CA2611586A1 - Pharmaceutical formulations of amyloid inhibiting compounds - Google Patents

Info

Publication number

CA2611586A1

CA2611586A1 CA002611586A CA2611586A CA2611586A1 CA 2611586 A1 CA2611586 A1 CA 2611586A1 CA 002611586 A CA002611586 A CA 002611586A CA 2611586 A CA2611586 A CA 2611586A CA 2611586 A1 CA2611586 A1 CA 2611586A1

Authority

CA

Canada

Prior art keywords

active agent

mean

formulation

disease

dose

Prior art date

2005-04-12

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
• CIPO
• Discuss

• 230000002401 inhibitory effect Effects 0.000 title abstract description 73
• 150000001875 compounds Chemical class 0.000 title description 308
• 239000008194 pharmaceutical composition Substances 0.000 title description 73
• 239000000203 mixture Substances 0.000 claims abstract description 398
• 238000009472 formulation Methods 0.000 claims abstract description 348
• 238000000034 method Methods 0.000 claims abstract description 178
• 239000013543 active substance Substances 0.000 claims description 146
• 208000024827 Alzheimer disease Diseases 0.000 claims description 137
• SNKZJIOFVMKAOJ-UHFFFAOYSA-N 3-Amino-1-propanesulfonic acid Natural products NCCCS(O)(=O)=O SNKZJIOFVMKAOJ-UHFFFAOYSA-N 0.000 claims description 105
• 230000002496 gastric effect Effects 0.000 claims description 103
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 99
• 150000003839 salts Chemical class 0.000 claims description 68
• 210000004556 brain Anatomy 0.000 claims description 64
• 230000036470 plasma concentration Effects 0.000 claims description 63
• 239000003795 chemical substances by application Substances 0.000 claims description 61
• LZXHHNKULPHARO-UHFFFAOYSA-M (3,4-dichlorophenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].C1=C(Cl)C(Cl)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LZXHHNKULPHARO-UHFFFAOYSA-M 0.000 claims description 48
• 238000011282 treatment Methods 0.000 claims description 42
• 239000003814 drug Substances 0.000 claims description 38
• 230000007423 decrease Effects 0.000 claims description 26
• 206010012289 Dementia Diseases 0.000 claims description 23
• 230000003920 cognitive function Effects 0.000 claims description 22
• 238000012360 testing method Methods 0.000 claims description 21
• 230000000694 effects Effects 0.000 claims description 20
• 230000006872 improvement Effects 0.000 claims description 20
• 230000001965 increasing effect Effects 0.000 claims description 20
• 230000009467 reduction Effects 0.000 claims description 19
• 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 17
• 230000003111 delayed effect Effects 0.000 claims description 15
• 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 15
• 239000002552 dosage form Substances 0.000 claims description 12
• 230000003247 decreasing effect Effects 0.000 claims description 11
• 206010003694 Atrophy Diseases 0.000 claims description 10
• 230000037444 atrophy Effects 0.000 claims description 10
• 230000000087 stabilizing effect Effects 0.000 claims description 10
• 239000000090 biomarker Substances 0.000 claims description 8
• 230000003204 osmotic effect Effects 0.000 claims description 8
• 238000013270 controlled release Methods 0.000 claims description 7
• 238000013265 extended release Methods 0.000 claims description 7
• 238000013268 sustained release Methods 0.000 claims description 7
• 210000001353 entorhinal cortex Anatomy 0.000 claims description 6
• 230000000971 hippocampal effect Effects 0.000 claims description 6
• 239000012730 sustained-release form Substances 0.000 claims description 6
• 230000000541 pulsatile effect Effects 0.000 claims description 5
• 102000044159 Ubiquitin Human genes 0.000 claims description 4
• 108090000848 Ubiquitin Proteins 0.000 claims description 4
• 230000001991 pathophysiological effect Effects 0.000 claims description 4
• 229940124597 therapeutic agent Drugs 0.000 claims description 4
• 229940122041 Cholinesterase inhibitor Drugs 0.000 claims description 2
• 229940099433 NMDA receptor antagonist Drugs 0.000 claims description 2
• 239000000544 cholinesterase inhibitor Substances 0.000 claims description 2
• 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 abstract description 369
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 138
• 230000003941 amyloidogenesis Effects 0.000 abstract description 124
• 201000010099 disease Diseases 0.000 abstract description 121
• 206010002022 amyloidosis Diseases 0.000 abstract description 99
• -1 e.g. Proteins 0.000 description 72
• 125000000217 alkyl group Chemical group 0.000 description 67
• 239000003826 tablet Substances 0.000 description 61
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 55
• 229910052739 hydrogen Inorganic materials 0.000 description 54
• 239000001257 hydrogen Substances 0.000 description 54
• 125000003118 aryl group Chemical group 0.000 description 52
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 49
• 108090000765 processed proteins & peptides Proteins 0.000 description 45
• 102000009091 Amyloidogenic Proteins Human genes 0.000 description 43
• 108010048112 Amyloidogenic Proteins Proteins 0.000 description 43
• 238000000151 deposition Methods 0.000 description 41
• 239000002253 acid Substances 0.000 description 38
• 238000000576 coating method Methods 0.000 description 38
• 150000002148 esters Chemical class 0.000 description 37
• 108090000623 proteins and genes Proteins 0.000 description 37
• 210000004027 cell Anatomy 0.000 description 36
• 230000008021 deposition Effects 0.000 description 35
• 229940079593 drug Drugs 0.000 description 35
• 208000037259 Amyloid Plaque Diseases 0.000 description 34
• 235000018102 proteins Nutrition 0.000 description 34
• 102000004169 proteins and genes Human genes 0.000 description 34
• 238000013103 analytical ultracentrifugation Methods 0.000 description 31
• 125000003342 alkenyl group Chemical group 0.000 description 30
• 229910052757 nitrogen Inorganic materials 0.000 description 30
• 239000011248 coating agent Substances 0.000 description 29
• 125000000753 cycloalkyl group Chemical group 0.000 description 29
• 239000003981 vehicle Substances 0.000 description 29
• 125000000304 alkynyl group Chemical group 0.000 description 28
• 230000035772 mutation Effects 0.000 description 27
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 26
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 26
• 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 26
• 239000000314 lubricant Substances 0.000 description 26
• 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 25
• 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 25
• 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 25
• 229920002683 Glycosaminoglycan Polymers 0.000 description 25
• 230000006870 function Effects 0.000 description 25
• 125000000623 heterocyclic group Chemical group 0.000 description 25
• 239000002702 enteric coating Substances 0.000 description 23
• 238000009505 enteric coating Methods 0.000 description 23
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 23
• 239000004480 active ingredient Substances 0.000 description 22
• 229910052760 oxygen Inorganic materials 0.000 description 21
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 20
• 125000002883 imidazolyl group Chemical group 0.000 description 20
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 19
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 19
• 125000005358 mercaptoalkyl group Chemical group 0.000 description 19
• 239000001301 oxygen Substances 0.000 description 19
• 229920000642 polymer Polymers 0.000 description 19
• 230000002265 prevention Effects 0.000 description 19
• 125000000335 thiazolyl group Chemical group 0.000 description 19
• 125000001425 triazolyl group Chemical group 0.000 description 19
• 238000004090 dissolution Methods 0.000 description 18
• 239000012634 fragment Substances 0.000 description 18
• 239000002775 capsule Substances 0.000 description 17
• 125000004432 carbon atom Chemical group C* 0.000 description 17
• 208000035475 disorder Diseases 0.000 description 17
• 239000000463 material Substances 0.000 description 17
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
• 229920002472 Starch Polymers 0.000 description 16
• 230000003942 amyloidogenic effect Effects 0.000 description 16
• 239000011324 bead Substances 0.000 description 16
• 239000004615 ingredient Substances 0.000 description 16
• 230000003993 interaction Effects 0.000 description 16
• 102000004196 processed proteins & peptides Human genes 0.000 description 16
• 235000019698 starch Nutrition 0.000 description 16
• 150000007513 acids Chemical class 0.000 description 15
• 210000002469 basement membrane Anatomy 0.000 description 15
