolism' Research, 37th, 2005, pp. 79-83
- biguanides which are conventional drugs that improve insulin resistance, sometimes cause gastrointestinal disorders and rarely lactic acidosis.
- thiazolidine derivatives the same drug, may cause serious side effects such as body fluid retention, weight gain, and liver dysfunction.
- diabetic drugs it has been difficult to use diabetic drugs in practice for insulin resistance in a condition that is not diabetes or hyperglycemia. Under these circumstances, there has been a strong demand for the development of functional materials that are safe, can be taken on a daily basis, and can efficiently improve insulin resistance without causing as much pain as possible.
- the present inventors have found that insulin resistance leading to lifestyle-related diseases such as hypertension, diabetes, hyperlipidemia (hypertriglyceridemia, low HDL cholesterolemia), obesity, etc.
- lifestyle-related diseases such as hypertension, diabetes, hyperlipidemia (hypertriglyceridemia, low HDL cholesterolemia), obesity, etc.
- adipocyte power-in which is a factor involved in the onset and seriousness of insulin resistance.
- compounds with a cyclolanostane skeleton have adiposite strength such as free fatty acids, TNF-a, and MCP-1. Effects of regulating the production of adipocytes, especially adipocyte power inducing insulin resistance It has been found that insulin resistance is improved by the action of effectively reducing the production of insulin.
- Patent Document 9 the above-mentioned plant extract has an effect of preventing cultured adipocytes from being separated, the synthesis route of cycloartane-type triterpene derivatives, and ergosterol.
- adiponectin secretion by cycloartol which is a cycloartane-type triterpene or a derivative thereof, as shown in the above-mentioned promotion of adiponectin secretion. There was no mention or suggestion about.
- glucose clamp method which is a conventional method for evaluating insulin resistance
- a first invention of the present application for solving the above-mentioned problems is an insulin resistance improving agent comprising a compound represented by the following general formula (1) as an active ingredient.
- R1 is a linear or branched alkyl group having 6 to 8 carbon atoms, an alkyl group containing one or two double bonds, or a hydroxyl group and Z or A substituted alkyl group or a substituted alkenyl group containing one or two carbocycle groups
- R2 and R3 each independently represent a hydrogen atom or a methyl group
- R4 together with the carbon atoms constituting the ring C o Or any one of the following formulas :
- the R1 is represented by a deviation of the following formula, the R2 and R3 are both a methyl group, and the R4 is a hydroxyl group,
- Ra is a hydrogen atom, a hydroxyl group or a methyl group
- Rb is a hydrogen atom or a hydroxyl group
- Rc is a hydrogen atom, a hydroxyl group, or a methylol group
- the second invention of the present application that solves the above-described problems includes an organic solvent extract of a plant, a hot water extract, or a fraction thereof containing a compound represented by the following general formula (1).
- An insulin resistance ameliorating agent comprising a composition containing 0.001% by mass as an active ingredient.
- Rl is a linear or branched alkyl group having 6 to 8 carbon atoms, an alkyl group containing one or two double bonds, or a hydroxyl group and Z or A substituted alkyl group or a substituted alkenyl group containing one or two carbocycle groups
- R2 and R3 each independently represent a hydrogen atom or a methyl group
- R4 together with the carbon atoms constituting the ring C o Or any one of the following formulas :
- the plant is a lily family or gramineous plant
- the R1 is represented by a deviation of the following formula, the R2 and R3 are both a methyl group, and the R4 is a hydroxyl group,
- Ra is a hydrogen atom, a hydroxyl group or a methyl group
- Rb is a hydrogen atom or a hydroxyl group
- Rc is a hydrogen atom, a hydroxyl group or a methyl group
- a third invention of the present application for solving the above problems is a food or drink containing the insulin resistance improving agent according to the first or second invention.
- the food or drink contains 0.0001% by mass or more of the compound represented by the general formula (1).
- the fourth invention of the present application for solving the above-mentioned problems is a compound represented by the above general formula (1) for the production of an insulin resistance improving agent, or at least 0.001% by mass of the compound as a dry mass. It is the use of the organic solvent extract of the contained plant, or the hot water extract, or a fraction thereof.
- a fifth invention of the present application for solving the above-mentioned problems is a method for improving insulin resistance, wherein the compound represented by the general formula (1) or the compound is at least 0.001% by mass in dry mass.
- a preferred embodiment of the compound represented by the general formula (1) in the use and method of the present invention is the same as in the second invention of the present application.
- the insulin resistance improving agent of the present invention and foods and drinks containing the same can be safely administered or ingested, and have a preventive effect on lifestyle-related diseases that are considered to be caused by insulin resistance.
- the active ingredient of the insulin resistance improving agent of the present invention can be easily produced from lily family plants such as Aloe barbadensis Miller, which can be safely ingested and easily obtained, for example, based on dietary experience.
- FIG. 1 is a diagram showing changes in blood glucose level in an insulin tolerance test.
- the compound used as an active ingredient of the insulin resistance-improving agent of the present invention (hereinafter also referred to as “the pharmaceutical of the present invention! /”) is a compound having the structure represented by the general formula (1). As long as the compound has an action to improve insulin resistance (hereinafter also referred to as “the compound of the present invention”), any derivative or the like is included as an active ingredient.
- the purity of the compound of the present invention used as an active ingredient of the insulin resistance ameliorating agent of the present invention is most preferably 100%, but is appropriately set within a range having an action of improving insulin resistance. Is possible.
- composition used as an active ingredient of the insulin sensitizer of the present invention is a compound having the structure represented by the general formula (1).
