TWI238720B - Pharmaceutical composition for use in the treatment of heterozygous familial hypercholesterolemia - Google Patents
Pharmaceutical composition for use in the treatment of heterozygous familial hypercholesterolemia Download PDFInfo
- Publication number
- TWI238720B TWI238720B TW090128858A TW90128858A TWI238720B TW I238720 B TWI238720 B TW I238720B TW 090128858 A TW090128858 A TW 090128858A TW 90128858 A TW90128858 A TW 90128858A TW I238720 B TWI238720 B TW I238720B
- Authority
- TW
- Taiwan
- Prior art keywords
- pharmaceutical composition
- ldl
- methyl
- isopropyl
- treatment
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 39
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 title claims abstract description 37
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 108010028554 LDL Cholesterol Proteins 0.000 claims description 46
- 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 claims description 32
- 108010023302 HDL Cholesterol Proteins 0.000 claims description 22
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 102000005666 Apolipoprotein A-I Human genes 0.000 claims description 7
- 108010059886 Apolipoprotein A-I Proteins 0.000 claims description 7
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 claims description 5
- 201000001386 familial hypercholesterolemia Diseases 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 4
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 159000000007 calcium salts Chemical class 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 208000019622 heart disease Diseases 0.000 claims description 3
- 230000007423 decrease Effects 0.000 claims description 2
- 208000019553 vascular disease Diseases 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims 4
- -1 methyl Sulfosulfonyl Chemical group 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 2
- PDBMVYIMAMQDCW-UHFFFAOYSA-N 3,5-dihydroxyheptanoic acid Chemical compound CCC(O)CC(O)CC(O)=O PDBMVYIMAMQDCW-UHFFFAOYSA-N 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract 1
- 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 abstract 1
- LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical compound [Ca+2].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.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 LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 description 52
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 13
- 235000012000 cholesterol Nutrition 0.000 description 12
- 230000009467 reduction Effects 0.000 description 11
- 150000002632 lipids Chemical class 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 108010074051 C-Reactive Protein Proteins 0.000 description 7
- 102100032752 C-reactive protein Human genes 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000001603 reducing effect Effects 0.000 description 6
- 108010082126 Alanine transaminase Proteins 0.000 description 5
- 206010003210 Arteriosclerosis Diseases 0.000 description 5
- 208000035150 Hypercholesterolemia Diseases 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
- 102000007330 LDL Lipoproteins Human genes 0.000 description 5
- 102000004895 Lipoproteins Human genes 0.000 description 5
- 108090001030 Lipoproteins Proteins 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 4
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 4
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 4
- 102000004420 Creatine Kinase Human genes 0.000 description 4
- 108010042126 Creatine kinase Proteins 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 208000029078 coronary artery disease Diseases 0.000 description 4
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 4
- 239000007937 lozenge Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940125753 fibrate Drugs 0.000 description 3
- 229960003627 gemfibrozil Drugs 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-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[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 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 description 2
- 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 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
