AU2001242669A1 - Pharmaceutical compositions of glycogen phosphorylase inhibitors - Google Patents

Pharmaceutical compositions of glycogen phosphorylase inhibitors

Info

Publication number: AU2001242669A1
Authority: AU; Australia
Prior art keywords: alkyl; composition; cellulose acetate; hydroxy; strand
Prior art date: 2000-03-16
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

AU2001242669A

Other languages

English (en)

Inventor

Dwayne Thomas Friesen

Dennis Jay Hoover

Douglas Alan Lorenz

James Alan Schriver Nightingale

Ravi Mysore Shanker

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.)

Pfizer Products Inc

Original Assignee

Pfizer Products Inc

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.)

2000-03-16

Filing date

2001-03-16

Publication date

2001-09-24

2001-03-16 Application filed by Pfizer Products Inc filed Critical Pfizer Products Inc

2001-09-24 Publication of AU2001242669A1 publication Critical patent/AU2001242669A1/en

Status Abandoned legal-status Critical Current

Links

102000007390 Glycogen Phosphorylase Human genes 0.000 title claims description 37
108010046163 Glycogen Phosphorylase Proteins 0.000 title claims description 37
239000008194 pharmaceutical composition Substances 0.000 title claims description 15
239000003112 inhibitor Substances 0.000 title description 21
ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 claims description 280
229920000642 polymer Polymers 0.000 claims description 267
239000000203 mixture Substances 0.000 claims description 254
125000000217 alkyl group Chemical group 0.000 claims description 244
-1 trifuloromethyl Chemical group 0.000 claims description 174
125000003545 alkoxy group Chemical group 0.000 claims description 71
238000000034 method Methods 0.000 claims description 68
229920002301 cellulose acetate Polymers 0.000 claims description 58
125000005843 halogen group Chemical group 0.000 claims description 57
239000002904 solvent Substances 0.000 claims description 56
239000006185 dispersion Substances 0.000 claims description 53
150000001875 compounds Chemical class 0.000 claims description 48
125000001424 substituent group Chemical group 0.000 claims description 45
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
FUQOTYRCMBZFOL-UHFFFAOYSA-N 5-chloro-1H-indole-2-carboxylic acid Chemical group ClC1=CC=C2NC(C(=O)O)=CC2=C1 FUQOTYRCMBZFOL-UHFFFAOYSA-N 0.000 claims description 34
229910052799 carbon Inorganic materials 0.000 claims description 34
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 33
229940081735 acetylcellulose Drugs 0.000 claims description 32
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 29
235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 29
125000004093 cyano group Chemical group *C#N 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 28
239000001863 hydroxypropyl cellulose Substances 0.000 claims description 28
206010012601 diabetes mellitus Diseases 0.000 claims description 27
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 26
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 25
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 24
229910052757 nitrogen Inorganic materials 0.000 claims description 24
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 23
239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 21
238000001694 spray drying Methods 0.000 claims description 21
GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 claims description 20
125000003282 alkyl amino group Chemical group 0.000 claims description 20
239000007787 solid Substances 0.000 claims description 20
125000005591 trimellitate group Chemical group 0.000 claims description 20
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 20
239000001257 hydrogen Substances 0.000 claims description 19
230000002209 hydrophobic effect Effects 0.000 claims description 18
125000003118 aryl group Chemical group 0.000 claims description 17
239000000651 prodrug Substances 0.000 claims description 17
229940002612 prodrug Drugs 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 17
125000000623 heterocyclic group Chemical group 0.000 claims description 16
229920000609 methyl cellulose Polymers 0.000 claims description 16
235000010981 methylcellulose Nutrition 0.000 claims description 16
239000001923 methylcellulose Substances 0.000 claims description 16
229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 15
239000007864 aqueous solution Substances 0.000 claims description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
229940081734 cellulose acetate phthalate Drugs 0.000 claims description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 15
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims description 15
238000001727 in vivo Methods 0.000 claims description 15
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
125000004076 pyridyl group Chemical group 0.000 claims description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 13
230000002708 enhancing effect Effects 0.000 claims description 13
125000001475 halogen functional group Chemical group 0.000 claims description 13
239000006069 physical mixture Substances 0.000 claims description 13
IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 claims description 12
125000001153 fluoro group Chemical group F* 0.000 claims description 12
125000002541 furyl group Chemical group 0.000 claims description 12
125000002883 imidazolyl group Chemical group 0.000 claims description 12
125000001786 isothiazolyl group Chemical group 0.000 claims description 12
125000000842 isoxazolyl group Chemical group 0.000 claims description 12
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
125000002971 oxazolyl group Chemical group 0.000 claims description 12
125000003373 pyrazinyl group Chemical group 0.000 claims description 12
125000003226 pyrazolyl group Chemical group 0.000 claims description 12
125000002098 pyridazinyl group Chemical group 0.000 claims description 12
125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
125000000168 pyrrolyl group Chemical group 0.000 claims description 12
125000000335 thiazolyl group Chemical group 0.000 claims description 12
125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims description 11
201000001320 Atherosclerosis Diseases 0.000 claims description 11
229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
238000012545 processing Methods 0.000 claims description 11
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
206010020772 Hypertension Diseases 0.000 claims description 10
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 10
125000005842 heteroatom Chemical group 0.000 claims description 10
208000028867 ischemia Diseases 0.000 claims description 10
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 10
208000002177 Cataract Diseases 0.000 claims description 9
229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims description 9
208000035150 Hypercholesterolemia Diseases 0.000 claims description 9
208000031226 Hyperlipidaemia Diseases 0.000 claims description 9
206010022489 Insulin Resistance Diseases 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
201000001421 hyperglycemia Diseases 0.000 claims description 9
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 9
229910052717 sulfur Inorganic materials 0.000 claims description 9
208000007342 Diabetic Nephropathies Diseases 0.000 claims description 8
208000032131 Diabetic Neuropathies Diseases 0.000 claims description 8
239000001856 Ethyl cellulose Substances 0.000 claims description 8
241001465754 Metazoa Species 0.000 claims description 8
125000000676 alkoxyimino group Chemical group 0.000 claims description 8
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 8
229920006218 cellulose propionate Polymers 0.000 claims description 8
208000033679 diabetic kidney disease Diseases 0.000 claims description 8
235000019325 ethyl cellulose Nutrition 0.000 claims description 8
229920001249 ethyl cellulose Polymers 0.000 claims description 8
125000001072 heteroaryl group Chemical group 0.000 claims description 8
125000002757 morpholinyl group Chemical group 0.000 claims description 8
125000004043 oxo group Chemical group O=* 0.000 claims description 8
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 8
125000004193 piperazinyl group Chemical group 0.000 claims description 8
125000003386 piperidinyl group Chemical group 0.000 claims description 8
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 8
125000003072 pyrazolidinyl group Chemical group 0.000 claims description 8
125000002755 pyrazolinyl group Chemical group 0.000 claims description 8
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
206010012689 Diabetic retinopathy Diseases 0.000 claims description 7
241000282414 Homo sapiens Species 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
SOGNHUJSAKAIRG-UHFFFAOYSA-N 2-chloro-6h-thieno[2,3-b]pyrrole-5-carboxylic acid Chemical group C1=C(Cl)SC2=C1C=C(C(=O)O)N2 SOGNHUJSAKAIRG-UHFFFAOYSA-N 0.000 claims description 6
239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 6
229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 6
ZNPLZHBZUSCANM-UHFFFAOYSA-N acetic acid;benzene-1,3-dicarboxylic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC(C(O)=O)=C1 ZNPLZHBZUSCANM-UHFFFAOYSA-N 0.000 claims description 6
PLEULVPCZZDBNB-UHFFFAOYSA-N acetic acid;butanedioic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O PLEULVPCZZDBNB-UHFFFAOYSA-N 0.000 claims description 6
FMTQGBMMIVVKSN-UHFFFAOYSA-N acetic acid;terephthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=C(C(O)=O)C=C1 FMTQGBMMIVVKSN-UHFFFAOYSA-N 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 6
230000005764 inhibitory process Effects 0.000 claims description 6
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
125000000304 alkynyl group Chemical group 0.000 claims description 5
125000001589 carboacyl group Chemical group 0.000 claims description 5
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
238000000338 in vitro Methods 0.000 claims description 5
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 5
229960004889 salicylic acid Drugs 0.000 claims description 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
125000006529 (C3-C6) alkyl group Chemical group 0.000 claims description 4
VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 claims description 4
ZNNQGSGPVUYWOS-UHFFFAOYSA-N 2-(3-hydroxypropoxy)benzoic acid Chemical compound OCCCOC1=CC=CC=C1C(O)=O ZNNQGSGPVUYWOS-UHFFFAOYSA-N 0.000 claims description 4
OEXIDSNKGPWFGB-UHFFFAOYSA-N 2-ethyl-3-(3-hydroxypropyl)benzoic acid Chemical compound CCC1=C(CCCO)C=CC=C1C(O)=O OEXIDSNKGPWFGB-UHFFFAOYSA-N 0.000 claims description 4