• 230000015572 biosynthetic process Effects 0.000 description 15
• 150000001768 cations Chemical class 0.000 description 15
• 238000000338 in vitro Methods 0.000 description 15
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 15
• 208000010877 cognitive disease Diseases 0.000 description 14
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 14
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 14
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 14
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 14
• 239000010410 layer Substances 0.000 description 14
• 230000004048 modification Effects 0.000 description 14
• 238000012986 modification Methods 0.000 description 14
• 125000001424 substituent group Chemical group 0.000 description 14
• 208000024891 symptom Diseases 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
• 239000000470 constituent Substances 0.000 description 13
• 229910052736 halogen Inorganic materials 0.000 description 13
• 150000002367 halogens Chemical class 0.000 description 13
• 238000004519 manufacturing process Methods 0.000 description 13
• 239000008107 starch Substances 0.000 description 13
• 229940032147 starch Drugs 0.000 description 13
• 201000010374 Down Syndrome Diseases 0.000 description 12
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 12
• 206010044688 Trisomy 21 Diseases 0.000 description 12
• 238000009825 accumulation Methods 0.000 description 12
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 12
• 229910052799 carbon Inorganic materials 0.000 description 12
• 230000007541 cellular toxicity Effects 0.000 description 12
• 230000008859 change Effects 0.000 description 12
• 239000003085 diluting agent Substances 0.000 description 12
• 210000002784 stomach Anatomy 0.000 description 12
• 102000019034 Chemokines Human genes 0.000 description 11
• 108010012236 Chemokines Proteins 0.000 description 11
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 11
• 102000016611 Proteoglycans Human genes 0.000 description 11
• 108010067787 Proteoglycans Proteins 0.000 description 11
• 230000035508 accumulation Effects 0.000 description 11
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 11
• 229940024606 amino acid Drugs 0.000 description 11
• 235000001014 amino acid Nutrition 0.000 description 11
• 125000000539 amino acid group Chemical group 0.000 description 11
• 150000001413 amino acids Chemical class 0.000 description 11
• 235000010980 cellulose Nutrition 0.000 description 11
• 229920002678 cellulose Polymers 0.000 description 11
• 239000001913 cellulose Substances 0.000 description 11
• 235000019441 ethanol Nutrition 0.000 description 11
• 239000003607 modifier Substances 0.000 description 11
• 210000000056 organ Anatomy 0.000 description 11
• 239000008188 pellet Substances 0.000 description 11
• 239000000843 powder Substances 0.000 description 11
• 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 11
• 125000003831 tetrazolyl group Chemical group 0.000 description 11
• 208000023769 AA amyloidosis Diseases 0.000 description 10
• 206010008111 Cerebral haemorrhage Diseases 0.000 description 10
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
• 235000021355 Stearic acid Nutrition 0.000 description 10
• 125000004429 atom Chemical group 0.000 description 10
• 210000004204 blood vessel Anatomy 0.000 description 10
• 125000002091 cationic group Chemical group 0.000 description 10
• 238000005755 formation reaction Methods 0.000 description 10
• 229940125396 insulin Drugs 0.000 description 10
• 208000027061 mild cognitive impairment Diseases 0.000 description 10
• 230000004770 neurodegeneration Effects 0.000 description 10
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 10
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 10
• 239000008117 stearic acid Substances 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• 208000035143 Bacterial infection Diseases 0.000 description 9
• 108091016585 CD44 antigen Proteins 0.000 description 9
• 102000008055 Heparan Sulfate Proteoglycans Human genes 0.000 description 9
• 229920002971 Heparan sulfate Polymers 0.000 description 9
• 102000004877 Insulin Human genes 0.000 description 9
• 108090001061 Insulin Proteins 0.000 description 9
• 206010035226 Plasma cell myeloma Diseases 0.000 description 9
• 108010071690 Prealbumin Proteins 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• 108090000054 Syndecan-2 Proteins 0.000 description 9
• 208000036142 Viral infection Diseases 0.000 description 9
• 125000001931 aliphatic group Chemical group 0.000 description 9
• 125000003545 alkoxy group Chemical group 0.000 description 9
• 125000003277 amino group Chemical group 0.000 description 9
• 125000003710 aryl alkyl group Chemical group 0.000 description 9
• 125000005129 aryl carbonyl group Chemical group 0.000 description 9
• 208000022362 bacterial infectious disease Diseases 0.000 description 9
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 9
• 235000019700 dicalcium phosphate Nutrition 0.000 description 9
• 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 9
• 239000002662 enteric coated tablet Substances 0.000 description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
• 239000000243 solution Substances 0.000 description 9
• 210000001519 tissue Anatomy 0.000 description 9
• 230000009385 viral infection Effects 0.000 description 9
• 208000034846 Familial Amyloid Neuropathies Diseases 0.000 description 8
• 206010019889 Hereditary neuropathic amyloidosis Diseases 0.000 description 8
• 208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 description 8
• 229930006000 Sucrose Natural products 0.000 description 8
• 206010012601 diabetes mellitus Diseases 0.000 description 8
• 230000008030 elimination Effects 0.000 description 8
• 238000003379 elimination reaction Methods 0.000 description 8
• 125000001072 heteroaryl group Chemical group 0.000 description 8
• 230000000670 limiting effect Effects 0.000 description 8
• 208000002780 macular degeneration Diseases 0.000 description 8
• 235000019359 magnesium stearate Nutrition 0.000 description 8
• 229920001223 polyethylene glycol Polymers 0.000 description 8
• 239000005720 sucrose Substances 0.000 description 8
• 230000002459 sustained effect Effects 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• 201000007905 transthyretin amyloidosis Diseases 0.000 description 8
• 208000023761 AL amyloidosis Diseases 0.000 description 7
• 102000001049 Amyloid Human genes 0.000 description 7
• 108010094108 Amyloid Proteins 0.000 description 7
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 7
• 208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 description 7
• 206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 description 7
• 102000029797 Prion Human genes 0.000 description 7
• 108091000054 Prion Proteins 0.000 description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
• 102000009190 Transthyretin Human genes 0.000 description 7
• 125000002723 alicyclic group Chemical group 0.000 description 7
• 125000003282 alkyl amino group Chemical group 0.000 description 7
• 230000015556 catabolic process Effects 0.000 description 7
• 230000002490 cerebral effect Effects 0.000 description 7
• 238000003776 cleavage reaction Methods 0.000 description 7
• 125000004093 cyano group Chemical group *C#N 0.000 description 7
• 230000001419 dependent effect Effects 0.000 description 7
• 239000003937 drug carrier Substances 0.000 description 7
• 230000002068 genetic effect Effects 0.000 description 7
• 125000005842 heteroatom Chemical group 0.000 description 7
• 238000001727 in vivo Methods 0.000 description 7
• 201000008319 inclusion body myositis Diseases 0.000 description 7
• 239000002502 liposome Substances 0.000 description 7
• 230000007170 pathology Effects 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 239000002243 precursor Substances 0.000 description 7
• 230000007017 scission Effects 0.000 description 7
• 229910052717 sulfur Inorganic materials 0.000 description 7
• 239000011593 sulfur Chemical group 0.000 description 7
• 230000009885 systemic effect Effects 0.000 description 7
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 6
• 206010002023 Amyloidoses Diseases 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 6
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 6
• 229920003134 Eudragit® polymer Polymers 0.000 description 6
• 206010016207 Familial Mediterranean fever Diseases 0.000 description 6
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 6
• 238000004220 aggregation Methods 0.000 description 6
• 150000001408 amides Chemical class 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 210000004369 blood Anatomy 0.000 description 6
