ES2673165T3 - Dispersión sólida amorfa para la utilización en el tratamiento del cáncer cerebral - Google Patents
Dispersión sólida amorfa para la utilización en el tratamiento del cáncer cerebral Download PDFInfo
- Publication number
- ES2673165T3 ES2673165T3 ES13714497.8T ES13714497T ES2673165T3 ES 2673165 T3 ES2673165 T3 ES 2673165T3 ES 13714497 T ES13714497 T ES 13714497T ES 2673165 T3 ES2673165 T3 ES 2673165T3
- Authority
- ES
- Spain
- Prior art keywords
- certain embodiments
- dispersion
- yloxy
- methylphenyl
- triazolo
- 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.)
- Active
Links
- 208000003174 Brain Neoplasms Diseases 0.000 title claims abstract description 82
- 239000006185 dispersion Substances 0.000 title claims abstract description 82
- 238000011282 treatment Methods 0.000 title claims abstract description 76
- 239000007787 solid Substances 0.000 title claims abstract description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 124
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 64
- -1 (4 - ((4 - ([1,2,4] triazolo [1,5-a] pyridin-7-yloxy)) - 3- methylphenyl) amino) quinazolin-6-yl Chemical group 0.000 claims abstract description 54
- 229920000642 polymer Polymers 0.000 claims abstract description 34
- 210000004556 brain Anatomy 0.000 claims abstract description 23
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 17
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 17
- 230000003321 amplification Effects 0.000 claims abstract description 11
- 230000001394 metastastic effect Effects 0.000 claims abstract description 11
- 206010061289 metastatic neoplasm Diseases 0.000 claims abstract description 11
- 238000003199 nucleic acid amplification method Methods 0.000 claims abstract description 11
- 230000002018 overexpression Effects 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims description 75
- 239000004815 dispersion polymer Substances 0.000 claims description 41
- 239000003814 drug Substances 0.000 claims description 40
- 125000004547 quinazolin-6-yl group Chemical group N1=CN=CC2=CC(=CC=C12)* 0.000 claims description 26
- FYUWIEKAVLOHSE-UHFFFAOYSA-N ethenyl acetate;1-ethenylpyrrolidin-2-one Chemical compound CC(=O)OC=C.C=CN1CCCC1=O FYUWIEKAVLOHSE-UHFFFAOYSA-N 0.000 claims description 25
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 25
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 21
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 21
- 239000003826 tablet Substances 0.000 claims description 18
- 229920001577 copolymer Polymers 0.000 claims description 17
- ZUAAPNNKRHMPKG-UHFFFAOYSA-N acetic acid;butanedioic acid;methanol;propane-1,2-diol Chemical compound OC.CC(O)=O.CC(O)CO.OC(=O)CCC(O)=O ZUAAPNNKRHMPKG-UHFFFAOYSA-N 0.000 claims description 16
- 238000001959 radiotherapy Methods 0.000 claims description 15
- RNWDENXDCQXZLH-UHFFFAOYSA-N quinazoline-4,6-diamine Chemical compound N1=CN=C(N)C2=CC(N)=CC=C21 RNWDENXDCQXZLH-UHFFFAOYSA-N 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 11
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 9
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 9
- 229960000575 trastuzumab Drugs 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 8
- 229930012538 Paclitaxel Natural products 0.000 claims description 8
- 229960000397 bevacizumab Drugs 0.000 claims description 8
- 229960001592 paclitaxel Drugs 0.000 claims description 8
- 238000001356 surgical procedure Methods 0.000 claims description 8
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 8
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 7
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 7
- DACWQSNZECJJGG-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=CC=CN2N=CN=C21 DACWQSNZECJJGG-UHFFFAOYSA-N 0.000 claims description 7
