CA3001627A1 - Treatment of mixed dyslipidemia - Google Patents
Treatment of mixed dyslipidemia Download PDFInfo
- Publication number
- CA3001627A1 CA3001627A1 CA3001627A CA3001627A CA3001627A1 CA 3001627 A1 CA3001627 A1 CA 3001627A1 CA 3001627 A CA3001627 A CA 3001627A CA 3001627 A CA3001627 A CA 3001627A CA 3001627 A1 CA3001627 A1 CA 3001627A1
- Authority
- CA
- Canada
- Prior art keywords
- gemcabene
- subject
- atorvastatin
- statin
- daily dose
- 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.)
- Abandoned
Links
- 238000011282 treatment Methods 0.000 title claims description 83
- 208000032928 Dyslipidaemia Diseases 0.000 title description 7
- 208000017170 Lipid metabolism disease Diseases 0.000 title description 7
- 238000000034 method Methods 0.000 claims abstract description 176
- 108010049003 Fibrinogen Proteins 0.000 claims abstract description 50
- 102000008946 Fibrinogen Human genes 0.000 claims abstract description 50
- 229940012952 fibrinogen Drugs 0.000 claims abstract description 50
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims abstract description 49
- 239000000203 mixture Substances 0.000 claims abstract description 17
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims abstract description 11
- 230000007211 cardiovascular event Effects 0.000 claims abstract description 7
- 206010019668 Hepatic fibrosis Diseases 0.000 claims abstract description 5
- SDMBRCRVFFHJKR-UHFFFAOYSA-N 6-(5-carboxy-5-methylhexoxy)-2,2-dimethylhexanoic acid Chemical compound OC(=O)C(C)(C)CCCCOCCCCC(C)(C)C(O)=O SDMBRCRVFFHJKR-UHFFFAOYSA-N 0.000 claims description 379
- 229950004781 gemcabene Drugs 0.000 claims description 370
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 178
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 161
- 229960005370 atorvastatin Drugs 0.000 claims description 161
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 144
- 210000004185 liver Anatomy 0.000 claims description 88
- 229940000425 combination drug Drugs 0.000 claims description 61
- 206010045263 Type IIb hyperlipidaemia Diseases 0.000 claims description 50
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 49
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 48
- 229960002855 simvastatin Drugs 0.000 claims description 48
- 230000000694 effects Effects 0.000 claims description 45
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 44
- 150000001875 compounds Chemical class 0.000 claims description 37
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 31
- 229960004844 lovastatin Drugs 0.000 claims description 31
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 31
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 31
- 229960000672 rosuvastatin Drugs 0.000 claims description 31
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 31
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 30
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 30
- 229960003765 fluvastatin Drugs 0.000 claims description 30
- 229960002965 pravastatin Drugs 0.000 claims description 30
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 30
- 229960002797 pitavastatin Drugs 0.000 claims description 28
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 28
- 238000009825 accumulation Methods 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 231100000240 steatosis hepatitis Toxicity 0.000 claims description 24
- 230000002829 reductive effect Effects 0.000 claims description 21
- 208000019423 liver disease Diseases 0.000 claims description 19
- 230000009467 reduction Effects 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 230000007863 steatosis Effects 0.000 claims description 16
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 15
- 210000003494 hepatocyte Anatomy 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 201000001376 Familial Combined Hyperlipidemia Diseases 0.000 claims description 10
- 206010061218 Inflammation Diseases 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001475 halogen functional group Chemical group 0.000 claims description 8
- 230000004054 inflammatory process Effects 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 7
- 108010027006 Apolipoproteins B Proteins 0.000 claims description 6
- 102000018616 Apolipoproteins B Human genes 0.000 claims description 6
- -1 COOR3 Chemical group 0.000 claims description 6
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims description 6
- 238000008214 LDL Cholesterol Methods 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 239000003529 anticholesteremic agent Substances 0.000 claims description 6
- 229940127226 anticholesterol agent Drugs 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 5
- 206010039020 Rhabdomyolysis Diseases 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- 235000021323 fish oil Nutrition 0.000 claims description 4
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 3
- 229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 claims description 3
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 claims description 3
- 229960000815 ezetimibe Drugs 0.000 claims description 3
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 3
- 230000006641 stabilisation Effects 0.000 claims description 3
- 238000011105 stabilization Methods 0.000 claims description 3
- 208000021642 Muscular disease Diseases 0.000 claims description 2
- 201000009623 Myopathy Diseases 0.000 claims description 2