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 206010013710 Drug interaction Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010001831 LDL receptors Proteins 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 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 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- 102000003929 Transaminases Human genes 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229960005370 atorvastatin Drugs 0.000 description 2
- 239000003613 bile acid Substances 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000013213 extrapolation Methods 0.000 description 2
- 229960002297 fenofibrate Drugs 0.000 description 2
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 238000007477 logistic regression Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000004060 metabolic process Effects 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
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229960002855 simvastatin Drugs 0.000 description 2
- 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 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic 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)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- JSLISSGEILAIOU-UHFFFAOYSA-N (4-chloro-2-iodophenyl)hydrazine Chemical compound NNC1=CC=C(Cl)C=C1I JSLISSGEILAIOU-UHFFFAOYSA-N 0.000 description 1
- NPOAOTPXWNWTSH-UHFFFAOYSA-N 3-hydroxy-3-methylglutaric acid Chemical compound OC(=O)CC(O)(C)CC(O)=O NPOAOTPXWNWTSH-UHFFFAOYSA-N 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 229920002911 Colestipol Polymers 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 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
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 101710105047 Lipoprotein B Proteins 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 229920001007 Nylon 4 Polymers 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 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 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940039409 ammonium valerate Drugs 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960002174 ciprofibrate Drugs 0.000 description 1
- KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 229960002604 colestipol Drugs 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960001545 hydrotalcite Drugs 0.000 description 1
- 229910001701 hydrotalcite Inorganic materials 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011283 initial treatment period Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000008604 lipoprotein metabolism Effects 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- 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 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009863 secondary prevention Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0028429.9A GB0028429D0 (en) | 2000-11-22 | 2000-11-22 | Therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TWI238720B true TWI238720B (en) | 2005-09-01 |
Family
ID=9903629
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW090128858A TWI238720B (en) | 2000-11-22 | 2001-11-21 | Pharmaceutical composition for use in the treatment of heterozygous familial hypercholesterolemia |
Country Status (34)
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0003305D0 (en) * | 2000-02-15 | 2000-04-05 | Zeneca Ltd | Pyrimidine derivatives |
| US7407965B2 (en) * | 2003-04-25 | 2008-08-05 | Gilead Sciences, Inc. | Phosphonate analogs for treating metabolic diseases |
| US20050261237A1 (en) * | 2003-04-25 | 2005-11-24 | Boojamra Constantine G | Nucleoside phosphonate analogs |
| US7452901B2 (en) * | 2003-04-25 | 2008-11-18 | Gilead Sciences, Inc. | Anti-cancer phosphonate analogs |
| EP1628685B1 (en) | 2003-04-25 | 2010-12-08 | Gilead Sciences, Inc. | Antiviral phosphonate analogs |
| US7470724B2 (en) * | 2003-04-25 | 2008-12-30 | Gilead Sciences, Inc. | Phosphonate compounds having immuno-modulatory activity |
| US20090247488A1 (en) * | 2003-04-25 | 2009-10-01 | Carina Cannizzaro | Anti-inflammatory phosphonate compounds |
| MXPA05011296A (es) * | 2003-04-25 | 2006-01-24 | Gilead Sciences Inc | Conjugados de fosfonato inhibidores de la cinasa. |
| WO2005023778A2 (en) * | 2003-08-28 | 2005-03-17 | Teva Pharmaceutical Industries Ltd. | Process for preparation of rosuvastatin calcium |
| GB0322552D0 (en) | 2003-09-26 | 2003-10-29 | Astrazeneca Uk Ltd | Therapeutic treatment |
| US7432273B2 (en) * | 2003-10-24 | 2008-10-07 | Gilead Sciences, Inc. | Phosphonate analogs of antimetabolites |
