CA2524034A1 - Utilisations de composes modulant les canaux ioniques - Google Patents

Utilisations de composes modulant les canaux ioniques Download PDF

Info

Publication number: CA2524034A1
Authority: CA; Canada
Prior art keywords: ion channel; channel modulating; hydrogen; subject; modulating compound
Prior art date: 2003-05-02
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

Application number

CA002524034A

Other languages

English (en)

Inventor

Gregory N. Beatch

Alan Ezrin

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Cardiome Pharma Corp

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

2003-05-02

Filing date

2004-05-03

Publication date

2004-11-18

2004-05-03 Application filed by Individual filed Critical Individual

2004-11-18 Publication of CA2524034A1 publication Critical patent/CA2524034A1/fr

Status Abandoned legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 883
102000004310 Ion Channels Human genes 0.000 title claims abstract description 598
239000000203 mixture Substances 0.000 claims abstract description 392
238000000034 method Methods 0.000 claims abstract description 270
238000009472 formulation Methods 0.000 claims abstract description 223
-1 cyclohexylamine ether compounds Chemical class 0.000 claims abstract description 219
206010003119 arrhythmia Diseases 0.000 claims abstract description 84
230000006793 arrhythmia Effects 0.000 claims abstract description 78
206010003658 Atrial Fibrillation Diseases 0.000 claims abstract description 48
239000001257 hydrogen Substances 0.000 claims description 203
229910052739 hydrogen Inorganic materials 0.000 claims description 203
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 184
150000003839 salts Chemical class 0.000 claims description 95
239000012453 solvate Substances 0.000 claims description 84
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 67
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 65
229910052760 oxygen Inorganic materials 0.000 claims description 63
229910052717 sulfur Inorganic materials 0.000 claims description 63
229910052757 nitrogen Inorganic materials 0.000 claims description 58
125000003118 aryl group Chemical group 0.000 claims description 54
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 53
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
210000002381 plasma Anatomy 0.000 claims description 44
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 41
239000001301 oxygen Substances 0.000 claims description 41
239000000460 chlorine Chemical group 0.000 claims description 39
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 38
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 38
229910052794 bromium Inorganic materials 0.000 claims description 38
229910052801 chlorine Inorganic materials 0.000 claims description 38
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 37
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 36
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 36
239000011737 fluorine Chemical group 0.000 claims description 36
229910052731 fluorine Inorganic materials 0.000 claims description 36
239000011593 sulfur Substances 0.000 claims description 32
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 31
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 30
125000001424 substituent group Chemical group 0.000 claims description 30
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 29
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 27
125000005842 heteroatom Chemical group 0.000 claims description 26
125000003003 spiro group Chemical group 0.000 claims description 25
125000000623 heterocyclic group Chemical group 0.000 claims description 23
229910052799 carbon Inorganic materials 0.000 claims description 21
125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
241000282414 Homo sapiens Species 0.000 claims description 20
241001465754 Metazoa Species 0.000 claims description 20
125000006413 ring segment Chemical group 0.000 claims description 20
125000001246 bromo group Chemical group Br* 0.000 claims description 19
238000001990 intravenous administration Methods 0.000 claims description 19
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
125000006828 (C2-C7) alkoxycarbonyl group Chemical group 0.000 claims description 15
125000000204 (C2-C4) acyl group Chemical group 0.000 claims description 11
125000004122 cyclic group Chemical group 0.000 claims description 9
125000004043 oxo group Chemical group O=* 0.000 claims description 9
125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
206010003662 Atrial flutter Diseases 0.000 claims description 5
208000004731 long QT syndrome Diseases 0.000 claims description 5
206010040639 Sick sinus syndrome Diseases 0.000 claims description 4
201000008803 Wolff-Parkinson-white syndrome Diseases 0.000 claims description 4
230000002028 premature Effects 0.000 claims description 4
206010003130 Arrhythmia supraventricular Diseases 0.000 claims description 3
206010003671 Atrioventricular Block Diseases 0.000 claims description 3
208000010271 Heart Block Diseases 0.000 claims description 3
208000003734 Supraventricular Tachycardia Diseases 0.000 claims description 3
208000009729 Ventricular Premature Complexes Diseases 0.000 claims description 3
206010047289 Ventricular extrasystoles Diseases 0.000 claims description 3
230000008602 contraction Effects 0.000 claims description 3
208000003663 ventricular fibrillation Diseases 0.000 claims description 3
206010047302 ventricular tachycardia Diseases 0.000 claims description 3
239000007909 solid dosage form Substances 0.000 claims description 2
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 8
239000008297 liquid dosage form Substances 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 38
201000010099 disease Diseases 0.000 abstract description 33
238000011282 treatment Methods 0.000 abstract description 27
230000002265 prevention Effects 0.000 abstract description 20
230000036470 plasma concentration Effects 0.000 abstract description 18
150000002170 ethers Chemical class 0.000 abstract description 3
PAFZNILMFXTMIY-UHFFFAOYSA-N Cyclohexylamine Natural products NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 abstract 1
108090000862 Ion Channels Proteins 0.000 description 505
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 111
MHWUUEBDNXLKJI-UHFFFAOYSA-N 1-(1-aminocyclohexyl)oxycyclohexan-1-amine Chemical class C1CCCCC1(N)OC1(N)CCCCC1 MHWUUEBDNXLKJI-UHFFFAOYSA-N 0.000 description 67
239000003814 drug Substances 0.000 description 60
229940079593 drug Drugs 0.000 description 59
230000037058 blood plasma level Effects 0.000 description 49
239000003826 tablet Substances 0.000 description 42
238000013270 controlled release Methods 0.000 description 41
125000000753 cycloalkyl group Chemical group 0.000 description 35
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
239000002552 dosage form Substances 0.000 description 32
230000000747 cardiac effect Effects 0.000 description 31
230000033764 rhythmic process Effects 0.000 description 28
238000010521 absorption reaction Methods 0.000 description 27
230000002209 hydrophobic effect Effects 0.000 description 25
BXQJYIXHTMSDRB-UHFFFAOYSA-N cyclohexane;hydrochloride Chemical compound Cl.C1CCCCC1 BXQJYIXHTMSDRB-UHFFFAOYSA-N 0.000 description 24
230000000694 effects Effects 0.000 description 24
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 24
239000000546 pharmaceutical excipient Substances 0.000 description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 22
239000011159 matrix material Substances 0.000 description 22
150000002148 esters Chemical class 0.000 description 21
230000000541 pulsatile effect Effects 0.000 description 21
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 20
239000011734 sodium Substances 0.000 description 20
239000000243 solution Substances 0.000 description 20
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 19
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 19
229910052708 sodium Inorganic materials 0.000 description 19
241000282472 Canis lupus familiaris Species 0.000 description 18
125000004423 acyloxy group Chemical group 0.000 description 18