- 201000002481 Myositis Diseases 0.000 claims description 2
- 239000003524 antilipemic agent Substances 0.000 claims 3
- 230000000087 stabilizing effect Effects 0.000 claims 3
- 102000030169 Apolipoprotein C-III Human genes 0.000 claims 2
- 108010056301 Apolipoprotein C-III Proteins 0.000 claims 2
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims 2
- 229940122392 PCSK9 inhibitor Drugs 0.000 claims 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims 2
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims 2
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims 2
- 239000012453 solvate Substances 0.000 claims 2
- 208000022309 Alcoholic Liver disease Diseases 0.000 claims 1
- 229910006069 SO3H Inorganic materials 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 abstract description 13
- 101710095342 Apolipoprotein B Proteins 0.000 abstract description 10
- 102100040202 Apolipoprotein B-100 Human genes 0.000 abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
- 238000009472 formulation Methods 0.000 abstract description 6
- 208000031226 Hyperlipidaemia Diseases 0.000 abstract description 5
- 208000035475 disorder Diseases 0.000 abstract 1
- 210000002381 plasma Anatomy 0.000 description 97
- 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 69
- 210000004369 blood Anatomy 0.000 description 39
- 239000008280 blood Substances 0.000 description 39
- 235000012000 cholesterol Nutrition 0.000 description 32
- 239000003814 drug Substances 0.000 description 32
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 28
- 150000003626 triacylglycerols Chemical class 0.000 description 28
- 229940079593 drug Drugs 0.000 description 26
- 239000000902 placebo Substances 0.000 description 26
- 229940068196 placebo Drugs 0.000 description 26
- 108010028554 LDL Cholesterol Proteins 0.000 description 25
- 230000008859 change Effects 0.000 description 25
- 206010012601 diabetes mellitus Diseases 0.000 description 25
- 241000699666 Mus <mouse, genus> Species 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 241000699670 Mus sp. Species 0.000 description 21
- 238000013231 NASH rodent model Methods 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 21
- 238000009097 single-agent therapy Methods 0.000 description 21
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 20
- 239000000523 sample Substances 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 16
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 16
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 16
- 206010016654 Fibrosis Diseases 0.000 description 15
- 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 15
- 230000037396 body weight Effects 0.000 description 15
- 239000008103 glucose Substances 0.000 description 15
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 14
- 241000700159 Rattus Species 0.000 description 14
- 229960005187 telmisartan Drugs 0.000 description 14
- 108010029485 Protein Isoforms Proteins 0.000 description 13
- 102000001708 Protein Isoforms Human genes 0.000 description 13
- 230000007423 decrease Effects 0.000 description 13
- 230000002440 hepatic effect Effects 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 230000004761 fibrosis Effects 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 10
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 10
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 10
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 10
- 229940125753 fibrate Drugs 0.000 description 10
- 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 10
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 9
- 108010082126 Alanine transaminase Proteins 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229960003627 gemfibrozil Drugs 0.000 description 9
- 229960002591 hydroxyproline Drugs 0.000 description 9
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000008186 active pharmaceutical agent Substances 0.000 description 8
- 229940109239 creatinine Drugs 0.000 description 8
- 208000010706 fatty liver disease Diseases 0.000 description 8
- 235000019136 lipoic acid Nutrition 0.000 description 8
- LFULEKSKNZEWOE-UHFFFAOYSA-N propanil Chemical compound CCC(=O)NC1=CC=C(Cl)C(Cl)=C1 LFULEKSKNZEWOE-UHFFFAOYSA-N 0.000 description 8
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 8
- 229960002663 thioctic acid Drugs 0.000 description 8
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 7
- 102100039205 Cytochrome P450 3A4 Human genes 0.000 description 7
- 208000004930 Fatty Liver Diseases 0.000 description 7
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 229940049950 atorvastatin 10 mg Drugs 0.000 description 7
- 229940050446 atorvastatin 40 mg Drugs 0.000 description 7
- 229940067134 atorvastatin 80 mg Drugs 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 150000002576 ketones Chemical class 0.000 description 7
- 229960001052 streptozocin Drugs 0.000 description 7
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 6
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 6
- 108020004206 Gamma-glutamyltransferase Proteins 0.000 description 6
- 108010023302 HDL Cholesterol Proteins 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZJKZKKPIKDNHDM-UHFFFAOYSA-L calcium;6-(5-carboxylato-5-methylhexoxy)-2,2-dimethylhexanoate Chemical compound [Ca+2].[O-]C(=O)C(C)(C)CCCCOCCCCC(C)(C)C([O-])=O ZJKZKKPIKDNHDM-UHFFFAOYSA-L 0.000 description 6
