AU2007205996A1 - Pharmaceutical compositions and methods to achieve and maintain a targeted and stable copper status and prevent and treat copper-related central nervous system diseases - Google Patents

Info

Publication number

AU2007205996A1

AU2007205996A1 AU2007205996A AU2007205996A AU2007205996A1 AU 2007205996 A1 AU2007205996 A1 AU 2007205996A1 AU 2007205996 A AU2007205996 A AU 2007205996A AU 2007205996 A AU2007205996 A AU 2007205996A AU 2007205996 A1 AU2007205996 A1 AU 2007205996A1

Authority

AU

Australia

Prior art keywords

copper

zinc

disease

formulation

composition

Prior art date

2006-01-10

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• Discuss

• 239000010949 copper Substances 0.000 title claims description 526
• 229910052802 copper Inorganic materials 0.000 title claims description 505
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 title claims description 499
• 238000000034 method Methods 0.000 title claims description 132
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 30
• 208000015114 central nervous system disease Diseases 0.000 title claims description 3
• 239000011701 zinc Substances 0.000 claims description 149
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 142
• 229910052725 zinc Inorganic materials 0.000 claims description 142
• 239000000203 mixture Substances 0.000 claims description 137
• CXVCSRUYMINUSF-UHFFFAOYSA-N tetrathiomolybdate(2-) Chemical compound [S-][Mo]([S-])(=S)=S CXVCSRUYMINUSF-UHFFFAOYSA-N 0.000 claims description 112
• 238000009472 formulation Methods 0.000 claims description 89
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 78
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 75
• -1 or blocker Substances 0.000 claims description 70
• 201000010099 disease Diseases 0.000 claims description 69
• 210000002784 stomach Anatomy 0.000 claims description 66
• 239000002775 capsule Substances 0.000 claims description 61
• 208000024827 Alzheimer disease Diseases 0.000 claims description 60
• 239000003795 chemical substances by application Substances 0.000 claims description 58
• 238000010521 absorption reaction Methods 0.000 claims description 53
• 210000002966 serum Anatomy 0.000 claims description 52
• 239000013078 crystal Substances 0.000 claims description 50
• 108090000623 proteins and genes Proteins 0.000 claims description 50
• 102000004169 proteins and genes Human genes 0.000 claims description 49
• 239000012730 sustained-release form Substances 0.000 claims description 48
• 235000018102 proteins Nutrition 0.000 claims description 46
• 238000013268 sustained release Methods 0.000 claims description 46
• UHXXJVYBIFPFFQ-DKWTVANSSA-N (2r)-2-amino-3-sulfanylpropanoic acid;zinc Chemical compound [Zn].SC[C@H](N)C(O)=O UHXXJVYBIFPFFQ-DKWTVANSSA-N 0.000 claims description 38
• 229910052742 iron Inorganic materials 0.000 claims description 37
• 235000013305 food Nutrition 0.000 claims description 35
• 210000004185 liver Anatomy 0.000 claims description 34
• 235000012054 meals Nutrition 0.000 claims description 34
• 241001465754 Metazoa Species 0.000 claims description 32
• OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 32
• 108010075016 Ceruloplasmin Proteins 0.000 claims description 31
• 102100023321 Ceruloplasmin Human genes 0.000 claims description 31
• 208000002972 Hepatolenticular Degeneration Diseases 0.000 claims description 31
• 208000018839 Wilson disease Diseases 0.000 claims description 31
• 239000002738 chelating agent Substances 0.000 claims description 30
• 238000000576 coating method Methods 0.000 claims description 29
• 210000000936 intestine Anatomy 0.000 claims description 29
• 238000011282 treatment Methods 0.000 claims description 29
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
• ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 28
• 239000011248 coating agent Substances 0.000 claims description 28
• 210000001035 gastrointestinal tract Anatomy 0.000 claims description 28
• 239000004246 zinc acetate Substances 0.000 claims description 28
• 235000013904 zinc acetate Nutrition 0.000 claims description 28
• 230000002496 gastric effect Effects 0.000 claims description 26
• ZKKLPDLKUGTPME-UHFFFAOYSA-N diazanium;bis(sulfanylidene)molybdenum;sulfanide Chemical group [NH4+].[NH4+].[SH-].[SH-].S=[Mo]=S ZKKLPDLKUGTPME-UHFFFAOYSA-N 0.000 claims description 25
• 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 25
• 239000008188 pellet Substances 0.000 claims description 24
• 230000029142 excretion Effects 0.000 claims description 22
• 239000003826 tablet Substances 0.000 claims description 22
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 20
• 206010025476 Malabsorption Diseases 0.000 claims description 20
• 208000004155 Malabsorption Syndromes Diseases 0.000 claims description 20
• 208000018737 Parkinson disease Diseases 0.000 claims description 19
• 230000027455 binding Effects 0.000 claims description 19
• 238000004090 dissolution Methods 0.000 claims description 18
• 229920000642 polymer Polymers 0.000 claims description 18
• 239000000463 material Substances 0.000 claims description 17
• 229910052751 metal Inorganic materials 0.000 claims description 17
• 239000002184 metal Substances 0.000 claims description 17
• 108010088751 Albumins Proteins 0.000 claims description 16
• 102000009027 Albumins Human genes 0.000 claims description 16
• FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims description 16
• OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 16
• 229960000304 folic acid Drugs 0.000 claims description 16
• 235000019152 folic acid Nutrition 0.000 claims description 16
• 239000011724 folic acid Substances 0.000 claims description 16
• 230000002440 hepatic effect Effects 0.000 claims description 16
• 239000006187 pill Substances 0.000 claims description 16
• 239000013589 supplement Substances 0.000 claims description 16
• 230000009885 systemic effect Effects 0.000 claims description 16
• 239000002253 acid Substances 0.000 claims description 15
• 239000002702 enteric coating Substances 0.000 claims description 15
• 238000009505 enteric coating Methods 0.000 claims description 15
• 230000001771 impaired effect Effects 0.000 claims description 15
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 15
• 239000000243 solution Substances 0.000 claims description 15
• 239000012530 fluid Substances 0.000 claims description 14
• 150000002739 metals Chemical class 0.000 claims description 14
• 201000000980 schizophrenia Diseases 0.000 claims description 14
• 239000003446 ligand Substances 0.000 claims description 13
• 210000000941 bile Anatomy 0.000 claims description 12
• 239000003613 bile acid Substances 0.000 claims description 12
• 230000006698 induction Effects 0.000 claims description 12
• 239000011159 matrix material Substances 0.000 claims description 12
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
• 210000000813 small intestine Anatomy 0.000 claims description 12
• 201000001320 Atherosclerosis Diseases 0.000 claims description 11
• 206010012289 Dementia Diseases 0.000 claims description 11
• 241000282412 Homo Species 0.000 claims description 11
• 208000023105 Huntington disease Diseases 0.000 claims description 11
• 229920001577 copolymer Polymers 0.000 claims description 11
• 239000007788 liquid Substances 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 11
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 11
• 150000003839 salts Chemical class 0.000 claims description 11
• 230000006870 function Effects 0.000 claims description 10
• 230000004224 protection Effects 0.000 claims description 10
• 241000124008 Mammalia Species 0.000 claims description 9
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 9
• 229920002125 Sokalan® Polymers 0.000 claims description 9
• 102000019197 Superoxide Dismutase Human genes 0.000 claims description 9
• 108010012715 Superoxide dismutase Proteins 0.000 claims description 9
• 238000009825 accumulation Methods 0.000 claims description 9
• 208000010877 cognitive disease Diseases 0.000 claims description 9
• 150000002632 lipids Chemical class 0.000 claims description 9
• 208000019423 liver disease Diseases 0.000 claims description 9
• 239000011859 microparticle Substances 0.000 claims description 9
• 239000000843 powder Substances 0.000 claims description 9
• 150000003751 zinc Chemical class 0.000 claims description 9
• RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 claims description 8
• 102000013455 Amyloid beta-Peptides Human genes 0.000 claims description 8
• 108010090849 Amyloid beta-Peptides Proteins 0.000 claims description 8
• 206010003805 Autism Diseases 0.000 claims description 8
• 208000020706 Autistic disease Diseases 0.000 claims description 8
• 235000010323 ascorbic acid Nutrition 0.000 claims description 8
• 239000011668 ascorbic acid Substances 0.000 claims description 8
• 229960005070 ascorbic acid Drugs 0.000 claims description 8
• 230000003908 liver function Effects 0.000 claims description 8
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 8
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 8
• RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical group C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 claims description 8
• 229960001661 ursodiol Drugs 0.000 claims description 8
• HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 7
• VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 claims description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
• QCDFBFJGMNKBDO-UHFFFAOYSA-N Clioquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(Cl)C2=C1 QCDFBFJGMNKBDO-UHFFFAOYSA-N 0.000 claims description 7
• 208000012902 Nervous system disease Diseases 0.000 claims description 7
• 235000001014 amino acid Nutrition 0.000 claims description 7
• 229960005228 clioquinol Drugs 0.000 claims description 7
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 7
• 239000007943 implant Substances 0.000 claims description 7
• 229910052750 molybdenum Inorganic materials 0.000 claims description 7
• 201000006417 multiple sclerosis Diseases 0.000 claims description 7
• 230000002829 reductive effect Effects 0.000 claims description 7
• 239000000126 substance Substances 0.000 claims description 7
• 229960001124 trientine Drugs 0.000 claims description 7