- 229960004117 capecitabine Drugs 0.000 claims description 7
- 229920002554 vinyl polymer Polymers 0.000 claims description 7
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 6
- 229920003134 Eudragit® polymer Polymers 0.000 claims description 6
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 6
- 229960003668 docetaxel Drugs 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 5
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 5
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 5
- 229960005167 everolimus Drugs 0.000 claims description 5
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 5
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 4
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 4
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 4
- 229960004562 carboplatin Drugs 0.000 claims description 4
- 190000008236 carboplatin Chemical compound 0.000 claims description 4
- 229920002301 cellulose acetate Polymers 0.000 claims description 4
- 238000002512 chemotherapy Methods 0.000 claims description 4
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 claims description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 4
- 229960002247 lomustine Drugs 0.000 claims description 4
- 229960000485 methotrexate Drugs 0.000 claims description 4
- 229920002689 polyvinyl acetate Polymers 0.000 claims description 4
- 239000011118 polyvinyl acetate Substances 0.000 claims description 4
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 4
- 229960000624 procarbazine Drugs 0.000 claims description 4
- 230000005855 radiation Effects 0.000 claims description 4
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 3
- 102000009027 Albumins Human genes 0.000 claims description 3
- 108010088751 Albumins Proteins 0.000 claims description 3
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 claims description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 3
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 3
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 claims description 3
- 229940050528 albumin Drugs 0.000 claims description 3
- 229960004397 cyclophosphamide Drugs 0.000 claims description 3
- 229960004679 doxorubicin Drugs 0.000 claims description 3
- 229960001904 epirubicin Drugs 0.000 claims description 3
- 229960000255 exemestane Drugs 0.000 claims description 3
- 229960002949 fluorouracil Drugs 0.000 claims description 3
- 229920000609 methyl cellulose Polymers 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 239000002105 nanoparticle Substances 0.000 claims description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 claims description 3
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 3
- 229960004528 vincristine Drugs 0.000 claims description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 2
- UGZICOVULPINFH-UHFFFAOYSA-N acetic acid;butanoic acid Chemical compound CC(O)=O.CCCC(O)=O UGZICOVULPINFH-UHFFFAOYSA-N 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 229960002932 anastrozole Drugs 0.000 claims description 2
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 claims description 2
- 238000001574 biopsy Methods 0.000 claims description 2
- 229920001400 block copolymer Polymers 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229960005243 carmustine Drugs 0.000 claims description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
- 229960004316 cisplatin Drugs 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 238000001794 hormone therapy Methods 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims description 2
- 239000007943 implant Substances 0.000 claims description 2
- 229960002087 pertuzumab Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims description 2
- 229920006316 polyvinylpyrrolidine Polymers 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims description 2