• 239000008280 blood Substances 0.000 description 6
• 230000008499 blood brain barrier function Effects 0.000 description 6
• 210000001218 blood-brain barrier Anatomy 0.000 description 6
• 229920002301 cellulose acetate Polymers 0.000 description 6
• DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
• 125000004122 cyclic group Chemical group 0.000 description 6
• 239000006185 dispersion Substances 0.000 description 6
• 239000007903 gelatin capsule Substances 0.000 description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• 239000008101 lactose Substances 0.000 description 6
• 210000002569 neuron Anatomy 0.000 description 6
• 239000000902 placebo Substances 0.000 description 6
• 229940068196 placebo Drugs 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 238000012545 processing Methods 0.000 description 6
• 239000000651 prodrug Substances 0.000 description 6
• 229940002612 prodrug Drugs 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 238000006467 substitution reaction Methods 0.000 description 6
• 235000000346 sugar Nutrition 0.000 description 6
• 108010071619 Apolipoproteins Proteins 0.000 description 5
• 102000007592 Apolipoproteins Human genes 0.000 description 5
• 108020004705 Codon Proteins 0.000 description 5
• 239000001856 Ethyl cellulose Substances 0.000 description 5
• 108010010803 Gelatin Proteins 0.000 description 5
• 206010061218 Inflammation Diseases 0.000 description 5
• 208000022435 Light chain deposition disease Diseases 0.000 description 5
• 206010028980 Neoplasm Diseases 0.000 description 5
• 208000002193 Pain Diseases 0.000 description 5
• 208000024777 Prion disease Diseases 0.000 description 5
• 102100029290 Transthyretin Human genes 0.000 description 5
• 208000016463 Wild type ABeta2M amyloidosis Diseases 0.000 description 5
• 230000002776 aggregation Effects 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 239000003963 antioxidant agent Substances 0.000 description 5
• 235000006708 antioxidants Nutrition 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
• 125000002837 carbocyclic group Chemical group 0.000 description 5
• 150000001721 carbon Chemical group 0.000 description 5
• 238000006243 chemical reaction Methods 0.000 description 5
• 239000003995 emulsifying agent Substances 0.000 description 5
• 230000002708 enhancing effect Effects 0.000 description 5
• 235000019325 ethyl cellulose Nutrition 0.000 description 5
• 229920001249 ethyl cellulose Polymers 0.000 description 5
• 239000000945 filler Substances 0.000 description 5
• 239000008273 gelatin Substances 0.000 description 5
• 229920000159 gelatin Polymers 0.000 description 5
• 235000019322 gelatine Nutrition 0.000 description 5
• 235000011852 gelatine desserts Nutrition 0.000 description 5
• 230000004054 inflammatory process Effects 0.000 description 5
• 230000003834 intracellular effect Effects 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 229910021645 metal ion Inorganic materials 0.000 description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 description 5
• 210000000496 pancreas Anatomy 0.000 description 5
• 239000002245 particle Substances 0.000 description 5
• 230000035515 penetration Effects 0.000 description 5
• 208000033808 peripheral neuropathy Diseases 0.000 description 5
• 239000006187 pill Substances 0.000 description 5
• 229940068917 polyethylene glycols Drugs 0.000 description 5
• 230000008569 process Effects 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 150000008163 sugars Chemical class 0.000 description 5
• 231100000331 toxic Toxicity 0.000 description 5
• 230000002588 toxic effect Effects 0.000 description 5
• 231100000419 toxicity Toxicity 0.000 description 5
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
• 208000020687 AH amyloidosis Diseases 0.000 description 4
• 102100040026 Agrin Human genes 0.000 description 4
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 4
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 4
• 102100036597 Basement membrane-specific heparan sulfate proteoglycan core protein Human genes 0.000 description 4
• 208000019736 Cranial nerve disease Diseases 0.000 description 4
• 206010016202 Familial Amyloidosis Diseases 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• 102000003886 Glycoproteins Human genes 0.000 description 4
• 108090000288 Glycoproteins Proteins 0.000 description 4
• 101000959594 Homo sapiens Agrin Proteins 0.000 description 4
• 101001000001 Homo sapiens Basement membrane-specific heparan sulfate proteoglycan core protein Proteins 0.000 description 4
• 101000772194 Homo sapiens Transthyretin Proteins 0.000 description 4
• 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 4
• 102100025818 Major prion protein Human genes 0.000 description 4
• 101710138751 Major prion protein Proteins 0.000 description 4
• 102100022033 Presenilin-1 Human genes 0.000 description 4
• 108010050254 Presenilins Proteins 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
• 102000054727 Serum Amyloid A Human genes 0.000 description 4
• 206010047700 Vomiting Diseases 0.000 description 4
• 230000009471 action Effects 0.000 description 4
• 125000004442 acylamino group Chemical group 0.000 description 4
• 206010064930 age-related macular degeneration Diseases 0.000 description 4
• 230000006933 amyloid-beta aggregation Effects 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 230000001746 atrial effect Effects 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 239000011230 binding agent Substances 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 208000014826 cranial nerve neuropathy Diseases 0.000 description 4
• 230000034994 death Effects 0.000 description 4
• 230000006735 deficit Effects 0.000 description 4
• 238000006731 degradation reaction Methods 0.000 description 4
• 230000001627 detrimental effect Effects 0.000 description 4
• 238000003745 diagnosis Methods 0.000 description 4
• 238000000502 dialysis Methods 0.000 description 4
• MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 4
• 208000015756 familial Alzheimer disease Diseases 0.000 description 4
• 230000009246 food effect Effects 0.000 description 4
• 210000001035 gastrointestinal tract Anatomy 0.000 description 4
• 235000011187 glycerol Nutrition 0.000 description 4
• 239000003701 inert diluent Substances 0.000 description 4
• 210000000936 intestine Anatomy 0.000 description 4
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
• 210000004185 liver Anatomy 0.000 description 4
• 238000004949 mass spectrometry Methods 0.000 description 4
• 239000011159 matrix material Substances 0.000 description 4
• 230000007246 mechanism Effects 0.000 description 4
• 230000002981 neuropathic effect Effects 0.000 description 4
• 150000002894 organic compounds Chemical class 0.000 description 4
• 238000004806 packaging method and process Methods 0.000 description 4
• 230000001575 pathological effect Effects 0.000 description 4
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 230000000750 progressive effect Effects 0.000 description 4
• 125000006413 ring segment Chemical group 0.000 description 4
• 230000000630 rising effect Effects 0.000 description 4
• 150000003384 small molecules Chemical class 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 159000000000 sodium salts Chemical class 0.000 description 4
• 229940045902 sodium stearyl fumarate Drugs 0.000 description 4
• 239000007787 solid Substances 0.000 description 4
• 239000007909 solid dosage form Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 239000000454 talc Substances 0.000 description 4
• 229910052623 talc Inorganic materials 0.000 description 4
• 235000012222 talc Nutrition 0.000 description 4
• 238000002560 therapeutic procedure Methods 0.000 description 4
• 150000003573 thiols Chemical class 0.000 description 4
• 238000002054 transplantation Methods 0.000 description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
• 239000001993 wax Substances 0.000 description 4
• 239000000080 wetting agent Substances 0.000 description 4
• 229920001817 Agar Polymers 0.000 description 3
• 241000416162 Astragalus gummifer Species 0.000 description 3
• 241000894006 Bacteria Species 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 102000055006 Calcitonin Human genes 0.000 description 3
• 108060001064 Calcitonin Proteins 0.000 description 3
• 241000282472 Canis lupus familiaris Species 0.000 description 3
• 241000282693 Cercopithecidae Species 0.000 description 3
• 208000028698 Cognitive impairment Diseases 0.000 description 3
• 102000012192 Cystatin C Human genes 0.000 description 3
• 108010061642 Cystatin C Proteins 0.000 description 3
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 description 3
• 241000282326 Felis catus Species 0.000 description 3
