CN1353610A - 口服用药物组合物 - Google Patents
口服用药物组合物 Download PDFInfo
- Publication number
- CN1353610A CN1353610A CN00808329A CN00808329A CN1353610A CN 1353610 A CN1353610 A CN 1353610A CN 00808329 A CN00808329 A CN 00808329A CN 00808329 A CN00808329 A CN 00808329A CN 1353610 A CN1353610 A CN 1353610A
- Authority
- CN
- China
- Prior art keywords
- acid
- oral administration
- medicinal composition
- ester
- oiliness base
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 150000004702 methyl esters Chemical class 0.000 claims abstract description 11
- 230000000087 stabilizing effect Effects 0.000 claims abstract description 10
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 33
- 239000000194 fatty acid Substances 0.000 claims description 33
- 229930195729 fatty acid Natural products 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 150000004665 fatty acids Chemical class 0.000 claims description 30
- 235000019441 ethanol Nutrition 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 150000002148 esters Chemical class 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 13
- 239000004215 Carbon black (E152) Substances 0.000 claims description 9
- 229930195733 hydrocarbon Natural products 0.000 claims description 9
- 150000002430 hydrocarbons Chemical class 0.000 claims description 9
- 229930182558 Sterol Natural products 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 150000003904 phospholipids Chemical class 0.000 claims description 8
- 150000003432 sterols Chemical class 0.000 claims description 8
- 235000003702 sterols Nutrition 0.000 claims description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 7
- -1 1-ethyl- Chemical group 0.000 abstract description 16
- 238000002360 preparation method Methods 0.000 abstract description 12
- 230000008485 antagonism Effects 0.000 abstract description 2
- VNHVYELYRCJCBA-UHFFFAOYSA-N 2-[4-[[3-[4-[(e)-n'-carboxycarbamimidoyl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]piperazin-1-yl]acetic acid Chemical compound C1=CC(C(=NC(O)=O)N)=CC=C1N1C(=O)OC(CN2CCN(CC(O)=O)CC2)C1 VNHVYELYRCJCBA-UHFFFAOYSA-N 0.000 abstract 3
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 60
- YNBHAPKHWDNTMZ-QGZVFWFLSA-N ethyl 2-[4-[[(5r)-3-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]piperazin-1-yl]acetate Chemical compound C1CN(CC(=O)OCC)CCN1C[C@H]1OC(=O)N(C=2C=CC(=CC=2)C(=N)NC(=O)OC)C1 YNBHAPKHWDNTMZ-QGZVFWFLSA-N 0.000 description 31
- 229950000438 gantofiban Drugs 0.000 description 31
- 239000002253 acid Substances 0.000 description 27
- 235000015165 citric acid Nutrition 0.000 description 20
- 239000000047 product Substances 0.000 description 14
- 239000003814 drug Substances 0.000 description 11
- 239000000843 powder Substances 0.000 description 10
- 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 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 238000002156 mixing Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003925 fat Substances 0.000 description 6
- 235000019197 fats Nutrition 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 235000021355 Stearic acid Nutrition 0.000 description 5
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 5
- 229960001375 lactose Drugs 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 5
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000008117 stearic acid Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- WRJZKSHNBALIGH-UHFFFAOYSA-N 2-piperazin-1-ium-1-ylacetate Chemical compound OC(=O)CN1CCNCC1 WRJZKSHNBALIGH-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-PICCSMPSSA-N D-Maltose Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 4
- 108010049003 Fibrinogen Proteins 0.000 description 4
- 102000008946 Fibrinogen Human genes 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 4
- 229940012952 fibrinogen Drugs 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 238000005507 spraying Methods 0.000 description 4