- the dry weight is at least 0.001% by weight, preferably 0.01% by weight or more, more preferably 0.1% by weight.
- the dry mass means the dry mass defined in the general test method "Dehydration loss test method" in the 14th revised Japanese Pharmacopoeia (March 30, 2001, Ministry of Health, Labor and Welfare Notification No. 111). According to the method, the mass measured after the compound was dried.For example, about 1 lg of the compound of the present invention was collected, dried at 105 ° C. for 4 hours, allowed to cool in a desiccator, and measured with a balance. It can be defined by measuring its mass.
- One form of the insulin resistance-improving agent of the present invention and foods and beverages containing the same are compounds having a cyclanostan skeleton, and containing a compound having an insulin resistance-improving action as an active ingredient.
- the cyclolanostane skeleton refers to a compound represented by the following general formula (2).
- Specific examples of the compound having a cyclolanostane skeleton include compounds represented by the general formula (1).
- the number of double bonds present in the compound having a cyclolanostane skeleton is not particularly limited.
- the number of double bonds present in the ring is not limited, and when two or more double bonds are present, they may be conjugated.
- the medicament or food or drink of the present invention may contain two or more kinds of the compound of the present invention.
- R1 is preferably any one of the groups represented by the following formulae.
- Ra is a hydrogen atom, a hydroxyl group or a methyl group
- R b is a hydrogen atom or a hydroxyl group
- Rc is a hydrogen atom, a hydroxyl group or a methyl group
- R2 and R3 are preferably both methyl groups, and R4 is preferably a hydroxyl group.
- the most preferred compound is 9, 19 cyclolanostane 1-ol (formula (3)) represented by the following formula, or 24-methylene 9, 19-cyclolanostane 3 ol (formula ( 4)).
- 9, 19-cyclolanostan-3ol is represented by the general formula (1), wherein R2 and R3 are methyl groups, R4 is a hydroxyl group, and R1 is the formula (i) It is a group represented. 24-Methylene 9, 19-cyclolanostane-3ol is represented by the general formula (1) In the formula, R2 and R3 are methyl groups, R4 is a hydroxyl group, and R1 is a group represented by the formula (vi).
- the compound of the present invention may be cycloartol (formula (5)) or 24-methylcycloartanol (formula (7)).
- R2 and R3 are methyl groups
- R4 is a hydroxyl group.
- cycloartol is a group represented by formula (vii)
- the compound of the present invention can be chemically produced according to a known production method.
- cycloartanol commonly name for 24-methylene-9,19-cyclolanostane-3-ol
- JP-A-57-018617 discloses a method for producing gamma-oryzanol-powered cycloartol ferrate (formula 6) and a method for synthesizing a compound using this hydrolyzate as a starting material. This is disclosed in Japanese Patent Laid-Open No. 2003-277269.
- a method in which the double bond part is converted into an aldehyde by an ozonolysis reaction and phosphine salt is bound to it, or water is added to the double bond.
- various derivative compounds can be produced.
- the production method is not limited to a chemical synthesis method, and it may be biologically produced using microorganisms. Some cocoons can be produced using microorganism-derived enzymes.
- the insulin resistance-improving agent of the present invention and foods and drinks containing the same may contain one kind of the compound alone, or may contain any two or more kinds.
- examples of the plant belonging to the lily family include plants belonging to the genus Aloe or Allium.
- Aloe vera Aloe barbadensis Miller
- Aloe ferox Miller Aloe ferox Miller
- Aloe africa na Miller Guna / 'mouth (Aloe arborescen Miller var.
- the whole plant may be used, but the mesophyll (transparent gel portion)
- a plant or a part thereof is preferably crushed and liquefied using a homogenizer, etc., and extracted with an organic solvent or hot water, such as methanol, ethanol, butanol, etc.
- Alcohols such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, etc .; ketones such as acetone, methyl isobutyl ketone; Ethers such as ether and petroleum ether; hydrocarbons such as hexane, cyclohexane, toluene and benzene; halogenated hydrocarbons such as carbon tetrachloride, dichloromethane and chloroform; heterocyclic compounds such as pyridine, ethylene glycol, etc. And polyalcohols such as polyethylene glycol, -tolyl solvents such as acetonitrile, and mixtures of these solvents, etc. These solvents may be anhydrous or may be in a water-containing state. May be. Of these solvents, ethyl acetate Z-butanol mixture (3: 1) or chloroform Z methanol mixture (2: 1) is preferred!
- an extraction method a method used for extraction of normal plant components can be used. Usually, 1 to 300 parts by mass of an organic solvent is used per 1 part by mass of a fresh or dried plant, and the mixture is heated to reflux at a temperature not higher than the boiling point of the solvent while stirring or shaking, or is subjected to ultrasonic extraction at room temperature. A method is mentioned.
- the crude extract can be obtained by separating the insoluble matter by an appropriate method such as filtration or centrifugation.
- the extract can be purified by various types of chromatography, for example, normal phase or reverse phase silica gel column chromatography.
- reverse phase silica gel column chromatography when a hexane: ethyl acetate mixture (4: 1) is used as an elution solvent, the compound of the present invention is eluted as the first fraction.
- the obtained fraction can be further purified by HPLC or the like.
- the compound used in the present invention may be produced by a chemical synthesis method, or a biological method or an enzymatic method using microorganisms or enzymes.
- the compound of the present invention can be used as it is as the active ingredient of the insulin resistance-improving agent of the present invention or a food or drink containing the same.
