JP2017535538A5 - ５−クロロ−ｎ４−［２−（ジメチルホスホリル）フェニル］−ｎ２−｛２−メトキシ−４−［４−（４−メチルピペラジン−１−イル）ピペリジン−１−イル］フェニル｝ピリミジン−２，４−ジアミンの結晶形態 - Google Patents
５−クロロ−ｎ４−［２−（ジメチルホスホリル）フェニル］−ｎ２−｛２−メトキシ−４−［４−（４−メチルピペラジン−１−イル）ピペリジン−１−イル］フェニル｝ピリミジン−２，４−ジアミンの結晶形態 Download PDFInfo
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title description 4
- -1 dimethylphosphoryl Chemical group 0.000 title description 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 title description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 title description 2
- AILRADAXUVEEIR-UHFFFAOYSA-N 5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1P(C)(C)=O AILRADAXUVEEIR-UHFFFAOYSA-N 0.000 claims description 7
- 229950004272 Brigatinib Drugs 0.000 claims description 7
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 4
- 238000002844 melting Methods 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- 208000002154 Non-Small-Cell Lung Carcinoma Diseases 0.000 claims 2
- 108009000071 Non-small cell lung cancer Proteins 0.000 claims 2
- 238000001157 Fourier transform infrared spectrum Methods 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000005712 crystallization Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000546 pharmaceutic aid Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 239000003981 vehicle Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 7
- 229940034982 ANTINEOPLASTIC AGENTS Drugs 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- ZROHGHOFXNOHSO-BNTLRKBRSA-L (1R,2R)-cyclohexane-1,2-diamine;oxalate;platinum(2+) Chemical compound [H][N]([C@@H]1CCCC[C@H]1[N]1([H])[H])([H])[Pt]11OC(=O)C(=O)O1 ZROHGHOFXNOHSO-BNTLRKBRSA-L 0.000 description 1
- OUPZKGBUJRBPGC-HLTSFMKQSA-N 1,5-bis[[(2R)-oxiran-2-yl]methyl]-3-[[(2S)-oxiran-2-yl]methyl]-1,3,5-triazinane-2,4,6-trione Chemical compound O=C1N(C[C@H]2OC2)C(=O)N(C[C@H]2OC2)C(=O)N1C[C@H]1CO1 OUPZKGBUJRBPGC-HLTSFMKQSA-N 0.000 description 1
- KHWIRCOLWPNBJP-UHFFFAOYSA-N 1-(2-chloroethyl)-3-(2,6-dioxopiperidin-3-yl)-1-nitrosourea Chemical compound ClCCN(N=O)C(=O)NC1CCC(=O)NC1=O KHWIRCOLWPNBJP-UHFFFAOYSA-N 0.000 description 1
- YJZJEQBSODVMTH-UHFFFAOYSA-N 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea Chemical compound OCCNC(=O)N(N=O)CCCl YJZJEQBSODVMTH-UHFFFAOYSA-N 0.000 description 1
