CN102600144A - 治疗糖尿病的罗氟司特 - Google Patents
治疗糖尿病的罗氟司特 Download PDFInfo
- Publication number
- CN102600144A CN102600144A CN2012100579547A CN201210057954A CN102600144A CN 102600144 A CN102600144 A CN 102600144A CN 2012100579547 A CN2012100579547 A CN 2012100579547A CN 201210057954 A CN201210057954 A CN 201210057954A CN 102600144 A CN102600144 A CN 102600144A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- iddm
- types
- treat
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 229960002586 roflumilast Drugs 0.000 title claims abstract description 62
- 206010012601 diabetes mellitus Diseases 0.000 title abstract description 29
- PCGSQNPMMSALEJ-UHFFFAOYSA-N roflumilast n-oxide Chemical compound ClC1=C[N+]([O-])=CC(Cl)=C1NC(=O)C1=CC=C(OC(F)F)C(OCC2CC2)=C1 PCGSQNPMMSALEJ-UHFFFAOYSA-N 0.000 claims abstract description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims description 319
- 150000001875 compounds Chemical class 0.000 claims description 299
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 207
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 115
- 239000008194 pharmaceutical composition Substances 0.000 claims description 101
- 238000000034 method Methods 0.000 claims description 83
- 239000013066 combination product Substances 0.000 claims description 56
- 229940127555 combination product Drugs 0.000 claims description 56
- 229940125396 insulin Drugs 0.000 claims description 54
- 108090001061 Insulin Proteins 0.000 claims description 49
- 102000004877 Insulin Human genes 0.000 claims description 49
- 239000008103 glucose Substances 0.000 claims description 44
- 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 claims description 43
- 239000000463 material Substances 0.000 claims description 42
- 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 claims description 39
- 239000012752 auxiliary agent Substances 0.000 claims description 34
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 33
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 33
- 208000002249 Diabetes Complications Diseases 0.000 claims description 29
- 206010012655 Diabetic complications Diseases 0.000 claims description 29
- 239000003112 inhibitor Substances 0.000 claims description 29
- 229940100389 Sulfonylurea Drugs 0.000 claims description 23
- 229940123208 Biguanide Drugs 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 22
- 238000012360 testing method Methods 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 21
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 20
- 230000002265 prevention Effects 0.000 claims description 20
- 238000011161 development Methods 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 229960003105 metformin Drugs 0.000 claims description 19
- 229960004586 rosiglitazone Drugs 0.000 claims description 19
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 18
- 208000008589 Obesity Diseases 0.000 claims description 18
- -1 PDE11 inhibitor Substances 0.000 claims description 18
- 239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 18
- 150000004283 biguanides Chemical class 0.000 claims description 17
- 229960005095 pioglitazone Drugs 0.000 claims description 16
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 16
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 claims description 15
- 239000004026 insulin derivative Substances 0.000 claims description 15
- 229960005371 tolbutamide Drugs 0.000 claims description 15
- LLJFMFZYVVLQKT-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea Chemical compound C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 LLJFMFZYVVLQKT-UHFFFAOYSA-N 0.000 claims description 13
- 239000005516 coenzyme A Substances 0.000 claims description 13
- 229940093530 coenzyme a Drugs 0.000 claims description 13
- 229960001381 glipizide Drugs 0.000 claims description 13
- 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 claims description 13
- 229960003468 gliquidone Drugs 0.000 claims description 13
- 229950004994 meglitinide Drugs 0.000 claims description 13
- 235000020824 obesity Nutrition 0.000 claims description 13
- 230000001575 pathological effect Effects 0.000 claims description 13
- XMSXOLDPMGMWTH-UHFFFAOYSA-N rivoglitazone Chemical compound CN1C2=CC(OC)=CC=C2N=C1COC(C=C1)=CC=C1CC1SC(=O)NC1=O XMSXOLDPMGMWTH-UHFFFAOYSA-N 0.000 claims description 13
- 229960002277 tolazamide Drugs 0.000 claims description 13
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 claims description 13
- GPCJDSXBRMKASP-UHFFFAOYSA-N 2,2-dichloro-12-(4-chlorophenyl)dodecanoic acid Chemical compound OC(=O)C(Cl)(Cl)CCCCCCCCCCC1=CC=C(Cl)C=C1 GPCJDSXBRMKASP-UHFFFAOYSA-N 0.000 claims description 12
- 229920001353 Dextrin Polymers 0.000 claims description 12
- 239000004375 Dextrin Substances 0.000 claims description 12
- 229960004346 glimepiride Drugs 0.000 claims description 12
- 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 claims description 12
