WO2021125805A1 - 폴리락트산염을 포함하는 약물전달용 나노입자 조성물 제조용 키트 - Google Patents
폴리락트산염을 포함하는 약물전달용 나노입자 조성물 제조용 키트 Download PDFInfo
- Publication number
- WO2021125805A1 WO2021125805A1 PCT/KR2020/018480 KR2020018480W WO2021125805A1 WO 2021125805 A1 WO2021125805 A1 WO 2021125805A1 KR 2020018480 W KR2020018480 W KR 2020018480W WO 2021125805 A1 WO2021125805 A1 WO 2021125805A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- weight
- kit
- nanoparticles
- parts
- chamber
- Prior art date
Links
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 96
- 239000000203 mixture Substances 0.000 title claims abstract description 57
- 229920000747 poly(lactic acid) Polymers 0.000 title claims abstract description 26
- 239000004626 polylactic acid Substances 0.000 title claims abstract description 21
- 150000003839 salts Chemical class 0.000 title claims abstract description 14
- 238000012377 drug delivery Methods 0.000 title abstract description 9
- 150000001767 cationic compounds Chemical class 0.000 claims abstract description 29
- 229920000469 amphiphilic block copolymer Polymers 0.000 claims abstract description 22
- 238000002156 mixing Methods 0.000 claims abstract description 22
- 239000004480 active ingredient Substances 0.000 claims description 30
- 241000700605 Viruses Species 0.000 claims description 21
- 230000003834 intracellular effect Effects 0.000 claims description 21
- 108020004707 nucleic acids Proteins 0.000 claims description 18
- 150000007523 nucleic acids Chemical class 0.000 claims description 18
- 102000039446 nucleic acids Human genes 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 150000001720 carbohydrates Chemical class 0.000 claims description 5
- 229920001184 polypeptide Polymers 0.000 claims description 5
- 239000002738 chelating agent Substances 0.000 claims description 4
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 4
- 239000003002 pH adjusting agent Substances 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 239000003125 aqueous solvent Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 13
- 239000003814 drug Substances 0.000 abstract description 13
- 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 28
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 24
- 229920001577 copolymer Polymers 0.000 description 22
- -1 cationic lipid Chemical class 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 108020004999 messenger RNA Proteins 0.000 description 15
- 239000011732 tocopherol Substances 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 235000012000 cholesterol Nutrition 0.000 description 14
- 229960001295 tocopherol Drugs 0.000 description 13
- 230000002209 hydrophobic effect Effects 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- 229930003799 tocopherol Natural products 0.000 description 10
- 239000002245 particle Substances 0.000 description 9
- 229920000642 polymer Polymers 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 8
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 8
- 235000010384 tocopherol Nutrition 0.000 description 8
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 8
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 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 description 7
- 230000003612 virological effect Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 6
- 125000002091 cationic group Chemical group 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 5
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 5
- 229920002873 Polyethylenimine Polymers 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 244000309459 oncolytic virus Species 0.000 description 5
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 241000701161 unidentified adenovirus Species 0.000 description 5
- 229920001661 Chitosan Polymers 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 125000000129 anionic group Chemical group 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 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 description 3
- 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 description 3
- VPVXHAANQNHFSF-UHFFFAOYSA-N 1,4-dioxan-2-one Chemical compound O=C1COCCO1 VPVXHAANQNHFSF-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
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 3
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 3
- 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 3
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 3
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 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 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 229920006317 cationic polymer Polymers 0.000 description 3
- 125000003074 decanoyl group Chemical group [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(*)=O 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000002296 dynamic light scattering Methods 0.000 description 3
- 230000009881 electrostatic interaction Effects 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 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 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 229960002510 mandelic acid Drugs 0.000 description 3
- 150000002772 monosaccharides Chemical class 0.000 description 3
- 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 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229920001610 polycaprolactone Polymers 0.000 description 3
- 239000004632 polycaprolactone Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 238000003260 vortexing Methods 0.000 description 3
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
- 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 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- GPWHCUUIQMGELX-VHQDNGOZSA-N 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCC GPWHCUUIQMGELX-VHQDNGOZSA-N 0.000 description 2
- FHQVHHIBKUMWTI-ZCXUNETKSA-N 1-palmitoyl-2-oleoyl phosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC FHQVHHIBKUMWTI-ZCXUNETKSA-N 0.000 description 2
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 2
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 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 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 108010039918 Polylysine Proteins 0.000 description 2
- 102000007327 Protamines Human genes 0.000 description 2
- 108010007568 Protamines Proteins 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 241000711975 Vesicular stomatitis virus Species 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229920000359 diblock copolymer Polymers 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 125000002463 lignoceryl 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])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 2