- RCLLNBVPCJDIPX-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[2-(dimethylsulfamoyl)ethyl]-1-nitrosourea Chemical compound CN(C)S(=O)(=O)CCNC(=O)N(N=O)CCCl RCLLNBVPCJDIPX-UHFFFAOYSA-N 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N 2,2,2-trifluoroethyl alcohol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- YAAWASYJIRZXSZ-UHFFFAOYSA-N 2,4-Diaminopyrimidine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 1
- QHMIEWWCNLMBMZ-UHFFFAOYSA-N 3-[8,13-bis(1-acetyloxyethyl)-18-(2-carboxyethyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-2-yl]propanoic acid Chemical compound N1C2=C(C)C(C(C)OC(C)=O)=C1C=C(N1)C(C)=C(C(OC(C)=O)C)C1=CC(C(C)=C1CCC(O)=O)=NC1=CC(C(CCC(O)=O)=C1C)=NC1=C2 QHMIEWWCNLMBMZ-UHFFFAOYSA-N 0.000 description 1
- GOJJWDOZNKBUSR-UHFFFAOYSA-N 7-sulfamoyloxyheptyl sulfamate Chemical compound NS(=O)(=O)OCCCCCCCOS(N)(=O)=O GOJJWDOZNKBUSR-UHFFFAOYSA-N 0.000 description 1
- QMGUSPDJTPDFSF-UHFFFAOYSA-N Aldophosphamide Chemical class ClCCN(CCCl)P(=O)(N)OCCC=O QMGUSPDJTPDFSF-UHFFFAOYSA-N 0.000 description 1
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N Altretamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Belustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- FVLVBPDQNARYJU-KYZUINATSA-N CHEMBL1967746 Chemical compound C[C@H]1CC[C@H](NC(=O)N(CCCl)N=O)CC1 FVLVBPDQNARYJU-KYZUINATSA-N 0.000 description 1
- 229960004562 Carboplatin Drugs 0.000 description 1
- OLESAACUTLOWQZ-UHFFFAOYSA-L Carboplatin Chemical compound O=C1O[Pt]([N]([H])([H])[H])([N]([H])([H])[H])OC(=O)C11CCC1 OLESAACUTLOWQZ-UHFFFAOYSA-L 0.000 description 1
- 229960004630 Chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N Chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004397 Cyclophosphamide Drugs 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 229950003860 Elmustine Drugs 0.000 description 1
- 229960001101 Ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N Ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229950010897 Iproplatin Drugs 0.000 description 1
- 241001527806 Iti Species 0.000 description 1
- ARKYUICTMUZVEW-UHFFFAOYSA-N N-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-[[4-[bis(2-chloroethyl)amino]benzoyl]amino]-1-methylpyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCCC(N)=N)N(C)C=C1NC(=O)C1=CC(NC(=O)C=2N(C=C(NC(=O)C=3C=CC(=CC=3)N(CCCl)CCCl)C=2)C)=CN1C ARKYUICTMUZVEW-UHFFFAOYSA-N 0.000 description 1