239000012729 immediate-release (IR) formulation Substances 0.000 description 18
238000001802 infusion Methods 0.000 description 18
239000000314 lubricant Substances 0.000 description 18
150000001408 amides Chemical class 0.000 description 17
125000003277 amino group Chemical group 0.000 description 17
125000004432 carbon atom Chemical group C* 0.000 description 17
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 16
150000002500 ions Chemical class 0.000 description 16
239000002207 metabolite Substances 0.000 description 16
229920000642 polymer Polymers 0.000 description 16
239000002243 precursor Substances 0.000 description 16
239000000651 prodrug Substances 0.000 description 16
229940002612 prodrug Drugs 0.000 description 16
239000013522 chelant Substances 0.000 description 15
239000000463 material Substances 0.000 description 15
230000002503 metabolic effect Effects 0.000 description 15
239000007787 solid Substances 0.000 description 15
239000003795 chemical substances by application Substances 0.000 description 14
239000003085 diluting agent Substances 0.000 description 14
230000006870 function Effects 0.000 description 14
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 13
229920002472 Starch Polymers 0.000 description 13
235000021355 Stearic acid Nutrition 0.000 description 13
125000000217 alkyl group Chemical group 0.000 description 13
239000007788 liquid Substances 0.000 description 13
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 13
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 13
235000019698 starch Nutrition 0.000 description 13
239000008117 stearic acid Substances 0.000 description 13
230000001225 therapeutic effect Effects 0.000 description 13
125000004183 alkoxy alkyl group Chemical group 0.000 description 12
235000010980 cellulose Nutrition 0.000 description 12
229920002678 cellulose Polymers 0.000 description 12
239000001913 cellulose Substances 0.000 description 12
150000002430 hydrocarbons Chemical group 0.000 description 12
239000001993 wax Substances 0.000 description 12
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 11
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 11
125000004453 alkoxycarbonyl group Chemical group 0.000 description 11
239000008101 lactose Substances 0.000 description 11
239000011777 magnesium Substances 0.000 description 11
229910052749 magnesium Inorganic materials 0.000 description 11
230000001404 mediated effect Effects 0.000 description 11
239000000843 powder Substances 0.000 description 11
229940032147 starch Drugs 0.000 description 11
239000008107 starch Substances 0.000 description 11
239000000126 substance Substances 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
108091006146 Channels Proteins 0.000 description 10
239000012458 free base Substances 0.000 description 10
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
239000000725 suspension Substances 0.000 description 10
239000004698 Polyethylene Substances 0.000 description 9
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
230000001154 acute effect Effects 0.000 description 9
238000000576 coating method Methods 0.000 description 9
125000002768 hydroxyalkyl group Chemical group 0.000 description 9
229920000573 polyethylene Polymers 0.000 description 9
230000008569 process Effects 0.000 description 9
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 8
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 8
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
239000011230 binding agent Substances 0.000 description 8
239000000969 carrier Substances 0.000 description 8
238000007906 compression Methods 0.000 description 8
230000006835 compression Effects 0.000 description 8
238000004090 dissolution Methods 0.000 description 8
239000000945 filler Substances 0.000 description 8
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 8
229920001223 polyethylene glycol Polymers 0.000 description 8
150000001412 amines Chemical class 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
238000012512 characterization method Methods 0.000 description 7
239000011248 coating agent Substances 0.000 description 7
230000001186 cumulative effect Effects 0.000 description 7
125000001033 ether group Chemical group 0.000 description 7
229930195733 hydrocarbon Natural products 0.000 description 7
239000004615 ingredient Substances 0.000 description 7
230000002401 inhibitory effect Effects 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
125000004430 oxygen atom Chemical group O* 0.000 description 7
239000001856 Ethyl cellulose Substances 0.000 description 6
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
125000003545 alkoxy group Chemical group 0.000 description 6
239000003416 antiarrhythmic agent Substances 0.000 description 6
239000003963 antioxidant agent Substances 0.000 description 6
235000006708 antioxidants Nutrition 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
DCKVRNILNZRZTH-UHFFFAOYSA-N cyclopentane;hydrochloride Chemical compound Cl.C1CCCC1 DCKVRNILNZRZTH-UHFFFAOYSA-N 0.000 description 6
239000007884 disintegrant Substances 0.000 description 6
239000006185 dispersion Substances 0.000 description 6
239000013583 drug formulation Substances 0.000 description 6
230000003628 erosive effect Effects 0.000 description 6
235000019325 ethyl cellulose Nutrition 0.000 description 6
229920001249 ethyl cellulose Polymers 0.000 description 6
239000000499 gel Substances 0.000 description 6
239000008187 granular material Substances 0.000 description 6
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 6
239000002609 medium Substances 0.000 description 6
239000011591 potassium Substances 0.000 description 6
229910052700 potassium Inorganic materials 0.000 description 6
238000011160 research Methods 0.000 description 6
230000000699 topical effect Effects 0.000 description 6
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 5
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 5
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
241000282326 Felis catus Species 0.000 description 5
108010010803 Gelatin Proteins 0.000 description 5
241000124008 Mammalia Species 0.000 description 5
229920003094 Methocel™ K4M Polymers 0.000 description 5
239000002202 Polyethylene glycol Substances 0.000 description 5
230000036982 action potential Effects 0.000 description 5
239000013543 active substance Substances 0.000 description 5
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 5
230000003126 arrythmogenic effect Effects 0.000 description 5
125000003710 aryl alkyl group Chemical group 0.000 description 5
230000009286 beneficial effect Effects 0.000 description 5
125000002619 bicyclic group Chemical group 0.000 description 5
239000011575 calcium Substances 0.000 description 5
229910052791 calcium Inorganic materials 0.000 description 5
239000002775 capsule Substances 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
208000035475 disorder Diseases 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
235000011187 glycerol Nutrition 0.000 description 5
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 5
208000028867 ischemia Diseases 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
238000002156 mixing Methods 0.000 description 5
239000000902 placebo Substances 0.000 description 5
229940068196 placebo Drugs 0.000 description 5
239000003755 preservative agent Substances 0.000 description 5
230000002336 repolarization Effects 0.000 description 5
239000007921 spray Substances 0.000 description 5
239000000758 substrate Substances 0.000 description 5
125000004434 sulfur atom Chemical group 0.000 description 5
239000000829 suppository Substances 0.000 description 5
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 4
229920003134 Eudragit® polymer Polymers 0.000 description 4
206010019280 Heart failures Diseases 0.000 description 4
241000282412 Homo Species 0.000 description 4
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 4
102000003982 Parathyroid hormone Human genes 0.000 description 4
108090000445 Parathyroid hormone Proteins 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
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 4