- 208000019425 cirrhosis of liver Diseases 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 102000004877 Insulin Human genes 0.000 description 5
- 108090001061 Insulin Proteins 0.000 description 5
- 230000008406 drug-drug interaction Effects 0.000 description 5
- 238000005805 hydroxylation reaction Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- SOZOATLLFFVAPM-KAYWLYCHSA-N p-hydroxyatorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=C(O)C=C1 SOZOATLLFFVAPM-KAYWLYCHSA-N 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 238000013222 sprague-dawley male rat Methods 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 108010074051 C-Reactive Protein Proteins 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 108010074922 Cytochrome P-450 CYP1A2 Proteins 0.000 description 4
- 108010000543 Cytochrome P-450 CYP2C9 Proteins 0.000 description 4
- 108010001237 Cytochrome P-450 CYP2D6 Proteins 0.000 description 4
- 102100026533 Cytochrome P450 1A2 Human genes 0.000 description 4
- 102100036194 Cytochrome P450 2A6 Human genes 0.000 description 4
- 102100029358 Cytochrome P450 2C9 Human genes 0.000 description 4
- 102100021704 Cytochrome P450 2D6 Human genes 0.000 description 4
- 206010022489 Insulin Resistance Diseases 0.000 description 4
- 208000000112 Myalgia Diseases 0.000 description 4
- 229940123934 Reductase inhibitor Drugs 0.000 description 4
- 238000000692 Student's t-test Methods 0.000 description 4
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 239000003146 anticoagulant agent Substances 0.000 description 4
- 230000037058 blood plasma level Effects 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 235000009200 high fat diet Nutrition 0.000 description 4
- 230000000260 hypercholesteremic effect Effects 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 description 3
- CZBPKFICAYVHHM-JWQCQUIFSA-N (3r,5r)-7-[2-(4-fluorophenyl)-4-[(2-hydroxyphenyl)carbamoyl]-3-phenyl-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1O CZBPKFICAYVHHM-JWQCQUIFSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 3
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 102100024889 Cytochrome P450 2E1 Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000015779 HDL Lipoproteins Human genes 0.000 description 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
- 206010019663 Hepatic failure Diseases 0.000 description 3
- 101000875170 Homo sapiens Cytochrome P450 2A6 Proteins 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- 108010007622 LDL Lipoproteins Proteins 0.000 description 3
- 102000007330 LDL Lipoproteins Human genes 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 229960001770 atorvastatin calcium Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 230000007882 cirrhosis Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000011260 co-administration Methods 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 230000036267 drug metabolism Effects 0.000 description 3
- 229920000669 heparin Polymers 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 231100000835 liver failure Toxicity 0.000 description 3
- 208000007903 liver failure Diseases 0.000 description 3
- 108010030696 low density lipoprotein triglyceride Proteins 0.000 description 3
- 230000037353 metabolic pathway Effects 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 230000003228 microsomal effect Effects 0.000 description 3
- 238000000329 molecular dynamics simulation Methods 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 235000020925 non fasting Nutrition 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 238000012353 t test Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- XUKUURHRXDUEBC-SVBPBHIXSA-N (3s,5s)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SVBPBHIXSA-N 0.000 description 2
- PJVWKTKQMONHTI-OAHLLOKOSA-N (R)-warfarin Chemical compound C1([C@@H](CC(=O)C)C=2C(OC3=CC=CC=C3C=2O)=O)=CC=CC=C1 PJVWKTKQMONHTI-OAHLLOKOSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- OUCSEDFVYPBLLF-KAYWLYCHSA-N 5-(4-fluorophenyl)-1-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-n,4-diphenyl-2-propan-2-ylpyrrole-3-carboxamide Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H]2OC(=O)C[C@H](O)C2)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 OUCSEDFVYPBLLF-KAYWLYCHSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 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
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000032064 Chronic Limb-Threatening Ischemia Diseases 0.000 description 2
- 241000725101 Clea Species 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- 108010026925 Cytochrome P-450 CYP2C19 Proteins 0.000 description 2
- 108010001202 Cytochrome P-450 CYP2E1 Proteins 0.000 description 2
- 102100029363 Cytochrome P450 2C19 Human genes 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000029549 Muscle injury Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- MNECBMZJZFGTIK-JWQCQUIFSA-N O-Hydroxyatorvastatin lactone Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H]2OC(=O)C[C@H](O)C2)C(C(C)C)=C1C(=O)NC1=CC=CC=C1O MNECBMZJZFGTIK-JWQCQUIFSA-N 0.000 description 2
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 2
- 206010034576 Peripheral ischaemia Diseases 0.000 description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 108010069201 VLDL Cholesterol Proteins 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