- 125000005645 linoleyl group Chemical group 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 2
- GLGLUQVVDHRLQK-WRBBJXAJSA-N n,n-dimethyl-2,3-bis[(z)-octadec-9-enoxy]propan-1-amine Chemical compound CCCCCCCC\C=C/CCCCCCCCOCC(CN(C)C)OCCCCCCCC\C=C/CCCCCCCC GLGLUQVVDHRLQK-WRBBJXAJSA-N 0.000 description 2
- 125000001117 oleyl 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])=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 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 229920000724 poly(L-arginine) polymer Polymers 0.000 description 2
- 229920000962 poly(amidoamine) Polymers 0.000 description 2
- 229920000768 polyamine Polymers 0.000 description 2
- 108010011110 polyarginine Proteins 0.000 description 2
- 229920002851 polycationic polymer Polymers 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229940048914 protamine Drugs 0.000 description 2
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000002640 tocopherol group Chemical class 0.000 description 2
- 235000019149 tocopherols Nutrition 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- NRWCNEBHECBWRJ-UHFFFAOYSA-M trimethyl(propyl)azanium;chloride Chemical compound [Cl-].CCC[N+](C)(C)C NRWCNEBHECBWRJ-UHFFFAOYSA-M 0.000 description 2
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 2
- 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 description 1
- OPVZUEPSMJNLOM-ZCXUNETKSA-N (1-hexadecanoyloxy-3-phosphonooxypropan-2-yl) (z)-octadec-9-enoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC OPVZUEPSMJNLOM-ZCXUNETKSA-N 0.000 description 1
- OKLASJZQBDJAPH-UHFFFAOYSA-N (2-dodecanoyloxy-3-phosphonooxypropyl) dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCCCCCC OKLASJZQBDJAPH-UHFFFAOYSA-N 0.000 description 1
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- VKQJCYCXUGUKQJ-MAZCIEHSSA-N (9Z,12Z)-N-[2-[2-[2-[2-[[(9Z,12Z)-octadeca-9,12-dienoyl]amino]ethylamino]ethylamino]ethylamino]ethyl]octadeca-9,12-dienamide Chemical compound N(CCNCCNC(CCCCCCC\C=C/C\C=C/CCCCC)=O)CCNCCNC(CCCCCCC\C=C/C\C=C/CCCCC)=O VKQJCYCXUGUKQJ-MAZCIEHSSA-N 0.000 description 1
- ZGAFPTGELYKMAW-CLFAGFIQSA-N (Z)-N-[2-[2-[2-[2-[2-[[(Z)-octadec-9-enoyl]amino]ethylamino]ethylamino]ethylamino]ethylamino]ethyl]octadec-9-enamide Chemical compound C(CNCCNCCNCCNCCNC(CCCCCCC\C=C/CCCCCCCC)=O)NC(CCCCCCC\C=C/CCCCCCCC)=O ZGAFPTGELYKMAW-CLFAGFIQSA-N 0.000 description 1
- GCAONVVVMAVFDE-NADBREJJSA-N (z)-n-[(e)-octadec-9-enyl]octadec-9-enamide Chemical compound CCCCCCCC\C=C\CCCCCCCCNC(=O)CCCCCCC\C=C/CCCCCCCC GCAONVVVMAVFDE-NADBREJJSA-N 0.000 description 1
- DKHSZSKSPXFGPM-HWAYABPNSA-N (z)-n-[2-[2-[[(z)-tetradec-9-enoyl]amino]ethylamino]ethyl]tetradec-9-enamide Chemical compound CCCC\C=C/CCCCCCCC(=O)NCCNCCNC(=O)CCCCCCC\C=C/CCCC DKHSZSKSPXFGPM-HWAYABPNSA-N 0.000 description 1
- 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 description 1
- PGPMCWZMPPZJML-NAFNZUQFSA-N 1,2-di-[(9Z)-hexadecenoyl]-sn-glycero-3-phosphoethanolamine Chemical compound CCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCC PGPMCWZMPPZJML-NAFNZUQFSA-N 0.000 description 1
- FVXDQWZBHIXIEJ-LNDKUQBDSA-N 1,2-di-[(9Z,12Z)-octadecadienoyl]-sn-glycero-3-phosphocholine Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC FVXDQWZBHIXIEJ-LNDKUQBDSA-N 0.000 description 1
- SLKDGVPOSSLUAI-PGUFJCEWSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCCCC SLKDGVPOSSLUAI-PGUFJCEWSA-N 0.000 description 1
- IJFVSSZAOYLHEE-SSEXGKCCSA-N 1,2-dilauroyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCC IJFVSSZAOYLHEE-SSEXGKCCSA-N 0.000 description 1
- YFWHNAWEOZTIPI-DIPNUNPCSA-N 1,2-dioctadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCCCC YFWHNAWEOZTIPI-DIPNUNPCSA-N 0.000 description 1
- 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 description 1
- LVNGJLRDBYCPGB-UHFFFAOYSA-N 1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-UHFFFAOYSA-N 0.000 description 1
- OZSITQMWYBNPMW-GDLZYMKVSA-N 1,2-ditetradecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCC OZSITQMWYBNPMW-GDLZYMKVSA-N 0.000 description 1
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- IDOQDZANRZQBTP-UHFFFAOYSA-N 2-[2-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=CC=C1OCCO IDOQDZANRZQBTP-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- UAXAYRSMIDOXCU-BJDJZHNGSA-N 2-[[(2r)-2-[[(2s)-2-[[2-[[(2s)-4-amino-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-sulfanylpropanoyl]amino]acetic acid Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O UAXAYRSMIDOXCU-BJDJZHNGSA-N 0.000 description 1
- NEZDNQCXEZDCBI-UHFFFAOYSA-N 2-azaniumylethyl 2,3-di(tetradecanoyloxy)propyl phosphate Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCC NEZDNQCXEZDCBI-UHFFFAOYSA-N 0.000 description 1
- ZLGYVWRJIZPQMM-HHHXNRCGSA-N 2-azaniumylethyl [(2r)-2,3-di(dodecanoyloxy)propyl] phosphate Chemical compound CCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCC ZLGYVWRJIZPQMM-HHHXNRCGSA-N 0.000 description 1
- CDOUZKKFHVEKRI-UHFFFAOYSA-N 3-bromo-n-[(prop-2-enoylamino)methyl]propanamide Chemical compound BrCCC(=O)NCNC(=O)C=C CDOUZKKFHVEKRI-UHFFFAOYSA-N 0.000 description 1
- GUCPYIYFQVTFSI-UHFFFAOYSA-N 4-methoxybenzamide Chemical compound COC1=CC=C(C(N)=O)C=C1 GUCPYIYFQVTFSI-UHFFFAOYSA-N 0.000 description 1
- ZXIATBNUWJBBGT-JXOAFFINSA-N 5-methoxyuridine Chemical compound O=C1NC(=O)C(OC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZXIATBNUWJBBGT-JXOAFFINSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose 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)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 1
- 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 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
- 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 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 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 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- AYRXSINWFIIFAE-SCLMCMATSA-N Isomaltose Natural products OC[C@H]1O[C@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)[C@@H](O)[C@@H](O)[C@@H]1O AYRXSINWFIIFAE-SCLMCMATSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 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 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 108010047562 NGR peptide Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical compound NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 description 1
