JP2008517921A - Ｄｐｐ−ｉｖ阻害剤、ｐｐａｒ抗糖尿病薬およびメトホルミンの組合わせ剤 - Google Patents
Ｄｐｐ−ｉｖ阻害剤、ｐｐａｒ抗糖尿病薬およびメトホルミンの組合わせ剤 Download PDFInfo
- Publication number
- JP2008517921A JP2008517921A JP2007538049A JP2007538049A JP2008517921A JP 2008517921 A JP2008517921 A JP 2008517921A JP 2007538049 A JP2007538049 A JP 2007538049A JP 2007538049 A JP2007538049 A JP 2007538049A JP 2008517921 A JP2008517921 A JP 2008517921A
- Authority
- JP
- Japan
- Prior art keywords
- metformin
- salt
- dpp
- administered
- laf237
- 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
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 title claims abstract description 131
- 229960003105 metformin Drugs 0.000 title claims abstract description 117
- 239000003112 inhibitor Substances 0.000 title claims abstract description 106
- 239000003472 antidiabetic agent Substances 0.000 title claims abstract description 54
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 title claims abstract description 36
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 title claims abstract description 36
- 229940125708 antidiabetic agent Drugs 0.000 title claims abstract description 16
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 title claims description 131
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 title 1
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 claims abstract description 136
- 238000000034 method Methods 0.000 claims abstract description 58
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 239000000556 agonist Substances 0.000 claims abstract description 36
- 102000023984 PPAR alpha Human genes 0.000 claims abstract description 32
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 claims abstract description 32
- 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 claims abstract description 31
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 31
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 27
- 208000002705 Glucose Intolerance Diseases 0.000 claims abstract description 22
- 108010016731 PPAR gamma Proteins 0.000 claims abstract description 22
- 229940123464 Thiazolidinedione Drugs 0.000 claims abstract description 22
- 230000001404 mediated effect Effects 0.000 claims abstract description 22
- 201000009104 prediabetes syndrome Diseases 0.000 claims abstract description 22
- 230000009977 dual effect Effects 0.000 claims abstract description 18
- 201000001421 hyperglycemia Diseases 0.000 claims abstract description 14
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 208000010444 Acidosis Diseases 0.000 claims abstract description 6
- 208000007976 Ketosis Diseases 0.000 claims abstract description 6
- 206010027417 Metabolic acidosis Diseases 0.000 claims abstract description 6
- 208000008589 Obesity Diseases 0.000 claims abstract description 6
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 6
- 206010003246 arthritis Diseases 0.000 claims abstract description 6
- 230000004140 ketosis Effects 0.000 claims abstract description 6
- 235000020824 obesity Nutrition 0.000 claims abstract description 6
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 144
- 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 110
- 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 106
- 150000003839 salts Chemical class 0.000 claims description 98
- 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 61
- 229960005095 pioglitazone Drugs 0.000 claims description 51
- 229960004586 rosiglitazone Drugs 0.000 claims description 51
- -1 3-hydroxy-1-adamantyl Chemical group 0.000 claims description 45
- 235000012054 meals Nutrition 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 30
- 238000013268 sustained release Methods 0.000 claims description 28
- 239000012730 sustained-release form Substances 0.000 claims description 28
- 229940079593 drug Drugs 0.000 claims description 23
- 230000003178 anti-diabetic effect Effects 0.000 claims description 22
- 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 19
- 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 claims description 17
