JP2020519688A - 抗糖尿病活性および他の有用な活性を有する植物抽出物 - Google Patents
抗糖尿病活性および他の有用な活性を有する植物抽出物 Download PDFInfo
- Publication number
- JP2020519688A JP2020519688A JP2020512782A JP2020512782A JP2020519688A JP 2020519688 A JP2020519688 A JP 2020519688A JP 2020512782 A JP2020512782 A JP 2020512782A JP 2020512782 A JP2020512782 A JP 2020512782A JP 2020519688 A JP2020519688 A JP 2020519688A
- Authority
- JP
- Japan
- Prior art keywords
- insulin
- irs2
- extract
- irs
- pharmaceutical composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000419 plant extract Substances 0.000 title claims abstract description 23
- 230000000694 effects Effects 0.000 title abstract description 82
- 230000003178 anti-diabetic effect Effects 0.000 title description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims abstract description 286
- 102000004877 Insulin Human genes 0.000 claims abstract description 143
- 108090001061 Insulin Proteins 0.000 claims abstract description 142
- 229940125396 insulin Drugs 0.000 claims abstract description 142
- 239000000284 extract Substances 0.000 claims abstract description 65
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 51
- 230000011664 signaling Effects 0.000 claims abstract description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 102100025092 Insulin receptor substrate 2 Human genes 0.000 claims description 125
- 206010012601 diabetes mellitus Diseases 0.000 claims description 63
- 238000000034 method Methods 0.000 claims description 39
- 206010022489 Insulin Resistance Diseases 0.000 claims description 38
- 239000008194 pharmaceutical composition Substances 0.000 claims description 36
- 235000015872 dietary supplement Nutrition 0.000 claims description 33
- 230000001404 mediated effect Effects 0.000 claims description 29
- 239000003826 tablet Substances 0.000 claims description 19
- 239000000843 powder Substances 0.000 claims description 18
- 240000008415 Lactuca sativa Species 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 16
- 235000003228 Lactuca sativa Nutrition 0.000 claims description 15
- 235000003092 Artemisia dracunculus Nutrition 0.000 claims description 14
- 240000001851 Artemisia dracunculus Species 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 14
- 239000001181 artemisia dracunculus Substances 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052804 chromium Inorganic materials 0.000 claims description 11
- 239000011651 chromium Substances 0.000 claims description 11
- 108010011459 Exenatide Proteins 0.000 claims description 10
- 230000001419 dependent effect Effects 0.000 claims description 10
- 229960001519 exenatide Drugs 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- 239000006286 aqueous extract Substances 0.000 claims description 9
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 8
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 7
- 229960003105 metformin Drugs 0.000 claims description 7
- 239000000377 silicon dioxide Substances 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- 235000021355 Stearic acid Nutrition 0.000 claims description 6
- 239000012676 herbal extract Substances 0.000 claims description 6
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 6
- 239000008117 stearic acid Substances 0.000 claims description 6
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 5
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 claims description 5
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 5
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims description 5
- 108010019598 Liraglutide Proteins 0.000 claims description 5
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 5
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 claims description 5
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 claims description 5
- 229960002701 liraglutide Drugs 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 235000012054 meals Nutrition 0.000 claims description 5
- 229950004994 meglitinide Drugs 0.000 claims description 5
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 claims description 5
- 229960004034 sitagliptin Drugs 0.000 claims description 5
- 230000004936 stimulating effect Effects 0.000 claims description 5
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 claims description 5
- 229960001254 vildagliptin Drugs 0.000 claims description 5
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 4
- 235000019739 Dicalciumphosphate Nutrition 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 4
- 229940125708 antidiabetic agent Drugs 0.000 claims description 4
- 239000003472 antidiabetic agent Substances 0.000 claims description 4
- 239000001506 calcium phosphate Substances 0.000 claims description 4
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 4
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 claims description 4
- 229940038472 dicalcium phosphate Drugs 0.000 claims description 4
- 229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 4
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- 235000012239 silicon dioxide Nutrition 0.000 claims description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 3
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 208000001280 Prediabetic State Diseases 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 229960001713 canagliflozin Drugs 0.000 claims description 3
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 claims description 3
- 229910052802 copper Inorganic materials 0.000 claims description 3
- 239000010949 copper Substances 0.000 claims description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 3
- 229960003834 dapagliflozin Drugs 0.000 claims description 3
- 229960003345 empagliflozin Drugs 0.000 claims description 3
- OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 3
- 229910052742 iron Inorganic materials 0.000 claims description 3
- 229940057948 magnesium stearate Drugs 0.000 claims description 3
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 3
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 3
- 229960001866 silicon dioxide Drugs 0.000 claims description 3
- 229960004274 stearic acid Drugs 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 2
- 229940100389 Sulfonylurea Drugs 0.000 claims description 2
- 229940123464 Thiazolidinedione Drugs 0.000 claims description 2
- 101001077600 Homo sapiens Insulin receptor substrate 2 Proteins 0.000 claims 2
- ODIHLEYTPVYAPY-UHFFFAOYSA-N 3-[2-fluoro-4-[[3-[2-methyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methylamino]phenyl]propanoic acid Chemical compound CC1=CC(OCCCS(C)(=O)=O)=CC=C1C1=CC=CC(CNC=2C=C(F)C(CCC(O)=O)=CC=2)=C1 ODIHLEYTPVYAPY-UHFFFAOYSA-N 0.000 claims 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 120
- 108090000623 proteins and genes Proteins 0.000 abstract description 62
- 102000004169 proteins and genes Human genes 0.000 abstract description 47
- 108010001127 Insulin Receptor Proteins 0.000 abstract description 43
- 102000003746 Insulin Receptor Human genes 0.000 abstract description 41
- 238000011282 treatment Methods 0.000 abstract description 22
- 239000000758 substrate Substances 0.000 abstract description 16
- 208000035475 disorder Diseases 0.000 abstract description 12
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 abstract description 10
- 230000009286 beneficial effect Effects 0.000 abstract description 10
- 235000016709 nutrition Nutrition 0.000 abstract description 10
- 230000001105 regulatory effect Effects 0.000 abstract description 10
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 abstract description 9
- 241001465754 Metazoa Species 0.000 abstract description 8
- 102000013275 Somatomedins Human genes 0.000 abstract description 8
- 102000005962 receptors Human genes 0.000 abstract description 8
- 230000002265 prevention Effects 0.000 abstract description 7
- 108020003175 receptors Proteins 0.000 abstract description 7
- 230000002473 insulinotropic effect Effects 0.000 abstract description 3
- 238000010586 diagram Methods 0.000 abstract 1
- 108010034219 Insulin Receptor Substrate Proteins Proteins 0.000 description 148
- 210000004027 cell Anatomy 0.000 description 78
- 239000000203 mixture Substances 0.000 description 50
- 235000018102 proteins Nutrition 0.000 description 43
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 36
- 230000006870 function Effects 0.000 description 35
- 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 31
- 239000008103 glucose Substances 0.000 description 31
- 241000196324 Embryophyta Species 0.000 description 30
- 102000009433 Insulin Receptor Substrate Proteins Human genes 0.000 description 28
- 230000014509 gene expression Effects 0.000 description 28
- 210000001519 tissue Anatomy 0.000 description 28
- 238000006366 phosphorylation reaction Methods 0.000 description 25
- 241000699670 Mus sp. Species 0.000 description 24
- 230000026731 phosphorylation Effects 0.000 description 24
- 239000003814 drug Substances 0.000 description 22
- 230000019491 signal transduction Effects 0.000 description 22
- 238000012360 testing method Methods 0.000 description 22
- 150000003839 salts Chemical class 0.000 description 20
- 238000009472 formulation Methods 0.000 description 18
- 230000007246 mechanism Effects 0.000 description 16
- 241000282412 Homo Species 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 15
- 230000003827 upregulation Effects 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 239000000463 material Substances 0.000 description 14
- 241000894007 species Species 0.000 description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 13
- 230000002093 peripheral effect Effects 0.000 description 13
- 230000004913 activation Effects 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- -1 AKT Proteins 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 230000015556 catabolic process Effects 0.000 description 11
- 239000002552 dosage form Substances 0.000 description 11
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 10
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 10
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- 230000009102 absorption Effects 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- 230000035755 proliferation Effects 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- 208000008589 Obesity Diseases 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 238000006731 degradation reaction Methods 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000003914 insulin secretion Effects 0.000 description 9
- 235000020824 obesity Nutrition 0.000 description 9
- 102100040758 CREB-regulated transcription coactivator 2 Human genes 0.000 description 8
- 101100287084 Homo sapiens IRS2 gene Proteins 0.000 description 8
