PT1863448E - Novas composições de lipossomas - Google Patents
Novas composições de lipossomas Download PDFInfo
- Publication number
- PT1863448E PT1863448E PT67377937T PT06737793T PT1863448E PT 1863448 E PT1863448 E PT 1863448E PT 67377937 T PT67377937 T PT 67377937T PT 06737793 T PT06737793 T PT 06737793T PT 1863448 E PT1863448 E PT 1863448E
- Authority
- PT
- Portugal
- Prior art keywords
- phosphatidyl ethanolamine
- liposome
- derivatized
- dicarboxylic acid
- lipid
- Prior art date
Links
- 239000002502 liposome Substances 0.000 title claims description 717
- 239000000203 mixture Substances 0.000 title claims description 441
- 150000002632 lipids Chemical class 0.000 claims description 608
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 495
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 440
- 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 description 301
- 239000003814 drug Substances 0.000 claims description 285
- 229940079593 drug Drugs 0.000 claims description 276
- 230000008685 targeting Effects 0.000 claims description 225
- -1 vinrodisine Chemical compound 0.000 claims description 189
- 150000003904 phospholipids Chemical class 0.000 claims description 177
- 235000012000 cholesterol Nutrition 0.000 claims description 151
- 238000000034 method Methods 0.000 claims description 145
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 145
- 150000001875 compounds Chemical class 0.000 claims description 134
- 229960001756 oxaliplatin Drugs 0.000 claims description 128
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 128
- 239000012581 transferrin Substances 0.000 claims description 103
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical group COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 claims description 102
- 102000004338 Transferrin Human genes 0.000 claims description 102
- 108090000901 Transferrin Proteins 0.000 claims description 102
- 239000003446 ligand Substances 0.000 claims description 97
- 125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 74
- 125000002252 acyl group Chemical group 0.000 claims description 73
- 238000004519 manufacturing process Methods 0.000 claims description 71
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims description 65
- 229920001223 polyethylene glycol Polymers 0.000 claims description 57
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 55
- 239000002202 Polyethylene glycol Substances 0.000 claims description 49
- 239000007864 aqueous solution Substances 0.000 claims description 48
- 206010028980 Neoplasm Diseases 0.000 claims description 45
- 239000002246 antineoplastic agent Substances 0.000 claims description 44
- 238000002156 mixing Methods 0.000 claims description 44
- 235000000346 sugar Nutrition 0.000 claims description 44
- 238000011282 treatment Methods 0.000 claims description 38
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 claims description 37
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 34
- 150000001841 cholesterols Chemical class 0.000 claims description 31
- 201000011510 cancer Diseases 0.000 claims description 29
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 24
- 125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
- 229930006000 Sucrose Natural products 0.000 claims description 22
- 239000005720 sucrose Substances 0.000 claims description 22
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 21
- 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 description 20
- 235000019152 folic acid Nutrition 0.000 claims description 19
- 239000011724 folic acid Substances 0.000 claims description 19
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- 238000001125 extrusion Methods 0.000 claims description 18
- 238000013019 agitation Methods 0.000 claims description 17
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 15
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- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 14
- 229920002674 hyaluronan Polymers 0.000 claims description 14
- 229960003160 hyaluronic acid Drugs 0.000 claims description 14
- 150000003058 platinum compounds Chemical class 0.000 claims description 14
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 11
- 229940122803 Vinca alkaloid Drugs 0.000 claims description 11
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- 108020004707 nucleic acids Proteins 0.000 claims description 10
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- 150000007523 nucleic acids Chemical class 0.000 claims description 10
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- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 8
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 claims description 8