- 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 description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- VNACOBVZDCLAEV-GXKRWWSZSA-N 6-[2-[[2-[(2s)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]ethylamino]pyridine-3-carbonitrile;dihydrochloride Chemical compound Cl.Cl.N1([C@@H](CCC1)C#N)C(=O)CNCCNC1=CC=C(C#N)C=N1 VNACOBVZDCLAEV-GXKRWWSZSA-N 0.000 claims description 13
- 229960001641 troglitazone Drugs 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 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 description 12
- 229960003271 rosiglitazone maleate Drugs 0.000 claims description 10
- ZHUTVLURGLOKMO-UHFFFAOYSA-N 1-acetylpyrrolidine-2-carbonitrile Chemical compound CC(=O)N1CCCC1C#N ZHUTVLURGLOKMO-UHFFFAOYSA-N 0.000 claims description 9
- 150000001467 thiazolidinediones Chemical class 0.000 claims description 9
- GHUUBYQTCDQWRA-UHFFFAOYSA-N Pioglitazone hydrochloride Chemical compound Cl.N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 GHUUBYQTCDQWRA-UHFFFAOYSA-N 0.000 claims description 8
- 229960002827 pioglitazone hydrochloride Drugs 0.000 claims description 8
- 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 8
- 229960004034 sitagliptin Drugs 0.000 claims description 8
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
- UIKDPMGTFQHKLC-UHFFFAOYSA-N 3-(aminomethyl)-2-(2-methylpropyl)-1-oxo-4-phenylisoquinoline-6-carboxamide Chemical compound C12=CC(C(N)=O)=CC=C2C(=O)N(CC(C)C)C(CN)=C1C1=CC=CC=C1 UIKDPMGTFQHKLC-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000006041 probiotic Substances 0.000 claims description 2
- 230000000529 probiotic effect Effects 0.000 claims description 2
- 235000018291 probiotics Nutrition 0.000 claims description 2
- 102100020751 Dipeptidyl peptidase 2 Human genes 0.000 claims 1
- 108090000212 dipeptidyl peptidase II Proteins 0.000 claims 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 abstract description 19
- 238000002360 preparation method Methods 0.000 abstract description 13
- 230000009286 beneficial effect Effects 0.000 abstract description 12
- 241001465754 Metazoa Species 0.000 abstract description 11
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 11
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 9
- 241000124008 Mammalia Species 0.000 abstract description 7
- 230000004580 weight loss Effects 0.000 abstract description 5
- 239000002537 cosmetic Substances 0.000 abstract description 4
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 abstract 5
- 239000003826 tablet Substances 0.000 description 34
- 239000002552 dosage form Substances 0.000 description 29
- 238000012360 testing method Methods 0.000 description 21
- 239000010410 layer Substances 0.000 description 20
- 102000000536 PPAR gamma Human genes 0.000 description 19
- 229940127003 anti-diabetic drug Drugs 0.000 description 19
- 235000021152 breakfast Nutrition 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 16
- 239000000546 pharmaceutical excipient Substances 0.000 description 14
- 239000007939 sustained release tablet Substances 0.000 description 14
- 239000008187 granular material Substances 0.000 description 13
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 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
- 238000009472 formulation Methods 0.000 description 11
- 239000008103 glucose Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 9
- NFFXEUUOMTXWCX-UHFFFAOYSA-N 5-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-methoxy-n-[[4-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C(F)(F)F)C(OC)=CC=C1CC1SC(=O)NC1=O NFFXEUUOMTXWCX-UHFFFAOYSA-N 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 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 description 8
- 239000000902 placebo Substances 0.000 description 8
- ITLAZBMGSXRIEF-UHFFFAOYSA-N 5-naphthalen-2-ylsulfonyl-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 ITLAZBMGSXRIEF-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 7
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 7
- 229960004329 metformin hydrochloride Drugs 0.000 description 7
- 229940068196 placebo Drugs 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 7