| US7777034B2 (en) | 2003-11-24 | 2010-08-17 | Teva Pharmaceutical Industries Ltd. | Crystalline ammonium salts of rosuvastatin |
| EP1689723B1 (en) * | 2003-12-02 | 2011-04-27 | Teva Pharmaceutical Industries, Ltd. | Reference standard for characterization of rosuvastatin |
| US20070179166A1 (en) * | 2003-12-24 | 2007-08-02 | Valerie Niddam-Hildesheim | Process for preparation of statins with high syn to anti ratio |
| US7851624B2 (en) * | 2003-12-24 | 2010-12-14 | Teva Pharamaceutical Industries Ltd. | Triol form of rosuvastatin and synthesis of rosuvastatin |
| US20060013861A1 (en) * | 2004-05-26 | 2006-01-19 | Kgk Synergize Inc. | Functional foods comprising flavonoids and tocotrienols and methods thereof |
| EP1673351A1 (en) * | 2004-07-13 | 2006-06-28 | Teva Pharmaceutical Industries Ltd. | A process for the preparation of rosuvastatin involving a tempo-mediated oxidation step |
| WO2006110157A2 (en) | 2004-07-27 | 2006-10-19 | Gilead Sciences, Inc. | Nucleoside phosphonate conjugates as anti hiv agents |
| CA2591439C (en) * | 2005-02-22 | 2013-03-26 | Teva Pharmaceutical Industries Ltd. | Rosuvastatin and salts thereof free of rosuvastatin alkylether and a process for the preparation thereof |
| US20070037979A1 (en) * | 2005-02-22 | 2007-02-15 | Valerie Niddam-Hildesheim | Preparation of rosuvastatin |
| US20070167625A1 (en) * | 2005-02-22 | 2007-07-19 | Anna Balanov | Preparation of rosuvastatin |
| MX2007004427A (es) * | 2005-08-16 | 2007-06-14 | Teva Pharma | Intermedio de rosuvastatina cristalina. |
| US8383614B2 (en) * | 2008-01-31 | 2013-02-26 | The Trustees Of The University Of Pennsylvania | Hypercholestrolemia and tendinous injuries |
| US9427437B2 (en) | 2008-01-31 | 2016-08-30 | The Trustees Of The University Of Pennsylvania | Hypercholesterolemia and tendinous injuries |
| WO2009143776A1 (zh) | 2008-05-27 | 2009-12-03 | 常州制药厂有限公司 | 瑞舒伐他汀钙盐的制备方法及其中间体 |
| HRP20120700T1 (hr) | 2008-07-08 | 2012-09-30 | Gilead Sciences | SOLI SPOJEVA INHIBITORA HIV-a |
| AR092872A1 (es) | 2012-09-17 | 2015-05-06 | Madrigal Pharmaceuticals Inc | Metodo para sintetizar analogos de la hormona tiroidea y polimorfos de los mismos |
| US9132117B2 (en) | 2013-06-17 | 2015-09-15 | Kgk Synergize, Inc | Compositions and methods for glycemic control of subjects with impaired fasting glucose |
| US10600502B2 (en) | 2016-12-20 | 2020-03-24 | Astrazeneca Uk Ltd. | Systems and methods for dispensing a statin medication over the counter |
| ES2892402T3 (es) | 2017-08-01 | 2022-02-04 | Gilead Sciences Inc | Formas cristalinas de ((S)-((((2R,5R)-5-(6-amino-9H-purin-9-il)-4-fluoro-2,5-dihidrofuran-2-il)oxi)metil)(fenoxi)fosforil)-L-alaninato de etilo para tratar infecciones virales |
| PE20220164A1 (es) | 2019-05-27 | 2022-01-28 | Immatics Us Inc | Vectores viricos y uso de los mismos en terapias celulares adoptivas |
| DE102020111571A1 (de) | 2020-03-11 | 2021-09-16 | Immatics US, Inc. | Wpre-mutantenkonstrukte, zusammensetzungen und zugehörige verfahren |
| US20220008519A1 (en) | 2020-07-09 | 2022-01-13 | Costa Rican Social Security Fund / Caja Costarricense de Seguro Social (CCSS) | Treatment of severe acute respiratory syndrome-related coronavirus infection with klotho |
| WO2022040631A1 (en) | 2020-08-21 | 2022-02-24 | Immatics US, Inc. | Methods for isolating cd8+ selected t cells |
| JP2024506848A (ja) * | 2021-02-01 | 2024-02-15 | マドリガル ファーマシューティカルズ インコーポレイテッド | 肝障害又は脂質障害の治療のためのロスバスタチンとレスメチロムの治療的組み合わせ |
| US12377104B1 (en) | 2024-02-06 | 2025-08-05 | Madrigal Pharmaceuticals, Inc. | Methods for treating a fatty liver disease |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2051907C1 (ru) * | 1989-05-22 | 1996-01-10 | Сандос АГ | Способ получения 7-замещенной гептен-6-овой кислоты |
| JP2648897B2 (ja) * | 1991-07-01 | 1997-09-03 | 塩野義製薬株式会社 | ピリミジン誘導体 |
| US5631365A (en) * | 1993-09-21 | 1997-05-20 | Schering Corporation | Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents |
| US6369103B1 (en) * | 1994-01-18 | 2002-04-09 | Bristol-Myers Squibb Company | Method for preventing or reducing risk of onset of cardiovascular events employing an HMG CoA reductase inhibitor |
| GB0001621D0 (en) * | 2000-01-26 | 2000-03-15 | Astrazeneca Ab | Pharmaceutical compositions |
| AU6294501A (en) * | 2000-09-20 | 2002-04-02 | Rtp Pharma Inc | Spray drying process and compositions of fenofibrate |
