JP2006510733A - カルジオリピン分子および合成方法 - Google Patents
カルジオリピン分子および合成方法 Download PDFInfo
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- JP2006510733A JP2006510733A JP2005501873A JP2005501873A JP2006510733A JP 2006510733 A JP2006510733 A JP 2006510733A JP 2005501873 A JP2005501873 A JP 2005501873A JP 2005501873 A JP2005501873 A JP 2005501873A JP 2006510733 A JP2006510733 A JP 2006510733A
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- Prior art keywords
- cardiolipin
- composition
- liposome
- acid
- mmol
- Prior art date
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- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 title claims abstract description 154
- 238000001308 synthesis method Methods 0.000 title description 3
- -1 phosphate triester Chemical class 0.000 claims abstract description 108
- 238000000034 method Methods 0.000 claims abstract description 104
- 239000002502 liposome Substances 0.000 claims abstract description 73
- 239000013543 active substance Substances 0.000 claims abstract description 47
- 150000008300 phosphoramidites Chemical class 0.000 claims abstract description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 23
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 21
- 201000010099 disease Diseases 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 19
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 17
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 16
- 229930195729 fatty acid Natural products 0.000 claims abstract description 16
- 239000000194 fatty acid Substances 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 15
- 239000010452 phosphate Substances 0.000 claims abstract description 11
- 239000003446 ligand Substances 0.000 claims abstract description 8
- 230000008685 targeting Effects 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 133
- 229920006395 saturated elastomer Polymers 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 150000002632 lipids Chemical class 0.000 claims description 18
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims description 16
- 235000021317 phosphate Nutrition 0.000 claims description 16
- 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 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 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 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 102000004169 proteins and genes Human genes 0.000 claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 claims description 8
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 239000002246 antineoplastic agent Substances 0.000 claims description 7
- 235000012000 cholesterol Nutrition 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 7
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 6
- 239000003377 acid catalyst Substances 0.000 claims description 6
- 230000032683 aging Effects 0.000 claims description 6
- 150000001720 carbohydrates Chemical class 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- 229920001184 polypeptide Polymers 0.000 claims description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 5
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 5
- QAJJXHRQPLATMK-UHFFFAOYSA-N 4,5-dichloro-1h-imidazole Chemical group ClC=1N=CNC=1Cl QAJJXHRQPLATMK-UHFFFAOYSA-N 0.000 claims description 4
- 108010016626 Dipeptides Proteins 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 4
- 229930182558 Sterol Natural products 0.000 claims description 4
- QYIXCDOBOSTCEI-UHFFFAOYSA-N alpha-cholestanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 QYIXCDOBOSTCEI-UHFFFAOYSA-N 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 238000001727 in vivo Methods 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 150000003432 sterols Chemical class 0.000 claims description 4
- 235000003702 sterols Nutrition 0.000 claims description 4
- ZBBUFYIXSWZOIF-UHFFFAOYSA-N 1-methyl-1h-imidazol-1-ium;perchlorate Chemical compound OCl(=O)(=O)=O.CN1C=CN=C1 ZBBUFYIXSWZOIF-UHFFFAOYSA-N 0.000 claims description 3
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 3
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 3
- MIUOBAHGBPSRKY-UHFFFAOYSA-N 5-(4-nitrophenyl)-2h-tetrazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NNN=N1 MIUOBAHGBPSRKY-UHFFFAOYSA-N 0.000 claims description 3
- 208000031295 Animal disease Diseases 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- YTFJQDNGSQJFNA-UHFFFAOYSA-L benzyl phosphate Chemical compound [O-]P([O-])(=O)OCC1=CC=CC=C1 YTFJQDNGSQJFNA-UHFFFAOYSA-L 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- 125000006245 phosphate protecting group Chemical group 0.000 claims description 3
- 108091033319 polynucleotide Proteins 0.000 claims description 3
- 102000040430 polynucleotide Human genes 0.000 claims description 3
- 239000002157 polynucleotide Substances 0.000 claims description 3
- 208000017520 skin disease Diseases 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- QYIXCDOBOSTCEI-QCYZZNICSA-N (5alpha)-cholestan-3beta-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-QCYZZNICSA-N 0.000 claims description 2
- XIIAYQZJNBULGD-UHFFFAOYSA-N (5alpha)-cholestane Natural products C1CC2CCCCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 XIIAYQZJNBULGD-UHFFFAOYSA-N 0.000 claims description 2