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
• 102000004190 Enzymes Human genes 0.000 claims description 6
• 108090000790 Enzymes Proteins 0.000 claims description 6
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 6
• 208000008948 Menkes Kinky Hair Syndrome Diseases 0.000 claims description 6
• 208000012583 Menkes disease Diseases 0.000 claims description 6
• ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 6
• 208000025966 Neurological disease Diseases 0.000 claims description 6
• XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 6
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
• 239000011230 binding agent Substances 0.000 claims description 6
• 230000015556 catabolic process Effects 0.000 claims description 6
• 230000001419 dependent effect Effects 0.000 claims description 6
• 229940088598 enzyme Drugs 0.000 claims description 6
• 239000000835 fiber Substances 0.000 claims description 6
• 238000002347 injection Methods 0.000 claims description 6
• 239000007924 injection Substances 0.000 claims description 6
• 230000001404 mediated effect Effects 0.000 claims description 6
• 230000002503 metabolic effect Effects 0.000 claims description 6
• 239000011733 molybdenum Substances 0.000 claims description 6
• 208000018360 neuromuscular disease Diseases 0.000 claims description 6
• 239000006186 oral dosage form Substances 0.000 claims description 6
• 230000000717 retained effect Effects 0.000 claims description 6
• 238000002560 therapeutic procedure Methods 0.000 claims description 6
• 229920003134 Eudragit® polymer Polymers 0.000 claims description 5
• 108010006519 Molecular Chaperones Proteins 0.000 claims description 5
• 201000002481 Myositis Diseases 0.000 claims description 5
• 239000005862 Whey Substances 0.000 claims description 5
• 102000007544 Whey Proteins Human genes 0.000 claims description 5
• 108010046377 Whey Proteins Proteins 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 239000000544 cholinesterase inhibitor Substances 0.000 claims description 5
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 5
• 235000018417 cysteine Nutrition 0.000 claims description 5
• 238000006731 degradation reaction Methods 0.000 claims description 5
• 230000003111 delayed effect Effects 0.000 claims description 5
• 230000035622 drinking Effects 0.000 claims description 5
• 230000004907 flux Effects 0.000 claims description 5
• 210000001630 jejunum Anatomy 0.000 claims description 5
• 238000012423 maintenance Methods 0.000 claims description 5
• 229920000609 methyl cellulose Polymers 0.000 claims description 5
• 235000010981 methylcellulose Nutrition 0.000 claims description 5
• 239000001923 methylcellulose Substances 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 238000004806 packaging method and process Methods 0.000 claims description 5
• 229960001639 penicillamine Drugs 0.000 claims description 5
• 210000003296 saliva Anatomy 0.000 claims description 5
• 230000000087 stabilizing effect Effects 0.000 claims description 5
• 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 claims description 4
• UOACKFBJUYNSLK-XRKIENNPSA-N Estradiol Cypionate Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H](C4=CC=C(O)C=C4CC3)CC[C@@]21C)C(=O)CCC1CCCC1 UOACKFBJUYNSLK-XRKIENNPSA-N 0.000 claims description 4
• 102000010750 Metalloproteins Human genes 0.000 claims description 4
• 108010063312 Metalloproteins Proteins 0.000 claims description 4
• BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 4
• 208000018262 Peripheral vascular disease Diseases 0.000 claims description 4
• 108090000901 Transferrin Proteins 0.000 claims description 4
• 102000004338 Transferrin Human genes 0.000 claims description 4
• 230000002159 abnormal effect Effects 0.000 claims description 4
• 208000007502 anemia Diseases 0.000 claims description 4
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 4
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 4
• 108091008324 binding proteins Proteins 0.000 claims description 4
• 239000000969 carrier Substances 0.000 claims description 4
• 229920002301 cellulose acetate Polymers 0.000 claims description 4
• 235000013350 formula milk Nutrition 0.000 claims description 4
• 210000004051 gastric juice Anatomy 0.000 claims description 4
• 201000008319 inclusion body myositis Diseases 0.000 claims description 4
• 230000000366 juvenile effect Effects 0.000 claims description 4
• BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical group C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 claims description 4
• 229960004640 memantine Drugs 0.000 claims description 4
• 239000002245 particle Substances 0.000 claims description 4
• 208000023516 stroke disease Diseases 0.000 claims description 4
• 239000012581 transferrin Substances 0.000 claims description 4
• 210000002700 urine Anatomy 0.000 claims description 4
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
• NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 3
• 229920002126 Acrylic acid copolymer Polymers 0.000 claims description 3
• 208000023275 Autoimmune disease Diseases 0.000 claims description 3
• VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 claims description 3
• 206010019799 Hepatitis viral Diseases 0.000 claims description 3
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
• CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 3
• 230000003510 anti-fibrotic effect Effects 0.000 claims description 3
• 239000003529 anticholesteremic agent Substances 0.000 claims description 3
• 229940127226 anticholesterol agent Drugs 0.000 claims description 3
• 229910052786 argon Inorganic materials 0.000 claims description 3
• 239000000227 bioadhesive Substances 0.000 claims description 3
• 239000011575 calcium Substances 0.000 claims description 3
• 229920002678 cellulose Polymers 0.000 claims description 3
• 239000001913 cellulose Substances 0.000 claims description 3
• 239000008139 complexing agent Substances 0.000 claims description 3
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• 230000029087 digestion Effects 0.000 claims description 3
• 238000009826 distribution Methods 0.000 claims description 3
• 210000005095 gastrointestinal system Anatomy 0.000 claims description 3
• 235000020256 human milk Nutrition 0.000 claims description 3
• 229930195733 hydrocarbon Natural products 0.000 claims description 3
• 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
• 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
• 235000010755 mineral Nutrition 0.000 claims description 3
• 239000011707 mineral Substances 0.000 claims description 3
• 229910052757 nitrogen Inorganic materials 0.000 claims description 3
• 229920000058 polyacrylate Polymers 0.000 claims description 3
• 235000008476 powdered milk Nutrition 0.000 claims description 3
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 3
• 230000000153 supplemental effect Effects 0.000 claims description 3
• 229920002554 vinyl polymer Polymers 0.000 claims description 3
• 201000001862 viral hepatitis Diseases 0.000 claims description 3
• 239000011787 zinc oxide Substances 0.000 claims description 3
• 235000014692 zinc oxide Nutrition 0.000 claims description 3
• LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 claims description 2
• SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
• JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 2
• 239000001856 Ethyl cellulose Substances 0.000 claims 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 claims description 2
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
• 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
• IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 claims description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
• JUUFBMODXQKSTD-UHFFFAOYSA-N N-[2-amino-6-[(4-fluorophenyl)methylamino]-3-pyridinyl]carbamic acid ethyl ester Chemical compound N1=C(N)C(NC(=O)OCC)=CC=C1NCC1=CC=C(F)C=C1 JUUFBMODXQKSTD-UHFFFAOYSA-N 0.000 claims description 2
• 208000028017 Psychotic disease Diseases 0.000 claims description 2
• 229920001800 Shellac Polymers 0.000 claims description 2
• 229920002807 Thiomer Polymers 0.000 claims description 2
• FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 claims description 2
• WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims description 2
• AJXBTRZGLDTSST-UHFFFAOYSA-N amino 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)ON AJXBTRZGLDTSST-UHFFFAOYSA-N 0.000 claims description 2
• 229910052791 calcium Inorganic materials 0.000 claims description 2
• 239000005018 casein Substances 0.000 claims description 2
• BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical group NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 claims description 2
• 235000021240 caseins Nutrition 0.000 claims description 2
• 239000002274 desiccant Substances 0.000 claims description 2
• SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 claims description 2
• 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
• 229920001249 ethyl cellulose Polymers 0.000 claims description 2
• 229960003667 flupirtine Drugs 0.000 claims description 2
• 239000011888 foil Substances 0.000 claims description 2
• 239000007789 gas Substances 0.000 claims description 2
• 210000004251 human milk Anatomy 0.000 claims description 2
• 150000002430 hydrocarbons Chemical class 0.000 claims description 2
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
• 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 claims description 2
• 238000001727 in vivo Methods 0.000 claims description 2
• 229910052749 magnesium Inorganic materials 0.000 claims description 2
• 239000011777 magnesium Substances 0.000 claims description 2
• 238000009448 modified atmosphere packaging Methods 0.000 claims description 2
• PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 2
• 235000002949 phytic acid Nutrition 0.000 claims description 2
• 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 claims description 2
• 229920002689 polyvinyl acetate Polymers 0.000 claims description 2
• 239000011118 polyvinyl acetate Substances 0.000 claims description 2
• 229940075065 polyvinyl acetate Drugs 0.000 claims description 2
• 229940100467 polyvinyl acetate phthalate Drugs 0.000 claims description 2