229930006000 Sucrose Natural products 0.000 description 4
230000002159 abnormal effect Effects 0.000 description 4
125000004450 alkenylene group Chemical group 0.000 description 4
125000002947 alkylene group Chemical group 0.000 description 4
230000003288 anthiarrhythmic effect Effects 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
230000001746 atrial effect Effects 0.000 description 4
239000002585 base Substances 0.000 description 4
239000006071 cream Substances 0.000 description 4
238000011161 development Methods 0.000 description 4
230000018109 developmental process Effects 0.000 description 4
238000009792 diffusion process Methods 0.000 description 4
238000007907 direct compression Methods 0.000 description 4
239000003937 drug carrier Substances 0.000 description 4
238000013195 electrical cardioversion Methods 0.000 description 4
235000019441 ethanol Nutrition 0.000 description 4
230000009969 flowable effect Effects 0.000 description 4
239000006260 foam Substances 0.000 description 4
210000002837 heart atrium Anatomy 0.000 description 4
239000012943 hotmelt Substances 0.000 description 4
239000012728 immediate-release (IR) tablet Substances 0.000 description 4
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 4
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 4
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000003921 oil Substances 0.000 description 4
239000000199 parathyroid hormone Substances 0.000 description 4
229960001319 parathyroid hormone Drugs 0.000 description 4
239000002245 particle Substances 0.000 description 4
239000006072 paste Substances 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
239000006187 pill Substances 0.000 description 4
229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 4
125000000719 pyrrolidinyl group Chemical group 0.000 description 4
229940080313 sodium starch Drugs 0.000 description 4
239000002904 solvent Substances 0.000 description 4
239000005720 sucrose Substances 0.000 description 4
239000007916 tablet composition Substances 0.000 description 4
JMHYCBFEEFHTMK-RWVUOVKPSA-N 1-[(1s,2s)-2-[2-(3,4-dimethoxyphenyl)ethoxy]cyclohexyl]pyrrolidin-3-ol;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCO[C@@H]1[C@@H](N2CC(O)CC2)CCCC1 JMHYCBFEEFHTMK-RWVUOVKPSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
229920001817 Agar Polymers 0.000 description 3
241000283690 Bos taurus Species 0.000 description 3
206010007559 Cardiac failure congestive Diseases 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 3
206010061218 Inflammation Diseases 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
208000006011 Stroke Diseases 0.000 description 3
206010047139 Vasoconstriction Diseases 0.000 description 3
206010047281 Ventricular arrhythmia Diseases 0.000 description 3
239000000654 additive Substances 0.000 description 3
230000002411 adverse Effects 0.000 description 3
235000010419 agar Nutrition 0.000 description 3
235000010443 alginic acid Nutrition 0.000 description 3
229920000615 alginic acid Polymers 0.000 description 3
125000004448 alkyl carbonyl group Chemical group 0.000 description 3
230000003444 anaesthetic effect Effects 0.000 description 3
125000000129 anionic group Chemical group 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
230000008901 benefit Effects 0.000 description 3
235000012216 bentonite Nutrition 0.000 description 3
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000006172 buffering agent Substances 0.000 description 3
125000002837 carbocyclic group Chemical group 0.000 description 3
238000013194 cardioversion Methods 0.000 description 3
229960000541 cetyl alcohol Drugs 0.000 description 3
210000001072 colon Anatomy 0.000 description 3
238000011109 contamination Methods 0.000 description 3
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 3
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 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
229960003887 dichlorophen Drugs 0.000 description 3
238000012377 drug delivery Methods 0.000 description 3
238000001035 drying Methods 0.000 description 3
210000001198 duodenum Anatomy 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
229940088598 enzyme Drugs 0.000 description 3
239000012530 fluid Substances 0.000 description 3
230000004907 flux Effects 0.000 description 3
239000012634 fragment Substances 0.000 description 3
125000001072 heteroaryl group Chemical group 0.000 description 3
UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 3
238000007327 hydrogenolysis reaction Methods 0.000 description 3
229920001477 hydrophilic polymer Polymers 0.000 description 3
230000001771 impaired effect Effects 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
230000000670 limiting effect Effects 0.000 description 3
238000011068 loading method Methods 0.000 description 3
229960001344 methylphenidate Drugs 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
125000002757 morpholinyl group Chemical group 0.000 description 3
208000031225 myocardial ischemia Diseases 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
239000002674 ointment Substances 0.000 description 3
210000000056 organ Anatomy 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
230000001575 pathological effect Effects 0.000 description 3
239000011148 porous material Substances 0.000 description 3
229960004063 propylene glycol Drugs 0.000 description 3
230000004648 relaxation of smooth muscle Effects 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 3
235000012239 silicon dioxide Nutrition 0.000 description 3
238000004513 sizing Methods 0.000 description 3
239000007790 solid phase Substances 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
241000894007 species Species 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
150000008163 sugars Chemical class 0.000 description 3
239000004094 surface-active agent Substances 0.000 description 3
239000000375 suspending agent Substances 0.000 description 3
230000002459 sustained effect Effects 0.000 description 3
238000013268 sustained release Methods 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
150000003512 tertiary amines Chemical class 0.000 description 3
125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
230000025033 vasoconstriction Effects 0.000 description 3
230000002861 ventricular Effects 0.000 description 3
238000005550 wet granulation Methods 0.000 description 3
PZIDJKOIMRBQLL-UHFFFAOYSA-N $l^{2}-azanylidenemethane Chemical compound [N]=C PZIDJKOIMRBQLL-UHFFFAOYSA-N 0.000 description 2
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
AUTWIRMPGHMXAD-SUNYJGFJSA-N (1r,2s)-2-[(2s)-2-(aminomethyl)butyl]-1-(1-phenylimidazol-4-yl)cyclopropane-1-carboxylic acid Chemical compound CC[C@H](CN)C[C@H]1C[C@]1(C(O)=O)C1=CN(C=2C=CC=CC=2)C=N1 AUTWIRMPGHMXAD-SUNYJGFJSA-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
JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 2
125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
YAZBMYSXOHXTDS-HLRBRJAUSA-N 1-[(1s,2s)-2-(3-cyclohexylpropoxy)cyclohexyl]pyrrolidin-3-one;hydrochloride Chemical compound Cl.C1C(=O)CCN1[C@@H]1[C@@H](OCCCC2CCCCC2)CCCC1 YAZBMYSXOHXTDS-HLRBRJAUSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 description 2
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
KPUSZZFAYGWAHZ-UHFFFAOYSA-N 3-azabicyclo[2.2.2]octane Chemical compound C1CC2CCC1NC2 KPUSZZFAYGWAHZ-UHFFFAOYSA-N 0.000 description 2
HGWUUOXXAIISDB-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane Chemical compound C1NCC2CC21 HGWUUOXXAIISDB-UHFFFAOYSA-N 0.000 description 2
NEOIOGUWEUTYIH-UHFFFAOYSA-N 3-azabicyclo[3.2.0]heptane Chemical compound C1NCC2CCC21 NEOIOGUWEUTYIH-UHFFFAOYSA-N 0.000 description 2
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 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
241000837181 Andina 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
241000416162 Astragalus gummifer Species 0.000 description 2
201000006474 Brain Ischemia Diseases 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
208000024172 Cardiovascular disease Diseases 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
241000283086 Equidae Species 0.000 description 2