- AYRXSINWFIIFAE-UHFFFAOYSA-N O6-alpha-D-Galactopyranosyl-D-galactose Natural products OCC1OC(OCC(O)C(O)C(O)C(O)C=O)C(O)C(O)C1O AYRXSINWFIIFAE-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 229920001363 Polidocanol Polymers 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 229920002642 Polysorbate 65 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 102000007238 Transferrin Receptors Human genes 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- 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 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004929 Triton X-114 Polymers 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003761 Vitamin B9 Natural products 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- HIHOWBSBBDRPDW-PTHRTHQKSA-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-yl] n-[2-(dimethylamino)ethyl]carbamate Chemical compound C1C=C2C[C@@H](OC(=O)NCCN(C)C)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 HIHOWBSBBDRPDW-PTHRTHQKSA-N 0.000 description 1
- OBXRDFNCKFWKNY-MAZCIEHSSA-N [2-[(9z,12z)-octadeca-9,12-dienoyl]oxy-3-phosphonooxypropyl] (9z,12z)-octadeca-9,12-dienoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC OBXRDFNCKFWKNY-MAZCIEHSSA-N 0.000 description 1
- SSCDRSKJTAQNNB-WVZYQCMWSA-N [3-[2-aminoethoxy(hydroxy)phosphoryl]oxy-2-[(9e,12e)-octadeca-9,12-dienoyl]oxypropyl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC SSCDRSKJTAQNNB-WVZYQCMWSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 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 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 125000004097 arachidonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001204 arachidyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 125000002511 behenyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
- 229960001091 chenodeoxycholic acid Drugs 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UMGXUWVIJIQANV-UHFFFAOYSA-M didecyl(dimethyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCC[N+](C)(C)CCCCCCCCCC UMGXUWVIJIQANV-UHFFFAOYSA-M 0.000 description 1
- PSLWZOIUBRXAQW-UHFFFAOYSA-M dimethyl(dioctadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC PSLWZOIUBRXAQW-UHFFFAOYSA-M 0.000 description 1
- UAKOZKUVZRMOFN-JDVCJPALSA-M dimethyl-bis[(z)-octadec-9-enyl]azanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC[N+](C)(C)CCCCCCCC\C=C/CCCCCCCC UAKOZKUVZRMOFN-JDVCJPALSA-M 0.000 description 1
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 125000003438 dodecyl group Chemical group [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])* 0.000 description 1
- PZZHMLOHNYWKIK-UHFFFAOYSA-N eddha Chemical compound C=1C=CC=C(O)C=1C(C(=O)O)NCCNC(C(O)=O)C1=CC=CC=C1O PZZHMLOHNYWKIK-UHFFFAOYSA-N 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229960003082 galactose Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- DLRVVLDZNNYCBX-CQUJWQHSSA-N gentiobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-CQUJWQHSSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 229940027278 hetastarch Drugs 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229940050526 hydroxyethylstarch Drugs 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 229950006462 lauromacrogol 400 Drugs 0.000 description 1
- 239000002479 lipoplex Substances 0.000 description 1
- YFVGRULMIQXYNE-UHFFFAOYSA-M lithium;dodecyl sulfate Chemical compound [Li+].CCCCCCCCCCCCOS([O-])(=O)=O YFVGRULMIQXYNE-UHFFFAOYSA-M 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 229940041290 mannose Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 125000001421 myristyl 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])[H] 0.000 description 1
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 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
- 239000000123 paper Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
- 229940099429 polyoxyl 40 stearate Drugs 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940099511 polysorbate 65 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000131 polyvinylidene Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108700004121 sarkosyl Proteins 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000002924 silencing RNA Substances 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical group [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- HRQDCDQDOPSGBR-UHFFFAOYSA-M sodium;octane-1-sulfonate Chemical compound [Na+].CCCCCCCCS([O-])(=O)=O HRQDCDQDOPSGBR-UHFFFAOYSA-M 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000004079 stearyl 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])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019159 vitamin B9 Nutrition 0.000 description 1
- 239000011727 vitamin B9 Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- 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
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- 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
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
- A61K9/5153—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5192—Processes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle
Definitions
- the present invention relates to a kit for preparing a nanoparticle composition for drug delivery, and more specifically, a drug can be prepared by simply mixing the amphiphilic block copolymer, cationic compound, polylactate, and drug, which are kit components. It relates to a kit for preparing a nanoparticle composition for drug delivery designed to easily form nanoparticles encapsulated therein.
- the delivery system is largely divided into a viral delivery system using adenovirus or retrovirus, etc. and a non-viral delivery system using cationic lipids and cationic polymers.
- a viral carrier it is known that there are many problems in commercialization because it is exposed to risks such as non-specific immune reaction and the production process is complicated. Therefore, the recent research direction is in the direction of improving the shortcomings by using a non-viral carrier.
- the non-viral delivery system has the advantages of fewer side effects in terms of in vivo safety and a low production price in terms of economic feasibility.
- Non-viral carriers used for the delivery of nucleic acid substances are a complex (lipoplex) of a cationic lipid and a nucleic acid using a cationic lipid, and a complex (polyplex) of a polycationic polymer and a nucleic acid.
- cationic lipids or polycationic polymers have been studied in that they stabilize the anionic drug by forming a complex through electrostatic interaction with the anionic drug and increase intracellular delivery (De Paula D) , Bentley MV, Mahato RI, Hydrophobization and bioconjugation for enhanced siRNA delivery and targeting, RNA 13 (2007) 431-56; Gary DJ, Puri N, Won YY, Polymer-based siRNA delivery: Perspectives on the fundamental and phenomenological distinctions from polymer -based DNA delivery, J Control release 121 (2007) 64-73).