• 102000004878 Gelsolin Human genes 0.000 description 3
• 108090001064 Gelsolin Proteins 0.000 description 3
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
• 102000015779 HDL Lipoproteins Human genes 0.000 description 3
• 108010010234 HDL Lipoproteins Proteins 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 3
• 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 240000007472 Leucaena leucocephala Species 0.000 description 3
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
• 229930195725 Mannitol Natural products 0.000 description 3
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
• 102100040243 Microtubule-associated protein tau Human genes 0.000 description 3
• 208000034578 Multiple myelomas Diseases 0.000 description 3
• 102000016943 Muramidase Human genes 0.000 description 3
• 108010014251 Muramidase Proteins 0.000 description 3
• 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 3
• 206010028813 Nausea Diseases 0.000 description 3
• 102100022036 Presenilin-2 Human genes 0.000 description 3
• 102000015499 Presenilins Human genes 0.000 description 3
• 206010036673 Primary amyloidosis Diseases 0.000 description 3
• 102000001708 Protein Isoforms Human genes 0.000 description 3
• 108010029485 Protein Isoforms Proteins 0.000 description 3
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
• 206010062237 Renal impairment Diseases 0.000 description 3
• 229910006069 SO3H Inorganic materials 0.000 description 3
• 206010039811 Secondary amyloidosis Diseases 0.000 description 3
• 108700028909 Serum Amyloid A Proteins 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 229920001615 Tragacanth Polymers 0.000 description 3
• 241000700605 Viruses Species 0.000 description 3
• 230000002159 abnormal effect Effects 0.000 description 3
• 238000010521 absorption reaction Methods 0.000 description 3
• 239000008186 active pharmaceutical agent Substances 0.000 description 3
• 125000002252 acyl group Chemical group 0.000 description 3
• 235000010419 agar Nutrition 0.000 description 3
• 230000032683 aging Effects 0.000 description 3
• 235000010443 alginic acid Nutrition 0.000 description 3
• 229920000615 alginic acid Polymers 0.000 description 3
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 3
• 125000004947 alkyl aryl amino group Chemical group 0.000 description 3
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 3
• 125000003275 alpha amino acid group Chemical group 0.000 description 3
• 101150031224 app gene Proteins 0.000 description 3
• 125000001769 aryl amino group Chemical group 0.000 description 3
• 125000005199 aryl carbonyloxy group Chemical group 0.000 description 3
• 125000005110 aryl thio group Chemical group 0.000 description 3
• 125000005200 aryloxy carbonyloxy group Chemical group 0.000 description 3
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
• 210000004958 brain cell Anatomy 0.000 description 3
• BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 3
• 229960004015 calcitonin Drugs 0.000 description 3
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
• 235000013539 calcium stearate Nutrition 0.000 description 3
• 239000008116 calcium stearate Substances 0.000 description 3
• 201000011510 cancer Diseases 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 230000001684 chronic effect Effects 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000011247 coating layer Substances 0.000 description 3
• 230000001149 cognitive effect Effects 0.000 description 3
• 238000007596 consolidation process Methods 0.000 description 3
• 230000001276 controlling effect Effects 0.000 description 3
• 229940109239 creatinine Drugs 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 125000004663 dialkyl amino group Chemical group 0.000 description 3
• 125000004986 diarylamino group Chemical group 0.000 description 3
• 235000014113 dietary fatty acids Nutrition 0.000 description 3
• 239000007884 disintegrant Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 210000000981 epithelium Anatomy 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 201000006061 fatal familial insomnia Diseases 0.000 description 3
• 239000000194 fatty acid Substances 0.000 description 3
• 229930195729 fatty acid Natural products 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 238000001631 haemodialysis Methods 0.000 description 3
• 208000019855 heavy chain deposition disease Diseases 0.000 description 3
• 230000000322 hemodialysis Effects 0.000 description 3
• 201000001421 hyperglycemia Diseases 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 239000005414 inactive ingredient Substances 0.000 description 3
• 125000001041 indolyl group Chemical group 0.000 description 3
• 208000015181 infectious disease Diseases 0.000 description 3
• 230000007794 irritation Effects 0.000 description 3
• 210000004153 islets of langerhan Anatomy 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 208000017169 kidney disease Diseases 0.000 description 3
• 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 3
• 230000007774 longterm Effects 0.000 description 3
• 239000000594 mannitol Substances 0.000 description 3
• 235000010355 mannitol Nutrition 0.000 description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
• 229940016286 microcrystalline cellulose Drugs 0.000 description 3
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
• 239000008108 microcrystalline cellulose Substances 0.000 description 3
• 230000007388 microgliosis Effects 0.000 description 3
• 201000000050 myeloid neoplasm Diseases 0.000 description 3
• 230000008693 nausea Effects 0.000 description 3
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 230000036961 partial effect Effects 0.000 description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
• 239000004014 plasticizer Substances 0.000 description 3
• 125000003367 polycyclic group Chemical group 0.000 description 3
• 231100000857 poor renal function Toxicity 0.000 description 3
• 208000022256 primary systemic amyloidosis Diseases 0.000 description 3
• 229960004063 propylene glycol Drugs 0.000 description 3
• 235000013772 propylene glycol Nutrition 0.000 description 3
• 125000004076 pyridyl group Chemical group 0.000 description 3
• 229910052705 radium Inorganic materials 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 description 3
• 229910052701 rubidium Inorganic materials 0.000 description 3
• 235000010356 sorbitol Nutrition 0.000 description 3
• 239000000600 sorbitol Substances 0.000 description 3
• 210000000952 spleen Anatomy 0.000 description 3
• 230000006641 stabilisation Effects 0.000 description 3
• 238000011105 stabilization Methods 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• 230000008685 targeting Effects 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
• 125000001544 thienyl group Chemical group 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 235000010487 tragacanth Nutrition 0.000 description 3
• 239000000196 tragacanth Substances 0.000 description 3
• 229940116362 tragacanth Drugs 0.000 description 3
• 230000009466 transformation Effects 0.000 description 3
• 230000009278 visceral effect Effects 0.000 description 3
• 229920003176 water-insoluble polymer Polymers 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
• 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
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 208000000044 Amnesia Diseases 0.000 description 2
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 2
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 2
• 206010059245 Angiopathy Diseases 0.000 description 2
• 241000272517 Anseriformes Species 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 241000283707 Capra Species 0.000 description 2
• 101710132601 Capsid protein Proteins 0.000 description 2
• 208000031229 Cardiomyopathies Diseases 0.000 description 2
• 229920008347 Cellulose acetate propionate Polymers 0.000 description 2
• 102000008186 Collagen Human genes 0.000 description 2
• 108010035532 Collagen Proteins 0.000 description 2
• 108010042086 Collagen Type IV Proteins 0.000 description 2
• 102000004266 Collagen Type IV Human genes 0.000 description 2
• 229920002785 Croscarmellose sodium Polymers 0.000 description 2
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
• 206010011878 Deafness Diseases 0.000 description 2
• 206010012735 Diarrhoea Diseases 0.000 description 2
• 206010061818 Disease progression Diseases 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
• 102000016359 Fibronectins Human genes 0.000 description 2
• 108010067306 Fibronectins Proteins 0.000 description 2
• 241000206672 Gelidium Species 0.000 description 2
• 206010018341 Gliosis Diseases 0.000 description 2