- an organic solvent extract of plants, a hot water extract, or a fraction thereof hereinafter referred to as “extracts” containing the compound of the present invention or an insulin resistance improving agent or You may utilize as an active ingredient of the food-drinks to contain.
- extracts organic solvent extract of plants, a hot water extract, or a fraction thereof
- You may utilize as an active ingredient of the food-drinks to contain.
- the total content of alloin and aloe emodin contained in the outer skin of aloe vera leaves is preferably 5 ppm or less.
- the extract or the like contained in the insulin resistance improving agent preferably contains at least 0.001% by mass of the compound of the present invention in a dry mass of 0.01 to 1% by mass. It is more preferable to contain 0.05 to 1% by mass. Furthermore, the extract or the like to be contained in food or drink, that the compounds of the present invention, comprise at least 0.000 1 weight% including the preferred instrument from 0.001 to 1 mass 0/0 that are in a dry weight It is particularly preferable to contain 0.005 to 1% by mass.
- the extract or the like may contain two or more kinds of the compounds of the present invention.
- the extract or the like may be in the form of a solution, and can be used after being freeze-dried or spray-dried by conventional methods and stored as a powder.
- the insulin resistance-improving agent of the present invention is a composition of the present invention or an extract containing the same as it is or in combination with a pharmaceutically acceptable pharmaceutical carrier, orally, or It can be administered parenterally to mammals including humans.
- the compound of the present invention can be converted to a pharmaceutically acceptable salt.
- Pharmaceutically acceptable salts include both metal salts (inorganic salts) and organic salts, the list of which is “Remington's Pharmaceutical Sciences, 17th Edition, 1418”. Page, 1985 ”is an example.
- inorganic acid salts such as hydrochloride, sulfate, phosphate, diphosphate and hydrobromide, malate, maleate, fumarate, tartrate, succinate,
- Organic salts such as citrate, acetate, lactate, methanesulfonate, p-toluenesulfonate, pamoate, salicylate and stearate are included without limitation.
- it may be a salt of a metal such as sodium, potassium, calcium, magnesium or aluminum, or a salt with an amino acid such as lysine.
- solvates such as hydrates of the above compounds or pharmaceutically acceptable salts thereof are also included in the present invention.
- the preparation form of the insulin resistance-improving agent of the present invention is not particularly limited, and can be appropriately selected depending on the purpose of treatment. Specifically, tablets, pills, powders, solutions, suspensions, emulsions, granules Agents, strengths, pushells, syrups, suppositories, injections, ointments, patches, eye drops, nasal drops and the like.
- Additives such as solvents can be used.
- the compound of the present invention or an extract containing the compound and other insulin resistance improving actions May be used in combination with other drugs.
- the amount of the compound of the present invention or the extract containing the compound contained in the insulin resistance-improving agent of the present invention is not particularly limited and may be appropriately selected.
- the amount of the compound of the present invention as, at least 0.001% by weight in the formulation, preferably 0.01 to 1% by weight, particularly good Mashiku preferably set to 0.05 to 1 mass 0/0.
- the insulin resistance improving action refers to preventing or preventing various health hazards caused by a decrease in insulin sensitivity, such as lifestyle-related diseases. Improves action. Specifically, adipocyte activity that induces insulin resistance such as plasminogen activity inhibitor (PAI-1), free fatty acid (FFA), tumor necrosis factor (TNF- ⁇ ), MCP-1, resistin, etc. It effectively suppresses the rise or production of intestines, and is effective in reducing, preventing, ameliorating, or treating the pathological conditions related to insulin resistance. Therefore, the insulin resistance improving agent of the present invention can be defined as an insulin sensitivity enhancer, an adipocyte force-in production regulator, particularly an adipocyte force-in production inhibitor that induces insulin resistance.
- Insulin resistance can be assessed by glucose clamp method, SSPG (Steady state plasma glucose) method, minimal model method, fasting blood glucose level and blood insulin concentration based on HOMA-IR (nomeostasis model assessment). Insulin resistance) The number of numerators calculated and semi-determined, the insulin tolerance test (insulin tolerance test) is exemplified, and the ability to evaluate insulin resistance is possible with either method. It is preferable to use an insulin tolerance test (insulin tolerance test) using animals that is not affected by the insulin secretion ability and can directly examine insulin sensitivity.
- the compound of the present invention has an action of enhancing insulin sensitivity, and as a result, it is possible to prevent or ameliorate a pathological condition caused by insulin resistance. Therefore, it can be used as an active ingredient of an insulin resistance improver or a food or drink containing the insulin resistance improver. Insulin sensitivity can also be evaluated by measuring the blood glucose lowering response after insulin administration.
- the insulin resistance ameliorating agent of the present invention can be used for various diseases caused by insulin resistance. It is possible to reduce the risk of complications, etc. prevention and improvement, or treatment, and these diseases. Moreover, the insulin resistance improving agent of the present invention can be suitably used for patients whose insulin resistance is lower than that of healthy people. In general, insulin resistance is defined as a fasting plasma insulin level of 10-15 UZm 1 or higher and a HOMA index of 1.73 or higher.
- Examples of various diseases caused by strong insulin resistance include hypertension, hyperlipidemia, diabetes, impaired glucose tolerance, arteriosclerosis, hyperinsulinemia, obesity and the like. Complications resulting from these diseases include: i) stroke due to hypertension, nephrosclerosis, renal failure, mouth) arteriosclerosis due to hyperlipidemia, splenitis, c) diabetic retinopathy due to diabetes, kidney , Neuropathy, diabetic gangrene, 2) stroke due to arteriosclerosis, cardiovascular diseases such as cerebral infarction, angina pectoris and myocardial infarction, nephropathy such as uremia, nephrosclerosis and renal failure, etc. An example can be shown.