• 239000004208 shellac Substances 0.000 claims description 2
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 claims description 2
• 229940113147 shellac Drugs 0.000 claims description 2
• 235000013874 shellac Nutrition 0.000 claims description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
• 230000008359 toxicosis Effects 0.000 claims description 2
• 125000005591 trimellitate group Chemical group 0.000 claims description 2
• 229920006163 vinyl copolymer Polymers 0.000 claims description 2
• 239000011667 zinc carbonate Substances 0.000 claims description 2
• 235000004416 zinc carbonate Nutrition 0.000 claims description 2
• 229910000010 zinc carbonate Inorganic materials 0.000 claims description 2
• 239000011592 zinc chloride Substances 0.000 claims description 2
• 235000005074 zinc chloride Nutrition 0.000 claims description 2
• 229960001939 zinc chloride Drugs 0.000 claims description 2
• 239000011670 zinc gluconate Substances 0.000 claims description 2
• 235000011478 zinc gluconate Nutrition 0.000 claims description 2
• 229960000306 zinc gluconate Drugs 0.000 claims description 2
• 229960001296 zinc oxide Drugs 0.000 claims description 2
• XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 2
• 229940057977 zinc stearate Drugs 0.000 claims description 2
• NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 2
• 229960001763 zinc sulfate Drugs 0.000 claims description 2
• 229910000368 zinc sulfate Inorganic materials 0.000 claims description 2
• 238000013213 extrapolation Methods 0.000 claims 4
• 238000005259 measurement Methods 0.000 claims 4
• 239000000651 prodrug Substances 0.000 claims 4
• 229940002612 prodrug Drugs 0.000 claims 4
• 229960000314 zinc acetate Drugs 0.000 claims 4
• 201000011240 Frontotemporal dementia Diseases 0.000 claims 3
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims 3
• 239000003638 chemical reducing agent Substances 0.000 claims 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
• 201000001981 dermatomyositis Diseases 0.000 claims 3
• 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims 3
• 229920001897 terpolymer Polymers 0.000 claims 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical group 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 claims 2
• 239000004698 Polyethylene Substances 0.000 claims 2
• 239000004743 Polypropylene Substances 0.000 claims 2
• 239000004793 Polystyrene Substances 0.000 claims 2
• 125000002947 alkylene group Chemical group 0.000 claims 2
• 229920005603 alternating copolymer Polymers 0.000 claims 2
• 229960004977 anhydrous lactose Drugs 0.000 claims 2
• 102000023732 binding proteins Human genes 0.000 claims 2
• 238000009833 condensation Methods 0.000 claims 2
• 230000005494 condensation Effects 0.000 claims 2
• 230000003176 fibrotic effect Effects 0.000 claims 2
• 239000011261 inert gas Substances 0.000 claims 2
• 208000027866 inflammatory disease Diseases 0.000 claims 2
• 239000004005 microsphere Substances 0.000 claims 2
• 229920000570 polyether Polymers 0.000 claims 2
• 229920000573 polyethylene Polymers 0.000 claims 2
• 229920001155 polypropylene Polymers 0.000 claims 2
• 229920002223 polystyrene Polymers 0.000 claims 2
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims 1
• WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical group O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims 1
• 208000009137 Behcet syndrome Diseases 0.000 claims 1
• 208000020925 Bipolar disease Diseases 0.000 claims 1
• 229920000623 Cellulose acetate phthalate Polymers 0.000 claims 1
• 206010017943 Gastrointestinal conditions Diseases 0.000 claims 1
• 229940099433 NMDA receptor antagonist Drugs 0.000 claims 1
• IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 claims 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 claims 1
• 229920002845 Poly(methacrylic acid) Polymers 0.000 claims 1
• 229920002319 Poly(methyl acrylate) Polymers 0.000 claims 1
• 239000004952 Polyamide Substances 0.000 claims 1
• 239000005062 Polybutadiene Substances 0.000 claims 1
• 229920002367 Polyisobutene Polymers 0.000 claims 1
• 239000004721 Polyphenylene oxide Substances 0.000 claims 1
• 229920001328 Polyvinylidene chloride Polymers 0.000 claims 1
• 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 1
• 230000001430 anti-depressive effect Effects 0.000 claims 1
• 230000003110 anti-inflammatory effect Effects 0.000 claims 1
• 230000000561 anti-psychotic effect Effects 0.000 claims 1
• 239000000935 antidepressant agent Substances 0.000 claims 1
• 229940005513 antidepressants Drugs 0.000 claims 1
• 239000000164 antipsychotic agent Substances 0.000 claims 1
• 229920001400 block copolymer Polymers 0.000 claims 1
• INLLPKCGLOXCIV-UHFFFAOYSA-N bromoethene Chemical compound BrC=C INLLPKCGLOXCIV-UHFFFAOYSA-N 0.000 claims 1
• 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims 1
• 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims 1
• 239000000679 carrageenan Substances 0.000 claims 1
• 235000010418 carrageenan Nutrition 0.000 claims 1
• 229920001525 carrageenan Polymers 0.000 claims 1
• 229940113118 carrageenan Drugs 0.000 claims 1
• 229940081734 cellulose acetate phthalate Drugs 0.000 claims 1
• 239000013522 chelant Substances 0.000 claims 1
• 229960004106 citric acid Drugs 0.000 claims 1
• 150000004699 copper complex Chemical class 0.000 claims 1
• FMSOAWSKCWYLBB-VBGLAJCLSA-N deferasirox Chemical compound C1=CC(C(=O)O)=CC=C1N(N\C(N\1)=C\2C(C=CC=C/2)=O)C/1=C\1C(=O)C=CC=C/1 FMSOAWSKCWYLBB-VBGLAJCLSA-N 0.000 claims 1
• 229960001489 deferasirox Drugs 0.000 claims 1
• 150000001993 dienes Chemical class 0.000 claims 1
• 235000015872 dietary supplement Nutrition 0.000 claims 1
• 238000004108 freeze drying Methods 0.000 claims 1
• 229920000578 graft copolymer Polymers 0.000 claims 1
• 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims 1
• 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims 1
• GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical compound IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 claims 1
• 150000002535 isoprostanes Chemical class 0.000 claims 1
• 229960001021 lactose monohydrate Drugs 0.000 claims 1
• 239000002480 mineral oil Substances 0.000 claims 1
• 235000010446 mineral oil Nutrition 0.000 claims 1
• 229920001778 nylon Polymers 0.000 claims 1
• 229940068041 phytic acid Drugs 0.000 claims 1
• 239000000467 phytic acid Substances 0.000 claims 1
• 229920002863 poly(1,4-phenylene oxide) polymer Polymers 0.000 claims 1
• 229920002493 poly(chlorotrifluoroethylene) Polymers 0.000 claims 1
• 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims 1
• 229920003205 poly(diphenylsiloxane) Polymers 0.000 claims 1
• 229920001483 poly(ethyl methacrylate) polymer Polymers 0.000 claims 1
• 229920003229 poly(methyl methacrylate) Polymers 0.000 claims 1
• 229920003216 poly(methylphenylsiloxane) Polymers 0.000 claims 1
• 229920000548 poly(silane) polymer Polymers 0.000 claims 1
• 229920002239 polyacrylonitrile Polymers 0.000 claims 1
• 229920002647 polyamide Polymers 0.000 claims 1
• 229920002857 polybutadiene Polymers 0.000 claims 1
• 229920001707 polybutylene terephthalate Polymers 0.000 claims 1
• 229920000728 polyester Polymers 0.000 claims 1
• 229920000120 polyethyl acrylate Polymers 0.000 claims 1
• 229920000139 polyethylene terephthalate Polymers 0.000 claims 1
• 239000005020 polyethylene terephthalate Substances 0.000 claims 1
• 239000004926 polymethyl methacrylate Substances 0.000 claims 1
• 229920000306 polymethylpentene Polymers 0.000 claims 1
• 239000011116 polymethylpentene Substances 0.000 claims 1
• 229920001451 polypropylene glycol Polymers 0.000 claims 1
• 229920001296 polysiloxane Polymers 0.000 claims 1
• 229920001343 polytetrafluoroethylene Polymers 0.000 claims 1
• 229920002215 polytrimethylene terephthalate Polymers 0.000 claims 1
• 229920000915 polyvinyl chloride Polymers 0.000 claims 1
• 239000004800 polyvinyl chloride Substances 0.000 claims 1
• 229920002620 polyvinyl fluoride Polymers 0.000 claims 1
• 229920002981 polyvinylidene fluoride Polymers 0.000 claims 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 claims 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 1
• 229920005604 random copolymer Polymers 0.000 claims 1
• 229920002994 synthetic fiber Polymers 0.000 claims 1
• 238000005303 weighing Methods 0.000 claims 1
• 229940043825 zinc carbonate Drugs 0.000 claims 1
• UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims 1
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 72
• 210000004556 brain Anatomy 0.000 description 47
• 239000003814 drug Substances 0.000 description 37
• 210000003169 central nervous system Anatomy 0.000 description 35
• 229940079593 drug Drugs 0.000 description 33
• 108010026424 tau Proteins Proteins 0.000 description 31
• 102000013498 tau Proteins Human genes 0.000 description 31
• 230000008901 benefit Effects 0.000 description 25
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 25
• 235000012000 cholesterol Nutrition 0.000 description 25
• 210000004027 cell Anatomy 0.000 description 21
• 230000000694 effects Effects 0.000 description 20
• 210000002569 neuron Anatomy 0.000 description 20
• 235000005911 diet Nutrition 0.000 description 19
• 230000001965 increasing effect Effects 0.000 description 19
• 235000020188 drinking water Nutrition 0.000 description 18
• 239000003651 drinking water Substances 0.000 description 18
• 231100000331 toxic Toxicity 0.000 description 18
• 230000002588 toxic effect Effects 0.000 description 18
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 17
• 102000003802 alpha-Synuclein Human genes 0.000 description 16
• 108090000185 alpha-Synuclein Proteins 0.000 description 16
• 230000015572 biosynthetic process Effects 0.000 description 15
• 239000002552 dosage form Substances 0.000 description 15
• 230000004770 neurodegeneration Effects 0.000 description 15
• 230000001839 systemic circulation Effects 0.000 description 15
• 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 14
• 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 14
• 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 14
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 14
• 210000004369 blood Anatomy 0.000 description 14
• 239000008280 blood Substances 0.000 description 14