- 229950010764 rivoglitazone Drugs 0.000 claims description 12
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 claims description 11
- OKJHGOPITGTTIM-DEOSSOPVSA-N Naveglitazar Chemical compound C1=CC(C[C@H](OC)C(O)=O)=CC=C1OCCCOC(C=C1)=CC=C1OC1=CC=CC=C1 OKJHGOPITGTTIM-DEOSSOPVSA-N 0.000 claims description 11
- 229960003362 carbutamide Drugs 0.000 claims description 11
- VDTNNGKXZGSZIP-UHFFFAOYSA-N carbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 VDTNNGKXZGSZIP-UHFFFAOYSA-N 0.000 claims description 11
- ZZCHHVUQYRMYLW-HKBQPEDESA-N farglitazar Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCC=1N=C(OC=1C)C=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 ZZCHHVUQYRMYLW-HKBQPEDESA-N 0.000 claims description 11
- 229960004580 glibenclamide Drugs 0.000 claims description 11
- 229960001764 glibornuride Drugs 0.000 claims description 11
- RMTYNAPTNBJHQI-LLDVTBCESA-N glibornuride Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)N[C@H]1[C@H](C2(C)C)CC[C@@]2(C)[C@H]1O RMTYNAPTNBJHQI-LLDVTBCESA-N 0.000 claims description 11
- 229960000346 gliclazide Drugs 0.000 claims description 11
- NSJYMFYVNWVGON-UHFFFAOYSA-N glisentide Chemical compound COC1=CC=CC=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCC2)C=C1 NSJYMFYVNWVGON-UHFFFAOYSA-N 0.000 claims description 11
- 229950008402 glisentide Drugs 0.000 claims description 11
- 229960003236 glisoxepide Drugs 0.000 claims description 11
- ZKUDBRCEOBOWLF-UHFFFAOYSA-N glisoxepide Chemical compound O1C(C)=CC(C(=O)NCCC=2C=CC(=CC=2)S(=O)(=O)NC(=O)NN2CCCCCC2)=N1 ZKUDBRCEOBOWLF-UHFFFAOYSA-N 0.000 claims description 11
- 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 claims description 11
- PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 claims description 11
- ZUGQWAYOWCBWGM-UHFFFAOYSA-N 2-[4-[[2-[2-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1,3-thiazol-5-yl]methylsulfanyl]-2-methylphenoxy]-2-methylpropanoic acid Chemical compound CC=1N=C(C=2C(=CC(=CC=2)C(F)(F)F)F)SC=1CSC1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 ZUGQWAYOWCBWGM-UHFFFAOYSA-N 0.000 claims description 10
- UYGZODVVDUIDDQ-UHFFFAOYSA-N 3-[(2,4-dichlorophenyl)methyl]-2-methyl-n-pentylsulfonylbenzimidazole-5-carboxamide Chemical compound C12=CC(C(=O)NS(=O)(=O)CCCCC)=CC=C2N=C(C)N1CC1=CC=C(Cl)C=C1Cl UYGZODVVDUIDDQ-UHFFFAOYSA-N 0.000 claims description 10
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 claims description 10
- 235000019425 dextrin Nutrition 0.000 claims description 10
- 229950003707 farglitazar Drugs 0.000 claims description 10
- 229950000958 halofenate Drugs 0.000 claims description 10
- 229950003494 naveglitazar Drugs 0.000 claims description 10
- 229950001628 netoglitazone Drugs 0.000 claims description 10
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 claims description 10
- 229950008257 ragaglitazar Drugs 0.000 claims description 10
- CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 claims description 10
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 9
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 claims description 9
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 claims description 9
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 9
- 101150014691 PPARA gene Proteins 0.000 claims description 9
- 229940122353 Phosphodiesterase 11 inhibitor Drugs 0.000 claims description 9
- 239000000556 agonist Substances 0.000 claims description 9
- 229950004704 tesaglitazar Drugs 0.000 claims description 9
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims description 8
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims description 8
- RUBKYBIDEVUTQU-UHFFFAOYSA-N 6-chloro-2-phenyl-3a,4-dihydroindeno[1,2-d][1,3]thiazol-8b-ol Chemical compound S1C(CC=2C3=CC=C(Cl)C=2)C3(O)N=C1C1=CC=CC=C1 RUBKYBIDEVUTQU-UHFFFAOYSA-N 0.000 claims description 8
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 claims description 8
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 claims description 8
- 229960002632 acarbose Drugs 0.000 claims description 8
- 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 claims description 8
- 230000003579 anti-obesity Effects 0.000 claims description 8
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 claims description 8
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 229960001110 miglitol Drugs 0.000 claims description 8
- WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 claims description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims description 7
- 101100407341 Drosophila melanogaster Pde9 gene Proteins 0.000 claims description 7
- 229940126033 PPAR agonist Drugs 0.000 claims description 7
- 229960003365 mitiglinide Drugs 0.000 claims description 7
- 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 claims description 7
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 claims description 7
- 229960004425 sibutramine Drugs 0.000 claims description 7
