KR20230097021A - 약학 조성물 - Google Patents
약학 조성물 Download PDFInfo
- Publication number
- KR20230097021A KR20230097021A KR1020237014087A KR20237014087A KR20230097021A KR 20230097021 A KR20230097021 A KR 20230097021A KR 1020237014087 A KR1020237014087 A KR 1020237014087A KR 20237014087 A KR20237014087 A KR 20237014087A KR 20230097021 A KR20230097021 A KR 20230097021A
- Authority
- KR
- South Korea
- Prior art keywords
- pharmaceutical composition
- acid
- amorphous solid
- solid dispersion
- amount
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 566
- 239000008186 active pharmaceutical agent Substances 0.000 claims abstract description 386
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- 239000007962 solid dispersion Substances 0.000 claims abstract description 257
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- 239000003463 adsorbent Substances 0.000 claims abstract description 161
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- 239000000203 mixture Substances 0.000 claims abstract description 108
- 239000005536 L01XE08 - Nilotinib Substances 0.000 claims abstract description 102
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- 238000000034 method Methods 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims description 168
- -1 acetate-polyethylene Chemical group 0.000 claims description 167
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 145
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- 150000007524 organic acids Chemical class 0.000 claims description 119
- 150000007522 mineralic acids Chemical class 0.000 claims description 112
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- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 44
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- VTGGYCCJUPYZSX-UHFFFAOYSA-N 4-methyl-n-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide;hydrochloride Chemical group Cl.C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 VTGGYCCJUPYZSX-UHFFFAOYSA-N 0.000 claims description 27
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- 229920001400 block copolymer Polymers 0.000 claims description 23
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- 150000001875 compounds Chemical class 0.000 claims description 22
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- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 17
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- 239000011975 tartaric acid Substances 0.000 claims description 17
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 16
- 239000003937 drug carrier Substances 0.000 claims description 16
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 15
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 235000015165 citric acid Nutrition 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
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- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 14
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- 125000002619 bicyclic group Chemical group 0.000 claims description 14
- 235000011087 fumaric acid Nutrition 0.000 claims description 14
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- 229910052736 halogen Inorganic materials 0.000 claims description 14
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- 125000002950 monocyclic group Chemical group 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 13
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 13
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- 239000001630 malic acid Substances 0.000 claims description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 13
- GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 12
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 claims description 12
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 claims description 12
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 12
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- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 230000000996 additive effect Effects 0.000 claims description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
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- 125000004434 sulfur atom Chemical group 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 10
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 10
- 229940030721 nilotinib hydrochloride Drugs 0.000 claims description 10
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 10
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 9
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
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- 239000012535 impurity Substances 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
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- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 claims description 8
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| EP4221690A1 (en) | 2023-08-09 |
| US20230414613A1 (en) | 2023-12-28 |
| AU2021353684A1 (en) | 2023-06-08 |
| EP4221690A4 (en) | 2024-10-30 |
| CA3193829A1 (en) | 2022-04-07 |
| US12527793B2 (en) | 2026-01-20 |
| US20240226102A1 (en) | 2024-07-11 |
| US20260115192A1 (en) | 2026-04-30 |
| US12186316B2 (en) | 2025-01-07 |
| MX2023003556A (es) | 2023-06-13 |
| CN116635015A (zh) | 2023-08-22 |
| WO2022068876A1 (en) | 2022-04-07 |
| AU2021353684A9 (en) | 2025-03-13 |
| JP2023543815A (ja) | 2023-10-18 |
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