- UPBAOYRENQEPJO-UHFFFAOYSA-N N-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylpyrrole-2-carboxamide Chemical class CN1C=C(NC=O)C=C1C(=O)NC1=CN(C)C(C(=O)NC2=CN(C)C(C(=O)NCCC(N)=N)=C2)=C1 UPBAOYRENQEPJO-UHFFFAOYSA-N 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Nitrumon Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N Phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- HFVNWDWLWUCIHC-GUPDPFMOSA-N Prednimustine Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 HFVNWDWLWUCIHC-GUPDPFMOSA-N 0.000 description 1
- AHHFEZNOXOZZQA-ZEBDFXRSSA-N Ranimustine Chemical compound CO[C@H]1O[C@H](CNC(=O)N(CCCl)N=O)[C@@H](O)[C@H](O)[C@H]1O AHHFEZNOXOZZQA-ZEBDFXRSSA-N 0.000 description 1
- 229950010168 Tauromustine Drugs 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temodal Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- 229950008703 Teroxirone Drugs 0.000 description 1
- LJBKHHZPVCABCX-ZYUZMQFOSA-N [(2R,3R,4R,5R)-2,5-dihydroxy-3,4-dimethoxy-6-methylsulfonyloxyhexyl] methanesulfonate Chemical compound CS(=O)(=O)OC[C@@H](O)[C@@H](OC)[C@H](OC)[C@H](O)COS(C)(=O)=O LJBKHHZPVCABCX-ZYUZMQFOSA-N 0.000 description 1
- MHVFYGIQJNFWGQ-UHFFFAOYSA-N [[4,6-bis[hydroxymethyl(methyl)amino]-1,3,5-triazin-2-yl]-methylamino]methanol Chemical compound OCN(C)C1=NC(N(C)CO)=NC(N(C)CO)=N1 MHVFYGIQJNFWGQ-UHFFFAOYSA-N 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N carbodiimide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 230000000875 corresponding Effects 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 229960004750 estramustine phosphate Drugs 0.000 description 1
- ADFOJJHRTBFFOF-RBRWEJTLSA-N estramustine phosphate Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)OP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 ADFOJJHRTBFFOF-RBRWEJTLSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- FXSKHQLAUMGYJK-UHFFFAOYSA-J platinum(4+);propan-2-amine;dichloride;dihydroxide Chemical compound [OH-].[OH-].[Cl-].[Cl-].[Pt+4].CC(C)N.CC(C)N FXSKHQLAUMGYJK-UHFFFAOYSA-J 0.000 description 1
- 229960004694 prednimustine Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229960002185 ranimustine Drugs 0.000 description 1
- 229960003440 semustine Drugs 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- LXZZYRPGZAFOLE-UHFFFAOYSA-L transplatin Chemical compound [H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H] LXZZYRPGZAFOLE-UHFFFAOYSA-L 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly Effects 0.000 description 1
- 235000020138 yakult Nutrition 0.000 description 1
Description
本出願は、５−クロロ−Ｎ４−［２−（ジメチルホスホリル）フェニル］−Ｎ２−｛２−メトキシ−４−［４−（４−メチルピペラジン−１−イル）ピペリジン−１−イル］フェニル｝ピリミジン−２，４−ジアミン（「ＡＰ２６１１３」及び「ブリガチニブ」とも称される）の新規の結晶形態、かかる結晶形態を含む組成物、ならびにそれらの調製方法及び使用方法を対象とする。