- 210000005005 sentinel lymph node Anatomy 0.000 claims description 2
- 238000002719 stereotactic radiosurgery Methods 0.000 claims description 2
- 238000002626 targeted therapy Methods 0.000 claims description 2
- 229960004964 temozolomide Drugs 0.000 claims description 2
- 229960005026 toremifene Drugs 0.000 claims description 2
- 229960001612 trastuzumab emtansine Drugs 0.000 claims description 2
- 125000005591 trimellitate group Chemical group 0.000 claims description 2
- PWATWSYOIIXYMA-UHFFFAOYSA-N Pentylbenzene Chemical compound CCCCCC1=CC=CC=C1 PWATWSYOIIXYMA-UHFFFAOYSA-N 0.000 claims 1
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 claims 1
- 229920000578 graft copolymer Polymers 0.000 claims 1
- 229920013819 hydroxyethyl ethylcellulose Polymers 0.000 claims 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
- 239000006186 oral dosage form Substances 0.000 claims 1
- 238000002203 pretreatment Methods 0.000 claims 1
- 229920006163 vinyl copolymer Polymers 0.000 claims 1
- SDEAXTCZPQIFQM-UHFFFAOYSA-N 6-n-(4,4-dimethyl-5h-1,3-oxazol-2-yl)-4-n-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]quinazoline-4,6-diamine Chemical compound C=1C=C(OC2=CC3=NC=NN3C=C2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2NC1=NC(C)(C)CO1 SDEAXTCZPQIFQM-UHFFFAOYSA-N 0.000 abstract description 42
- 239000007962 solid dispersion Substances 0.000 description 129
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- 239000002904 solvent Substances 0.000 description 49
- 241000699670 Mus sp. Species 0.000 description 33
- 239000007921 spray Substances 0.000 description 33
- 239000000126 substance Substances 0.000 description 33
- 230000000144 pharmacologic effect Effects 0.000 description 30
- 229940079593 drug Drugs 0.000 description 28
- 238000001035 drying Methods 0.000 description 27
- 239000008194 pharmaceutical composition Substances 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- 239000007789 gas Substances 0.000 description 23
- 239000007884 disintegrant Substances 0.000 description 22
- 241000894007 species Species 0.000 description 21
- 239000000314 lubricant Substances 0.000 description 20
- 238000001694 spray drying Methods 0.000 description 20
- 229920008347 Cellulose acetate propionate Polymers 0.000 description 19
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 16
- 229960004853 betadex Drugs 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 239000003085 diluting agent Substances 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 239000011230 binding agent Substances 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 229960004891 lapatinib Drugs 0.000 description 13
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- 125000003944 tolyl group Chemical group 0.000 description 13
- TWEMIPSDKADNMC-UHFFFAOYSA-N [4-methyl-2-[[4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)anilino]quinazolin-6-yl]amino]-5h-1,3-oxazol-4-yl]methanol Chemical compound C=1C=C(OC2=CC3=NC=NN3C=C2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2NC1=NC(C)(CO)CO1 TWEMIPSDKADNMC-UHFFFAOYSA-N 0.000 description 12
- 238000004090 dissolution Methods 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 229920003139 Eudragit® L 100 Polymers 0.000 description 11
- 239000007853 buffer solution Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 239000008363 phosphate buffer Substances 0.000 description 11
- 238000007922 dissolution test Methods 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 210000004881 tumor cell Anatomy 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 206010003571 Astrocytoma Diseases 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 108010079943 Pentagastrin Proteins 0.000 description 6