- 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 claims description 6
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 claims description 6
- 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 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 6
- 108010065920 Insulin Lispro Proteins 0.000 claims description 6
- 229940123464 Thiazolidinedione Drugs 0.000 claims description 6
- MVCQKIKWYUURMU-UHFFFAOYSA-N cetilistat Chemical compound C1=C(C)C=C2C(=O)OC(OCCCCCCCCCCCCCCCC)=NC2=C1 MVCQKIKWYUURMU-UHFFFAOYSA-N 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 229950006213 etomoxir Drugs 0.000 claims description 6
- 230000004060 metabolic process Effects 0.000 claims description 6
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 claims description 6
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 claims description 6
- VFFZWMWTUSXDCB-ZDUSSCGKSA-N 6-[2-[[2-[(2s)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]ethylamino]pyridine-3-carbonitrile Chemical compound N1([C@@H](CCC1)C#N)C(=O)CNCCNC1=CC=C(C#N)C=N1 VFFZWMWTUSXDCB-ZDUSSCGKSA-N 0.000 claims description 5
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 5
- URRAHSMDPCMOTH-LNLFQRSKSA-N Denagliptin Chemical compound C=1C=C(F)C=CC=1C([C@H](N)C(=O)N1[C@@H](C[C@H](F)C1)C#N)C1=CC=C(F)C=C1 URRAHSMDPCMOTH-LNLFQRSKSA-N 0.000 claims description 5
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 claims description 5
- 108010011459 Exenatide Proteins 0.000 claims description 5
- XVVOERDUTLJJHN-UHFFFAOYSA-N Lixisenatide Chemical compound C=1NC2=CC=CC=C2C=1CC(C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(=O)NCC(=O)NCC(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N1C(CCC1)C(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)CC)NC(=O)C(NC(=O)C(CC(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCSC)NC(=O)C(CCC(N)=O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC=1C=CC=CC=1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)CNC(=O)C(N)CC=1NC=NC=1)C(C)O)C(C)O)C(C)C)CC1=CC=CC=C1 XVVOERDUTLJJHN-UHFFFAOYSA-N 0.000 claims description 5
- 101150098694 PDE5A gene Proteins 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 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 claims description 5
- 239000002830 appetite depressant Substances 0.000 claims description 5
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 claims description 5
- 229950002397 cetilistat Drugs 0.000 claims description 5
- 229960001519 exenatide Drugs 0.000 claims description 5
- AIWAEWBZDJARBJ-PXUUZXDZSA-N fz7co35x2s 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](CCCN=C(N)N)C(=O)N[C@@H](CCCCNC(=O)COCCOCCNC(=O)CCN1C(C=CC1=O)=O)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 AIWAEWBZDJARBJ-PXUUZXDZSA-N 0.000 claims description 5
- 229960000698 nateglinide Drugs 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 229960002354 repaglinide Drugs 0.000 claims description 5
- 230000036186 satiety Effects 0.000 claims description 5
- 235000019627 satiety Nutrition 0.000 claims description 5
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 claims description 5
- 229960004034 sitagliptin Drugs 0.000 claims description 5
- WRGVLTAWMNZWGT-VQSPYGJZSA-N taspoglutide 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)NC(C)(C)C(=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(C)(C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 WRGVLTAWMNZWGT-VQSPYGJZSA-N 0.000 claims description 5
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 claims description 5
- 229960001729 voglibose Drugs 0.000 claims description 5
- 108700001281 BIM 51077 Proteins 0.000 claims description 4
- 108010055448 CJC 1131 Proteins 0.000 claims description 4
- 101001117089 Drosophila melanogaster Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1 Proteins 0.000 claims description 4
- 201000005569 Gout Diseases 0.000 claims description 4
- 201000001431 Hyperuricemia Diseases 0.000 claims description 4
- 238000002266 amputation Methods 0.000 claims description 4
- 229950010300 denagliptin Drugs 0.000 claims description 4
- 108010004367 lixisenatide Proteins 0.000 claims description 4
- 208000010125 myocardial infarction Diseases 0.000 claims description 4
- 229960004937 saxagliptin Drugs 0.000 claims description 4
- 108010033693 saxagliptin Proteins 0.000 claims description 4
- 229960000835 tadalafil Drugs 0.000 claims description 4
- 229950007151 taspoglutide Drugs 0.000 claims description 4
- 229960001254 vildagliptin Drugs 0.000 claims description 4
- 108010089308 Insulin Detemir Proteins 0.000 claims description 3
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 claims description 3
- 108010077977 Lente Insulin Proteins 0.000 claims description 3
- 108010019598 Liraglutide Proteins 0.000 claims description 3
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims description 3
- 208000007443 Neurasthenia Diseases 0.000 claims description 3
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 3
