CN105935352A - 制备小粒径脂质体的方法 - Google Patents
制备小粒径脂质体的方法 Download PDFInfo
- Publication number
- CN105935352A CN105935352A CN201610381865.6A CN201610381865A CN105935352A CN 105935352 A CN105935352 A CN 105935352A CN 201610381865 A CN201610381865 A CN 201610381865A CN 105935352 A CN105935352 A CN 105935352A
- Authority
- CN
- China
- Prior art keywords
- liposome
- organic solvent
- lipid
- compositions
- muc
- 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.)
- Pending
Links
- 239000002502 liposome Substances 0.000 title claims abstract description 75
- 238000004519 manufacturing process Methods 0.000 title description 7
- 150000002632 lipids Chemical class 0.000 claims abstract description 71
- 239000000203 mixture Substances 0.000 claims abstract description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 50
- 239000003960 organic solvent Substances 0.000 claims abstract description 48
- 239000002245 particle Substances 0.000 claims abstract description 43
- 238000002156 mixing Methods 0.000 claims abstract description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 55
- 239000007788 liquid Substances 0.000 claims description 33
- 150000001413 amino acids Chemical group 0.000 claims description 20
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 20
- 108010008707 Mucin-1 Proteins 0.000 claims description 17
- 102100034256 Mucin-1 Human genes 0.000 claims description 17
- 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 10
- -1 palmityl phospholipid Chemical class 0.000 claims description 10
- 238000009472 formulation Methods 0.000 claims description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 8
- 150000003904 phospholipids Chemical class 0.000 claims description 8
- 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 6
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 claims description 6
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 5
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 5
- 229930182558 Sterol Natural products 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 230000013595 glycosylation Effects 0.000 claims description 5
- 238000006206 glycosylation reaction Methods 0.000 claims description 5
- 235000003702 sterols Nutrition 0.000 claims description 5
- 150000003432 sterols Chemical class 0.000 claims description 5
- 230000007704 transition Effects 0.000 claims description 5
- 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 description 4
- 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 4
- ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 claims description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 4
- 239000004472 Lysine Substances 0.000 claims description 4
- 101001000212 Rattus norvegicus Decorin Proteins 0.000 claims description 4
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 claims description 4
- FVJZSBGHRPJMMA-UHFFFAOYSA-N distearoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCCCC FVJZSBGHRPJMMA-UHFFFAOYSA-N 0.000 claims description 4
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 4
- 230000001954 sterilising effect Effects 0.000 claims description 4
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims description 3
- 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 3
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 claims description 3
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- BIABMEZBCHDPBV-UHFFFAOYSA-N dipalmitoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCC BIABMEZBCHDPBV-UHFFFAOYSA-N 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- KLFKZIQAIPDJCW-GPOMZPHUSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCC KLFKZIQAIPDJCW-GPOMZPHUSA-N 0.000 claims description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=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 IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- JLVSRWOIZZXQAD-UHFFFAOYSA-N 2,3-disulfanylpropane-1-sulfonic acid Chemical compound OS(=O)(=O)CC(S)CS JLVSRWOIZZXQAD-UHFFFAOYSA-N 0.000 claims description 2
