JP2017526744A5 - - Google Patents

Info

Publication number

JP2017526744A5

JP2017526744A5 JP2017528765A JP2017528765A JP2017526744A5 JP 2017526744 A5 JP2017526744 A5 JP 2017526744A5 JP 2017528765 A JP2017528765 A JP 2017528765A JP 2017528765 A JP2017528765 A JP 2017528765A JP 2017526744 A5 JP2017526744 A5 JP 2017526744A5

Authority

JP

Japan

Prior art keywords

liposome

peg

antifolate

poly

dspe

Prior art date

2015-08-14

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

• Espacenet
• Global Dossier
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• 239000000203 mixture Substances 0.000 claims 41
• 239000002502 liposome Substances 0.000 claims 36
• 239000004052 folic acid antagonist Substances 0.000 claims 33
• 230000003432 anti-folate effect Effects 0.000 claims 27
• 229940127074 antifolate Drugs 0.000 claims 27
• 229920001223 polyethylene glycol Polymers 0.000 claims 23
• 102000004169 proteins and genes Human genes 0.000 claims 15
• 108090000623 proteins and genes Proteins 0.000 claims 15
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 14
• 239000002202 Polyethylene glycol Substances 0.000 claims 12
• 230000000975 bioactive effect Effects 0.000 claims 12
• 239000007864 aqueous solution Substances 0.000 claims 11
• 239000003381 stabilizer Substances 0.000 claims 11
• 239000003937 drug carrier Substances 0.000 claims 8
• 238000000034 method Methods 0.000 claims 8
• HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims 7
• LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 claims 7
• PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 claims 7
• 101001105486 Homo sapiens Proteasome subunit alpha type-7 Proteins 0.000 claims 7
• 102100021201 Proteasome subunit alpha type-7 Human genes 0.000 claims 7
• HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims 7
• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims 7
• 235000012000 cholesterol Nutrition 0.000 claims 7
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims 6
• 229920000729 poly(L-lysine) polymer Polymers 0.000 claims 6
• 229920002401 polyacrylamide Polymers 0.000 claims 6
• -1 DSPE-PEG-maleimide Chemical compound 0.000 claims 4
• 239000012867 bioactive agent Substances 0.000 claims 4
• 102000006815 folate receptor Human genes 0.000 claims 4
• 108020005243 folate receptor Proteins 0.000 claims 4
• 239000002904 solvent Substances 0.000 claims 4
• 210000004881 tumor cell Anatomy 0.000 claims 4
• 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 claims 3
• 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 claims 3
• 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 claims 3
• 150000008575 L-amino acids Chemical class 0.000 claims 3
• 229930195725 Mannitol Natural products 0.000 claims 3
• 239000004372 Polyvinyl alcohol Substances 0.000 claims 3
• 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 claims 3
• 229930006000 Sucrose Natural products 0.000 claims 3
• 239000000427 antigen Substances 0.000 claims 3
• 102000036639 antigens Human genes 0.000 claims 3
• 108091007433 antigens Proteins 0.000 claims 3
• 229920006187 aquazol Polymers 0.000 claims 3
• 239000012861 aquazol Substances 0.000 claims 3
• 229920005601 base polymer Polymers 0.000 claims 3
• 229960001438 immunostimulant agent Drugs 0.000 claims 3
• 239000003022 immunostimulating agent Substances 0.000 claims 3
• 230000003308 immunostimulating effect Effects 0.000 claims 3
• 239000000594 mannitol Substances 0.000 claims 3
• 235000010355 mannitol Nutrition 0.000 claims 3
• 230000007935 neutral effect Effects 0.000 claims 3
• 229920000773 poly(2-methyl-2-oxazoline) polymer Polymers 0.000 claims 3
• 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 claims 3
• 229920002187 poly[N-2-(hydroxypropyl) methacrylamide] polymer Polymers 0.000 claims 3
• 229920002451 polyvinyl alcohol Polymers 0.000 claims 3
• 239000000600 sorbitol Substances 0.000 claims 3
• 239000005720 sucrose Substances 0.000 claims 3
• TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 claims 2
• 229920002498 Beta-glucan Polymers 0.000 claims 2
• 102000010451 Folate receptor alpha Human genes 0.000 claims 2
• 108050001931 Folate receptor alpha Proteins 0.000 claims 2
• 102000010449 Folate receptor beta Human genes 0.000 claims 2
• 108050001930 Folate receptor beta Proteins 0.000 claims 2