- 241000282412 Homo Species 0.000 description 6
- 229940062328 actos Drugs 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 230000002641 glycemic effect Effects 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 230000003914 insulin secretion Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 208000030159 metabolic disease Diseases 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 238000009097 single-agent therapy Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 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 description 5
- 230000002195 synergetic effect Effects 0.000 description 5
- GWZJXMRSPIFFAK-UHFFFAOYSA-N 5-[(2-naphthalen-2-yl-1,3-benzoxazol-5-yl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(OC(=N2)C=3C=C4C=CC=CC4=CC=3)C2=C1 GWZJXMRSPIFFAK-UHFFFAOYSA-N 0.000 description 4
- MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 description 4
- YVQKIDLSVHRBGZ-UHFFFAOYSA-N 5-[[4-[2-hydroxy-2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(O)COC(C=C1)=CC=C1CC1SC(=O)NC1=O YVQKIDLSVHRBGZ-UHFFFAOYSA-N 0.000 description 4
- 102000004420 Creatine Kinase Human genes 0.000 description 4
- 108010042126 Creatine kinase Proteins 0.000 description 4
- 102000001554 Hemoglobins Human genes 0.000 description 4
- 108010054147 Hemoglobins Proteins 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 229940062310 avandia Drugs 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- QQKNSPHAFATFNQ-UHFFFAOYSA-N darglitazone Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCC(=O)C(C=C1)=CC=C1CC1SC(=O)NC1=O QQKNSPHAFATFNQ-UHFFFAOYSA-N 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 229950002375 englitazone Drugs 0.000 description 4
- 229940095884 glucophage Drugs 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 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 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- FTRMOJIRMFXZJV-UHFFFAOYSA-N n-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenyl]-1-phenylcyclopropane-1-carboxamide Chemical compound C1CC1(C=1C=CC=CC=1)C(=O)NC(C=C1)=CC=C1CC1SC(=O)NC1=O FTRMOJIRMFXZJV-UHFFFAOYSA-N 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 229960004937 saxagliptin Drugs 0.000 description 4
- 108010033693 saxagliptin Proteins 0.000 description 4
- FQCUYGFIIAZMLU-UHFFFAOYSA-N 5-[[2-(naphthalen-2-ylmethyl)-1,3-benzoxazol-5-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(OC(CC=2C=C3C=CC=CC3=CC=2)=N2)C2=C1 FQCUYGFIIAZMLU-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 3
- 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 3
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 3
- 206010022489 Insulin Resistance Diseases 0.000 description 3
- 229940122355 Insulin sensitizer Drugs 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 229940054739 avandamet Drugs 0.000 description 3
- 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 3
- 229950009226 ciglitazone Drugs 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000002301 combined effect Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000004584 weight gain Effects 0.000 description 3
- 235000019786 weight gain Nutrition 0.000 description 3
- WCRLBFHWFPELKW-YUMQZZPRSA-N (2s,3s)-2-amino-3-methyl-1-(1,3-thiazolidin-3-yl)pentan-1-one Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCSC1 WCRLBFHWFPELKW-YUMQZZPRSA-N 0.000 description 2
- QBQLYIISSRXYKL-UHFFFAOYSA-N 4-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,2-oxazolidine-3,5-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1C(=O)NOC1=O QBQLYIISSRXYKL-UHFFFAOYSA-N 0.000 description 2
- AUTCHGUUOVSZOZ-UHFFFAOYSA-N 5-[(4-methylphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(C)=CC=C1CC1C(=O)NC(=O)S1 AUTCHGUUOVSZOZ-UHFFFAOYSA-N 0.000 description 2
- WWGVNZWSVJDZLH-UHFFFAOYSA-N 5-[[4-[2-(2,3-dihydroindol-1-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCCN1C2=CC=CC=C2CC1 WWGVNZWSVJDZLH-UHFFFAOYSA-N 0.000 description 2