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 8
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- 230000009471 action Effects 0.000 description 8
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 8
- 235000018927 edible plant Nutrition 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- 235000007542 Cichorium intybus Nutrition 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- 230000003213 activating effect Effects 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 238000000423 cell based assay Methods 0.000 description 7
- 230000004663 cell proliferation Effects 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 230000002708 enhancing effect Effects 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 239000002674 ointment Substances 0.000 description 7
- 239000006072 paste Substances 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000007921 spray Substances 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 208000024827 Alzheimer disease Diseases 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 6
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 6
- 102000040945 Transcription factor Human genes 0.000 description 6
- 108091023040 Transcription factor Proteins 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000003963 antioxidant agent Substances 0.000 description 6
- 235000006708 antioxidants Nutrition 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 235000005911 diet Nutrition 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 239000008273 gelatin Substances 0.000 description 6
- 229920000159 gelatin Polymers 0.000 description 6
- 235000019322 gelatine Nutrition 0.000 description 6
- 235000011852 gelatine desserts Nutrition 0.000 description 6
- 210000003494 hepatocyte Anatomy 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 231100000252 nontoxic Toxicity 0.000 description 6
- 230000003000 nontoxic effect Effects 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 6
- 208000024172 Cardiovascular disease Diseases 0.000 description 5
- 244000298479 Cichorium intybus Species 0.000 description 5
- 102100035427 Forkhead box protein O1 Human genes 0.000 description 5
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 5
- 101000891901 Homo sapiens CREB-regulated transcription coactivator 2 Proteins 0.000 description 5
- 101000877727 Homo sapiens Forkhead box protein O1 Proteins 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 101710183548 Pyridoxal 5'-phosphate synthase subunit PdxS Proteins 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 5
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 5
- 102100028507 Transcription factor E3 Human genes 0.000 description 5
- 101710162515 Transcription factor E3 Proteins 0.000 description 5
- 102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 description 5
- 239000012190 activator Substances 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 238000013270 controlled release Methods 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 230000008482 dysregulation Effects 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 230000002440 hepatic effect Effects 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 230000002608 insulinlike Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 208000030159 metabolic disease Diseases 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 238000007911 parenteral administration Methods 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 230000001737 promoting effect Effects 0.000 description 5
- 230000008929 regeneration Effects 0.000 description 5
- 238000011069 regeneration method Methods 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 239000000454 talc Substances 0.000 description 5
- 229910052623 talc Inorganic materials 0.000 description 5
- 235000012222 talc Nutrition 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 230000008733 trauma Effects 0.000 description 5
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
- 102100037263 3-phosphoinositide-dependent protein kinase 1 Human genes 0.000 description 4
- 102100031786 Adiponectin Human genes 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 241000416162 Astragalus gummifer Species 0.000 description 4
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 4
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 4
- 101000600756 Homo sapiens 3-phosphoinositide-dependent protein kinase 1 Proteins 0.000 description 4
- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 4
- 101001087394 Homo sapiens Tyrosine-protein phosphatase non-receptor type 1 Proteins 0.000 description 4
- 101001117146 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Proteins 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- 241000218922 Magnoliophyta Species 0.000 description 4
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- CWEZAWNPTYBADX-UHFFFAOYSA-N Procyanidin Natural products OC1C(OC2C(O)C(Oc3c2c(O)cc(O)c3C4C(O)C(Oc5cc(O)cc(O)c45)c6ccc(O)c(O)c6)c7ccc(O)c(O)c7)c8c(O)cc(O)cc8OC1c9ccc(O)c(O)c9 CWEZAWNPTYBADX-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 108010074436 Sterol Regulatory Element Binding Protein 1 Proteins 0.000 description 4
- 102100026839 Sterol regulatory element-binding protein 1 Human genes 0.000 description 4
- 229920001615 Tragacanth Polymers 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000005714 functional activity Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000004190 glucose uptake Effects 0.000 description 4
- 125000004383 glucosinolate group Chemical group 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 230000013632 homeostatic process Effects 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- 230000002218 hypoglycaemic effect Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 229920002414 procyanidin Polymers 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 235000010487 tragacanth Nutrition 0.000 description 4
- 239000000196 tragacanth Substances 0.000 description 4
- 229940116362 tragacanth Drugs 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 230000001228 trophic effect Effects 0.000 description 4
- 235000013311 vegetables Nutrition 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108010076365 Adiponectin Proteins 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 3
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 3
- 101001059929 Caenorhabditis elegans Forkhead box protein O Proteins 0.000 description 3
- 101100315624 Caenorhabditis elegans tyr-1 gene Proteins 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 241000723343 Cichorium Species 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 208000032928 Dyslipidaemia Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 101150106966 FOXO1 gene Proteins 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 101150088952 IGF1 gene Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 101710201820 Insulin receptor substrate 2 Proteins 0.000 description 3
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 3
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 description 3
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 3
- 101710156785 Insulin-like receptor Proteins 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- ZQISRDCJNBUVMM-UHFFFAOYSA-N L-Histidinol Natural products OCC(N)CC1=CN=CN1 ZQISRDCJNBUVMM-UHFFFAOYSA-N 0.000 description 3
- ZQISRDCJNBUVMM-YFKPBYRVSA-N L-histidinol Chemical compound OC[C@@H](N)CC1=CNC=N1 ZQISRDCJNBUVMM-YFKPBYRVSA-N 0.000 description 3
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 201000002451 Overnutrition Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 108091007960 PI3Ks Proteins 0.000 description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 description 3
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 3
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 3
- 229920002732 Polyanhydride Polymers 0.000 description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- 108091027981 Response element Proteins 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 3
- 108700012920 TNF Proteins 0.000 description 3
- 102100031638 Tuberin Human genes 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 210000001789 adipocyte Anatomy 0.000 description 3
- 235000010419 agar Nutrition 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 235000012216 bentonite Nutrition 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000036755 cellular response Effects 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 235000003733 chicria Nutrition 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000030609 dephosphorylation Effects 0.000 description 3
- 238000006209 dephosphorylation reaction Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000007783 downstream signaling Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 210000001508 eye Anatomy 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 230000010030 glucose lowering effect Effects 0.000 description 3
- 229940087559 grape seed Drugs 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000003701 inert diluent Substances 0.000 description 3
- 230000006362 insulin response pathway Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 239000004816 latex Substances 0.000 description 3
- 229920000126 latex Polymers 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 235000020823 overnutrition Nutrition 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- 230000004853 protein function Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 229960001052 streptozocin Drugs 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- 102100032358 Adiponectin receptor protein 2 Human genes 0.000 description 2
- 230000007730 Akt signaling Effects 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 235000015894 Averrhoa bilimbi Nutrition 0.000 description 2
- 240000005697 Averrhoa bilimbi Species 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 235000017647 Brassica oleracea var italica Nutrition 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- 101710094470 CREB-regulated transcription coactivator 2 Proteins 0.000 description 2
- 102000004007 Calpain-10 Human genes 0.000 description 2
- 108090000451 Calpain-10 Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 240000006740 Cichorium endivia Species 0.000 description 2
- 244000259764 Cucurbita melanosperma Species 0.000 description 2
- 235000000861 Cucurbita melanosperma Nutrition 0.000 description 2
- 102100032218 Cytokine-inducible SH2-containing protein Human genes 0.000 description 2
- 101710132484 Cytokine-inducible SH2-containing protein Proteins 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 2
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 2