- 230000006641 stabilisation Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- YWWVWXASSLXJHU-AATRIKPKSA-N (9E)-tetradecenoic acid Chemical compound CCCC\C=C\CCCCCCCC(O)=O YWWVWXASSLXJHU-AATRIKPKSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 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 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000002702 enteric coating Substances 0.000 description 3
- 238000009505 enteric coating Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 210000000582 semen Anatomy 0.000 description 3
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 3
- GDTXICBNEOEPAZ-BQYQJAHWSA-N trans-10-heptadecenoic acid Chemical compound CCCCCC\C=C\CCCCCCCCC(O)=O GDTXICBNEOEPAZ-BQYQJAHWSA-N 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- BITHHVVYSMSWAG-KTKRTIGZSA-N (11Z)-icos-11-enoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCC(O)=O BITHHVVYSMSWAG-KTKRTIGZSA-N 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 2
- ULQISTXYYBZJSJ-UHFFFAOYSA-N 12-hydroxyoctadecanoic acid Chemical compound CCCCCCC(O)CCCCCCCCCCC(O)=O ULQISTXYYBZJSJ-UHFFFAOYSA-N 0.000 description 2
- WWASUAHHCLARMF-UHFFFAOYSA-N 13-methylpentadecanoic acid Chemical compound CCC(C)CCCCCCCCCCCC(O)=O WWASUAHHCLARMF-UHFFFAOYSA-N 0.000 description 2
- BRCMIDDAOIVEAZ-MDZDMXLPSA-N 14E-tricosenoic acid Chemical compound CCCCCCCC\C=C\CCCCCCCCCCCCC(O)=O BRCMIDDAOIVEAZ-MDZDMXLPSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- PCGKIWPTIJPQHI-UHFFFAOYSA-N 16-methyloctadecanoic acid Chemical compound CCC(C)CCCCCCCCCCCCCCC(O)=O PCGKIWPTIJPQHI-UHFFFAOYSA-N 0.000 description 2
- MXNRLFUSFKVQSK-UHFFFAOYSA-N 2-Amino-6-(trimethylazaniumyl)hexanoate Chemical compound C[N+](C)(C)CCCCC(N)C([O-])=O MXNRLFUSFKVQSK-UHFFFAOYSA-N 0.000 description 2
- GHPVDCPCKSNJDR-UHFFFAOYSA-N 2-hydroxydecanoic acid Chemical compound CCCCCCCCC(O)C(O)=O GHPVDCPCKSNJDR-UHFFFAOYSA-N 0.000 description 2
- JGHSBPIZNUXPLA-UHFFFAOYSA-N 2-hydroxyhexadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)C(O)=O JGHSBPIZNUXPLA-UHFFFAOYSA-N 0.000 description 2
- JYZJYKOZGGEXSX-UHFFFAOYSA-N 2-hydroxymyristic acid Chemical compound CCCCCCCCCCCCC(O)C(O)=O JYZJYKOZGGEXSX-UHFFFAOYSA-N 0.000 description 2
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- YWWVWXASSLXJHU-UHFFFAOYSA-N 9E-tetradecenoic acid Natural products CCCCC=CCCCCCCCC(O)=O YWWVWXASSLXJHU-UHFFFAOYSA-N 0.000 description 2
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 235000021357 Behenic acid Nutrition 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 208000019838 Blood disease Diseases 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 208000031481 Pathologic Constriction Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 208000033626 Renal failure acute Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 108010031318 Vitronectin Proteins 0.000 description 2
- 102100035140 Vitronectin Human genes 0.000 description 2
- 235000011054 acetic acid Nutrition 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
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 201000011040 acute kidney failure Diseases 0.000 description 2
- 208000012998 acute renal failure Diseases 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- QYIXCDOBOSTCEI-UHFFFAOYSA-N alpha-cholestanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 QYIXCDOBOSTCEI-UHFFFAOYSA-N 0.000 description 2
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 229940116226 behenic acid Drugs 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 235000019504 cigarettes Nutrition 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- 150000001991 dicarboxylic acids Chemical class 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- BITHHVVYSMSWAG-UHFFFAOYSA-N eicosenoic acid Natural products CCCCCCCCC=CCCCCCCCCCC(O)=O BITHHVVYSMSWAG-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 229960002733 gamolenic acid Drugs 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 235000021299 gondoic acid Nutrition 0.000 description 2
- 208000014951 hematologic disease Diseases 0.000 description 2
- 208000018706 hematopoietic system disease Diseases 0.000 description 2