- QFSMMXJBEBXTJP-UHFFFAOYSA-N 7-benzyl-1,3-dimethyl-8-piperazin-1-yl-3,7-dihydropurine-2,6-dione Chemical compound C=1C=CC=CC=1CN1C=2C(=O)N(C)C(=O)N(C)C=2N=C1N1CCNCC1 QFSMMXJBEBXTJP-UHFFFAOYSA-N 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 206010033307 Overweight Diseases 0.000 description 2
- 229940124754 PPAR-alpha/gamma agonist Drugs 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 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 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 125000004586 dihydrobenzopyranyl group Chemical group O1C(CCC2=C1C=CC=C2)* 0.000 description 2
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000008240 homogeneous mixture Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 125000001151 peptidyl group Chemical group 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- 229960001254 vildagliptin Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZHUTVLURGLOKMO-ZETCQYMHSA-N (2s)-1-acetylpyrrolidine-2-carbonitrile Chemical compound CC(=O)N1CCC[C@H]1C#N ZHUTVLURGLOKMO-ZETCQYMHSA-N 0.000 description 1
- BLWKWOVOFWHFLD-FQEVSTJZSA-N (2s)-2-(2-benzoylanilino)-3-(4-hydroxyphenyl)propanoic acid Chemical class C([C@@H](C(=O)O)NC=1C(=CC=CC=1)C(=O)C=1C=CC=CC=1)C1=CC=C(O)C=C1 BLWKWOVOFWHFLD-FQEVSTJZSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- GQPYTJVDPQTBQC-KLQYNRQASA-N (3r)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F GQPYTJVDPQTBQC-KLQYNRQASA-N 0.000 description 1
- SODPIMGUZLOIPE-UHFFFAOYSA-N (4-chlorophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1 SODPIMGUZLOIPE-UHFFFAOYSA-N 0.000 description 1
- LHEKNHSVYGREGA-UHFFFAOYSA-N 1-acetyl-2-[(3-hydroxy-1-adamantyl)amino]pyrrolidine-2-carbonitrile Chemical compound CC(=O)N1CCCC1(C#N)NC1(C2)CC(O)(C3)CC2CC3C1 LHEKNHSVYGREGA-UHFFFAOYSA-N 0.000 description 1
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 1
- MENAYYMPBRSAAE-AWEZNQCLSA-N 3-[[5-[[(2s)-1-carboxy-3-oxopropan-2-yl]carbamoyl]pyridin-2-yl]methylsulfamoyl]benzoic acid Chemical compound N1=CC(C(=O)N[C@@H](CC(=O)O)C=O)=CC=C1CNS(=O)(=O)C1=CC=CC(C(O)=O)=C1 MENAYYMPBRSAAE-AWEZNQCLSA-N 0.000 description 1
- PCAZCAZVHLGDBA-UHFFFAOYSA-N 5-[[4-(2-indol-1-ylethoxy)phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCCN1C2=CC=CC=C2C=C1 PCAZCAZVHLGDBA-UHFFFAOYSA-N 0.000 description 1
- NMTKJEZOWHRAQY-UHFFFAOYSA-N 8-[(6-methoxyisoquinolin-4-yl)methyl]-1-methyl-3-(2-methylpropyl)-7h-purine-2,6-dione Chemical group CC(C)CN1C(=O)N(C)C(=O)C(N2)=C1N=C2CC1=CN=CC2=CC=C(OC)C=C21 NMTKJEZOWHRAQY-UHFFFAOYSA-N 0.000 description 1
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 description 1
- 238000008789 Direct Bilirubin Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108020004206 Gamma-glutamyltransferase Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 108700040460 Hexokinases Proteins 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 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 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 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
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 206010054805 Macroangiopathy Diseases 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101710098398 Probable alanine aminotransferase, mitochondrial Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 102000003929 Transaminases Human genes 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
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- FHKYMEGVIVZQAD-UHFFFAOYSA-N [N].ON Chemical group [N].ON FHKYMEGVIVZQAD-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000006383 alkylpyridyl group Chemical group 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 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
- 229960004111 buformin Drugs 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 229950006689 darglitazone Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical group 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940126904 hypoglycaemic agent Drugs 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000007942 layered tablet Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- FJQXCDYVZAHXNS-UHFFFAOYSA-N methadone hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 FJQXCDYVZAHXNS-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 239000008183 oral pharmaceutical preparation Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 229960003243 phenformin Drugs 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