- 101100015729 Drosophila melanogaster drk gene Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 102100027541 GTP-binding protein Rheb Human genes 0.000 description 2
- 206010064571 Gene mutation Diseases 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- 108010051696 Growth Hormone Proteins 0.000 description 2
- 101000589401 Homo sapiens Adiponectin receptor protein 2 Proteins 0.000 description 2
- 101000852815 Homo sapiens Insulin receptor Proteins 0.000 description 2
- 101000994101 Homo sapiens Insulin receptor substrate 4 Proteins 0.000 description 2
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 2
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 2
- 101000688606 Homo sapiens Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 Proteins 0.000 description 2
- 101000707152 Homo sapiens SH2B adapter protein 1 Proteins 0.000 description 2
- 101150030450 IRS1 gene Proteins 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
- 102100025087 Insulin receptor substrate 1 Human genes 0.000 description 2
- 101710201824 Insulin receptor substrate 1 Proteins 0.000 description 2
- 102100031419 Insulin receptor substrate 4 Human genes 0.000 description 2
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- 102000016267 Leptin Human genes 0.000 description 2
- 108010092277 Leptin Proteins 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 2
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 235000001412 Mediterranean diet Nutrition 0.000 description 2
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 102000038030 PI3Ks Human genes 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108010016731 PPAR gamma Proteins 0.000 description 2
- 101150014691 PPARA gene Proteins 0.000 description 2
- 102100041030 Pancreas/duodenum homeobox protein 1 Human genes 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 2
- 102100024242 Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 Human genes 0.000 description 2
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 2
- 235000011613 Pinus brutia Nutrition 0.000 description 2
- 241000018646 Pinus brutia Species 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 102000010995 Pleckstrin homology domains Human genes 0.000 description 2
- 108050001185 Pleckstrin homology domains Proteins 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 2
- 101150020518 RHEB gene Proteins 0.000 description 2
- 201000007737 Retinal degeneration Diseases 0.000 description 2
- 108010000605 Ribosomal Proteins Proteins 0.000 description 2
- 102000002278 Ribosomal Proteins Human genes 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 102100031770 SH2B adapter protein 1 Human genes 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 101150045565 Socs1 gene Proteins 0.000 description 2
- 101150043341 Socs3 gene Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 description 2
- 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 description 2
- 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 description 2
- 102000004584 Somatomedin Receptors Human genes 0.000 description 2
- 108010017622 Somatomedin Receptors Proteins 0.000 description 2
- 102100038803 Somatotropin Human genes 0.000 description 2
- 108010020396 Sterol Regulatory Element Binding Proteins Proteins 0.000 description 2
- 102000009822 Sterol Regulatory Element Binding Proteins Human genes 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108700027336 Suppressor of Cytokine Signaling 1 Proteins 0.000 description 2
- 108700027337 Suppressor of Cytokine Signaling 3 Proteins 0.000 description 2
- 102100024779 Suppressor of cytokine signaling 1 Human genes 0.000 description 2
- 102100024283 Suppressor of cytokine signaling 3 Human genes 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 108700011001 Transcription Factor 7-Like 2 Proteins 0.000 description 2
- 102100035101 Transcription factor 7-like 2 Human genes 0.000 description 2
- 108090000848 Ubiquitin Proteins 0.000 description 2
- 102000044159 Ubiquitin Human genes 0.000 description 2
- 102000008219 Uncoupling Protein 2 Human genes 0.000 description 2
- 108010021111 Uncoupling Protein 2 Proteins 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 230000004900 autophagic degradation Effects 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 208000037887 cell injury Diseases 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 244000116025 chicria Species 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 230000001447 compensatory effect Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000002385 cottonseed oil Substances 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
- 229940093471 ethyl oleate Drugs 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 230000004907 flux Effects 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 235000012055 fruits and vegetables Nutrition 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000014101 glucose homeostasis Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 101150098203 grb2 gene Proteins 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000000122 growth hormone Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 235000009200 high fat diet Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 102000047882 human INSR Human genes 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 238000002013 hydrophilic interaction chromatography Methods 0.000 description 2
- 201000008980 hyperinsulinism Diseases 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 108010042209 insulin receptor tyrosine kinase Proteins 0.000 description 2
- 229940068935 insulin-like growth factor 2 Drugs 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 229940039781 leptin Drugs 0.000 description 2
- 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 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 239000006194 liquid suspension Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000010120 metabolic dysregulation Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 210000000885 nephron Anatomy 0.000 description 2
- 239000012457 nonaqueous media Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000002417 nutraceutical Substances 0.000 description 2
- 235000021436 nutraceutical agent Nutrition 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 230000009894 physiological stress Effects 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
- 229920000728 polyester Polymers 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 102000016914 ras Proteins Human genes 0.000 description 2
- 108010014186 ras Proteins Proteins 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
- 230000004258 retinal degeneration Effects 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 230000009919 sequestration Effects 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 230000009131 signaling function Effects 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 210000001082 somatic cell Anatomy 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 238000011146 sterile filtration Methods 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- SUVMJBTUFCVSAD-UHFFFAOYSA-N sulforaphane Chemical compound CS(=O)CCCCN=C=S SUVMJBTUFCVSAD-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 238000010798 ubiquitination Methods 0.000 description 2
- 230000034512 ubiquitination Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 208000019553 vascular disease Diseases 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 230000036642 wellbeing Effects 0.000 description 2
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- XFZJEEAOWLFHDH-UHFFFAOYSA-N (2R,2'R,3R,3'R,4R)-3,3',4',5,7-Pentahydroxyflavan(48)-3,3',4',5,7-pentahydroxyflavan Natural products C=12OC(C=3C=C(O)C(O)=CC=3)C(O)CC2=C(O)C=C(O)C=1C(C1=C(O)C=C(O)C=C1O1)C(O)C1C1=CC=C(O)C(O)=C1 XFZJEEAOWLFHDH-UHFFFAOYSA-N 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- KOHIRBRYDXPAMZ-YHBROIRLSA-N (S,R,R,R)-nebivolol Chemical compound C1CC2=CC(F)=CC=C2O[C@H]1[C@H](O)CNC[C@@H](O)[C@H]1OC2=CC=C(F)C=C2CC1 KOHIRBRYDXPAMZ-YHBROIRLSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 1
- JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- SUVMJBTUFCVSAD-JTQLQIEISA-N 4-Methylsulfinylbutyl isothiocyanate Natural products C[S@](=O)CCCCN=C=S SUVMJBTUFCVSAD-JTQLQIEISA-N 0.000 description 1
- 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 101001082110 Acanthamoeba polyphaga mimivirus Eukaryotic translation initiation factor 4E homolog Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000219317 Amaranthaceae Species 0.000 description 1
- 229940123073 Angiotensin antagonist Drugs 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000208838 Asteraceae Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- 241000219198 Brassica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000011293 Brassica napus Nutrition 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000004221 Brassica oleracea var gemmifera Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 244000308368 Brassica oleracea var. gemmifera Species 0.000 description 1
- 240000008100 Brassica rapa Species 0.000 description 1
- 244000221633 Brassica rapa subsp chinensis Species 0.000 description 1
- 235000010149 Brassica rapa subsp chinensis Nutrition 0.000 description 1
- 235000000540 Brassica rapa subsp rapa Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 241000219193 Brassicaceae Species 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 235000009467 Carica papaya Nutrition 0.000 description 1
- 240000006432 Carica papaya Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- YDDGKXBLOXEEMN-IABMMNSOSA-L Chicoric acid Natural products C1=C(O)C(O)=CC=C1\C=C\C(=O)O[C@@H](C([O-])=O)[C@H](C([O-])=O)OC(=O)\C=C\C1=CC=C(O)C(O)=C1 YDDGKXBLOXEEMN-IABMMNSOSA-L 0.000 description 1
- 235000018536 Cichorium endivia Nutrition 0.000 description 1
- 244000223760 Cinnamomum zeylanicum 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
- 108091026890 Coding region Proteins 0.000 description 1
- 241000218631 Coniferophyta Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 102100033270 Cyclin-dependent kinase inhibitor 1 Human genes 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 101001082109 Danio rerio Eukaryotic translation initiation factor 4E-1B Proteins 0.000 description 1
- 102100031598 Dedicator of cytokinesis protein 1 Human genes 0.000 description 1
- 102100031597 Dedicator of cytokinesis protein 2 Human genes 0.000 description 1
- YDDGKXBLOXEEMN-UHFFFAOYSA-N Di-E-caffeoyl-meso-tartaric acid Natural products C=1C=C(O)C(O)=CC=1C=CC(=O)OC(C(O)=O)C(C(=O)O)OC(=O)C=CC1=CC=C(O)C(O)=C1 YDDGKXBLOXEEMN-UHFFFAOYSA-N 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 1