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 229960000913 crospovidone Drugs 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 6
- 229960001596 famotidine Drugs 0.000 description 6
- 206010017758 gastric cancer Diseases 0.000 description 6
- ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 6
- 229960000444 pentagastrin Drugs 0.000 description 6
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 6
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 6
- 239000001103 potassium chloride Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
- 239000012527 feed solution Substances 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 208000010749 gastric carcinoma Diseases 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 238000007917 intracranial administration Methods 0.000 description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 5
- 239000008108 microcrystalline cellulose Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000013557 residual solvent Substances 0.000 description 5
- 201000000498 stomach carcinoma Diseases 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 206010059282 Metastases to central nervous system Diseases 0.000 description 4
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
- 208000013938 anaplastic oligoastrocytoma Diseases 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 206010027191 meningioma Diseases 0.000 description 4
- 230000000926 neurological effect Effects 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 3
- 208000000172 Medulloblastoma Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 201000010133 Oligodendroglioma Diseases 0.000 description 3
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 206010002224 anaplastic astrocytoma Diseases 0.000 description 3
- 230000008499 blood brain barrier function Effects 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 208000022080 low-grade astrocytoma Diseases 0.000 description 3
- 206010073131 oligoastrocytoma Diseases 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000009492 tablet coating Methods 0.000 description 3
- 239000002700 tablet coating Substances 0.000 description 3
- YQXFIPBLJLFCTO-UHFFFAOYSA-N 2-(4,4-dimethyl-5h-1,3-oxazol-2-yl)quinazoline-4,6-diamine Chemical compound CC1(C)COC(C=2N=C3C=CC(N)=CC3=C(N)N=2)=N1 YQXFIPBLJLFCTO-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- 206010073128 Anaplastic oligodendroglioma Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 206010006143 Brain stem glioma Diseases 0.000 description 2
- 206010055113 Breast cancer metastatic Diseases 0.000 description 2
- 201000009047 Chordoma Diseases 0.000 description 2
- 208000009798 Craniopharyngioma Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 206010014967 Ependymoma Diseases 0.000 description 2
- 208000000527 Germinoma Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 206010073338 Optic glioma Diseases 0.000 description 2
- 201000007286 Pilocytic astrocytoma Diseases 0.000 description 2
- 206010057846 Primitive neuroectodermal tumour Diseases 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 208000001662 Subependymal Glioma Diseases 0.000 description 2
- 208000014070 Vestibular schwannoma Diseases 0.000 description 2
- 208000004064 acoustic neuroma Diseases 0.000 description 2
- 239000003570 air Substances 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 229960003649 eribulin Drugs 0.000 description 2
- UFNVPOGXISZXJD-XJPMSQCNSA-N eribulin Chemical compound C([C@H]1CC[C@@H]2O[C@@H]3[C@H]4O[C@H]5C[C@](O[C@H]4[C@H]2O1)(O[C@@H]53)CC[C@@H]1O[C@H](C(C1)=C)CC1)C(=O)C[C@@H]2[C@@H](OC)[C@@H](C[C@H](O)CN)O[C@H]2C[C@@H]2C(=C)[C@H](C)C[C@H]1O2 UFNVPOGXISZXJD-XJPMSQCNSA-N 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 201000003115 germ cell cancer Diseases 0.000 description 2