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 3
- 206010003549 asthenia Diseases 0.000 claims description 3
- LEMUFSYUPGXXCM-JNEQYSBXSA-N caninsulin Chemical compound [Zn].C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3N=CN=C3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 claims description 3
- 201000005577 familial hyperlipidemia Diseases 0.000 claims description 3
- 229960003948 insulin detemir Drugs 0.000 claims description 3
- 229960002869 insulin glargine Drugs 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- UGOZVNFCFYTPAZ-IOXYNQHNSA-N levemir Chemical compound CCCCCCCCCCCCCC(=O)NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=2C=CC=CC=2)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 UGOZVNFCFYTPAZ-IOXYNQHNSA-N 0.000 claims description 3
- 229960002701 liraglutide Drugs 0.000 claims description 3
- 201000005665 thrombophilia Diseases 0.000 claims description 3
- 238000003149 assay kit Methods 0.000 claims 32
- WMUIIGVAWPWQAW-DEOSSOPVSA-N (2s)-2-ethoxy-3-{4-[2-(10h-phenoxazin-10-yl)ethoxy]phenyl}propanoic acid Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCN1C2=CC=CC=C2OC2=CC=CC=C21 WMUIIGVAWPWQAW-DEOSSOPVSA-N 0.000 claims 8
- 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 claims 2
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 claims 2
- 229940076380 PDE9 inhibitor Drugs 0.000 claims 2
- 229940121836 Phosphodiesterase 1 inhibitor Drugs 0.000 claims 2
- 229960001466 acetohexamide Drugs 0.000 claims 2
- VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 claims 2
- RVEJWGYZBXCGGM-DNVCBOLYSA-N chembl2179094 Chemical compound C([C@H]([C@@H](C1)C=2NC(=O)C=3C=NN(C=3N=2)C2CCOCC2)C)N1CC1=CC=CC=C1 RVEJWGYZBXCGGM-DNVCBOLYSA-N 0.000 claims 2
- 229960001761 chlorpropamide Drugs 0.000 claims 2
- 229950006376 clomoxir Drugs 0.000 claims 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims 2
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 claims 2
- 229960001641 troglitazone Drugs 0.000 claims 2
- 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 claims 2
- 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 claims 2
- BJBCSGQLZQGGIQ-UHFFFAOYSA-N 2-acetamidoethyl 2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetate Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)OCCNC(=O)C)OC1=CC=CC(C(F)(F)F)=C1 BJBCSGQLZQGGIQ-UHFFFAOYSA-N 0.000 claims 1
- 239000013543 active substance Substances 0.000 abstract 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 78
- 239000002552 dosage form Substances 0.000 description 25
- 230000000694 effects Effects 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 14
- 201000001421 hyperglycemia Diseases 0.000 description 14
- 239000003826 tablet Substances 0.000 description 12
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000003203 everyday effect Effects 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 230000008878 coupling Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 239000000443 aerosol Substances 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000890 drug combination Substances 0.000 description 6
- 230000003914 insulin secretion Effects 0.000 description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 210000000496 pancreas Anatomy 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000003380 propellant Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000011125 single therapy Methods 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 229940122199 Insulin secretagogue Drugs 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 210000000577 adipose tissue Anatomy 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
- 230000002440 hepatic effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 235000012054 meals Nutrition 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 229960002381 vardenafil Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WMUIIGVAWPWQAW-XMMPIXPASA-N (2r)-2-ethoxy-3-[4-(2-phenoxazin-10-ylethoxy)phenyl]propanoic acid Chemical compound C1=CC(C[C@@H](OCC)C(O)=O)=CC=C1OCCN1C2=CC=CC=C2OC2=CC=CC=C21 WMUIIGVAWPWQAW-XMMPIXPASA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- 150000001204 N-oxides Chemical class 0.000 description 3
- 102000000536 PPAR gamma Human genes 0.000 description 3
- 108010016731 PPAR gamma Proteins 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000002269 analeptic agent Substances 0.000 description 3
- 230000002421 anti-septic effect Effects 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- WOXKDUGGOYFFRN-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 WOXKDUGGOYFFRN-IIBYNOLFSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical group C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 2
- YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 229920002527 Glycogen Polymers 0.000 description 2
- 206010018473 Glycosuria Diseases 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 2