- KEMQGTRYUADPNZ-UHFFFAOYSA-N heptadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(O)=O KEMQGTRYUADPNZ-UHFFFAOYSA-N 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- ZOCYQVNGROEVLU-UHFFFAOYSA-N isopentadecanoic acid Chemical compound CC(C)CCCCCCCCCCCC(O)=O ZOCYQVNGROEVLU-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 239000011812 mixed powder Substances 0.000 description 2
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- ISYWECDDZWTKFF-UHFFFAOYSA-N nonadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCCC(O)=O ISYWECDDZWTKFF-UHFFFAOYSA-N 0.000 description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
- 235000014593 oils and fats Nutrition 0.000 description 2
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000036262 stenosis Effects 0.000 description 2
- 208000037804 stenosis Diseases 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 description 2
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 108010047303 von Willebrand Factor Proteins 0.000 description 2
- 102100036537 von Willebrand factor Human genes 0.000 description 2
- 229960001134 von willebrand factor Drugs 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- XBUXARJOYUQNTC-UHFFFAOYSA-N ()-3-Hydroxynonanoic acid Chemical compound CCCCCCC(O)CC(O)=O XBUXARJOYUQNTC-UHFFFAOYSA-N 0.000 description 1
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 1
- GWHCXVQVJPWHRF-KTKRTIGZSA-N (15Z)-tetracosenoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-KTKRTIGZSA-N 0.000 description 1
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- SBHCLVQMTBWHCD-METXMMQOSA-N (2e,4e,6e,8e,10e)-icosa-2,4,6,8,10-pentaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C(O)=O SBHCLVQMTBWHCD-METXMMQOSA-N 0.000 description 1
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 1
- QYIXCDOBOSTCEI-QCYZZNICSA-N (5alpha)-cholestan-3beta-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-QCYZZNICSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- RMUJWENALAQPCS-VOTSOKGWSA-N (E)-icos-14-enoic acid Chemical compound CCCCC\C=C\CCCCCCCCCCCCC(O)=O RMUJWENALAQPCS-VOTSOKGWSA-N 0.000 description 1
- INLBKXOFAJTNKG-OUKQBFOZSA-N (E)-icos-8-enoic acid Chemical compound CCCCCCCCCCC\C=C\CCCCCCC(O)=O INLBKXOFAJTNKG-OUKQBFOZSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- YSDBJKNOEWSFGA-UHFFFAOYSA-N 1-(4-methylpiperazin-1-yl)ethanone Chemical compound CN1CCN(C(C)=O)CC1 YSDBJKNOEWSFGA-UHFFFAOYSA-N 0.000 description 1
- JHULURRVRLTSRD-UHFFFAOYSA-N 1-cyclohexylpyrrolidine-2,5-dione Chemical compound O=C1CCC(=O)N1C1CCCCC1 JHULURRVRLTSRD-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- JIPTZBYHWFNYFB-UHFFFAOYSA-N 11-methyltridecanoic acid Natural products CCC(C)CCCCCCCCCC(O)=O JIPTZBYHWFNYFB-UHFFFAOYSA-N 0.000 description 1
- 229940114072 12-hydroxystearic acid Drugs 0.000 description 1
- FXUKWLSZZHVEJD-UHFFFAOYSA-N 14-methylhexadecanoic acid Chemical compound CCC(C)CCCCCCCCCCCCC(O)=O FXUKWLSZZHVEJD-UHFFFAOYSA-N 0.000 description 1
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 1
- YETXGSGCWODRAA-UHFFFAOYSA-N 17-methyloctadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCCC(O)=O YETXGSGCWODRAA-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 1
- UXFQFBNBSPQBJW-UHFFFAOYSA-N 2-amino-2-methylpropane-1,3-diol Chemical compound OCC(N)(C)CO UXFQFBNBSPQBJW-UHFFFAOYSA-N 0.000 description 1
- MYWSBJKVOUZCIA-UHFFFAOYSA-N 2-hydroxy-3,5-diiodobenzaldehyde Chemical compound OC1=C(I)C=C(I)C=C1C=O MYWSBJKVOUZCIA-UHFFFAOYSA-N 0.000 description 1
- RPGJJWLCCOPDAZ-UHFFFAOYSA-N 2-hydroxybehenic acid Chemical compound CCCCCCCCCCCCCCCCCCCCC(O)C(O)=O RPGJJWLCCOPDAZ-UHFFFAOYSA-N 0.000 description 1
- YDZIJQXINJLRLL-UHFFFAOYSA-N 2-hydroxydodecanoic acid Chemical compound CCCCCCCCCCC(O)C(O)=O YDZIJQXINJLRLL-UHFFFAOYSA-N 0.000 description 1
- NOCWDMQAHCQAKS-UHFFFAOYSA-N 2-hydroxyoctadeca-2,4-dienoic acid Chemical compound CCCCCCCCCCCCCC=CC=C(O)C(O)=O NOCWDMQAHCQAKS-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ATRNZOYKSNPPBF-UHFFFAOYSA-N 3-hydroxytetradecanoic acid Chemical compound CCCCCCCCCCCC(O)CC(O)=O ATRNZOYKSNPPBF-UHFFFAOYSA-N 0.000 description 1