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 210000002321 radial artery Anatomy 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012475 sodium chloride buffer Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P3/08—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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62189104P | 2004-10-25 | 2004-10-25 | |
| PCT/US2005/037819 WO2006047248A1 (en) | 2004-10-25 | 2005-10-21 | Combination of dpp-iv inhibitor, ppar antidiabetic and metformin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008517921A true JP2008517921A (ja) | 2008-05-29 |
| JP2008517921A5 JP2008517921A5 (https=) | 2008-11-27 |
Family
ID=35717718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007538049A Pending JP2008517921A (ja) | 2004-10-25 | 2005-10-21 | Ｄｐｐ−ｉｖ阻害剤、ｐｐａｒ抗糖尿病薬およびメトホルミンの組合わせ剤 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US20090253752A1 (https=) |
| EP (1) | EP1807066A1 (https=) |
| JP (1) | JP2008517921A (https=) |
| KR (1) | KR20070068407A (https=) |
| CN (1) | CN101035522B (https=) |
| AU (2) | AU2005299808B2 (https=) |
| BR (1) | BRPI0518409A2 (https=) |
| CA (1) | CA2581298A1 (https=) |
| MX (1) | MX2007004934A (https=) |
| RU (1) | RU2007119320A (https=) |
| WO (1) | WO2006047248A1 (https=) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010074271A1 (ja) * | 2008-12-26 | 2010-07-01 | 武田薬品工業株式会社 | 糖尿病治療剤 |
| JP2012509891A (ja) * | 2008-11-26 | 2012-04-26 | サティオゲン ファーマシューティカルズ，インク． | 肥満症及び糖尿病を治療するための胆汁酸再循環阻害剤 |
| JP2012520883A (ja) * | 2009-03-16 | 2012-09-10 | アイピントゥル，エルエルシー | アルツハイマー病及び骨粗鬆症の治療並びに老化の軽減 |
| JP2013510873A (ja) * | 2009-11-13 | 2013-03-28 | ブリストル−マイヤーズ スクイブ カンパニー | 二層錠製剤 |
| JP2014507456A (ja) * | 2011-03-07 | 2014-03-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | メトホルミン及びｄｐｐ−４阻害剤又はｓｇｌｔ−２阻害剤を含む医薬組成物 |
| US10188646B2 (en) | 2010-05-26 | 2019-01-29 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
| US10512657B2 (en) | 2011-10-28 | 2019-12-24 | Lumena Pharmaceutials Llc | Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases |
| US12145959B2 (en) | 2011-10-28 | 2024-11-19 | Shire Human Genetic Therapies, Inc. | Bile acid recycling inhibitors for treatment of hypercholemia and cholestatic liver disease |
Families Citing this family (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| DOP2006000008A (es) * | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| MY152185A (en) * | 2005-06-10 | 2014-08-29 | Novartis Ag | Modified release 1-[(3-hydroxy-adamant-1-ylamino)-acetyl]-pyrrolidine-2(s)-carbonitrile formulation |
| GT200600218A (es) * | 2005-06-10 | 2007-03-28 | Formulación y proceso de compresión directa | |
| DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| PL1931350T5 (pl) * | 2005-09-14 | 2021-11-15 | Takeda Pharmaceutical Company Limited | Podanie inhibitorów dipeptydylo-peptydazy |
| AU2011202574B2 (en) * | 2005-09-20 | 2012-02-02 | Emisphere Technologies, Inc. | Use of a DPP-IV inhibitor to reduce hypoglycemic events |
| CA2622579C (en) * | 2005-09-20 | 2013-12-31 | Novartis Ag | Use of a dpp-iv inhibitor to reduce hypoglycemic events |
| BRPI0616694B8 (pt) * | 2005-09-29 | 2021-05-25 | Novartis Ag | processo para preparar comprimido farmacêutico com 80 e 96% em peso com base no peso seco de vildagliptina e metformina ou seus sais farmaceuticamente aceitáveis |
| CN101365432B (zh) * | 2005-12-16 | 2011-06-22 | 默沙东公司 | 二肽基肽酶-4抑制剂与二甲双胍的组合的药物组合物 |
| US20090054512A1 (en) * | 2006-01-06 | 2009-02-26 | Foley James E | Use of organic compounds |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
| KR101452915B1 (ko) | 2006-05-04 | 2014-10-21 | 베링거 인겔하임 인터내셔날 게엠베하 | 다형태 |
| PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
| AU2007318059A1 (en) * | 2006-11-01 | 2008-05-15 | Novartis Ag | Use of Dipeptidyl peptidase IV inhibitors for preventing, delaying or reducing the occurance of edema |