- the present inventors have found that the compound of the present invention has an action of reducing hemoglobin Ale value and improving hyperglycemia (International Publication No. 2006Z03 5525). It is preferable that the disease to which the insulin resistance-improving agent of the present invention is applied is such that the value of hemoglobin Ale is higher than that of a healthy person and is not in a state.
- adipocyte power-in that induces insulin resistance such as TNF 1 ⁇ , MCP-1, FFA, etc.
- various diseases such as rheumatoid arthritis, Crohn's disease, nephritis, splenitis, hepatitis, and pneumonia, which are autoimmune diseases, are caused by the increase in the adipocyte activity It also has the effect of preventing and / or improving cachexia in inflammatory diseases, vascular disorders, sepsis and malignant tumors.
- the insulin resistance-improving agent of the present invention is preferably used also for a patient in a state where the production of the adipocyte force-in is enhanced, particularly in a state where the production of adipocyte force-in causing insulin resistance is enhanced. Is possible.
- the administration time of the medicament of the present invention is not particularly limited, and the administration time can be appropriately selected according to the treatment method for the target disease.
- the dosage form is preferably determined according to the dosage form, the patient's age, sex, other conditions, the degree of symptoms of the patient, and the like.
- the dosage of the medicament of the present invention depends on the usage, patient age, sex, degree of disease, and other conditions. It is appropriately selected depending on the above.
- the amount of the compound of the present invention as an active ingredient should be in the range of 0.001 to 50 mg / kg / day, preferably 0.01 to 1 mgZkgZ days.
- the dry mass of the extract etc. is 0.1 to: LOOOmg / kg / ⁇ , preferably 1 to: L00 mg / kg / ⁇ . It is good to use as a guide. In either case, it can be administered once or multiple times a day.
- the compound of the present invention or a composition containing the compound can be contained in a food or drink (beverage or food) to obtain a food or drink having an effect of improving insulin resistance.
- the food and drink are not particularly limited in form and properties as long as they can be taken orally without impairing the effects of the active ingredients. Except for the inclusion of the active ingredients, the raw materials usually used for food and drinks are used. Can be produced by a usual method.
- the amount of the compound of the present invention or an extract containing the compound of the present invention contained in the food or drink of the present invention is not particularly limited and may be appropriately selected.
- the amount of the compound of the present invention the food or drink The content is at least 0.0001% by mass, preferably 0.001 to 1% by mass, particularly preferably 0.001 to 1% by mass.
- the food / beverage products of the present invention can be used in various applications that utilize the effect of improving insulin resistance. For example, it is possible to exemplify uses such as foods and drinks that are useful for reducing and eliminating risk factors for lifestyle-related diseases that are considered to be caused by insulin resistance.
- the food and drink according to the present invention can prevent and reduce the risk of diseases caused by insulin resistance, such as hypertension, hyperlipidemia, and diabetes.
- the food and drink of the present invention has various complications caused by insulin resistance, such as stroke due to hypertension, nephrosclerosis, renal failure or arteriosclerosis due to hyperlipidemia, splenitis, etc., diabetic retinopathy due to diabetes, Prevention of nephropathy, neuropathy, diabetic gangrene, stroke and cerebral infarction due to arteriosclerosis, cardiovascular diseases such as angina pectoris and myocardial infarction, nephropathy such as uremia, nephrosclerosis and renal failure And the risk can be reduced.
- the food and drink of the present invention is expected to have an effect of suppressing the production / increase of adipocyte force-in that induces insulin resistance such as TNF-a, MCP-1, and FFA.
- adipocyte force-in that induces insulin resistance
- the joint joint is an autoimmune disease. It also has the effect of preventing and reducing the risk of inflammatory diseases, vascular disorders, sepsis, cachexia in malignant tumors in various organs such as gusset, Crohn's disease, nephritis, knee inflammation, hepatitis, pneumonia, etc. .
- the food / beverage product of the present invention can be suitably ingested by a patient in a state in which the production of the adipocyte force-in is increased, particularly in a state in which the production of adipocyte force-in causing insulin resistance is increased. It is.
- the food / beverage product of the present invention is a food / beverage product with an indication that it is used for improving insulin resistance, for example, “insulin resistance improving effect displayed as“ insulin resistance improving ”.
- Food or drink containing the compound having "or” food or drink containing plant extract "indicated as” improving insulin resistance "or” food or drink containing aloe vera extract described as “improving insulin resistance” It is preferable to sell as “goods”.
- the indication of the improvement in insulin resistance is considered to have a meaning of enhancing insulin sensitivity. Therefore, the food and drink of the present invention can be displayed as “for insulin sensitivity enhancement”. That is, the display for improving insulin resistance may be such a display for “increasing insulin sensitivity”.
- the wording used for the display as described above is not limited to the words “for insulin resistance improvement” or “for insulin sensitivity enhancement”, but other words. Even if it is a word which expresses the effect which raises insulin sensitivity or prevents and improves insulin resistance, it cannot be overemphasized that it is included in the scope of the present invention. As such a wording, for example, it is possible to display on the basis of various uses that allow the consumer to recognize the effect of improving insulin resistance or enhancing insulin sensitivity. For example, it is possible to exemplify indications such as “suitable for those who tend to have insulin resistance” and “useful in reducing or removing risk factors (risks) of lifestyle-related diseases”.