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- FPAQLJHSZVFKES-UHFFFAOYSA-N 5-Eicosenoic acid Natural products CCCCCCCCCCCCCCC=CCCCC(O)=O FPAQLJHSZVFKES-UHFFFAOYSA-N 0.000 description 1
- FPAQLJHSZVFKES-FOCLMDBBSA-N 5E-eicosenoic acid Chemical compound CCCCCCCCCCCCCC\C=C\CCCC(O)=O FPAQLJHSZVFKES-FOCLMDBBSA-N 0.000 description 1
- XIIAYQZJNBULGD-XWLABEFZSA-N 5α-cholestane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 XIIAYQZJNBULGD-XWLABEFZSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QZCDMZMKQOGSQO-UHFFFAOYSA-N 9-methyl-undecanoic acid Chemical compound CCC(C)CCCCCCCC(O)=O QZCDMZMKQOGSQO-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- LTEBWFCXGOBPFA-UHFFFAOYSA-N C(CCC(=O)OC)(=O)OCCCO.C(C)(=O)O Chemical compound C(CCC(=O)OC)(=O)OCCCO.C(C)(=O)O LTEBWFCXGOBPFA-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- BDCFUHIWJODVNG-UHFFFAOYSA-N Desmosterol Natural products C1C=C2CC(O)C=CC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 BDCFUHIWJODVNG-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- QYIXCDOBOSTCEI-KKFSNPNRSA-N Epi-coprostanol Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-KKFSNPNRSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 description 1
- 229920003138 Eudragit® L 30 D-55 Polymers 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 1
- 235000000072 L-ascorbyl-6-palmitate Nutrition 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 235000021353 Lignoceric acid Nutrition 0.000 description 1
- CQXMAMUUWHYSIY-UHFFFAOYSA-N Lignoceric acid Natural products CCCCCCCCCCCCCCCCCCCCCCCC(=O)OCCC1=CC=C(O)C=C1 CQXMAMUUWHYSIY-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229920000305 Nylon 6,10 Polymers 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000021319 Palmitoleic acid Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 235000019484 Rapeseed oil Nutrition 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 1
- HXWJFEZDFPRLBG-UHFFFAOYSA-N Timnodonic acid Natural products CCCC=CC=CCC=CCC=CCC=CCCCC(O)=O HXWJFEZDFPRLBG-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000010495 camellia oil Substances 0.000 description 1
- 125000003739 carbamimidoyl group Chemical class C(N)(=N)* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 229950010118 cellacefate Drugs 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000007765 cera alba Substances 0.000 description 1
- 239000007766 cera flava Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000000280 densification Methods 0.000 description 1
- AVSXSVCZWQODGV-DPAQBDIFSA-N desmosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCC=C(C)C)C)[C@@]1(C)CC2 AVSXSVCZWQODGV-DPAQBDIFSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 1
- IQLUYYHUNSSHIY-HZUMYPAESA-N eicosatetraenoic acid Chemical compound CCCCCCCCCCC\C=C\C=C\C=C\C=C\C(O)=O IQLUYYHUNSSHIY-HZUMYPAESA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 1
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- VZCCETWTMQHEPK-UHFFFAOYSA-N gamma-Linolensaeure Natural products CCCCCC=CCC=CCC=CCCCCC(O)=O VZCCETWTMQHEPK-UHFFFAOYSA-N 0.000 description 1
- VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 description 1
- 235000020664 gamma-linolenic acid Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- NVBODECJSYHQIE-UHFFFAOYSA-N henicos-9-ene Chemical compound CCCCCCCCCCCC=CCCCCCCCC NVBODECJSYHQIE-UHFFFAOYSA-N 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- YAQXGBBDJYBXKL-UHFFFAOYSA-N iron(2+);1,10-phenanthroline;dicyanide Chemical compound [Fe+2].N#[C-].N#[C-].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 YAQXGBBDJYBXKL-UHFFFAOYSA-N 0.000 description 1
- IIUXHTGBZYEGHI-UHFFFAOYSA-N isoheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCC(O)=O IIUXHTGBZYEGHI-UHFFFAOYSA-N 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 1
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 1
- SIOLDWZBFABPJU-UHFFFAOYSA-N isotridecanoic acid Chemical compound CC(C)CCCCCCCCCC(O)=O SIOLDWZBFABPJU-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 1
- 229940058690 lanosterol Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 1