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA 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)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 230000003510 anti-fibrotic effect Effects 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 238000012754 cardiac puncture Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 229960003850 dabigatran Drugs 0.000 description 2
- YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012317 liver biopsy Methods 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 231100000483 muscle toxicity Toxicity 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 210000004738 parenchymal cell Anatomy 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 208000030613 peripheral artery disease Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000013424 sirius red staining Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 2
- 230000022814 xenobiotic metabolic process Effects 0.000 description 2
- FGMPLJWBKKVCDB-BYPYZUCNSA-N (2s)-1-hydroxypyrrolidine-2-carboxylic acid Chemical compound ON1CCC[C@H]1C(O)=O FGMPLJWBKKVCDB-BYPYZUCNSA-N 0.000 description 1
- GMHKMTDVRCWUDX-LBPRGKRZSA-N (S)-Mephenytoin Chemical compound C=1C=CC=CC=1[C@]1(CC)NC(=O)N(C)C1=O GMHKMTDVRCWUDX-LBPRGKRZSA-N 0.000 description 1
- PJVWKTKQMONHTI-HNNXBMFYSA-N (S)-warfarin Chemical compound C1([C@H](CC(=O)C)C=2C(OC3=CC=CC=C3C=2O)=O)=CC=CC=C1 PJVWKTKQMONHTI-HNNXBMFYSA-N 0.000 description 1
- GEHAEMCVKDPMKO-HXUWFJFHSA-N 1-[1-[(2s)-3-(6-chloronaphthalen-2-yl)sulfonyl-2-hydroxypropanoyl]piperidin-4-yl]-1,3-diazinan-2-one Chemical compound O=C([C@@H](CS(=O)(=O)C=1C=C2C=CC(Cl)=CC2=CC=1)O)N(CC1)CCC1N1CCCNC1=O GEHAEMCVKDPMKO-HXUWFJFHSA-N 0.000 description 1
- XJNPNXSISMKQEX-UHFFFAOYSA-N 4-nitrocatechol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1O XJNPNXSISMKQEX-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-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
- 102000000452 Acetyl-CoA carboxylase Human genes 0.000 description 1
- 108010016219 Acetyl-CoA carboxylase Proteins 0.000 description 1
- QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 description 1
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical group CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- 108010027612 Batroxobin Proteins 0.000 description 1
- 108010018763 Biotin carboxylase Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 239000011547 Bouin solution Substances 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101150022946 CYP3 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 206010065941 Central obesity Diseases 0.000 description 1
- 208000031288 Combined hyperlipidaemia Diseases 0.000 description 1
- 108010000080 Cytochrome P-450 CYP2A6 Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010011906 Death Diseases 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 101100137368 Dictyostelium discoideum cypD gene Proteins 0.000 description 1
- HGVDHZBSSITLCT-JLJPHGGASA-N Edoxaban Chemical compound N([C@H]1CC[C@@H](C[C@H]1NC(=O)C=1SC=2CN(C)CCC=2N=1)C(=O)N(C)C)C(=O)C(=O)NC1=CC=C(Cl)C=N1 HGVDHZBSSITLCT-JLJPHGGASA-N 0.000 description 1
- 206010014486 Elevated triglycerides Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 208000027472 Galactosemias Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 206010019837 Hepatocellular injury Diseases 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 108010007267 Hirudins Proteins 0.000 description 1
- 102000007625 Hirudins Human genes 0.000 description 1
- 101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 1
- 101000909131 Homo sapiens Cytochrome P450 2E1 Proteins 0.000 description 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 101150009380 PPIF gene Proteins 0.000 description 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
- 102100034943 Peptidyl-prolyl cis-trans isomerase F, mitochondrial Human genes 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 101150069124 RAN1 gene Proteins 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 101100222691 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CPR3 gene Proteins 0.000 description 1
- 101100276454 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYC7 gene Proteins 0.000 description 1
- YIQKLZYTHXTDDT-UHFFFAOYSA-H Sirius red F3B Chemical compound C1=CC(=CC=C1N=NC2=CC(=C(C=C2)N=NC3=C(C=C4C=C(C=CC4=C3[O-])NC(=O)NC5=CC6=CC(=C(C(=C6C=C5)[O-])N=NC7=C(C=C(C=C7)N=NC8=CC=C(C=C8)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+] YIQKLZYTHXTDDT-UHFFFAOYSA-H 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010043784 Thyroiditis subacute Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960002054 acenocoumarol Drugs 0.000 description 1
- VABCILAOYCMVPS-UHFFFAOYSA-N acenocoumarol Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=C([N+]([O-])=O)C=C1 VABCILAOYCMVPS-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 239000003741 agents affecting lipid metabolism Substances 0.000 description 1
- 230000002300 anti-fibrosis Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000713 anti-steatotic effect Effects 0.000 description 1
- 229960003886 apixaban Drugs 0.000 description 1
- KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 description 1
- 229960003856 argatroban Drugs 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- FKQQKMGWCJGUCS-UHFFFAOYSA-N atromentin Chemical compound O=C1C(O)=C(C=2C=CC(O)=CC=2)C(=O)C(O)=C1C1=CC=C(O)C=C1 FKQQKMGWCJGUCS-UHFFFAOYSA-N 0.000 description 1