- 241001597008 Nomeidae Species 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- BPHQZTVXXXJVHI-UHFFFAOYSA-N dimyristoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-UHFFFAOYSA-N 0.000 claims description 2
- 229940067606 lecithin Drugs 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 230000026792 palmitoylation Effects 0.000 claims description 2
- ALPWRKFXEOAUDR-GKEJWYBXSA-M sodium;[(2r)-2,3-di(octadecanoyloxy)propyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)([O-])=O)OC(=O)CCCCCCCCCCCCCCCCC ALPWRKFXEOAUDR-GKEJWYBXSA-M 0.000 claims description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 2
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 claims 1
- 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 1
- 238000001816 cooling Methods 0.000 abstract description 18
- 239000002904 solvent Substances 0.000 description 32
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 14
- 229940024606 amino acid Drugs 0.000 description 14
- 239000000463 material Substances 0.000 description 10
- 230000000975 bioactive effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- 239000012530 fluid Substances 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000002045 lasting effect Effects 0.000 description 3
- 235000018977 lysine Nutrition 0.000 description 3
- 210000002706 plastid Anatomy 0.000 description 3
- 230000003252 repetitive effect Effects 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 241000272525 Anas platyrhynchos Species 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 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 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 1
- PMRVNBLFPMPZHZ-WHDSNZPESA-N (3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol 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.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 PMRVNBLFPMPZHZ-WHDSNZPESA-N 0.000 description 1
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 235000017858 Laurus nobilis Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108010063954 Mucins Proteins 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 244000125380 Terminalia tomentosa Species 0.000 description 1
- 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000005233 alkylalcohol group Chemical group 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 102000057593 human F8 Human genes 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
- 125000003473 lipid group Chemical group 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000000913 palmityl group Chemical group [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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 229940047431 recombinate Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 235000002374 tyrosine Nutrition 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/775—Apolipopeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- A61K38/1735—Mucins, e.g. human intestinal mucin
-
- 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
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1277—Preparation processes; Proliposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Dispersion Chemistry (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Marine Sciences & Fisheries (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13835308P | 2008-12-17 | 2008-12-17 | |
| US61/138353 | 2008-12-17 | ||
| CN2009801509533A CN102256595A (zh) | 2008-12-17 | 2009-12-17 | 制备小粒径脂质体的方法 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801509533A Division CN102256595A (zh) | 2008-12-17 | 2009-12-17 | 制备小粒径脂质体的方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105935352A true CN105935352A (zh) | 2016-09-14 |
Family
ID=42310550
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610381865.6A Pending CN105935352A (zh) | 2008-12-17 | 2009-12-17 | 制备小粒径脂质体的方法 |
| CN2009801509533A Pending CN102256595A (zh) | 2008-12-17 | 2009-12-17 | 制备小粒径脂质体的方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801509533A Pending CN102256595A (zh) | 2008-12-17 | 2009-12-17 | 制备小粒径脂质体的方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20120034294A1 (https=) |