- 101100508533 Drosophila melanogaster IKKbeta gene Proteins 0.000 description 1
- 108091035710 E-box Proteins 0.000 description 1
- 241000792913 Ebenaceae Species 0.000 description 1
- 101710088791 Elongation factor 2 Proteins 0.000 description 1
- 108010003751 Elongin Proteins 0.000 description 1
- 102000004662 Elongin Human genes 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000989735 Euclea undulata Species 0.000 description 1
- 108010014863 Eukaryotic Initiation Factors Proteins 0.000 description 1
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
- 208000007984 Female Infertility Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 108090000852 Forkhead Transcription Factors Proteins 0.000 description 1
- 102000004315 Forkhead Transcription Factors Human genes 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 101150101862 GRB14 gene Proteins 0.000 description 1
- 102100037740 GRB2-associated-binding protein 1 Human genes 0.000 description 1
- 102100037759 GRB2-associated-binding protein 2 Human genes 0.000 description 1
- 102100029974 GTPase HRas Human genes 0.000 description 1
- 101710091881 GTPase HRas Proteins 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 102000058061 Glucose Transporter Type 4 Human genes 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 108010001483 Glycogen Synthase Proteins 0.000 description 1
- 101150090959 Grb10 gene Proteins 0.000 description 1
- 102100033067 Growth factor receptor-bound protein 2 Human genes 0.000 description 1
- 101150113453 Gsk3a gene Proteins 0.000 description 1
- 241000208253 Gymnema sylvestre Species 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 102300052097 Hepatocyte nuclear factor 4-alpha isoform HNF4-Alpha-2 Human genes 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 102000009331 Homeodomain Proteins Human genes 0.000 description 1
- 108010048671 Homeodomain Proteins Proteins 0.000 description 1
- 101000614701 Homo sapiens ATP-sensitive inward rectifier potassium channel 11 Proteins 0.000 description 1
- 101000775469 Homo sapiens Adiponectin Proteins 0.000 description 1
- 101000944380 Homo sapiens Cyclin-dependent kinase inhibitor 1 Proteins 0.000 description 1
- 101000866235 Homo sapiens Dedicator of cytokinesis protein 1 Proteins 0.000 description 1
- 101000866237 Homo sapiens Dedicator of cytokinesis protein 2 Proteins 0.000 description 1
- 101001024897 Homo sapiens GRB2-associated-binding protein 1 Proteins 0.000 description 1
- 101001024902 Homo sapiens GRB2-associated-binding protein 2 Proteins 0.000 description 1
- 101000871017 Homo sapiens Growth factor receptor-bound protein 2 Proteins 0.000 description 1
- 101600072310 Homo sapiens Hepatocyte nuclear factor 4-alpha (isoform HNF4-Alpha-2) Proteins 0.000 description 1
- 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 description 1
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 1
- 101000604565 Homo sapiens Phosphatidylinositol glycan anchor biosynthesis class U protein Proteins 0.000 description 1
- 101001026864 Homo sapiens Protein kinase C gamma type Proteins 0.000 description 1
- 101000798015 Homo sapiens RAC-beta serine/threonine-protein kinase Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000038455 IGF Type 1 Receptor Human genes 0.000 description 1
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 1
- 101150002416 Igf2 gene Proteins 0.000 description 1
- 206010021928 Infertility female Diseases 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- 101710190529 Insulin-like peptide Proteins 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 102000000704 Interleukin-7 Human genes 0.000 description 1
- 102000000585 Interleukin-9 Human genes 0.000 description 1
- 229920001202 Inulin Polymers 0.000 description 1
- 102000017792 KCNJ11 Human genes 0.000 description 1
- 206010023379 Ketoacidosis Diseases 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 108010034057 Mechanistic Target of Rapamycin Complex 2 Proteins 0.000 description 1
- 101100287085 Mus musculus Irs2 gene Proteins 0.000 description 1
- 241000238367 Mya arenaria Species 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 241001611263 Myrtina Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 235000017879 Nasturtium officinale Nutrition 0.000 description 1
- 240000005407 Nasturtium officinale Species 0.000 description 1
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108010015847 Non-Receptor Type 1 Protein Tyrosine Phosphatase Proteins 0.000 description 1
- 239000005480 Olmesartan Substances 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 101710144033 Pancreas/duodenum homeobox protein 1 Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 108010089430 Phosphoproteins Proteins 0.000 description 1
- 102000007982 Phosphoproteins Human genes 0.000 description 1
- 241000425347 Phyla <beetle> Species 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 241000985694 Polypodiopsida Species 0.000 description 1
- 206010063493 Premature ageing Diseases 0.000 description 1
- 208000032038 Premature aging Diseases 0.000 description 1
- 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
- MOJZMWJRUKIQGL-FWCKPOPSSA-N Procyanidin C2 Natural products O[C@@H]1[C@@H](c2cc(O)c(O)cc2)Oc2c([C@H]3[C@H](O)[C@@H](c4cc(O)c(O)cc4)Oc4c3c(O)cc(O)c4)c(O)cc(O)c2[C@@H]1c1c(O)cc(O)c2c1O[C@@H]([C@H](O)C2)c1cc(O)c(O)cc1 MOJZMWJRUKIQGL-FWCKPOPSSA-N 0.000 description 1
- 102100024819 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 102100037314 Protein kinase C gamma type Human genes 0.000 description 1
- 241000932933 Pseudomassaria Species 0.000 description 1
- 206010037596 Pyelonephritis Diseases 0.000 description 1
- 102100032315 RAC-beta serine/threonine-protein kinase Human genes 0.000 description 1
- 102000046951 Ras Homolog Enriched in Brain Human genes 0.000 description 1
- 108700019578 Ras Homolog Enriched in Brain Proteins 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000027032 Renal vascular disease Diseases 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 102000007156 Resistin Human genes 0.000 description 1
- 108010047909 Resistin Proteins 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 101710108924 Ribosomal protein S6 kinase beta-1 Proteins 0.000 description 1
- 102100024908 Ribosomal protein S6 kinase beta-1 Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102000014400 SH2 domains Human genes 0.000 description 1
- 108050003452 SH2 domains Proteins 0.000 description 1
- 108091006300 SLC2A4 Proteins 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 101710204410 Scaffold protein Proteins 0.000 description 1
- 241000533293 Sesbania emerus Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 108050009309 Tuberin Proteins 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 241000219095 Vitis Species 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 230000037328 acute stress Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000011759 adipose tissue development Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 239000002369 angiotensin antagonist Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000021229 appetite regulation Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 210000003295 arcuate nucleus Anatomy 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 229940069765 bean extract Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 229910052790 beryllium Inorganic materials 0.000 description 1
- ATBAMAFKBVZNFJ-UHFFFAOYSA-N beryllium atom Chemical compound [Be] ATBAMAFKBVZNFJ-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 230000003491 cAMP production Effects 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
- 210000001043 capillary endothelial cell Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000032677 cell aging Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- 150000001783 ceramides Chemical class 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- YDDGKXBLOXEEMN-IABMMNSOSA-N chicoric acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C(O)=O)C(=O)\C=C\C1=CC=C(O)C(O)=C1 YDDGKXBLOXEEMN-IABMMNSOSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 229940074393 chlorogenic acid Drugs 0.000 description 1
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 description 1
- 235000001368 chlorogenic acid Nutrition 0.000 description 1
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 229940046374 chromium picolinate Drugs 0.000 description 1
- GJYSUGXFENSLOO-UHFFFAOYSA-N chromium;pyridine-2-carboxylic acid Chemical compound [Cr].OC(=O)C1=CC=CC=N1.OC(=O)C1=CC=CC=N1.OC(=O)C1=CC=CC=N1 GJYSUGXFENSLOO-UHFFFAOYSA-N 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 229930016920 cichoric acid Natural products 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000003081 coactivator Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- YDDGKXBLOXEEMN-PMACEKPBSA-N dicaffeoyl-D-tartaric acid Natural products O([C@H](C(=O)O)[C@H](OC(=O)C=CC=1C=C(O)C(O)=CC=1)C(O)=O)C(=O)C=CC1=CC=C(O)C(O)=C1 YDDGKXBLOXEEMN-PMACEKPBSA-N 0.000 description 1
- YDDGKXBLOXEEMN-WOJBJXKFSA-N dicaffeoyl-L-tartaric acid Natural products O([C@@H](C(=O)O)[C@@H](OC(=O)C=CC=1C=C(O)C(O)=CC=1)C(O)=O)C(=O)C=CC1=CC=C(O)C(O)=C1 YDDGKXBLOXEEMN-WOJBJXKFSA-N 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000001819 effect on gene Effects 0.000 description 1
- 230000000667 effect on insulin Effects 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 235000020937 fasting conditions Nutrition 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 230000009123 feedback regulation Effects 0.000 description 1
- 230000004634 feeding behavior Effects 0.000 description 1
- 229930182486 flavonoid glycoside Natural products 0.000 description 1
- 150000007955 flavonoid glycosides Chemical class 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- IXZISFNWUWKBOM-ARQDHWQXSA-N fructosamine Chemical compound NC[C@@]1(O)OC[C@@H](O)[C@@H](O)[C@@H]1O IXZISFNWUWKBOM-ARQDHWQXSA-N 0.000 description 1
- 235000020983 fruit intake Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 239000000054 fungal extract Substances 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 239000011491 glass wool Substances 0.000 description 1
- 230000001890 gluconeogenic effect Effects 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 239000003324 growth hormone secretagogue Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229930005346 hydroxycinnamic acid Natural products 0.000 description 1
- DEDGUGJNLNLJSR-UHFFFAOYSA-N hydroxycinnamic acid group Chemical class OC(C(=O)O)=CC1=CC=CC=C1 DEDGUGJNLNLJSR-UHFFFAOYSA-N 0.000 description 1