• 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 206010023230 Joint stiffness Diseases 0.000 description 2
• 102000007547 Laminin Human genes 0.000 description 2
• 108010085895 Laminin Proteins 0.000 description 2
• 208000007054 Medullary Carcinoma Diseases 0.000 description 2
• 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
• 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
• 208000026139 Memory disease Diseases 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 208000010190 Monoclonal Gammopathy of Undetermined Significance Diseases 0.000 description 2
• 201000002795 Muckle-Wells syndrome Diseases 0.000 description 2
• 229910003827 NRaRb Inorganic materials 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• 206010029164 Nephrotic syndrome Diseases 0.000 description 2
• 206010029350 Neurotoxicity Diseases 0.000 description 2
• 229910004727 OSO3H Inorganic materials 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 241001494479 Pecora Species 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• 206010044221 Toxic encephalopathy Diseases 0.000 description 2
• DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 2
• 208000024780 Urticaria Diseases 0.000 description 2
• 208000027418 Wounds and injury Diseases 0.000 description 2
• 238000002441 X-ray diffraction Methods 0.000 description 2
• 240000008042 Zea mays Species 0.000 description 2
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
• 229920002494 Zein Polymers 0.000 description 2
• 230000023445 activated T cell autonomous cell death Effects 0.000 description 2
• 210000001642 activated microglia Anatomy 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 125000006323 alkenyl amino group Chemical group 0.000 description 2
• 125000005108 alkenylthio group Chemical group 0.000 description 2
• 125000002877 alkyl aryl group Chemical group 0.000 description 2
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
• 125000004691 alkyl thio carbonyl group Chemical group 0.000 description 2
• 125000004414 alkyl thio group Chemical group 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
• 150000001412 amines Chemical group 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 230000000844 anti-bacterial effect Effects 0.000 description 2
• 239000003429 antifungal agent Substances 0.000 description 2
• 229940121375 antifungal agent Drugs 0.000 description 2
• 210000002565 arteriole Anatomy 0.000 description 2
• 210000001367 artery Anatomy 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• 208000037875 astrocytosis Diseases 0.000 description 2
• 230000007341 astrogliosis Effects 0.000 description 2
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 239000006172 buffering agent Substances 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
• 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 2
• 150000007942 carboxylates Chemical class 0.000 description 2
• 230000005779 cell damage Effects 0.000 description 2
• 208000037887 cell injury Diseases 0.000 description 2
• 229920006217 cellulose acetate butyrate Polymers 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 208000019902 chronic diarrheal disease Diseases 0.000 description 2
• 208000037976 chronic inflammation Diseases 0.000 description 2
• 208000035850 clinical syndrome Diseases 0.000 description 2
• 229920001436 collagen Polymers 0.000 description 2
• IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 2
• 238000010276 construction Methods 0.000 description 2
• 239000012792 core layer Substances 0.000 description 2
• 235000005822 corn Nutrition 0.000 description 2
• 230000001054 cortical effect Effects 0.000 description 2
• 235000012343 cottonseed oil Nutrition 0.000 description 2
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
• 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 2
• 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 description 2
• 150000001925 cycloalkenes Chemical class 0.000 description 2
• ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
• 231100000895 deafness Toxicity 0.000 description 2
• 230000007850 degeneration Effects 0.000 description 2
• 230000005750 disease progression Effects 0.000 description 2
• 239000002270 dispersing agent 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
• 239000008298 dragée Substances 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 230000004064 dysfunction Effects 0.000 description 2
• 230000002124 endocrine Effects 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• 230000008579 epileptogenesis Effects 0.000 description 2
• 125000004185 ester group Chemical group 0.000 description 2
• MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 210000002744 extracellular matrix Anatomy 0.000 description 2
• 210000001723 extracellular space Anatomy 0.000 description 2
• 235000019197 fats Nutrition 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 230000003619 fibrillary effect Effects 0.000 description 2
• 230000035557 fibrillogenesis Effects 0.000 description 2
• 239000007888 film coating Substances 0.000 description 2
• 238000009501 film coating Methods 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 235000021471 food effect Nutrition 0.000 description 2
• 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 2
• 230000030136 gastric emptying Effects 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 230000035876 healing Effects 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 208000016354 hearing loss disease Diseases 0.000 description 2
• 210000002216 heart Anatomy 0.000 description 2
• 210000005003 heart tissue Anatomy 0.000 description 2
• 150000002390 heteroarenes Chemical class 0.000 description 2
• 210000001320 hippocampus Anatomy 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
• 238000003384 imaging method Methods 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 238000002329 infrared spectrum Methods 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 238000011835 investigation Methods 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• 238000002595 magnetic resonance imaging Methods 0.000 description 2
• 230000006984 memory degeneration Effects 0.000 description 2
• 208000023060 memory loss Diseases 0.000 description 2
• 230000000813 microbial effect Effects 0.000 description 2
• 239000007912 modified release tablet Substances 0.000 description 2
• 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 description 2
• 230000000877 morphologic effect Effects 0.000 description 2
• 238000000465 moulding Methods 0.000 description 2
• 210000001087 myotubule Anatomy 0.000 description 2
• 210000004898 n-terminal fragment Anatomy 0.000 description 2
• 210000002241 neurite Anatomy 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 230000000926 neurological effect Effects 0.000 description 2
• 230000016273 neuron death Effects 0.000 description 2
• 230000007823 neuropathy Effects 0.000 description 2
• 201000001119 neuropathy Diseases 0.000 description 2
• 230000007135 neurotoxicity Effects 0.000 description 2
• 231100000228 neurotoxicity Toxicity 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 230000004768 organ dysfunction Effects 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 239000002357 osmotic agent Substances 0.000 description 2
• 230000001717 pathogenic effect Effects 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 239000002304 perfume Substances 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 210000000578 peripheral nerve Anatomy 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 150000004804 polysaccharides Polymers 0.000 description 2
• 229920002689 polyvinyl acetate Polymers 0.000 description 2
• 239000011118 polyvinyl acetate Substances 0.000 description 2
• 239000011148 porous material Substances 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000011241 protective layer Substances 0.000 description 2
• 230000012846 protein folding Effects 0.000 description 2
• 230000006337 proteolytic cleavage Effects 0.000 description 2
• 239000008213 purified water Substances 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000002207 retinal effect Effects 0.000 description 2
• 238000005070 sampling Methods 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 229930195734 saturated hydrocarbon Natural products 0.000 description 2
• 208000008864 scrapie Diseases 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 230000003248 secreting effect Effects 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
• 235000012239 silicon dioxide Nutrition 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• 239000008109 sodium starch glycolate Substances 0.000 description 2
• 229920003109 sodium starch glycolate Polymers 0.000 description 2