- 208000002409 gliosarcoma Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 208000007538 neurilemmoma Diseases 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 208000008511 optic nerve glioma Diseases 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 206010039667 schwannoma Diseases 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 208000030819 subependymoma Diseases 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- HZCZAJGNAXZBTF-UHFFFAOYSA-N 1-(1-hydroxy-2-methylpropan-2-yl)-3-[4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)anilino]quinazolin-6-yl]thiourea Chemical compound C1=CN2N=CN=C2C=C1OC1=CC=C(NC=2C3=CC(NC(=S)NC(C)(C)CO)=CC=C3N=CN=2)C=C1C HZCZAJGNAXZBTF-UHFFFAOYSA-N 0.000 description 1
- VNKYLVIITITJCY-UHFFFAOYSA-N 1-[3-cyano-4-(dimethylaminomethylideneamino)phenyl]-3-(1-hydroxy-2-methylpropan-2-yl)thiourea Chemical compound CN(C)C=NC1=CC=C(NC(=S)NC(C)(C)CO)C=C1C#N VNKYLVIITITJCY-UHFFFAOYSA-N 0.000 description 1
- DFMSLMUVJUMZPA-UHFFFAOYSA-N 3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)aniline Chemical compound CC1=CC(N)=CC=C1OC1=CC2=NC=NN2C=C1 DFMSLMUVJUMZPA-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- QVMNYGOVNWWFKF-UHFFFAOYSA-N 6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]-n-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]quinazolin-4-amine Chemical compound C=1C=C(OC2=CC3=NC=NN3C=C2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C1=CC=C(CNCCS(C)(=O)=O)O1 QVMNYGOVNWWFKF-UHFFFAOYSA-N 0.000 description 1
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 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 1
- 108010019673 Darbepoetin alfa Proteins 0.000 description 1
- 108010074604 Epoetin Alfa Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010029961 Filgrastim Proteins 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 229940125497 HER2 kinase inhibitor Drugs 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010066882 Metastatic salivary gland cancer Diseases 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 102000018658 Myotonin-Protein Kinase Human genes 0.000 description 1
- 108010052185 Myotonin-Protein Kinase Proteins 0.000 description 1
- 239000006057 Non-nutritive feed additive Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 108010050144 Triptorelin Pamoate Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229960005029 darbepoetin alfa Drugs 0.000 description 1
- 239000008380 degradant Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229960001251 denosumab Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000011833 dog model Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000002036 drum drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229960003388 epoetin alfa Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 235000020937 fasting conditions Nutrition 0.000 description 1
- 229960004177 filgrastim Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229960001751 fluoxymesterone Drugs 0.000 description 1
- YLRFCQOZQXIBAB-RBZZARIASA-N fluoxymesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)C[C@@H]2O YLRFCQOZQXIBAB-RBZZARIASA-N 0.000 description 1
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 229960002014 ixabepilone Drugs 0.000 description 1
- FABUFPQFXZVHFB-CFWQTKTJSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-CFWQTKTJSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001786 megestrol Drugs 0.000 description 1
- JBVNBBXAMBZTMQ-CEGNMAFCSA-N megestrol Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 JBVNBBXAMBZTMQ-CEGNMAFCSA-N 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 201000004058 mixed glioma Diseases 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 229950008835 neratinib Drugs 0.000 description 1