229920003141 Eudragit® S 100 Polymers 0.000 description 2
241000206672 Gelidium Species 0.000 description 2
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 2
102000003855 L-lactate dehydrogenase Human genes 0.000 description 2
108700023483 L-lactate dehydrogenases Proteins 0.000 description 2
240000007472 Leucaena leucocephala Species 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
229920003102 Methocel™ E4M Polymers 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
208000007101 Muscle Cramp Diseases 0.000 description 2
206010061533 Myotonia Diseases 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
241001494479 Pecora Species 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
108091000080 Phosphotransferase Proteins 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
206010063837 Reperfusion injury Diseases 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
208000005392 Spasm Diseases 0.000 description 2
241000282887 Suidae Species 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
241000282898 Sus scrofa Species 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
208000007536 Thrombosis Diseases 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 2
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
150000001241 acetals Chemical class 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
125000002252 acyl group Chemical group 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
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
IYIKLHRQXLHMJQ-UHFFFAOYSA-N amiodarone Chemical compound CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCCN(CC)CC)C(I)=C1 IYIKLHRQXLHMJQ-UHFFFAOYSA-N 0.000 description 2
229960005260 amiodarone Drugs 0.000 description 2
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
238000013459 approach Methods 0.000 description 2
239000000440 bentonite Substances 0.000 description 2
229910000278 bentonite Inorganic materials 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
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-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
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 2
229920002988 biodegradable polymer Polymers 0.000 description 2
239000004621 biodegradable polymer Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
239000000872 buffer Substances 0.000 description 2
235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
229940095259 butylated hydroxytoluene Drugs 0.000 description 2
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
208000015114 central nervous system disease Diseases 0.000 description 2
229940082500 cetostearyl alcohol Drugs 0.000 description 2
239000002738 chelating agent Substances 0.000 description 2
125000003636 chemical group Chemical group 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
230000035602 clotting Effects 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
239000003086 colorant Substances 0.000 description 2
238000005056 compaction Methods 0.000 description 2
229940125782 compound 2 Drugs 0.000 description 2
230000001276 controlling effect Effects 0.000 description 2
235000012343 cottonseed oil Nutrition 0.000 description 2
DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
239000004914 cyclooctane Substances 0.000 description 2
230000007423 decrease Effects 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 2
229960004166 diltiazem Drugs 0.000 description 2
125000005805 dimethoxy phenyl group Chemical group 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000008298 dragée Substances 0.000 description 2
238000007908 dry granulation Methods 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
230000005284 excitation Effects 0.000 description 2
239000003925 fat Substances 0.000 description 2
235000019197 fats Nutrition 0.000 description 2
239000007888 film coating Substances 0.000 description 2
238000009501 film coating Methods 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
238000012817 gel-diffusion technique Methods 0.000 description 2
239000008103 glucose Substances 0.000 description 2
238000005469 granulation Methods 0.000 description 2
230000003179 granulation Effects 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical group 0.000 description 2
230000036541 health Effects 0.000 description 2
208000019622 heart disease Diseases 0.000 description 2
210000003709 heart valve Anatomy 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical group FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 description 2
230000006872 improvement Effects 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
239000003701 inert diluent Substances 0.000 description 2
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 2
238000001361 intraarterial administration Methods 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000010255 intramuscular injection Methods 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
238000007913 intrathecal administration Methods 0.000 description 2
235000010445 lecithin Nutrition 0.000 description 2
239000000787 lecithin Substances 0.000 description 2
229940067606 lecithin Drugs 0.000 description 2
210000000265 leukocyte Anatomy 0.000 description 2
239000002502 liposome Substances 0.000 description 2
244000144972 livestock Species 0.000 description 2
230000007774 longterm Effects 0.000 description 2
239000006210 lotion Substances 0.000 description 2
229910001425 magnesium ion Inorganic materials 0.000 description 2
238000007726 management method Methods 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
230000005226 mechanical processes and functions Effects 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
239000012528 membrane Substances 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
238000000465 moulding Methods 0.000 description 2
239000002324 mouth wash Substances 0.000 description 2
201000006417 multiple sclerosis Diseases 0.000 description 2
208000010125 myocardial infarction Diseases 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
239000012457 nonaqueous media Substances 0.000 description 2
BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
239000004006 olive oil Substances 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
230000003204 osmotic effect Effects 0.000 description 2
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
239000000825 pharmaceutical preparation Substances 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
102000020233 phosphotransferase Human genes 0.000 description 2
230000035790 physiological processes and functions Effects 0.000 description 2
125000004193 piperazinyl group Chemical group 0.000 description 2
229920003023 plastic Polymers 0.000 description 2
239000004033 plastic Substances 0.000 description 2
229920005862 polyol Polymers 0.000 description 2
150000003077 polyols Chemical class 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
150000003141 primary amines Chemical class 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
238000012545 processing Methods 0.000 description 2
239000003380 propellant Substances 0.000 description 2
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
230000002685 pulmonary effect Effects 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
230000009467 reduction Effects 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
229960001860 salicylate Drugs 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
239000008159 sesame oil Substances 0.000 description 2
235000011803 sesame oil Nutrition 0.000 description 2
230000035939 shock Effects 0.000 description 2
238000004088 simulation Methods 0.000 description 2
238000009491 slugging Methods 0.000 description 2
210000002460 smooth muscle Anatomy 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000001509 sodium citrate Substances 0.000 description 2
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 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
235000010199 sorbic acid Nutrition 0.000 description 2
239000004334 sorbic acid Substances 0.000 description 2
229940075582 sorbic acid Drugs 0.000 description 2
238000005563 spheronization Methods 0.000 description 2
239000008223 sterile water Substances 0.000 description 2