- LZLVZIFMYXDKCN-QJWFYWCHSA-N 1,2-di-O-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC LZLVZIFMYXDKCN-QJWFYWCHSA-N 0.000 claims description 2
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 claims description 2
- 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 2
- 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 2
- BIABMEZBCHDPBV-MPQUPPDSSA-N 1,2-palmitoyl-sn-glycero-3-phospho-(1'-sn-glycerol) Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCCCC BIABMEZBCHDPBV-MPQUPPDSSA-N 0.000 claims description 2
- XGDRLCRGKUCBQL-UHFFFAOYSA-N 1h-imidazole-4,5-dicarbonitrile Chemical compound N#CC=1N=CNC=1C#N XGDRLCRGKUCBQL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- QSIFOTQDNVCTTM-UHFFFAOYSA-N 3-methyl-1h-imidazol-3-ium;trifluoromethanesulfonate Chemical compound CN1C=CN=C1.OS(=O)(=O)C(F)(F)F QSIFOTQDNVCTTM-UHFFFAOYSA-N 0.000 claims description 2
- MOYJTNHLJBMWFK-UHFFFAOYSA-N 5-(3,5-dinitrophenyl)-2h-tetrazole Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC(C=2NN=NN=2)=C1 MOYJTNHLJBMWFK-UHFFFAOYSA-N 0.000 claims description 2
- GONFBOIJNUKKST-UHFFFAOYSA-N 5-ethylsulfanyl-2h-tetrazole Chemical compound CCSC=1N=NNN=1 GONFBOIJNUKKST-UHFFFAOYSA-N 0.000 claims description 2
- ZBXNFTFKKOSPLD-UHFFFAOYSA-N 5-methylsulfanyl-2h-tetrazole Chemical compound CSC1=NN=NN1 ZBXNFTFKKOSPLD-UHFFFAOYSA-N 0.000 claims description 2
- BHYOQNUELFTYRT-UHFFFAOYSA-N Cholesterol sulfate Natural products C1C=C2CC(OS(O)(=O)=O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 BHYOQNUELFTYRT-UHFFFAOYSA-N 0.000 claims description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 2
- FVJZSBGHRPJMMA-IOLBBIBUSA-N PG(18:0/18:0) Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCCCCCC FVJZSBGHRPJMMA-IOLBBIBUSA-N 0.000 claims description 2
- 229940059260 amidate Drugs 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 150000001768 cations Chemical class 0.000 claims description 2
- XIIAYQZJNBULGD-LDHZKLTISA-N cholestane Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 XIIAYQZJNBULGD-LDHZKLTISA-N 0.000 claims description 2
- BHYOQNUELFTYRT-DPAQBDIFSA-N cholesterol sulfate Chemical compound C1C=C2C[C@@H](OS(O)(=O)=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 BHYOQNUELFTYRT-DPAQBDIFSA-N 0.000 claims description 2
- 150000001841 cholesterols Chemical class 0.000 claims description 2
- WLNARFZDISHUGS-MIXBDBMTSA-N cholesteryl hemisuccinate Chemical compound C1C=C2C[C@@H](OC(=O)CCC(O)=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 WLNARFZDISHUGS-MIXBDBMTSA-N 0.000 claims description 2
- QYIXCDOBOSTCEI-NWKZBHTNSA-N coprostanol Chemical compound C([C@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-NWKZBHTNSA-N 0.000 claims description 2
- 239000002577 cryoprotective agent Substances 0.000 claims description 2
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 claims description 2
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 claims description 2
- 229960005160 dimyristoylphosphatidylglycerol Drugs 0.000 claims description 2
- BPHQZTVXXXJVHI-AJQTZOPKSA-N ditetradecanoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-AJQTZOPKSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 claims description 2
- 208000019622 heart disease Diseases 0.000 claims description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 2
- 150000004668 long chain fatty acids Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 239000002777 nucleoside Substances 0.000 claims description 2
- 239000000813 peptide hormone Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
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- 230000003683 cardiac damage Effects 0.000 claims 1
- 125000004969 haloethyl group Chemical group 0.000 claims 1
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 1
- 235000021391 short chain fatty acids Nutrition 0.000 claims 1
- 239000002356 single layer Substances 0.000 claims 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 abstract description 51
- 238000006243 chemical reaction Methods 0.000 abstract description 11
- 230000002209 hydrophobic effect Effects 0.000 abstract description 5
- 238000012801 analytical assay Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- 239000002253 acid Substances 0.000 description 66
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 43
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- 235000019439 ethyl acetate Nutrition 0.000 description 37
- 239000011734 sodium Substances 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- 229910004298 SiO 2 Inorganic materials 0.000 description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000012267 brine Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 238000009472 formulation Methods 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
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- 210000004027 cell Anatomy 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
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- 239000011541 reaction mixture Substances 0.000 description 11