CGMMPMYKMDITEA-UHFFFAOYSA-N 2-ethylbenzoic acid Chemical compound CCC1=CC=CC=C1C(O)=O CGMMPMYKMDITEA-UHFFFAOYSA-N 0.000 claims description 4
RESGCFMULOVHHB-UHFFFAOYSA-N 2-ethylpyridine-3-carboxylic acid Chemical compound CCC1=NC=CC=C1C(O)=O RESGCFMULOVHHB-UHFFFAOYSA-N 0.000 claims description 4
NMGBFVPQUCLJGM-UHFFFAOYSA-N 3-ethylphthalic acid Chemical compound CCC1=CC=CC(C(O)=O)=C1C(O)=O NMGBFVPQUCLJGM-UHFFFAOYSA-N 0.000 claims description 4
VFTOHJFKIJLYKN-UHFFFAOYSA-N 7-nitro-9h-fluoren-2-ol Chemical group [O-][N+](=O)C1=CC=C2C3=CC=C(O)C=C3CC2=C1 VFTOHJFKIJLYKN-UHFFFAOYSA-N 0.000 claims description 4
DQEFEBPAPFSJLV-UHFFFAOYSA-N Cellulose propionate Chemical compound CCC(=O)OCC1OC(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C1OC1C(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C(COC(=O)CC)O1 DQEFEBPAPFSJLV-UHFFFAOYSA-N 0.000 claims description 4
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 4
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 claims description 4
GZRANGIRVYGSDJ-UHFFFAOYSA-N acetic acid;pyridine-2,3-dicarboxylic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CN=C1C(O)=O GZRANGIRVYGSDJ-UHFFFAOYSA-N 0.000 claims description 4
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 4
VHEMBTYWURNBQQ-UHFFFAOYSA-N butanoic acid;phthalic acid Chemical compound CCCC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O VHEMBTYWURNBQQ-UHFFFAOYSA-N 0.000 claims description 4
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 4
239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
229920001727 cellulose butyrate Polymers 0.000 claims description 4
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
208000031225 myocardial ischemia Diseases 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
230000002441 reversible effect Effects 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
229920002554 vinyl polymer Polymers 0.000 claims description 4
INTNEELQXPKMNM-UHFFFAOYSA-N 3-ethylpyridine-2-carboxylic acid Chemical compound CCC1=CC=CN=C1C(O)=O INTNEELQXPKMNM-UHFFFAOYSA-N 0.000 claims description 3
XULPAMMHMRIVOO-UHFFFAOYSA-N 5-acetyl-n-[3-[(4-bromophenyl)carbamoyl]phenyl]-1-methyl-2-oxo-3h-indole-3-carboxamide Chemical compound C12=CC(C(C)=O)=CC=C2N(C)C(=O)C1C(=O)NC(C=1)=CC=CC=1C(=O)NC1=CC=C(Br)C=C1 XULPAMMHMRIVOO-UHFFFAOYSA-N 0.000 claims description 3
QUWRSNVQONCPEX-UHFFFAOYSA-N 5-chloro-n-[2-oxo-2-(1-oxo-1,3-thiazolidin-3-yl)ethyl]-1h-indole-2-carboxamide Chemical compound C=1C2=CC(Cl)=CC=C2NC=1C(=O)NCC(=O)N1CCS(=O)C1 QUWRSNVQONCPEX-UHFFFAOYSA-N 0.000 claims description 3
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 3
SIOXPEMLGUPBBT-UHFFFAOYSA-N Picolinic acid Natural products OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 3
239000008112 carboxymethyl-cellulose Substances 0.000 claims description 3
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 3
210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
230000002401 inhibitory effect Effects 0.000 claims description 3
229960002900 methylcellulose Drugs 0.000 claims description 3
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims description 3
125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 claims description 2
125000004317 1,3,5-triazin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=N1 0.000 claims description 2
125000005987 1-oxo-thiomorpholinyl group Chemical group 0.000 claims description 2
RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 2
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 2
WAAVFJWSRFFSSW-BETUJISGSA-N 5-chloro-n-[2-[(3s,4r)-3,4-dihydroxypyrrolidin-1-yl]-2-oxoethyl]-1h-indole-2-carboxamide Chemical group C1[C@@H](O)[C@@H](O)CN1C(=O)CNC(=O)C1=CC2=CC(Cl)=CC=C2N1 WAAVFJWSRFFSSW-BETUJISGSA-N 0.000 claims description 2
208000035143 Bacterial infection Diseases 0.000 claims description 2
208000032781 Diabetic cardiomyopathy Diseases 0.000 claims description 2
XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 2
208000022362 bacterial infectious disease Diseases 0.000 claims description 2
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
VYGAQHDGEYQIJU-UHFFFAOYSA-N butanedioic acid;phthalic acid Chemical compound OC(=O)CCC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O VYGAQHDGEYQIJU-UHFFFAOYSA-N 0.000 claims description 2
CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical group C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
229920003064 carboxyethyl cellulose Polymers 0.000 claims description 2
229910021419 crystalline silicon Inorganic materials 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
229920013819 hydroxyethyl ethylcellulose Polymers 0.000 claims description 2
125000001041 indolyl group Chemical group 0.000 claims description 2
DOTMOQHOJINYBL-UHFFFAOYSA-N molecular nitrogen;molecular oxygen Chemical compound N#N.O=O DOTMOQHOJINYBL-UHFFFAOYSA-N 0.000 claims description 2
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
229940081066 picolinic acid Drugs 0.000 claims description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
230000004614 tumor growth Effects 0.000 claims description 2
229920006163 vinyl copolymer Polymers 0.000 claims description 2
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical group CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 claims 6
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 2
VFFMCGXIWQUAEL-UHFFFAOYSA-N 5-acetyl-1-ethyl-2-oxo-n-[3-(phenylcarbamoyl)phenyl]-3h-indole-3-carboxamide Chemical group C12=CC(C(C)=O)=CC=C2N(CC)C(=O)C1C(=O)NC(C=1)=CC=CC=1C(=O)NC1=CC=CC=C1 VFFMCGXIWQUAEL-UHFFFAOYSA-N 0.000 claims 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
KFPUKDCJSXIZJN-OEEJBDNKSA-N 5-chloro-N-[2-[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]-2-oxoethyl]-1H-indole-2-carboxamide 5-chloro-1H-indole-2-carboxylic acid Chemical group ClC=1C=C2C=C(NC2=CC1)C(=O)O.O[C@@H]1CN(C[C@@H]1O)C(CNC(=O)C=1NC2=CC=C(C=C2C1)Cl)=O KFPUKDCJSXIZJN-OEEJBDNKSA-N 0.000 claims 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
208000006575 hypertriglyceridemia Diseases 0.000 claims 1
125000003107 substituted aryl group Chemical group 0.000 claims 1
229940079593 drug Drugs 0.000 description 133
239000003814 drug Substances 0.000 description 133
239000000243 solution Substances 0.000 description 65
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 53
239000002552 dosage form Substances 0.000 description 48
238000012360 testing method Methods 0.000 description 45
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
238000010922 spray-dried dispersion Methods 0.000 description 41
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 38
239000003826 tablet Substances 0.000 description 35
230000008569 process Effects 0.000 description 32
239000000463 material Substances 0.000 description 27
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 26
238000007922 dissolution test Methods 0.000 description 25
238000002156 mixing Methods 0.000 description 24
239000002245 particle Substances 0.000 description 23
238000000576 coating method Methods 0.000 description 22
239000011248 coating agent Substances 0.000 description 19
235000019359 magnesium stearate Nutrition 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
239000011324 bead Substances 0.000 description 17
239000000546 pharmaceutical excipient Substances 0.000 description 17
210000004369 blood Anatomy 0.000 description 16
239000008280 blood Substances 0.000 description 16
239000002775 capsule Substances 0.000 description 16
239000007921 spray Substances 0.000 description 16
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 15
239000002953 phosphate buffered saline Substances 0.000 description 15
239000002253 acid Substances 0.000 description 14
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 14
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 14
239000000843 powder Substances 0.000 description 14
239000007962 solid dispersion Substances 0.000 description 14
239000003288 aldose reductase inhibitor Substances 0.000 description 13
235000010980 cellulose Nutrition 0.000 description 13
229920002678 cellulose Polymers 0.000 description 13
239000001913 cellulose Substances 0.000 description 13
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 13
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 12
238000001035 drying Methods 0.000 description 12
210000002381 plasma Anatomy 0.000 description 12
239000000725 suspension Substances 0.000 description 12
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 11
229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 11
238000004090 dissolution Methods 0.000 description 11
239000008103 glucose Substances 0.000 description 11
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 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
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 10
150000001721 carbon Chemical group 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
230000000694 effects Effects 0.000 description 10
239000011159 matrix material Substances 0.000 description 10
229920006395 saturated elastomer Polymers 0.000 description 10
210000001519 tissue Anatomy 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
239000007788 liquid Substances 0.000 description 9
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 9
239000012530 fluid Substances 0.000 description 8
230000002440 hepatic effect Effects 0.000 description 8
239000001993 wax Substances 0.000 description 8
102000003676 Glucocorticoid Receptors Human genes 0.000 description 7
108090000079 Glucocorticoid Receptors Proteins 0.000 description 7
206010060378 Hyperinsulinaemia Diseases 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
230000009229 glucose formation Effects 0.000 description 7
230000003451 hyperinsulinaemic effect Effects 0.000 description 7
201000008980 hyperinsulinism Diseases 0.000 description 7
230000007935 neutral effect Effects 0.000 description 7
238000001556 precipitation Methods 0.000 description 7
241000282472 Canis lupus familiaris Species 0.000 description 6
102000004877 Insulin Human genes 0.000 description 6
108090001061 Insulin Proteins 0.000 description 6
108010009384 L-Iditol 2-Dehydrogenase Proteins 0.000 description 6
102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 description 6
230000002411 adverse Effects 0.000 description 6
230000008901 benefit Effects 0.000 description 6
239000003850 glucocorticoid receptor antagonist Substances 0.000 description 6
230000004116 glycogenolysis Effects 0.000 description 6
108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
239000004615 ingredient Substances 0.000 description 6