• 229940079832 sodium starch glycolate Drugs 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 238000010186 staining Methods 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 2
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 238000013269 sustained drug release Methods 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 230000008961 swelling Effects 0.000 description 2
• 239000007916 tablet composition Substances 0.000 description 2
• 230000004797 therapeutic response Effects 0.000 description 2
• 210000001685 thyroid gland Anatomy 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 230000009261 transgenic effect Effects 0.000 description 2
• 230000007704 transition Effects 0.000 description 2
• URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 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
• 201000008827 tuberculosis Diseases 0.000 description 2
• 210000002700 urine Anatomy 0.000 description 2
• 210000003462 vein Anatomy 0.000 description 2
• 230000008673 vomiting Effects 0.000 description 2
• 208000027121 wild type ATTR amyloidosis Diseases 0.000 description 2
• 239000005019 zein Substances 0.000 description 2
• 229940093612 zein Drugs 0.000 description 2
• QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
• 125000006729 (C2-C5) alkenyl group Chemical group 0.000 description 1
• 125000006730 (C2-C5) alkynyl group Chemical group 0.000 description 1
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
• GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-UHFFFAOYSA-N 0.000 description 1
• DSIHEWRAJBNNLQ-UHFFFAOYSA-N 3-(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)propane-1-sulfonic acid Chemical compound C1N(CCCS(=O)(=O)O)CCC(C=2C=CC=CC=2)=C1 DSIHEWRAJBNNLQ-UHFFFAOYSA-N 0.000 description 1
• VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)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](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 1
• PEPBFCOIJRULGJ-UHFFFAOYSA-N 3h-1,2,3-benzodioxazole Chemical compound C1=CC=C2NOOC2=C1 PEPBFCOIJRULGJ-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
• BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• 208000024667 ABeta amyloidosis, Dutch type Diseases 0.000 description 1
• 208000023697 ABri amyloidosis Diseases 0.000 description 1
• 208000018282 ACys amyloidosis Diseases 0.000 description 1
• 208000017227 ADan amyloidosis Diseases 0.000 description 1
• QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 1
• 102100033639 Acetylcholinesterase Human genes 0.000 description 1
• 108010022752 Acetylcholinesterase Proteins 0.000 description 1
• 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
• 206010048998 Acute phase reaction Diseases 0.000 description 1
• 102100034112 Alkyldihydroxyacetonephosphate synthase, peroxisomal Human genes 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 241000272525 Anas platyrhynchos Species 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 235000003276 Apios tuberosa Nutrition 0.000 description 1
• 108010060159 Apolipoprotein E4 Proteins 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• 208000036487 Arthropathies Diseases 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 101800001288 Atrial natriuretic factor Proteins 0.000 description 1
• 102400001282 Atrial natriuretic peptide Human genes 0.000 description 1
• 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
• 206010061666 Autonomic neuropathy Diseases 0.000 description 1
• 230000007082 Aβ accumulation Effects 0.000 description 1
• 206010004146 Basal cell carcinoma Diseases 0.000 description 1
• 208000027496 Behcet disease Diseases 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• 102100021257 Beta-secretase 1 Human genes 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 201000004569 Blindness Diseases 0.000 description 1
• 229940123923 Butyrylcholinesterase inhibitor Drugs 0.000 description 1
• 108010075254 C-Peptide Proteins 0.000 description 1
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
• 201000000166 CST3-related cerebral amyloid angiopathy Diseases 0.000 description 1
• 101100016363 Caenorhabditis elegans his-67 gene Proteins 0.000 description 1
• 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
• 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 208000005024 Castleman disease Diseases 0.000 description 1
• 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
• 241000606161 Chlamydia Species 0.000 description 1
• 229920001287 Chondroitin sulfate Polymers 0.000 description 1
• NYNKCGWJPNZJMI-UHFFFAOYSA-N Clebopride malate Chemical compound [O-]C(=O)C(O)CC(O)=O.COC1=CC(N)=C(Cl)C=C1C(=O)NC1CC[NH+](CC=2C=CC=CC=2)CC1 NYNKCGWJPNZJMI-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 208000031124 Dementia Alzheimer type Diseases 0.000 description 1
• 229920000045 Dermatan sulfate Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 101100456896 Drosophila melanogaster metl gene Proteins 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 229920003163 Eudragit® NE 30 D Polymers 0.000 description 1
• 244000207620 Euterpe oleracea Species 0.000 description 1
• 235000012601 Euterpe oleracea Nutrition 0.000 description 1
• 108050001049 Extracellular proteins Proteins 0.000 description 1
• 101710163305 Fibril protein Proteins 0.000 description 1
• 108010049003 Fibrinogen Proteins 0.000 description 1
• 102000008946 Fibrinogen Human genes 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• 229930091371 Fructose Natural products 0.000 description 1
• RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
• 239000005715 Fructose Substances 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 244000194101 Ginkgo biloba Species 0.000 description 1
• 235000008100 Ginkgo biloba Nutrition 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 241000282575 Gorilla Species 0.000 description 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 208000028782 Hereditary disease Diseases 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
• 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 101000799143 Homo sapiens Alkyldihydroxyacetonephosphate synthase, peroxisomal Proteins 0.000 description 1
• 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 1
• YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
• 208000035150 Hypercholesterolemia Diseases 0.000 description 1
• 201000000162 ITM2B-related cerebral amyloid angiopathy 1 Diseases 0.000 description 1
• 201000000194 ITM2B-related cerebral amyloid angiopathy 2 Diseases 0.000 description 1
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
• 208000026350 Inborn Genetic disease Diseases 0.000 description 1
• 206010022489 Insulin Resistance Diseases 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 208000012659 Joint disease Diseases 0.000 description 1
• 206010023232 Joint swelling Diseases 0.000 description 1
• 208000003456 Juvenile Arthritis Diseases 0.000 description 1
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
• 229920000288 Keratan sulfate Polymers 0.000 description 1
• 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
• QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• 206010024229 Leprosy Diseases 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 206010025391 Macroglossia Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 229920002774 Maltodextrin Polymers 0.000 description 1
• 239000005913 Maltodextrin Substances 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229920003091 Methocel™ Polymers 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 241000238367 Mya arenaria Species 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010057178 Osteoarthropathies Diseases 0.000 description 1
• 206010031256 Osteomyelitis chronic Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 241000282579 Pan Species 0.000 description 1
• 208000002774 Paraproteinemias Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 102000015731 Peptide Hormones Human genes 0.000 description 1
• 108010038988 Peptide Hormones Proteins 0.000 description 1
• 208000037581 Persistent Infection Diseases 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000004952 Polyamide Substances 0.000 description 1
• 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
• 206010036105 Polyneuropathy Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 108010036933 Presenilin-1 Proteins 0.000 description 1
• 108010036908 Presenilin-2 Proteins 0.000 description 1
• 208000004210 Pressure Ulcer Diseases 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 229920003110 Primojel Polymers 0.000 description 1
• 108010076181 Proinsulin Proteins 0.000 description 1
• 102000003946 Prolactin Human genes 0.000 description 1