- 235000010359 hydroxycinnamic acids Nutrition 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000008799 immune stress Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000006759 inflammatory activation Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 230000004155 insulin signaling pathway Effects 0.000 description 1
- 230000002486 insulinomimetic effect Effects 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229940029339 inulin Drugs 0.000 description 1
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 1
- 239000012500 ion exchange media Substances 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 229960001632 labetalol Drugs 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940118019 malondialdehyde Drugs 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000003584 mesangial cell Anatomy 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 230000006609 metabolic stress Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 229960000619 nebivolol Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000030147 nuclear export Effects 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 1
- 229960005117 olmesartan Drugs 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 230000008723 osmotic stress Effects 0.000 description 1
- 210000004409 osteocyte Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000015031 pancreas development Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000011340 peptidyl-tyrosine autophosphorylation Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 239000009010 plant mixture extract P-9801091 Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910001848 post-transition metal Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000009862 primary prevention Effects 0.000 description 1
- 230000003244 pro-oxidative effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- HGVVOUNEGQIPMS-UHFFFAOYSA-N procyanidin Chemical compound O1C2=CC(O)=CC(O)=C2C(O)C(O)C1(C=1C=C(O)C(O)=CC=1)OC1CC2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 HGVVOUNEGQIPMS-UHFFFAOYSA-N 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 208000015670 renal artery disease Diseases 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 210000001116 retinal neuron Anatomy 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 235000012045 salad Nutrition 0.000 description 1
- 235000019695 salad leaves Nutrition 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 229910052706 scandium Inorganic materials 0.000 description 1
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229940100996 sodium bisulfate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 230000004960 subcellular localization Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 229960005559 sulforaphane Drugs 0.000 description 1
- 235000015487 sulforaphane Nutrition 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 102000013498 tau Proteins Human genes 0.000 description 1
- 108010026424 tau Proteins Proteins 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 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
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- SZCZSKMCTGEJKI-UHFFFAOYSA-N tuberin Natural products COC1=CC=C(C=CNC=O)C=C1 SZCZSKMCTGEJKI-UHFFFAOYSA-N 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 230000009750 upstream signaling Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- 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
- 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
- A23L33/16—Inorganic salts, minerals or trace elements
-
- 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
- A23L33/30—Dietetic or nutritional methods, e.g. for losing weight
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/26—Iron; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/32—Manganese; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/34—Copper; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/282—Artemisia, e.g. wormwood or sagebrush
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/287—Chrysanthemum, e.g. daisy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/10—General cosmetic use
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Botany (AREA)
- Inorganic Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Alternative & Traditional Medicine (AREA)
- Medical Informatics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Birds (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Physiology (AREA)
Abstract
Description
本出願は、2017年5月12日に出願された米国仮特許出願第62/505,494号の利益および優先権を主張し、該仮出願は、参照することによりその全体が本明細書に明示的に組み込まれる。
哺乳動物は、インスリン受容体(IR)遺伝子およびインスリン様成長因子−1受容体(IGF1R)遺伝子によりコードされる5つの相同的なインスリン様受容体チロシンキナーゼを活性化させる3つのインスリン様ペプチド、すなわち、インスリン、インスリン様成長因子 1(IGF 1)およびインスリン様成長因子−2(IGF−2)を産生する(図1A/B)。インスリンは、循環性グルコース濃度に応答して膵臓のβ細胞において産生される一方、内分泌性IGF 1は、概ね、栄養分および成長ホルモンにより刺激された肝細胞から分泌され、IGF 1およびIGF 2はまた、中枢神経系などの多くの組織および細胞において局所的に産生される(9)。IGF1は、インスリンと調和的に働いて、栄養ホメオスタシス、インスリン感受性および膵臓β細胞機能を調節することができる(9)。インスリン受容体およびIGF受容体遺伝子は、共有結合により連結された二量体を形成する相同的な前駆体をコードし、この二量体はタンパク質加水分解により切断されて、2つの細胞外α−サブユニットおよび2つの膜貫通β−サブユニットを有する四量体を生成する。細胞外α−サブユニットは、膜貫通β−サブユニットの細胞内部分上のチロシンキナーゼの活性を調節するリガンド結合ドメインを生成する(10)。
細胞ベースおよびマウスベースの実験により、全てでないにしてもほとんどのインスリンシグナルは、IRS1、IRS2もしくはこれらのホモログ;またはSHC、CBL、APSおよびSH2B、GAB1、GAB2、DOCK1、およびDOCK2などの他のスキャフォールドタンパク質のチロシンリン酸化を通じて生成またはモジュレ―トされることが示されている(15)。これらの各基質の役割は注目に値するが、トランスジェニックマウスを用いた研究により、多くのインスリン応答、特に、体細胞増殖および栄養ホメオスタシスと関連付けられるものは、IRS1またはIRS2を通じて媒介されることが示唆されている(1)。
最もよく研究されているインスリン様シグナル伝達カスケードの1つは、ホスファチジルイノシトール3キナーゼ(PI3キナーゼ)によるPI−3,4,5−P3の産生を伴う。1型PI3キナーゼは、2つのsrc相同2(SH2)ドメインを含有する調節サブユニットおよび触媒サブユニットから構成され、触媒サブユニットは、そのSH2ドメインがIRSタンパク質中のリン酸化されたチロシン残基により占められるまで調節サブユニットにより阻害される(23)。PI−3,4,5−P3は、Ser/ThrキナーゼPDK1およびAKT(PKBとしても公知)を形質膜に誘引し、そこでAKTは、PDK1媒介性のリン酸化により活性化される(図1A/B)。AKTは、細胞生存、成長、増殖、血管新生、代謝、および遊走において中心的役割を果たす多くのタンパク質をリン酸化する(24)。いくつもの真性のAKT基質のリン酸化は、特にインスリン様シグナル伝達に関連し、それらは、GSK3a/p(グリコーゲンシンターゼの阻害を遮断する)、AS160(GLUT4転座を促進する)、BAD・BCL2ヘテロ二量体(アポトーシスを阻害する)、FOXO転写因子(遺伝子発現を調節する)、p21CIP1およびp27KIP1(細胞周期阻害を遮断する)、eNOS(NO合成および血管拡張を刺激する)、ならびにPDE3b(cAMPを加水分解する)である(図1A/B)。AKTはまた、ツベリン(TSC2)をリン酸化し、ツベリン(TSC2)は、mTORを活性化させるRHEB’GTP複合体の蓄積を促進する小Gタンパク質RHEBへのそのGAP活性を阻害し(24)。この経路は、インスリンシグナル伝達と細胞増殖のために必要とされるタンパク質合成との直接的な連結を提供する(図1A/B)。
IRSタンパク質シグナル伝達の調節は、様々な組織の間でインスリン応答の強度および持続時間を協調させるための重要な方法であるが、これらの機序の障害はインスリン抵抗性を引き起こし得る。IRS1遺伝子の転写は一般に安定である。対照的に、IRS2の産生は、cAMP応答エレメント結合タンパク質(CREB)およびその結合パートナーCRTC2、フォークヘッドボックスO1(FOXO1)、転写因子E3(TFE3)、ならびにステロール調節エレメント結合因子−1c(SREBF−1c)などの複数の栄養感受性転写因子により調節される(26、27)。興味深いことに、cAMP応答エレメント(CRE)に結合するCREB/CRTC2転写複合体は、β細胞および肝臓においてIRS2発現に対して反対の効果を有する。食事後に、グルコース酸化からのATPの産生はβ細胞を脱分極させ、それが、CREB/CRTC2の活性化などの多くの重要な効果を有するCa2+流入およびcAMP産生の両方を促進する(26)。こうして、グルコースは、β細胞においてIRS2発現に直接的に連結され、それによりβ細胞増殖および代償的なインスリン分泌が刺激される。対照的に、CREB/CRTC2は、空腹時の肝臓においてIRS2発現を促進し、それにより、基礎インスリン応答を増大させることにより糖新生プログラムを阻害することができる。
インスリン抵抗性は、肥満症、高血圧、慢性感染症、女性の生殖調節異常、ならびに腎臓および心臓血管疾患といった多くの健康障害と関連付けられる一般的な病的状態である(1)。過去15年間にわたって、マウスベースの実験は、どのようにしてインスリンシグナルを媒介する遺伝子における突然変異がインスリンシグナルをモジュレ―トし、またはインスリンシグナルへの応答がインスリン抵抗性および糖尿病に寄与するかを明らかにしてきた。遺伝子突然変異は生涯にわたるインスリン抵抗性の自明な原因であるが、それらは通常、希少な代謝障害と関連付けられる。環境上の、生理学的な、および免疫学的なストレスは、複雑な遺伝学的背景により協調される異種要素からなるシグナル伝達カスケードを通じてインスリン抵抗性を引き起こす(1)。
Irs1またはIrs2の遺伝子を欠いたマウスはインスリン抵抗性であり、末梢グルコース利用に障害を有する。両方の種類のノックアウトマウスは代謝調節異常を示すが、Irs2−/−マウスのみが膵臓β細胞の完全に近い喪失により8〜12週齢の間に糖尿病を発症する(32)。この結果は、IRS2を通じたインスリン様シグナル伝達カスケードをβ細胞機能の中心に置く。
インスリン感作単位−(IS単位)
インスリン感作活性−(ISA単位)
インスリン最適化活性−(IOA単位)
インスリン最適化単位−(IO単位)
インスリンブースト活性−(IBA単位)
インスリンブースト単位−(IB単位)
インスリン増幅単位−(IA単位)
インスリン増幅活性−(IAA単位)
インスリン増強単位−(IIn単位)
インスリン増強活性−(IInA単位)
インスリン増大活性−(IAA単位)
インスリン向上活性−(IImA単位)
インスリン向上単位−(IIm単位)
インスリン強化単位−(ISt単位)
インスリン濃縮単位−(IEn単位)
インスリン等価単位−(IEq単位)
インスリン等価活性−(IEA単位)
Artemisia dracunculusの乾燥薬草抽出物;
dehor ia endiviaの乾燥薬草抽出物;
Lactuca sativaの乾燥薬草抽出物;および
任意選択的にクロム
を含む。
0.7mgのArtemisia dracunculusの乾燥薬草抽出物;
962.7mgのCichoria endiviaの乾燥薬草抽出物;
16.7mgのLactuca sativaの乾燥薬草抽出物;および
1.2megのクロム
を含み、
任意選択的にまた、リン酸二カルシウム、微結晶性セルロース、二酸化ケイ素、ヒドロキシプロピルセルロース、ステアリン酸、クロスカルメロースナトリウム、およびステアリン酸マグネシウム;ならびにこれらの組合せからなる群から選択される少なくとも1つの薬学的に許容される賦形剤を含む。
合計で50mg〜1,500mgの、
Artemisia dracunculusの乾燥薬草抽出物;
Cichoria endiviaの乾燥薬草抽出物;
Lactuca sativaの乾燥薬草抽出物;および
任意選択的にクロム
を含み、
任意選択的にまた、リン酸二カルシウム、微結晶性セルロース、二酸化ケイ素、ヒドロキシプロピルセルロース、ステアリン酸、クロスカルメロースナトリウム、およびステアリン酸マグネシウム;ならびにこれらの組合せからなる群から選択される少なくとも1つの薬学的に許容される賦形剤を含む。
1. White MF. Insulin signaling in health and disease. Science 2003 Dec 5; 302 (5651):1710-1.
2. Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D, et al. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature 2005 May 12; 435 (7039):220-3.
3. Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC. Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration? Diabetologia 2005 Nov; 48 (11):2221-8.
4. Semple RK, Sleigh A, Murgatroyd PR, Adams CA, Bluck L, Jackson S, et al. Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. J Clin Invest 2009 Feb; 119 (2):315-22.
5. Vaxillaire M, Veslot J, Dina C, Proenca C, Cauchi S, Charpentier G, et al. Impact of common type 2 diabetes risk polymorphisms in the DESIR prospective study. Diabetes 2008 Jan; 57 (1):244-54.
6. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 2004 Jul; 88 4):787-835, ix.
7. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005 Jun; 54 (6):1615-25.
8. Barbieri M, Rizzo MR, Manzella D, Grella R, Ragno E, Carbonella M, et al. Glucose regulation and oxidative stress in healthy centenarians. Exp Gerontol 2003 Jan; 38 (1-2):137-43.
9. Clemmons DR. Involvement of insulin-like growth factor-I in the control of glucose homeostasis. Curr Opin Pharmacol 2006 Dec; 6 (6):620-5.
10. White MF, Kahn CR. The insulin signaling system. J Biol Chem 1994; 269 (1):1-4.
11. White MF, Shoelson SE, Keutmann H, Kahn CR. A cascade of tyrosine autophosphorylation in the beta-subunit activates the phosphotransferase of the insulin receptor. J Biol Chem 1988 Feb 25; 263 (6):2969-80.
12. Till JH, Ablooglu AJ, Frankel M, Bishop SM, Kohanski RA, Hubbard SR. Crystallographic and solution studies of an activation loop mutant of the insulin receptor tyrosine kinase: insights into kinase mechanism. J Biol Chem 2001 Mar 30; 276 (13):10049-55.
13. Hubbard SR. Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog. EMBO J 1997; 16 (18):5572-81.
14. White MF, Livingston JN, Backer JM, Lauris V, Dull TJ, Ullrich A, et al. Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity. Cell 1988; 54:641-9.
15. Yenush L, White MF. The IRS-signaling system during insulin and cytokine action. Bio Essays 1997; 19 (6):491-500.
16. White, M.F., Maron, R. & Kahn, C.R. Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells. Nature 1985; 318: 183-186.
17. Kahn, C.R., White, M.F., Rothenberg, P.L. Isolated DNA encoding an insulin receptor substrate. US patent No:5,620,200. Filed 10/15/92. Issued 11/9/93.
18. Sun, X.J. et al. Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 1991; 352: 73-77.
19. White, M.F., Sun, X.J., Pierce, J.H. DNA encoding an insulin receptor substrate. Us patent No:5,858,701. Filed 10/03/94. Issued 01/12/99.