229940125396 insulin Drugs 0.000 description 6
210000004185 liver Anatomy 0.000 description 6
238000003801 milling Methods 0.000 description 6
229920000036 polyvinylpyrrolidone Polymers 0.000 description 6
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
238000005507 spraying Methods 0.000 description 6
229910001220 stainless steel Inorganic materials 0.000 description 6
239000010935 stainless steel Substances 0.000 description 6
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 6
239000004094 surface-active agent Substances 0.000 description 6
230000000929 thyromimetic effect Effects 0.000 description 6
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 5
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 5
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 5
229910019142 PO4 Inorganic materials 0.000 description 5
102100026974 Sorbitol dehydrogenase Human genes 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
239000000654 additive Substances 0.000 description 5
125000004414 alkyl thio group Chemical group 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
230000000712 assembly Effects 0.000 description 5
238000000429 assembly Methods 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
150000001735 carboxylic acids Chemical class 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
239000003862 glucocorticoid Substances 0.000 description 5
239000008187 granular material Substances 0.000 description 5
150000002431 hydrogen Chemical group 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
235000021317 phosphate Nutrition 0.000 description 5
235000015424 sodium Nutrition 0.000 description 5
239000011734 sodium Substances 0.000 description 5
229940083542 sodium Drugs 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000008279 sol Substances 0.000 description 5
230000007480 spreading Effects 0.000 description 5
238000003892 spreading Methods 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
239000011593 sulfur Substances 0.000 description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
BCSVCWVQNOXFGL-UHFFFAOYSA-N 3,4-dihydro-4-oxo-3-((5-trifluoromethyl-2-benzothiazolyl)methyl)-1-phthalazine acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(C(F)(F)F)=CC=C2S1 BCSVCWVQNOXFGL-UHFFFAOYSA-N 0.000 description 4
208000002249 Diabetes Complications Diseases 0.000 description 4
206010012655 Diabetic complications Diseases 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
241000124008 Mammalia Species 0.000 description 4
229920000168 Microcrystalline cellulose Polymers 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000013103 analytical ultracentrifugation Methods 0.000 description 4
125000002619 bicyclic group Chemical group 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000000872 buffer Substances 0.000 description 4
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
WZNRVWBKYDHTKI-UHFFFAOYSA-N cellulose, acetate 1,2,4-benzenetricarboxylate Chemical compound OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.OC(=O)C1=CC(C(=O)O)=CC=C1C(=O)OCC1C(OC2C(C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(COC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)O2)OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)O1 WZNRVWBKYDHTKI-UHFFFAOYSA-N 0.000 description 4
230000008859 change Effects 0.000 description 4
238000013270 controlled release Methods 0.000 description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000001125 extrusion Methods 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
239000008108 microcrystalline cellulose Substances 0.000 description 4
235000019813 microcrystalline cellulose Nutrition 0.000 description 4
229940016286 microcrystalline cellulose Drugs 0.000 description 4
230000026731 phosphorylation Effects 0.000 description 4
238000006366 phosphorylation reaction Methods 0.000 description 4
235000018102 proteins Nutrition 0.000 description 4
102000004169 proteins and genes Human genes 0.000 description 4
108090000623 proteins and genes Proteins 0.000 description 4
239000002002 slurry Substances 0.000 description 4
235000019333 sodium laurylsulphate Nutrition 0.000 description 4
239000006104 solid solution Substances 0.000 description 4
239000008107 starch Substances 0.000 description 4
229940032147 starch Drugs 0.000 description 4
239000005495 thyroid hormone Substances 0.000 description 4
229940036555 thyroid hormone Drugs 0.000 description 4
238000013518 transcription Methods 0.000 description 4
230000035897 transcription Effects 0.000 description 4
229950005346 zopolrestat Drugs 0.000 description 4
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
RIIVBOIBIOLLPO-UHFFFAOYSA-N 2-phthalazin-1-ylacetic acid Chemical compound C1=CC=C2C(CC(=O)O)=NN=CC2=C1 RIIVBOIBIOLLPO-UHFFFAOYSA-N 0.000 description 3
229920003084 Avicel® PH-102 Polymers 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
101100136727 Caenorhabditis elegans psd-1 gene Proteins 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
229920002527 Glycogen Polymers 0.000 description 3
102000004316 Oxidoreductases Human genes 0.000 description 3
108090000854 Oxidoreductases Proteins 0.000 description 3
239000004698 Polyethylene Substances 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
208000017442 Retinal disease Diseases 0.000 description 3
206010038923 Retinopathy Diseases 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229940100389 Sulfonylurea Drugs 0.000 description 3
WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 3
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 3
150000007513 acids Chemical class 0.000 description 3
239000000556 agonist Substances 0.000 description 3
125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 3
125000002877 alkyl aryl group Chemical group 0.000 description 3
125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
239000003472 antidiabetic agent Substances 0.000 description 3
238000000889 atomisation Methods 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000000052 comparative effect Effects 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
229920001577 copolymer Polymers 0.000 description 3
125000000392 cycloalkenyl group Chemical group 0.000 description 3
230000007423 decrease Effects 0.000 description 3
239000008367 deionised water Substances 0.000 description 3
229910021641 deionized water Inorganic materials 0.000 description 3
235000014113 dietary fatty acids Nutrition 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
230000002183 duodenal effect Effects 0.000 description 3
229930195729 fatty acid Natural products 0.000 description 3
239000000194 fatty acid Substances 0.000 description 3
235000019000 fluorine Nutrition 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000007789 gas Substances 0.000 description 3
229940124750 glucocorticoid receptor agonist Drugs 0.000 description 3
229940096919 glycogen Drugs 0.000 description 3
239000007970 homogeneous dispersion Substances 0.000 description 3
229940126904 hypoglycaemic agent Drugs 0.000 description 3
230000002218 hypoglycaemic effect Effects 0.000 description 3
230000001965 increasing effect Effects 0.000 description 3
208000017169 kidney disease Diseases 0.000 description 3
239000000155 melt Substances 0.000 description 3
239000000693 micelle Substances 0.000 description 3
201000001119 neuropathy Diseases 0.000 description 3
230000007823 neuropathy Effects 0.000 description 3
229940042126 oral powder Drugs 0.000 description 3
125000004430 oxygen atom Chemical group O* 0.000 description 3
208000033808 peripheral neuropathy Diseases 0.000 description 3
229920000058 polyacrylate Polymers 0.000 description 3
229920000573 polyethylene Polymers 0.000 description 3
229920000193 polymethacrylate Polymers 0.000 description 3
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
229940068968 polysorbate 80 Drugs 0.000 description 3
229920000053 polysorbate 80 Polymers 0.000 description 3
229920002451 polyvinyl alcohol Polymers 0.000 description 3
235000019422 polyvinyl alcohol Nutrition 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
230000002265 prevention Effects 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
238000005070 sampling Methods 0.000 description 3
239000001488 sodium phosphate Substances 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
239000008223 sterile water Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
150000003871 sulfonates Chemical class 0.000 description 3
239000006228 supernatant Substances 0.000 description 3
229940037128 systemic glucocorticoids Drugs 0.000 description 3
WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical compound C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 3
239000012085 test solution Substances 0.000 description 3
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
238000005550 wet granulation Methods 0.000 description 3
238000009736 wetting Methods 0.000 description 3
FOZFSEMFCIPOSZ-SPCKQMHLSA-N (2r,3r,4r,5s)-2-(hydroxymethyl)-1-[[(2r,3s,4s,5r,6s)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]methyl]piperidine-3,4,5-triol;trihydrate Chemical compound O.O.O.O[C@H]1[C@H](O)[C@@H](O)[C@@H](OC)O[C@@H]1CN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1.O[C@H]1[C@H](O)[C@@H](O)[C@@H](OC)O[C@@H]1CN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 FOZFSEMFCIPOSZ-SPCKQMHLSA-N 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 2
XDZMPRGFOOFSBL-UHFFFAOYSA-N 2-ethoxybenzoic acid Chemical group CCOC1=CC=CC=C1C(O)=O XDZMPRGFOOFSBL-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
NKOHRVBBQISBSB-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1CC1C(=O)NC(=O)S1 NKOHRVBBQISBSB-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
208000030507 AIDS Diseases 0.000 description 2
229940118148 Aldose reductase inhibitor Drugs 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
229940123208 Biguanide Drugs 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
125000004399 C1-C4 alkenyl group Chemical group 0.000 description 2
125000006374 C2-C10 alkenyl group Chemical group 0.000 description 2
125000006375 C2-C10 alkynyl group Chemical group 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 2
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 2
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 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
208000036119 Frailty Diseases 0.000 description 2
208000002705 Glucose Intolerance Diseases 0.000 description 2
229920002907 Guar gum Polymers 0.000 description 2
241000282412 Homo Species 0.000 description 2
241000725303 Human immunodeficiency virus Species 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
