JP2013529617A5

JP2013529617A5 -

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Publication number: JP2013529617A5
Authority: JP; Japan
Prior art keywords: insulin; dpp; inhibitor; diabetes; combination according
Prior art date: 2011-06-22
Legal status : Granted

Application number

JP2013515884A

Other languages

English (en)

Japanese (ja)

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JP2013529617A (ja

JP5843855B2 (ja

Filing date

2011-06-22

Publication date

2013-08-29

2011-06-22 Application filed filed Critical

2011-06-22 Priority claimed from PCT/EP2011/060449 external-priority patent/WO2011161161A1/en

2013-07-22 Publication of JP2013529617A publication Critical patent/JP2013529617A/ja

2013-08-29 Publication of JP2013529617A5 publication Critical patent/JP2013529617A5/ja

2016-01-13 Application granted granted Critical

2016-01-13 Publication of JP5843855B2 publication Critical patent/JP5843855B2/ja

Status Active legal-status Critical Current

2031-06-22 Anticipated expiration legal-status Critical

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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 18
229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 claims 15
108010092217 Long-Acting Insulin Proteins 0.000 claims 10
102000016261 Long-Acting Insulin Human genes 0.000 claims 10
229940100066 Long-acting insulin Drugs 0.000 claims 10
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 10
238000011282 treatment Methods 0.000 claims 10
208000001072 type 2 diabetes mellitus Diseases 0.000 claims 10
102000004877 Insulin Human genes 0.000 claims 9
108090001061 Insulin Proteins 0.000 claims 9
229940125396 insulin Drugs 0.000 claims 9
238000000034 method Methods 0.000 claims 9
239000008194 pharmaceutical composition Substances 0.000 claims 9
LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 claims 7
229960002397 linagliptin Drugs 0.000 claims 7
230000002265 prevention Effects 0.000 claims 7
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 6
239000008103 glucose Substances 0.000 claims 6
208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 6
108010057186 Insulin Glargine Proteins 0.000 claims 5
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 5
239000003472 antidiabetic agent Substances 0.000 claims 5
239000003814 drug Substances 0.000 claims 5
229960002869 insulin glargine Drugs 0.000 claims 5
210000004185 liver Anatomy 0.000 claims 5
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims 5
229960003105 metformin Drugs 0.000 claims 5
229960005095 pioglitazone Drugs 0.000 claims 5
201000009104 prediabetes syndrome Diseases 0.000 claims 5
238000007920 subcutaneous administration Methods 0.000 claims 5
208000002249 Diabetes Complications Diseases 0.000 claims 4
206010012655 Diabetic complications Diseases 0.000 claims 4
208000002705 Glucose Intolerance Diseases 0.000 claims 4
108010089308 Insulin Detemir Proteins 0.000 claims 4
FYZPCMFQCNBYCY-WIWKJPBBSA-N Insulin degludec Chemical compound CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=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](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC(O)=O)C(O)=O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC FYZPCMFQCNBYCY-WIWKJPBBSA-N 0.000 claims 4
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
108010050259 insulin degludec Proteins 0.000 claims 4
229960004225 insulin degludec Drugs 0.000 claims 4
229960003948 insulin detemir Drugs 0.000 claims 4
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 4
230000001225 therapeutic effect Effects 0.000 claims 4
201000001320 Atherosclerosis Diseases 0.000 claims 3