• 230000000378 dietary effect Effects 0.000 description 14
• 230000000968 intestinal effect Effects 0.000 description 14
• 102000004311 liver X receptors Human genes 0.000 description 14
• 108090000865 liver X receptors Proteins 0.000 description 14
• 230000014759 maintenance of location Effects 0.000 description 14
• 230000007246 mechanism Effects 0.000 description 14
• DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 13
• 206010010957 Copper deficiency Diseases 0.000 description 13
• 108090000157 Metallothionein Proteins 0.000 description 13
• 102000003792 Metallothionein Human genes 0.000 description 13
• 102000034527 Retinoid X Receptors Human genes 0.000 description 13
• 108010038912 Retinoid X Receptors Proteins 0.000 description 13
• 108010034748 copper-binding protein Proteins 0.000 description 13
• 208000015122 neurodegenerative disease Diseases 0.000 description 13
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 13
• 241000700159 Rattus Species 0.000 description 11
• 230000008499 blood brain barrier function Effects 0.000 description 11
• 210000001218 blood-brain barrier Anatomy 0.000 description 11
• 230000003232 mucoadhesive effect Effects 0.000 description 11
• 230000008569 process Effects 0.000 description 11
• 206010016654 Fibrosis Diseases 0.000 description 10
• 230000000536 complexating effect Effects 0.000 description 10
• 239000012634 fragment Substances 0.000 description 10
• 210000004558 lewy body Anatomy 0.000 description 10
• 230000001225 therapeutic effect Effects 0.000 description 10
• 230000001988 toxicity Effects 0.000 description 10
• 231100000419 toxicity Toxicity 0.000 description 10
• JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 9
• 230000004087 circulation Effects 0.000 description 9
• 208000035475 disorder Diseases 0.000 description 9
• 238000012377 drug delivery Methods 0.000 description 9
• 238000009115 maintenance therapy Methods 0.000 description 9
• 230000035772 mutation Effects 0.000 description 9
• 210000000056 organ Anatomy 0.000 description 9
• 210000001519 tissue Anatomy 0.000 description 9
• 101150037123 APOE gene Proteins 0.000 description 8
• 101100216294 Danio rerio apoeb gene Proteins 0.000 description 8
• 208000030886 Traumatic Brain injury Diseases 0.000 description 8
• 230000035508 accumulation Effects 0.000 description 8
• 229910001431 copper ion Inorganic materials 0.000 description 8
• 230000006378 damage Effects 0.000 description 8
• 230000001976 improved effect Effects 0.000 description 8
• 230000004060 metabolic process Effects 0.000 description 8
• 230000001537 neural effect Effects 0.000 description 8
• 229920001223 polyethylene glycol Polymers 0.000 description 8
• 150000003254 radicals Chemical class 0.000 description 8
• 230000002459 sustained effect Effects 0.000 description 8
• 239000008399 tap water Substances 0.000 description 8
• 235000020679 tap water Nutrition 0.000 description 8
• 230000032258 transport Effects 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
• 206010021143 Hypoxia Diseases 0.000 description 7
• 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 7
• 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 7
• 230000002776 aggregation Effects 0.000 description 7
• 238000004220 aggregation Methods 0.000 description 7
• 238000002474 experimental method Methods 0.000 description 7
• 230000013632 homeostatic process Effects 0.000 description 7
• 239000000017 hydrogel Substances 0.000 description 7
• 230000003647 oxidation Effects 0.000 description 7
• 238000007254 oxidation reaction Methods 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 229920003137 Eudragit® S polymer Polymers 0.000 description 6
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
• 102000019355 Synuclein Human genes 0.000 description 6
• 108050006783 Synuclein Proteins 0.000 description 6
• 239000013543 active substance Substances 0.000 description 6
• 239000003963 antioxidant agent Substances 0.000 description 6
• 235000006708 antioxidants Nutrition 0.000 description 6
• 238000013459 approach Methods 0.000 description 6
• 238000013270 controlled release Methods 0.000 description 6
• 230000007423 decrease Effects 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 6
• 230000014509 gene expression Effects 0.000 description 6
• 229930195712 glutamate Natural products 0.000 description 6
• 210000004379 membrane Anatomy 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• 230000000626 neurodegenerative effect Effects 0.000 description 6
• 239000000902 placebo Substances 0.000 description 6
• 229940068196 placebo Drugs 0.000 description 6
• 210000002381 plasma Anatomy 0.000 description 6
• 230000002035 prolonged effect Effects 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 230000001105 regulatory effect Effects 0.000 description 6
• 235000001508 sulfur Nutrition 0.000 description 6
• 239000006228 supernatant Substances 0.000 description 6
• 230000009469 supplementation Effects 0.000 description 6
• URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 6
• 108091004554 Copper Transport Proteins Proteins 0.000 description 5
• 102000020856 Copper Transport Proteins Human genes 0.000 description 5
• 102100027591 Copper-transporting ATPase 2 Human genes 0.000 description 5
• 101000936280 Homo sapiens Copper-transporting ATPase 2 Proteins 0.000 description 5
• 206010061218 Inflammation Diseases 0.000 description 5
• 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 5
• 201000010829 Spina bifida Diseases 0.000 description 5
• 208000006097 Spinal Dysraphism Diseases 0.000 description 5
• 229930182558 Sterol Natural products 0.000 description 5
• 230000002378 acidificating effect Effects 0.000 description 5
• 230000032683 aging Effects 0.000 description 5
• 229940024606 amino acid Drugs 0.000 description 5
• 150000001413 amino acids Chemical group 0.000 description 5
• 238000010171 animal model Methods 0.000 description 5
• 230000009286 beneficial effect Effects 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 230000001684 chronic effect Effects 0.000 description 5
• 230000007882 cirrhosis Effects 0.000 description 5
• 208000019425 cirrhosis of liver Diseases 0.000 description 5
• 238000011161 development Methods 0.000 description 5
• 230000018109 developmental process Effects 0.000 description 5
• 230000037213 diet Effects 0.000 description 5
• 230000004761 fibrosis Effects 0.000 description 5
• 230000004054 inflammatory process Effects 0.000 description 5
• 230000004941 influx Effects 0.000 description 5
• 208000014674 injury Diseases 0.000 description 5
• 208000028867 ischemia Diseases 0.000 description 5
• 239000002502 liposome Substances 0.000 description 5
• 230000010534 mechanism of action Effects 0.000 description 5
• 201000010193 neural tube defect Diseases 0.000 description 5
• 230000016273 neuron death Effects 0.000 description 5
• 230000001575 pathological effect Effects 0.000 description 5
• 230000037361 pathway Effects 0.000 description 5
• 239000002243 precursor Substances 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 210000001187 pylorus Anatomy 0.000 description 5
• 150000003432 sterols Chemical class 0.000 description 5
• 235000003702 sterols Nutrition 0.000 description 5
• 229910052717 sulfur Inorganic materials 0.000 description 5
• 239000011593 sulfur Substances 0.000 description 5
• 208000035581 susceptibility to neural tube defects Diseases 0.000 description 5
• 230000009529 traumatic brain injury Effects 0.000 description 5
• 230000003827 upregulation Effects 0.000 description 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 208000037259 Amyloid Plaque Diseases 0.000 description 4
• 101800001718 Amyloid-beta protein Proteins 0.000 description 4
• 108010022637 Copper-Transporting ATPases Proteins 0.000 description 4
• 102100027587 Copper-transporting ATPase 1 Human genes 0.000 description 4
• 102000008133 Iron-Binding Proteins Human genes 0.000 description 4
• 108010035210 Iron-Binding Proteins Proteins 0.000 description 4
• 102000006386 Myelin Proteins Human genes 0.000 description 4
• 108010083674 Myelin Proteins Proteins 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 239000005557 antagonist Substances 0.000 description 4
• 230000003466 anti-cipated effect Effects 0.000 description 4
• 210000000988 bone and bone Anatomy 0.000 description 4
• 210000001072 colon Anatomy 0.000 description 4
• 230000034994 death Effects 0.000 description 4
• 231100000517 death Toxicity 0.000 description 4
• 230000007547 defect Effects 0.000 description 4
• 230000002950 deficient Effects 0.000 description 4
• 230000006735 deficit Effects 0.000 description 4
• DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 4
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
• 230000004064 dysfunction Effects 0.000 description 4
• 210000001842 enterocyte Anatomy 0.000 description 4
• 230000037406 food intake Effects 0.000 description 4
• 235000012631 food intake Nutrition 0.000 description 4
• 229940118198 galzin Drugs 0.000 description 4
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 4
• 210000003734 kidney Anatomy 0.000 description 4
• 210000003712 lysosome Anatomy 0.000 description 4
• 230000001868 lysosomic effect Effects 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 210000005012 myelin Anatomy 0.000 description 4
• 230000001590 oxidative effect Effects 0.000 description 4
• 230000036542 oxidative stress Effects 0.000 description 4
• 230000001681 protective effect Effects 0.000 description 4
• 102000005962 receptors Human genes 0.000 description 4
• 108020003175 receptors Proteins 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 210000000278 spinal cord Anatomy 0.000 description 4
• IOWMKBFJCNLRTC-XWXSNNQWSA-N (24S)-24-hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@H](O)C(C)C)[C@@]1(C)CC2 IOWMKBFJCNLRTC-XWXSNNQWSA-N 0.000 description 3
• IOWMKBFJCNLRTC-UHFFFAOYSA-N 24S-hydroxycholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(O)C(C)C)C1(C)CC2 IOWMKBFJCNLRTC-UHFFFAOYSA-N 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 3
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 3
• 208000024806 Brain atrophy Diseases 0.000 description 3
• 208000014644 Brain disease Diseases 0.000 description 3
• 102000003908 Cathepsin D Human genes 0.000 description 3