- the nanoparticles formed by these complexes often lose stability easily depending on the storage environment, so they are vulnerable to long-term storage and there is a risk that the quality may be damaged during transportation.
- it is very difficult to manufacture because it requires a complicated manufacturing process to ensure sufficient stability.
- An object of the present invention is to easily form drug-containing nanoparticles by simply mixing the kit components so that it is easy for the end consumer to use, and drug-containing nanoparticles can be easily formed immediately before use.
- An object of the present invention is to provide a kit for preparing a nanoparticle composition for drug delivery, which can effectively deliver a drug into the body without the influence of storage or transportation environment.
- the present invention provides a first chamber containing an amphiphilic block copolymer, a cationic compound, and a polylactate; and a second chamber containing an active ingredient selected from a nucleic acid, a polypeptide, a virus, or a combination thereof; provides a kit for preparing a nanoparticle composition comprising a.
- the kit is for forming nanoparticles that deliver an intracellular active ingredient.
- At least one selected from the group consisting of the first chamber and the second chamber further includes an additional solvent.
- the solvent is an aqueous solvent, a water-miscible solvent, or a mixture thereof.
- the second chamber further includes a pH adjusting agent, an inorganic salt, a saccharide, a surfactant, a chelating agent, or a combination thereof.
- the amount of the amphiphilic block copolymer may be 0.01 to 50 parts by weight based on 1 part by weight of the cationic compound.
- the amount of the polylactic acid salt may be 0.1 to 100 parts by weight based on 1 part by weight of the cationic compound.
- the mixture of the amphiphilic block copolymer, the cationic compound, and the polylactate in the first chamber may be filtered one or more times with a hydrophilic filter after mixing.
- the kit for preparing a nanoparticle composition according to the present invention includes the components for forming the drug-containing nanoparticles separated in separate chambers, unlike the already formed nanoparticles, it is not affected by the storage or transportation environment, and uses the same. Thus, the end user can successfully form nanoparticles having an effective drug delivery effect by simply mixing the components of the chamber.
- Example 3 is a graph showing the results of evaluation of the formation of nanoparticles performed in Experimental Example 3 of the present invention using dynamic light scattering (Dynamic Light Scattering).
- FIG. 4 is a graph showing the results of an intracellular delivery efficiency experiment of nanoparticles performed in Experimental Example 4 of the present invention.
- Example 5 is a graph showing the results of the intracellular delivery efficiency test before and after the accelerated test performed in Experimental Example 5 of the present invention.
- a kit for preparing a nanoparticle composition according to the present invention includes: a first chamber containing an amphiphilic block copolymer, a cationic compound, and a polylactate; and a second chamber containing an active ingredient selected from nucleic acids, polypeptides, viruses, or combinations thereof.
- the kit of the present invention is composed of two or more chambers, and the end user can easily form nanoparticles by simply mixing the chambers.
- the term “simple mixing” may include all acts of “mixing”, and means that no specific conditions are imposed on the act of mixing to form nanoparticles.
- the mixing may be accomplished by various methods such as dripping, stirring (vortexing), decanting, and the like, but is not limited thereto.
- 90% or more, 95% or more, or 99% or more of the theoretically formable amount of nanoparticles is rapidly, for example, within 1 minute, within 30 seconds, or within 15 seconds. can be formed within
- the active ingredient in the nanoparticles formed by simple mixing by the end user can form a complex through electrostatic interaction with the cationic compound, and the complex is inside the nanoparticle structure formed by the amphiphilic block copolymer and polylactate. can be enclosed in
- the hydrophilic portion of the amphiphilic block copolymer forms the outer wall of the nanoparticles, and the hydrophobic portion of the amphiphilic block copolymer and polylactic acid contained as separate components from the amphiphilic block copolymer
- the salt forms the inner wall of the nanoparticles, and the complex of the active ingredient and the cationic compound may be encapsulated inside the formed nanoparticles.
- This nanoparticle structure improves the stability of the active ingredient in blood or body fluid.
- nucleic acid may be, for example, DNA, RNA, siRNA, shRNA, miRNA, mRNA, aptamer, antisense oligonucleotide, or a combination thereof, but is not limited thereto.
- polypeptide includes a polypeptide sequence of an antibody or fragment thereof, a protein having activity in the body, such as a cytokine, a hormone or an analog thereof, or an antigen, an analog or a precursor thereof, and is recognized as an antigen through a series of processes in the body. It may mean a protein that can be
- the "virus” may be an oncolytic virus, for example, adenovirus, vaccinia virus, herpes simplex virus (HSV), and may be one or more selected from the group consisting of vesicular stomatitis virus (VSV). .
- the oncolytic virus is an adenovirus.
- the adenovirus used in the embodiment of the present invention contains a luciferase gene, which can be confirmed through imaging.
- the virus can express several types of therapeutic genes in the body of an individual, and is not limited to a specific molecular weight, protein, bioactivity, or therapeutic field.
- the prophylactic virus can induce immunity in the body of a subject against a target disease.
- a composition containing a virus for disease prevention can reduce the induction of immunity by the virus itself, can designate or expand target cells, and reduce hyperimmune response to the virus upon re-administration to obtain an effective effect by inoculating several times. have an advantage
- the particle size of the nanoparticles may be defined as a Z-average value, for example, 800 nm or less, 600 nm or less, 500 nm or less, 400 nm or less, 300 nm or less, 200 nm or less, or 150 nm or less. and may be 10 nm or more, 50 nm or more, or 100 nm or more.
- the particle size of the nanoparticles as defined by the Z-average value is, for example, 10-800 nm, 10-600 nm, 10-500 nm, 10-400 nm, 10-300 nm, 10 to 200 nm or from 10 to 150 nm.