- OYHQOLUKZRVURQ-AVQMFFATSA-N linoelaidic acid Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-AVQMFFATSA-N 0.000 description 1
- 229960004232 linoleic acid Drugs 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- ZMKDEQUXYDZSNN-UHFFFAOYSA-N linolelaidic acid Natural products CCCCCCCCC=CCC=CCCCCC(O)=O ZMKDEQUXYDZSNN-UHFFFAOYSA-N 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- CHWMPPNDIBLYMB-UHFFFAOYSA-N n',n'-bis(prop-2-enyl)ethane-1,2-diamine Chemical compound NCCN(CC=C)CC=C CHWMPPNDIBLYMB-UHFFFAOYSA-N 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- XEZVDURJDFGERA-UHFFFAOYSA-N n-Tricosanoic acid Natural products CCCCCCCCCCCCCCCCCCCCCCC(O)=O XEZVDURJDFGERA-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- CNVZJPUDSLNTQU-SEYXRHQNSA-N petroselinic acid Chemical compound CCCCCCCCCCC\C=C/CCCCC(O)=O CNVZJPUDSLNTQU-SEYXRHQNSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- WBHHMMIMDMUBKC-XLNAKTSKSA-N ricinelaidic acid Chemical compound CCCCCC[C@@H](O)C\C=C\CCCCCCCC(O)=O WBHHMMIMDMUBKC-XLNAKTSKSA-N 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
- 229960004291 sucralfate Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- QZZGJDVWLFXDLK-UHFFFAOYSA-N tetracosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(O)=O QZZGJDVWLFXDLK-UHFFFAOYSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- IBYFOBGPNPINBU-OUKQBFOZSA-N trans-2-tetradecenoic acid Chemical compound CCCCCCCCCCC\C=C\C(O)=O IBYFOBGPNPINBU-OUKQBFOZSA-N 0.000 description 1
- DPUOLQHDNGRHBS-MDZDMXLPSA-N trans-Brassidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-MDZDMXLPSA-N 0.000 description 1
- LKOVPWSSZFDYPG-WUKNDPDISA-N trans-octadec-2-enoic acid Chemical compound CCCCCCCCCCCCCCC\C=C\C(O)=O LKOVPWSSZFDYPG-WUKNDPDISA-N 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- 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
Abstract
本发明提供含有4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐和油性基剂的稳定化了的口服用药物组合物及其制造方法。本发明还提供由于在4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐中掺入油性基剂而得到稳定的医药组合物的制造方法。此外,本发明还提供使药物组合物稳定化的方法,在该方法中,在4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐中掺入油性基剂。
Description
技术领域
本发明涉及4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐的稳定的口服用药物组合物及其制造方法。此外,本发明还涉及使含有4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐的药物组合物稳定化的方法。
背景技术
日本特许公开公报1996年第301857号公报(对应于欧洲专利第741133号)报告说,一系列的脒基衍生物可抑制整联蛋白受体与配体之间的相互反应,尤其可抑制纤维蛋白原、粘连蛋白和von Willebrand因子与血小板的纤维蛋白原受体(糖蛋白IIb/IIIa)的结合,并可抑制粘着蛋白(如玻连蛋白、胶原和海带氨酸等)与各种细胞种表面上的相应受体的结合,尤其可抑制血小板凝血酶的表达,从而可用来治疗血栓症、中风、心肌梗塞、狭心症、溶骨性疾病(尤其是骨质疏松)、血管形成后的复发性狭窄症、虚血疾病、炎症、动脉硬化症和急性肾衰竭。尤其是4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐(以下称“化合物A”)、特别是作为其光学异构体的5R体(一般名:甘托非邦(Gantofiban)。以下称“甘托非邦”)、尤其是该5R体的柠檬酸盐(柠檬酸甘托非邦)具有良好的活性,目前正在研究开发,有望成为药品。
发明的揭示
本发明者的目的是提供一种以化合物A(尤其是柠檬酸甘托非邦)为活性成分的药品。本发明者设计了口服用药剂,结果发现,虽然柠檬酸甘托非邦自身是稳定的,但在制剂时,柠檬酸甘托非邦会渐渐分解。对其原因进行了深入的研究,结果发现,柠檬酸甘托非邦与制成口服用制剂时通常添加的赋形剂、粘合剂和崩解剂(尤其是乳糖、D-甘露糖醇、微晶纤维素、玉米淀粉、磷酸氢钙、轻质无水硅酸、交联羧甲基纤维素钠等)配伍时会发生变化,渐渐分解。
因此,本发明的目的是提供一种含有化合物A(尤其是甘托非邦,更好的是柠檬酸甘托非邦)的稳定的口服用药剂。本发明的目的还在于提供一种制造含有化合物A(尤其是甘托非邦,更好的是柠檬酸甘托非邦)的稳定的口服用药剂的方法。本发明的另一个目的是提供一种使含有化合物A(尤其是甘托非邦,更好的是柠檬酸甘托非邦)的药物组合物稳定化的方法。
鉴于上述实际情况,本发明者对含有化合物A的药物组合物的稳定化进行了深入的研究,结果发现,通常,用油性基剂包覆药物时,由于油性基剂是疏水性的,因此,难以被水湿润,药物的释放变慢,但在化合物A中掺入油性基剂后,很意外地,油性基剂不影响药物的快速释放,从而能够得到稳定的药物组合物。本发明者在此发现的基础上完成了本发明。
即,本发明涉及4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐的稳定的口服用药物组合物及其制造方法。此外,本发明还涉及含有4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐和油性基剂的口服用药物组合物,尤其涉及油性基剂选自高级饱和脂肪酸、脂肪酸与醇的酯、高级醇、磷脂、甾醇或其酯和烃中的一种或多种的上述口服用药物组合物。在上述口服用药物组合物中,油性基剂较好地选自高级饱和脂肪酸、脂肪酸与醇的酯、高级醇中的一种或多种,更好的是,化合物A为5R型甘托非邦(尤其是其柠檬酸盐),此外,相对于化合物A1重量份,油性基剂为0.001-1000重量份,另外,化合物A被油性基剂包覆。本发明还涉及在化合物A中掺入油性基剂的口服用药物组合物的制造方法,特别是用油性基剂包覆化合物A的口服用药物组合物的方法,尤其是油性基剂选自高级饱和脂肪酸、脂肪酸与醇的酯、高级醇、磷脂、甾醇或其酯和烃中的一种或多种的上述口服用药物组合物的制造方法。在上述制造方法中,化合物A最好为5R型甘托非邦,尤其是其柠檬酸盐。另外,本发明还涉及在化合物A中掺入油性基剂、使含有化合物A的药物组合物稳定化的方法,特别是用油性基剂包覆化合物A、使含有化合物A的药物组合物稳定化的方法,尤其是油性基剂选自高级饱和脂肪酸、脂肪酸与醇的酯、高级醇、磷脂、甾醇或其酯和烃中的一种或多种的上述口服用药物组合物的制造方法。在上述方法中,化合物A最好为5R型甘托非邦,尤其是其柠檬酸盐。