• 108090000258 Cathepsin D Proteins 0.000 description 3
• 206010010904 Convulsion Diseases 0.000 description 3
• 241000196324 Embryophyta Species 0.000 description 3
• 208000004930 Fatty Liver Diseases 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 208000035150 Hypercholesterolemia Diseases 0.000 description 3
• 208000013016 Hypoglycemia Diseases 0.000 description 3
• 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 3
• 206010022998 Irritability Diseases 0.000 description 3
• HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 3
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 3
• YXLXNENXOJSQEI-UHFFFAOYSA-L Oxine-copper Chemical compound [Cu+2].C1=CN=C2C([O-])=CC=CC2=C1.C1=CN=C2C([O-])=CC=CC2=C1 YXLXNENXOJSQEI-UHFFFAOYSA-L 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 208000006011 Stroke Diseases 0.000 description 3
• OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 3
• 208000032859 Synucleinopathies Diseases 0.000 description 3
• DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 3
• PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 3
• 230000005856 abnormality Effects 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 206010002320 anencephaly Diseases 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 229960005370 atorvastatin Drugs 0.000 description 3
• 230000004888 barrier function Effects 0.000 description 3
• 235000013361 beverage Nutrition 0.000 description 3
• 239000002981 blocking agent Substances 0.000 description 3
• 150000001875 compounds Chemical class 0.000 description 3
• 230000008602 contraction Effects 0.000 description 3
• 208000029078 coronary artery disease Diseases 0.000 description 3
• 230000007812 deficiency Effects 0.000 description 3
• 235000018823 dietary intake Nutrition 0.000 description 3
• 210000005064 dopaminergic neuron Anatomy 0.000 description 3
• 230000003291 dopaminomimetic effect Effects 0.000 description 3
• 210000000981 epithelium Anatomy 0.000 description 3
• 238000007667 floating Methods 0.000 description 3
• 238000005188 flotation Methods 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 230000002068 genetic effect Effects 0.000 description 3
• 239000001087 glyceryl triacetate Substances 0.000 description 3
• 235000013773 glyceryl triacetate Nutrition 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 230000036541 health Effects 0.000 description 3
• 210000003494 hepatocyte Anatomy 0.000 description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
• 230000002218 hypoglycaemic effect Effects 0.000 description 3
• 230000006872 improvement Effects 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 230000003902 lesion Effects 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 230000037356 lipid metabolism Effects 0.000 description 3
• 230000007774 longterm Effects 0.000 description 3
• 238000002595 magnetic resonance imaging Methods 0.000 description 3
• 230000007102 metabolic function Effects 0.000 description 3
• 210000000653 nervous system Anatomy 0.000 description 3
• 230000000926 neurological effect Effects 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 102000006255 nuclear receptors Human genes 0.000 description 3
• 108020004017 nuclear receptors Proteins 0.000 description 3
• 235000016709 nutrition Nutrition 0.000 description 3
• 210000004789 organ system Anatomy 0.000 description 3
• 230000035790 physiological processes and functions Effects 0.000 description 3
• 239000004014 plasticizer Substances 0.000 description 3
• 230000035935 pregnancy Effects 0.000 description 3
• 210000004129 prosencephalon Anatomy 0.000 description 3
• GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 238000004611 spectroscopical analysis Methods 0.000 description 3
• 239000003270 steroid hormone Substances 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 210000003523 substantia nigra Anatomy 0.000 description 3
• 230000001052 transient effect Effects 0.000 description 3
• 229960002622 triacetin Drugs 0.000 description 3
• GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
• PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 241000251468 Actinopterygii Species 0.000 description 2
• 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 2
• 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 2
• 102100029470 Apolipoprotein E Human genes 0.000 description 2
• 101710095339 Apolipoprotein E Proteins 0.000 description 2
• 102100021257 Beta-secretase 1 Human genes 0.000 description 2
• 102000004506 Blood Proteins Human genes 0.000 description 2
• 108010017384 Blood Proteins Proteins 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 102000014914 Carrier Proteins Human genes 0.000 description 2
• 102000005600 Cathepsins Human genes 0.000 description 2
• 108010084457 Cathepsins Proteins 0.000 description 2
• 229920001661 Chitosan Polymers 0.000 description 2
• 208000006154 Chronic hepatitis C Diseases 0.000 description 2
• 208000032170 Congenital Abnormalities Diseases 0.000 description 2
• 206010010356 Congenital anomaly Diseases 0.000 description 2
• 108091006566 Copper transporters Proteins 0.000 description 2
• 241000699800 Cricetinae Species 0.000 description 2
• ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
• 208000005176 Hepatitis C Diseases 0.000 description 2
• 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 238000012404 In vitro experiment Methods 0.000 description 2
• 208000026350 Inborn Genetic disease Diseases 0.000 description 2
• 102000006541 Ionotropic Glutamate Receptors Human genes 0.000 description 2
• 108010008812 Ionotropic Glutamate Receptors Proteins 0.000 description 2
• VLSMHEGGTFMBBZ-OOZYFLPDSA-M Kainate Chemical compound CC(=C)[C@H]1C[NH2+][C@H](C([O-])=O)[C@H]1CC([O-])=O VLSMHEGGTFMBBZ-OOZYFLPDSA-M 0.000 description 2
• WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
• WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 2
• 241000699660 Mus musculus Species 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 206010028813 Nausea Diseases 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• 108010029485 Protein Isoforms Proteins 0.000 description 2
• 102000001708 Protein Isoforms Human genes 0.000 description 2
• 206010040844 Skin exfoliation Diseases 0.000 description 2
• 108010048349 Steroidogenic Factor 1 Proteins 0.000 description 2
• 102100029856 Steroidogenic factor 1 Human genes 0.000 description 2
• 102000008221 Superoxide Dismutase-1 Human genes 0.000 description 2
• 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 description 2
• 229930003268 Vitamin C Natural products 0.000 description 2
• 208000027418 Wounds and injury Diseases 0.000 description 2
• 238000002835 absorbance Methods 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 230000003078 antioxidant effect Effects 0.000 description 2
• 229940009098 aspartate Drugs 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 239000011324 bead Substances 0.000 description 2
• 230000008033 biological extinction Effects 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 230000007698 birth defect Effects 0.000 description 2
• 210000001124 body fluid Anatomy 0.000 description 2
• 239000010839 body fluid Substances 0.000 description 2
• 208000029028 brain injury Diseases 0.000 description 2
• 239000007853 buffer solution Substances 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 230000009920 chelation Effects 0.000 description 2
• QMPATRQNERZOMF-YJBOKZPZSA-N chembl2179950 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)C=[N+]=[N-])NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 QMPATRQNERZOMF-YJBOKZPZSA-N 0.000 description 2
• 201000001883 cholelithiasis Diseases 0.000 description 2
• 230000001149 cognitive effect Effects 0.000 description 2
• 230000001010 compromised effect Effects 0.000 description 2
• 239000000599 controlled substance Substances 0.000 description 2
• 150000001879 copper Chemical class 0.000 description 2
• 238000009145 copper supplementation Methods 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000007850 degeneration Effects 0.000 description 2
• 229920006237 degradable polymer Polymers 0.000 description 2
• 230000002939 deleterious effect Effects 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 239000012153 distilled water Substances 0.000 description 2
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
• XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 description 2
• 229960003135 donepezil hydrochloride Drugs 0.000 description 2
• 229960003638 dopamine Drugs 0.000 description 2
• 238000002651 drug therapy Methods 0.000 description 2
• 210000001198 duodenum Anatomy 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 210000003238 esophagus Anatomy 0.000 description 2
• 125000004185 ester group Chemical group 0.000 description 2
• 230000003492 excitotoxic effect Effects 0.000 description 2
• 231100000063 excitotoxicity Toxicity 0.000 description 2
• 239000004060 excitotoxin Substances 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 238000010579 first pass effect Methods 0.000 description 2
• 239000013505 freshwater Substances 0.000 description 2
• 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
• 230000030136 gastric emptying Effects 0.000 description 2
• 208000016361 genetic disease Diseases 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
• 230000012010 growth Effects 0.000 description 2
• 208000010710 hepatitis C virus infection Diseases 0.000 description 2
• 230000000971 hippocampal effect Effects 0.000 description 2
• 210000001320 hippocampus Anatomy 0.000 description 2
• 230000003284 homeostatic effect Effects 0.000 description 2
• 230000006951 hyperphosphorylation Effects 0.000 description 2
• 230000007954 hypoxia Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 210000003000 inclusion body Anatomy 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 230000031891 intestinal absorption Effects 0.000 description 2
• 210000004347 intestinal mucosa Anatomy 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 230000007794 irritation Effects 0.000 description 2
• 208000037906 ischaemic injury Diseases 0.000 description 2
• 210000002429 large intestine Anatomy 0.000 description 2
• 208000018637 late onset Parkinson disease Diseases 0.000 description 2