• 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 2
• PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims 2
• 101710160107 Outer membrane protein A Proteins 0.000 claims 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims 2
• 102100023119 Sperm-egg fusion protein Juno Human genes 0.000 claims 2
• 101710093389 Sperm-egg fusion protein Juno Proteins 0.000 claims 2
• 229960003896 aminopterin Drugs 0.000 claims 2
• 239000008365 aqueous carrier Substances 0.000 claims 2
• 239000003125 aqueous solvent Substances 0.000 claims 2
• VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims 2
• 239000001639 calcium acetate Substances 0.000 claims 2
• 229960005147 calcium acetate Drugs 0.000 claims 2
• 235000011092 calcium acetate Nutrition 0.000 claims 2
• 239000007979 citrate buffer Substances 0.000 claims 2
• CTSPAMFJBXKSOY-UHFFFAOYSA-N ellipticine Chemical group N1=CC=C2C(C)=C(NC=3C4=CC=CC=3)C4=C(C)C2=C1 CTSPAMFJBXKSOY-UHFFFAOYSA-N 0.000 claims 2
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 claims 2
• 238000004108 freeze drying Methods 0.000 claims 2
• 150000002632 lipids Chemical class 0.000 claims 2
• 239000012528 membrane Substances 0.000 claims 2
• 229960000485 methotrexate Drugs 0.000 claims 2
• 229960005079 pemetrexed Drugs 0.000 claims 2
• WBXPDJSOTKVWSJ-ZDUSSCGKSA-L pemetrexed(2-) Chemical group C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-L 0.000 claims 2
• 239000003944 phosphoribosylglycinamide formyltransferase inhibitor Substances 0.000 claims 2
• OGSBUKJUDHAQEA-WMCAAGNKSA-N pralatrexate Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CC(CC#C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OGSBUKJUDHAQEA-WMCAAGNKSA-N 0.000 claims 2
• 229960000214 pralatrexate Drugs 0.000 claims 2
• SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 claims 2
• 229960005385 proguanil Drugs 0.000 claims 2
• WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 claims 2
• 229960000611 pyrimethamine Drugs 0.000 claims 2
• 150000004944 pyrrolopyrimidines Chemical class 0.000 claims 2
• 239000001632 sodium acetate Substances 0.000 claims 2
• 235000017281 sodium acetate Nutrition 0.000 claims 2
• ZUQBAQVRAURMCL-DOMZBBRYSA-N (2s)-2-[[4-[2-[(6r)-2-amino-4-oxo-5,6,7,8-tetrahydro-1h-pyrido[2,3-d]pyrimidin-6-yl]ethyl]benzoyl]amino]pentanedioic acid Chemical compound C([C@@H]1CC=2C(=O)N=C(NC=2NC1)N)CC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZUQBAQVRAURMCL-DOMZBBRYSA-N 0.000 claims 1
• FYGDTMLNYKFZSV-URKRLVJHSA-N (2s,3r,4s,5s,6r)-2-[(2r,4r,5r,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5r,6s)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1[C@@H](CO)O[C@@H](OC2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-URKRLVJHSA-N 0.000 claims 1
• 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 claims 1
• 108010047041 Complementarity Determining Regions Proteins 0.000 claims 1
• 229920001503 Glucan Polymers 0.000 claims 1
• ZIXGXMMUKPLXBB-UHFFFAOYSA-N Guatambuinine Natural products N1C2=CC=CC=C2C2=C1C(C)=C1C=CN=C(C)C1=C2 ZIXGXMMUKPLXBB-UHFFFAOYSA-N 0.000 claims 1
• 229930012538 Paclitaxel Natural products 0.000 claims 1
• SUYXJDLXGFPMCQ-INIZCTEOSA-N SJ000287331 Natural products CC1=c2cnccc2=C(C)C2=Nc3ccccc3[C@H]12 SUYXJDLXGFPMCQ-INIZCTEOSA-N 0.000 claims 1
• 108010003723 Single-Domain Antibodies Proteins 0.000 claims 1
• 239000002671 adjuvant Substances 0.000 claims 1
• 125000000129 anionic group Chemical group 0.000 claims 1
• 239000012830 cancer therapeutic Substances 0.000 claims 1
• 210000004027 cell Anatomy 0.000 claims 1
• 239000002577 cryoprotective agent Substances 0.000 claims 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 claims 1
• 239000012634 fragment Substances 0.000 claims 1
• 229950000909 lometrexol Drugs 0.000 claims 1
• 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims 1
• 230000003211 malignant effect Effects 0.000 claims 1
• 210000004882 non-tumor cell Anatomy 0.000 claims 1
• 229960001592 paclitaxel Drugs 0.000 claims 1
• 230000008685 targeting Effects 0.000 claims 1
• 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 1
• 229940124597 therapeutic agent Drugs 0.000 claims 1
• IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 claims 1
• 229960001082 trimethoprim Drugs 0.000 claims 1