- 239000005639 Lauric acid Substances 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- IRLWJILLXJGJTD-UHFFFAOYSA-N Muraglitazar Chemical compound C1=CC(OC)=CC=C1OC(=O)N(CC(O)=O)CC(C=C1)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IRLWJILLXJGJTD-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002738 chelating agent Substances 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
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000021588 free fatty acids Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229950006191 gluconic acid Drugs 0.000 description 2
- 230000004190 glucose uptake Effects 0.000 description 2
- 229940096919 glycogen Drugs 0.000 description 2
- 150000002357 guanidines Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 2
- 239000002050 international nonproprietary name Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229960003194 meglumine Drugs 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 2
- 239000006201 parenteral dosage form Substances 0.000 description 2
- 239000003961 penetration enhancing agent Substances 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000008299 semisolid dosage form Substances 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 229910052719 titanium Inorganic materials 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
- NOIHTGOGFDFCBN-UHFFFAOYSA-N 2-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylphenyl]-5-methyl-7-propyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one;dihydrochloride Chemical compound Cl.Cl.CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 NOIHTGOGFDFCBN-UHFFFAOYSA-N 0.000 description 1
- 208000004611 Abdominal Obesity Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010065941 Central obesity Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 101100135868 Dictyostelium discoideum pde3 gene Proteins 0.000 description 1
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 102000017011 Glycated Hemoglobin A Human genes 0.000 description 1
- 108010014663 Glycated Hemoglobin A Proteins 0.000 description 1
- 108010001483 Glycogen Synthase Proteins 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 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 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 229920000538 Poly[(phenyl isocyanate)-co-formaldehyde] Polymers 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-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
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 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 1
- 238000010876 biochemical test Methods 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229940019700 blood coagulation factors Drugs 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 235000021258 carbohydrate absorption Nutrition 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000002079 cooperative effect Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 230000000344 gluconeogenetic effect Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
- 201000008980 hyperinsulinism Diseases 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 108010042209 insulin receptor tyrosine kinase Proteins 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000006443 lactic acidosis Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000013190 lipid storage Effects 0.000 description 1
- 230000004132 lipogenesis Effects 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229950001135 muraglitazar Drugs 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000006965 reversible inhibition Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
- 229950005741 rolipram Drugs 0.000 description 1
- 229960003271 rosiglitazone maleate Drugs 0.000 description 1
- SUFUKZSWUHZXAV-BTJKTKAUSA-N rosiglitazone maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O SUFUKZSWUHZXAV-BTJKTKAUSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229960004115 sitagliptin phosphate Drugs 0.000 description 1
- 230000009943 skeletal muscle blood flow Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- DCLNDZSELPYYAX-UHFFFAOYSA-M sodium;n'-cyclohexyl-n-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)ethyl]phenyl]sulfonylcarbamimidate Chemical class [Na+].C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC([O-])=NC1CCCCC1 DCLNDZSELPYYAX-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- RTZRUVMEWWPNRR-UHFFFAOYSA-N tert-butyl n-(3-iodo-1h-pyrrolo[2,3-b]pyridin-5-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CN=C2NC=C(I)C2=C1 RTZRUVMEWWPNRR-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000001467 thiazolidinediones Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05101772.1 | 2005-03-08 | ||
| EP05101772 | 2005-03-08 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006800072465A Division CN101137368B (zh) | 2005-03-08 | 2006-03-03 | 治疗糖尿病的罗氟司特 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102600144A true CN102600144A (zh) | 2012-07-25 |
Family
ID=34938922