• 201000010901 lateral sclerosis Diseases 0.000 description 2
• 229960004502 levodopa Drugs 0.000 description 2
• 230000033001 locomotion Effects 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 229910052748 manganese Inorganic materials 0.000 description 2
• 239000011572 manganese Substances 0.000 description 2
• 238000002483 medication Methods 0.000 description 2
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
• 229910052753 mercury Inorganic materials 0.000 description 2
• 230000037353 metabolic pathway Effects 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 208000005264 motor neuron disease Diseases 0.000 description 2
• 210000004877 mucosa Anatomy 0.000 description 2
• 239000002105 nanoparticle Substances 0.000 description 2
• 230000008693 nausea Effects 0.000 description 2
• 239000002858 neurotransmitter agent Substances 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 210000003254 palate Anatomy 0.000 description 2
• 230000008506 pathogenesis Effects 0.000 description 2
• 230000007310 pathophysiology Effects 0.000 description 2
• 230000002572 peristaltic effect Effects 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• 229940127557 pharmaceutical product Drugs 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 239000008363 phosphate buffer Substances 0.000 description 2
• 210000002826 placenta Anatomy 0.000 description 2
• 229920003023 plastic Polymers 0.000 description 2
• 239000004033 plastic Substances 0.000 description 2
• 210000003240 portal vein Anatomy 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 230000002028 premature Effects 0.000 description 2
• 230000000750 progressive effect Effects 0.000 description 2
• 210000000664 rectum Anatomy 0.000 description 2
• 238000009877 rendering Methods 0.000 description 2
• 102200036626 rs104893877 Human genes 0.000 description 2
• 102200036620 rs104893878 Human genes 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 238000004062 sedimentation Methods 0.000 description 2
• 210000003625 skull Anatomy 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 208000020431 spinal cord injury Diseases 0.000 description 2
• 230000007863 steatosis Effects 0.000 description 2
• 231100000240 steatosis hepatitis Toxicity 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 125000004149 thio group Chemical group *S* 0.000 description 2
• 230000036962 time dependent Effects 0.000 description 2
• 231100000027 toxicology Toxicity 0.000 description 2
• 229910021654 trace metal Inorganic materials 0.000 description 2
• 238000011830 transgenic mouse model Methods 0.000 description 2
• 230000005945 translocation Effects 0.000 description 2
• 230000008733 trauma Effects 0.000 description 2
• 239000001069 triethyl citrate Substances 0.000 description 2
• VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 2
• 235000013769 triethyl citrate Nutrition 0.000 description 2
• 235000019154 vitamin C Nutrition 0.000 description 2
• 239000011718 vitamin C Substances 0.000 description 2
• LUKFBBVWTIMTHT-DKWTVANSSA-N (2r)-2-amino-3-sulfanylpropanoic acid;copper Chemical class [Cu].SC[C@H](N)C(O)=O LUKFBBVWTIMTHT-DKWTVANSSA-N 0.000 description 1
• WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
• VSKCCZIUZNTICH-ZPYUXNTASA-N (e)-but-2-enoic acid;ethenyl acetate Chemical compound C\C=C\C(O)=O.CC(=O)OC=C VSKCCZIUZNTICH-ZPYUXNTASA-N 0.000 description 1
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
• RZPAXNJLEKLXNO-UKNNTIGFSA-N 22-Hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)C(O)CCC(C)C)[C@@]1(C)CC2 RZPAXNJLEKLXNO-UKNNTIGFSA-N 0.000 description 1
• OSENKJZWYQXHBN-XVYZBDJZSA-N 24(S),25-epoxycholesterol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2CC1)C)C[C@@H]1OC1(C)C OSENKJZWYQXHBN-XVYZBDJZSA-N 0.000 description 1
• HVYWMOMLDIMFJA-UHFFFAOYSA-N 3-cholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 HVYWMOMLDIMFJA-UHFFFAOYSA-N 0.000 description 1
• 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 1
• 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 description 1
• 101150075644 ATP7B gene Proteins 0.000 description 1
• 108091006112 ATPases Proteins 0.000 description 1
• 206010000234 Abortion spontaneous Diseases 0.000 description 1
• 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
• 208000007848 Alcoholism Diseases 0.000 description 1
• 201000004384 Alopecia Diseases 0.000 description 1
• 208000025298 Alzheimer disease 15 Diseases 0.000 description 1
• 208000022099 Alzheimer disease 2 Diseases 0.000 description 1
• 208000012920 Alzheimer disease without neurofibrillary tangles Diseases 0.000 description 1
• ITPDYQOUSLNIHG-UHFFFAOYSA-N Amiodarone hydrochloride Chemical compound [Cl-].CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCC[NH+](CC)CC)C(I)=C1 ITPDYQOUSLNIHG-UHFFFAOYSA-N 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
• 101150102415 Apob gene Proteins 0.000 description 1
• 108010060159 Apolipoprotein E4 Proteins 0.000 description 1
• 102000018616 Apolipoproteins B Human genes 0.000 description 1
• 108010027006 Apolipoproteins B Proteins 0.000 description 1
• 108010025628 Apolipoproteins E Proteins 0.000 description 1
• 102000013918 Apolipoproteins E Human genes 0.000 description 1
• 206010003694 Atrophy 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
• 238000012935 Averaging Methods 0.000 description 1
• 206010006100 Bradykinesia Diseases 0.000 description 1
• 229940127291 Calcium channel antagonist Drugs 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 206010008635 Cholestasis Diseases 0.000 description 1
• 229920001268 Cholestyramine Polymers 0.000 description 1
• 102000003914 Cholinesterases Human genes 0.000 description 1
• 108090000322 Cholinesterases Proteins 0.000 description 1
• 206010057573 Chronic hepatic failure Diseases 0.000 description 1
• 108010004103 Chylomicrons Proteins 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
• 206010009269 Cleft palate Diseases 0.000 description 1
• ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
• 229920002911 Colestipol Polymers 0.000 description 1
• 101000746263 Conus leopardus Conotoxin Lp5.1 Proteins 0.000 description 1
• 102000021421 Copper Transporter 1 Human genes 0.000 description 1
• 108010003232 Copper Transporter 1 Proteins 0.000 description 1
• QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
• 239000005751 Copper oxide Substances 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000288030 Coturnix coturnix Species 0.000 description 1
• 206010012442 Dermatitis contact Diseases 0.000 description 1
• 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
• 208000012661 Dyskinesia Diseases 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 208000010334 End Stage Liver Disease Diseases 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 206010053155 Epigastric discomfort Diseases 0.000 description 1
• 229920003136 Eudragit® L polymer Polymers 0.000 description 1
• 208000001308 Fasciculation Diseases 0.000 description 1
• 102000008857 Ferritin Human genes 0.000 description 1
• 108050000784 Ferritin Proteins 0.000 description 1
• 238000008416 Ferritin Methods 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
• 208000031448 Genomic Instability Diseases 0.000 description 1
• 102400000321 Glucagon Human genes 0.000 description 1
• 108060003199 Glucagon Proteins 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 208000004547 Hallucinations Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 102000001554 Hemoglobins Human genes 0.000 description 1
• 108010054147 Hemoglobins Proteins 0.000 description 1
• 108010017480 Hemosiderin Proteins 0.000 description 1
• 206010019708 Hepatic steatosis Diseases 0.000 description 1
• 102100027619 Histidine-rich glycoprotein Human genes 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
• 208000033892 Hyperhomocysteinemia Diseases 0.000 description 1
• 208000031226 Hyperlipidaemia Diseases 0.000 description 1
• 208000006083 Hypokinesia Diseases 0.000 description 1
• 102000000589 Interleukin-1 Human genes 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• 108090001030 Lipoproteins Proteins 0.000 description 1
• 102000004895 Lipoproteins Human genes 0.000 description 1
• 206010067125 Liver injury Diseases 0.000 description 1
• 241000282560 Macaca mulatta Species 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
• 102000029749 Microtubule Human genes 0.000 description 1
• 108091022875 Microtubule Proteins 0.000 description 1
• 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
• 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
• 208000002740 Muscle Rigidity Diseases 0.000 description 1
• 206010028293 Muscle contractions involuntary Diseases 0.000 description 1
• NRFJZTXWLKPZAV-UHFFFAOYSA-N N-(2-oxo-3-thiolanyl)acetamide Chemical compound CC(=O)NC1CCSC1=O NRFJZTXWLKPZAV-UHFFFAOYSA-N 0.000 description 1
• 102000003797 Neuropeptides Human genes 0.000 description 1
• 108090000189 Neuropeptides Proteins 0.000 description 1
• 206010029350 Neurotoxicity Diseases 0.000 description 1
• 101710138657 Neurotoxin Proteins 0.000 description 1
• 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 206010070818 Oesophageal irritation Diseases 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 102000003697 P-type ATPases Human genes 0.000 description 1
• 108090000069 P-type ATPases Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 102100026456 POU domain, class 3, transcription factor 3 Human genes 0.000 description 1
• 101710133393 POU domain, class 3, transcription factor 3 Proteins 0.000 description 1
• 206010033864 Paranoia Diseases 0.000 description 1
• 208000027099 Paranoid disease Diseases 0.000 description 1
• 208000027089 Parkinsonian disease Diseases 0.000 description 1
• 241001442654 Percnon planissimum Species 0.000 description 1
• 206010034719 Personality change Diseases 0.000 description 1
• 108010089430 Phosphoproteins Proteins 0.000 description 1
• 102000007982 Phosphoproteins Human genes 0.000 description 1
• PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
• 108010089814 Plant Lectins Proteins 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• 208000035977 Rare disease Diseases 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 108091027981 Response element Proteins 0.000 description 1