| EP2089383B1 (en) | 2006-11-09 | 2015-09-16 | Probiodrug AG | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
| US9126987B2 (en) | 2006-11-30 | 2015-09-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| ATE488227T1 (de) | 2007-02-01 | 2010-12-15 | Takeda Pharmaceutical | Feste zubereitung mit alogliptin und pioglitazon |
| CA2681092A1 (en) * | 2007-03-15 | 2008-09-18 | Nectid, Inc. | Anti-diabetic combinations comprising a slow release biguanide composition and an immediate release dipeptidyl peptidase iv inhibitor composition |
| JP5667440B2 (ja) | 2007-04-18 | 2015-02-12 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのチオ尿素誘導体 |
| PE20090938A1 (es) | 2007-08-16 | 2009-08-08 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un derivado de benceno sustituido con glucopiranosilo |
| US20100330177A1 (en) * | 2008-02-05 | 2010-12-30 | Merck Sharp & Dohme Corp. | Pharmaceutical compositions of a combination of metformin and a dipeptidyl peptidase-iv inhibitor |
| US8551524B2 (en) | 2008-03-14 | 2013-10-08 | Iycus, Llc | Anti-diabetic combinations |
| PE20091730A1 (es) | 2008-04-03 | 2009-12-10 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
| EP2108960A1 (en) | 2008-04-07 | 2009-10-14 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditons modulated by PYY |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| KR20190016601A (ko) | 2008-08-06 | 2019-02-18 | 베링거 인겔하임 인터내셔날 게엠베하 | 메트포르민 요법이 부적합한 환자에서의 당뇨병 치료 |
| CA2736421A1 (en) | 2008-09-10 | 2010-03-18 | Boehringer Ingelheim International Gmbh | Combination therapy for the treatment of diabetes and related conditions |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
| JO2870B1 (en) | 2008-11-13 | 2015-03-15 | ميرك شارب اند دوهم كورب | Amino Tetra Hydro Pirans as Inhibitors of Peptide Dipeptide IV for the Treatment or Prevention of Diabetes |
| GB2465796A (en) * | 2008-12-01 | 2010-06-02 | Bee Kang Tan | Metformin for the therapeutic use of conditions with raised serum amyloid A levels |
| JP2012512848A (ja) | 2008-12-23 | 2012-06-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 有機化合物の塩の形態 |
| TW201036975A (en) | 2009-01-07 | 2010-10-16 | Boehringer Ingelheim Int | Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy |
| EP2395988A2 (en) * | 2009-02-13 | 2011-12-21 | Boehringer Ingelheim International GmbH | Antidiabetic medications comprising a dpp-4 inhibitor (linagliptin) optionally in combination with other antidiabetics |
| BRPI1008560B1 (pt) | 2009-02-13 | 2021-08-31 | Boehringer Ingelheim International Gmbh | Composição farmacêutica compreendendo um inibidor de sglt2, um inibidor de dpp-iv e opcionalmente um outro agente antidiabético e usos dos mesmos |
| CA2771352A1 (en) | 2009-09-02 | 2011-03-10 | Merck Sharp & Dohme Corp. | Aminotetrahydropyrans as dipeptidyl peptidase-iv inhibitors for the treatment or prevention of diabetes |
| JP5934645B2 (ja) | 2009-09-11 | 2016-06-15 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体 |
| WO2011037793A1 (en) | 2009-09-25 | 2011-03-31 | Merck Sharp & Dohme Corp. | Substituted aminopiperidines as dipeptidyl peptidase-iv inhibitors for the treatment of diabetes |
| WO2011049773A1 (en) * | 2009-10-23 | 2011-04-28 | Merck Sharp & Dohme Corp. | Pharmaceutical compositions of combinations of dipeptidyl peptidase-4 inhibitors with pioglitazone |
| KR20240090632A (ko) | 2009-11-27 | 2024-06-21 | 베링거 인겔하임 인터내셔날 게엠베하 | 리나글립틴과 같은 ｄｐｐ－ｉｖ 억제제를 사용한 유전자형 검사된 당뇨병 환자의 치료 |
| WO2011080276A1 (en) | 2009-12-29 | 2011-07-07 | Genfit | Pharmaceutical combinations comprising a dpp-4 inhibitor and a 1,3-diphenylprop-2-en-1-one derivative |
| EP2356985A1 (en) | 2010-02-10 | 2011-08-17 | LEK Pharmaceuticals d.d. | Novel pharmaceutical compositions comprising a combination of metformin and sitagliptin |
| WO2011107530A2 (en) | 2010-03-03 | 2011-09-09 | Probiodrug Ag | Novel inhibitors |
| JP5688745B2 (ja) | 2010-03-10 | 2015-03-25 | プロビオドルグ エージー | グルタミニルシクラーゼ（ｑｃ、ｅｃ２．３．２．５）の複素環阻害剤 |
| WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