- ZNHPZUKZSNBOSQ-BQYQJAHWSA-N neratinib Chemical compound C=12C=C(NC\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZNHPZUKZSNBOSQ-BQYQJAHWSA-N 0.000 description 1
- 208000023833 nerve sheath neoplasm Diseases 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229940046231 pamidronate Drugs 0.000 description 1
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- HQQSBEDKMRHYME-UHFFFAOYSA-N pefloxacin mesylate Chemical compound [H+].CS([O-])(=O)=O.C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)CC1 HQQSBEDKMRHYME-UHFFFAOYSA-N 0.000 description 1
- 108010044644 pegfilgrastim Proteins 0.000 description 1
- 229960001373 pegfilgrastim Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 201000005528 peripheral nervous system neoplasm Diseases 0.000 description 1
- 235000020030 perry Nutrition 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 238000001907 polarising light microscopy Methods 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 238000002661 proton therapy Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
- 229960004824 triptorelin Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261615082P | 2012-03-23 | 2012-03-23 | |
| US201261615082P | 2012-03-23 | ||
| PCT/US2013/033751 WO2013142875A1 (en) | 2012-03-23 | 2013-03-25 | Treatment of brain cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2673165T3 true ES2673165T3 (es) | 2018-06-20 |
Family
ID=48048296
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18162971T Active ES2855142T3 (es) | 2012-03-23 | 2013-03-25 | Compuestos para la utilización en el tratamiento de las metástasis cerebrales en un paciente con cáncer de mama ErbB2+ |
| ES13714497.8T Active ES2673165T3 (es) | 2012-03-23 | 2013-03-25 | Dispersión sólida amorfa para la utilización en el tratamiento del cáncer cerebral |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18162971T Active ES2855142T3 (es) | 2012-03-23 | 2013-03-25 | Compuestos para la utilización en el tratamiento de las metástasis cerebrales en un paciente con cáncer de mama ErbB2+ |
Country Status (30)
| Country | Link |
|---|---|
| US (3) | US20150110780A1 (OSRAM) |
| EP (4) | EP2827900B1 (OSRAM) |
| JP (6) | JP2015514075A (OSRAM) |
| KR (3) | KR102317166B1 (OSRAM) |
| CN (2) | CN109223791A (OSRAM) |
| AU (4) | AU2013234921A1 (OSRAM) |
| CA (1) | CA2867723C (OSRAM) |
| CL (1) | CL2014002497A1 (OSRAM) |
| CO (1) | CO7071139A2 (OSRAM) |
| CY (2) | CY1120204T1 (OSRAM) |
| DK (2) | DK3400943T3 (OSRAM) |
| ES (2) | ES2855142T3 (OSRAM) |
| HR (1) | HRP20180659T1 (OSRAM) |
| HU (2) | HUE037966T2 (OSRAM) |
| IL (3) | IL234627B (OSRAM) |
| LT (1) | LT2827900T (OSRAM) |
| MX (1) | MX354024B (OSRAM) |
| MY (2) | MY174883A (OSRAM) |
| NZ (4) | NZ630843A (OSRAM) |
| PH (2) | PH12021550360A1 (OSRAM) |
| PL (2) | PL2827900T3 (OSRAM) |
| PT (2) | PT2827900T (OSRAM) |
| RS (1) | RS57140B1 (OSRAM) |
| RU (2) | RU2672575C2 (OSRAM) |
| SG (1) | SG11201405954YA (OSRAM) |
| SI (2) | SI2827900T1 (OSRAM) |
| SM (1) | SMT201800251T1 (OSRAM) |
| TR (1) | TR201808450T4 (OSRAM) |
| UA (1) | UA122044C2 (OSRAM) |
| WO (1) | WO2013142875A1 (OSRAM) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2012322039C1 (en) | 2011-10-14 | 2021-04-29 | Array Biopharma Inc. | Solid dispersions of a Erb2 (HER2) inhibitor |
| KR102061917B1 (ko) | 2011-10-14 | 2020-01-02 | 어레이 바이오파마 인크. | 선택적인 herb2 저해제인 arry-380의 다형체 및 이를 함유하는 약제학적 조성물 |
| SI2827900T1 (en) | 2012-03-23 | 2018-06-29 | Array Biopharma, Inc. | Amorphous solid dispersion for use in the treatment of brain cancer |
| US11078272B2 (en) | 2017-03-09 | 2021-08-03 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of pediatric brain tumors with targeting of CD47 pathway |
| JP7328151B2 (ja) | 2017-04-28 | 2023-08-16 | シージェン インコーポレイテッド | Ｈｅｒ２陽性がんの処置 |
| KR102708050B1 (ko) | 2018-01-31 | 2024-09-24 | 데시페라 파마슈티칼스, 엘엘씨. | 비만 세포증의 치료를 위한 병용 요법 |