- the “Z-average” may mean an average of hydrodynamic diameters of particle distributions measured using dynamic light scattering (DSL).
- the nanoparticles have a monodisperse particle distribution, and the polydispersity index may be, for example, 0.01 to 0.30, 0.05 to 0.25, or 0.1 to 0.2.
- the surface charge of the nanoparticles for example, -40 mV or more, -30 mV or more, -20 mV or more, or -10 mV or more, and also 40 mV or less, 30 mV or less, 20 mV or less, or It may be 10 mV or less.
- the surface charge of the nanoparticles may be, for example, -40 to 40 mV, -30 to 30 mV, -20 to 20 mV, or -10 to 10 mV.
- the surface charge may be measured in an environment close to a biological environment, for example, may be measured in 8 to 12 mM HEPES buffer (pH 7.0 to 7.5).
- the active ingredient is a nucleic acid
- one or more ends of the nucleic acid may be modified with one or more selected from the group consisting of cholesterol, tocopherol, and fatty acids having 10 to 24 carbon atoms.
- the cholesterol, tocopherol and fatty acids having 10 to 24 carbon atoms include cholesterol, tocopherols and their respective analogs, derivatives, and metabolites of fatty acids.
- the active ingredient is, based on the total weight of nanoparticles formed by the kit of the present invention, for example, 30% by weight or less, 25% by weight or less, 20% by weight or less, 15% by weight or less, 10% by weight or less, or 5 % by weight or less, and may also be 0.001 wt% or more, 0.01 wt% or more, 0.05 wt% or more, 0.1 wt% or more, 0.25 wt% or more, 0.5 wt% or more, or 1 wt% or more.
- the active ingredient is based on the total weight of the composition, for example, 0.05 to 30% by weight, 0.1 to 25% by weight, 0.25 to 20% by weight, 0.5 to 15% by weight, 1 to 10% by weight, or 1 to 5% by weight. If the content of the active ingredient is less than the above range based on the weight of the entire composition, the amount of the carrier used compared to the drug is too large, and there may be side effects due to the carrier rather than the drug. If it exceeds the above range, the size of the nanoparticles is too large It increases, the stability of nanoparticles is reduced, and there is a fear that the loss rate during filter sterilization increases.
- the nanoparticles may include a virus 1x10 6 to 1x10 14 VP (Virus particle), 1x10 7 to 1x10 13 VP, 1x10 8 to 1x10 12 VP, or 1x10 9 to 1x10 11 VP.
- virus 1x10 6 to 1x10 14 VP Virus particle
- 1x10 7 to 1x10 13 VP 1x10 8 to 1x10 12 VP
- 1x10 9 to 1x10 11 VP 1x10 6 to 1x10 14 VP (Virus particle)
- the cationic compound may be a cationic lipid or a cationic polymer, and more specifically, a cationic lipid.
- the cationic lipid is N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-( 1-(2,3-dioleoyloxy)propyl-N,N,N-trimethylammonium chloride (DOTAP), N,N-dimethyl-(2,3-dioleoyloxy)propylamine (DODMA), N ,N,N-Trimethyl-(2,3-dioleoyloxy)propylamine (DOTMA), 1,2-Diacyl-3-trimethylammonium-propane (TAP), 1,2-Diacyl-3-dimethyl Ammonium-propane (DAP), 3beta-[N-(N',N',N'-trimethylaminoethane)carbamoyl]cholesterol (TC-cholesterol), 3beta-
- cationic lipids When using such cationic lipids, it is preferable to use less polycationic lipids having a high cation density in the molecule in order to reduce the toxicity caused by the cationic lipids, and more specifically, it is possible to represent cations in aqueous solution per molecule. It is preferable to use a cationic lipid having one functional group.
- the cationic lipid is 3beta-[N-(N',N',N'-trimethylaminoethane)carbamoyl]cholesterol (TC-cholesterol), 3beta[N-( N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-cholesterol), 3beta[N-(N'-monomethylaminoethane)carbamoyl]cholesterol (MC-cholesterol), 3beta[N-( Aminoethane)carbamoyl]cholesterol (AC-cholesterol), N-(1-(2,3-dioleoyloxy)propyl-N,N,N-trimethylammonium chloride (DOTAP), N,N-dimethyl-( 2,3-dioleoyloxy)propylamine (DODMA), and N,N,N-trimethyl-(2,3-
- the cationic polymer is chitosan (chitosan), glycol chitosan (glycol chitosan), protamine (protamine), polylysine (polylysine), polyarginine (polyarginine), polyamidoamine (PAMAM), It may be selected from the group consisting of polyethyleneimine, dextran, hyaluronic acid, albumin, high molecular weight polyethyleneimine (PEI), polyamine and polyvinylamine (PVAm), and more specifically It may be at least one selected from the group consisting of polyethyleneimine (PEI), polyamine, and polyvinylamine (PVAm).
- PEI polyethyleneimine
- PVAm polyvinylamine
- the cationic lipid may be a cationic lipid of Formula 1:
- n and m are each independently 0 to 12, 2 ⁇ n + m ⁇ 12,
- a and b are each independently 1 to 6,
- R 1 and R 2 are each independently selected from the group consisting of saturated and unsaturated hydrocarbon groups having 11 to 25 carbon atoms.
- n and m are each independently 1 to 9, and 2 ⁇ n+m ⁇ 10.
- a and b may each independently be 2 to 4.
- R 1 and R 2 are each independently, lauryl, myristyl, palmityl, stearyl, arachidyl, be Henyl (behenyl), lignoceryl (lignoceryl), cerotyl (cerotyl), myristoleyl (myristoleyl), palmitoleyl (palmitoleyl), sapienyl (sapienyl), oleyl (oleyl), linoleyl ( linoleyl), arachidonyl, eicosapentaenyl, erucyl, docosahexaenyl, and cerotyl may be selected from the group consisting of.