-
2000
- 2000-11-22 GB GBGB0028429.9A patent/GB0028429D0/en not_active Ceased
-
2001
- 2001-11-16 CZ CZ20031406A patent/CZ301583B6/cs not_active IP Right Cessation
- 2001-11-16 JP JP2002544073A patent/JP5062940B2/ja not_active Expired - Lifetime
- 2001-11-16 NZ NZ525754A patent/NZ525754A/en not_active IP Right Cessation
- 2001-11-16 BR BR0115511-3A patent/BR0115511A/pt not_active Application Discontinuation
- 2001-11-16 PT PT01982623T patent/PT1339409E/pt unknown
- 2001-11-16 CA CA002429263A patent/CA2429263C/en not_active Expired - Fee Related
- 2001-11-16 MX MXPA03004336A patent/MXPA03004336A/es unknown
- 2001-11-16 EE EEP200300239A patent/EE05507B1/xx not_active IP Right Cessation
- 2001-11-16 PL PL01365386A patent/PL365386A1/xx not_active Application Discontinuation
- 2001-11-16 DK DK01982623T patent/DK1339409T3/da active
- 2001-11-16 SI SI200130839T patent/SI1339409T1/sl unknown
- 2001-11-16 AU AU2002214165A patent/AU2002214165B9/en not_active Revoked
- 2001-11-16 AT AT01982623T patent/ATE394103T1/de active
- 2001-11-16 EP EP01982623A patent/EP1339409B1/en not_active Revoked
- 2001-11-16 HU HU0301380A patent/HUP0301380A3/hu not_active Application Discontinuation
- 2001-11-16 IL IL15591901A patent/IL155919A0/xx unknown
- 2001-11-16 WO PCT/GB2001/005041 patent/WO2002041895A1/en not_active Ceased
- 2001-11-16 DE DE60133921T patent/DE60133921D1/de not_active Expired - Lifetime
- 2001-11-16 ES ES01982623T patent/ES2305118T3/es not_active Expired - Lifetime
- 2001-11-16 RU RU2003114300/15A patent/RU2294744C2/ru not_active IP Right Cessation
- 2001-11-16 UA UA2003054394A patent/UA75614C2/uk unknown
- 2001-11-16 KR KR1020037006791A patent/KR100815042B1/ko not_active Ceased
- 2001-11-16 SK SK621-2003A patent/SK6212003A3/sk not_active Application Discontinuation
- 2001-11-16 CN CNB018221599A patent/CN1268339C/zh not_active Expired - Lifetime
- 2001-11-16 AU AU1416502A patent/AU1416502A/xx active Pending
- 2001-11-16 US US10/432,402 patent/US6858618B2/en not_active Expired - Lifetime
- 2001-11-20 MY MYPI20015303A patent/MY134902A/en unknown
- 2001-11-21 TW TW090128858A patent/TWI238720B/zh not_active IP Right Cessation
- 2001-11-22 AR ARP010105452A patent/AR031766A1/es unknown
-
2003
- 2003-05-12 ZA ZA200303636A patent/ZA200303636B/en unknown
- 2003-05-13 BG BG107811A patent/BG66009B1/bg unknown
- 2003-05-14 IL IL155919A patent/IL155919A/en unknown
- 2003-05-19 IS IS6819A patent/IS6819A/is unknown
- 2003-05-21 NO NO20032292A patent/NO326245B1/no not_active IP Right Cessation
-
2008
- 2008-07-07 CY CY20081100703T patent/CY1110428T1/el unknown
-
2009
- 2009-11-09 JP JP2009255813A patent/JP2010031047A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI238720B (en) | Pharmaceutical composition for use in the treatment of heterozygous familial hypercholesterolemia | |
| AU2002214165A1 (en) | Use of rosuvastatin (ZD-4522) in the treatment of heterozygous familial hypercholesterolemia | |
| US20250064767A1 (en) | Fixed dose combinations and formulations comprising etc1002 and one or more statins and methods of treating or reducing the risk of cardiovascular disease | |
| US6982157B1 (en) | Drug combinations comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methylsulfonyl)amino] pyrimidin-5-yl] (3r,5s) -3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3A4 | |
| KR20020086749A (ko) | 베타 블록커 및 콜레스테롤 저하제의 신규한 조합물 | |
| CN1230173C (zh) | 糖尿病合并症预防及治疗剂 | |
| EP1714648A1 (en) | Combination drug | |
| US8501759B2 (en) | Use of fibrates | |
| Shimpi et al. | Bempedoic acid a novel drug used for the treatment of Hyperlipidaemia: A Review | |
| WO2004096276A9 (ja) | 糖取り込み能増強剤 | |
| HK1056691B (en) | Use of rosuvastatin (zd-4522) in the treatment of heterozygous familial hypercholesterolemia | |
| KR20070015114A (ko) | 3,3,14,14 테트라메틸 헥사데칸 1,16 이산의 투여 방법 | |
| Zhang et al. | Effect of Xuezhikang Combined with Rosuvastatin on Lipid Regulation in Patients with Atherosclerotic Cardiovascular Disease: A Real-World Study | |
| CN118001273A (zh) | 血脂异常治疗剂 | |
| HK1041817B (en) | Drug combinations comprising (e)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3r, 5s)-3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3a4 | |
| JP2006520813A (ja) | 低分子量トロンビン阻害剤のコレステロール低下療法における使用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4A | Expiration of patent term of an invention patent |