- the "display” means all actions for informing the consumer of the use, and if the display can recall and analogize the use, the purpose of the display, Regardless of the content, the object to be displayed, the medium, etc., all correspond to the “display” of the present invention. However, it is preferable to display it in such an expression that the consumer can directly recognize the use. Specifically, the above-mentioned use is applied to the product related to the food or drink of the present invention or the packaging of the product.
- the display is preferably a display approved by the government or the like (for example, a display that is approved based on various systems determined by the government, and that is performed in a manner based on such approval).
- indications such as health foods, functional foods, enteral nutritional foods, special-purpose foods, nutritional functional foods, quasi-drugs, etc. can be exemplified, and other cases by the Ministry of Health, Labor and Welfare.
- Approved indications for example, indications approved by foods for specified health use and similar systems can be exemplified. Examples of the latter include labeling as food for specified health use, labeling as conditionally specified food for specified health use, labeling that affects the structure and function of the body, labeling for reducing disease risk, etc.
- Speaking of health promotion law enforcement regulations (April 30, 2003 Ministry of Health, Labor and Welfare Ordinance No. 86) labeling as food for specified health use (especially labeling of health use), and similar
- the display can be listed as a typical example.
- ⁇ -Oryzanol (manufactured by Oriza Oil Chemical Co., Ltd.) 8. Distilled water 250ml, sodium hydroxide 50g, isopropanol 150ml, ethanol 150ml, methanol 150ml in Og was heated to reflux with a mantle heater for 2 hours. . After the reaction, the reaction solution was poured into 1300 ml of water, and the resulting white precipitate was collected by suction filtration. In order to wash away the remaining alkali, the residue collected by filtration was suspended in 1000 ml of water, and then subjected to suction filtration again. This operation was repeated twice, and the final residue was freeze-dried under reduced pressure to obtain 5.91 g of oryzanol hydrolyzate. The hydrolyzate was purified by HPLC, and 2435 mg of 9, 19-cyclolanostane-3-ol, and 1543 mg of 24-methylene-1,9,19-cyclolanostane. 3-Oll got.
- the reaction solution was filtered to remove the catalyst, concentrated, and then purified by silica gel column chromatography (developing solvent: chloroform 100%) to obtain 275 mg of cycloartanol.
- the synthesis of 24-methylcycloartanol was performed using 24-methylene 9,19-cyclolanostane 3ol as a starting material.
- 24-Methylene-1,9,19 Cyclolanostane-3-ol 78 mg, Isopronool V-150 ml, and powdered 5% palladium on carbon catalyst 1.
- Charge Og then seal it in an autoclave, After replacing with nitrogen gas, hydrogen gas was introduced while applying a pressure of 3 kgZcm 2 .
- the mixture was heated with stirring, and when the temperature reached 50 ° C., the hydrogen pressure was adjusted to 5 kg / cm 2, and the reaction was performed for 6 hours while maintaining the pressure at 5 kg / cm 2 by supplementing the absorbed hydrogen.
- the reaction solution was filtered to remove the catalyst, concentrated, and then purified by silica gel column chromatography (developing solvent: chloroform 100%) to obtain 69 mg of 24-methylcycloartanol.
- the change in the amount of free fatty acid (FFA) in serum by the insulin resistance-improving agent of the present invention was performed using an AKR mouse in which insulin resistance is induced by breeding on a high-fat diet. Went to evaluate.
- test sample 1 6 weeks old, male AKR mice (purchased from Jackson, USA) were pre-bred for 2 months using a high-fat diet (manufactured by Research Diet). They were divided into groups. To each group of mice, test sample 1, test sample 2, or negative sample was orally administered daily at a dose of 40 g per day (25 gZkg body weight) using a sonde once a day. On the 60th day, the administration of the sample was also sampled under fasting, and the amount of free fatty acid in the serum was measured with NE FA C-Test Sakai (manufactured by Wako Pure Chemical Industries, Ltd.).
- Table 1 shows the free fatty acid concentration in the serum of mice 60 days after the start of administration. Compared to the negative sample administration group, both test sample 1 and test sample 2 were administered. It was confirmed that the free fatty acid level in Qing decreased to 81.1%. Therefore, it became clear that administration of the insulin resistance improving agent of the present invention reduces the free fatty acid concentration systemically and prevents the induction of insulin resistance.
- This example uses an AKR mouse in which insulin resistance is induced by breeding with a high-fat diet, and T of each cell force in an adipose tissue by the insulin resistance-improving agent of the present invention is used. This was carried out in order to evaluate the influence on the production amount of NF-a and MCP-1.
- test samples 1 and 2 and a negative sample similar to those prepared in Example 1 were used.
- mice 6 weeks old, male AKR mice (purchased from Jackson, USA) were pre-bred for 2 months using a high-fat diet (manufactured by Research Diet). They were divided into groups. To each group of mice, test sample 1, test sample 2, or negative sample was orally administered daily at a dose of 40 g per day (25 gZkg body weight) using a sonde once a day. On the 60th day after the start of sample administration, fat around the testis collected in fasting is supplemented with 1.5 ml of D—MEM / F12 medium containing 0.5% ushi serum albumin at 37 ° C. Incubated with The concentrations of TNF-spleen and MCP-1 in the culture supernatant collected after 1 hour of culture were measured by EL IS A method (manufactured by Biosource).
- Table 2 shows the amount of TNF- ⁇ produced from adipose tissue.
- Table 3 also shows the MCP 1 represents the production amount.