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012100579547A Pending CN102600144A (zh) | 2005-03-08 | 2006-03-03 | 治疗糖尿病的罗氟司特 |
| CN2006800072465A Expired - Fee Related CN101137368B (zh) | 2005-03-08 | 2006-03-03 | 治疗糖尿病的罗氟司特 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006800072465A Expired - Fee Related CN101137368B (zh) | 2005-03-08 | 2006-03-03 | 治疗糖尿病的罗氟司特 |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US8017633B2 (enExample) |
| EP (1) | EP1874308A1 (enExample) |
| JP (2) | JP5091106B2 (enExample) |
| KR (1) | KR101302838B1 (enExample) |
| CN (2) | CN102600144A (enExample) |
| AU (1) | AU2006222060B2 (enExample) |
| BR (1) | BRPI0609371A2 (enExample) |
| CA (1) | CA2599376C (enExample) |
| EA (1) | EA015382B1 (enExample) |
| IL (2) | IL185277A (enExample) |
| MX (1) | MX2007010560A (enExample) |
| NO (1) | NO20074943L (enExample) |
| NZ (1) | NZ560269A (enExample) |
| WO (1) | WO2006094933A1 (enExample) |
| ZA (1) | ZA200706294B (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2475573C (en) | 2002-02-11 | 2013-03-26 | Antares Pharma, Inc. | Intradermal injector |
| EP1850892B2 (en) | 2005-01-24 | 2023-04-19 | Antares Pharma, Inc. | Prefilled needle assisted syringe jet injector |
| CN102600144A (zh) * | 2005-03-08 | 2012-07-25 | 奈科明有限责任公司 | 治疗糖尿病的罗氟司特 |
| TW200738266A (en) * | 2005-09-29 | 2007-10-16 | Sankyo Co | Pharmaceutical agent containing insulin resistance improving agent |
| US8251947B2 (en) | 2006-05-03 | 2012-08-28 | Antares Pharma, Inc. | Two-stage reconstituting injector |
| WO2007131025A1 (en) | 2006-05-03 | 2007-11-15 | Antares Pharma, Inc. | Injector with adjustable dosing |
| NZ574710A (en) * | 2006-09-07 | 2012-02-24 | Nycomed Gmbh | Combination treatment comprising the PDE4 inhibitor Compound A ((2R,4aR, 10bR)6-(2,6-Dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1 ,2,3,4,4a,10b-hexahydrophenanthridin-2-ol) for diabetes mellitus |
| EP2990067B1 (en) | 2008-03-10 | 2019-09-04 | Antares Pharma, Inc. | Injector safety device |
| CN101548972B (zh) * | 2008-04-03 | 2012-10-17 | 万特制药(海南)有限公司 | 一种含有瑞格列奈的固体药物组合物 |
| ES2738539T3 (es) | 2008-08-05 | 2020-01-23 | Antares Pharma Inc | Inyector de dosis múltiples |
| ES2988196T3 (es) | 2009-03-20 | 2024-11-19 | Antares Pharma Inc | Sistema de inyección de agentes peligrosos |
| US9220660B2 (en) | 2011-07-15 | 2015-12-29 | Antares Pharma, Inc. | Liquid-transfer adapter beveled spike |
| US8496619B2 (en) | 2011-07-15 | 2013-07-30 | Antares Pharma, Inc. | Injection device with cammed ram assembly |
| US20130172303A1 (en) * | 2012-01-03 | 2013-07-04 | Forest Laboratories Holdings Ltd. | Roflumilast compositions for the treatment of copd |
| DK2822618T3 (da) | 2012-03-06 | 2024-01-22 | Antares Pharma Inc | Forfyldt nål med brudkraftfunktion |
| EP4186545A1 (en) | 2012-04-06 | 2023-05-31 | Antares Pharma, Inc. | Needle assisted jet injection administration of testosterone compositions |
| US9364611B2 (en) | 2012-05-07 | 2016-06-14 | Antares Pharma, Inc. | Needle assisted jet injection device having reduced trigger force |
| FI3659647T3 (fi) | 2013-02-11 | 2024-03-28 | Antares Pharma Inc | Neula-avusteinen suihkuinjektiolaite, jolla on pienennetty liipaisinvoima |
| WO2014124860A1 (en) | 2013-02-14 | 2014-08-21 | Boehringer Ingelheim International Gmbh | Specific pde4b-inhibitors for the treatment of diabetes mellitus |
| EP3572108A1 (en) | 2013-03-11 | 2019-11-27 | Antares Pharma, Inc. | Dosage injector with pinion system |
| WO2014165136A1 (en) | 2013-03-12 | 2014-10-09 | Antares Pharma, Inc. | Constant volume prefilled syringes and kits thereof |
| EP3165224A1 (en) * | 2015-11-09 | 2017-05-10 | Albert-Ludwigs-Universität Freiburg | Use of pde4 inhibitors for the prophylaxis and/or therapy of dyslipoproteinaemia and related disorders |
| AU2017252015A1 (en) | 2016-04-19 | 2018-11-08 | Ureka Sarl | Peptide-oligourea foldamer compounds and methods of their use |
| GB202306663D0 (en) * | 2023-05-05 | 2023-06-21 | Union Therapeutics As | Combination therapy |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020002191A1 (en) * | 2000-05-25 | 2002-01-03 | Richard Friesen | Fluoroalkoxy-substituted benzamide dichloropyridinyl N-oxide PDE4 inhibitor |
| US20050049258A1 (en) * | 2001-01-31 | 2005-03-03 | Pfizer Inc | Ether derivatives useful as inhibitors of PDE4 isozymes |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3174901A (en) * | 1963-01-31 | 1965-03-23 | Jan Marcel Didier Aron Samuel | Process for the oral treatment of diabetes |
| JPS5869812A (ja) | 1981-10-22 | 1983-04-26 | Chugai Pharmaceut Co Ltd | 血糖降下剤 |
| AR240698A1 (es) * | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
| NZ225447A (en) | 1987-07-20 | 1991-12-23 | Merck & Co Inc | Piperazinyl derivatives of purine and purine isosteres and pharmaceutical compositions |
| US5698711A (en) | 1991-01-28 | 1997-12-16 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| GB9215633D0 (en) | 1992-07-23 | 1992-09-09 | Smithkline Beecham Plc | Novel treatment |