- 230000002194 synthesizing effect Effects 0.000 description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- OZQJTTOWXPKJFG-UHFFFAOYSA-N azane;propane-1,2,3-triol Chemical compound N.N.OCC(O)CO OZQJTTOWXPKJFG-UHFFFAOYSA-N 0.000 description 9
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 9
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- OQQOAWVKVDAJOI-VWLOTQADSA-N 1,2-dilauroyl-sn-glycerol Chemical compound CCCCCCCCCCCC(=O)OC[C@H](CO)OC(=O)CCCCCCCCCCC OQQOAWVKVDAJOI-VWLOTQADSA-N 0.000 description 6
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- ANPWLBTUUNFQIO-UHFFFAOYSA-N n-bis(phenylmethoxy)phosphanyl-n-propan-2-ylpropan-2-amine Chemical compound C=1C=CC=CC=1COP(N(C(C)C)C(C)C)OCC1=CC=CC=C1 ANPWLBTUUNFQIO-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
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Classifications
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
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- C07F9/08—Esters of oxyacids of phosphorus
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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- 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
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- 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
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- A61K31/7072—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 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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Landscapes
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- Life Sciences & Earth Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
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- Organic Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Virology (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
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US60/438,659 | 2003-01-07 | ||
US46733103P | 2003-05-02 | 2003-05-02 | |
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USPCT/US03/13917 | 2003-05-04 | ||
PCT/US2003/013917 WO2004062569A2 (en) | 2003-01-07 | 2003-05-04 | Cardiolipin compositions their methods of preparation and use |
PCT/US2003/016412 WO2003099830A2 (en) | 2002-05-24 | 2003-05-23 | Cardiolipin compositions, methods of preparation and use |
USPCT/US03/16412 | 2003-05-23 | ||
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EA (2) | EA200500659A1 (de) |
HK (1) | HK1080087A1 (de) |
WO (2) | WO2004039817A1 (de) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2015514123A (ja) * | 2012-04-11 | 2015-05-18 | リポクセン テクノロジーズ リミテッド | ミエリン塩基性タンパク質のオリゴペプチドフラグメントを含有するリポソーム、医薬組成物および多発性硬化症の治療方法 |
JP2017048188A (ja) * | 2008-09-27 | 2017-03-09 | ジャイナ ファーマシューティカルズ,インコーポレーテッド | 経口適用および局所適用のための脂質系薬学的調製物、ならびにそれらの組成物、方法、および使用 |
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US8815599B2 (en) | 2004-06-01 | 2014-08-26 | Pronai Therapeutics, Inc. | Methods and compositions for the inhibition of gene expression |
US20080286351A1 (en) * | 2004-06-29 | 2008-11-20 | Ahmad Moghis U | Pegylated Cardiolipin Analogs, Methods of Synthesis, and Uses Thereof |
WO2006052906A2 (en) * | 2004-11-08 | 2006-05-18 | Neopharm, Inc. | Synthesis of cardiolipin analogues and uses thereof |
WO2006113679A2 (en) | 2005-04-15 | 2006-10-26 | Board Of Regents, The University Of Texas System | Delivery of sirna by neutral lipid compositions |
WO2007014150A2 (en) * | 2005-07-22 | 2007-02-01 | Neopharm, Inc. | Method of administering liposomes containing oligonucleotides |
WO2007065017A2 (en) * | 2005-12-01 | 2007-06-07 | Pronai Therapeutics, Inc. | Oligonucleotide cationic liposomal delivery system |
WO2007064857A2 (en) | 2005-12-01 | 2007-06-07 | Pronai Therapeutics, Inc. | Amphoteric liposome formulation |
JP2009527576A (ja) * | 2006-02-24 | 2009-07-30 | ネオフアーム・インコーポレイテツド | カルジオリピン調製の方法および工程 |
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US2113606A (en) * | 1934-05-24 | 1938-04-12 | Alba Pharmaceutical Company In | Quaternary ammonium compounds |
US6461637B1 (en) * | 2000-09-01 | 2002-10-08 | Neopharm, Inc. | Method of administering liposomal encapsulated taxane |
NZ512244A (en) * | 1998-11-12 | 2003-12-19 | Invitrogen Corp | Polycationic transfection reagents for introducing anions into a cell |
CA2375727C (en) * | 1999-05-28 | 2010-05-25 | Vical Incorporated | Cytofectin dimers and methods of use thereof |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2017048188A (ja) * | 2008-09-27 | 2017-03-09 | ジャイナ ファーマシューティカルズ,インコーポレーテッド | 経口適用および局所適用のための脂質系薬学的調製物、ならびにそれらの組成物、方法、および使用 |
JP2015514123A (ja) * | 2012-04-11 | 2015-05-18 | リポクセン テクノロジーズ リミテッド | ミエリン塩基性タンパク質のオリゴペプチドフラグメントを含有するリポソーム、医薬組成物および多発性硬化症の治療方法 |
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WO2004039817A1 (en) | 2004-05-13 |
EA200500661A1 (ru) | 2005-10-27 |
EP1556392A1 (de) | 2005-07-27 |
EA200500659A1 (ru) | 2005-10-27 |
WO2004035523B1 (en) | 2004-08-26 |
WO2004035523A1 (en) | 2004-04-29 |
WO2004039817A9 (en) | 2004-07-22 |
AU2003268478A1 (en) | 2004-05-25 |
AU2003277445A1 (en) | 2004-05-04 |
CA2501990A1 (en) | 2004-04-29 |
EP1558562A1 (de) | 2005-08-03 |
JP2006503112A (ja) | 2006-01-26 |
HK1080087A1 (zh) | 2006-04-21 |
CA2502285A1 (en) | 2004-05-13 |
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