| CA3070513C (en) | 2010-05-05 | 2023-01-03 | Boehringer Ingelheim International Gmbh | A dpp-4 inhibitor for use in treatment of skin-alterations or necrosis |
| EA201201509A1 (ru) * | 2010-05-05 | 2013-04-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Фармацевтические составы, содержащие пиоглитазон и линаглиптин |
| KR20130093012A (ko) | 2010-06-24 | 2013-08-21 | 베링거 인겔하임 인터내셔날 게엠베하 | 당뇨병 요법 |
| AR083878A1 (es) | 2010-11-15 | 2013-03-27 | Boehringer Ingelheim Int | Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento |
| TR201010683A1 (tr) * | 2010-12-21 | 2012-07-23 | Sanovel İlaç San. Ve Ti̇c. A.Ş. | Vildagliptin formülasyonları. |
| WO2012090225A2 (en) * | 2010-12-29 | 2012-07-05 | Nutracryst Therapeutics Private Limited | Novel cocrystals / molecular salts of metformin with oleoylethanolamide as an effective anti-diabetic + anti- obesity agent |
| EP2686313B1 (en) | 2011-03-16 | 2016-02-03 | Probiodrug AG | Benzimidazole derivatives as inhibitors of glutaminyl cyclase |
| DK2731947T3 (en) | 2011-07-15 | 2019-04-23 | Boehringer Ingelheim Int | SUBSTITUTED DIMERIC QUINAZOLINE DERIVATIVE, PREPARATION AND USE thereof IN PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OF TYPE I AND TYPE II DIABETES |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| WO2013171167A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
| WO2013171166A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp-4 inhibitor for use in the treatment of sirs and/or sepsis |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
| EP3110449B1 (en) | 2014-02-28 | 2023-06-28 | Boehringer Ingelheim International GmbH | Medical use of a dpp-4 inhibitor |
| CN106706768B (zh) * | 2015-11-17 | 2021-05-11 | 重庆医药工业研究院有限责任公司 | 一种分离测定恩格列净及其有关物质的方法 |
| EP4233840A3 (en) | 2016-06-10 | 2023-10-18 | Boehringer Ingelheim International GmbH | Combinations of linagliptin and metformin |
| ES2812698T3 (es) | 2017-09-29 | 2021-03-18 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
| EP3958857A1 (en) | 2019-09-17 | 2022-03-02 | Novartis AG | Combination therapy with vildagliptin and metformin |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002529417A (ja) * | 1998-11-09 | 2002-09-10 | ワーナー−ランバート・カンパニー | スルホニル尿素、グリタゾンおよびビグアニドを含有する糖尿病用組み合わせ薬剤 |
| JP2003520226A (ja) * | 2000-01-21 | 2003-07-02 | ノバルティス アクチエンゲゼルシャフト | ジペプチジルペプチダーゼ−ｉｖ阻害剤および抗糖尿病薬剤を含む組合せ物 |
| JP2003535898A (ja) * | 2000-06-19 | 2003-12-02 | スミスクライン ビーチャム パブリック リミテッド カンパニー | 真性糖尿病の治療用のジペプチジルペプチダーゼｉｖ阻害剤および他の抗糖尿病剤の組み合わせ |
| JP2004532220A (ja) * | 2001-04-12 | 2004-10-21 | ブリストル−マイヤーズ スクイブ カンパニー | ジペプチジル・ペプチダーゼｉｖの２，１−オキサゾリンおよび１，２−ピラゾリンに基づくインヒビターおよび方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CO5150173A1 (es) * | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
-
2005
- 2005-10-21 US US11/577,941 patent/US20090253752A1/en not_active Abandoned
- 2005-10-21 BR BRPI0518409-6A patent/BRPI0518409A2/pt not_active IP Right Cessation
- 2005-10-21 RU RU2007119320/15A patent/RU2007119320A/ru unknown
- 2005-10-21 AU AU2005299808A patent/AU2005299808B2/en not_active Ceased
- 2005-10-21 CN CN2005800343814A patent/CN101035522B/zh not_active Expired - Fee Related
- 2005-10-21 JP JP2007538049A patent/JP2008517921A/ja active Pending
- 2005-10-21 CA CA002581298A patent/CA2581298A1/en not_active Abandoned
- 2005-10-21 WO PCT/US2005/037819 patent/WO2006047248A1/en not_active Ceased
- 2005-10-21 EP EP05816082A patent/EP1807066A1/en not_active Withdrawn
- 2005-10-21 MX MX2007004934A patent/MX2007004934A/es unknown
- 2005-10-21 KR KR1020077009270A patent/KR20070068407A/ko not_active Ceased
-
2009
- 2009-10-01 AU AU2009222515A patent/AU2009222515A1/en not_active Abandoned
-
2011
- 2011-08-15 US US13/209,890 patent/US20110301172A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002529417A (ja) * | 1998-11-09 | 2002-09-10 | ワーナー−ランバート・カンパニー | スルホニル尿素、グリタゾンおよびビグアニドを含有する糖尿病用組み合わせ薬剤 |
| JP2003520226A (ja) * | 2000-01-21 | 2003-07-02 | ノバルティス アクチエンゲゼルシャフト | ジペプチジルペプチダーゼ−ｉｖ阻害剤および抗糖尿病薬剤を含む組合せ物 |
| JP2003535898A (ja) * | 2000-06-19 | 2003-12-02 | スミスクライン ビーチャム パブリック リミテッド カンパニー | 真性糖尿病の治療用のジペプチジルペプチダーゼｉｖ阻害剤および他の抗糖尿病剤の組み合わせ |