- the cationic lipid is 1,6-dioleoyltriethylenetetramide (N,N'-((ethane-1,2-diylbis(azanediyl))bis(ethane-2,1-diyl) ) dioleamide), 1,8-dilinoleoyltetraethylenepentamide ((9Z,9'Z,12Z,12'Z)-N,N'-(((azanediylbis(ethane-2,1-diyl)) bis(azanediyl))bis(ethane-2,1-diyl))bis(octadeca-9,12-dienamide)), 1,4-dimyristoleoyldiethylenetriamide ((9Z,9'Z)-N ,N'-(azanediylbis(ethane-2,1-diyl))bis(tetradec-9-enamide)), 1,10
- the content of the cationic compound in the composition formed by the kit of the present invention is, based on 1 part by weight of the active ingredient, for example, 25 parts by weight or less, 20 parts by weight or less, 18 parts by weight or less, 15 parts by weight or less, 12 parts by weight or less. It may be parts by weight or less, 10 parts by weight or less, or 8 parts by weight or less, and may also be 1 part by weight or more, 1.5 parts by weight or more, 2 parts by weight or more, 2.5 parts by weight or more, 3 parts by weight or more, or 3.5 parts by weight or more.
- the content of the cationic compound in the composition based on 1 part by weight of the active ingredient, 1 to 25 parts by weight, 1.5 to 10 parts by weight, 2 to 15 parts by weight, 2.5 to 10 parts by weight, or 3 to 8 parts by weight.
- the content of the cationic compound is 1 ⁇ g or more, 5 ⁇ g or more, 10 ⁇ g or more, 15 ⁇ g or more, or 18 ⁇ g or more, based on 1x10 10 VP of the virus, and 150 ⁇ g or less, 100 ⁇ g or less, 50 ⁇ g or less, or 30 ⁇ g or less, for example, 1 ⁇ g to 150 ⁇ g, 5 ⁇ g to 100 ⁇ g, 10 ⁇ g to 50 ⁇ g, 15 ⁇ g to 30 ⁇ g.
- the content of the cationic compound in the composition is less than the above range, it may not be possible to form a stable complex with the active ingredient, and if it exceeds the above range, the size of the nanoparticles becomes too large to decrease stability and there is a risk that the loss rate during filter sterilization may increase.
- the cationic compound and the nucleic acid are combined through an electrostatic interaction to form a complex.
- the ratio of the charge amount of the nucleic acid (P) and the cationic compound (N) is 0.5 or more, 1 or more, 2 or more , or 3.5 or more, and may be 100 or less, 50 or less, 20 or less, for example, 0.5 to 100, 1 to 50, 2 to 20, 5 to 15, or 7 to 12.
- the ratio (N/P) When the ratio (N/P) is less than the above range, it may be difficult to form a complex including a sufficient amount of nucleic acid, whereas when the ratio (N/P) exceeds the above range, there is a risk of causing toxicity. .
- the N/P value may play an important role in the specific expression of the active ingredient in the spleen.
- the amphiphilic block copolymer may be an A-B type block copolymer including a hydrophilic A block and a hydrophobic B block.
- the A-B type block copolymer forms core-shell type polymer nanoparticles in which the hydrophobic B block forms a core (inner wall) and the hydrophilic A block forms a shell (outer wall) in an aqueous solution.
- the hydrophilic A block may be at least one selected from the group consisting of polyalkylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylamide, and derivatives thereof.
- the hydrophilic block A may be at least one selected from the group consisting of monomethoxypolyethylene glycol, monoacetoxypolyethylene glycol, polyethylene glycol, a copolymer of polyethylene and propylene glycol, and polyvinylpyrrolidone.
- the hydrophilic A block may have a number average molecular weight of 200 to 50,000 Daltons, more specifically 1,000 to 20,000 Daltons, and even more specifically 1,000 to 5,000 Daltons.
- amphiphilic block copolymer and polylactate are chemically bound to the end of the hydrophilic A block with a functional group capable of reaching a specific tissue or cell, a ligand, or a functional group capable of facilitating intracellular delivery. It is possible to control the distribution in the body of the polymer nanoparticle delivery system formed with the above, or to increase the efficiency of the delivery of the nanoparticle delivery system into cells.
- the functional group or ligand may be at least one selected from the group consisting of monosaccharides, polysaccharides, vitamins, peptides, proteins, and antibodies to cell surface receptors.
- the functional group or ligand is anisamide, vitamin B9 (folic acid), vitamin B12, vitamin A, galactose, lactose, mannose, hyaluronic acid, RGD peptide, NGR peptide, transferrin, antibody against transferrin receptor It may be one or more selected from the group consisting of.
- the hydrophobic B block is a biocompatible biodegradable polymer, and in one embodiment, it may be one or more selected from the group consisting of polyester, polyanhydride, polyamino acid, polyorthoester, and polyphosphazine.
- the hydrophobic B block is polylactide, polyglycolide, polycaprolactone, polydioxan-2-one, a copolymer of polylactide and glycolide, polylactide and polydioxan-2-one It may be at least one selected from the group consisting of a copolymer of, a copolymer of polylactide and polycaprolactone, and a copolymer of polyglycolide and polycaprolactone.
- the hydrophobic B block may have a number average molecular weight of 50 to 50,000 Daltons, more specifically 200 to 20,000 Daltons, and even more specifically 1,000 to 5,000 Daltons.
- the hydrophobic B block in order to increase the hydrophobicity of the hydrophobic B block to improve the stability of the nanoparticles, tocopherol, cholesterol, or a fatty acid having 10 to 24 carbon atoms in the hydroxy group at the end of the hydrophobic B block is chemically It may be modified by combining with .