238000010254 subcutaneous injection Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
150000003555 thioacetals Chemical class 0.000 description 2
125000004001 thioalkyl group Chemical group 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
235000010487 tragacanth Nutrition 0.000 description 2
239000000196 tragacanth Substances 0.000 description 2
229940116362 tragacanth Drugs 0.000 description 2
230000001052 transient effect Effects 0.000 description 2
230000002485 urinary effect Effects 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
229920002554 vinyl polymer Polymers 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound 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 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
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
229940058015 1,3-butylene glycol Drugs 0.000 description 1
DRTJSDAHQWSNFI-UHFFFAOYSA-N 1,3-dichloro-2-(cyclohexyloxymethyl)benzene;hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1COC1CCCCC1 DRTJSDAHQWSNFI-UHFFFAOYSA-N 0.000 description 1
YAZBMYSXOHXTDS-STYNFMPRSA-N 1-[(1r,2r)-2-(3-cyclohexylpropoxy)cyclohexyl]pyrrolidin-3-one;hydrochloride Chemical compound Cl.C1C(=O)CCN1[C@H]1[C@H](OCCCC2CCCCC2)CCCC1 YAZBMYSXOHXTDS-STYNFMPRSA-N 0.000 description 1
WGXAQCYMUFQJSA-IAGOWNOFSA-N 1-[(1r,2r)-2-[(2,6-dichlorophenyl)methoxy]cyclohexyl]pyrrolidin-3-one Chemical compound ClC1=CC=CC(Cl)=C1CO[C@H]1[C@H](N2CC(=O)CC2)CCCC1 WGXAQCYMUFQJSA-IAGOWNOFSA-N 0.000 description 1
AOUFGFULHFSAID-CTGIZLNPSA-N 1-[(1r,2r)-2-[2-(2,6-dichlorophenyl)ethoxy]cyclohexyl]pyrrolidin-3-ol;hydrochloride Chemical compound Cl.C1C(O)CCN1[C@H]1[C@H](OCCC=2C(=CC=CC=2Cl)Cl)CCCC1 AOUFGFULHFSAID-CTGIZLNPSA-N 0.000 description 1
KRCDDYNOSQYZRA-QZTJIDSGSA-N 1-[(1r,2r)-2-[2-(2,6-dichlorophenyl)ethoxy]cyclohexyl]pyrrolidin-3-one Chemical compound ClC1=CC=CC(Cl)=C1CCO[C@H]1[C@H](N2CC(=O)CC2)CCCC1 KRCDDYNOSQYZRA-QZTJIDSGSA-N 0.000 description 1
DFVBVSNZKYWCMO-UKOKCHKQSA-N 1-[(1s,2s)-2-(2,2-diphenylethoxy)cyclohexyl]pyrrolidin-3-one;hydrochloride Chemical compound Cl.C1C(=O)CCN1[C@@H]1[C@@H](OCC(C=2C=CC=CC=2)C=2C=CC=CC=2)CCCC1 DFVBVSNZKYWCMO-UKOKCHKQSA-N 0.000 description 1
XBZGZASGVCLUPR-QJHJCNPRSA-N 1-[(1s,2s)-2-[(2,6-dichlorophenyl)methoxy]cyclohexyl]pyrrolidin-3-one;hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1CO[C@@H]1[C@@H](N2CC(=O)CC2)CCCC1 XBZGZASGVCLUPR-QJHJCNPRSA-N 0.000 description 1
AOUFGFULHFSAID-URNQBSGWSA-N 1-[(1s,2s)-2-[2-(2,6-dichlorophenyl)ethoxy]cyclohexyl]pyrrolidin-3-ol;hydrochloride Chemical compound Cl.C1C(O)CCN1[C@@H]1[C@@H](OCCC=2C(=CC=CC=2Cl)Cl)CCCC1 AOUFGFULHFSAID-URNQBSGWSA-N 0.000 description 1
KRCDDYNOSQYZRA-ROUUACIJSA-N 1-[(1s,2s)-2-[2-(2,6-dichlorophenyl)ethoxy]cyclohexyl]pyrrolidin-3-one Chemical compound ClC1=CC=CC(Cl)=C1CCO[C@@H]1[C@@H](N2CC(=O)CC2)CCCC1 KRCDDYNOSQYZRA-ROUUACIJSA-N 0.000 description 1
SRHMVSNHWVRBPR-QJHJCNPRSA-N 1-[(1s,2s)-2-[2-(2,6-dichlorophenyl)ethoxy]cyclopentyl]pyrrolidin-3-one;hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1CCO[C@@H]1[C@@H](N2CC(=O)CC2)CCC1 SRHMVSNHWVRBPR-QJHJCNPRSA-N 0.000 description 1
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
SRQAJMUHZROVHW-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)ethanol Chemical compound COC1=CC=C(CCO)C=C1OC SRQAJMUHZROVHW-UHFFFAOYSA-N 0.000 description 1
KAWIOCMUARENDQ-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfanyl-n-(4-pyridin-2-yl-1,3-thiazol-2-yl)acetamide Chemical compound C1=CC(Cl)=CC=C1SCC(=O)NC1=NC(C=2N=CC=CC=2)=CS1 KAWIOCMUARENDQ-UHFFFAOYSA-N 0.000 description 1
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-UHFFFAOYSA-N 0.000 description 1
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
NNXZVHFQSQQXQF-GBNZRNLASA-N 3-[(1r,2r)-2-[2-(2,6-dichlorophenyl)ethoxy]cyclohexyl]-1,3-thiazolidine;hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1CCO[C@H]1[C@H](N2CSCC2)CCCC1 NNXZVHFQSQQXQF-GBNZRNLASA-N 0.000 description 1
NNXZVHFQSQQXQF-QJHJCNPRSA-N 3-[(1s,2s)-2-[2-(2,6-dichlorophenyl)ethoxy]cyclohexyl]-1,3-thiazolidine;hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1CCO[C@@H]1[C@@H](N2CSCC2)CCCC1 NNXZVHFQSQQXQF-QJHJCNPRSA-N 0.000 description 1
LICHZOBEUWVYSY-UHFFFAOYSA-N 3-azabicyclo[3.2.2]nonane Chemical compound C1CC2CCC1CNC2 LICHZOBEUWVYSY-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
KBAWIFPZMASYLQ-UHFFFAOYSA-N 4-(2-cyclohexyloxyethyl)-1,2-dimethoxybenzene Chemical compound C1=C(OC)C(OC)=CC=C1CCOC1CCCCC1 KBAWIFPZMASYLQ-UHFFFAOYSA-N 0.000 description 1
IOKIWBXLDJKSIK-UHFFFAOYSA-N 4-(2-cyclohexyloxyethyl)-1,2-dimethoxybenzene;hydrochloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CCOC1CCCCC1 IOKIWBXLDJKSIK-UHFFFAOYSA-N 0.000 description 1
BNFSPYSVBPJHMM-GBNZRNLASA-N 4-[(1r,2r)-2-[(2,6-dichlorophenyl)methoxy]cyclohexyl]morpholine;hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1CO[C@H]1[C@H](N2CCOCC2)CCCC1 BNFSPYSVBPJHMM-GBNZRNLASA-N 0.000 description 1
BNFSPYSVBPJHMM-QJHJCNPRSA-N 4-[(1s,2s)-2-[(2,6-dichlorophenyl)methoxy]cyclohexyl]morpholine;hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1CO[C@@H]1[C@@H](N2CCOCC2)CCCC1 BNFSPYSVBPJHMM-QJHJCNPRSA-N 0.000 description 1
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
206010065040 AIDS dementia complex Diseases 0.000 description 1
108091006112 ATPases Proteins 0.000 description 1
102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
206010001605 Alcohol poisoning Diseases 0.000 description 1
201000004384 Alopecia Diseases 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
235000003276 Apios tuberosa Nutrition 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
208000032845 Atrial Remodeling Diseases 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
208000008035 Back Pain Diseases 0.000 description 1
206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
102100026189 Beta-galactosidase Human genes 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
241000282832 Camelidae Species 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
208000020446 Cardiac disease Diseases 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
CCPHAMSKHBDMDS-UHFFFAOYSA-N Chetoseminudin B Natural products C=1NC2=CC=CC=C2C=1CC1(SC)NC(=O)C(CO)(SC)N(C)C1=O CCPHAMSKHBDMDS-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
206010053567 Coagulopathies Diseases 0.000 description 1
102000016726 Coat Protein Complex I Human genes 0.000 description 1
108010092897 Coat Protein Complex I Proteins 0.000 description 1
208000002330 Congenital Heart Defects Diseases 0.000 description 1
208000029323 Congenital myotonia Diseases 0.000 description 1
241000777300 Congiopodidae Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
206010011224 Cough Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
206010011703 Cyanosis Diseases 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 description 1
108050008072 Cytochrome c oxidase subunit IV Proteins 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
239000004606 Fillers/Extenders Substances 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
241000282818 Giraffidae Species 0.000 description 1
208000010412 Glaucoma Diseases 0.000 description 1
AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
102000001554 Hemoglobins Human genes 0.000 description 1
108010054147 Hemoglobins Proteins 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
101700012268 Holin Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
208000007599 Hyperkalemic periodic paralysis Diseases 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
206010020844 Hyperthermia malignant Diseases 0.000 description 1
206010020850 Hyperthyroidism Diseases 0.000 description 1
208000001953 Hypotension Diseases 0.000 description 1
208000006877 Insect Bites and Stings Diseases 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
229930194542 Keto Natural products 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
108010059881 Lactase Proteins 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
206010049694 Left Ventricular Dysfunction Diseases 0.000 description 1
208000018717 Malignant hyperthermia of anesthesia Diseases 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
229920003091 Methocel™ Polymers 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