| EP (1) | EP2367532A4 (https=) |
| JP (2) | JP2012512260A (https=) |
| KR (1) | KR101452033B1 (https=) |
| CN (2) | CN105935352A (https=) |
| AU (1) | AU2009333177B2 (https=) |
| BR (1) | BRPI0923001A2 (https=) |
| CA (1) | CA2747182C (https=) |
| EA (1) | EA020604B1 (https=) |
| MX (1) | MX2011006562A (https=) |
| SG (1) | SG172257A1 (https=) |
| WO (1) | WO2010078045A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2026011417A1 (en) * | 2024-07-12 | 2026-01-15 | The Hong Kong University Of Science And Technology | Compositions and methods involving artificial poly (a) sequences |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI395591B (zh) * | 2004-04-01 | 2013-05-11 | Oncothyreon Inc | 黏液性糖蛋白（ｍｕｃ-１）疫苗 |
| JP5771366B2 (ja) * | 2009-09-02 | 2015-08-26 | 株式会社バイオメッドコア | リポソーム製造装置及び方法 |
| EP2678005A4 (en) | 2011-02-24 | 2015-06-10 | Oncothyreon Inc | GLUCOLOPOPEPTIDE MUC1-BASED VACCINE WITH AN ADJUVANS |
| KR101387575B1 (ko) * | 2012-08-10 | 2014-04-23 | 서울대학교산학협력단 | 인지질 및 아세틸렌기를 포함하는 리포좀 및 그의 용도 |
| US9693958B2 (en) * | 2013-03-15 | 2017-07-04 | Cureport, Inc. | Methods and devices for preparation of lipid nanoparticles |
| MX372810B (es) * | 2013-10-02 | 2020-07-03 | Univ Leland Stanford Junior | Composiciones de wnt y metodos para purificacion. |
| CA2977827C (en) * | 2015-03-19 | 2023-10-17 | University Of Connecticut | Systems and methods for continuous manufacturing of liposomal drug formulations |
| CN110520214B (zh) * | 2017-04-13 | 2023-03-21 | 国立大学法人北海道大学 | 使用流路构造体的脂质粒子或微胞的形成方法 |
| SG11202110036RA (en) | 2019-03-19 | 2021-10-28 | Arcturus Therapeutics Inc | Method of making lipid-encapsulated rna nanoparticles |
| EP3711749A1 (en) * | 2019-03-19 | 2020-09-23 | Polymun Scientific Immunbiologische Forschung GmbH | Method of making lipid nanoparticles |
| EP4401706A1 (en) | 2021-09-14 | 2024-07-24 | ADVAPHARM GmbH | Novel lipopeptide formulation |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050112184A1 (en) * | 2003-11-26 | 2005-05-26 | Andreas Jahn | Controlled vesicle self-assembly in continuous two phase flow microfluidic channels |
| CN1674870A (zh) * | 2002-06-21 | 2005-09-28 | 皮埃蒙特医药品有限公司 | 含有生物活性化合物的脂质体 |
| CN101267805A (zh) * | 2005-07-27 | 2008-09-17 | 普洛体维生物治疗公司 | 制造脂质体的系统和方法 |
| CN101309697A (zh) * | 2005-06-28 | 2008-11-19 | 拜奥米拉公司 | 用一种粘蛋白状糖蛋白(muc-1)疫苗治疗患者的方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11139961A (ja) * | 1997-11-06 | 1999-05-25 | Taisho Pharmaceut Co Ltd | リポソームの製造方法 |
| AU756570B2 (en) * | 1998-01-16 | 2003-01-16 | Biomira Inc. | Lipomatrix preparation |
| BR0012624B1 (pt) * | 1999-07-15 | 2011-08-09 | métodos para a preparação de agentes terapêuticos envolvidos por lipìdeos. | |
| ATE518874T1 (de) * | 1999-11-15 | 2011-08-15 | Oncothyreon Inc | Synthetische lipid-a analogen und verwendungen davon |
| AU2002219998B2 (en) * | 2000-12-01 | 2006-03-02 | Biomira, Inc. | Preparation of large liposomes by infusion into peg |
| US7595195B2 (en) * | 2003-02-11 | 2009-09-29 | The Regents Of The University Of California | Microfluidic devices for controlled viscous shearing and formation of amphiphilic vesicles |
| TWI395591B (zh) * | 2004-04-01 | 2013-05-11 | Oncothyreon Inc | 黏液性糖蛋白（ｍｕｃ-１）疫苗 |
| US20090028931A1 (en) * | 2005-01-28 | 2009-01-29 | Bc Cancer Agency | Liposomal compositions for parenteral delivery of agents |
| EP2012750B1 (en) * | 2006-04-06 | 2018-02-21 | Insmed Incorporated | Methods for coacervation induced liposomal encapsulation and formulations thereof |
| US7811603B2 (en) * | 2006-05-09 | 2010-10-12 | The Regents Of The University Of California | Microfluidic device for forming monodisperse lipoplexes |
| JP5126874B2 (ja) * | 2007-05-21 | 2013-01-23 | 国立大学法人神戸大学 | リポソーム製剤の製造方法 |
-
2009
- 2009-12-17 EA EA201100829A patent/EA020604B1/ru not_active IP Right Cessation
- 2009-12-17 BR BRPI0923001A patent/BRPI0923001A2/pt not_active IP Right Cessation
- 2009-12-17 US US13/140,786 patent/US20120034294A1/en not_active Abandoned