20. Sun, X.J. et al. Role of IRS-2 in insulin and cytokine signalling. Nature 1995; 377: 173-177.
21. Burks DJ, Wang J, Towery H, Ishibashi O, Lowe D, Riedel H, et al. IRS pleckstrin homology domains bind to acidic motifs in proteins. J Biol Chem 1998 Nov 20; 273 (47):31061-7.
22. Wu J, Tseng YD, Xu CF, Neubert TA, White MF, Hubbard SR. Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nat Struct Mol Biol 2008 March 15(3) 251-8.
23. Backer JM, Myers MG, Jr., Shoelson SE, Chin DJ, Sun XJ, Miralpeix M, et al. Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation. EMBO J 1992; 11:3469-79.
24. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell 2007 Jun 29; 129 (7):1261-74.
25. Dong XC, Copps KD, Guo S, Li Y, Kollipara R, DePinho RA, et al. Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab 2008 Jul; 8 (1):65-76.
26. Jhala US, Canettieri G, Screaton RA, Kulkarni RN, Krajewski S, Reed J, et al. cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev 2003 Jul 1; 17 (13):1575-80.
27. Shimano H. SREBP-1c and TFE3, energy transcription factors that regulate hepatic insulin signaling. J Mol Med 2007 May; 85 (5):437-44.
28. Ide T, Shimano H, Yahagi N, Matsuzaka T, Nakakuki M, Yamamoto T, et al. SREBPs suppress IRS-2-mediated insulin signalling in the liver. Nat Cell Biol 2004 Apr; 6 (4):351-7.
29. Zick Y. Ser/Thr phosphorylation of IRS proteins: a molecular basis for insulin resistance. Sci STKE 2005 Jan 25; 2005 (268):e4.
30. White MF. Regulating insulin signaling and beta-cell function through IRS proteins. Can J Physiol Pharmacol 2006 Jul; 84 (7):725-37.
31. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005 May; 115 (5):1111-9.
32. Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, et al. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 1998; 391 (6670):900-4.
33. Jonsson J, Carlsson L, Edlund T, Edlund H. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 1994; 371 (6498):606-9.
34. Weir GC, Bonner-Weir S. A dominant role for glucose in beta cell compensation of insulin resistance. J Clin Invest 2007 Jan;117(1):81-3.
35. Krebs, D.L., Hilton, D.J. A new role for SOCS in insulin action. Suppressor of cytokine signaling. Sci STKE. 2003 Feb 11; (169): PE6.
36. Haj, F.G., Verveer, P.J., Squire, A., Neel, B.G., Bastiaens, P.I. Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science. 2002 Mar 1; 295(5560):1708-1711
37. Berge, S.M., Bighley, L.D., Monkhouse, D.C. Pharmaceutical salts. J Pharm Sci. 1977 Jan; 66(1):1-19.
38. Housey, GM, White, MF, Method of Screening Activators and/or Inhibitors of Insulin Receptor Substrate 2. US Patent 8,557,512 B2. Serial No. 10/541,263. Filed 12/31/2003. Issued 10/15/2013.
39. Housey, G.M., Balash M. (2010) IRS Modulators. US Provisional Patent Application. Filed June 3, 2010.
40. Liu S, Serdula M, Janket SJ, Cook NR, Sesso HD, Willett WC, Manson JE, Buring JE. A prospective study of fruit and vegetable intake and the risk of type 2 diabetes in women. Diabetes Care. 2004 Dec; 27 (12):2993-6.
41. Bazzano LA, Li TY, Joshipura KJ, Hu FB. Intake of fruit, vegetables, and fruit juices and risk of diabetes in women. Diabetes Care. 2008 Jul; 31 (7):1311-7
42. Montonen J, Jarvinen R, Heliovaara M, Reunanen A, Aromaa A, Knekt P. Food consumption and the incidence of type II diabetes mellitus. Eur J Clin Nutr. 2005 Mar; 59 (3):441-8.
43. Meyer KA, Kushi LH, Jacobs DR Jr, Slavin J, Sellers TA, Folsom AR. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr. 2000 Apr; 71 (4):921-30.
44. Villegas R, Shu XO, Gao YT, Yang G, Elasy T, Li H, Zheng W. Vegetable but not fruit consumption reduces the risk of type 2 diabetes in Chinese women. J Nutr. 2008 Mar; 138 (3):574-80.
45. Carter P, Gray LJ, Troughton J, Khunti K, Davies MJ. Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis. BMJ. 2010 Aug 18; 341:c4229.
46. Muthusamy VS, Saravanababu C, Ramanathan M, Bharathi Raja R, Sudhagar S, Anand S, Lakshmi BS. Inhibition of protein tyrosine phosphatase 1B and regulation of insulin signalling markers by caffeoyl derivatives of chicory ( Cichorium intybus) salad leaves. Br J Nutr. 2010 Sep; 104 (6):813-23.
47. Ahmed N, Tarannum S. Acetylcholinesterase activity in the brain of alloxan diabetic albino rats: Presence of an inhibitor of this enzyme activity in the cerebral extract. Int J Diabetes Dev Ctries. 2009 Oct; 29 (4):174-7.
48. Muthusamy VS, Anand S, Sangeetha KN, Sujatha S, Arun B, Lakshmi BS. Tannins present in Cichorium intybus enhance glucose uptake and inhibit adipogenesis in 3T3-L1 adipocytes through PTP1B inhibition. Chem Biol Interact. 2008 Jul 10; 174 (1):69-78.
49. Pushparaj PN, Low HK, Manikandan J, Tan BK, Tan CH. Anti-diabetic effects of Cichorium intybus in streptozotocin-induced diabetic rats. J Ethnopharmacol. 2007 May 4; 111 (2):430-4.
50. Petlevski R, Hadzija M, Slijepcevic M, Juretic D, Petrik J. Glutathione S-transferases and malondialdehyde in the liver of NOD mice on short-term treatment with plant mixture extract P-9801091. Phytother Res. 2003 Apr; 17 (4):311-4.
51. Petlevski R, Hadzija M, Slijepcevic M, Juretic D. Effect of 'antidiabetis' herbal preparation on serum glucose and fructosamine in NOD mice. J Ethnopharmacol. 2001 May; 75 (2-3):181-4.
52. Estruch R, Ros E, Salas-Salvado J, Covas MI, D Pharm, Corella D, Aros F, Gomez-Gracia E, Ruiz-Gutierrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA, Martinez-Gonzalez MA; the PREDIMED Study Investigators. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med. 2013 Feb 25.
53. Mascherpa D, Carazzone C, Marrubini G, Gazzani G, Papetti A. Identification of phenolic constituents in Cichorium endivia var. crispum and var. latifolium salads by high-performance liquid chromatography with diode array detection and electrospray ioniziation tandem mass spectrometry. J Agric Food Chem. 2012 Dec 12; 60 (49):12142-50.
54. Papetti A, Daglia M, Gazzani G. Anti- and pro-oxidant water soluble activity of Cichorium genus vegetables and effect of thermal treatment. J Agric Food Chem. 2002 Jul 31; 50 (16):4696-704.
55. Diabetes Prevention Program Research Group. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. N Engl J Med 2002 Feb 7; 346 (6): 393-403
56. Campbell, IW. Metformin-life begins at 50: A symposium held on the occasion of the 43rd Annual Meeting of the European Association for the Study of Diabetes, Amsterdam, The Netherlands, September 2007, The British Journal of Diabetes & Vascular Disease. 2007 Sept 7: 247-252.
57. Papetti A, Daglia M, Aceti C, Sordelli B, Spini V, Carazzone C, Gazzani G. Hydroxycinnamic acid derivatives occurring in Cichorium endivia vegetables. J Pharm Biomed Anal. 2008 Sep 29; 48 (2):472-6.
58. Pushparaj P, Tan CH, Tan BK. Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats. J Ethnopharmacol. 2000 Sep; 72 (1-2):69-76.
59. Suntar I, Kupeli Akkol E, Keles H, Yesilada E, Sarker SD, Baykal T. Comparative evaluation of traditional prescriptions from Cichorium intybus L. for wound healing: stepwise isolation of an active component by in vivo bioassay and its mode of activity. J Ethnopharmacol. 2012 Aug 30; 143 (1):299-309.
60. Pinent M, Blay M, Blade MC, Salvado MJ, Arola L, Ardevol A. Grape seed-derived procyanidins have an antihyperglycemic effect in streptozotocin-induced diabetic rats and insulinomimetic activity in insulin-sensitive cell lines. Endocrinology. 2004 Nov; 145 (11):4985-90.
61. Xavier-Filho J, Oliveira A.E.A., Silva L.B. da, Azevedo C.R., Venancio T.M., Machado O.L.T., Oliva M.L., Fernandes K.V.S., Xavier-Neto J. Plant insulin or glucokinin: a conflicting issue. Braz. J. Plant Physiol. 2003 May/Aug; 15 (2):67-78.
62. Andrade-Cetto A, Heinrich M. Mexican plants with hypoglycaemic effect used in the treatment of diabetes. J Ethnopharmacol. 2005 Jul 14; 99 (3):325-48.
63. Diaz-Flores M, Angeles-Mejia S, Baiza-Gutman LA, Medina-Navarro R, Hernandez-Saavedra D, Ortega-Camarillo C, Roman-Ramos R, Cruz M, Alarcon-Aguilar FJ. Effect of an aqueous extract of Cucurbita ficifolia Bouche on the glutathione redox cycle in mice with STZ-induced diabetes. J Ethnopharmacol. 2012 Oct 31; 144 (1):101-8.
64. Deutschlander MS, Lall N, Van de Venter M, Hussein AA. Hypoglycemic evaluation of a new triterpene and other compounds isolated from Euclea undulata Thunb. var. myrtina (Ebenaceae) root bark. J Ethnopharmacol. 2011 Feb 16; 133 (3):1091-5.