本发明中使用的化合物A包括其药用盐,通常,由化合物与药用无机酸或有机酸形成。用于形成上述盐的无机酸的例子有硫酸、硝酸、盐酸、氢卤酸(如盐酸、氢溴酸等)、磷酸(如正磷酸等)、氨基磺酸等,有机酸的例子有脂肪族、脂环族、芳香族-脂肪族、芳香族或杂环状一元羧酸或它们的聚羧酸、磺酸或硫酸等。这些有机酸的更具体的例子有甲酸、乙酸、丙酸、三氟乙酸、丙酸、新戊酸、二乙基乙酸、丙二酸、丁二酸、庚二酸、富马酸、马来酸、乳酸、酒石酸、苹果酸、柠檬酸、葡糖酸、抗坏血酸、烟酸、异烟酸、甲磺酸、乙磺酸、乙烷二磺酸、2-羟基乙磺酸、苯磺酸、对甲苯磺酸、萘单磺酸、萘二磺酸、月桂基硫酸等。
本发明中使用的油性基剂只要是通常制药学上可接受的即可,无特别限定,例如,可以是脂肪酸与醇的酯、油脂、蜡、高级饱和脂肪酸、高级醇、磷脂、甾醇或其脂、烃等。本发明中使用的油性基剂以在常温下不熔融或不溶解而在加热时熔融的为佳。
脂肪酸与醇的脂是指下面分别列举的脂肪酸与醇的脂。脂肪酸例如可以是一元羧酸,也可以是二元羧酸,具体地说,二元羧酸的例子有草酸、丙二酸、丁二酸、戊二酸、己二酸、马来酸、富马酸、邻苯二甲酸、间苯二甲酸、对苯二甲酸、癸二酸等。此外,一元羧酸的例子有乙酸、丙酸、丁酸、戊酸、己酸、庚酸、辛酸、壬酸、癸酸、十一酸、十二酸、十三酸、肉豆蔻酸、十五酸、棕榈酸、十七酸、硬脂酸、十九酸、花生酸、二十酸、二十二酸、二十三酸、二十四酸等直链饱和脂肪酸;10-十一碳烯酸、11-十二碳烯酸、12-十三碳烯酸、反-2-十四碳烯酸、肉豆蔻脑酸、反-9-十四碳烯酸、10-十五碳烯酸、反-2-十六碳烯酸、棕榈油酸、反棕榈油酸(palmitoelaidic acid)、10-十七碳烯酸、反-10-十七碳烯酸、反-10-十七碳烯酸、反-2-十八碳烯酸、岩芹酸、反岩芹酸(petroelaidic acid)、油酸、反油酸、顺花生油酸、反花生油酸、α-亚油酸、反亚油酸、γ-亚麻酸、α-亚麻酸、7-十九碳烯酸、10-十九碳烯酸、反-10-十九碳烯酸、10,13-十九碳二烯酸、反-10,反-13-十九碳二烯酸、5-二十碳烯酸、8-二十碳烯酸、11-碳烯酸、反-11-二十碳烯酸、11,14-二十碳烯酸、8,11-二十碳烯酸、meed acid、高-γ-亚麻酸、11,14,17-二十碳三烯酸、5,8,11-二十碳三烯酸、二十碳四烯酸、5,8,11,14,17-二十碳五烯酸(EPA)、12-二十一碳烯酸、芥酸、巴西烯酸、13,16-二十二碳二烯酸、13,16,19-二十二碳三烯酸、7,10,13,16-二十二碳四烯酸、7,10,13,16,19-二十二碳五烯酸、7,10,13,16,19-二十二碳六烯酸(DHA)、14-二十三碳烯酸、反-14-二十三碳烯酸和15-二十四碳烯酸等直链不饱和脂肪酸;异月桂酸、11-甲基月桂酸、异肉豆蔻酸、13-甲基十四酸、异棕榈酸、15-甲基十六酸、异硬脂酸、17-甲基十八酸、异花生酸、19-甲基二十酸、9-甲基十一酸、10-甲基十二酸、11-甲基十三酸、12-甲基十四酸、13-甲基十五酸、14-甲基十六酸、15-甲基十七酸和16-甲基十八酸等支链脂肪酸;β-羟基丁酸、γ-羟基丁酸、3-羟基壬酸、2-羟基癸酸、2-羟基月桂酸、2-羟基十四酸、3-羟基肉豆蔻酸、2-羟基十六酸、2-羟基十八酸、12-羟基硬脂酸、2-羟基二十酸、2-羟基二十二酸、蓖麻油酸和反蓖麻油酸等羟基脂肪酸;等等。
脂肪酸与醇的酯中的醇的例子有甲醇、乙醇、正丙醇、正丁醇、正戊醇、正己醇、正庚醇、正辛醇、正癸醇、正月桂醇、正肉豆蔻醇、正十六醇、正十八醇、异丙醇、异丁醇、仲丁醇、叔丁醇、异戊醇、叔戊醇等直链或支链的伯醇;乙二醇、丙二醇、1,3-丙二醇等仲醇;丙三醇等叔醇;等等。
这些脂肪酸与醇的酯只要是由上述脂肪酸与醇形成的即可,可以是天然的,也可以是化学合成的。当为天然产物时,可以如油脂、蜡等那样,在一种或多种脂肪酸与醇的酯中混杂有脂肪酸和烃等其它成分。
油脂的例子有豆油、橄榄油、菜籽油、薄荷油、麻油、蓖麻油、山茶油、麦胚芽油、茴香油、玉米油、向日葵油、棉籽油、椰子油、花生油等以及它们的氢化油等。其中,以氢化蓖麻油、氢化菜籽油等氢化油为佳。蜡的例子有巴西棕榈蜡、鲸蜡、蜂蜡、白蜡等。高级饱和脂肪酸的例子有辛酸、癸酸、肉豆蔻酸、棕榈酸、硬脂酸、山萮酸等。高级醇的例子有鲸蜡醇、硬脂醇等。磷脂的例子有氢化卵磷脂等。甾醇或其脂的例子有胆固醇、α-胆甾烷、β-胆甾烷醇、表粪烷醇、链甾醇、岩藻甾醇、羊毛甾醇、麦角甾醇、β-谷甾醇等。烃的例子有石蜡、微晶蜡等。
本发明中使用的油性基剂可以是一种,也可以是二种以上的组合。其中,以高级饱和脂肪酸、脂肪酸与醇的酯、高级醇为佳。
本发明的药物组合物是使化合物A(特别是甘托非邦,更好的是柠檬酸甘托非邦)在制药学上稳定化了的口服用药物组合物。该药物组合物例如可用于以粉剂、颗粒剂、片剂等固体形态给药。这些固体形态可用公知的方法制造。例如,可用以下方法制造。在室温(5-30℃)使用液体的或半固体的油性基剂时,在油性基剂中加入化合物A,通过搅拌等方法加以分散,制成组合物。在室温(5-30℃)使用固体的油性基剂时,用公知的方法,例如,将油性基剂加热至熔点以上的温度,使其成为液体,用使化合物A溶解或搅拌等方法进行分散后,冷却、固化,制成组合物。此外,固化时,视需要,也可成形成粒子状或丸状。成形方法可使用公知的方法。例如,制成粒子时,最好制成粒径约为0.1-1000μm的球状微粒。成形方法可以是公知的方法。例如,将上述化合物A溶解或分散在油性基剂中的油液以微小油滴快速冷却、固化的喷雾冷却的方法;将化合物A和油性基剂溶解或分散在溶剂中的混合物喷雾干燥的方法;将化合物A溶解或分散在油性基剂中的混合物分散在水相中的方法;和喷雾冷凝的方法等。此时,为了避免粒子之间凝集,可视需要,将含有例如分散剂(例如,吐温80、羧甲基纤维素、聚乙烯醇等)等的水溶液作为水相。
本发明中使用的油性基剂的添加量可根据组合物中的油性基剂和化合物A的物理化学性质(例如,溶解性、分散性等)、化合物A的有效用量或剂型而适当选择。该添加量只要是制药学上通常许可的且可使化合物A稳定化的量即可,无特别限制。但通常相对于化合物A1重量份,为0.001-1000重量份,较好地为0.01-100重量份,更好地为0.1-10重量份。此外,视需要,还可使用例如保存剂(例如,苄醇、乙醇、氯苄扎铵、苯酚、氯丁醇等)、抗氧化剂(例如,丁基羟基茴香醚、没食子酸丙酯、棕榈酸抗坏血酸酯、α-生育酚、DHT等)、增粘剂(例如,卵磷脂、羟丙基纤维素、硬脂酸铝等)等。
在本发明的口服用药物组合物的制造中,为了控制主药的释放和制成制剂,可添加在制造口服用药剂时通常使用的添加剂。所述添加量的例子有赋形剂(例如,玉米淀粉、滑石粉、结晶纤维素、粉状糖、硬脂酸镁、甘露糖醇、轻质无水硅酸、碳酸镁、碳酸钙、L-半胱氨酸等)、粘合剂(例如,淀粉、蔗糖、明胶、阿拉伯胶粉末、甲基纤维素、羧甲基纤维素、羧甲基纤维素钠、羟丙基纤维素、羟丙基甲基纤维素、聚乙烯基吡咯烷酮、支链淀粉、葡聚糖等)、崩解剂(例如,羧甲基纤维素钙、低取代的羟丙基纤维素等)、阴离子型表面活性剂(例如,烷基硫酸钠等)、非离子型表面活性剂(例如,聚氧乙烯山梨糖醇酐脂肪酸酯、聚氧乙烯脂肪酸酯、聚氧乙烯蓖麻油衍生物等)、抗酸剂和粘膜保护剂(例如,氢氧化镁、氧化镁、氢氧化铝、硫酸铝、偏硅酸铝酸镁、硅酸铝酸镁、硫糖铝等)、环糊精及其羧酸(例如,麦芽糖基-β-环糊精、麦芽糖基-β-环糊精羧酸等)、着色剂、矫味剂、吸附剂、防腐剂、湿润剂、抗静电剂、崩解延长剂等。这些添加剂的添加量可根据主药的稳定性和吸收性,在不影响油性基剂的添加效果的范围内适当选择。
将本发明的口服用药物组合物制成粉末状剂型时,也可由固体形态的药物组合物加以制造。即,制造粉末状剂型时,可将上述固体形态的药物组合物与上述添加剂均匀混合或用水等合适溶剂造粒。造粒时,可使用转动造粒机、搅拌造粒机、流动造粒机、离心转动造粒机、转动流动造粒机等一般的造粒机、滚动压片机等加压造粒机或转动压密型机械。此外,混合时,可使用上述造粒机,也可使用一般的混合机,例如,可使用转筒型、双圆锥型、V型、带式、螺旋式混合机等。将这样得到的混合粉末或造粒用粉末充填入胶囊中,可制造硬胶囊。此时,一般可使用内容积约为0.13-1.37mL的明胶硬胶囊,用盘式、压缩式或Auger式充填机充填。此外,将所得混合粉末或造粒用粉末压片,可将本发明的药物组合物制成片剂。片剂的形状、大小等可适当选择,例如,可制成椭圆形的、足球形的、心形的,等等,也可刻上刻痕。所用的压片机可以是偏心型的,也可以是旋转型的。
本发明的药物组合物可用肠溶性包衣剂包覆,制成肠溶性制剂。肠溶性包衣剂是指在酸性区域基本上不溶但在弱酸性至碱性区域至少部分可溶的肠溶性聚合物。这里,酸性区域是指pH约为0.5-4.5,较好地约为1.0-2.0,弱酸性至碱性区域是指pH约为5.0-9.0,较好地约为6.0-7.5。具体例子有乙酸邻苯二甲酸纤维素、羟丙基甲基纤维素、羟丙基甲基纤维素邻苯二甲酸酯、乙酸丁二酸羟丙基甲酯(信越化学(株))、甲基丙烯酸共聚物(Rhm GmbH公司产品,商品名:Eudragit L-30D-55、L100-55、L100、S100等)等。这些聚合物直接作为肠溶性制剂使用,在稳定性等方面仍然是有效的。
包覆时,可采用常用方法,例如,盘式涂布法、流涂法、转涂法等。当包衣剂为含有水或有机溶剂的溶液或分散液时,也可采用喷涂法。对制造包衣剂时的水和有机溶剂的使用比例无特别限制,可以任意比例使用。对有机溶剂的种类无特别限制,例如,可以是醇(例如,甲醇、乙醇、异丙醇等)、酮(例如,丙酮等)、卤代烃(例如,氯仿、二氯甲烷等)。此外,将本发明的药物组合物充填入用上述肠溶性包衣剂包覆过的胶囊、作为肠溶性胶囊使用,在稳定性等方面也是有效的。胶囊例如可以是明胶胶囊等。