210000002237 B-cell of pancreatic islet Anatomy 0.000 claims 3
206010020772 Hypertension Diseases 0.000 claims 3
230000003178 anti-diabetic effect Effects 0.000 claims 3
230000037396 body weight Effects 0.000 claims 3
208000035475 disorder Diseases 0.000 claims 3
201000001421 hyperglycemia Diseases 0.000 claims 3
208000017169 kidney disease Diseases 0.000 claims 3
208000001921 latent autoimmune diabetes in adults Diseases 0.000 claims 3
208000010125 myocardial infarction Diseases 0.000 claims 3
229940124597 therapeutic agent Drugs 0.000 claims 3
230000002792 vascular Effects 0.000 claims 3
208000004476 Acute Coronary Syndrome Diseases 0.000 claims 2
206010002388 Angina unstable Diseases 0.000 claims 2
208000031229 Cardiomyopathies Diseases 0.000 claims 2
208000024172 Cardiovascular disease Diseases 0.000 claims 2
208000002177 Cataract Diseases 0.000 claims 2
208000007342 Diabetic Nephropathies Diseases 0.000 claims 2
208000008960 Diabetic foot Diseases 0.000 claims 2
206010056340 Diabetic ulcer Diseases 0.000 claims 2
206010048554 Endothelial dysfunction Diseases 0.000 claims 2
208000004930 Fatty Liver Diseases 0.000 claims 2
206010019280 Heart failures Diseases 0.000 claims 2
206010019708 Hepatic steatosis Diseases 0.000 claims 2
208000013016 Hypoglycemia Diseases 0.000 claims 2
206010061218 Inflammation Diseases 0.000 claims 2
206010022489 Insulin Resistance Diseases 0.000 claims 2
206010054805 Macroangiopathy Diseases 0.000 claims 2
208000026139 Memory disease Diseases 0.000 claims 2
208000001145 Metabolic Syndrome Diseases 0.000 claims 2
208000008589 Obesity Diseases 0.000 claims 2
206010033307 Overweight Diseases 0.000 claims 2
208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims 2
208000017442 Retinal disease Diseases 0.000 claims 2
206010038923 Retinopathy Diseases 0.000 claims 2
208000007718 Stable Angina Diseases 0.000 claims 2
229940100389 Sulfonylurea Drugs 0.000 claims 2
208000007814 Unstable Angina Diseases 0.000 claims 2
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 2
230000005856 abnormality Effects 0.000 claims 2
239000004480 active ingredient Substances 0.000 claims 2
210000001789 adipocyte Anatomy 0.000 claims 2
210000000577 adipose tissue Anatomy 0.000 claims 2
239000008280 blood Substances 0.000 claims 2
210000004369 blood Anatomy 0.000 claims 2
208000026106 cerebrovascular disease Diseases 0.000 claims 2
208000010877 cognitive disease Diseases 0.000 claims 2
206010012601 diabetes mellitus Diseases 0.000 claims 2
208000033679 diabetic kidney disease Diseases 0.000 claims 2
239000002552 dosage form Substances 0.000 claims 2
229940079593 drug Drugs 0.000 claims 2
230000002526 effect on cardiovascular system Effects 0.000 claims 2
230000008694 endothelial dysfunction Effects 0.000 claims 2
208000010706 fatty liver disease Diseases 0.000 claims 2
230000002641 glycemic effect Effects 0.000 claims 2
230000002218 hypoglycaemic effect Effects 0.000 claims 2
230000004054 inflammatory process Effects 0.000 claims 2
201000004332 intermediate coronary syndrome Diseases 0.000 claims 2
208000028867 ischemia Diseases 0.000 claims 2
230000003902 lesion Effects 0.000 claims 2
208000030159 metabolic disease Diseases 0.000 claims 2
210000000663 muscle cell Anatomy 0.000 claims 2
208000015122 neurodegenerative disease Diseases 0.000 claims 2
201000001119 neuropathy Diseases 0.000 claims 2
230000007823 neuropathy Effects 0.000 claims 2
206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 2
235000020824 obesity Nutrition 0.000 claims 2
208000033808 peripheral neuropathy Diseases 0.000 claims 2