65. Acosta-Patino JL, Jimenez-Balderas E, Juarez-Oropeza MA, Diaz-Zagoya JC. Hypoglycemic action of Cucurbita ficifolia on Type 2 diabetic patients with moderately high blood glucose levels. J Ethnopharmacol. 2001 Sep;77(1):99-101.
66. Van de Venter M, Roux S, Bungu LC, Louw J, Crouch NR, Grace OM, Maharaj V, Pillay P, Sewnarian P, Bhagwandin N, Folb P. Antidiabetic screening and scoring of 11 plants traditionally used in South Africa. J Ethnopharmacol. 2008 Sep 2; 119 (1):81-6.
67. Vinson JA, Burnham BR, Nagendran MV. Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects. Diabetes Metab Syndr Obes. 2012;5:21-7.
68. Hamza N, Berke B, Cheze C, Le Garrec R, Lassalle R, Agli AN, Robinson P, Gin H, Moore N. Treatment of high fat diet induced type 2 diabetes in C57BL/6J mice by two medicinal plants used in traditional treatment of diabetes in the east of Algeria. J Ethnopharmacol. 2011 Jan 27; 133 (2):931-3.
69. Ahmed AB, Rao AS, Rao MV. In vitro callus and in vivo leaf extract of Gymnema sylvestre stimulate β-cells regeneration and anti-diabetic activity in Wistar rats. Phytomedicine. 2010 Nov; 17 (13):1033-9.
70. Roman-Ramos R, Flores-Saenz JL, Alarcon-Aguilar FJ. Anti-hyperglycemic effect of some edible plants. J Ethnopharmacol. 1995 Aug 11; 48 (1):25-32.
71. Zhang B, Salituro G, Szalkowski D, Li Z, Zhang Y, Royo I, Vilella D, Diez MT, Pelaez F, Ruby C, Kendall RL, Mao X, Griffin P, Calaycay J, Zierath JR, Heck JV, Smith RG, Moller DE. Discovery of a small molecule insulin mimetic with antidiabetic activity in mice. Science. 1999 May 7;284(5416):974-7.
72. Ghamarian A, Abdollahi M, Su X, Amiri A, Ahadi A, Nowrouzi A. Effect of chicory seed extract on glucose tolerance test (GTT) and metabolic profile in early and late stage diabetic rats. Daru. 2012 Oct 15;20(1):56.
73. DuPont MS, Mondin Z, Williamson G, Price KR. Effect of variety, processing, and storage on the flavonoid glycoside content and composition of lettuce and endive. J Agric Food Chem. 2000 Sep; 48 (9):3957-64.
74. Tousch D, Lajoix AD, Hosy E, Azay-Milhau J, Ferrare K, Jahannault C, Cros G, Petit P. Chicoric acid, a new compound able to enhance insulin release and glucose uptake. Biochem Biophys Res Commun. 2008 Dec 5; 377 (1):131-5.
75. Kamel ZH, Daw I, Marzouk M. Effect of Cichorium endivia leaves on some biochemical parameters in streptozotocin-induced diabetic rats. Aus J Basic and App Sci. 2011; 5 (7):387-96
76. Park KJ, de Oliveira RA, Brod FPR. Drying Operational Parameters Influence on Chicory Roots Drying and Inulin Extraction. Food and Bioproducts Processing. 2007 Sep; 85 (3);184-92
77. Hagel JM, Yeung EC, Facchini PJ. Got milk? The secret life of laticifers. Trends Plant Sci. 2008 Dec;13(12):631-9.
78. Lewinsohn TM. The geographical distribution of plant latex. Chemoecology 1991;2(1):64-8
79. Montagut G, Onnockx S, Vaque M, Blade C, Blay M, Fernandez-Larrea J, Pujadas G, Salvado MJ, Arola L, Pirson I, Ardevol A, Pinent M. Oligomers of grape-seed procyanidin extract activate the insulin receptor and key targets of the insulin signaling pathway differently from insulin. J Nutr Biochem. 2010 Jun; 21 (6):476-81.
80. Obanda DN, Hernandez A, Ribnicky D, Yu Y, Zhang XH, Wang ZQ, Cefalu WT. Bioactives of Artemisia dracunculus L. mitigate the role of ceramides in attenuating insulin signaling in rat skeletal muscle cells. Diabetes. 2012 Mar; 61 (3):597-605.
81. Pushparaj PN, Tan BK, Tan CH. The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats. Life Sci. 2001 Dec 21;70 (5):535-47.
82. Layne J. Characterization and comparison of the chromatographic performance of conventional, polar-embedded, and polar-endcapped reversed-phase liquid chromatography stationary phases. Journal of Chromatography A,2002 957: 149-164.
83. Wolfender JL, Ndjoko K, Hostettmann, K. Liquid chromatography with ultraviolet absorbance-mass spectrometric detection and with nuclear magnetic resonance spectrometry: a powerful combination for the on-line structural investigation of plant metabolites. Journal of Chromatography A 1000 2003: 437-455.
84. Buszewski B, Noga S. Hydrophilic interaction liquid chromatography (HILIC)-a powerful separation technique. Analytical and bioanalytical chemistry, 2012; 402(1): 231-247.
85. Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry. 2001 Jan; 56 (1):5-51.
86. Oxford Dictionary of Chemistry (7 ed.) 2016, Oxford University Press
Claims (17)
- Artemisia dracunculus、Cichoria endiviaおよびLactuca sativaからの抽出物を含み、1ミリリットル中に少なくとも1×104のインスリン等価単位を提供する、植物抽出物。
- 金属を含む、請求項1に記載の植物抽出物。
- 前記金属が、クロム、鉄、マンガン、亜鉛、および銅からなる群から選択される、請求項2に記載の植物抽出物。
- 前記金属がクロムである、請求項2に記載の植物抽出物。
- Artemisia dracunculus、Cichoria endiviaおよびLactuca sativaからの前記抽出物が、乾燥した水性抽出物である、請求項5に記載の植物抽出物。
- Artemisia dracunculusの乾燥薬草抽出物;
Cichoria endiviaの乾燥薬草抽出物;
Lactuca sativaの乾燥薬草抽出物;および
任意選択的にクロム
を含む、錠剤、カプセル、または粉末形態の医薬組成物または栄養サプリメント。 - 0.7mgのArtemisia dracunculusの乾燥薬草抽出物;
962.7mgのCichoria endiviaの乾燥薬草抽出物;
16.7mgのLactuca sativaの乾燥薬草抽出物;および
1.2megのクロム
を含み、錠剤形態である、請求項6に記載の医薬組成物または栄養サプリメント。 - 合計で50mg〜1,500mgの、
Artemisia dracunculusの乾燥薬草抽出物;
Cichoria endiviaの乾燥薬草抽出物;
Lactuca sativaの乾燥薬草抽出物;および
任意選択的にクロム
を含む、請求項6に記載の医薬組成物または栄養サプリメント。 - リン酸二カルシウム、微結晶性セルロース、二酸化ケイ素、ヒドロキシプロピルセルロース、ステアリン酸、クロスカルメロースナトリウム、およびステアリン酸マグネシウム;ならびにこれらの組合せからなる群から選択される少なくとも1つの薬学的に許容される賦形剤をさらに含む、請求項6に記載の錠剤、カプセル、または粉末形態の医薬組成物または栄養サプリメント。
- 前記少なくとも1つの薬学的に許容される賦形剤が、総質量の15〜25%の量で存在する、請求項9に記載の錠剤、カプセル、または粉末形態の医薬組成物または栄養サプリメント。
- Artemisia dracunculus、Cichoria endiviaおよびLactuca sativaの前記抽出物が、約1:1,375:24(w/w/w)の比で存在する、請求項6に記載の錠剤形態の医薬組成物または栄養サプリメント。
- 有効量の請求項6に記載の医薬組成物または栄養サプリメントを、それを必要とする対象に投与することを含む、IRS媒介性の疾患または状態を治療する方法。
- 前記IRS媒介性の疾患または状態が、糖尿病、前糖尿病、メタボリックシンドローム、インスリン抵抗性、または認知症である、請求項12に記載の方法。
- 抗糖尿病剤、インスリン、メトホルミン、エキセナチド、スルホニル尿素、ビルダグリプチン、シタグリプチン、DPP4阻害剤、メグリチニド、エキセンジン−4、リラグルチド、チアゾリジンジオン、エンパグリフロジン、カナグリフロジン、ダパグリフロジンまたはGLP1アゴニストを投与することをさらに含む、請求項12に記載の方法。
- 前記医薬組成物または栄養サプリメントが、食事の30〜60分前に1日2回経口投与される、請求項12に記載の方法。
- 有効量の請求項6に記載の医薬組成物または栄養サプリメントを、それを必要とする対象に投与することを含む、前記対象においてIRS2依存的なシグナル伝達を刺激する方法。
- 細胞を請求項1に記載の植物抽出物または請求項6に記載の医薬組成物もしくは栄養サプリメントと接触させることを含む、IRS2依存的なシグナル伝達を刺激する方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762505494P | 2017-05-12 | 2017-05-12 | |
US62/505,494 | 2017-05-12 | ||
PCT/US2018/032273 WO2018209202A1 (en) | 2017-05-12 | 2018-05-11 | Plant extracts with anti-diabetic and other useful activities |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2020519688A true JP2020519688A (ja) | 2020-07-02 |
JP2020519688A5 JP2020519688A5 (ja) | 2021-07-26 |
Family
ID=64102791
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020512782A Pending JP2020519688A (ja) | 2017-05-12 | 2018-05-11 | 抗糖尿病活性および他の有用な活性を有する植物抽出物 |
Country Status (13)
Country | Link |
---|---|
US (2) | US11633446B2 (ja) |
EP (1) | EP3634453A4 (ja) |
JP (1) | JP2020519688A (ja) |
KR (1) | KR20200016252A (ja) |
CN (1) | CN111032065A (ja) |
AU (1) | AU2018265439A1 (ja) |
BR (1) | BR112019023818A2 (ja) |
CA (1) | CA3063110A1 (ja) |
IL (1) | IL270577B2 (ja) |
MA (1) | MA49466A (ja) |
MX (1) | MX2019013453A (ja) |
WO (1) | WO2018209202A1 (ja) |