• 206010071390 Resting tremor Diseases 0.000 description 1
• XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• 206010039966 Senile dementia Diseases 0.000 description 1
• 108010071390 Serum Albumin Proteins 0.000 description 1
• 102000007562 Serum Albumin Human genes 0.000 description 1
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
• 108010052164 Sodium Channels Proteins 0.000 description 1
• 102000018674 Sodium Channels Human genes 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 108010056088 Somatostatin Proteins 0.000 description 1
• 102000005157 Somatostatin Human genes 0.000 description 1
• 239000005864 Sulphur Substances 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 241000611306 Taeniopygia guttata Species 0.000 description 1
• 206010044221 Toxic encephalopathy Diseases 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• 108090000848 Ubiquitin Proteins 0.000 description 1
• 102000044159 Ubiquitin Human genes 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• 238000006023 Wilson reaction Methods 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 208000030668 Zinc disease Diseases 0.000 description 1
• SDNRMTHGLKKEAW-DFWYDOINSA-N [Cu].OC(=O)[C@@H](N)CCS Chemical compound [Cu].OC(=O)[C@@H](N)CCS SDNRMTHGLKKEAW-DFWYDOINSA-N 0.000 description 1
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 1
• 229940060199 actigall Drugs 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 206010001584 alcohol abuse Diseases 0.000 description 1
• 208000025746 alcohol use disease Diseases 0.000 description 1
• 229960001445 alitretinoin Drugs 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 229960005260 amiodarone Drugs 0.000 description 1
• 210000004727 amygdala Anatomy 0.000 description 1
• 230000006933 amyloid-beta aggregation Effects 0.000 description 1
• 235000021120 animal protein Nutrition 0.000 description 1
• 125000000129 anionic group Chemical group 0.000 description 1
• 229920006318 anionic polymer Polymers 0.000 description 1
• 229940069428 antacid Drugs 0.000 description 1
• 239000003159 antacid agent Substances 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 230000002059 anti-epileptogenic effect Effects 0.000 description 1
• 230000000539 anti-peristaltic effect Effects 0.000 description 1
• 229940125681 anticonvulsant agent Drugs 0.000 description 1
• 239000001961 anticonvulsive agent Substances 0.000 description 1
• 239000002518 antifoaming agent Substances 0.000 description 1
• 230000000890 antigenic effect Effects 0.000 description 1
• 230000037444 atrophy Effects 0.000 description 1
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• 210000000013 bile duct Anatomy 0.000 description 1
• 230000010234 biliary secretion Effects 0.000 description 1
• 230000035587 bioadhesion Effects 0.000 description 1
• 238000006065 biodegradation reaction Methods 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000033558 biomineral tissue development Effects 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 239000003114 blood coagulation factor Substances 0.000 description 1
• 235000012206 bottled water Nutrition 0.000 description 1
• 230000006931 brain damage Effects 0.000 description 1
• 231100000874 brain damage Toxicity 0.000 description 1
• 230000003925 brain function Effects 0.000 description 1
• 210000000133 brain stem Anatomy 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 229910052793 cadmium Inorganic materials 0.000 description 1
• BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
• 239000000480 calcium channel blocker Substances 0.000 description 1
• 238000004364 calculation method Methods 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
• 239000001768 carboxy methyl cellulose Substances 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
• 150000003943 catecholamines Chemical class 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 235000013339 cereals Nutrition 0.000 description 1
• 208000013677 cerebrovascular dementia Diseases 0.000 description 1
• 238000006243 chemical reaction Methods 0.000 description 1
• WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
• 229960003677 chloroquine Drugs 0.000 description 1
• 231100000359 cholestasis Toxicity 0.000 description 1
• 230000007870 cholestasis Effects 0.000 description 1
• 230000003312 cholesterol blood level Effects 0.000 description 1
• 230000031154 cholesterol homeostasis Effects 0.000 description 1
• 235000020974 cholesterol intake Nutrition 0.000 description 1
• 150000001841 cholesterols Chemical class 0.000 description 1
• 229940048961 cholinesterase Drugs 0.000 description 1
• 208000011444 chronic liver failure Diseases 0.000 description 1
• 229960004753 citiolone Drugs 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 206010009259 cleft lip Diseases 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 235000017471 coenzyme Q10 Nutrition 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 230000006999 cognitive decline Effects 0.000 description 1
• GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
• 229960002604 colestipol Drugs 0.000 description 1
• 238000010668 complexation reaction Methods 0.000 description 1
• 208000028831 congenital heart disease Diseases 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 208000010247 contact dermatitis Diseases 0.000 description 1
• 238000010924 continuous production Methods 0.000 description 1
• 230000008094 contradictory effect Effects 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 239000003984 copper intrauterine device Substances 0.000 description 1
• 229910000431 copper oxide Inorganic materials 0.000 description 1
• 229910000365 copper sulfate Inorganic materials 0.000 description 1
• ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
• OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 230000000875 corresponding effect Effects 0.000 description 1
• 210000003618 cortical neuron Anatomy 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 235000020247 cow milk Nutrition 0.000 description 1
• 150000001944 cysteine derivatives Chemical class 0.000 description 1
• 239000002852 cysteine proteinase inhibitor Substances 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 210000004292 cytoskeleton Anatomy 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000000254 damaging effect Effects 0.000 description 1
• CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 230000035618 desquamation Effects 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 230000009547 development abnormality Effects 0.000 description 1
• 230000001079 digestive effect Effects 0.000 description 1
• 239000012470 diluted sample Substances 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 230000003467 diminishing effect Effects 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• 150000002009 diols Chemical class 0.000 description 1
• 229960003530 donepezil Drugs 0.000 description 1
• 230000006739 dopaminergic cell death Effects 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 230000000857 drug effect Effects 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 239000000428 dust Substances 0.000 description 1
• 235000013399 edible fruits Nutrition 0.000 description 1
• 210000001163 endosome Anatomy 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940095399 enema Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002662 enteric coated tablet Substances 0.000 description 1
• 210000001353 entorhinal cortex Anatomy 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• 210000003743 erythrocyte Anatomy 0.000 description 1
• 230000010437 erythropoiesis Effects 0.000 description 1
• 235000021321 essential mineral Nutrition 0.000 description 1
• 235000020774 essential nutrients Nutrition 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 239000003687 estradiol congener Substances 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000002964 excitative effect Effects 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 238000013401 experimental design Methods 0.000 description 1
• 210000001723 extracellular space Anatomy 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 230000002550 fecal effect Effects 0.000 description 1
• 229960005191 ferric oxide Drugs 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 235000021588 free fatty acids Nutrition 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 229960003980 galantamine Drugs 0.000 description 1
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 1
• WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
• 210000001156 gastric mucosa Anatomy 0.000 description 1
• 210000003736 gastrointestinal content Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 229960003627 gemfibrozil Drugs 0.000 description 1
• 230000009395 genetic defect Effects 0.000 description 1
• 230000002518 glial effect Effects 0.000 description 1
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=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](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)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(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
• 229960004666 glucagon Drugs 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• 208000024963 hair loss Diseases 0.000 description 1
• 230000003676 hair loss Effects 0.000 description 1
• 230000009931 harmful effect Effects 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 230000007407 health benefit Effects 0.000 description 1
• 230000004217 heart function Effects 0.000 description 1
• 231100000234 hepatic damage Toxicity 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 239000000833 heterodimer Substances 0.000 description 1
• 108010044853 histidine-rich proteins Proteins 0.000 description 1
• 230000002962 histologic effect Effects 0.000 description 1
• 230000009097 homeostatic mechanism Effects 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• 235000006486 human diet Nutrition 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• DLINORNFHVEIFE-UHFFFAOYSA-N hydrogen peroxide;zinc Chemical compound [Zn].OO DLINORNFHVEIFE-UHFFFAOYSA-N 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• ZUFVXZVXEJHHBN-UHFFFAOYSA-N hydron;1,2,3,4-tetrahydroacridin-9-amine;chloride Chemical compound [Cl-].C1=CC=C2C([NH3+])=C(CCCC3)C3=NC2=C1 ZUFVXZVXEJHHBN-UHFFFAOYSA-N 0.000 description 1