| IL106517A0 (en) | 1992-07-28 | 1994-08-26 | Rhone Poulenc Rorer Ltd | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic or heteroatom containing linking group |
| JPH08509203A (ja) | 1992-10-15 | 1996-10-01 | ダナ−ファーバー キャンサー インステテュート インコーポレイテッド | ＴＮＦ−α作用の拮抗剤を用いる肥満関連糖尿病▲ＩＩ▼型のインスリン耐性の治療 |
| US5712298A (en) | 1993-07-02 | 1998-01-27 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Fluoroalkoxy-substituted benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors |
| KR970705562A (ko) | 1994-08-29 | 1997-10-09 | 오노다 마사요시 | 신규한 나프티리딘 유도체 및 이의 의약 조성물(Novel naphthyridine derivatives and medicinal composition thereof) |
| HU221380B1 (en) | 1996-01-31 | 2002-09-28 | Byk Gulden Lomberg Chem Fab | Phosphodiesterase inhibitor phenanthridines derivatives and use thereof |
| DE19617864A1 (de) | 1996-04-23 | 1997-10-30 | Schering Ag | Neue chirale Phenyldihydrofuranone |
| US6331543B1 (en) * | 1996-11-01 | 2001-12-18 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
| WO1999014239A1 (de) | 1997-09-12 | 1999-03-25 | Wolf Georg Forssmann | Zusammensetzung zur therapie von diabetes mellitus und fettsucht |
| SE9801992D0 (sv) * | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl-2-hydroxypropionic acid derivative I |
| CZ300366B6 (cs) | 1999-01-15 | 2009-05-06 | Nycomed Gmbh | Fenylfenanthridinová sloucenina, farmaceutický prostredek s jejím obsahem a její použití |
| WO2000042034A1 (en) | 1999-01-15 | 2000-07-20 | Byk Gulden | Phenanthridine-n-oxides with pde-iv inhibiting activity |
| US7323496B2 (en) * | 1999-11-08 | 2008-01-29 | Theracos, Inc. | Compounds for treatment of inflammation, diabetes and related disorders |
| AU3270301A (en) | 1999-11-13 | 2001-05-30 | Icos Corporation | Combined pde3 and pde4 inhibitor therapy for the treatment of obesity |
| DE60008917T2 (de) | 1999-12-08 | 2005-03-10 | Grelan Pharmaceutical Co., Ltd., Hamura | Neue 1,8-naphtyridin-2(1h)-on-derivate |
| US6423714B2 (en) | 2000-03-13 | 2002-07-23 | Ortho Mcneil-Pharmaceutical, Inc.. | Cyclohexene derivatives useful as antagonists of the motilin receptor |
| US6924292B2 (en) | 2000-03-23 | 2005-08-02 | Takeda Chemical Industries, Ltd. | Furoisoquinoline derivatives, process for producing the same and use thereof |
| CA2418313C (en) | 2000-08-11 | 2008-09-23 | Ono Pharmaceutical Co., Ltd. | Piperidine derivatives and agent comprising the derivative as active ingredient |
| AU2001276607A1 (en) | 2000-08-11 | 2002-02-25 | Pfizer Inc. | Treatment of the insulin resistance syndrome with selective CGMP PDE5 inhibitors |
| JP4223287B2 (ja) | 2001-01-22 | 2009-02-12 | メモリー・ファーマスーティカルズ・コーポレーション | 新規な化合物及び製薬上許容し得るそれらの塩並びにそれらを用いた薬剤組成物 |
| PL365443A1 (en) | 2001-01-31 | 2005-01-10 | Pfizer Products Inc. | Thiazolyl-, oxazolyl-, pyrrolyl-, and imidazolyl-acid amide derivatives useful as inhibitors of pde4 isozymes |
| JP4301812B2 (ja) | 2001-02-15 | 2009-07-22 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｐｄｅ４インヒビターとしてのフタラインオン−ピペリジノ−誘導体 |
| CA2439691A1 (en) * | 2001-03-02 | 2002-09-12 | Bristol-Myers Squibb Company | Co-administration of melanocortin receptor agonist and phosphodiesterase inhibitor for treatment of cyclic-amp associated disorders |
| UA74912C2 (en) | 2001-07-06 | 2006-02-15 | Merck & Co Inc | Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes |
| DE10150517A1 (de) | 2001-10-12 | 2003-04-17 | Merck Patent Gmbh | Verwendung von Phosphodiesterase IV-Inhibitoren |
| US20030181461A1 (en) | 2002-01-25 | 2003-09-25 | Lautt Wilfred Wayne | Use of phosphodiesterase antagonists to treat insulin resistance |
| NZ537308A (en) * | 2002-05-28 | 2009-09-25 | Nycomed Gmbh | Ophthalmological use of roflumilast for the treatment of diseases of the eye |
| WO2004016596A1 (en) * | 2002-08-19 | 2004-02-26 | Glenmark Pharmaceuticals Limited | Condensed heterocyclic compounds as pde-iv inhibitors for the treatment of inflammatory and allergic disorders |
| WO2004067006A1 (en) * | 2003-01-27 | 2004-08-12 | Pharmacia Corporation | Combination of a pde iv inhibitor and a tnf-alpha antagonist |
| WO2004098598A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | COMPOSITION COMPRISING ROFLUMILAST AND A TNFα ANTAGONIST |
| WO2004098597A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | Composition comprising roflumilast and shuil-1r ii |
| WO2004098595A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | COMPOSITION COMPRISING ROFLUMILAST AND A TNFα ANTAGONIST |
| WO2004098596A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | Composition comprising roflumilast and il-1 trap |
| EP1628682B1 (en) * | 2003-05-22 | 2013-09-25 | Takeda GmbH | Composition comprising a pde4 inhibitor and a pde5 inhibitor for the treatment of copd |
| WO2005020926A2 (en) * | 2003-08-28 | 2005-03-10 | Pharmacia Corporation | Treatment or prevention of vascular disorders with cox-2 inhibitors in combination with cyclic amp-specific phosphodiesterase inhibitors |