208000021642 Muscular disease Diseases 0.000 description 1
208000009525 Myocarditis Diseases 0.000 description 1
201000009623 Myopathy Diseases 0.000 description 1
208000010316 Myotonia congenita Diseases 0.000 description 1
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
240000007817 Olea europaea Species 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
241000282376 Panthera tigris Species 0.000 description 1
206010033799 Paralysis Diseases 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
208000004983 Phantom Limb Diseases 0.000 description 1
206010056238 Phantom pain Diseases 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
229920002732 Polyanhydride Polymers 0.000 description 1
229920000954 Polyglycolide Polymers 0.000 description 1
229920001710 Polyorthoester Polymers 0.000 description 1
241000288906 Primates Species 0.000 description 1
208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
208000010378 Pulmonary Embolism Diseases 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
241000700159 Rattus Species 0.000 description 1
235000004443 Ricinus communis Nutrition 0.000 description 1
235000019485 Safflower oil Nutrition 0.000 description 1
206010039897 Sedation Diseases 0.000 description 1
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
108010052164 Sodium Channels Proteins 0.000 description 1
102000018674 Sodium Channels Human genes 0.000 description 1
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
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
206010042434 Sudden death Diseases 0.000 description 1
206010042600 Supraventricular arrhythmias Diseases 0.000 description 1
208000018452 Torsade de pointes Diseases 0.000 description 1
208000002363 Torsades de Pointes Diseases 0.000 description 1
206010070863 Toxicity to various agents Diseases 0.000 description 1
102000003929 Transaminases Human genes 0.000 description 1
108090000340 Transaminases Proteins 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
206010046543 Urinary incontinence Diseases 0.000 description 1
206010047163 Vasospasm Diseases 0.000 description 1
238000006959 Williamson synthesis reaction Methods 0.000 description 1
102100033220 Xanthine oxidase Human genes 0.000 description 1
108010093894 Xanthine oxidase Proteins 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 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
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000000674 adrenergic antagonist Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
230000032683 aging Effects 0.000 description 1
239000000556 agonist Substances 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
125000005157 alkyl carboxy group Chemical group 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
231100000360 alopecia Toxicity 0.000 description 1
229940087168 alpha tocopherol Drugs 0.000 description 1
HUMHYXGDUOGHTG-HEZXSMHISA-N alpha-D-GalpNAc-(1->3)-[alpha-L-Fucp-(1->2)]-D-Galp Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](O)[C@@H](CO)OC1O HUMHYXGDUOGHTG-HEZXSMHISA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
239000002269 analeptic agent Substances 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
230000000507 anthelmentic effect Effects 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000001772 anti-angiogenic effect Effects 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
230000003502 anti-nociceptive effect Effects 0.000 description 1
230000002141 anti-parasite Effects 0.000 description 1
230000000561 anti-psychotic effect Effects 0.000 description 1
230000001147 anti-toxic effect Effects 0.000 description 1
230000002303 anti-venom Effects 0.000 description 1
230000000840 anti-viral effect Effects 0.000 description 1
230000010100 anticoagulation Effects 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
239000003429 antifungal agent Substances 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
239000003096 antiparasitic agent Substances 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
230000002763 arrhythmic effect Effects 0.000 description 1
206010003246 arthritis Diseases 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
208000006673 asthma Diseases 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
229960002903 benzyl benzoate Drugs 0.000 description 1
108010005774 beta-Galactosidase Proteins 0.000 description 1
125000005841 biaryl group Chemical group 0.000 description 1
125000002527 bicyclic carbocyclic group Chemical group 0.000 description 1
210000000941 bile Anatomy 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
229920000249 biocompatible polymer Polymers 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
239000000090 biomarker Substances 0.000 description 1
229960000074 biopharmaceutical Drugs 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
230000036760 body temperature Effects 0.000 description 1
238000010322 bone marrow transplantation Methods 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
230000036471 bradycardia Effects 0.000 description 1
208000006218 bradycardia Diseases 0.000 description 1
239000007975 buffered saline Substances 0.000 description 1
239000001273 butane Substances 0.000 description 1
235000019437 butane-1,3-diol Nutrition 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
229960001948 caffeine Drugs 0.000 description 1
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
235000012241 calcium silicate Nutrition 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
206010061592 cardiac fibrillation Diseases 0.000 description 1
238000007675 cardiac surgery Methods 0.000 description 1
239000002327 cardiovascular agent Substances 0.000 description 1
229940125692 cardiovascular agent Drugs 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
229940081733 cetearyl alcohol Drugs 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
239000004927 clay Substances 0.000 description 1
238000011260 co-administration Methods 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
238000013329 compounding Methods 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
208000028831 congenital heart disease Diseases 0.000 description 1
230000009091 contractile dysfunction Effects 0.000 description 1
230000008828 contractile function Effects 0.000 description 1
238000013267 controlled drug release Methods 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
235000005822 corn Nutrition 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
239000002385 cottonseed oil Substances 0.000 description 1
229940109239 creatinine Drugs 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
150000001932 cycloheptanes Chemical class 0.000 description 1
OCDXZFSOHJRGIL-UHFFFAOYSA-N cyclohexyloxycyclohexane Chemical class C1CCCCC1OC1CCCCC1 OCDXZFSOHJRGIL-UHFFFAOYSA-N 0.000 description 1
WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 description 1
150000001938 cyclooctanes Chemical class 0.000 description 1
150000001940 cyclopentanes Chemical class 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
229960001305 cysteine hydrochloride Drugs 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
229920006237 degradable polymer Polymers 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
DUGOZIWVEXMGBE-CHWSQXEVSA-N dexmethylphenidate Chemical compound C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 DUGOZIWVEXMGBE-CHWSQXEVSA-N 0.000 description 1
229960001042 dexmethylphenidate Drugs 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
230000035487 diastolic blood pressure Effects 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
125000003963 dichloro group Chemical group Cl* 0.000 description 1
125000004188 dichlorophenyl group Chemical group 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
229960005156 digoxin Drugs 0.000 description 1
LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000002612 dispersion medium Substances 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
235000013601 eggs Nutrition 0.000 description 1
229920001971 elastomer Polymers 0.000 description 1
238000002565 electrocardiography Methods 0.000 description 1
239000003792 electrolyte Substances 0.000 description 1