• 229920001477 hydrophilic polymer Polymers 0.000 description 1
• 229920001600 hydrophobic polymer Polymers 0.000 description 1
• 208000013403 hyperactivity Diseases 0.000 description 1
• 230000003225 hyperhomocysteinemia Effects 0.000 description 1
• 230000001146 hypoxic effect Effects 0.000 description 1
• 210000003405 ileum Anatomy 0.000 description 1
• 230000036737 immune function Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000002055 immunohistochemical effect Effects 0.000 description 1
• 230000008676 import Effects 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 238000011419 induction treatment Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000011221 initial treatment Methods 0.000 description 1
• 206010022437 insomnia Diseases 0.000 description 1
• 210000002011 intestinal secretion Anatomy 0.000 description 1
• 230000010189 intracellular transport Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• KFZAUHNPPZCSCR-UHFFFAOYSA-N iron zinc Chemical compound [Fe].[Zn] KFZAUHNPPZCSCR-UHFFFAOYSA-N 0.000 description 1
• 208000016696 isolated cleft lip Diseases 0.000 description 1
• 201000009712 isolated cleft palate Diseases 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 239000008141 laxative Substances 0.000 description 1
• 229940125722 laxative agent Drugs 0.000 description 1
• 230000003859 lipid peroxidation Effects 0.000 description 1
• 229940002661 lipitor Drugs 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 230000008818 liver damage Effects 0.000 description 1
• 238000012153 long-term therapy Methods 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
• 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 230000001926 lymphatic effect Effects 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 238000011418 maintenance treatment Methods 0.000 description 1
• 235000009973 maize Nutrition 0.000 description 1
• 238000000691 measurement method Methods 0.000 description 1
• 230000008099 melanin synthesis Effects 0.000 description 1
• 230000006984 memory degeneration Effects 0.000 description 1
• 230000006386 memory function Effects 0.000 description 1
• 208000023060 memory loss Diseases 0.000 description 1
• 230000006996 mental state Effects 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 229960001952 metrifonate Drugs 0.000 description 1
• 210000004688 microtubule Anatomy 0.000 description 1
• 238000003801 milling Methods 0.000 description 1
• 208000015994 miscarriage Diseases 0.000 description 1
• 210000003470 mitochondria Anatomy 0.000 description 1
• 230000004065 mitochondrial dysfunction Effects 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• MEFBJEMVZONFCJ-UHFFFAOYSA-N molybdate Chemical compound [O-][Mo]([O-])(=O)=O MEFBJEMVZONFCJ-UHFFFAOYSA-N 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 239000000178 monomer Substances 0.000 description 1
• 210000002161 motor neuron Anatomy 0.000 description 1
• 210000004400 mucous membrane Anatomy 0.000 description 1
• 210000003097 mucus Anatomy 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 229960002362 neostigmine Drugs 0.000 description 1
• LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 description 1
• 201000008383 nephritis Diseases 0.000 description 1
• 210000000276 neural tube Anatomy 0.000 description 1
• 230000001272 neurogenic effect Effects 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 230000002981 neuropathic effect Effects 0.000 description 1
• 230000000324 neuroprotective effect Effects 0.000 description 1
• 230000007135 neurotoxicity Effects 0.000 description 1
• 231100000228 neurotoxicity Toxicity 0.000 description 1
• 239000002581 neurotoxin Substances 0.000 description 1
• 231100000618 neurotoxin Toxicity 0.000 description 1
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 231100000956 nontoxicity Toxicity 0.000 description 1
• 239000002417 nutraceutical Substances 0.000 description 1
• 230000035764 nutrition Effects 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
• 229940012843 omega-3 fatty acid Drugs 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 229940126701 oral medication Drugs 0.000 description 1
• 210000003463 organelle Anatomy 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 102000004164 orphan nuclear receptors Human genes 0.000 description 1
• 108090000629 orphan nuclear receptors Proteins 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 238000012261 overproduction Methods 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000010627 oxidative phosphorylation Effects 0.000 description 1
• 210000004738 parenchymal cell Anatomy 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 231100000915 pathological change Toxicity 0.000 description 1
• 230000036285 pathological change Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 235000020030 perry Nutrition 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 239000002831 pharmacologic agent Substances 0.000 description 1
• 230000006611 pharmacological activation Effects 0.000 description 1
• 210000003800 pharynx Anatomy 0.000 description 1
• CMEHRSPFSMBENE-UHFFFAOYSA-N phenyl n-ethyl-n-methylcarbamate Chemical compound CCN(C)C(=O)OC1=CC=CC=C1 CMEHRSPFSMBENE-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000003014 phosphoric acid esters Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
• 229960001697 physostigmine Drugs 0.000 description 1
• PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
• 239000003726 plant lectin Substances 0.000 description 1
• 235000021118 plant-derived protein Nutrition 0.000 description 1
• 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 210000002729 polyribosome Anatomy 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 230000008092 positive effect Effects 0.000 description 1
• 230000000291 postprandial effect Effects 0.000 description 1
• 230000001242 postsynaptic effect Effects 0.000 description 1
• 230000001144 postural effect Effects 0.000 description 1
• 235000012015 potatoes Nutrition 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 230000003244 pro-oxidative effect Effects 0.000 description 1
• FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
• 229960003912 probucol Drugs 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 230000009979 protective mechanism Effects 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 238000010926 purge Methods 0.000 description 1
• 210000004203 pyloric antrum Anatomy 0.000 description 1
• 210000002763 pyramidal cell Anatomy 0.000 description 1
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 238000011555 rabbit model Methods 0.000 description 1
• 239000000700 radioactive tracer Substances 0.000 description 1
• 210000001609 raphe nuclei Anatomy 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000029964 regulation of glucose metabolic process Effects 0.000 description 1
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
• 230000008844 regulatory mechanism Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 150000004492 retinoid derivatives Chemical class 0.000 description 1
• 229960004136 rivastigmine Drugs 0.000 description 1
• 230000002000 scavenging effect Effects 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 230000009919 sequestration Effects 0.000 description 1
• 235000004400 serine Nutrition 0.000 description 1
• 150000003355 serines Chemical class 0.000 description 1
• 235000015170 shellfish Nutrition 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
• 229960000553 somatostatin Drugs 0.000 description 1
• 210000005070 sphincter Anatomy 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 208000000995 spontaneous abortion Diseases 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 125000004354 sulfur functional group Chemical group 0.000 description 1
• 229940032362 superoxide dismutase Drugs 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 230000009747 swallowing Effects 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
• 229960003565 tacrine hydrochloride Drugs 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 210000003478 temporal lobe Anatomy 0.000 description 1
• TUGDLVFMIQZYPA-UHFFFAOYSA-N tetracopper;tetrazinc Chemical compound [Cu+2].[Cu+2].[Cu+2].[Cu+2].[Zn+2].[Zn+2].[Zn+2].[Zn+2] TUGDLVFMIQZYPA-UHFFFAOYSA-N 0.000 description 1
• 210000001103 thalamus Anatomy 0.000 description 1
• 229920001187 thermosetting polymer Polymers 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 210000002978 thoracic duct Anatomy 0.000 description 1
• 230000008364 tissue synthesis Effects 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000167 toxic agent Toxicity 0.000 description 1
• 231100000721 toxic potential Toxicity 0.000 description 1
• 239000003440 toxic substance Substances 0.000 description 1
• 239000011573 trace mineral Substances 0.000 description 1
• 235000013619 trace mineral Nutrition 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000008736 traumatic injury Effects 0.000 description 1
• NFACJZMKEDPNKN-UHFFFAOYSA-N trichlorfon Chemical compound COP(=O)(OC)C(O)C(Cl)(Cl)Cl NFACJZMKEDPNKN-UHFFFAOYSA-N 0.000 description 1
• WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• PBYZMCDFOULPGH-UHFFFAOYSA-N tungstate Chemical compound [O-][W]([O-])(=O)=O PBYZMCDFOULPGH-UHFFFAOYSA-N 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
• 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 231100000925 very toxic Toxicity 0.000 description 1
• 235000019156 vitamin B Nutrition 0.000 description 1
• 239000011720 vitamin B Substances 0.000 description 1
• 235000019165 vitamin E Nutrition 0.000 description 1
• 229940046009 vitamin E Drugs 0.000 description 1
• 239000011709 vitamin E Substances 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 238000003466 welding Methods 0.000 description 1
• DJWUNCQRNNEAKC-UHFFFAOYSA-L zinc acetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O DJWUNCQRNNEAKC-UHFFFAOYSA-L 0.000 description 1
• 229940006486 zinc cation Drugs 0.000 description 1
• 108010088577 zinc-binding protein Proteins 0.000 description 1
• BEAZKUGSCHFXIQ-UHFFFAOYSA-L zinc;diacetate;dihydrate Chemical compound O.O.[Zn+2].CC([O-])=O.CC([O-])=O BEAZKUGSCHFXIQ-UHFFFAOYSA-L 0.000 description 1