形態Ｆ：
形態Ｆは、ＴＦＥ／水を使用するフリーズドライ実験から得られ、ＴＦＥ溶媒和化合物である。ＸＲＰＤにより測定すると、形態Ｆは、加熱または周囲条件での８週間の保管により、脱溶媒和して形態Ａになる。ＴＧＡ／ＳＤＴＡによる分析（図２２）は、ブリガチニブ分子当たり１．２４トリフルオロエタノール分子に対応する、４０〜１６０℃の温度範囲における１７．５％の質量損失を示した。ＳＤＴＡ信号及び示された融解点によると、脱溶媒和すると発生する固体は、形態Ａである。
形態Ｆは、ＴＦＥ／水を使用するフリーズドライ実験から得られ、ＴＦＥ溶媒和化合物である。ＸＲＰＤにより測定すると、形態Ｆは、加熱または周囲条件での８週間の保管により、脱溶媒和して形態Ａになる。ＴＧＡ／ＳＤＴＡによる分析（図２２）は、ブリガチニブ分子当たり１．２４トリフルオロエタノール分子に対応する、４０〜１６０℃の温度範囲における１７．５％の質量損失を示した。ＳＤＴＡ信号及び示された融解点によると、脱溶媒和すると発生する固体は、形態Ａである。
図３３Ａ／Ｂ：２５℃でのＳＧＦ中の形態ＡのＩＤＲは、最初の５分間は３７℃でのものより高いように見え、測定の最初において錠剤粒子の脱離の可能性があり、これが、濃度を強めている。その後、２５及び３７℃での両方での形態ＡのＩＤＲ値は、類似しているように見える。形態ＢのＩＤＲは、予想されるように２５℃でより３７℃で高い。ｐＨ１．０の緩衝液及びＳＧＦ中の形態Ａ及びＢの両方のＩＤＲは、両方の温度で比較可能である（図３１及び図３３Ａ／Ｂを参照されたい）。０．３ｍｇ／ｍＬ周辺の濃度で、検出器はほぼ飽和状態になる。
いくつかの実施形態において、本明細書に提供されるような化合物が、複数回の投薬で投与され得る。投薬は、１日当たり約１回、２回、３回、４回、５回、または６回以上になり得る。投薬は、月に約１回、２週間に約１回、１週間に約１回、または約１日おきになり得る。別の実施形態において、本明細書で開示されるような化合物及び別の薬剤が共に、１日当たり約１回〜１日当たり約６回投与される。例えば、化合物は、無期限に、または例えば４〜１０週間の期間の間、毎週（例えば、毎週月曜日）１日当たり１回以上投与され得る。あるいは、それは、何日かの期間の間（例えば、２〜１０日）毎日投与され得、その後何日かの期間の間（例えば、１〜３０日）化合物は投与されず、このサイクルが、無期限、または所定の数のサイクルの間、例えば、４〜１０サイクル繰り返される。例として、本明細書に提供される化合物は、毎日５日間投与され得、次いで、９日間中止され、次いで、さらに毎日５日間投与され、次いで、９日間中止され、無期限に、または合計４〜１０回このサイクルを繰り返す。別の実施形態において、本明細書に提供されるような化合物及び薬剤の投与の継続は、約７日未満である。さらに別の実施形態において、投与は、約６日、約１０日、約１４日、約２８日、約２ヶ月、約６ヶ月、または約１年を超えて継続する。いくつかの事例において、継続的投薬は達成され得、必要な限り維持され得る。
本明細書で開示されるような化合物と組み合わせて使用され得る抗悪性腫瘍剤の第２のファミリーは、アルキル化型抗悪性腫瘍剤からなる。好適なアルキル化型抗悪性腫瘍剤は、塩野義２５４−Ｓ、アルド−ホスファミドアナログ、アルトレタミン、アナキシロン、Ｂｏｅｈｒｉｎｇｅｒ Ｍａｎｎｈｅｉｍ ＢＢＲ−２２０７、ベストラブシル（ｂｅｓｔｒａｂｕｃｉｌ，）、ブドチタン、湧永ＣＡ−１０２、カルボプラチン、カルムスチン、Ｃｈｉｎｏｉｎ−１３９、Ｃｈｉｎｏｉｎ−１５３、クロラムブシル、シスプラチン、シクロホスファミド、Ａｍｅｒｉｃａｎ Ｃｙａｎａｍｉｄ ＣＬ−２８６５５８、Ｓａｎｏｆｉ ＣＹ−２３３、シプラテート（ｃｙｐｌａｔａｔｅ）、Ｄｅｇｕｓｓａ Ｄ３８４、住友ＤＡＣＨＰ（Ｍｙｒ）２、ジフェニルスピロムスチン、二白金細胞増殖抑制剤、Ｅｒｂａジスタマイシン誘導体、中外ＤＷＡ−２１１４Ｒ、ＩＴＩ Ｅ０９、エルムスチン、Ｅｒｂａｍｏｎｔ ＦＣＥ−２４５１７、リン酸エストラムスチンナトリウム、ホテムスチン、Ｕｎｉｍｅｄ Ｇ Ｍ、Ｃｈｉｎｏｉｎ ＧＹＫＩ−１７２３０、ヘプスルファム（ｈｅｐｓｕｌｆａｍ）、イホスファミド、イプロプラチン、ロムスチン、マホスファミド、ミトラクトフ日本化薬ＮＫ−１２１、ＮＣＩ ＮＳＣ−２６４３９５、ＮＣＩ ＮＳＣ−３４２２１５、オキサリプラチン、Ｕｐｊｏｈｎ ＰＣＮＵ、プレドニムスチン、Ｐｒｏｔｅｒ ＰＴＴ−１１９、ラニムスチン、セムスチン、ＳｍｉｔｈＫｌｉｎｅ ＳＫ＆Ｆ−１０１７７２、ヤクルト本社ＳＮ−２２、スピロムスチン、田辺製薬ＴＡ−０７７、タウロムスチン、テモゾロミド、テロキシロン、テトラプラチン、及びトリメラモール（ｔｒｉｍｅｌａｍｏｌ）から選択され得るが、これらに限定されない。
Claims (14)
- 下記構造式を有するブリガチニブの結晶形態であって、
- ９．６、１７．２、１９．４、２０．１、２３．１、及び２７．７°２θ（±０．３°２θの偏差を有する）から選択される少なくとも２つのピークを有するｘ線粉末回折パターンを有する、請求項１に記載の結晶形態。
- ９．６、１７．２、１９．４、２０．１、２３．１、及び２７．７°２θ（±０．３°２θの偏差を有する）のピークを有するｘ線粉末回折パターンを有する、請求項１に記載の結晶形態。
- 実質的に図２に示されるｘ線粉末回折パターンを有する、請求項１に記載の結晶形態。
- 無水である、請求項１〜４のいずれか一項に記載の結晶形態。
- ２１４．５℃の開始融解温度を有する、請求項１〜５のいずれか一項に記載の結晶形態。