- the composition ratio of the hydrophilic block (A) and the hydrophobic block (B), based on the total weight of the copolymer may be in the range of 40 to 70% by weight. And, more specifically, it may be in the range of 50 to 60% by weight. If the proportion of the hydrophilic block (A) is less than 40% by weight based on the total weight of the copolymer, the solubility of the polymer in water is low and it is difficult to form nanoparticles, so that the copolymer has sufficient solubility in water to form nanoparticles.
- the proportion of the hydrophilic block (A) is 40% by weight or more in order to have a
- the proportion of the hydrophilic block (A) exceeds 70% by weight based on the total weight of the copolymer, the hydrophilicity is too high and the stability of the polymer nanoparticles is lowered, so it is difficult to use it as a solubilization composition of the active ingredient/cationic compound complex, In consideration of particle stability, it is preferable that the proportion of the hydrophilic block (A) is 70% by weight or less.
- the polylactic acid salt in the composition formed by the kit of the present invention is distributed in the core (inner wall) of the nanoparticles to strengthen the hydrophobicity of the core to stabilize the nanoparticles and at the same time, the reticuloendothelial system (RES) in the body ) to effectively avoid That is, the carboxylate anion of polylactic acid binds to the cationic complex more effectively than polylactic acid and reduces the surface potential of the polymer nanoparticles. It is less captured by the endothelial system, and thus has the advantage of excellent delivery efficiency to a target site (eg, cancer cells, inflammatory cells, etc.).
- a target site eg, cancer cells, inflammatory cells, etc.
- the polylactic acid salt included as a component of the inner wall of the nanoparticles may have a number average molecular weight of 500 to 50,000 Daltons, and more specifically, 1,000 to 10,000 Daltons. it could be If the number average molecular weight of the polylactate is less than 500 Daltons, hydrophobicity may be too low to exist in the core (inner wall) of the nanoparticles, and if it exceeds 50,000 Daltons, there may be a problem in that the particles of the polymer nanoparticles become large.
- the terminal opposite to the metal carboxylate (eg, sodium carboxylate) among the ends of the polylactate (eg, sodium polylactate) is hydroxy, acetoxy, benzoyloxy, decanoyloxy , may be substituted with one selected from the group consisting of palmitoyloxy and alkoxy having 1 to 2 carbon atoms.
- A is -COO-CHZ-;
- B is -COO-CHY-, -COO-CH 2 CH 2 CH 2 CH 2 CH 2 - or -COO-CH 2 CH 2 OCH 2 -;
- R is a hydrogen atom or an acetyl, benzoyl, decanoyl, palmitoyl, methyl, or ethyl group;
- Z and Y are each a hydrogen atom, or a methyl or phenyl group;
- M is Na, K, or Li;
- n is an integer from 1 to 30;
- m is an integer from 0 to 20;
- X is a methyl group
- Y' is a hydrogen atom or a phenyl group
- p is an integer from 0 to 25
- q is an integer from 0 to 25, with the proviso that p+q is an integer from 5 to 25
- R is a hydrogen atom or an acetyl, benzoyl, decanoyl, palmitoyl, methyl or ethyl group
- M is Na, K, or Li
- Z is a hydrogen atom, a methyl or phenyl group
- W-M' is or ego
- PAD is D,L-polylactic acid, D-polylactic acid, polymandelic acid, a copolymer of D,L-lactic acid and glycolic acid, a copolymer of D,L-lactic acid and mandelic acid, D,L-lactic acid and copolymers of caprolactone and copolymers of D,L-lactic acid and 1,4-dioxan-2-one
- R is a hydrogen atom or an acetyl, benzoyl, decanoyl, palmitoyl, methyl or ethyl group
- M is independently Na, K, or Li
- S is ego;
- L is -NR 1 - or -0-, wherein R 1 is a hydrogen atom or C 1-10 alkyl;
- Q is CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH 2 CH 2 CH 2 CH 3 , or CH 2 C 6 H 5 ;
- a is an integer from 0 to 4;
- b is an integer from 1 to 10;
- M is Na, K, or Li;
- PAD is D,L-polylactic acid, D-polylactic acid, polymandelic acid, a copolymer of D,L-lactic acid and glycolic acid, a copolymer of D,L-lactic acid and mandelic acid, D,L-lactic acid and at least one selected from the group consisting of a copolymer of caprolactone, and a copolymer of D,L-lactic acid and 1,4-dioxan-2-one;
- R' is -PAD-OC(O)-CH 2 CH 2 -C(O)-OM, wherein PAD is D,L-polylactic acid, D-polylactic acid, polymandelic acid, D ,L-lactic acid and glycolic acid copolymer, D,L-lactic acid and mandelic acid copolymer, D,L-lactic acid and caprolactone copolymer, D,L-lactic acid and 1,4-dioxane-2 -one is selected from the group consisting of copolymers, M is Na, K, or Li; a is an integer from 1 to 4;
- X and X' are independently hydrogen, alkyl having 1 to 10 carbons, or aryl having 6 to 20 carbons; Y and Z are independently Na, K, or Li; m and n are independently integers from 0 to 95, provided that 5 ⁇ m + n ⁇ 100; a and b are independently integers from 1 to 6; R is -(CH 2 ) k -, divalent alkenyl having 2 to 10 carbon atoms, divalent aryl having 6 to 20 carbon atoms, or a combination thereof, where k is 0 to 10 is the integer of
- the polylactate may be a compound of Formula 2 or Formula 3 above.
- the kit of the present invention in order to increase the intracellular delivery efficiency of mRNA, 0.01 to 50% by weight based on the total weight of the composition formed by the kit of the present invention, more specifically 0.1 to 10 It may further comprise fusible lipids in weight percent.
- the fusible lipid When the fusible lipid is mixed with the complex of mRNA and cationic lipid, it binds by hydrophobic interaction to form a complex of mRNA, cationic lipid and fused lipid, and the complex including the fused lipid is amphiphilic block air Encapsulated within the composite nanoparticle structure.