- AAEDGQBSNHENEM-UHFFFAOYSA-N atromentin Natural products OCC1(O)C2=C(C(=O)C(=C(C2=O)c3ccc(O)cc3)O)c4ccc(O)cc14 AAEDGQBSNHENEM-UHFFFAOYSA-N 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 229960002210 batroxobin Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- HYHMLYSLQUKXKP-UHFFFAOYSA-N bempedoic acid Chemical compound OC(=O)C(C)(C)CCCCCC(O)CCCCCC(C)(C)C(O)=O HYHMLYSLQUKXKP-UHFFFAOYSA-N 0.000 description 1
- 229950002974 bempedoic acid Drugs 0.000 description 1
- 229950011103 betrixaban Drugs 0.000 description 1
- XHOLNRLADUSQLD-UHFFFAOYSA-N betrixaban Chemical compound C=1C=C(Cl)C=NC=1NC(=O)C1=CC(OC)=CC=C1NC(=O)C1=CC=C(C(=N)N(C)C)C=C1 XHOLNRLADUSQLD-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
- 229960001500 bivalirudin Drugs 0.000 description 1
- 108010055460 bivalirudin Proteins 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- PNDKCRDVVKJPKG-WHERJAGFSA-N cenicriviroc Chemical compound C1=CC(OCCOCCCC)=CC=C1C1=CC=C(N(CC(C)C)CCC\C(=C/2)C(=O)NC=3C=CC(=CC=3)[S@@](=O)CC=3N(C=NC=3)CCC)C\2=C1 PNDKCRDVVKJPKG-WHERJAGFSA-N 0.000 description 1
- 229950011033 cenicriviroc Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960005110 cerivastatin Drugs 0.000 description 1
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 description 1
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 208000026758 coronary atherosclerosis Diseases 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 229940072645 coumadin Drugs 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 229960000622 edoxaban Drugs 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- QQBKAVAGLMGMHI-WIYYLYMNSA-N eribaxaban Chemical compound N1([C@H](C[C@H](C1)OC)C(=O)NC=1C(=CC(=CC=1)N1C(C=CC=C1)=O)F)C(=O)NC1=CC=C(Cl)C=C1 QQBKAVAGLMGMHI-WIYYLYMNSA-N 0.000 description 1
- 229950007830 eribaxaban Drugs 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 230000001815 facial effect Effects 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
- 229950003499 fibrin Drugs 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 208000007345 glycogen storage disease Diseases 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 108010005808 hementin Proteins 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 230000002443 hepatoprotective effect Effects 0.000 description 1
- 229940006607 hirudin Drugs 0.000 description 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 238000011850 initial investigation Methods 0.000 description 1
- 238000012528 insulin ELISA Methods 0.000 description 1
- 210000001596 intra-abdominal fat Anatomy 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 229960004408 lepirudin Drugs 0.000 description 1
- OTQCKZUSUGYWBD-BRHMIFOHSA-N lepirudin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)C(C)C)[C@@H](C)O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)[C@@H](C)O)C1=CC=C(O)C=C1 OTQCKZUSUGYWBD-BRHMIFOHSA-N 0.000 description 1
- 229950001775 letaxaban Drugs 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 208000018191 liver inflammation Diseases 0.000 description 1
- 238000011551 log transformation method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- ZXERDUOLZKYMJM-ZWECCWDJSA-N obeticholic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCC(O)=O)CC[C@H]21 ZXERDUOLZKYMJM-ZWECCWDJSA-N 0.000 description 1
- 229960001601 obeticholic acid Drugs 0.000 description 1
- 208000001797 obstructive sleep apnea Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960000280 phenindione Drugs 0.000 description 1
- NFBAXHOPROOJAW-UHFFFAOYSA-N phenindione Chemical compound O=C1C2=CC=CC=C2C(=O)C1C1=CC=CC=C1 NFBAXHOPROOJAW-UHFFFAOYSA-N 0.000 description 1
- 229960004923 phenprocoumon Drugs 0.000 description 1
- DQDAYGNAKTZFIW-UHFFFAOYSA-N phenprocoumon Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC)C1=CC=CC=C1 DQDAYGNAKTZFIW-UHFFFAOYSA-N 0.000 description 1
- 238000003322 phosphorimaging Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000013105 post hoc analysis Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 229960001148 rivaroxaban Drugs 0.000 description 1
- KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 229950009513 simtuzumab Drugs 0.000 description 1
- XWLXKKNPFMNSFA-HGQWONQESA-N simvastatin hydroxy acid Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)C(C)(C)CC)C[C@@H](C)C=C21 XWLXKKNPFMNSFA-HGQWONQESA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 108091008012 small dense LDL Proteins 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 201000007497 subacute thyroiditis Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- 229940125670 thienopyridine Drugs 0.000 description 1
- 239000002175 thienopyridine Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 125000005457 triglyceride group Chemical group 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 229960001522 ximelagatran Drugs 0.000 description 1
- ZXIBCJHYVWYIKI-PZJWPPBQSA-N ximelagatran Chemical compound C1([C@@H](NCC(=O)OCC)C(=O)N2[C@@H](CC2)C(=O)NCC=2C=CC(=CC=2)C(\N)=N\O)CCCCC1 ZXIBCJHYVWYIKI-PZJWPPBQSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- 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
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- 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
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
- A61K9/4825—Proteins, e.g. gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Inorganic Chemistry (AREA)
- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562252195P | 2015-11-06 | 2015-11-06 | |
| US201562252147P | 2015-11-06 | 2015-11-06 | |
| US62/252,195 | 2015-11-06 | ||
| US62/252,147 | 2015-11-06 | ||
| PCT/US2016/060837 WO2017079748A1 (en) | 2015-11-06 | 2016-11-07 | Treatment of mixed dyslipidemia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3001627A1 true CA3001627A1 (en) | 2017-05-11 |
Family
ID=58663111
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3001627A Abandoned CA3001627A1 (en) | 2015-11-06 | 2016-11-07 | Treatment of mixed dyslipidemia |
| CA3000016A Abandoned CA3000016A1 (en) | 2015-11-06 | 2016-11-07 | Gemcabene combinations for the treatment of cardiovascular disease |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3000016A Abandoned CA3000016A1 (en) | 2015-11-06 | 2016-11-07 | Gemcabene combinations for the treatment of cardiovascular disease |
Country Status (16)
| Country | Link |
|---|---|
| US (4) | US9849104B2 (enExample) |
| EP (2) | EP3370713A4 (enExample) |
| JP (2) | JP2018532808A (enExample) |
| KR (2) | KR20180073665A (enExample) |
| CN (2) | CN108366957A (enExample) |
| AU (2) | AU2016349634A1 (enExample) |
| BR (2) | BR112018009238A8 (enExample) |
| CA (2) | CA3001627A1 (enExample) |
| HK (2) | HK1257929A1 (enExample) |
| IL (2) | IL258819A (enExample) |
| MA (1) | MA43190A (enExample) |
| MX (2) | MX2018005540A (enExample) |
| PH (1) | PH12018500972A1 (enExample) |
| RU (2) | RU2018120599A (enExample) |
| SG (2) | SG11201803442UA (enExample) |
| WO (2) | WO2017079755A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9719068B2 (en) | 2010-05-06 | 2017-08-01 | Children's Hospital Medical Center | Methods and systems for converting precursor cells into intestinal tissues through directed differentiation |
| CA2949834A1 (en) | 2014-05-28 | 2015-12-03 | James Macormack Wells | Methods and systems for converting precursor cells into gastric tissues through directed differentiation |
| CA2963704A1 (en) | 2014-10-17 | 2016-04-21 | Children's Hospital Medical Center | In vivo model of human small intestine using pluripotent stem cells and methods of making and using same |
| SG10201912713YA (en) | 2014-11-14 | 2020-02-27 | Gemphire Therapeutics Inc | PROCESSES AND INTERMEDIATES FOR PREPARING α,ω-DICARBOXYLIC ACID-TERMINATED DIALKANE ETHERS |
| BR112018009238A8 (pt) * | 2015-11-06 | 2019-02-26 | Gemphire Therapeutics Inc | tratamento de dislipidemia mista |
| EP4177335A1 (en) | 2016-05-05 | 2023-05-10 | Children's Hospital Medical Center | Methods for the in vitro manufacture of gastric fundus tissue and compositions related to same |
| KR20190039937A (ko) | 2016-07-08 | 2019-04-16 | 스태튼 바이오테크놀로지 비.브이. | 항-ApoC3 항체 및 이의 사용 방법 |
| KR102399254B1 (ko) | 2016-09-28 | 2022-05-17 | 아이거 바이오파마슈티컬스 인코포레이티드 | 비-알코올성 지방간염의 치료를 위한 방법 및 약제학적 조성물 |
| EP3534919A4 (en) | 2016-11-04 | 2020-11-11 | Children's Hospital Medical Center | Liver organoid compositions and methods of making and using same |
| KR20250068799A (ko) | 2016-12-05 | 2025-05-16 | 칠드런즈 호스피탈 메디칼 센터 | 결장 유사장기 및 이를 제조 및 사용하는 방법 |
| WO2018191673A1 (en) | 2017-04-14 | 2018-10-18 | Children's Hospital Medical Center | Multi donor stem cell compositions and methods of making same |
| US20180297929A1 (en) * | 2017-04-18 | 2018-10-18 | Gemphire Therapeutics Inc. | Gemcabene, pharmaceutically acceptable salts thereof, compositions thereof and methods of use therefor |
| CA3059133A1 (en) | 2017-04-21 | 2018-10-25 | Staten Biotechnology B.V. | Anti-apoc3 antibodies and methods of use thereof |
| US20180338922A1 (en) * | 2017-05-26 | 2018-11-29 | Esperion Therapeutics, Inc. | Fixed dose formulations |
| JP6937195B2 (ja) * | 2017-09-01 | 2021-09-22 | 興和株式会社 | 医薬組成物 |
| CA3077442A1 (en) | 2017-10-10 | 2019-04-18 | Children's Hospital Medical Center | Esophageal tissue and/or organoid compositions and methods of making same |
| MA50516A (fr) | 2017-10-31 | 2020-09-09 | Staten Biotechnology B V | Anticorps anti-apoc3 et leurs procédés d'utilisation |
| US10538583B2 (en) | 2017-10-31 | 2020-01-21 | Staten Biotechnology B.V. | Anti-APOC3 antibodies and compositions thereof |
| CA3082178A1 (en) * | 2017-11-28 | 2019-06-06 | Eiger Biopharmaceuticals, Inc. | Methods and pharmaceutical compositions for the treatment of non-alcoholic steatohepatitis |
| EP3727394A4 (en) | 2017-12-21 | 2021-09-08 | Children's Hospital Medical Center | DIGITALIZED HUMAN ORGANOIDS AND METHOD OF USING THEREOF |
| US12421500B2 (en) | 2018-07-26 | 2025-09-23 | Children's Hospital Medical Center | Hepato-biliary-pancreatic tissues and methods of making same |
| KR20210057781A (ko) | 2018-09-12 | 2021-05-21 | 칠드런즈 호스피탈 메디칼 센터 | 조혈 줄기세포 및 이의 파생체의 생산을 위한 오르가노이드 조성물 |
| CA3113016A1 (en) | 2018-09-18 | 2020-03-26 | 1Globe Biomedical Co., Ltd. | Treatment for non-alcoholic fatty liver disease |
| JP2022504736A (ja) * | 2018-10-12 | 2022-01-13 | アイカーン スクール オブ メディシン アット マウント サイナイ | 非アルコール性脂肪性肝炎（ｎａｓｈ）、肝線維症、および他の肝臓状態の処置および予防のためのａｚｄ３３５５（レソガベラン） |
| EP3867222A4 (en) * | 2018-10-18 | 2022-07-06 | Gemphire Therapeutics Inc. | GEMCABENE, PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, COMPOSITIONS THEREOF, AND METHODS OF USE THEREOF |
| CN112851660B (zh) * | 2019-11-12 | 2022-03-18 | 广东药科大学 | 含有小檗碱的酸-碱加成盐、其制备方法及其作为药物的用途 |
| CN114957119B (zh) * | 2022-05-05 | 2023-06-16 | 武汉大学中南医院 | 一种四氢喹啉螺1,3-茚二酮类衍生物及其制备方法与应用 |