| JP2004532220A (ja) * | 2001-04-12 | 2004-10-21 | ブリストル−マイヤーズ スクイブ カンパニー | ジペプチジル・ペプチダーゼｉｖの２，１−オキサゾリンおよび１，２−ピラゾリンに基づくインヒビターおよび方法 |
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9339480B2 (en) | 2008-11-26 | 2016-05-17 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of obesity and diabetes |
| JP2012509891A (ja) * | 2008-11-26 | 2012-04-26 | サティオゲン ファーマシューティカルズ，インク． | 肥満症及び糖尿病を治療するための胆汁酸再循環阻害剤 |
| US10555950B2 (en) | 2008-11-26 | 2020-02-11 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of obesity and diabetes |
| JP2014144961A (ja) * | 2008-11-26 | 2014-08-14 | Satiogen Pharmaceuticals Inc | 肥満症及び糖尿病を治療するための胆汁酸再循環阻害剤 |
| WO2010074271A1 (ja) * | 2008-12-26 | 2010-07-01 | 武田薬品工業株式会社 | 糖尿病治療剤 |
| JP2012520883A (ja) * | 2009-03-16 | 2012-09-10 | アイピントゥル，エルエルシー | アルツハイマー病及び骨粗鬆症の治療並びに老化の軽減 |
| JP2017081943A (ja) * | 2009-11-13 | 2017-05-18 | アストラゼネカ・アクチエボラーグＡｓｔｒａｚｅｎｅｃａ Ａｋｔｉｅｂｏｌａｇ | 二層錠製剤 |
| JP2015110630A (ja) * | 2009-11-13 | 2015-06-18 | アストラゼネカ・アクチエボラーグＡｓｔｒａｚｅｎｅｃａ Ａｋｔｉｅｂｏｌａｇ | 二層錠製剤 |
| JP2013510873A (ja) * | 2009-11-13 | 2013-03-28 | ブリストル−マイヤーズ スクイブ カンパニー | 二層錠製剤 |
| US10188646B2 (en) | 2010-05-26 | 2019-01-29 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
| US10251880B2 (en) | 2010-05-26 | 2019-04-09 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
| US11260053B2 (en) | 2010-05-26 | 2022-03-01 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
| JP2014507456A (ja) * | 2011-03-07 | 2014-03-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | メトホルミン及びｄｐｐ−４阻害剤又はｓｇｌｔ−２阻害剤を含む医薬組成物 |
| US10512657B2 (en) | 2011-10-28 | 2019-12-24 | Lumena Pharmaceutials Llc | Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases |
| US11229661B2 (en) | 2011-10-28 | 2022-01-25 | Shire Human Genetic Therapies, Inc. | Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases |
| US11376251B2 (en) | 2011-10-28 | 2022-07-05 | Shire Human Genetic Therapies, Inc. | Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases |
| US12145959B2 (en) | 2011-10-28 | 2024-11-19 | Shire Human Genetic Therapies, Inc. | Bile acid recycling inhibitors for treatment of hypercholemia and cholestatic liver disease |
| US12350267B2 (en) | 2011-10-28 | 2025-07-08 | Shire Human Genetic Therapies, Inc. | Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1807066A1 (en) | 2007-07-18 |
| US20090253752A1 (en) | 2009-10-08 |
| US20110301172A1 (en) | 2011-12-08 |
| KR20070068407A (ko) | 2007-06-29 |
| CA2581298A1 (en) | 2006-05-04 |
| MX2007004934A (es) | 2007-06-12 |
| AU2009222515A1 (en) | 2009-10-22 |
| AU2005299808B2 (en) | 2009-08-20 |
| CN101035522A (zh) | 2007-09-12 |
| WO2006047248A1 (en) | 2006-05-04 |
| BRPI0518409A2 (pt) | 2008-11-18 |
| AU2005299808A1 (en) | 2006-05-04 |
| CN101035522B (zh) | 2011-12-07 |
| RU2007119320A (ru) | 2008-11-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101035522B (zh) | Dpp-ⅳ抑制剂、ppar抗糖尿病剂和二甲双胍的组合 | |
| CA2673615C (en) | Combinations comprising dipeptidylpeptidase-iv inhibitors and antidiabetic agents | |
| KR100544244B1 (ko) | 대사 장애, 특히 당뇨병 또는 당뇨병 관련 질환 또는증상의 치료 방법 | |
| JP5072848B2 (ja) | 低血糖イベントを低減するためのｄｐｐ−ｉｖ阻害剤の使用 | |
| EP1894567A1 (en) | Concomitant pharmaceutical agents and use thereof | |
| CN1413107A (zh) | 降血糖剂用于治疗葡萄糖代谢障碍 | |
| MXPA04009227A (es) | Combinacion que comprende un inhibidor de reductasa hmg-coa y un mejorador de sercrecion de insulina o un sintetizador de insulina. | |
| US20080261864A1 (en) | Combination of nateglinide or repaglinide with at least one further antidiabetic compound | |
| US20140142145A1 (en) | Combinations comprising a dipeptidylpeptidase - iv inhibitor | |
| CN101478969A (zh) | Pkc抑制剂在糖尿病并发症中的用途 | |
| CN101557811A (zh) | 用于预防、延缓或降低水肿发生的二肽基肽酶iv抑制剂的用途 | |
| HK1102424B (en) | Combinations comprising dipeptidylpeptidase-iv inhibitors and antidiabetic agents | |
| HK1108359B (en) | Combinations comprising dipeptidylpeptidase-iv inhibitors and antidiabetic agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081008 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20081008 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111122 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120417 |