- both the TNF-a and MCP-1 groups showed a significant production-suppressing effect in the group administered test sample 1 and test sample 2 compared to the negative sample administration group. It was. From the results of the present example, administration of the insulin resistance improving agent of the present invention reduces the production of adipocyte power in in adipose tissue that exacerbates insulin resistance, and prevents the induction of insulin resistance. It became clear that it was done.
- the p-value in the table indicates the significance probability by Tukey-Kramer's test.
- Test sample 2 33. 59 ⁇ 0. 59 * 0. 0365
- the insulin resistance test of the insulin resistance-improving agent of the present invention was performed by performing an insulin tolerance test using an AKR mouse in which insulin resistance is induced by breeding with a high-fat diet. This was done to confirm the enhancing action.
- test samples 1, 2 and a negative sample similar to those prepared in Example 1 or 2 were used.
- mice 6 weeks old, male AKR mice (purchased from Jackson, USA) were pre-bred for 2 months using a high-fat diet (manufactured by Research Diet). They were divided into groups. To each group of mice, test sample 1, test sample 2, or negative sample was orally administered daily at a dose of 40 g per day (25 gZkg body weight) using a sonde once a day. Insulin tolerance test was also performed on the 45th day of administration of the sample. In the insulin tolerance test in this example, after fasting the mice for 4 hours, human 'insulin (manufactured by Eli Lilly) was intraperitoneally administered at a dose of 0.75 UZkg body weight, and the insulin administration starting force was also increased over time until 60 minutes passed. This was done by measuring changes in blood glucose level.
- human 'insulin manufactured by Eli Lilly
- FIG. Figure 1 shows the results of the insulin tolerance test.
- the blood glucose level of the group administered with test sample 1 and test sample 2 was not observed in the group administered with the negative sample for 15 minutes from the start of insulin administration, whereas In both cases, a rapid decrease in blood glucose level was observed. From the results of this Example, it was found that administration of the insulin resistance improving agent of the present invention enhances insulin sensitivity.
- the present invention relates to a safe insulin resistance improving agent capable of enhancing insulin sensitivity without causing side effects, and a functional food and drink such as a food for specified health use containing the insulin resistance improving agent. Improvement or prevention of diseases, complications, etc. caused by reduced insulin sensitivity, such as hypertension, diabetes, hyperlipidemia, arteriosclerosis, etc. It also has the effect of reducing such risks.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Botany (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Polymers & Plastics (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/064,607 US7947669B2 (en) | 2005-09-30 | 2006-09-22 | Agent for improving insulin resistance |
AU2006300640A AU2006300640C1 (en) | 2005-09-30 | 2006-09-22 | Agent for improving insulin resistance |
EP06810426.4A EP1930014B1 (en) | 2005-09-30 | 2006-09-22 | Agent for amelioration of insulin resistance |
JP2007539848A JP4176140B2 (ja) | 2005-09-30 | 2006-09-22 | インスリン抵抗性改善剤 |
CN2006800365150A CN101277705B (zh) | 2005-09-30 | 2006-09-22 | 用于改善胰岛素抗性的药剂 |
ES06810426.4T ES2626792T3 (es) | 2005-09-30 | 2006-09-22 | Agente para mejorar la resistencia a la insulina |
CA2623639A CA2623639C (en) | 2005-09-30 | 2006-09-22 | Agent for improving insulin resistance |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2005-287885 | 2005-09-30 | ||
JP2005287885 | 2005-09-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007043305A1 true WO2007043305A1 (ja) | 2007-04-19 |
Family
ID=37942556
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2006/318813 WO2007043305A1 (ja) | 2005-09-30 | 2006-09-22 | インスリン抵抗性改善剤 |
Country Status (10)
Country | Link |
---|---|
US (1) | US7947669B2 (ja) |
EP (1) | EP1930014B1 (ja) |
JP (1) | JP4176140B2 (ja) |
KR (2) | KR100999317B1 (ja) |
CN (1) | CN101277705B (ja) |
AU (1) | AU2006300640C1 (ja) |