| WO2019152711A1 (en) | 2018-01-31 | 2019-08-08 | Diciphera Pharmaceuticals Llc. | Combination therapy for the treatment of gastrointestinal stromal tumors |
| JP7139448B2 (ja) * | 2018-04-09 | 2022-09-20 | ノボキュア ゲーエムベーハー | ＴＴＦｉｅｌｄｓ及びオーロラキナーゼ阻害剤による腫瘍の治療 |
| CN109942576B (zh) * | 2019-03-07 | 2020-09-11 | 上海工程技术大学 | Irbinitinib及中间体的制备方法 |
| CN111825604A (zh) * | 2019-04-16 | 2020-10-27 | 宁波药腾医药科技有限公司 | 一种图卡替尼及其中间产物的合成方法 |
| CA3150433A1 (en) | 2019-08-12 | 2021-02-18 | Deciphera Pharmaceuticals, Llc | Ripretinib for treating gastrointestinal stromal tumors |
| FI4084778T3 (fi) * | 2019-12-30 | 2023-12-18 | Deciphera Pharmaceuticals Llc | Amorfisia kinaasi-inhibiittoriformulaatioita ja menetelmiä niiden käyttämiseksi |
| CN115243681B (zh) | 2019-12-30 | 2024-08-16 | 德西费拉制药有限责任公司 | 1-(4-溴-5-(1-乙基-7-(甲氨基)-2-侧氧基-1,2-二氢-1,6-萘啶-3-基)-2-氟苯基)-3-苯基脲的组合物 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH690163A5 (fr) * | 1995-07-28 | 2000-05-31 | Symphar Sa | Dérivés gem-diphosphonates substitués utiles en tant qu'agents anti-cancers. |
| US6350786B1 (en) | 1998-09-22 | 2002-02-26 | Hoffmann-La Roche Inc. | Stable complexes of poorly soluble compounds in ionic polymers |
| RU2255765C2 (ru) * | 2000-01-21 | 2005-07-10 | Чилдренз Хоспитал Лос-Анджелес | Способ ингибирования роста опухолей головного мозга с помощью отобранных антагонистов интегринов |
| WO2001091794A2 (en) | 2000-05-30 | 2001-12-06 | Virginia Commonwealth University | Vitamin d3 analogs as radiosensitizers for the treatment of cancer |
| KR100953246B1 (ko) | 2003-08-14 | 2010-04-16 | 어레이 바이오파마 인크. | 수용체 티로신 키나아제 억제제로서의 퀴나졸린 유사체 |
| US20100063074A1 (en) | 2004-06-03 | 2010-03-11 | Berger Mark S | Cancer Treatment Method |
| CN1989112A (zh) * | 2004-06-03 | 2007-06-27 | 史密丝克莱恩比彻姆（科克）有限公司 | 癌症治疗方法 |
| DE602006009968D1 (de) | 2005-11-15 | 2009-12-03 | Array Biopharma Inc | N4-phenyl-chinazolin-4-aminderivate und verwandte verbindungen als inhibitoren der erbb-typ-i-rezeptortyrosinkinase zur behandlung hyperproliferativer krankheiten |
| AU2007235199B8 (en) | 2006-01-31 | 2010-10-28 | Novartis Ag | IL-17 antagonistic antibodies for treating cancer |
| JP2010540460A (ja) * | 2007-09-24 | 2010-12-24 | トラガラ ファーマシューティカルズ，インク． | ＣＯＸ‐２阻害薬と抗ＨＥＲ２［ＥｒｂＢ２］抗体の混合物又はＣＯＸ‐２阻害薬とＨＥＲ２［ＥｒｂＢ２］受容体チロシンキナーゼ阻害薬の混合物を用いた癌の治療 |
| HUE035182T2 (hu) | 2008-03-18 | 2018-05-02 | Genentech Inc | Anti-HER2 antitest-hatóanyag-konjugátum és pertuzumab kombinációi |
| AU2012322039C1 (en) | 2011-10-14 | 2021-04-29 | Array Biopharma Inc. | Solid dispersions of a Erb2 (HER2) inhibitor |
| KR102061917B1 (ko) | 2011-10-14 | 2020-01-02 | 어레이 바이오파마 인크. | 선택적인 herb2 저해제인 arry-380의 다형체 및 이를 함유하는 약제학적 조성물 |
| SI2827900T1 (en) | 2012-03-23 | 2018-06-29 | Array Biopharma, Inc. | Amorphous solid dispersion for use in the treatment of brain cancer |
-
2013
- 2013-03-25 SI SI201331019T patent/SI2827900T1/en unknown
- 2013-03-25 RU RU2014142700A patent/RU2672575C2/ru active
- 2013-03-25 PL PL13714497T patent/PL2827900T3/pl unknown
- 2013-03-25 PT PT137144978T patent/PT2827900T/pt unknown
- 2013-03-25 WO PCT/US2013/033751 patent/WO2013142875A1/en not_active Ceased
- 2013-03-25 CN CN201811150918.9A patent/CN109223791A/zh active Pending
- 2013-03-25 EP EP13714497.8A patent/EP2827900B1/en active Active
- 2013-03-25 EP EP23163332.2A patent/EP4252855A3/en not_active Withdrawn
- 2013-03-25 JP JP2015501952A patent/JP2015514075A/ja active Pending
- 2013-03-25 RU RU2018138976A patent/RU2018138976A/ru unknown
- 2013-03-25 SI SI201331844T patent/SI3400943T1/sl unknown
- 2013-03-25 RS RS20180484A patent/RS57140B1/sr unknown
- 2013-03-25 KR KR1020207027176A patent/KR102317166B1/ko active Active
- 2013-03-25 CA CA2867723A patent/CA2867723C/en active Active
- 2013-03-25 US US14/387,533 patent/US20150110780A1/en not_active Abandoned