| JP2007504201A (ja) | 2003-09-05 | 2007-03-01 | アルタナ ファルマ アクチエンゲゼルシャフト | 真性糖尿病の治療のためのｐｄｅ４阻害剤の使用 |
| BRPI0415753A (pt) | 2003-10-21 | 2006-12-19 | Pharmacia Corp | método para tratamento e prevenção da inflamação respiratória com um inibidor de ciclooxigenase-2 em associação com um inibidor de fosfodiesterase 4 e composições que os contêm |
| CA2564139A1 (en) | 2004-04-13 | 2005-12-08 | Arena Pharmaceuticals, Inc. | Modulators of human g protein-coupled receptors for the treatment of hyperglycemia and related disorders |
| CN102600144A (zh) * | 2005-03-08 | 2012-07-25 | 奈科明有限责任公司 | 治疗糖尿病的罗氟司特 |
-
2006
- 2006-03-03 CN CN2012100579547A patent/CN102600144A/zh active Pending
- 2006-03-03 AU AU2006222060A patent/AU2006222060B2/en not_active Ceased
- 2006-03-03 CA CA2599376A patent/CA2599376C/en not_active Expired - Fee Related
- 2006-03-03 KR KR1020077022434A patent/KR101302838B1/ko not_active Expired - Fee Related
- 2006-03-03 EP EP06708617A patent/EP1874308A1/en not_active Withdrawn
- 2006-03-03 BR BRPI0609371-0A patent/BRPI0609371A2/pt not_active IP Right Cessation
- 2006-03-03 NZ NZ560269A patent/NZ560269A/en not_active IP Right Cessation
- 2006-03-03 MX MX2007010560A patent/MX2007010560A/es not_active Application Discontinuation
- 2006-03-03 JP JP2008500172A patent/JP5091106B2/ja not_active Expired - Fee Related
- 2006-03-03 EA EA200701845A patent/EA015382B1/ru not_active IP Right Cessation
- 2006-03-03 CN CN2006800072465A patent/CN101137368B/zh not_active Expired - Fee Related
- 2006-03-03 US US11/885,450 patent/US8017633B2/en not_active Expired - Fee Related
- 2006-03-03 WO PCT/EP2006/060418 patent/WO2006094933A1/en not_active Ceased
-
2007
- 2007-07-27 ZA ZA200706294A patent/ZA200706294B/xx unknown
- 2007-08-14 IL IL185277A patent/IL185277A/en not_active IP Right Cessation
- 2007-10-01 NO NO20074943A patent/NO20074943L/no not_active Application Discontinuation
-
2011
- 2011-07-11 US US13/179,895 patent/US8541456B2/en not_active Expired - Fee Related
-
2012
- 2012-06-07 JP JP2012129982A patent/JP5611275B2/ja not_active Expired - Fee Related
- 2012-07-18 IL IL221006A patent/IL221006A0/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020002191A1 (en) * | 2000-05-25 | 2002-01-03 | Richard Friesen | Fluoroalkoxy-substituted benzamide dichloropyridinyl N-oxide PDE4 inhibitor |
| US20050049258A1 (en) * | 2001-01-31 | 2005-03-03 | Pfizer Inc | Ether derivatives useful as inhibitors of PDE4 isozymes |
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0609371A2 (pt) | 2010-03-30 |
| EA200701845A1 (ru) | 2008-02-28 |
| IL221006A0 (en) | 2012-08-30 |
| US20110269750A1 (en) | 2011-11-03 |
| AU2006222060A1 (en) | 2006-09-14 |
| AU2006222060B2 (en) | 2011-09-01 |
| CA2599376A1 (en) | 2006-09-14 |
| JP2008532974A (ja) | 2008-08-21 |
| IL185277A (en) | 2013-08-29 |
| US8017633B2 (en) | 2011-09-13 |
| JP2012188448A (ja) | 2012-10-04 |
| US20080214625A1 (en) | 2008-09-04 |
| KR101302838B1 (ko) | 2013-09-03 |
| IL185277A0 (en) | 2008-02-09 |
| JP5611275B2 (ja) | 2014-10-22 |
| US8541456B2 (en) | 2013-09-24 |
| WO2006094933A1 (en) | 2006-09-14 |
| EA015382B1 (ru) | 2011-08-30 |
| CA2599376C (en) | 2014-05-13 |
| HK1116077A1 (en) | 2008-12-19 |
| CN101137368B (zh) | 2012-05-16 |
| ZA200706294B (en) | 2008-09-25 |
| NO20074943L (no) | 2007-10-01 |
| JP5091106B2 (ja) | 2012-12-05 |
| EP1874308A1 (en) | 2008-01-09 |
| KR20070111539A (ko) | 2007-11-21 |
| NZ560269A (en) | 2010-12-24 |
| CN101137368A (zh) | 2008-03-05 |
| MX2007010560A (es) | 2008-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101137368B (zh) | 治疗糖尿病的罗氟司特 | |
| KR20090047546A (ko) | 당뇨병을 위한 조합 치료 | |
| CN1960735B (zh) | 药物组合在治疗胰岛素抗性中的应用 | |
| Hossain et al. | Current antidiabetic drugs: review of their efficacy and safety | |
| AU2025201814A1 (en) | Therapeutic uses of GLP1R agonists | |
| TW201006488A (en) | Use of ultrarapid acting insulin | |
| CN104968341B (zh) | Glp1r激动剂和二甲双胍的组合及其在制备治疗2型糖尿病和其他障碍的药物中的用途 | |
| US11974989B2 (en) | Therapeutic uses of glucokinase activators in combination with insulin or insulin analogs | |
| CN102858155A (zh) | 使用双醋瑞因作为糖尿病的辅助治疗的方法 | |
| Kadhe et al. | Advances in drug delivery of oral hypoglycemic agents | |
| CN113559088A (zh) | 一种含二甲双胍和西格列汀的复方降糖药物制剂 | |
| CN114306601A (zh) | 一种l型氨基酸转运蛋白抑制剂或拮抗剂有效干预糖尿病的方法 | |
| Houglum et al. | Drugs for Treating Diabetes Mellitus | |
| WO2006094942A1 (en) | Roflumilast for the treatment of diabetes mellitus | |
| HK40042198A (en) | Therapeutic uses of glucokinase activators in combination with insulin or insulin analogs | |
| Bates | Overdose of insulin and other diabetic medication | |
| HK1210424B (zh) | Glp1r 激动剂和二甲双胍的组合及其在制备治疗 2 型糖尿病和其他障碍的药物中的用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1171663 Country of ref document: HK |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120725 |
|
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1171663 Country of ref document: HK |