本发明的药物组合物可在保持化合物A的优异的药理作用的同时安全地给药于哺乳动物(例如,小鼠、大鼠、仓鼠、兔子、猫、狗、牛、马、羊、猴、人等)。更具体地说,本发明中使用的化合物A可抑制整联蛋白受体与配体之间的相互反应、尤其可抑制纤维蛋白原、粘连蛋白和von Willebrand因子与血小板的纤维蛋白原受体(糖蛋白IIb/IIIa)的结合,并可抑制粘着蛋白(如玻连蛋白、胶原和海带氨酸等)与各种细胞种表面上的相应受体的结合,尤其可抑制血小板凝血酶的表达,从而可用来治疗血栓症、中风、心肌梗塞、狭心症、溶骨性疾病(尤其是骨质疏松)、血管形成后的复发性狭窄症、虚血疾病、炎症、动脉硬化症和急性肾衰竭,特别是可用作血小板凝集抑制剂。此外,本发明的药物组合物可含有化合物A以外的其它药物成分作为活性成分,只要能达到本发明的目的,对这些成分无特别限定,可适当地以合适比例使用。
在本发明的药物组合物中,由不配伍性引起的稳定性的下降不仅可在保管或贮藏过程中进行抑制或防止,而且,可抑制制剂过程中化合物A的药理活性的下降。因此,本发明的制剂中的化合物A在通常的保管期间,其活性得到充分保持,从而可期待其具有更确切的疗效。
本发明的最佳实施方式
下面结合实施例、比较例对本发明作更具体的说明,但本发明不限于这些实例。实施例1
将柠檬酸甘托非邦1重量份、氢化油(K3Wax,川研精细化学株式会社产品)5重量份用研钵混合后,用32目筛过筛,再添加部分α化的淀粉(PCS,旭化成工业株式会社产品)94重量份,混合后,用32目筛过筛,得到散剂。
实施例2
将硬脂酸5重量份放入容器中,在温水浴中加热熔融后,添加柠檬酸甘托非邦1重量份,搅拌、分散。将该熔融分散液用喷雾干燥器(L-8型,大川原制作所产品,圆盘直径50mm,旋转数30,000rpm)喷雾,固化,用42目筛过筛,得到微小球粒。往该微小球粒6重量份中添加部分α化的淀粉(PCS,旭化成工业株式会社产品)94重量份,混合后,用32目筛过筛,得到散剂。
实施例3
将硬脂醇5重量份放入容器中,在温水浴中加热熔融后,添加柠檬酸甘托非邦1重量份,搅拌、分散。将该熔融分散液用喷雾干燥器(L-8型,大川原制作所产品,圆盘直径50mm,旋转数30,000rpm)喷雾,固化,用42目筛过筛,得到微小球粒。往该微小球粒6重量份中添加D-甘露糖醇(东和化成工业株式会社产品)94重量份,混合后,用32目筛过筛,得到散剂。为了比较,将柠檬酸甘托非邦1重量份和D-甘露糖醇(东和化成工业株式会社产品)99重量份在研钵中混合后,用32目筛过筛,得到散剂,作为对照。将这些试样分别放入塑料瓶中,在开放状态下于40℃、相对湿度75%RH的条件下保存,比较它们在1个月中的稳定性。稳定性比较结果(分解率)如表1所示。稳定性用残存率(%)表示,通过用高速液相色谱测定作为活性成分的游离的4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯、由保存试验开始前和结束后的有效成分量算出。
表1
<结果和考察>
期间 | 残存率(%) | |
本发明 | 对照 | |
初期值 | 100 | 100 |
1个月 | 101.0 | 89.4 |
在对照制剂中,观察到残存率的下降,而本发明的制剂(散剂)未见残存率下降。这被认为是由于柠檬酸甘托非邦被硬脂醇(油性基剂)包覆从而抑制了与会导致不配伍性的D-甘露糖醇的接触的缘故。
实施例4
将硬脂酸5重量份放入容器中,在温水浴中加热熔融后,添加柠檬酸甘托非邦1重量份,搅拌、分散。将该熔融分散液用喷雾干燥器(L-8型,大川原制作所产品,圆盘直径50mm,旋转数30,000rpm)喷雾,固化,用42目筛过筛,得到微小球粒。往该微小球粒6重量份中添加乳糖(Dilactose S)73.5重量份、部分α化的淀粉(PCS,旭化成工业株式会社产品)20重量份和硬脂酸镁0.5重量份,混合后,用旋转式压片机(烟铁工所产品,HT-P-22)压片,得到片剂。为了比较,将柠檬酸甘托非邦1重量份、乳糖(Dilactose S)78.5重量份、部分α化的淀粉(PCS,旭化成工业株式会社产品)20重量份和硬脂酸镁(日本油脂株式会社产品)0.5重量份混合后,用旋转式压片机(烟铁工所产品,HT-P-22)压片,得到片剂,作为对照。将这些试样分别放入塑料瓶中,在开放状态下于40℃、相对湿度75%RH的条件下保存1个月,比较稳定性。稳定性比较结果(残存率)如表2所示。
表2
<结果和考察>
期间 | 残存率(%) | |
本发明 | 对照 | |
初期值 | 100 | 100 |
1个月 | 93.5 | 78.4 |
在对照制剂中,观察到显著的残存率下降,而在本发明的制剂(片剂)中,与对照制剂相比,残存率的下降得到抑制。这被认为是由于柠檬酸甘托非邦被硬脂酸(油性基剂)包覆使得柠檬酸甘托非邦与赋形剂的接触面积减少的缘故。
产业上应用的可能性
根据本发明,将具有GPIIb/IIIa受体拮抗作用的4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐与油性基剂混合或用油性基剂包覆,可制造稳定的药物组合物,从而可提供可更长期保存的药物组合物。
Claims (17)
1.一种口服用药物组合物,它包含4-[3-[p-(羧基脒基)苯基]-2-氧代-5-噁唑烷基]甲基]-1-哌嗪乙酸1-乙酯甲酯或其药用盐和油性基剂。
2.如权利要求1所述的口服用药物组合物,其中,油性基剂选自高级饱和脂肪酸、脂肪酸与醇的酯、高级醇、磷脂、甾醇或其酯和烃中的一种或多种。
3.如权利要求1所述的口服用药物组合物,其中,油性基剂选自高级饱和脂肪酸、脂肪酸与醇的酯、高级醇中的一种或多种。
4.如权利要求1-3中任一项所述的口服用药物组合物,其中,相对于权利要求1的化合物或其药用盐1重量份,油性基剂的含量为0.001-1000重量份。
5.如权利要求1-4中任一项所述的口服用药物组合物,其中,权利要求1的化合物为5R型。
6.如权利要求5所述的口服用药物组合物,其中,权利要求1的化合物为5R型的柠檬酸盐。
7.如权利要求1-6中任一项所述的口服用药物组合物,其中,权利要求1的化合物或其药用盐被油性基剂包覆。
8.口服用药物组合物的制造方法,其中,在权利要求1的化合物或其药用盐中掺入油性基剂。
9.如权利要求8所述的口服用药物组合物的制造方法,其中,用油性基剂包覆权利要求1的化合物或其药用盐。
10.如权利要求8或9所述的口服用药物组合物的制造方法,其中,油性基剂选自高级饱和脂肪酸、脂肪酸与醇的酯、高级醇、磷脂、甾醇或其酯和烃中的一种或多种。
11.如权利要求8-10中任一项所述的口服用药物组合物的制造方法,其中,权利要求1的化合物为5R型。
12.如权利要求11所述的口服用药物组合物的制造方法,其中,权利要求1的化合物为5R型的柠檬酸盐。
13.使药物组合物稳定化的方法,其中,在权利要求1的化合物或其药用盐中掺入油性基剂。
14.如权利要求13所述的使药物组合物稳定化的方法,其中,用油性基剂包覆权利要求1的化合物或其药用盐。
15.如权利要求13或14所述的使药物组合物稳定化的方法,其中,油性基剂选自高级饱和脂肪酸、脂肪酸与醇的酯、高级醇、磷脂、甾醇或其酯和烃中的一种或多种。
16.如权利要求13-15中任一项所述的使药物组合物稳定化的方法,其中,权利要求1的化合物为5R型。
17.如权利要求16所述的使药物组合物稳定化的方法,,其中,权利要求1的化合物为5R型的柠檬酸盐。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP17223799 | 1999-06-18 | ||
JP172237/99 | 1999-06-18 | ||
JP172237/1999 | 1999-06-18 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1353610A true CN1353610A (zh) | 2002-06-12 |
CN1172671C CN1172671C (zh) | 2004-10-27 |
Family
ID=15938170
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB008083290A Expired - Fee Related CN1172671C (zh) | 1999-06-18 | 2000-06-16 | 口服用药物组合物 |
Country Status (8)
Country | Link |
---|---|
US (1) | US6525058B1 (zh) |
EP (1) | EP1188440A4 (zh) |
KR (1) | KR20020038591A (zh) |
CN (1) | CN1172671C (zh) |
AR (1) | AR024570A1 (zh) |
AU (1) | AU5249500A (zh) |
CA (1) | CA2376155A1 (zh) |
WO (1) | WO2000078318A1 (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITMI20012366A1 (it) * | 2001-11-09 | 2003-05-09 | Farmatron Ltd | Sistemi terapeutici stabilizzati a rilascio immediato e/o modificato per la somministrazione orale di principi attivi e/o eccipienti e/o ali |