- ３２４１．０、３１６５．１、２９８０．０〜２７９３．２、１６１６．４〜１４１７．６、１４４１．１〜１２１９．８、１３５４．６〜１２７８．０、１３０７．４〜１１９６．１、１１６３．６〜１１３５．０、１０９４．９〜７９４．６，８６７．４、及び７６８．６〜７１６．８ｃｍ−１の周波数帯域のうちの少なくともいずれか１つを有するＦＴ−ＩＲスペクトルを有する、請求項１〜６のいずれか一項に記載の結晶形態。
- 吸湿性ではない、請求項１〜７のいずれか一項に記載の結晶形態。
- ３０℃〜１００℃で加熱すると０．２３％の質量損失を示す、請求項１〜８のいずれか一項に記載の結晶形態。
- ａ＝９．６Å、ｂ＝１０．８Å、ｃ＝１５．０Å、α＝７６°β＝８０°及びγ＝７４°のユニットセルディメンション（Ｕｎｉｔ Ｃｅｌｌ Ｄｉｍｅｎｓｉｏｎ）を有する、請求項１〜９のいずれか一項に記載の結晶形態。
- 結晶化温度を６０℃まで上昇させること、及びＮａＯＨ溶液を低速で添加すること、を含む、請求項１に記載の結晶形態の調製方法。
- 請求項１〜１０のいずれか一項に記載のブリガチニブの結晶形態、並びに薬学的に許容される担体、薬学的に許容されるビヒクル、及び薬学的に許容される賦形剤からなる群から選ばれた少なくとも１つの構成成分とを含む薬学的組成物。
- 請求項１〜１０のいずれか一項に記載のブリガチニブの結晶形態を含む、非小細胞肺癌の治療をするための薬学的組成物。
- 非小細胞肺癌の治療をするための薬剤の製造における、請求項１〜１０のいずれか一項に記載のブリガチニブの結晶形態の使用。
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| PE (1) | PE20171344A1 (ja) |
| PH (1) | PH12017500732A1 (ja) |
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| UA (1) | UA119794C2 (ja) |
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2015
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- 2015-10-21 CN CN202010394064.XA patent/CN111888368B/zh active Active
- 2015-10-21 CN CN201580069762.XA patent/CN107108559B/zh active Active
- 2015-10-21 TN TN2017000157A patent/TN2017000157A1/en unknown
- 2015-10-21 LT LTEP15787846.3T patent/LT3209647T/lt unknown
- 2015-10-21 EP EP20177579.8A patent/EP3760618A1/en active Pending
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2017
- 2017-04-18 ZA ZA2017/02737A patent/ZA201702737B/en unknown
- 2017-04-20 DO DO2017000101A patent/DOP2017000101A/es unknown
- 2017-04-20 CL CL2017000979A patent/CL2017000979A1/es unknown
- 2017-04-20 IL IL251818A patent/IL251818B/en active IP Right Grant
- 2017-04-20 PH PH12017500732A patent/PH12017500732A1/en unknown
- 2017-05-10 CO CONC2017/0004714A patent/CO2017004714A2/es unknown
- 2017-05-18 EC ECIEPI201730878A patent/ECSP17030878A/es unknown
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2019
- 2019-06-03 US US16/429,988 patent/US10934317B2/en active Active
- 2019-12-11 JP JP2019223360A patent/JP2020063276A/ja active Pending
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2020
- 2020-08-26 HR HRP20201343TT patent/HRP20201343T1/hr unknown
- 2020-09-02 CY CY20201100826T patent/CY1123295T1/el unknown
- 2020-12-16 US US17/124,407 patent/US11427605B2/en active Active
- 2020-12-31 IL IL279910A patent/IL279910A/en unknown
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2023
- 2023-08-08 US US18/366,976 patent/US20240043457A1/en not_active Abandoned
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