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 claims description 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 description 7
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 7
- 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 description 7
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- 229930195725 Mannitol Natural products 0.000 claims description 7
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- 229960004768 irinotecan Drugs 0.000 claims description 7
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 7
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- 150000004671 saturated fatty acids Chemical class 0.000 claims description 7
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- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 6
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 6
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- 229960004316 cisplatin Drugs 0.000 claims description 6
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 6
- 239000002254 cytotoxic agent Substances 0.000 claims description 6
- HZSBSRAVNBUZRA-RQDPQJJXSA-J (1r,2r)-cyclohexane-1,2-diamine;tetrachloroplatinum(2+) Chemical compound Cl[Pt+2](Cl)(Cl)Cl.N[C@@H]1CCCC[C@H]1N HZSBSRAVNBUZRA-RQDPQJJXSA-J 0.000 claims description 5
- OOMDVERDMZLRFX-UHFFFAOYSA-N 2,2-bis(aminomethyl)propane-1,3-diol;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound [Pt].NCC(CN)(CO)CO.OC(=O)C1(C(O)=O)CCC1 OOMDVERDMZLRFX-UHFFFAOYSA-N 0.000 claims description 5
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 claims description 5
- 102000053642 Catalytic RNA Human genes 0.000 claims description 5
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- KMLCRELJHYKIIL-UHFFFAOYSA-N [1-(azanidylmethyl)cyclohexyl]methylazanide;platinum(2+);sulfuric acid Chemical compound [Pt+2].OS(O)(=O)=O.[NH-]CC1(C[NH-])CCCCC1 KMLCRELJHYKIIL-UHFFFAOYSA-N 0.000 claims description 5
- XSMVECZRZBFTIZ-UHFFFAOYSA-M [2-(aminomethyl)cyclobutyl]methanamine;2-oxidopropanoate;platinum(4+) Chemical compound [Pt+4].CC([O-])C([O-])=O.NCC1CCC1CN XSMVECZRZBFTIZ-UHFFFAOYSA-M 0.000 claims description 5
- NAFFDQVVNWTDJD-UHFFFAOYSA-L [4-(azanidylmethyl)oxan-4-yl]methylazanide;cyclobutane-1,1-dicarboxylate;platinum(4+) Chemical compound [Pt+4].[NH-]CC1(C[NH-])CCOCC1.[O-]C(=O)C1(C([O-])=O)CCC1 NAFFDQVVNWTDJD-UHFFFAOYSA-L 0.000 claims description 5
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| JP5854559B2 (ja) * | 2009-07-06 | 2016-02-09 | ヴァリエーション バイオテクノロジーズ インコーポレイテッド | 小胞を調製する方法及びこれから製造される製剤 |
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-
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- 2005-03-10 JP JP2005067469A patent/JP2006248978A/ja active Pending
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2006
- 2006-03-08 PL PL06737793T patent/PL1863448T3/pl unknown
- 2006-03-08 EP EP06737793.7A patent/EP1863448B1/en not_active Expired - Lifetime
- 2006-03-08 BR BRPI0608297-1A patent/BRPI0608297A2/pt not_active IP Right Cessation
- 2006-03-08 DK DK06737793.7T patent/DK1863448T3/en active
- 2006-03-08 CA CA002600446A patent/CA2600446A1/en not_active Abandoned
- 2006-03-08 SI SI200631892T patent/SI1863448T1/sl unknown
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- 2006-03-08 CN CN2006800159670A patent/CN101170995B/zh not_active Expired - Fee Related
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- 2006-03-08 PT PT67377937T patent/PT1863448E/pt unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1863448A2 (en) | 2007-12-12 |
| MX2007010996A (es) | 2007-11-07 |
| WO2006099169A2 (en) | 2006-09-21 |
| NZ561569A (en) | 2011-03-31 |
| US20140363491A1 (en) | 2014-12-11 |
| PL1863448T3 (pl) | 2015-05-29 |
| US20110081404A1 (en) | 2011-04-07 |
| ES2529453T3 (es) | 2015-02-20 |
| DK1863448T3 (en) | 2015-02-16 |
| AU2006223329A1 (en) | 2006-09-21 |
| JP5438317B2 (ja) | 2014-03-12 |
| KR101352490B1 (ko) | 2014-02-04 |
| BRPI0608297A2 (pt) | 2009-12-08 |
| JP2008538105A (ja) | 2008-10-09 |
| EP1863448B1 (en) | 2014-11-26 |
| JP2006248978A (ja) | 2006-09-21 |
| WO2006099169A3 (en) | 2007-02-22 |
| CY1116075T1 (el) | 2017-02-08 |
| NO20075136L (no) | 2007-12-07 |
| CN101170995A (zh) | 2008-04-30 |
| HUE024290T2 (en) | 2016-01-28 |
| ZA200708600B (en) | 2009-01-28 |
| CA2600446A1 (en) | 2006-09-21 |
| RU2454229C2 (ru) | 2012-06-27 |
| HK1111625A1 (en) | 2008-08-15 |
| CN101170995B (zh) | 2013-01-16 |
| RU2007137492A (ru) | 2009-04-20 |
| SI1863448T1 (sl) | 2015-03-31 |
| US7829113B2 (en) | 2010-11-09 |
| KR20080002819A (ko) | 2008-01-04 |
| AU2006223329B2 (en) | 2011-11-17 |
| US20060222696A1 (en) | 2006-10-05 |
| US8758810B2 (en) | 2014-06-24 |
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