- 2013-03-25 UA UAA201411479A patent/UA122044C2/uk unknown
- 2013-03-25 NZ NZ630843A patent/NZ630843A/en unknown
- 2013-03-25 SM SM20180251T patent/SMT201800251T1/it unknown
- 2013-03-25 HU HUE13714497A patent/HUE037966T2/hu unknown
- 2013-03-25 ES ES18162971T patent/ES2855142T3/es active Active
- 2013-03-25 NZ NZ756264A patent/NZ756264A/en unknown
- 2013-03-25 SG SG11201405954YA patent/SG11201405954YA/en unknown
- 2013-03-25 DK DK18162971.8T patent/DK3400943T3/da active
- 2013-03-25 NZ NZ724544A patent/NZ724544A/en unknown
- 2013-03-25 MY MYPI2014702686A patent/MY174883A/en unknown
- 2013-03-25 CN CN201380015856.XA patent/CN104203279B/zh active Active
- 2013-03-25 PT PT181629718T patent/PT3400943T/pt unknown
- 2013-03-25 KR KR1020217033686A patent/KR102490961B1/ko active Active
- 2013-03-25 LT LTEP13714497.8T patent/LT2827900T/lt unknown
- 2013-03-25 EP EP18162971.8A patent/EP3400943B1/en not_active Revoked
- 2013-03-25 DK DK13714497.8T patent/DK2827900T3/en active
- 2013-03-25 HU HUE18162971A patent/HUE053156T2/hu unknown
- 2013-03-25 KR KR1020147029340A patent/KR102160462B1/ko active Active
- 2013-03-25 HR HRP20180659TT patent/HRP20180659T1/hr unknown
- 2013-03-25 EP EP20210661.3A patent/EP3842044A1/en not_active Withdrawn
- 2013-03-25 PL PL18162971T patent/PL3400943T3/pl unknown
- 2013-03-25 NZ NZ74161513A patent/NZ741615A/en unknown
- 2013-03-25 ES ES13714497.8T patent/ES2673165T3/es active Active
- 2013-03-25 MY MYPI2019003395A patent/MY202114A/en unknown
- 2013-03-25 AU AU2013234921A patent/AU2013234921A1/en not_active Abandoned
- 2013-03-25 TR TR2018/08450T patent/TR201808450T4/tr unknown
- 2013-03-25 MX MX2014011437A patent/MX354024B/es active IP Right Grant
- 2013-03-25 PH PH1/2021/550360A patent/PH12021550360A1/en unknown
-
2014
- 2014-09-12 PH PH12014502032A patent/PH12014502032A1/en unknown
- 2014-09-14 IL IL234627A patent/IL234627B/en active IP Right Grant
- 2014-09-19 CO CO14208829A patent/CO7071139A2/es unknown
- 2014-09-22 CL CL2014002497A patent/CL2014002497A1/es unknown
-
2017
- 2017-05-25 JP JP2017103957A patent/JP2017141302A/ja active Pending
- 2017-12-06 AU AU2017272232A patent/AU2017272232C1/en active Active
-
2018
- 2018-05-14 CY CY20181100493T patent/CY1120204T1/el unknown
- 2018-09-06 IL IL261659A patent/IL261659A/en unknown
-
2019
- 2019-02-27 JP JP2019034250A patent/JP6898960B2/ja active Active
- 2019-05-02 US US16/402,068 patent/US11504370B2/en active Active
- 2019-05-23 AU AU2019203618A patent/AU2019203618B2/en active Active
- 2019-09-09 IL IL269205A patent/IL269205B/en active IP Right Grant
-
2021
- 2021-02-16 CY CY20211100126T patent/CY1123837T1/el unknown
- 2021-06-11 JP JP2021097676A patent/JP2021178820A/ja active Pending
- 2021-11-01 AU AU2021261849A patent/AU2021261849A1/en not_active Abandoned
-
2022
- 2022-10-28 US US17/975,709 patent/US20230190749A1/en active Pending
- 2022-11-04 JP JP2022177278A patent/JP7404485B2/ja active Active
-
2023
- 2023-12-13 JP JP2023209972A patent/JP2024019526A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2673165T3 (es) | Dispersión sólida amorfa para la utilización en el tratamiento del cáncer cerebral | |
| CA2985379A1 (en) | Micronized pharmaceutical compositions for treatment of angiogenisis conditions | |
| HK40102024A (en) | Compounds for use in the treatment of brain metastases in a patient with erbb2+ breast cancer | |
| HK40000406B (en) | Compounds for use in the treatment of brain metastases in a patient with erbb2+ breast cancer | |
| HK40000406A (en) | Compounds for use in the treatment of brain metastases in a patient with erbb2+ breast cancer | |
| HK40055793A (en) | Compounds for use in the treatment of brain metastases in a patient with erbb2+ breast cancer | |
| HK1206276B (en) | Amorphous solid dispersion for use in the treatment of brain cancer |