• 108010057464 Prolactin Proteins 0.000 description 1
• 206010036832 Prolactinoma Diseases 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
• 206010037601 Pyelonephritis chronic Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 208000033464 Reiter syndrome Diseases 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 206010038748 Restrictive cardiomyopathy Diseases 0.000 description 1
• 235000004443 Ricinus communis Nutrition 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
• 241000283984 Rodentia Species 0.000 description 1
• 229910006127 SO3X Inorganic materials 0.000 description 1
• 235000019485 Safflower oil Nutrition 0.000 description 1
• 201000010848 Schnitzler Syndrome Diseases 0.000 description 1
• 241000555745 Sciuridae Species 0.000 description 1
• 206010039966 Senile dementia Diseases 0.000 description 1
• 101710190759 Serum amyloid A protein Proteins 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 241000282458 Ursus sp. Species 0.000 description 1
• FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• TYVWBCMQECJNSK-UHFFFAOYSA-N [2-methyl-3-(2-methylprop-2-enoyloxy)butan-2-yl]azanium;chloride Chemical compound [Cl-].CC([NH3+])(C)C(C)OC(=O)C(C)=C TYVWBCMQECJNSK-UHFFFAOYSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• 239000003070 absorption delaying agent Substances 0.000 description 1
• 235000003650 acai Nutrition 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 238000001994 activation Methods 0.000 description 1
• 230000004658 acute-phase response Effects 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000003302 alkenyloxy group Chemical group 0.000 description 1
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
• 125000005233 alkylalcohol group Chemical group 0.000 description 1
• FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
• 229940087168 alpha tocopherol Drugs 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 230000007450 amyloidogenic pathway Effects 0.000 description 1
• 210000003484 anatomy Anatomy 0.000 description 1
• 238000000848 angular dependent Auger electron spectroscopy Methods 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 125000003435 aroyl group Chemical group 0.000 description 1
• 208000011775 arteriosclerosis disease Diseases 0.000 description 1
• 125000004658 aryl carbonyl amino group Chemical group 0.000 description 1
• 125000004350 aryl cycloalkyl group Chemical group 0.000 description 1
• 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 208000006521 atrial standstill Diseases 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 229910052788 barium Inorganic materials 0.000 description 1
• DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 230000008436 biogenesis Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 230000002051 biphasic effect Effects 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 1
• 208000025698 brain inflammatory disease Diseases 0.000 description 1
• 201000009267 bronchiectasis Diseases 0.000 description 1
• 239000006189 buccal tablet Substances 0.000 description 1
• 235000019437 butane-1,3-diol Nutrition 0.000 description 1
• 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 235000012241 calcium silicate Nutrition 0.000 description 1
• UEJWRQDKIBEMCR-UHFFFAOYSA-L calcium;sodium;carbonate Chemical compound [Na+].[Ca+2].[O-]C([O-])=O UEJWRQDKIBEMCR-UHFFFAOYSA-L 0.000 description 1
• 239000007894 caplet Substances 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
• NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 230000006652 catabolic pathway Effects 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 235000013330 chicken meat Nutrition 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 229940059329 chondroitin sulfate Drugs 0.000 description 1
• 210000002987 choroid plexus Anatomy 0.000 description 1
• 230000006020 chronic inflammation Effects 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 201000006368 chronic pyelonephritis Diseases 0.000 description 1
• 239000004927 clay Substances 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 230000007278 cognition impairment Effects 0.000 description 1
• 230000006999 cognitive decline Effects 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000009500 colour coating Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 238000013329 compounding Methods 0.000 description 1
• 239000007891 compressed tablet Substances 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000002285 corn oil Substances 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
• 239000002385 cottonseed oil Substances 0.000 description 1
• 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 201000003278 cryoglobulinemia Diseases 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 0.000 description 1
• 125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• KDUIUFJBNGTBMD-VXMYFEMYSA-N cyclooctatetraene Chemical compound C1=C\C=C/C=C\C=C1 KDUIUFJBNGTBMD-VXMYFEMYSA-N 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 229960001305 cysteine hydrochloride Drugs 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000000994 depressogenic effect Effects 0.000 description 1
• AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
• 229940051593 dermatan sulfate Drugs 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 229940096516 dextrates Drugs 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 1
• 229940031954 dibutyl sebacate Drugs 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
• 125000005056 dihydrothiazolyl group Chemical group S1C(NC=C1)* 0.000 description 1
• UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
• 230000003467 diminishing effect Effects 0.000 description 1
• 231100000676 disease causative agent Toxicity 0.000 description 1
• 238000007922 dissolution test Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 229960003530 donepezil Drugs 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 229940126534 drug product Drugs 0.000 description 1
• 229940088679 drug related substance Drugs 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 208000036536 dutch type ABeta amyloidosis Diseases 0.000 description 1
• 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 206010014599 encephalitis Diseases 0.000 description 1
• 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 229940012952 fibrinogen Drugs 0.000 description 1
• 102000034240 fibrous proteins Human genes 0.000 description 1
• 108091005899 fibrous proteins Proteins 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 238000009093 first-line therapy Methods 0.000 description 1
• 229940014144 folate Drugs 0.000 description 1
• OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 1
• 235000019152 folic acid Nutrition 0.000 description 1
• 239000011724 folic acid Substances 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 229960003980 galantamine Drugs 0.000 description 1
• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-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
• 239000000499 gel Substances 0.000 description 1
• 208000016361 genetic disease Diseases 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 230000009229 glucose formation Effects 0.000 description 1
• 238000007446 glucose tolerance test Methods 0.000 description 1
• 150000004676 glycans Polymers 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
• 239000001087 glyceryl triacetate Substances 0.000 description 1
• 235000013773 glyceryl triacetate Nutrition 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 210000002288 golgi apparatus Anatomy 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 201000009277 hairy cell leukemia Diseases 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 208000017105 hereditary amyloidosis Diseases 0.000 description 1
• 125000004475 heteroaralkyl group Chemical group 0.000 description 1
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 229920002674 hyaluronan Polymers 0.000 description 1
• KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
• 229940099552 hyaluronan Drugs 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
• 150000002433 hydrophilic molecules Chemical class 0.000 description 1
• 229920001477 hydrophilic polymer Polymers 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
• 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
• 125000001841 imino group Chemical group [H]N=* 0.000 description 1
• 238000007654 immersion Methods 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 230000004968 inflammatory condition Effects 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 208000021005 inheritance pattern Diseases 0.000 description 1
• 208000019715 inherited Creutzfeldt-Jakob disease Diseases 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 230000000266 injurious effect Effects 0.000 description 1
• 230000003914 insulin secretion Effects 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 229960004903 invert sugar Drugs 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 210000001503 joint Anatomy 0.000 description 1
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 239000004816 latex Substances 0.000 description 1
• 229920000126 latex Polymers 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 210000003712 lysosome Anatomy 0.000 description 1
• 230000001868 lysosomic effect Effects 0.000 description 1
• 239000004325 lysozyme Substances 0.000 description 1
• 235000010335 lysozyme Nutrition 0.000 description 1
• 229960000274 lysozyme Drugs 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 239000000347 magnesium hydroxide Substances 0.000 description 1
• 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
• HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 235000019792 magnesium silicate Nutrition 0.000 description 1
• 229910052919 magnesium silicate Inorganic materials 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 229940035034 maltodextrin Drugs 0.000 description 1
• 150000008146 mannosides Chemical class 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 239000013563 matrix tablet Substances 0.000 description 1
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
• BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
• 229960004640 memantine Drugs 0.000 description 1
• 230000003340 mental effect Effects 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 125000005397 methacrylic acid ester group Chemical group 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 150000002741 methionine derivatives Chemical class 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 210000003632 microfilament Anatomy 0.000 description 1
• 210000000274 microglia Anatomy 0.000 description 1
• 230000006724 microglial activation Effects 0.000 description 1
• 239000004005 microsphere Substances 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000007932 molded tablet Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 239000002324 mouth wash Substances 0.000 description 1
• 210000004457 myocytus nodalis Anatomy 0.000 description 1
• 210000004897 n-terminal region Anatomy 0.000 description 1
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
• 229960002009 naproxen Drugs 0.000 description 1
• 230000001452 natriuretic effect Effects 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 230000036403 neuro physiology Effects 0.000 description 1
• 231100000189 neurotoxic Toxicity 0.000 description 1
• 230000002887 neurotoxic effect Effects 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 210000004789 organ system Anatomy 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 230000004203 pancreatic function Effects 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 210000004738 parenchymal cell Anatomy 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000000813 peptide hormone Substances 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 238000012831 peritoneal equilibrium test Methods 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 239000008063 pharmaceutical solvent Substances 0.000 description 1
• 238000011422 pharmacological therapy Methods 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 235000011007 phosphoric acid Nutrition 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 125000005498 phthalate group Chemical group 0.000 description 1
• 230000010399 physical interaction Effects 0.000 description 1
• 230000007505 plaque formation Effects 0.000 description 1
• 208000010626 plasma cell neoplasm Diseases 0.000 description 1
• 210000004180 plasmocyte Anatomy 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229920002647 polyamide Polymers 0.000 description 1
• 230000007824 polyneuropathy Effects 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
• 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
• 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
• 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
• 238000012636 positron electron tomography Methods 0.000 description 1
• 238000012877 positron emission topography Methods 0.000 description 1
• 230000001323 posttranslational effect Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 238000004321 preservation Methods 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 229940097325 prolactin Drugs 0.000 description 1
• 150000003147 proline derivatives Chemical class 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 239000000473 propyl gallate Substances 0.000 description 1
• 235000010388 propyl gallate Nutrition 0.000 description 1
• 229940075579 propyl gallate Drugs 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 239000011253 protective coating Substances 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 230000004845 protein aggregation Effects 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 201000001474 proteinuria Diseases 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 201000010174 renal carcinoma Diseases 0.000 description 1
• 208000012263 renal involvement Diseases 0.000 description 1
• 239000003340 retarding agent Substances 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 229960004136 rivastigmine Drugs 0.000 description 1
• 235000005713 safflower oil Nutrition 0.000 description 1
• 239000003813 safflower oil Substances 0.000 description 1
• 238000013341 scale-up Methods 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 238000009094 second-line therapy Methods 0.000 description 1
• 230000000580 secretagogue effect Effects 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 210000001625 seminal vesicle Anatomy 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• 238000002603 single-photon emission computed tomography Methods 0.000 description 1
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
• 229940100996 sodium bisulfate Drugs 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
• 229940001584 sodium metabisulfite Drugs 0.000 description 1
• 235000010262 sodium metabisulphite Nutrition 0.000 description 1
• 229940001482 sodium sulfite Drugs 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• CPCPXZQVVRATNS-UHFFFAOYSA-M sodium;1-aminopropane-1-sulfonate Chemical compound [Na+].CCC(N)S([O-])(=O)=O CPCPXZQVVRATNS-UHFFFAOYSA-M 0.000 description 1
• KMGJRCNLDZGSFX-UHFFFAOYSA-M sodium;3-aminopropane-1-sulfonate Chemical compound [Na+].NCCCS([O-])(=O)=O KMGJRCNLDZGSFX-UHFFFAOYSA-M 0.000 description 1
• 239000008279 sol Substances 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000007480 spreading Effects 0.000 description 1
• 238000003892 spreading Methods 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 239000003206 sterilizing agent Substances 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
• 125000000542 sulfonic acid group Chemical group 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 108010033090 surfactant protein A receptor Proteins 0.000 description 1
• 239000007939 sustained release tablet Substances 0.000 description 1
• 238000002636 symptomatic treatment Methods 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 229960001685 tacrine Drugs 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
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000004001 thioalkyl group Chemical group 0.000 description 1
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 229940036555 thyroid hormone Drugs 0.000 description 1
• 239000005495 thyroid hormone Substances 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 235000010215 titanium dioxide Nutrition 0.000 description 1
• AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
• 229960000984 tocofersolan Drugs 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 229960002622 triacetin Drugs 0.000 description 1
• 150000003852 triazoles Chemical class 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
• 238000010977 unit operation Methods 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 201000010653 vesiculitis Diseases 0.000 description 1
• 210000001835 viscera Anatomy 0.000 description 1
• 230000004393 visual impairment Effects 0.000 description 1
• 235000019155 vitamin A Nutrition 0.000 description 1
• 239000011719 vitamin A 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
• 229940045997 vitamin a Drugs 0.000 description 1
• 235000012431 wafers Nutrition 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1
• 230000036642 wellbeing Effects 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 239000002076 α-tocopherol Substances 0.000 description 1
• 235000004835 α-tocopherol Nutrition 0.000 description 1