208000013016 Hypoglycemia Diseases 0.000 description 2
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
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 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
239000004743 Polypropylene Substances 0.000 description 2
239000004372 Polyvinyl alcohol Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 2
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
UYWNJNXEHSUWLE-HFWGUVFESA-N [(2R)-3-hexadecanoyloxy-2-[(Z)-octadec-9-enoxy]propyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC UYWNJNXEHSUWLE-HFWGUVFESA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
229960001466 acetohexamide Drugs 0.000 description 2
VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 2
125000004423 acyloxy group Chemical group 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
150000001323 aldoses Chemical class 0.000 description 2
125000005236 alkanoylamino group Chemical group 0.000 description 2
125000005422 alkyl sulfonamido group Chemical group 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
125000000129 anionic group Chemical group 0.000 description 2
206010003549 asthenia Diseases 0.000 description 2
229960000686 benzalkonium chloride Drugs 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
150000004283 biguanides Chemical class 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
235000010290 biphenyl Nutrition 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
239000007853 buffer solution Substances 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
229960001948 caffeine Drugs 0.000 description 2
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-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
150000001720 carbohydrates Chemical group 0.000 description 2
229960004424 carbon dioxide Drugs 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
229940105329 carboxymethylcellulose Drugs 0.000 description 2
230000000747 cardiac effect Effects 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
229960001761 chlorpropamide Drugs 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000006071 cream Substances 0.000 description 2
229960000913 crospovidone Drugs 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 2
239000007884 disintegrant Substances 0.000 description 2
238000007908 dry granulation Methods 0.000 description 2
230000003628 erosive effect Effects 0.000 description 2
150000004665 fatty acids Chemical class 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
230000006870 function Effects 0.000 description 2
230000004927 fusion Effects 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
230000014509 gene expression Effects 0.000 description 2
230000009477 glass transition Effects 0.000 description 2
235000010417 guar gum Nutrition 0.000 description 2
239000000665 guar gum Substances 0.000 description 2
229960002154 guar gum Drugs 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
150000002475 indoles Chemical class 0.000 description 2
230000003993 interaction Effects 0.000 description 2
230000000968 intestinal effect Effects 0.000 description 2
210000004731 jugular vein Anatomy 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
150000002632 lipids Chemical class 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
229920002521 macromolecule Polymers 0.000 description 2
238000010297 mechanical methods and process Methods 0.000 description 2
230000005226 mechanical processes and functions Effects 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
238000002844 melting Methods 0.000 description 2
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
229960003105 metformin Drugs 0.000 description 2
IQSHMXAZFHORGY-UHFFFAOYSA-N methyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound COC(=O)C=C.CC(=C)C(O)=O IQSHMXAZFHORGY-UHFFFAOYSA-N 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
210000003205 muscle Anatomy 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
238000003305 oral gavage Methods 0.000 description 2
239000002357 osmotic agent Substances 0.000 description 2
SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical class NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 2
239000003002 pH adjusting agent Substances 0.000 description 2
230000036961 partial effect Effects 0.000 description 2
239000006072 paste Substances 0.000 description 2
229960003243 phenformin Drugs 0.000 description 2
ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
125000005498 phthalate group Chemical group 0.000 description 2
HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
229920001155 polypropylene Polymers 0.000 description 2
229920000136 polysorbate Polymers 0.000 description 2
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
201000009104 prediabetes syndrome Diseases 0.000 description 2
GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
238000007711 solidification Methods 0.000 description 2
230000008023 solidification Effects 0.000 description 2
241000894007 species Species 0.000 description 2
238000003860 storage Methods 0.000 description 2
239000001384 succinic acid Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 2
239000010414 supernatant solution Substances 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
239000002562 thickening agent Substances 0.000 description 2
150000003566 thiocarboxylic acids Chemical class 0.000 description 2
125000003396 thiol group Chemical class [H]S* 0.000 description 2
230000000451 tissue damage Effects 0.000 description 2
231100000827 tissue damage Toxicity 0.000 description 2
229960005371 tolbutamide Drugs 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
229910000406 trisodium phosphate Inorganic materials 0.000 description 2
235000019801 trisodium phosphate Nutrition 0.000 description 2
DZLOHEOHWICNIL-QGZVFWFLSA-N (2R)-2-[6-(4-chlorophenoxy)hexyl]-2-oxiranecarboxylic acid ethyl ester Chemical compound C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)OCC)CO1 DZLOHEOHWICNIL-QGZVFWFLSA-N 0.000 description 1
JOBIFMUBWMXUJJ-XFMZQWNHSA-L (2r)-2-amino-3-(octylamino)-3-oxopropane-1-thiolate;oxovanadium(2+) Chemical compound [V+2]=O.CCCCCCCCNC(=O)[C@@H](N)C[S-].CCCCCCCCNC(=O)[C@@H](N)C[S-] JOBIFMUBWMXUJJ-XFMZQWNHSA-L 0.000 description 1
JAKAFSGZUXCHLF-LSCFUAHRSA-N (2r,3r,4r,5r)-5-[6-(cyclohexylamino)purin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NC3CCCCC3)=C2N=C1 JAKAFSGZUXCHLF-LSCFUAHRSA-N 0.000 description 1
VSWSDTLXDWESGZ-AWEZNQCLSA-N (2s)-3-[4-(4-hydroxyphenoxy)phenyl]-2-(iodoamino)propanoic acid Chemical class C1=CC(C[C@@H](C(=O)O)NI)=CC=C1OC1=CC=C(O)C=C1 VSWSDTLXDWESGZ-AWEZNQCLSA-N 0.000 description 1
WAAPEIZFCHNLKK-UFBFGSQYSA-N (2s,4s)-6-fluoro-2',5'-dioxospiro[2,3-dihydrochromene-4,4'-imidazolidine]-2-carboxamide Chemical compound C([C@H](OC1=CC=C(F)C=C11)C(=O)N)[C@@]21NC(=O)NC2=O WAAPEIZFCHNLKK-UFBFGSQYSA-N 0.000 description 1
SRJRJOYFPZRDNH-NSHDSACASA-N (4s)-6-fluorospiro[3h-chromene-4,5'-imidazolidine]-2,4'-dione Chemical compound C12=CC(F)=CC=C2OC(=O)C[C@@]21NCNC2=O SRJRJOYFPZRDNH-NSHDSACASA-N 0.000 description 1
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 description 1
OPPLDIXFHYTSSR-GLECISQGSA-N (ne)-n-(1-methylpyrrolidin-2-ylidene)-n'-phenylmorpholine-4-carboximidamide Chemical compound CN1CCC\C1=N/C(N1CCOCC1)=NC1=CC=CC=C1 OPPLDIXFHYTSSR-GLECISQGSA-N 0.000 description 1
UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
CWMYWRMDANXCSB-UHFFFAOYSA-N 1-oxoethanesulfonic acid Chemical compound CC(=O)S(O)(=O)=O CWMYWRMDANXCSB-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
QCCHBHSAIQIQGO-UHFFFAOYSA-N 2,7-difluorospiro[fluorene-9,5'-imidazolidine]-2',4'-dione Chemical compound C12=CC(F)=CC=C2C2=CC=C(F)C=C2C21NC(=O)NC2=O QCCHBHSAIQIQGO-UHFFFAOYSA-N 0.000 description 1
SNTGHASAODNGHV-UHFFFAOYSA-N 2-(1,2-dihydroquinazolin-2-yl)acetic acid Chemical compound C1=CC=C2C=NC(CC(=O)O)NC2=C1 SNTGHASAODNGHV-UHFFFAOYSA-N 0.000 description 1
RATZLMXRALDSJW-UHFFFAOYSA-N 2-(2-ethyl-3H-benzofuran-2-yl)-4,5-dihydro-1H-imidazole Chemical compound C1C2=CC=CC=C2OC1(CC)C1=NCCN1 RATZLMXRALDSJW-UHFFFAOYSA-N 0.000 description 1
TYZQFNOLWJGHRZ-UHFFFAOYSA-N 2-[2-(4,5-dihydro-1h-imidazol-2-yl)-1-phenylethyl]pyridine Chemical compound N=1CCNC=1CC(C=1N=CC=CC=1)C1=CC=CC=C1 TYZQFNOLWJGHRZ-UHFFFAOYSA-N 0.000 description 1
XSHTXZXPLDNDKC-UHFFFAOYSA-N 2-[3-[(5,7-dichloro-1,3-benzothiazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(Cl)=CC(Cl)=C2S1 XSHTXZXPLDNDKC-UHFFFAOYSA-N 0.000 description 1
FTPBFNMYCGQFGU-UHFFFAOYSA-N 2-[3-[(5,7-dichloro-1,3-benzoxazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(Cl)=CC(Cl)=C2O1 FTPBFNMYCGQFGU-UHFFFAOYSA-N 0.000 description 1
KNWXUWPPDTZSFW-UHFFFAOYSA-N 2-[3-[(5,7-difluoro-1,3-benzothiazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(F)=CC(F)=C2S1 KNWXUWPPDTZSFW-UHFFFAOYSA-N 0.000 description 1
GDULRSFIHLMHJW-UHFFFAOYSA-N 2-[3-[(5,7-difluoro-1,3-benzoxazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(F)=CC(F)=C2O1 GDULRSFIHLMHJW-UHFFFAOYSA-N 0.000 description 1
LNCWRJYGGOAOMU-UHFFFAOYSA-N 2-[3-[(5-chloro-1,3-benzothiazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(Cl)=CC=C2S1 LNCWRJYGGOAOMU-UHFFFAOYSA-N 0.000 description 1
LURVWPRCGVAWKT-UHFFFAOYSA-N 2-[3-[(5-chloro-1,3-benzoxazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(Cl)=CC=C2O1 LURVWPRCGVAWKT-UHFFFAOYSA-N 0.000 description 1
QUBABKJOUGUHAK-UHFFFAOYSA-N 2-[3-[(5-fluoro-1,3-benzothiazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(F)=CC=C2S1 QUBABKJOUGUHAK-UHFFFAOYSA-N 0.000 description 1
WXNKRTWVLOSZPW-UHFFFAOYSA-N 2-[3-[(5-fluoro-1,3-benzoxazol-2-yl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(F)=CC=C2O1 WXNKRTWVLOSZPW-UHFFFAOYSA-N 0.000 description 1
BUYWFAJWTSIACV-UHFFFAOYSA-N 2-[3-oxo-4-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1,4-benzothiazin-2-yl]acetic acid Chemical compound FC1=CC(F)=C2SC(CN3C4=CC=CC=C4SC(C3=O)CC(=O)O)=NC2=C1F BUYWFAJWTSIACV-UHFFFAOYSA-N 0.000 description 1
NCPQFFSHHWRZQW-UHFFFAOYSA-N 2-[3-oxo-4-[2-(4,5,7-trifluoro-1,3-benzothiazol-2-yl)ethyl]-1,4-benzothiazin-2-yl]acetic acid Chemical compound FC1=CC(F)=C2SC(CCN3C4=CC=CC=C4SC(C3=O)CC(=O)O)=NC2=C1F NCPQFFSHHWRZQW-UHFFFAOYSA-N 0.000 description 1
ZGGNJJJYUVRADP-ACJLOTCBSA-N 2-[4-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(Cl)C=CC=1)C1=CC=C(OCC(O)=O)C=C1 ZGGNJJJYUVRADP-ACJLOTCBSA-N 0.000 description 1
RVMBDLSFFNKKLG-SFHVURJKSA-N 2-[4-[2-[[(2s)-2-hydroxy-3-phenoxypropyl]amino]ethoxy]phenoxy]-n-(2-methoxyethyl)acetamide Chemical compound C1=CC(OCC(=O)NCCOC)=CC=C1OCCNC[C@H](O)COC1=CC=CC=C1 RVMBDLSFFNKKLG-SFHVURJKSA-N 0.000 description 1