ZA (1) | ZA201908121B (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20220016025A1 (en) * | 2020-07-08 | 2022-01-20 | Vinayak Dinesh DENDUKURI | Formulations of nebivolol |
CN113143962B (zh) * | 2021-05-11 | 2022-08-05 | 四川九章生物科技有限公司 | 一种治疗高脂血症的药物组合物及其制备方法 |
KR20230065066A (ko) | 2021-11-04 | 2023-05-11 | 류승진 | 건조대를 부착한 빨래바구니 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016514146A (ja) * | 2013-03-12 | 2016-05-19 | エイチエムアイ・メディカル・イノヴェイションズ・エルエルシー | 抗糖尿病及び他の有用な活性を有する植物抽出物 |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5260200A (en) | 1991-01-18 | 1993-11-09 | Joslin Diabetes Center, Inc. | Isolated DNA encoding an insulin receptor substrate |
US5858701A (en) | 1994-10-03 | 1999-01-12 | Joslin Diabetes Center, Inc. | DNA encoding an insulin receptor substrate |
US5620200A (en) | 1995-10-31 | 1997-04-15 | Morton International, Inc. | Airbag module reaction canister endwall with airbag inflator mount |
EP1429602B1 (en) | 2001-08-31 | 2009-12-16 | Rutgers, The State University Of New Jersey | Methods for treating disorders using plant extracts |
CN1382734A (zh) | 2002-03-15 | 2002-12-04 | 林忠平 | 利用转基因生菜生产人胰岛素的方法 |
CN100540666C (zh) | 2002-03-15 | 2009-09-16 | 林忠平 | 利用转基因生菜、番茄和烟草生产人胰岛素的方法 |
WO2004060316A2 (en) | 2003-01-02 | 2004-07-22 | Housey Gerard M | Irs modulators |
CN1994146A (zh) * | 2005-12-29 | 2007-07-11 | 于天飞 | 菊苣减肥茶 |
US10752909B2 (en) | 2007-03-30 | 2020-08-25 | The Trustees Of The University Of Pennsylvania | Chloroplasts engineered to express pharmaceutical proteins in edible plants |
TW200841826A (en) * | 2007-04-20 | 2008-11-01 | Bion Tech Inc | Composition comprising five kinds of process fruit/vegetable |
IL184312A0 (en) * | 2007-06-28 | 2008-01-20 | Ascarit Ltd | Herbal compositions for the treatment of diabetes and/or conditions associated therewith |
US20090264520A1 (en) | 2008-04-21 | 2009-10-22 | Asha Lipid Sciences, Inc. | Lipid-containing compositions and methods of use thereof |
EP2130443A1 (en) * | 2008-06-06 | 2009-12-09 | Finzelberg GmbH & Co. KG | Water-soluble extracts of Artemisia dracunculus (tarragon) for improvement of glucose metabolism |
WO2010010949A1 (ja) | 2008-07-24 | 2010-01-28 | 味の素株式会社 | リパーゼ阻害剤 |
AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
US20110118180A1 (en) | 2009-11-13 | 2011-05-19 | Sanofi-Aventis Deutschland Gmbh | Method of treatment of diabetes type 2 comprising add-on therapy to metformin |
CN102178294B (zh) | 2011-04-08 | 2012-11-07 | 上海交通大学 | 功能性芹苣清凉饮料及其生产方法 |
CN102228116B (zh) | 2011-07-08 | 2013-02-27 | 徐州绿之野生物食品有限公司 | 一种苦菊茶饮料 |
JP6346564B2 (ja) | 2011-11-18 | 2018-06-20 | ナチュレックス | チコリ抽出物を含む組成物 |
-
2018
- 2018-05-11 CA CA3063110A patent/CA3063110A1/en active Pending
- 2018-05-11 EP EP18799410.8A patent/EP3634453A4/en active Pending
- 2018-05-11 BR BR112019023818-2A patent/BR112019023818A2/pt not_active Application Discontinuation
- 2018-05-11 WO PCT/US2018/032273 patent/WO2018209202A1/en active Application Filing
- 2018-05-11 KR KR1020197036666A patent/KR20200016252A/ko not_active Application Discontinuation
- 2018-05-11 MX MX2019013453A patent/MX2019013453A/es unknown
- 2018-05-11 CN CN201880046502.4A patent/CN111032065A/zh active Pending
- 2018-05-11 IL IL270577A patent/IL270577B2/en unknown
- 2018-05-11 US US16/612,545 patent/US11633446B2/en active Active
- 2018-05-11 JP JP2020512782A patent/JP2020519688A/ja active Pending
- 2018-05-11 MA MA049466A patent/MA49466A/fr unknown
- 2018-05-11 AU AU2018265439A patent/AU2018265439A1/en active Pending
-
2019
- 2019-12-05 ZA ZA2019/08121A patent/ZA201908121B/en unknown
-
2023
- 2023-03-02 US US18/116,440 patent/US20230248792A1/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016514146A (ja) * | 2013-03-12 | 2016-05-19 | エイチエムアイ・メディカル・イノヴェイションズ・エルエルシー | 抗糖尿病及び他の有用な活性を有する植物抽出物 |
Also Published As
Publication number | Publication date |
---|---|
MA49466A (fr) | 2020-04-29 |
EP3634453A1 (en) | 2020-04-15 |
IL270577B2 (en) | 2023-09-01 |
CA3063110A1 (en) | 2018-11-15 |
US20230248792A1 (en) | 2023-08-10 |
US20200197468A1 (en) | 2020-06-25 |
BR112019023818A2 (pt) | 2020-06-02 |
AU2018265439A1 (en) | 2019-12-05 |
ZA201908121B (en) | 2021-04-28 |
IL270577A (ja) | 2019-12-31 |
IL270577B1 (en) | 2023-05-01 |
KR20200016252A (ko) | 2020-02-14 |
MX2019013453A (es) | 2020-11-06 |
EP3634453A4 (en) | 2021-02-24 |
WO2018209202A1 (en) | 2018-11-15 |
US11633446B2 (en) | 2023-04-25 |
CN111032065A (zh) | 2020-04-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2018278958B2 (en) | Plant extracts with anti-diabetic and other useful activities | |
US20230248792A1 (en) | Plant extracts with anti-diabetic and other useful activities | |
de Matos et al. | Bridging type 2 diabetes and Alzheimer's disease: assembling the puzzle pieces in the quest for the molecules with therapeutic and preventive potential | |
KR20130020623A (ko) | 유홍초 추출물을 함유하는 당뇨합병증 예방 또는 치료용 조성물 | |
R Dias et al. | Emerging potential of natural products as an alternative strategy to pharmacological agents used against metabolic disorders | |
KR101668443B1 (ko) | 아모디아퀸을 유효성분으로 함유하는 대사성 질환의 예방, 개선, 또는 치료용 조성물 | |
KR101185137B1 (ko) | 스테레오카울론 알피넘 유래 화합물을 함유하는 당뇨병 또는 비만의 예방 또는 치료용 약학 조성물 | |
KR101684735B1 (ko) | Gpr119를 활성화시킬 수 있는 에스키난투스 아쿠미나투스 추출물을 함유하는 대사성 질환 예방 또는 치료용 조성물 | |
Rangari et al. | 4-Hydroxyisoleucine: A potential antidiabetic agent from Trigonella foenum-graecum | |
Prasanth et al. | Hylocereus undatus extends lifespan and exerts neuroprotection in Caenorhabditis elegans via DAF-16 mediated pathway | |
KR20190135378A (ko) | Lgi3 유래 펩타이드를 유효성분으로 포함하는 비만의 예방, 치료, 또는 개선용 조성물 | |
KR102206998B1 (ko) | Lgi3 유래 펩타이드를 유효성분으로 포함하는 당뇨병의 예방, 치료, 또는 개선용 조성물 | |
Tsuda | Prevention and Treatment of Diabetes Using Polyphenols via Activation of AMP‐Activated Protein Kinase and Stimulation of Glucagon‐like Peptide‐1 Secretion | |
KR102174613B1 (ko) | 밀랍으로 코팅된 봉독 비드를 유효성분으로 포함하는 당뇨병 예방 또는 치료용 조성물 | |
KR101833428B1 (ko) | 구릿대 추출물, 이의 분획물 또는 이로부터 분리한 펠로프테린 화합물을 유효성분으로 함유하는 당뇨 예방 및 치료용 약학적 조성물 | |
Alblooshi | THE EFFECT OF LICOGLIFLOZIN (SGLT1/2 INHIBITOR) ON DIABETES AND CARDIAC COMPLICATIONS | |
Nagler-Bunker | Neural Cells in High Glucose Conditions: Anti-Apoptotic Effect of Gtf-Anti Diabetic Material Extracted from Yeast | |
de Sousa Madeira et al. | Brain Dysfunction and Cell Death in Type 2 Diabetes: A neuroprotective role for the peripheral treatment with Exendin-4 | |
Kapakos | Modulation of Endothelin-1 and Insulin-like Growth Factor Type 1-induced Signaling by Curcumin in A-10 Vascular Smooth Muscle Cells | |
KR20160043519A (ko) | 제미글립틴 및 제미글립틴 활성 대사체를 이용한 혈관 합병증의 예방 및 치료 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210510 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210510 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220118 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20220121 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220415 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220617 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220719 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20220719 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20221018 |