CA (1) | CA2623639C (ja) |
ES (1) | ES2626792T3 (ja) |
RU (1) | RU2380103C2 (ja) |
WO (1) | WO2007043305A1 (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010058795A1 (ja) | 2008-11-19 | 2010-05-27 | 森永乳業株式会社 | 抗酸化剤 |
JP2012515140A (ja) * | 2009-01-16 | 2012-07-05 | 花王株式会社 | 食後血糖上昇抑制剤 |
JP2014221733A (ja) * | 2013-05-13 | 2014-11-27 | 花王株式会社 | 精製トリテルペンアルコールの製造方法 |
WO2023054477A1 (ja) * | 2021-09-28 | 2023-04-06 | 森永乳業株式会社 | アロエ抽出物の製造方法 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101434129B1 (ko) * | 2008-11-19 | 2014-08-26 | 모리나가 뉴교 가부시키가이샤 | 항산화제 |
JP6039955B2 (ja) * | 2011-07-28 | 2016-12-07 | 花王株式会社 | 加工玄米の製造方法 |
WO2016084957A1 (ja) * | 2014-11-28 | 2016-06-02 | 森永乳業株式会社 | マトリックスメタロプロテアーゼ産生阻害剤 |
CN107652349A (zh) * | 2017-08-30 | 2018-02-02 | 右江民族医学院 | 一种从薏苡茎叶中分离纯化环阿乔醇的方法 |
JP7239489B2 (ja) * | 2017-12-19 | 2023-03-14 | 森永乳業株式会社 | アロエ粉末の製造方法 |
KR102495181B1 (ko) | 2020-12-21 | 2023-02-06 | 현대제철 주식회사 | 충격인성이 우수한 강관용 고강도 열연강판 및 그 제조방법 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH1036283A (ja) * | 1996-07-18 | 1998-02-10 | Ichimaru Pharcos Co Ltd | 線維芽細胞増殖促進剤 |
JP2000319190A (ja) * | 1999-05-10 | 2000-11-21 | Nonogawa Shoji Kk | 肥満の予防改善剤 |
JP2003286185A (ja) * | 2002-03-29 | 2003-10-07 | Daily Foods Kk | アロエベラ圧搾液及び該圧搾液を有効成分とする血糖値降下剤 |
WO2005094838A1 (ja) * | 2004-03-31 | 2005-10-13 | Morinaga Milk Industry Co., Ltd. | 高血糖改善のための医薬及び飲食品 |
WO2005095436A1 (ja) * | 2004-03-31 | 2005-10-13 | Morinaga Milk Industry Co., Ltd. | 4-メチルエルゴスト-7-エン-3-オール骨格を有する配糖体及び高血糖改善剤 |
WO2006035525A1 (ja) * | 2004-09-29 | 2006-04-06 | Morinaga Milk Industry Co., Ltd. | 高血糖改善のための医薬及び飲食品 |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5927824A (ja) | 1982-08-05 | 1984-02-14 | Sankyo Co Ltd | 抗脂血剤 |
JPS60214741A (ja) | 1984-04-05 | 1985-10-28 | Toyo Yakushiyoku Kogyo Kk | 血糖降下剤 |
JP3862295B2 (ja) | 1993-09-30 | 2006-12-27 | 独立行政法人理化学研究所 | 抗肥満剤 |
JPH0812573A (ja) | 1994-06-24 | 1996-01-16 | Mitsubishi Chem Corp | 遊離脂肪酸低下剤 |
JP3685833B2 (ja) | 1995-02-06 | 2005-08-24 | 日本メナード化粧品株式会社 | 免疫抑制改善剤 |
JPH10298100A (ja) | 1997-05-06 | 1998-11-10 | Mitsubishi Chem Corp | インスリン抵抗性に起因する疾患の予防及び/又は治療剤 |
JP3873097B2 (ja) | 1997-11-06 | 2007-01-24 | 独立行政法人理化学研究所 | 抗肥満剤及び脂質代謝改善剤 |
JP3858055B2 (ja) | 2000-02-29 | 2006-12-13 | 独立行政法人理化学研究所 | 抗肥満剤及び脂質代謝改善剤 |
JP2001247473A (ja) | 2000-03-06 | 2001-09-11 | Kao Corp | インスリン抵抗性改善剤 |
JP2002193797A (ja) | 2000-12-22 | 2002-07-10 | Mitsukan Group Honsha:Kk | インスリン抵抗性改善用組成物 |
US6893627B2 (en) * | 2001-08-31 | 2005-05-17 | Rutgers, The State University Of New Jersey | Method for treating type 2 diabetes with an extract of Artemisia |
CA2474964C (en) | 2002-01-31 | 2012-05-15 | Japan Science And Technology Agency | An insulin improving agent containing adiponectin |
US6884783B2 (en) * | 2002-05-03 | 2005-04-26 | Unigen Pharmaceuticals, Inc. | 7-Hydroxy chromones as potent antioxidants |
US20060216362A1 (en) * | 2003-05-19 | 2006-09-28 | Tatsuji Enoki | Remedy |
JP4846990B2 (ja) | 2003-08-06 | 2011-12-28 | 株式会社テラ・ブレインズ | アディポネクチン分泌促進剤 |
JP4065018B2 (ja) * | 2005-05-17 | 2008-03-19 | 森永乳業株式会社 | 膵臓機能改善のための医薬又は飲食品 |
JP4065016B2 (ja) * | 2005-05-17 | 2008-03-19 | 森永乳業株式会社 | 膵臓機能改善のための医薬又は飲食品 |
-
2006
- 2006-09-22 KR KR1020107010955A patent/KR100999317B1/ko active IP Right Grant
- 2006-09-22 CN CN2006800365150A patent/CN101277705B/zh active Active
- 2006-09-22 RU RU2008112884/04A patent/RU2380103C2/ru not_active IP Right Cessation
- 2006-09-22 AU AU2006300640A patent/AU2006300640C1/en active Active
- 2006-09-22 EP EP06810426.4A patent/EP1930014B1/en active Active
- 2006-09-22 US US12/064,607 patent/US7947669B2/en active Active
- 2006-09-22 WO PCT/JP2006/318813 patent/WO2007043305A1/ja active Application Filing
- 2006-09-22 KR KR1020087003390A patent/KR100972952B1/ko active IP Right Grant
- 2006-09-22 CA CA2623639A patent/CA2623639C/en active Active
- 2006-09-22 ES ES06810426.4T patent/ES2626792T3/es active Active
- 2006-09-22 JP JP2007539848A patent/JP4176140B2/ja active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH1036283A (ja) * | 1996-07-18 | 1998-02-10 | Ichimaru Pharcos Co Ltd | 線維芽細胞増殖促進剤 |
JP2000319190A (ja) * | 1999-05-10 | 2000-11-21 | Nonogawa Shoji Kk | 肥満の予防改善剤 |
JP2003286185A (ja) * | 2002-03-29 | 2003-10-07 | Daily Foods Kk | アロエベラ圧搾液及び該圧搾液を有効成分とする血糖値降下剤 |