230000007831 electrophysiology Effects 0.000 description 1
238000002001 electrophysiology Methods 0.000 description 1
230000003073 embolic effect Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
102000006966 enzyme regulator activity proteins Human genes 0.000 description 1
108040000578 enzyme regulator activity proteins Proteins 0.000 description 1
230000001037 epileptic effect Effects 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 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
230000005713 exacerbation Effects 0.000 description 1
230000029142 excretion Effects 0.000 description 1
238000013265 extended release Methods 0.000 description 1
238000001125 extrusion Methods 0.000 description 1
239000003885 eye ointment Substances 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000002191 fatty alcohols Chemical class 0.000 description 1
230000002600 fibrillogenic effect Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
210000000232 gallbladder Anatomy 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
229940050410 gluconate Drugs 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
150000002334 glycols Chemical class 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
210000002064 heart cell Anatomy 0.000 description 1
230000004217 heart function Effects 0.000 description 1
210000005003 heart tissue Anatomy 0.000 description 1
230000000004 hemodynamic effect Effects 0.000 description 1
125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 description 1
239000003906 humectant Substances 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
239000000017 hydrogel Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229920001600 hydrophobic polymer Polymers 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
230000036543 hypotension Effects 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000028993 immune response Effects 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000002513 implantation Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
230000000266 injurious effect Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
206010022437 insomnia Diseases 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
238000007917 intracranial administration Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
230000004410 intraocular pressure Effects 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
238000007914 intraventricular administration Methods 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
230000007794 irritation Effects 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000007951 isotonicity adjuster Substances 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
238000004898 kneading Methods 0.000 description 1
229940116108 lactase Drugs 0.000 description 1
102000005861 leptin receptors Human genes 0.000 description 1
108010019813 leptin receptors Proteins 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
201000007004 malignant hyperthermia Diseases 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000007909 melt granulation Methods 0.000 description 1
230000028161 membrane depolarization Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229940071648 metered dose inhaler Drugs 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
239000004530 micro-emulsion Substances 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000004005 microsphere Substances 0.000 description 1
206010027599 migraine Diseases 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
239000007932 molded tablet Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
206010028417 myasthenia gravis Diseases 0.000 description 1
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
SIMWTRCFFSTNMG-AWEZNQCLSA-N n-[[(5s)-3-[3-fluoro-4-[4-(2-hydroxyacetyl)piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CO)CC1 SIMWTRCFFSTNMG-AWEZNQCLSA-N 0.000 description 1
IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
231100000344 non-irritating Toxicity 0.000 description 1
ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical compound NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
238000003305 oral gavage Methods 0.000 description 1
229940126701 oral medication Drugs 0.000 description 1
235000015205 orange juice Nutrition 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000036407 pain Effects 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
239000002304 perfume Substances 0.000 description 1
208000008494 pericarditis Diseases 0.000 description 1
230000002093 peripheral effect Effects 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
230000000144 pharmacologic effect Effects 0.000 description 1
238000011422 pharmacological therapy Methods 0.000 description 1
HTYIXCKSEQQCJO-UHFFFAOYSA-N phenaglycodol Chemical compound CC(C)(O)C(C)(O)C1=CC=C(Cl)C=C1 HTYIXCKSEQQCJO-UHFFFAOYSA-N 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
239000002953 phosphate buffered saline 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
238000000053 physical method Methods 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
150000004804 polysaccharides Chemical class 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
244000144977 poultry Species 0.000 description 1
230000000063 preceeding effect Effects 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
239000001294 propane Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 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
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000008439 repair process Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
230000004202 respiratory function Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
239000003340 retarding agent Substances 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
235000005713 safflower oil Nutrition 0.000 description 1
239000003813 safflower oil Substances 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
239000000523 sample Substances 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
230000036280 sedation Effects 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
238000007493 shaping process Methods 0.000 description 1
208000007056 sickle cell anemia Diseases 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
238000004467 single crystal X-ray diffraction Methods 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
239000000779 smoke Substances 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
229910000342 sodium bisulfate Inorganic materials 0.000 description 1
229940100996 sodium bisulfate Drugs 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
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
239000008109 sodium starch glycolate Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
229940001482 sodium sulfite Drugs 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000008279 sol Substances 0.000 description 1
239000007962 solid dispersion Substances 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000003206 sterilizing agent Substances 0.000 description 1
230000035882 stress Effects 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
230000002311 subsequent effect Effects 0.000 description 1
201000009032 substance abuse Diseases 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
230000035488 systolic blood pressure Effects 0.000 description 1
IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
230000009424 thromboembolic effect Effects 0.000 description 1
229960000984 tocofersolan Drugs 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
231100000440 toxicity profile Toxicity 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
230000002792 vascular Effects 0.000 description 1
235000019871 vegetable fat Nutrition 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000011787 zinc oxide Substances 0.000 description 1
235000014692 zinc oxide Nutrition 0.000 description 1
239000002076 α-tocopherol Substances 0.000 description 1
235000004835 α-tocopherol Nutrition 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Organic Chemistry (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CA002524034A 2003-05-02 2004-05-03 Utilisations de composes modulant les canaux ioniques Abandoned CA2524034A1 (fr)