| WO2025186785A1 (en) * | 2024-03-08 | 2025-09-12 | TECNIMEDE - Sociedade Técnico-medicinal, SA | Oral pharmaceutical composition of pitavastatin, method and uses thereof |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT381664B (de) | 1984-02-07 | 1986-11-10 | Steyr Daimler Puch Ag | Einrichtung zur ueberwachung elektrischer, von einer gesteuerten wechselstromquelle gespeister widerstandsschweissvorgaenge, insbesondere punktschweissungen |
| US5133974A (en) * | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| CA2039763A1 (en) | 1990-04-30 | 1991-10-31 | Henry Y. Pan | Combination of pravastatin and a fibric acid derivative, and method for treating dyslipidemia using such combination |
| US5298627A (en) | 1993-03-03 | 1994-03-29 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5648387A (en) * | 1995-03-24 | 1997-07-15 | Warner-Lambert Company | Carboxyalkylethers, formulations, and treatment of vascular diseases |
| NO318765B1 (no) | 1995-07-03 | 2005-05-02 | Sankyo Co | Anvendelse av en HMG-CoA reduktaseinhibitor og en insulinsensibilisator til fremstilling av et medikament for forebyggelse eller behandling av arteriosklerose eller xantom, samt pakket farmasoytisk preparat som omfatter de to midlene i separate porsjoner. |
| WO1997016187A1 (en) | 1995-10-31 | 1997-05-09 | Merck & Co., Inc. | Muscarine antagonists |
| AU7669496A (en) | 1995-11-03 | 1997-05-22 | University Of Kentucky | Method for the intranasal administration of l-dopa prodrugs |
| DE69837610T2 (de) * | 1997-07-31 | 2008-01-03 | Kos Life Sciences, Inc., Weston | Manteltablette enthaltend nikotinsäure oder einen stoff, der zu nikotinsäure metabolisiert wird in verzögert freigesetzter form und einen hmg-coa reduktasehemmer im mantel zur sofortigen freisetzung |
| NZ503982A (en) * | 1997-12-12 | 2002-03-28 | Warner Lambert Co | Statin-carboxyalkylether combinations useful for treating vascular disorders and diabetes mellitus |
| US20030105154A1 (en) * | 2001-10-24 | 2003-06-05 | Bisgaier Charles Larry | Statin-carboxyalkylether combinations |
| US6861555B2 (en) | 2000-01-25 | 2005-03-01 | Warner-Lambert Company | Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewith |
| US20040002537A1 (en) * | 2002-03-29 | 2004-01-01 | Zamvil Scott S. | Use of statins in the treatment of autoimmune disease |
| AR040588A1 (es) * | 2002-07-26 | 2005-04-13 | Schering Corp | Formulacion farmaceutica que comprende un inhibidor de la absorcion del colesterol y un inhibidor de una hmg- co a reductasa |
| WO2004045596A1 (en) * | 2002-11-15 | 2004-06-03 | Warner-Lambert Company Llc | Method of lowering crp and reducing systemic inflammation |
| US20040229954A1 (en) * | 2003-05-16 | 2004-11-18 | Macdougall Diane Elaine | Selective manipulation of triglyceride, HDL and LDL parameters with 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt |
| JP2006131559A (ja) * | 2004-11-05 | 2006-05-25 | Takeda Chem Ind Ltd | 含窒素複素環化合物 |
| AU2005305460B2 (en) * | 2004-11-22 | 2011-04-21 | Dexcel Pharma Technologies Ltd. | Stable atorvastatin formulations |
| EA200701913A1 (ru) * | 2005-03-08 | 2008-08-29 | Релайэнт Фармасьютикалз, Инк. | Лечение статином, омега-3 жирными кислотами и их комбинированным продуктом |
| US20090186834A1 (en) * | 2005-03-24 | 2009-07-23 | Microbia, Inc. | Diphenylheterocycle cholesterol absorption inhibitors |
| WO2007030375A2 (en) * | 2005-09-08 | 2007-03-15 | Children's Hospital Medical Center | Lysosomal acid lipase therapy for nafld and related diseases |
| FR2891459B1 (fr) * | 2005-09-30 | 2007-12-28 | Flamel Technologies Sa | Microparticules a liberation modifiee d'au moins un principe actif et forme galenique orale en comprenant |
| EP1962835A2 (en) * | 2005-12-21 | 2008-09-03 | Schering Corporation | Treatment of nonalcoholic fatty liver disease using cholesterol lowering agents and/or h3 receptor antagonist/inverse agonist |
| JP5457830B2 (ja) * | 2006-04-03 | 2014-04-02 | オディディ，イサ | オルガノゾル被膜を含む制御放出送達デバイス |
| MX2009001279A (es) | 2006-08-03 | 2009-02-11 | Tufts College | Analogos de niacina no eritematosos, y metodos para utilizar los mismos. |
| WO2008023869A1 (en) * | 2006-08-24 | 2008-02-28 | Hanall Pharmaceutical Co., Ltd. | Combined pharmeceutical formulation with controlled-release comprising dihydropyridine calcium channel blockers and hmg-coa reductase inhibitors |
| FI20080353A0 (fi) * | 2008-05-09 | 2008-05-09 | Atacama Labs Oy | Prosessi erittäin korkean lääkepitoisuuden tabletin valmistamiseksi |
| US20080176861A1 (en) | 2007-01-23 | 2008-07-24 | Kalypsys, Inc. | Sulfonyl-substituted bicyclic compounds as ppar modulators for the treatment of non-alcoholic steatohepatitis |
| US20100144864A1 (en) * | 2007-04-05 | 2010-06-10 | Ironwood Pharmaceuticals, Inc. | Soluble guanylate cyclase (sgc) modulators for treatment of lipid related disorders |
| US8969514B2 (en) * | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| US9307371B2 (en) | 2008-01-18 | 2016-04-05 | Verizon Patent And Licensing Inc. | Method and system for SMS/MMS messaging to a connected device |
| MX2010012514A (es) * | 2008-05-20 | 2011-05-30 | Cerenis Therapeutics S A | Niacina y un medicamento nsaid para tratamiento combinado. |
| WO2009151116A1 (ja) * | 2008-06-13 | 2009-12-17 | 持田製薬株式会社 | 非アルコール性脂肪肝炎の予防／改善・治療薬 |
| EP2488180A4 (en) | 2009-10-12 | 2013-03-27 | Ipca Lab Ltd | PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT / PROPHYLAXIS OF NON ALCOHOLIC HEPATIC STEATOSIS |