230000000291 postprandial effect Effects 0.000 claims 2
201000001474 proteinuria Diseases 0.000 claims 2
238000011084 recovery Methods 0.000 claims 2
208000037803 restenosis Diseases 0.000 claims 2
231100000240 steatosis hepatitis Toxicity 0.000 claims 2
YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims 2
210000001519 tissue Anatomy 0.000 claims 2
230000004584 weight gain Effects 0.000 claims 2
235000019786 weight gain Nutrition 0.000 claims 2
206010002383 Angina Pectoris Diseases 0.000 claims 1
206010012689 Diabetic retinopathy Diseases 0.000 claims 1
208000013600 Diabetic vascular disease Diseases 0.000 claims 1
208000032928 Dyslipidaemia Diseases 0.000 claims 1
206010018429 Glucose tolerance impaired Diseases 0.000 claims 1
102000017011 Glycated Hemoglobin A Human genes 0.000 claims 1
108010014663 Glycated Hemoglobin A Proteins 0.000 claims 1
208000035150 Hypercholesterolemia Diseases 0.000 claims 1
206010060378 Hyperinsulinaemia Diseases 0.000 claims 1
208000031226 Hyperlipidaemia Diseases 0.000 claims 1
208000031773 Insulin resistance syndrome Diseases 0.000 claims 1
208000020358 Learning disease Diseases 0.000 claims 1
208000017170 Lipid metabolism disease Diseases 0.000 claims 1
208000012902 Nervous system disease Diseases 0.000 claims 1
208000025966 Neurological disease Diseases 0.000 claims 1
208000001132 Osteoporosis Diseases 0.000 claims 1
208000001280 Prediabetic State Diseases 0.000 claims 1
230000002159 abnormal effect Effects 0.000 claims 1
238000009825 accumulation Methods 0.000 claims 1
230000002411 adverse Effects 0.000 claims 1
229940127003 anti-diabetic drug Drugs 0.000 claims 1
229940125708 antidiabetic agent Drugs 0.000 claims 1
230000001684 chronic effect Effects 0.000 claims 1
208000019425 cirrhosis of liver Diseases 0.000 claims 1
238000002648 combination therapy Methods 0.000 claims 1
230000007423 decrease Effects 0.000 claims 1
230000007850 degeneration Effects 0.000 claims 1
230000003111 delayed effect Effects 0.000 claims 1
201000009101 diabetic angiopathy Diseases 0.000 claims 1
201000002249 diabetic peripheral angiopathy Diseases 0.000 claims 1
201000010099 disease Diseases 0.000 claims 1
230000004064 dysfunction Effects 0.000 claims 1
230000000694 effects Effects 0.000 claims 1
210000002889 endothelial cell Anatomy 0.000 claims 1
230000003451 hyperinsulinaemic effect Effects 0.000 claims 1
201000008980 hyperinsulinism Diseases 0.000 claims 1
208000006575 hypertriglyceridemia Diseases 0.000 claims 1
230000003914 insulin secretion Effects 0.000 claims 1
238000007918 intramuscular administration Methods 0.000 claims 1
230000007794 irritation Effects 0.000 claims 1
230000003907 kidney function Effects 0.000 claims 1
201000003723 learning disability Diseases 0.000 claims 1
230000028252 learning or memory Effects 0.000 claims 1
238000002483 medication Methods 0.000 claims 1
210000005036 nerve Anatomy 0.000 claims 1
201000010065 polycystic ovary syndrome Diseases 0.000 claims 1
238000004321 preservation Methods 0.000 claims 1
230000001737 promoting effect Effects 0.000 claims 1
238000011321 prophylaxis Methods 0.000 claims 1
210000001525 retina Anatomy 0.000 claims 1
230000001568 sexual effect Effects 0.000 claims 1
238000009097 single-agent therapy Methods 0.000 claims 1
230000009861 stroke prevention Effects 0.000 claims 1
238000010254 subcutaneous injection Methods 0.000 claims 1
239000007929 subcutaneous injection Substances 0.000 claims 1
208000024891 symptom Diseases 0.000 claims 1
230000009885 systemic effect Effects 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1

JP2013515884A 2010-06-24 2011-06-22 糖尿病療法 Active JP5843855B2 (ja)