- 2009-12-17 AU AU2009333177A patent/AU2009333177B2/en not_active Ceased
- 2009-12-17 JP JP2011542440A patent/JP2012512260A/ja active Pending
- 2009-12-17 WO PCT/US2009/068499 patent/WO2010078045A2/en not_active Ceased
- 2009-12-17 CN CN201610381865.6A patent/CN105935352A/zh active Pending
- 2009-12-17 CN CN2009801509533A patent/CN102256595A/zh active Pending
- 2009-12-17 MX MX2011006562A patent/MX2011006562A/es active IP Right Grant
- 2009-12-17 EP EP09836955A patent/EP2367532A4/en not_active Withdrawn
- 2009-12-17 SG SG2011044831A patent/SG172257A1/en unknown
- 2009-12-17 CA CA2747182A patent/CA2747182C/en not_active Expired - Fee Related
- 2009-12-17 KR KR1020117015492A patent/KR101452033B1/ko not_active Expired - Fee Related
-
2013
- 2013-03-13 US US13/799,324 patent/US20130330398A1/en not_active Abandoned
-
2014
- 2014-07-14 JP JP2014143840A patent/JP5895030B2/ja not_active Expired - Fee Related
-
2015
- 2015-05-12 US US14/710,484 patent/US20150315217A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1674870A (zh) * | 2002-06-21 | 2005-09-28 | 皮埃蒙特医药品有限公司 | 含有生物活性化合物的脂质体 |
| US20050112184A1 (en) * | 2003-11-26 | 2005-05-26 | Andreas Jahn | Controlled vesicle self-assembly in continuous two phase flow microfluidic channels |
| CN101309697A (zh) * | 2005-06-28 | 2008-11-19 | 拜奥米拉公司 | 用一种粘蛋白状糖蛋白(muc-1)疫苗治疗患者的方法 |
| CN101267805A (zh) * | 2005-07-27 | 2008-09-17 | 普洛体维生物治疗公司 | 制造脂质体的系统和方法 |
Non-Patent Citations (2)
| Title |
|---|
| 王有森，等编辑: "《医疗产品消毒、灭菌和保藏》", 31 December 1986, 天威印务（香港）有限公司 * |
| 黄卫星，等主编: "《工程流体力学》", 31 August 2001, 化学工业出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2026011417A1 (en) * | 2024-07-12 | 2026-01-15 | The Hong Kong University Of Science And Technology | Compositions and methods involving artificial poly (a) sequences |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102256595A (zh) | 2011-11-23 |
| EP2367532A2 (en) | 2011-09-28 |
| EA020604B1 (ru) | 2014-12-30 |
| KR20110094114A (ko) | 2011-08-19 |
| MX2011006562A (es) | 2011-09-27 |
| AU2009333177A1 (en) | 2011-07-07 |
| CA2747182C (en) | 2014-11-18 |
| WO2010078045A2 (en) | 2010-07-08 |
| US20130330398A1 (en) | 2013-12-12 |
| KR101452033B1 (ko) | 2014-10-21 |
| CA2747182A1 (en) | 2010-07-08 |
| JP2012512260A (ja) | 2012-05-31 |
| EA201100829A1 (ru) | 2012-02-28 |
| SG172257A1 (en) | 2011-07-28 |
| US20150315217A1 (en) | 2015-11-05 |
| BRPI0923001A2 (pt) | 2018-09-18 |
| US20120034294A1 (en) | 2012-02-09 |
| WO2010078045A3 (en) | 2010-10-28 |
| JP5895030B2 (ja) | 2016-03-30 |
| EP2367532A4 (en) | 2012-12-12 |
| JP2014224127A (ja) | 2014-12-04 |
| AU2009333177B2 (en) | 2013-09-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105935352A (zh) | 制备小粒径脂质体的方法 | |
| JP7333563B2 (ja) | 脂質ナノ粒子 | |
| JP5192515B2 (ja) | リポソーム製造方法および装置 | |
| CA1215646A (en) | Method for producing liposomes | |
| ES2053722T4 (es) | Liposomas multivesiculares que tienen encapsulada en ellas una sustancia biologicamente activa en presencia de un hidrocloruro. | |
| KR20230050313A (ko) | 지질 나노입자 | |
| WO2021148511A1 (en) | Lipid nanoparticles | |
| JP6778306B1 (ja) | 脂質膜構造体形成用組成物およびその製造方法、脂質膜構造体含有組成物およびその製造方法、脂質膜構造体含有組成物を配合してなる化粧料、皮膚外用剤 | |
| IE860273L (en) | Microemulsification of small vesicles | |
| EP1196145A1 (en) | Methods and apparatus for preparation of lipid vesicles | |
| EP0643620A1 (en) | Particles, method of preparing said particles and uses thereof | |
| WO2011127255A1 (en) | Preparation of lipid nanoparticles | |
| WO1993006921A1 (en) | Particles, method of preparing said particles and uses thereof | |
| JP2011256199A (ja) | リポソームの製造方法ならびにコレステロール溶解方法 | |
| JP2022527830A (ja) | 治療に適したリポソームｒｎａ製剤の調製および保存 | |
| JP2008106001A (ja) | リポソーム製剤の製造方法 | |
| CN121668132A (zh) | 一种肿瘤-细菌膜嵌合的纳米颗粒的制备方法及其应用 | |
| CN118987193A (zh) | 一种阴离子脂质纳米佐剂及其制备方法和应用 | |
| AU2013273711A1 (en) | Method of making small liposomes | |
| JPWO2000072824A1 (ja) | 微小なリポソームおよびその製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160914 |
|
| WD01 | Invention patent application deemed withdrawn after publication |