| EP2521556B1 (en) * | 2010-01-08 | 2018-05-30 | Ionis Pharmaceuticals, Inc. | Modulation of angiopoietin-like 3 expression |
| WO2011163612A1 (en) * | 2010-06-24 | 2011-12-29 | Trustees Of Tufts College | Niacin mimetics, and methods of use thereof |
| TR201005325A2 (tr) * | 2010-06-30 | 2012-01-23 | Bi̇lgi̇ç Mahmut | Atorvastatin ve aspirin içeren farmasötik formülasyonlar |
| EP3170495B1 (en) * | 2010-12-27 | 2023-04-26 | Gemphire Therapeutics Inc. | Gemcabene for treating pancreatitis |
| EP2604256B1 (en) * | 2011-12-14 | 2016-04-13 | Hexal AG | Multi layer coatings |
| CN102525942A (zh) * | 2012-01-05 | 2012-07-04 | 金陵药业股份有限公司 | 一种阿托伐他汀钙肠溶微丸及其制备方法 |
| AU2013207423B2 (en) * | 2012-01-06 | 2017-10-12 | Gemphire Therapeutics Inc. | Methods of reducing risk of cardiovascular disease |
| JP6633609B2 (ja) * | 2014-03-20 | 2020-01-22 | エスペリオン・セラピューティクス・インコーポレイテッドＥｓｐｅｒｉｏｎ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | 肝疾患および他の医学的障害の処置のためのカルボキシ−シクロプロピルウンデカノール化合物 |
| CN104127391B (zh) * | 2014-08-05 | 2016-08-24 | 李宝齐 | 一种含有阿托伐他汀钙的固体药物组合物 |
| BR112018009238A8 (pt) * | 2015-11-06 | 2019-02-26 | Gemphire Therapeutics Inc | tratamento de dislipidemia mista |
| CN105434391A (zh) * | 2016-01-18 | 2016-03-30 | 上海蓝心医药科技有限公司 | 阿托伐他汀钙肠溶片及其制备方法和应用 |
-
2016
- 2016-11-07 BR BR112018009238A patent/BR112018009238A8/pt not_active Application Discontinuation
- 2016-11-07 KR KR1020187014906A patent/KR20180073665A/ko not_active Withdrawn
- 2016-11-07 CA CA3001627A patent/CA3001627A1/en not_active Abandoned
- 2016-11-07 KR KR1020187013334A patent/KR20180073597A/ko not_active Withdrawn
- 2016-11-07 MX MX2018005540A patent/MX2018005540A/es unknown
- 2016-11-07 WO PCT/US2016/060849 patent/WO2017079755A1/en not_active Ceased
- 2016-11-07 HK HK19100291.5A patent/HK1257929A1/zh unknown
- 2016-11-07 CN CN201680064715.0A patent/CN108366957A/zh active Pending
- 2016-11-07 EP EP16863170.3A patent/EP3370713A4/en not_active Withdrawn
- 2016-11-07 JP JP2018543079A patent/JP2018532808A/ja active Pending
- 2016-11-07 SG SG11201803442UA patent/SG11201803442UA/en unknown
- 2016-11-07 AU AU2016349634A patent/AU2016349634A1/en not_active Abandoned
- 2016-11-07 CA CA3000016A patent/CA3000016A1/en not_active Abandoned
- 2016-11-07 AU AU2016348638A patent/AU2016348638A1/en not_active Abandoned
- 2016-11-07 CN CN201680064197.2A patent/CN108348491A/zh active Pending
- 2016-11-07 HK HK19101864.0A patent/HK1259458A1/zh unknown
- 2016-11-07 JP JP2018543283A patent/JP2018536710A/ja active Pending
- 2016-11-07 RU RU2018120599A patent/RU2018120599A/ru not_active Application Discontinuation
- 2016-11-07 RU RU2018120726A patent/RU2018120726A/ru not_active Application Discontinuation
- 2016-11-07 BR BR112018007857A patent/BR112018007857A2/pt not_active Application Discontinuation
- 2016-11-07 SG SG10201912754UA patent/SG10201912754UA/en unknown
- 2016-11-07 EP EP16863175.2A patent/EP3370703A4/en not_active Withdrawn
- 2016-11-07 WO PCT/US2016/060837 patent/WO2017079748A1/en not_active Ceased
- 2016-11-07 MX MX2018005096A patent/MX2018005096A/es unknown
- 2016-11-07 MA MA043190A patent/MA43190A/fr unknown
-
2017
- 2017-01-26 US US15/416,911 patent/US9849104B2/en active Active
- 2017-02-03 US US15/424,620 patent/US20170172955A1/en not_active Abandoned
- 2017-11-16 US US15/814,557 patent/US10449154B2/en active Active
-
2018
- 2018-04-22 IL IL258819A patent/IL258819A/en unknown
- 2018-05-04 PH PH12018500972A patent/PH12018500972A1/en unknown
- 2018-05-04 US US15/971,491 patent/US20180325825A1/en not_active Abandoned
- 2018-05-04 IL IL259133A patent/IL259133A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10449154B2 (en) | Treatment of NASH with Gemcabene | |
| US20240148681A1 (en) | Fixed dose combinations and formulations comprising etc1002 and one or more statins and methods of treating or reducing the risk of cardiovascular disease | |
| Beltowski et al. | Adverse effects of statins-mechanisms and consequences | |
| RU2766085C2 (ru) | Фиксированные комбинации и составы, содержащие етс1002 и эзетимиб, и способы лечения или уменьшения риска развития сердечно-сосудистого заболевания | |
| JP2025131596A (ja) | 血液障害及び／又は関連疾患を治療する、又は予防するための１５－ｈｅｐｅを含む組成物 | |
| TW200306853A (en) | Therapeutic agent for glomerular disease | |
| US20230041138A1 (en) | Treatment of his hyporesponders | |
| TW201902471A (zh) | 賈卡賓尼（ｇｅｍｃａｂｅｎｅ）、其醫藥上可接受之鹽、彼等之組成物及使用彼等之方法 | |
| US6998422B2 (en) | Lipid peroxide-lowering compositions | |
| KR20210079275A (ko) | 고콜레스테롤 관련 병으로 치료 받고 있는 환자에서의 당뇨병의 위험 감소 방법 | |
| HK1256960A1 (en) | Treatment of mixed dyslipidemia | |
| WO2004096276A1 (ja) | 糖取り込み能増強剤 | |
| Abate et al. | Other than potency, are all statins the same? | |
| Chan et al. | Fluvastatin: efficacy and safety in reducing cardiac events | |
| HK40107190A (en) | Fixed dose combinations and formulations comprising etc1002 and one or more statins and methods of treating or reducing the risk of cardiovascular disease | |
| BR122025009675A2 (pt) | Usos de ácido 15-hidroxi-eicosapentaenoico (15-hepe) para o tratamento ou prevenção de distúrbios hematológicos e/ou doenças relacionadas | |
| Park et al. | KOREAN ROSUVASTATIN EFFECTIVENESS STUDY IN NONDIABETIC METABOLIC SYNDROME (KREST) | |
| JP2005232151A (ja) | 糖取り込み能増強剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20230131 |
|
| FZDE | Discontinued |
Effective date: 20230131 |