EP2327406A4 (en) | 2008-08-14 | 2014-04-09 | Kyorin Seiyaku Kk | STABILIZED PHARMACEUTICAL COMPOSITION |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4874795A (en) * | 1985-04-02 | 1989-10-17 | Yesair David W | Composition for delivery of orally administered drugs and other substances |
EP0448091B1 (en) * | 1990-03-23 | 1998-08-05 | The Green Cross Corporation | Pharmaceutical composition containing slightly water-soluble drug |
DE19516483A1 (de) * | 1995-05-05 | 1996-11-07 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
US5716928A (en) * | 1995-06-07 | 1998-02-10 | Avmax, Inc. | Use of essential oils to increase bioavailability of oral pharmaceutical compounds |
US6013665A (en) * | 1997-12-16 | 2000-01-11 | Abbott Laboratories | Method for enhancing the absorption and transport of lipid soluble compounds using structured glycerides |
US6579880B2 (en) * | 2000-06-06 | 2003-06-17 | Ortho-Mcneil Pharmaceutical, Inc. | Isoxazoles and oxadiazoles as anti-inflammatory inhibitors of IL-8 |
-
2000
- 2000-06-16 CN CNB008083290A patent/CN1172671C/zh not_active Expired - Fee Related
- 2000-06-16 AR ARP000102986A patent/AR024570A1/es unknown
- 2000-06-16 US US10/009,797 patent/US6525058B1/en not_active Expired - Fee Related
- 2000-06-16 EP EP00937275A patent/EP1188440A4/en not_active Withdrawn
- 2000-06-16 KR KR1020017016208A patent/KR20020038591A/ko not_active Application Discontinuation
- 2000-06-16 AU AU52495/00A patent/AU5249500A/en not_active Abandoned
- 2000-06-16 WO PCT/JP2000/003940 patent/WO2000078318A1/ja not_active Application Discontinuation
- 2000-06-16 CA CA002376155A patent/CA2376155A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
US6525058B1 (en) | 2003-02-25 |
WO2000078318A1 (fr) | 2000-12-28 |
AU5249500A (en) | 2001-01-09 |
EP1188440A4 (en) | 2004-04-14 |
KR20020038591A (ko) | 2002-05-23 |
EP1188440A1 (en) | 2002-03-20 |
CA2376155A1 (en) | 2000-12-28 |
AR024570A1 (es) | 2002-10-16 |
CN1172671C (zh) | 2004-10-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4868695B2 (ja) | 崩壊性が良好な経口製剤 | |
US5403593A (en) | Melt granulated compositions for preparing sustained release dosage forms | |
US20080095838A1 (en) | Solid pharmaceutical composition containing a lipophilic active principle and preparation method thereof | |
US20090304795A1 (en) | Tablets with improved drug substance dispersibility | |
US4620974A (en) | Pharmaceutical composition containing a liquid lubricant | |
JP2013521318A (ja) | ダビガトランエテキシラートを含有する医薬組成物 | |
US20090041829A1 (en) | Pharmaceutical dosage forms comprising a lipid phase | |
EP0377658A1 (en) | A FREE-FLOWING GRANULATE, CONTAINING IBUPROFEN AND A PRODUCTION PROCESS. | |
US4832952A (en) | Pharmaceutical composition containing a liquid lubricant | |
AU2006325658A1 (en) | Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same | |
WO2015141662A1 (ja) | 固体分散体 | |
HU219338B (en) | Pharmaceutical compositions containing nifedipine and process for the preparation thereof | |
TWI333858B (zh) | ||
JPH04312524A (ja) | 徐放性製剤およびその製造法 | |
MX2007011858A (es) | Formulaciones mejoradas de fenofibrato que contienen mentol o peg/poloxamero. | |
CN104918608A (zh) | Cetp抑制剂的药物组合物 | |
US20110244031A1 (en) | Porous tablets as carriers for liquid formulations | |
EP2050436A1 (en) | Pharmaceutical composition containing dutasteride | |
CN1172671C (zh) | 口服用药物组合物 | |
KR20140002810A (ko) | 안정한 나노입자 제형 | |
CN101094656A (zh) | 含低剂量雌二醇的口服固体剂型 | |
GB2142824A (en) | Pharmaceutical composition containing a liquid lubricant | |
US20100055177A1 (en) | Modified release composition of levetiracetam and process for the preparation thereof | |
JP2010519312A (ja) | 薬学的製剤 | |
US4777048A (en) | Pharmaceutical composition containing a liquid lubricant |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C06 | Publication | ||
PB01 | Publication | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C19 | Lapse of patent right due to non-payment of the annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |