KR100227156B1 - 저장 안정성이 개선된 약학조성물 및 그의 제조방법 - Google Patents
저장 안정성이 개선된 약학조성물 및 그의 제조방법 Download PDFInfo
- Publication number
- KR100227156B1 KR100227156B1 KR1019910012692A KR910012692A KR100227156B1 KR 100227156 B1 KR100227156 B1 KR 100227156B1 KR 1019910012692 A KR1019910012692 A KR 1019910012692A KR 910012692 A KR910012692 A KR 910012692A KR 100227156 B1 KR100227156 B1 KR 100227156B1
- Authority
- KR
- South Korea
- Prior art keywords
- composition
- hydrochloride
- hydrochloric acid
- converting enzyme
- acid donor
- 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.)
- Expired - Lifetime
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims description 10
- 238000002360 preparation method Methods 0.000 title description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 60
- 239000000203 mixture Substances 0.000 claims description 46
- 239000005541 ACE inhibitor Substances 0.000 claims description 25
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 25
- 229960002909 spirapril Drugs 0.000 claims description 10
- 108700035424 spirapril Proteins 0.000 claims description 10
- HRWCVUIFMSZDJS-SZMVWBNQSA-N spirapril Chemical group C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)CC1=CC=CC=C1 HRWCVUIFMSZDJS-SZMVWBNQSA-N 0.000 claims description 10
- 230000000087 stabilizing effect Effects 0.000 claims description 9
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical group Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 claims description 7
- 229960001269 glycine hydrochloride Drugs 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 5
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 4
- RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 claims description 3
- 229960003403 betaine hydrochloride Drugs 0.000 claims description 3
- HOPSCVCBEOCPJZ-UHFFFAOYSA-N carboxymethyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC(O)=O HOPSCVCBEOCPJZ-UHFFFAOYSA-N 0.000 claims description 3
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 claims description 3
- 229960003707 glutamic acid hydrochloride Drugs 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229960001455 quinapril Drugs 0.000 claims description 3
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical group C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 claims description 3
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 3
- JETBVOLWZWPMKR-UHFFFAOYSA-N (1-carboxy-2-methylpropyl)azanium;chloride Chemical compound Cl.CC(C)C(N)C(O)=O JETBVOLWZWPMKR-UHFFFAOYSA-N 0.000 claims description 2
- DWHMPBALQYTJFJ-DKWTVANSSA-N (2s)-2-aminobutanedioic acid;hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CC(O)=O DWHMPBALQYTJFJ-DKWTVANSSA-N 0.000 claims description 2
- ILYVXUGGBVATGA-DKWTVANSSA-N (2s)-2-aminopropanoic acid;hydrochloride Chemical compound Cl.C[C@H](N)C(O)=O ILYVXUGGBVATGA-DKWTVANSSA-N 0.000 claims description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 2
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 claims description 2
- 239000002841 Lewis acid Substances 0.000 claims description 2
- 229940024606 amino acid Drugs 0.000 claims description 2
- 235000001014 amino acid Nutrition 0.000 claims description 2
- 229960003589 arginine hydrochloride Drugs 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 150000007517 lewis acids Chemical class 0.000 claims description 2
- 229960005337 lysine hydrochloride Drugs 0.000 claims description 2
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims 5
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims 5
- 150000001413 amino acids Chemical group 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 abstract description 13
- 239000002253 acid Substances 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 description 23
- 239000004480 active ingredient Substances 0.000 description 13
- 239000003826 tablet Substances 0.000 description 8
- -1 alkaline earth metal salts Chemical class 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 7
- 238000006731 degradation reaction Methods 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 4
- 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 4
- 230000008901 benefit Effects 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 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
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000011976 maleic acid Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 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 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
- 108010061435 Enalapril Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229960000873 enalapril Drugs 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 238000009827 uniform distribution Methods 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 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
- 238000002679 ablation Methods 0.000 description 1
- 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 1
- 239000002535 acidifier Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000012730 carminic acid Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 229960005227 delapril Drugs 0.000 description 1
- WOUOLAUOZXOLJQ-MBSDFSHPSA-N delapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N(CC(O)=O)C1CC2=CC=CC=C2C1)CC1=CC=CC=C1 WOUOLAUOZXOLJQ-MBSDFSHPSA-N 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000001761 ethyl methyl cellulose Substances 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 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
- 239000010514 hydrogenated cottonseed oil Substances 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229950009810 indolapril Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000314 lubricant Substances 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
- 239000011159 matrix material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229960002582 perindopril Drugs 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 229960002051 trandolapril Drugs 0.000 description 1
- 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 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Biophysics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55723490A | 1990-07-25 | 1990-07-25 | |
| US557,234 | 1990-07-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR920002146A KR920002146A (ko) | 1992-02-28 |
| KR100227156B1 true KR100227156B1 (ko) | 1999-10-15 |
Family
ID=24224569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019910012692A Expired - Lifetime KR100227156B1 (ko) | 1990-07-25 | 1991-07-24 | 저장 안정성이 개선된 약학조성물 및 그의 제조방법 |
Country Status (30)
| Country | Link |
|---|---|
| EP (1) | EP0468929B1 (enExample) |
| JP (1) | JP2502849B2 (enExample) |
| KR (1) | KR100227156B1 (enExample) |
| AT (1) | AT400519B (enExample) |
| AU (1) | AU639354B2 (enExample) |
| CA (1) | CA2047802C (enExample) |
| CH (1) | CH683150A5 (enExample) |
| CZ (1) | CZ280184B6 (enExample) |
| DE (1) | DE4124409B4 (enExample) |
| DK (1) | DK0468929T3 (enExample) |
| ES (1) | ES2061218T3 (enExample) |
| FI (1) | FI98127C (enExample) |
| GB (1) | GB2246296B (enExample) |
| HU (1) | HU222489B1 (enExample) |
| IE (1) | IE66184B1 (enExample) |
| IL (1) | IL98934A (enExample) |
| IT (1) | IT1290797B1 (enExample) |
| LU (1) | LU87980A1 (enExample) |
| MX (1) | MX9100357A (enExample) |
| MY (1) | MY107183A (enExample) |
| NO (1) | NO912872D0 (enExample) |
| NZ (1) | NZ239078A (enExample) |
| PL (1) | PL167712B1 (enExample) |
| PT (1) | PT98417B (enExample) |
| RU (1) | RU2075310C1 (enExample) |
| SA (1) | SA92130106B1 (enExample) |
| SK (1) | SK278563B6 (enExample) |
| TW (1) | TW212757B (enExample) |
| UA (1) | UA26064A1 (enExample) |
| ZA (1) | ZA915861B (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996002564A1 (en) * | 1994-07-13 | 1996-02-01 | Lek, Tovarna Farmacevtskih In Kemicnih Izdelkov, D.D. | Process for the preparation of compounds having ace inhibitory action as well as novel compounds useful as starting materials or intermediates in said process |
| DE4444051A1 (de) * | 1994-12-10 | 1996-06-13 | Rhone Poulenc Rorer Gmbh | Pharmazeutische, oral anwendbare Zubereitung |
| HU222497B1 (hu) * | 1996-12-18 | 2003-07-28 | Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. | Enalapril-maleátot tartalmazó stabilizált gyógyszerkészítmény és eljárás előállítására |
| ES2242398T3 (es) * | 1998-06-05 | 2005-11-01 | Warner-Lambert Company Llc | Estabilizacion de composiciones que contienen inhibidores de la enzima de conversion de la angiotensina utilizando oxido de magnesio. |
| KR100483080B1 (ko) * | 2001-09-21 | 2005-04-14 | 한인규 | 염산·베타인(betaine·HCl), 판크레아틴, 제2인산 칼슘, 크롬 피콜리네이트, 락토바실러스속·비피도박테리아속·스트렙토코커스속·프럭토 올리고당, 비타민, 미네랄을 유효성분으로 구성된 것을 특징으로 하는 증체개선용 영양강화 사료첨가제 |
| US6462022B1 (en) † | 2001-09-24 | 2002-10-08 | Astrazeneca Ab | Lisinopril compositions having large-particle DCPD |
| ES2283774T3 (es) * | 2002-01-15 | 2007-11-01 | Actavis Group Hf. | Formulaciones de quinapril e inhibidores de la eca relacionados. |
| GB2411355B (en) | 2004-02-27 | 2006-02-22 | Niche Generics Ltd | Pharmaceutical composition |
| EP1815857A1 (en) | 2006-02-02 | 2007-08-08 | LEK Pharmaceuticals D.D. | A pharmaceutical composition comprising perindopril |
| ES2364011B1 (es) | 2009-11-20 | 2013-01-24 | Gp Pharm, S.A. | Cápsulas de principios activos farmacéuticos y ésteres de ácidos grasos poliinsaturados para el tratamiento de enfermedades cardiovasculares. |
| JP2020521795A (ja) | 2017-05-31 | 2020-07-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | （Ｅ）−４−（２−（アミノメチル）−３−フルオロアリルオキシ）−Ｎ−ｔｅｒｔ−ブチルベンズアミドを含む医薬組成物および医薬剤形、それらの調製方法、治療方法およびそれらの使用 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB895027A (en) * | 1959-08-03 | 1962-04-26 | Bristol Myers Co | Therapeutic tetracycline compositions |
| GB1437788A (en) * | 1973-01-31 | 1976-06-03 | Gist Brocades Nv | Therapeutic compositions |
| HU173823B (hu) * | 1975-07-25 | 1979-08-28 | Chinoin Gyogyszer Es Vegyeszet | Sposob poluchenija stabil'nogo lechebnogo preparata dlja oral'noj dozirovki, kotoryj soderzhit proizvodnyj gomopirimidazola |
| DE3124090A1 (de) * | 1981-06-19 | 1983-01-05 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue orale dipyridamolformen |
| US4442089A (en) * | 1982-07-06 | 1984-04-10 | E. R. Squibb & Sons, Inc. | Method for treating glaucoma with topical or systemic ACE inhibitor compositions |
| US4575539A (en) * | 1985-06-03 | 1986-03-11 | E. R. Squibb & Sons, Inc. | Drug delivery systems including novel interpenetrating polymer networks and method |
| US4900559A (en) * | 1985-12-12 | 1990-02-13 | Briston-Myers Company | Stabilized enteric coated aspirin granules and process of preparation |
| DE3627613A1 (de) * | 1986-08-14 | 1988-02-18 | Merck Patent Gmbh | Pharmazeutische zubereitung |
| US4793998A (en) * | 1986-10-20 | 1988-12-27 | Warner-Lambert Company | Stabilized drug compositions |
| US4830853A (en) * | 1986-10-20 | 1989-05-16 | Warner-Lambert Company | Drug compositions stabilized against oxidation |
| US4743450A (en) * | 1987-02-24 | 1988-05-10 | Warner-Lambert Company | Stabilized compositions |
| US4808413A (en) * | 1987-04-28 | 1989-02-28 | E. R. Squibb & Sons, Inc. | Pharmaceutical compositions in the form of beadlets and method |
| JP2603480B2 (ja) * | 1987-08-05 | 1997-04-23 | 住友製薬株式会社 | 安定化されたアンスラサイクリン系製剤 |
| AU608891B2 (en) * | 1987-09-24 | 1991-04-18 | Merck & Co., Inc. | Solubility modulated drug delivery device |
| US4912096A (en) * | 1989-06-26 | 1990-03-27 | E. R. Squibb & Sons, Inc. | Method for preventing or treating depression employing an ace inhibitor |
-
1991
- 1991-07-16 HU HU9102385A patent/HU222489B1/hu active IP Right Grant
- 1991-07-17 MY MYPI91001288A patent/MY107183A/en unknown
- 1991-07-22 CH CH2185/91A patent/CH683150A5/de not_active IP Right Cessation
- 1991-07-23 GB GB9115893A patent/GB2246296B/en not_active Expired - Lifetime
- 1991-07-23 SK SK2309-91A patent/SK278563B6/sk not_active IP Right Cessation
- 1991-07-23 LU LU87980A patent/LU87980A1/fr unknown
- 1991-07-23 AU AU81286/91A patent/AU639354B2/en not_active Expired
- 1991-07-23 EP EP91810591A patent/EP0468929B1/en not_active Expired - Lifetime
- 1991-07-23 CZ CS912309A patent/CZ280184B6/cs not_active IP Right Cessation
- 1991-07-23 PT PT98417A patent/PT98417B/pt not_active IP Right Cessation
- 1991-07-23 ES ES91810591T patent/ES2061218T3/es not_active Expired - Lifetime
- 1991-07-23 DE DE4124409A patent/DE4124409B4/de not_active Expired - Lifetime
- 1991-07-23 DK DK91810591.7T patent/DK0468929T3/da active
- 1991-07-23 JP JP3205603A patent/JP2502849B2/ja not_active Expired - Lifetime
- 1991-07-23 NZ NZ239078A patent/NZ239078A/xx not_active IP Right Cessation
- 1991-07-23 NO NO912872A patent/NO912872D0/no unknown
- 1991-07-23 IT IT91RM000554A patent/IT1290797B1/it active IP Right Grant
- 1991-07-23 IL IL9893491A patent/IL98934A/en not_active IP Right Cessation
- 1991-07-24 FI FI913554A patent/FI98127C/fi not_active IP Right Cessation
- 1991-07-24 UA UA5001271A patent/UA26064A1/uk unknown
- 1991-07-24 PL PL91291219A patent/PL167712B1/pl unknown
- 1991-07-24 AT AT0147691A patent/AT400519B/de not_active IP Right Cessation
- 1991-07-24 KR KR1019910012692A patent/KR100227156B1/ko not_active Expired - Lifetime
- 1991-07-24 MX MX9100357A patent/MX9100357A/es unknown
- 1991-07-24 CA CA002047802A patent/CA2047802C/en not_active Expired - Lifetime
- 1991-07-24 RU SU915001271A patent/RU2075310C1/ru active
- 1991-07-24 IE IE260891A patent/IE66184B1/en not_active IP Right Cessation
- 1991-07-25 ZA ZA915861A patent/ZA915861B/xx unknown
- 1991-08-13 TW TW080106368A patent/TW212757B/zh not_active IP Right Cessation
-
1992
- 1992-09-09 SA SA92130106A patent/SA92130106B1/ar unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4665081A (en) | Solid nifedipine preparations and a process for preparing same | |
| US5442008A (en) | Stabilized polymer film coated compounds and stabilized formulations in compressed from using same | |
| US5874106A (en) | Filled gelatin capsules | |
| KR100227156B1 (ko) | 저장 안정성이 개선된 약학조성물 및 그의 제조방법 | |
| US6300362B1 (en) | Stabilized pharmaceutical compositions comprising acid donors | |
| CN1301148A (zh) | 含有左甲状腺素钠的药物制剂 | |
| EP0952823B1 (en) | Stabilized pharmaceutical compositions and process for the preparation thereof | |
| JPH1192369A (ja) | 医薬品調製物、その製造方法及びシランセトロンの安定化のための酸性添加剤の使用 | |
| SK13022003A3 (sk) | Stabilná farmaceutická kompozícia pravastatínu | |
| EA008171B1 (ru) | Фармацевтическая композиция, содержащая фозиноприл | |
| WO1999020276A1 (fr) | Composition medicamenteuse stable | |
| EP1404303A1 (en) | Stable pharmaceutical compositions containing pravastatin | |
| KR100593795B1 (ko) | 안정성이 개선된 라미프릴을 포함하는 경구투여용 제제 | |
| NZ270729A (en) | Fluvastatin sodium in an alkaline carrier | |
| EP1911441A2 (en) | Controlled release color stable pharmaceutical dosage form of HMG-COA reductase inhibitors, free of alkalizing or buffering agents | |
| FR2665834A1 (fr) | Composition pharmaceutique stabilisee par un donneur d'acide chlorhydrique, et sa preparation. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0109 | Patent application |
Patent event code: PA01091R01D Comment text: Patent Application Patent event date: 19910724 |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 19960719 Comment text: Request for Examination of Application Patent event code: PA02011R01I Patent event date: 19910724 Comment text: Patent Application |
|
| N231 | Notification of change of applicant | ||
| PN2301 | Change of applicant |
Patent event date: 19980227 Comment text: Notification of Change of Applicant Patent event code: PN23011R01D |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 19981027 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 19990430 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 19990730 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 19990731 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20020614 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20030618 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 20040609 Start annual number: 6 End annual number: 6 |
|
| PR1001 | Payment of annual fee |
Payment date: 20050603 Start annual number: 7 End annual number: 7 |
|
| PR1001 | Payment of annual fee |
Payment date: 20060623 Start annual number: 8 End annual number: 8 |
|
| PR1001 | Payment of annual fee |
Payment date: 20070723 Start annual number: 9 End annual number: 9 |
|
| PR1001 | Payment of annual fee |
Payment date: 20080721 Start annual number: 10 End annual number: 10 |
|
| PR1001 | Payment of annual fee |
Payment date: 20090724 Start annual number: 11 End annual number: 11 |
|
| FPAY | Annual fee payment |
Payment date: 20100729 Year of fee payment: 12 |
|
| PR1001 | Payment of annual fee |
Payment date: 20100729 Start annual number: 12 End annual number: 12 |
|
| EXPY | Expiration of term | ||
| PC1801 | Expiration of term |
Termination date: 20121009 Termination category: Expiration of duration |