WO2005094838A1 (ja) * | 2004-03-31 | 2005-10-13 | Morinaga Milk Industry Co., Ltd. | 高血糖改善のための医薬及び飲食品 |
WO2005095436A1 (ja) * | 2004-03-31 | 2005-10-13 | Morinaga Milk Industry Co., Ltd. | 4-メチルエルゴスト-7-エン-3-オール骨格を有する配糖体及び高血糖改善剤 |
WO2006035525A1 (ja) * | 2004-09-29 | 2006-04-06 | Morinaga Milk Industry Co., Ltd. | 高血糖改善のための医薬及び飲食品 |
Non-Patent Citations (7)
Title |
---|
AHOU-ZEID A.H.S. ET AL.: "Chemical and Biological Study of the Leaves of Some Musa species", EGYPT. J. PHARM. SCI., vol. 39, no. 4-6, 1998, pages 379 - 398, XP003001271 * |
OKAYAR A. ET AL.: "Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models", PHYTOTHER. RES., vol. 15, no. 2, 2001, pages 157 - 161, XP003011588 * |
RAJASEKARAN S. ET AL.: "Hypoglycemic Effect of Aloe vera gel on streptozotocin-induced diabetes in experimental rats", JOURNAL OF MEDICINAL FOOD, vol. 7, no. 1, 2004, pages 61 - 66, XP003011589 * |
See also references of EP1930014A4 * |
TANAKA M. ET AL.: "Identification of Five Phytosterols from Aloe Vera Gel as Anti-diabetic Compounds", BIOL. PHARM. BULL., vol. 26, no. 7, July 2006 (2006-07-01), pages 1418 - 1422, XP003011592 * |
YEH G.Y. ET AL.: "Systematic review of herbs and dietary supplements for glycemic control in diabetes", DIABETES CARE, vol. 26, no. 4, 2003, pages 1277 - 1294, XP003011591 * |
YONGCHAIYUDHA S. ET AL.: "Antidiabetic activity of Aloe vera L.juice. I. Clinical trial in new cases of diabetes mellitus", PHYTOMEDICINE, vol. 3, no. 3, 1996, pages 241 - 243, XP003011590 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010058795A1 (ja) | 2008-11-19 | 2010-05-27 | 森永乳業株式会社 | 抗酸化剤 |
JP4590491B2 (ja) * | 2008-11-19 | 2010-12-01 | 森永乳業株式会社 | 過酸化脂質生成抑制のための医薬 |
CN102216317A (zh) * | 2008-11-19 | 2011-10-12 | 森永乳业株式会社 | 抗氧化剂 |
JPWO2010058795A1 (ja) * | 2008-11-19 | 2012-04-19 | 森永乳業株式会社 | 過酸化脂質生成抑制のための医薬 |
US8470807B2 (en) | 2008-11-19 | 2013-06-25 | Morinaga Milk Industry Co., Ltd. | Antioxidant |
CN102216317B (zh) * | 2008-11-19 | 2015-07-22 | 森永乳业株式会社 | 抗氧化剂 |
JP2012515140A (ja) * | 2009-01-16 | 2012-07-05 | 花王株式会社 | 食後血糖上昇抑制剤 |
JP2014221733A (ja) * | 2013-05-13 | 2014-11-27 | 花王株式会社 | 精製トリテルペンアルコールの製造方法 |
WO2023054477A1 (ja) * | 2021-09-28 | 2023-04-06 | 森永乳業株式会社 | アロエ抽出物の製造方法 |
Also Published As
Publication number | Publication date |
---|---|
RU2380103C2 (ru) | 2010-01-27 |
AU2006300640C1 (en) | 2010-04-08 |
RU2008112884A (ru) | 2009-10-10 |
ES2626792T3 (es) | 2017-07-26 |
KR100972952B1 (ko) | 2010-07-30 |
CA2623639C (en) | 2011-04-26 |
JP4176140B2 (ja) | 2008-11-05 |
JPWO2007043305A1 (ja) | 2009-04-16 |
EP1930014A4 (en) | 2011-08-31 |
KR20080031399A (ko) | 2008-04-08 |
AU2006300640A1 (en) | 2007-04-19 |
EP1930014A1 (en) | 2008-06-11 |
EP1930014B1 (en) | 2017-03-01 |
AU2006300640B2 (en) | 2009-07-30 |
CN101277705B (zh) | 2013-05-01 |
AU2006300640B8 (en) | 2009-08-20 |
CN101277705A (zh) | 2008-10-01 |
US7947669B2 (en) | 2011-05-24 |
KR20100061580A (ko) | 2010-06-07 |
CA2623639A1 (en) | 2007-04-19 |
KR100999317B1 (ko) | 2010-12-09 |
US20100035851A1 (en) | 2010-02-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2007043305A1 (ja) | インスリン抵抗性改善剤 | |
JP3924310B2 (ja) | 高血糖改善のための医薬及び飲食品 | |
JP4165658B2 (ja) | インスリン抵抗性改善剤 | |
JP4169777B2 (ja) | インスリン抵抗性改善剤 | |
WO2006123466A1 (ja) | 膵臓機能改善のための医薬又は飲食品 | |
JP4164538B2 (ja) | 内臓脂肪蓄積抑制剤 | |
WO2007034851A1 (ja) | 内臓脂肪蓄積抑制剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200680036515.0 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2007539848 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 621/CHENP/2008 Country of ref document: IN |
|
REEP | Request for entry into the european phase |
Ref document number: 2006810426 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006810426 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020087003390 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006300640 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12064607 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref document number: 2006300640 Country of ref document: AU Date of ref document: 20060922 Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2623639 Country of ref document: CA |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2008112884 Country of ref document: RU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020107010955 Country of ref document: KR |