QKRGDZKQCDTVMW-UHFFFAOYSA-N 2-[4-oxo-3-[[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]methyl]phthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(C(F)(F)F)=CC=C2O1 QKRGDZKQCDTVMW-UHFFFAOYSA-N 0.000 description 1
ACZKTJZXXSHIGF-UHFFFAOYSA-N 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1CCCCCC1(C(=O)O)CO1 ACZKTJZXXSHIGF-UHFFFAOYSA-N 0.000 description 1
XCMJQQOMGWGGSI-UHFFFAOYSA-N 2-ethoxypyridine-3-carboxylic acid Chemical compound CCOC1=NC=CC=C1C(O)=O XCMJQQOMGWGGSI-UHFFFAOYSA-N 0.000 description 1
JRGBXEJDIMXJAP-UHFFFAOYSA-N 2-fluorospiro[fluorene-9,5'-imidazolidine]-2',4'-dione Chemical compound C12=CC(F)=CC=C2C2=CC=CC=C2C21NC(=O)NC2=O JRGBXEJDIMXJAP-UHFFFAOYSA-N 0.000 description 1
OXOWWPXTTOCKKU-UHFFFAOYSA-N 2-propoxybenzoic acid Chemical compound CCCOC1=CC=CC=C1C(O)=O OXOWWPXTTOCKKU-UHFFFAOYSA-N 0.000 description 1
CDOUZKKFHVEKRI-UHFFFAOYSA-N 3-bromo-n-[(prop-2-enoylamino)methyl]propanamide Chemical compound BrCCC(=O)NCNC(=O)C=C CDOUZKKFHVEKRI-UHFFFAOYSA-N 0.000 description 1
QTVCNUYGSSNMDT-UHFFFAOYSA-N 3-ethoxypyridine-2-carboxylic acid Chemical compound CCOC1=CC=CN=C1C(O)=O QTVCNUYGSSNMDT-UHFFFAOYSA-N 0.000 description 1
SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
OPPQEWZOPDBGAS-UHFFFAOYSA-N 4-[3-[bis(2-hydroxy-2-phenylethyl)amino]butyl]benzamide Chemical compound C=1C=CC=CC=1C(O)CN(CC(O)C=1C=CC=CC=1)C(C)CCC1=CC=C(C(N)=O)C=C1 OPPQEWZOPDBGAS-UHFFFAOYSA-N 0.000 description 1
WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
AZRRZGIBBLWSSQ-UHFFFAOYSA-N 4-ethyl-7-phenyl-3,5-diazabicyclo[2.2.2]octane-2,6-dione Chemical compound N1C(=O)C2C(=O)NC1(CC)CC2C1=CC=CC=C1 AZRRZGIBBLWSSQ-UHFFFAOYSA-N 0.000 description 1
125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
JPXQQFCADYJMMN-UHFFFAOYSA-N 5-chloro-n-[2-(1,1-dioxo-1,3-thiazolidin-3-yl)-2-oxoethyl]-1h-indole-2-carboxamide Chemical compound C=1C2=CC(Cl)=CC=C2NC=1C(=O)NCC(=O)N1CCS(=O)(=O)C1 JPXQQFCADYJMMN-UHFFFAOYSA-N 0.000 description 1
125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
DJQOOSBJCLSSEY-UHFFFAOYSA-N Acipimox Chemical compound CC1=CN=C(C(O)=O)C=[N+]1[O-] DJQOOSBJCLSSEY-UHFFFAOYSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
208000026872 Addison Disease Diseases 0.000 description 1
101710152627 Aldose reductase A Proteins 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
206010003210 Arteriosclerosis Diseases 0.000 description 1
108010011485 Aspartame Proteins 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
208000010392 Bone Fractures Diseases 0.000 description 1
SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
BUELMBFSPQNFIS-UHFFFAOYSA-N C=1(C=CC2=CCC=CC12)O Chemical compound C=1(C=CC2=CCC=CC12)O BUELMBFSPQNFIS-UHFFFAOYSA-N 0.000 description 1
206010006895 Cachexia Diseases 0.000 description 1
208000031229 Cardiomyopathies Diseases 0.000 description 1
PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
206010010071 Coma Diseases 0.000 description 1
OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
208000014311 Cushing syndrome Diseases 0.000 description 1
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 1
108020004414 DNA Proteins 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
239000001692 EU approved anti-caking agent Substances 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
208000010412 Glaucoma Diseases 0.000 description 1
102000051325 Glucagon Human genes 0.000 description 1
108060003199 Glucagon Proteins 0.000 description 1
DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 description 1
FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
229940121931 Gluconeogenesis inhibitor Drugs 0.000 description 1
102000004366 Glucosidases Human genes 0.000 description 1
108010056771 Glucosidases Proteins 0.000 description 1
206010053240 Glycogen storage disease type VI Diseases 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010061598 Immunodeficiency Diseases 0.000 description 1
208000029462 Immunodeficiency disease Diseases 0.000 description 1
108010065920 Insulin Lispro Proteins 0.000 description 1
229940122199 Insulin secretagogue Drugs 0.000 description 1
OWYWGLHRNBIFJP-UHFFFAOYSA-N Ipazine Chemical compound CCN(CC)C1=NC(Cl)=NC(NC(C)C)=N1 OWYWGLHRNBIFJP-UHFFFAOYSA-N 0.000 description 1
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
206010054805 Macroangiopathy Diseases 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
GQWNECFJGBQMBO-UHFFFAOYSA-N Molindone hydrochloride Chemical compound Cl.O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 GQWNECFJGBQMBO-UHFFFAOYSA-N 0.000 description 1
125000000815 N-oxide group Chemical group 0.000 description 1
208000008589 Obesity Diseases 0.000 description 1
208000001132 Osteoporosis Diseases 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
108010016731 PPAR gamma Proteins 0.000 description 1
239000002033 PVDF binder Substances 0.000 description 1
102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
102100040918 Pro-glucagon Human genes 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
102000052126 Sodium-Hydrogen Exchangers Human genes 0.000 description 1
108091006672 Sodium–hydrogen antiporter Proteins 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
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 1
229930006000 Sucrose Natural products 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102000040945 Transcription factor Human genes 0.000 description 1
108091023040 Transcription factor Proteins 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical group CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
229960002632 acarbose Drugs 0.000 description 1
XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
LIPOUNRJVLNBCD-UHFFFAOYSA-N acetyl dihydrogen phosphate Chemical compound CC(=O)OP(O)(O)=O LIPOUNRJVLNBCD-UHFFFAOYSA-N 0.000 description 1
229960003526 acipimox Drugs 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
210000001789 adipocyte Anatomy 0.000 description 1
230000001919 adrenal effect Effects 0.000 description 1
238000013019 agitation Methods 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
125000005011 alkyl ether group Chemical group 0.000 description 1
230000007815 allergy Effects 0.000 description 1
HXXFSFRBOHSIMQ-VFUOTHLCSA-N alpha-D-glucose 1-phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(O)=O)[C@H](O)[C@@H](O)[C@@H]1O HXXFSFRBOHSIMQ-VFUOTHLCSA-N 0.000 description 1
229960004909 aminosalicylic acid Drugs 0.000 description 1
229920006125 amorphous polymer Polymers 0.000 description 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
208000022531 anorexia Diseases 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000003243 anti-lipolytic effect Effects 0.000 description 1
239000000883 anti-obesity agent Substances 0.000 description 1
239000003529 anticholesteremic agent Substances 0.000 description 1
229940127226 anticholesterol agent Drugs 0.000 description 1
239000003524 antilipemic agent Substances 0.000 description 1
229940125710 antiobesity agent Drugs 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
208000011775 arteriosclerosis disease Diseases 0.000 description 1
239000007961 artificial flavoring substance Substances 0.000 description 1
239000008122 artificial sweetener Substances 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000000605 aspartame Substances 0.000 description 1
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
235000010357 aspartame Nutrition 0.000 description 1
229960003438 aspartame Drugs 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
238000000498 ball milling Methods 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
229960001264 benfluorex Drugs 0.000 description 1
UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
CJAVTWRYCDNHSM-UHFFFAOYSA-N benzoic acid 2-[1-[3-(trifluoromethyl)phenyl]propan-2-ylamino]ethyl ester Chemical compound C=1C=CC=CC=1C(=O)OCCNC(C)CC1=CC=CC(C(F)(F)F)=C1 CJAVTWRYCDNHSM-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
229960004217 benzyl alcohol Drugs 0.000 description 1
239000003613 bile acid Substances 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229960004111 buformin Drugs 0.000 description 1
XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 description 1
JUNWLZAGQLJVLR-UHFFFAOYSA-J calcium diphosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O JUNWLZAGQLJVLR-UHFFFAOYSA-J 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
229950001261 camiglibose Drugs 0.000 description 1
239000007833 carbon precursor Substances 0.000 description 1
150000005323 carbonate salts Chemical class 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
210000003855 cell nucleus Anatomy 0.000 description 1
YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
229950009226 ciglitazone Drugs 0.000 description 1
229950006376 clomoxir Drugs 0.000 description 1
230000019771 cognition Effects 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000010668 complexation reaction Methods 0.000 description 1
239000008139 complexing agent Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
231100000867 compulsive behavior Toxicity 0.000 description 1
239000000470 constituent Substances 0.000 description 1
OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
229960001681 croscarmellose sodium Drugs 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
210000000172 cytosol Anatomy 0.000 description 1
206010061428 decreased appetite Diseases 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
BADQRNHAZHSOKC-UHFFFAOYSA-N deriglidole Chemical compound C1C(C2=3)=CC=CC=3CCN2C1(CCC)C1=NCCN1 BADQRNHAZHSOKC-UHFFFAOYSA-N 0.000 description 1
229950011527 deriglidole Drugs 0.000 description 1
238000011161 development Methods 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229910000393 dicalcium diphosphate Inorganic materials 0.000 description 1
235000019821 dicalcium diphosphate Nutrition 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
238000000113 differential scanning calorimetry Methods 0.000 description 1
238000007865 diluting Methods 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
229940113088 dimethylacetamide Drugs 0.000 description 1
150000002009 diols Chemical group 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
239000004815 dispersion polymer Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
229940018602 docusate Drugs 0.000 description 1
229960000878 docusate sodium Drugs 0.000 description 1
238000009837 dry grinding Methods 0.000 description 1
238000007580 dry-mixing Methods 0.000 description 1
229950001765 efaroxan Drugs 0.000 description 1
229920001971 elastomer Polymers 0.000 description 1
229950000269 emiglitate Drugs 0.000 description 1
229950002375 englitazone Drugs 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 description 1
229950010170 epalrestat Drugs 0.000 description 1
CHNUOJQWGUIOLD-UHFFFAOYSA-N epalrestate Natural products C=1C=CC=CC=1C=C(C)C=C1SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-UHFFFAOYSA-N 0.000 description 1
230000001667 episodic effect Effects 0.000 description 1
LUJQXGBDWAGQHS-UHFFFAOYSA-N ethenyl acetate;phthalic acid Chemical compound CC(=O)OC=C.OC(=O)C1=CC=CC=C1C(O)=O LUJQXGBDWAGQHS-UHFFFAOYSA-N 0.000 description 1
125000002573 ethenylidene group Chemical group [*]=C=C([H])[H] 0.000 description 1
NWWORXYTJRPSMC-QKPAOTATSA-N ethyl 4-[2-[(2r,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]ethoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCCN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 NWWORXYTJRPSMC-QKPAOTATSA-N 0.000 description 1
229950006213 etomoxir Drugs 0.000 description 1
229960001582 fenfluramine Drugs 0.000 description 1
NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
XSOUHEXVEOQRKJ-IUCAKERBSA-N fluparoxan Chemical compound O1[C@H]2CNC[C@@H]2OC2=C1C=CC=C2F XSOUHEXVEOQRKJ-IUCAKERBSA-N 0.000 description 1
229950006702 fluparoxan Drugs 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
229920001002 functional polymer Polymers 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
229960004580 glibenclamide Drugs 0.000 description 1
229960004346 glimepiride Drugs 0.000 description 1
WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
229960001381 glipizide Drugs 0.000 description 1
ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
229960004666 glucagon Drugs 0.000 description 1
229940126013 glucocorticoid receptor antagonist Drugs 0.000 description 1
230000004110 gluconeogenesis Effects 0.000 description 1
230000010030 glucose lowering effect Effects 0.000 description 1
229950010772 glucose-1-phosphate Drugs 0.000 description 1
ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
208000007345 glycogen storage disease Diseases 0.000 description 1
201000004510 glycogen storage disease VI Diseases 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
230000013632 homeostatic process Effects 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
229960000890 hydrocortisone Drugs 0.000 description 1
239000000017 hydrogel Substances 0.000 description 1
239000008172 hydrogenated vegetable oil Substances 0.000 description 1
229920001477 hydrophilic polymer Polymers 0.000 description 1
125000001165 hydrophobic group Chemical group 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
HPMRFMKYPGXPEP-UHFFFAOYSA-N idazoxan Chemical compound N1CCN=C1C1OC2=CC=CC=C2OC1 HPMRFMKYPGXPEP-UHFFFAOYSA-N 0.000 description 1
229950001476 idazoxan Drugs 0.000 description 1
150000002462 imidazolines Chemical class 0.000 description 1
230000002519 immonomodulatory effect Effects 0.000 description 1
230000007813 immunodeficiency Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000004941 influx Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
229950011269 isaglidole Drugs 0.000 description 1
208000037906 ischaemic injury Diseases 0.000 description 1
LVPMIMZXDYBCDF-UHFFFAOYSA-N isocinchomeronic acid Chemical class OC(=O)C1=CC=C(C(O)=O)N=C1 LVPMIMZXDYBCDF-UHFFFAOYSA-N 0.000 description 1
QQVIHTHCMHWDBS-UHFFFAOYSA-L isophthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC(C([O-])=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-L 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
230000007775 late Effects 0.000 description 1
239000007942 layered tablet Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229950004872 linogliride Drugs 0.000 description 1
230000002366 lipolytic effect Effects 0.000 description 1
238000011068 loading method Methods 0.000 description 1
230000007774 longterm Effects 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
239000000391 magnesium silicate Substances 0.000 description 1
229910052919 magnesium silicate Inorganic materials 0.000 description 1
235000019792 magnesium silicate Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
229950004994 meglitinide Drugs 0.000 description 1
230000008018 melting Effects 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
ZFLBZHXQAMUEFS-UHFFFAOYSA-N methyl 2-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OC)=CC=C1CC(C)NCC(O)C1=CC=CC(Cl)=C1 ZFLBZHXQAMUEFS-UHFFFAOYSA-N 0.000 description 1
229940043265 methyl isobutyl ketone Drugs 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
206010062198 microangiopathy Diseases 0.000 description 1
229950001332 midaglizole Drugs 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
239000000178 monomer Substances 0.000 description 1
230000036457 multidrug resistance Effects 0.000 description 1
230000002107 myocardial effect Effects 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
ZLVARELBORDLAV-UHFFFAOYSA-N n-(4,5-dihydro-1h-imidazol-2-yl)-4-fluoro-1,3-dihydroisoindol-2-amine Chemical compound C1C=2C(F)=CC=CC=2CN1NC1=NCCN1 ZLVARELBORDLAV-UHFFFAOYSA-N 0.000 description 1
YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
GZCNKQPANHRSAJ-UHFFFAOYSA-N n-[3,5-dimethyl-4-(nitromethylsulfonyl)phenyl]-2-(2-methylphenyl)acetamide Chemical compound CC1=CC=CC=C1CC(=O)NC1=CC(C)=C(S(=O)(=O)C[N+]([O-])=O)C(C)=C1 GZCNKQPANHRSAJ-UHFFFAOYSA-N 0.000 description 1
229950006031 naglivan Drugs 0.000 description 1
239000002159 nanocrystal Substances 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
239000003538 oral antidiabetic agent Substances 0.000 description 1
229940127209 oral hypoglycaemic agent Drugs 0.000 description 1
229940100692 oral suspension Drugs 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000000466 oxiranyl group Chemical group 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
235000020030 perry Nutrition 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
239000000049 pigment Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
229960005095 pioglitazone Drugs 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
239000004584 polyacrylic acid Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920002959 polymer blend Polymers 0.000 description 1
229950008882 polysorbate Drugs 0.000 description 1
229920002689 polyvinyl acetate Polymers 0.000 description 1
239000011118 polyvinyl acetate Substances 0.000 description 1
229920002744 polyvinyl acetate phthalate Polymers 0.000 description 1
229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
229920002981 polyvinylidene fluoride Polymers 0.000 description 1
230000000291 postprandial effect Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
235000007686 potassium Nutrition 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
238000000634 powder X-ray diffraction Methods 0.000 description 1
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
229960004618 prednisone Drugs 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
201000009395 primary hyperaldosteronism Diseases 0.000 description 1
229940090181 propyl acetate Drugs 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
GJAWHXHKYYXBSV-UHFFFAOYSA-N pyridinedicarboxylic acid Natural products OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 description 1
GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 1
238000007712 rapid solidification Methods 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
231100000628 reference dose Toxicity 0.000 description 1
229960002354 repaglinide Drugs 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000979 retarding effect Effects 0.000 description 1
210000001525 retina Anatomy 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
229960004586 rosiglitazone Drugs 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910052814 silicon oxide Inorganic materials 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 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
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
229960003885 sodium benzoate Drugs 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
235000011008 sodium phosphates 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
238000000935 solvent evaporation Methods 0.000 description 1
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
LXANPKRCLVQAOG-NSHDSACASA-N sorbinil Chemical compound C12=CC(F)=CC=C2OCC[C@@]21NC(=O)NC2=O LXANPKRCLVQAOG-NSHDSACASA-N 0.000 description 1
229950004311 sorbinil Drugs 0.000 description 1
238000005563 spheronization Methods 0.000 description 1
210000001032 spinal nerve Anatomy 0.000 description 1
ZVGYIXBHESYHCE-UHFFFAOYSA-N spiro[6H-quinoline-5,4'-imidazolidine] Chemical compound N1=CC=CC2=C1C=CCC21NCNC1 ZVGYIXBHESYHCE-UHFFFAOYSA-N 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
229940071117 starch glycolate Drugs 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
235000011044 succinic acid Nutrition 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000008961 swelling Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
239000003749 thyromimetic agent Substances 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
229960002277 tolazamide Drugs 0.000 description 1
OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
LUBHDINQXIHVLS-UHFFFAOYSA-N tolrestat Chemical compound OC(=O)CN(C)C(=S)C1=CC=CC2=C(C(F)(F)F)C(OC)=CC=C21 LUBHDINQXIHVLS-UHFFFAOYSA-N 0.000 description 1
229960003069 tolrestat Drugs 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
229960001641 troglitazone Drugs 0.000 description 1
GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
229960004418 trolamine Drugs 0.000 description 1
229940116269 uric acid Drugs 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
150000003681 vanadium Chemical class 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
229960001729 voglibose Drugs 0.000 description 1
229920003169 water-soluble polymer Polymers 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1
238000001238 wet grinding Methods 0.000 description 1
230000029663 wound healing Effects 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
SXONDGSPUVNZLO-UHFFFAOYSA-N zenarestat Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F SXONDGSPUVNZLO-UHFFFAOYSA-N 0.000 description 1
229950006343 zenarestat Drugs 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- 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
- A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Obesity (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Urology & Nephrology (AREA)
Immunology (AREA)
Vascular Medicine (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Oncology (AREA)
Gastroenterology & Hepatology (AREA)
Communicable Diseases (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Indole Compounds (AREA)

AU2001242669A 2000-03-16 2001-03-16 Pharmaceutical compositions of glycogen phosphorylase inhibitors Abandoned AU2001242669A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US18994200P	2000-03-16	2000-03-16
US60189942		2000-03-16
PCT/IB2001/000394 WO2001068055A1 (en)	2000-03-16	2001-03-16	Pharmaceutical compositions of glycogen phosphorylase inhibitors

Publications (1)

Publication Number	Publication Date
AU2001242669A1 true AU2001242669A1 (en)	2001-09-24

Family

ID=22699402

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU2001242669A Abandoned AU2001242669A1 (en)	2000-03-16	2001-03-16	Pharmaceutical compositions of glycogen phosphorylase inhibitors

Country Status (32)

Country	Link
US (1)	US20010053778A1 (tr)
EP (1)	EP1263414A1 (tr)
JP (1)	JP2003526654A (tr)
KR (1)	KR20020081445A (tr)
CN (1)	CN1418089A (tr)
AP (1)	AP2002002621A0 (tr)
AR (1)	AR027656A1 (tr)
AU (1)	AU2001242669A1 (tr)
BG (1)	BG107037A (tr)
BR (1)	BR0109189A (tr)
CA (1)	CA2403241A1 (tr)
CO (1)	CO5280087A1 (tr)
CZ (1)	CZ20022955A3 (tr)
EA (1)	EA200200858A1 (tr)
EE (1)	EE200200530A (tr)
HU (1)	HUP0204583A2 (tr)
IL (1)	IL151320A0 (tr)
IS (1)	IS6508A (tr)
MA (1)	MA26882A1 (tr)
MX (1)	MXPA02009097A (tr)
NO (1)	NO20024386L (tr)
OA (1)	OA12232A (tr)
PA (1)	PA8513601A1 (tr)
PE (1)	PE20011184A1 (tr)
PL (1)	PL360780A1 (tr)
SK (1)	SK12622002A3 (tr)
SV (1)	SV2002000343A (tr)
TN (1)	TNSN01040A1 (tr)
TR (1)	TR200202184T2 (tr)
WO (1)	WO2001068055A1 (tr)
YU (1)	YU67202A (tr)
ZA (1)	ZA200207290B (tr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU2002302903B9 (en) *	2001-06-22	2003-01-08	Pfizer Products Inc.	Pharmaceutical compositions of adsorbates of amorphous drug

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CZ20022047A3 (cs) *	1999-12-23	2003-09-17	Pfizer Products Inc.	Farmaceutické kompozice poskytující zvýšenou koncentraci léčiva
CO5271699A1 (es)	2000-01-24	2003-04-30	Pfizer Prod Inc	Procedimiento para el tratamiento de cardiomiopatia utilizando inhibidores de la glucogeno fosforilasa
WO2002070478A1 (en)	2001-03-06	2002-09-12	Astrazeneca Ab	Indolone derivatives having vascular-damaging activity
ES2333645T3 (es) *	2001-06-22	2010-02-25	Bend Research, Inc.	Composiciones farmaceuticas de dispersiones de medicamentos y polimeros neutros.
EP1269994A3 (en) *	2001-06-22	2003-02-12	Pfizer Products Inc.	Pharmaceutical compositions comprising drug and concentration-enhancing polymers
MXPA03011935A (es) *	2001-06-22	2004-03-26	Pfizer Prod Inc	Composiciones farmaceuticas que contienen conjuntos de polimero y farmaco.
JP4865989B2 (ja)	2002-02-01	2012-02-01	ベンド・リサーチ・インコーポレーテッド	改良された噴霧乾燥装置を使用する均質な噴霧乾燥された固体の非晶質薬物分散物を製造する方法
BR0307515A (pt)	2002-02-01	2004-12-07	Pfizer Prod Inc	Método para fabricar dispersões de drogas amorfas sólidas secas por aspersão homogêneas usando bicos de pressão
ES2305434T3 (es)	2002-02-01	2008-11-01	Pfizer Products Inc.	Composiciones framaceuticas de dispersiones amorfas de farmacos y materiales que forman microfases lipofilas.
GB0205175D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205176D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205162D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205170D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205166D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205165D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
US7405210B2 (en)	2003-05-21	2008-07-29	Osi Pharmaceuticals, Inc.	Pyrrolopyridine-2-carboxylic acid amide inhibitors of glycogen phosphorylase
CL2004001884A1 (es)	2003-08-04	2005-06-03	Pfizer Prod Inc	Procedimiento de secado por pulverizacion para la formacion de dispersiones solidas amorfas de un farmaco y polimeros.
BRPI0413277A (pt)	2003-08-04	2006-10-10	Pfizer Prod Inc	composições farmacêuticas de adsorvatos de medicamentos amorfos e materiais que formam microfases lipofìlicas
US7390503B1 (en)	2003-08-22	2008-06-24	Barr Laboratories, Inc.	Ondansetron orally disintegrating tablets
JP2007517016A (ja) *	2003-12-31	2007-06-28	ファイザー・プロダクツ・インク	低溶解性薬剤及びポロキサマーの固体組成物
ES2353309T3 (es)	2004-03-08	2011-03-01	Prosidion Ltd.	Hidrazidas del ácido pirrolopiridin-2-carboxílico como inhibidores de glucógeno fosforilasa.
WO2006059163A1 (en) *	2004-12-02	2006-06-08	Prosidion Limited	Treatment of diabetes with glycogen phosphorylase inhibitors
DE102005026755A1 (de) *	2005-06-09	2006-12-14	Basf Ag	Herstellung von festen Lösungen schwerlöslicher Wirkstoffe durch Kurzzeitüberhitzung und schnelle Trocknung
US20150202301A1 (en) *	2012-08-24	2015-07-23	Dow Global Technologies Llc	Novel esterified cellulose ethers of high molecular weight and homogeneity
EA033374B9 (ru)	2012-09-11	2019-12-18	Медивейшн Простейт Терапьютикс Ллк	Твердые фармацевтические композиции, содержащие энзалутамид, и способ лечения
US9670158B2 (en)	2013-07-19	2017-06-06	Siga Technologies, Inc.	Amorphous tecovirimat preparation
CN103709171B (zh) *	2014-01-20	2015-09-16	武汉大学	具有哒嗪并[3,4-b]吲哚骨架结构的衍生物及其合成方法
CA2987867C (en)	2015-06-09	2023-06-27	Capsugel Belgium Nv	Formulations to achieve rapid dissolution of drug from spray-dried dispersions in capsules
CN112442022B (zh) *	2019-09-02	2022-05-20	承德医学院	苯并嗪-4-酮类化合物、其制备方法及医药用途
US11291701B1 (en) *	2021-02-04	2022-04-05	Seed Edibles	Orally disintegrating, sublingual and buccal formulations

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE206702T1 (de) *	1995-06-06	2001-10-15	Pfizer	Substituierte n-(indol-2-carbonyl)-glycinamide und derivate als glycogen phosphorylase inhibitoren
EP0832066B1 (en) *	1995-06-06	2001-09-12	Pfizer Inc.	Substituted n-(indole-2-carbonyl-) amides and derivatives as glycogen phosphorylase inhibitors
DE69837903T2 (de) *	1997-08-11	2008-02-14	Pfizer Products Inc., Groton	Feste pharmazeutische Dispersionen mit erhöhter Bioverfügbarkeit
US5998463A (en) *	1998-02-27	1999-12-07	Pfizer Inc	Glycogen phosphorylase inhibitors

2001
- 2001-03-14 AR ARP010101185A patent/AR027656A1/es not_active Application Discontinuation
- 2001-03-14 US US09/805,828 patent/US20010053778A1/en not_active Abandoned
- 2001-03-14 PE PE2001000246A patent/PE20011184A1/es not_active Application Discontinuation
- 2001-03-15 SV SV2001000343A patent/SV2002000343A/es not_active Application Discontinuation
- 2001-03-15 TN TNTNSN01040A patent/TNSN01040A1/fr unknown
- 2001-03-16 CZ CZ20022955A patent/CZ20022955A3/cs unknown
- 2001-03-16 KR KR1020027012009A patent/KR20020081445A/ko not_active Ceased
- 2001-03-16 EA EA200200858A patent/EA200200858A1/ru unknown
- 2001-03-16 CO CO01021769A patent/CO5280087A1/es not_active Application Discontinuation
- 2001-03-16 IL IL15132001A patent/IL151320A0/xx unknown
- 2001-03-16 AP APAP/P/2002/002621A patent/AP2002002621A0/en unknown
- 2001-03-16 PA PA20018513601A patent/PA8513601A1/es unknown
- 2001-03-16 CA CA002403241A patent/CA2403241A1/en not_active Abandoned
- 2001-03-16 HU HU0204583A patent/HUP0204583A2/hu unknown
- 2001-03-16 OA OA1200200290A patent/OA12232A/en unknown
- 2001-03-16 SK SK1262-2002A patent/SK12622002A3/sk unknown
- 2001-03-16 EE EEP200200530A patent/EE200200530A/xx unknown
- 2001-03-16 BR BR0109189-1A patent/BR0109189A/pt not_active Application Discontinuation
- 2001-03-16 YU YU67202A patent/YU67202A/sh unknown
- 2001-03-16 TR TR2002/02184T patent/TR200202184T2/tr unknown
- 2001-03-16 PL PL36078001A patent/PL360780A1/xx not_active Application Discontinuation
- 2001-03-16 MX MXPA02009097A patent/MXPA02009097A/es unknown
- 2001-03-16 CN CN01806619A patent/CN1418089A/zh active Pending
- 2001-03-16 WO PCT/IB2001/000394 patent/WO2001068055A1/en not_active Ceased
- 2001-03-16 JP JP2001566619A patent/JP2003526654A/ja active Pending
- 2001-03-16 EP EP01915586A patent/EP1263414A1/en not_active Withdrawn
- 2001-03-16 AU AU2001242669A patent/AU2001242669A1/en not_active Abandoned
2002
- 2002-08-16 IS IS6508A patent/IS6508A/is unknown
- 2002-08-26 BG BG107037A patent/BG107037A/bg unknown
- 2002-09-11 MA MA26810A patent/MA26882A1/fr unknown
- 2002-09-11 ZA ZA200207290A patent/ZA200207290B/xx unknown
- 2002-09-13 NO NO20024386A patent/NO20024386L/no not_active Application Discontinuation

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU2002302903B9 (en) *	2001-06-22	2003-01-08	Pfizer Products Inc.	Pharmaceutical compositions of adsorbates of amorphous drug
AU2002302903B2 (en) *	2001-06-22	2007-05-17	Pfizer Products Inc.	Pharmaceutical compositions of adsorbates of amorphous drug

Also Published As

Publication number	Publication date
SK12622002A3 (sk)	2004-02-03
US20010053778A1 (en)	2001-12-20
BR0109189A (pt)	2003-05-27
EE200200530A (et)	2004-04-15
AP2002002621A0 (en)	2002-09-30
OA12232A (en)	2006-05-10
IS6508A (is)	2002-08-16
NO20024386D0 (no)	2002-09-13
MXPA02009097A (es)	2003-03-12
CZ20022955A3 (cs)	2003-09-17
CO5280087A1 (es)	2003-05-30
KR20020081445A (ko)	2002-10-26
EP1263414A1 (en)	2002-12-11
PE20011184A1 (es)	2001-11-15
ZA200207290B (en)	2003-09-11
YU67202A (sh)	2006-01-16
EA200200858A1 (ru)	2003-02-27
BG107037A (bg)	2003-04-30
WO2001068055A1 (en)	2001-09-20
HUP0204583A2 (hu)	2003-04-28
CA2403241A1 (en)	2001-09-20
CN1418089A (zh)	2003-05-14
TNSN01040A1 (fr)	2005-11-10
PL360780A1 (en)	2004-09-20
TR200202184T2 (tr)	2003-01-21
MA26882A1 (fr)	2004-12-20
IL151320A0 (en)	2003-04-10
PA8513601A1 (es)	2004-08-31
AR027656A1 (es)	2003-04-09
JP2003526654A (ja)	2003-09-09
NO20024386L (no)	2002-11-13
SV2002000343A (es)	2002-07-03

Publication	Publication Date	Title
US20010053778A1 (en)	2001-12-20	Pharmaceutical compositions of glycogen phosphorylase inhibitors
JP6932746B2 (ja)	2021-09-08	エンザルタミドの製剤
US8796341B2 (en)	2014-08-05	Pharmaceutical compositions providing enhanced drug concentrations
KR100717570B1 (ko)	2007-05-15	치료 효과를 신속하게 개시하는 시클로옥시게나제-2저해제 조성물
TW200821298A (en)	2008-05-16	Pharmaceutical compositions
JP2011530532A (ja)	2011-12-22	固体分子分散物中のｈｃｖプロテアーゼインヒビターの薬学的処方物
US20100316711A1 (en)	2010-12-16	Nifedipine containing opress coated tablet and method of preparing same
TWI867526B (zh)	2024-12-21	Glp1醫藥組合物
ES2366394T3 (es)	2011-10-19	Composiciones de eprosartán.
WO2021230849A1 (en)	2021-11-18	Pharmaceutical compositions prepared by dry milling method and containing celecoxib with increased dissolution rate
US20240216347A1 (en)	2024-07-04	Bezuclastinib formulations
WO2007102038A1 (en)	2007-09-13	Ziprasidone formulations
HK1051968A (en)	2003-08-29	Pharmaceutical compositions of glycogen phosphorylase inhibitors