Applications Claiming Priority (19)

Application Number	Priority Date	Filing Date	Title
US46715903P	2003-05-02	2003-05-02
US60/467,159		2003-05-02
US49339203P	2003-08-07	2003-08-07
US60/493,392		2003-08-07
US51624803P	2003-10-31	2003-10-31
US51648603P	2003-10-31	2003-10-31
US60/516,486		2003-10-31
US60/516,248		2003-10-31
US52691103P	2003-12-03	2003-12-03
US60/526,911		2003-12-03
US52716903P	2003-12-04	2003-12-04
US60/527,169		2003-12-04
US52825103P	2003-12-08	2003-12-08
US60/528,251		2003-12-08
US54494104P	2004-02-13	2004-02-13
US60/544,941		2004-02-13
US55940504P	2004-04-01	2004-04-01
US60/559,405		2004-04-01
PCT/US2004/013731 WO2004098525A2 (fr)	2003-05-02	2004-05-03	Utilisations de composes modulant les canaux ioniques

Publications (1)

Publication Number	Publication Date
CA2524034A1 true CA2524034A1 (fr)	2004-11-18

Family

ID=33437324

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002524034A Abandoned CA2524034A1 (fr)	2003-05-02	2004-05-03	Utilisations de composes modulant les canaux ioniques

Country Status (2)

Country	Link
CA (1)	CA2524034A1 (fr)
WO (1)	WO2004098525A2 (fr)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RO121028B1 (ro)	1998-04-01	2006-11-30	Nortran Pharmaceuticals Inc.	Compuşi aminociclohexil eteri şi utilizările acestora
US7507545B2 (en)	1999-03-31	2009-03-24	Cardiome Pharma Corp.	Ion channel modulating activity method
US7524879B2 (en)	2000-10-06	2009-04-28	Cardiome Pharma Corp.	Ion channel modulating compounds and uses thereof
US7057053B2 (en)	2000-10-06	2006-06-06	Cardiome Pharma Corp.	Ion channel modulating compounds and uses thereof
ATE529401T1 (de)	2003-05-02	2011-11-15	Cardiome Pharma Corp	Aminocyclohexylether-verbindungen und deren verwendung
US7345086B2 (en)	2003-05-02	2008-03-18	Cardiome Pharma Corp.	Uses of ion channel modulating compounds
WO2005018635A2 (fr)	2003-08-07	2005-03-03	Cardiome Pharma Corp.	Activite i modulant des canaux ioniques
US7345087B2 (en)	2003-10-31	2008-03-18	Cardiome Pharma Corp.	Aminocyclohexyl ether compounds and uses thereof
EP1729814A2 (fr)	2004-04-01	2006-12-13	Cardiome Pharma Corp.	Composes pegyles de modulation des canaux ioniques
US8058304B2 (en)	2004-04-01	2011-11-15	Cardiome Pharma Corp.	Merged ion channel modulating compounds and uses thereof
WO2005113011A2 (fr)	2004-04-01	2005-12-01	Cardiome Pharma Corp.	Promedicaments de composes modulant les canaux ioniques et leurs utilisations
US7569589B2 (en)	2004-07-29	2009-08-04	Merck & Co., Inc.	Potassium channel inhibitors
MX2007005496A (es) *	2004-11-08	2007-07-09	Cardiome Pharma Corp	Nuevo regimen de dosificacion para compuestos moduladores de canal de iones, para el tratamiento de fibrilacion auricular aguda en un humano.
EP1828099B1 (fr) *	2004-11-18	2020-01-22	Correvio International Sàrl	Processus de preparation par synthese de composes d'aminocyclohexyle ether
BRPI0612138B8 (pt)	2005-06-15	2021-05-25	Cardiome Pharma Corp	compostos éter aminocicloexílicos e método para fazer os mesmos
EA200971025A1 (ru) *	2007-05-04	2010-04-30	Кардиом Фарма Корп.	Пероральные композиции с регулируемым высвобождением соединений, модулирующих ионные каналы, и связанные с ними способы предупреждения аритмии
WO2009018547A1 (fr) *	2007-08-01	2009-02-05	Cardiome Pharma Corp.	Formulations à libération prolongée pour la prévention d'arythmies

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2268590A1 (fr) *	1999-04-12	2000-10-12	Nortran Pharmaceuticals Inc.	Composes de regulation des canaux ioniques et utilisations de ces produits

2004
- 2004-05-03 WO PCT/US2004/013731 patent/WO2004098525A2/fr not_active Ceased
- 2004-05-03 CA CA002524034A patent/CA2524034A1/fr not_active Abandoned

Also Published As

Publication number	Publication date
WO2004098525A2 (fr)	2004-11-18
WO2004098525A9 (fr)	2005-01-20
WO2004098525A3 (fr)	2005-04-14

Publication	Publication Date	Title
US7820712B2 (en)	2010-10-26	Uses of ion channel modulating compounds
CA2524034A1 (fr)	2004-11-18	Utilisations de composes modulant les canaux ioniques
US7687536B2 (en)	2010-03-30	Aminocycloalkyl cinnamide compounds for arrhythmia and as analgesics and anesthetics
EP1087934B1 (fr)	2004-02-25	Composes d'aminocyclohexyl ether et leurs applications
US20100210626A1 (en)	2010-08-19	Pharmaceutical composition comprising a monoamine neurotransmitter re-uptake inhibitor and an acetylcholinesterase inhibitor
KR20160108611A (ko)	2016-09-19	심방세동의 치료 방법
US7057053B2 (en)	2006-06-06	Ion channel modulating compounds and uses thereof
EP2501381B1 (fr)	2017-07-26	Traitement de la fibrillation atriale
JP5680412B2 (ja)	2015-03-04	レオヌリンの使用およびその組成物
RU2213560C2 (ru)	2003-10-10	Фармацевтическая композиция, содержащая сочетание правовращающего и левовращающего изомеров соталола
US20090041841A1 (en)	2009-02-12	Controlled release tablet formulations for the prevention of arrhythmias
CA2370834C (fr)	2007-09-25	Utilisation du saredutant et de ses sels pharmaceutiquement acceptables dans le traitement ou la prevention des troubles de l'humeur d'adaptation et de l'anxiete-depression
KR100352898B1 (ko)	2002-12-26	새로운3-벤조일-3,7-디아자바이사이클로[3,3,1]노난-화합물을함유하는약제
RU2358732C2 (ru)	2009-06-20	Жидкие фармацевтические композиции, содержащие производные 3,7-диазабицикло(3,3,1)нонана, для лечения антиаритмических реакций
EP1868598B1 (fr)	2014-04-23	Schemas posologiques pour modulateurs de canaux ioniques pour le traitement de la fibrillation auriculaire aigue chez l'homme
CA2533492A1 (fr)	2005-02-10	Utilisation de composes de 3,7-diazabicyclo[3,3,1]nonane pour traiter et/ou prevenir des evenements arythmiques chez des patients humains males
MXPA05011808A (en)	2006-10-17	Uses of ion channel modulating compounds
EA028995B1 (ru)	2018-01-31	Соль тезофензина и оптически активных ацетиламинокислот, их применение для лечения и/или профилактики нарушений, связанных с ожирением
US20050054667A1 (en)	2005-03-10	Method of treating or inhibiting anti-arrhythmic events in male human patients
JP2002255819A (ja)	2002-09-11	神経栄養因子的作用剤
HK1254495B (en)	2023-02-24	Use of sulcardine for the treatment of atrial fibrillation
HK1176859A (en)	2013-08-09	Treatment of atrial fibrillation
HK1176859B (en)	2018-05-04	Treatment of atrial fibrillation
JP2003026569A (ja)	2003-01-29	肝疾患治療剤
ZA200300220B (en)	2004-04-08	Compounds for the treatment of addictive disorders.

Legal Events

Date	Code	Title	Description
2009-04-29	EEER	Examination request
2019-06-15	FZDE	Dead	Effective date: 20190503