- the fusible lipid may be one or a combination of two or more selected from the group consisting of phospholipids, cholesterol, and tocopherol.
- the phospholipid may be at least one selected from the group consisting of phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidic acid.
- the phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidic acid may be combined with one or two C10-24 fatty acids.
- the cholesterol and tocopherols include each analog, derivative, and metabolite of cholesterol and tocopherol.
- the fusible lipids include dilauroyl phosphatidylethanolamine, dimyristoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, and distearoyl Ethanolamine (distearoyl phosphatidylethanolamine), dioleoyl phosphatidylethanolamine (DOPE), dipalmitoleoyl phosphoethanolamine (1,2-dipalmitoleoyl-sn-glycero-3-phosphoethanolamine, DPPE), dilinoleo yl phosphatidylethanolamine (dilinoleoyl phosphatidylethanolamine), 1-palmitoyl-2-oleoyl phosphatidylethanolamine (1-palmitoyl-2-oleoyl phosphatidylethanolamine), 1,2-dipitanoyl-3-sn-phosphatidylethanolamine (1, 2-diphytanoyl-3-s
- the fusible lipid is dioleoyl phosphatidylethanolamine (DOPE), dipalmitoleoyl phosphocholine (1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine, DPPC), diol as leoyl phosphocholine (1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC) and dipalmitoleoyl-sn-glycero-3-phosphoethanolamine (DPPE) It may be one or more selected from the group consisting of.
- DOPE dioleoyl phosphatidylethanolamine
- DOPC dipalmitoleoyl phosphocholine
- DOPC dipalmitoleoyl phosphocholine
- DOPC dipalmitoleoyl phosphocholine
- DOPC dipalmitoleoyl phosphocholine
- DOPC dipalmitoleoyl phosphocholine
- DOPC dipalmitoleoy
- the content of the amphiphilic block copolymer including the hydrophilic block (A) and the hydrophobic block (B) is 1 part by weight of the cationic compound based on 0.01 to 50 parts by weight, 0.01 to 30 parts by weight, 0.01 to 15 parts by weight, 0.01 to 12 parts by weight, 0.1 to 50 parts by weight, 0.1 to 30 parts by weight, 0.1 to 15 parts by weight, 0.1 to 12 parts by weight , 0.5 to 50 parts by weight, 0.5 to 30 parts by weight, 0.5 to 15 parts by weight, 0.5 to 12 parts by weight, 1 to 50 parts by weight, 1 to 30 parts by weight, 1 to 15 parts by weight, or 1 to 12 parts by weight. have.
- the content of the amphiphilic block copolymer may be adjusted according to the active ingredient within the above range.
- the content of the amphiphilic block copolymer may be 3 to 7 parts by weight based on 1 part by weight of the cationic compound, and in another embodiment, when the active ingredient is a nucleic acid, The content of the amphiphilic block copolymer may be 0.7 to 7 parts by weight, 1 to 5 parts by weight, or 1 to 3 parts by weight based on 1 part by weight of the cationic compound.
- the content of the polylactic acid salt is 0.1 to 100 parts by weight, 0.1 to 80 parts by weight, 0.1 to 100 parts by weight, based on 1 part by weight of the cationic compound. 50 parts by weight, 0.1 to 30 parts by weight, 0.1 to 10 parts by weight, 0.1 to 5 parts by weight, 0.5 to 100 parts by weight, 0.5 to 80 parts by weight, 0.5 to 50 parts by weight, 0.5 to 30 parts by weight, 1 to 100 parts by weight parts, 1 to 80 parts by weight, 1 to 50 parts by weight, 1 to 30 parts by weight, 2 to 100 parts by weight, 2 to 80 parts by weight, 2 to 50 parts by weight, or 2 to 30 parts by weight.
- the content of the polylactic acid salt may be adjusted according to the active ingredient within the above range.
- the content of the polylactic acid salt when the active ingredient is a virus, may be 3 to 15 parts by weight based on 1 part by weight of the cationic compound, and in another embodiment, when the active ingredient is a nucleic acid, the polylactic acid
- the content of the salt may be 0.2 to 4 parts by weight, 1 to 4 parts by weight, or 0.2 to 0.8 parts by weight based on 1 part by weight of the cationic compound.
- the first chamber and/or the second chamber may further include an aqueous solution, a water-miscible organic solvent, or a combination thereof.
- aqueous solution may be used in the same sense as an aqueous solution, for example, may refer to water, sterile purified water, buffer solution, injection solution, etc., may be a buffer solution further containing an organic acid.
- the aqueous solution may be, for example, a citric acid buffer, a PBS buffer, and the like, but is not limited thereto.
- the "water-miscible organic solvent” may be a C1 to C4 lower alcohol, acetone, acetonitrile, a water mixture thereof, or a mixture thereof, but is not limited thereto.
- the mixture of the amphiphilic block copolymer, the cationic compound, and the polylactic acid salt contained in the first chamber may be used as the contents of the first chamber by filtering one or more times with a hydrophilic filter after mixing.
- the material of the hydrophilic filter is, for example, nylon, mixed cellulose ester (MCE), polyethylsulfone (PES), polyvinylidene difluoridem PVDF, cellulose acetate (CA). , polytetrafluoroethylene (PTFE), and mixtures thereof.
- MCE mixed cellulose ester
- PES polyethylsulfone
- PVDF polyvinylidene difluoridem PVDF
- CA cellulose acetate
- PTFE polytetrafluoroethylene
- the active ingredient may be more successfully incorporated into the nanoparticles, and the stability of the nanoparticles may be increased.
- the second chamber may further include a stabilizer suitable for improving the stability of the active ingredient.
- the stabilizer may further include a pH adjuster, an inorganic salt, a saccharide, a surfactant, a chelating agent, and the like, but is not limited thereto.
- the “saccharide” may refer to monosaccharides, disaccharides, sugar alcohols that are reducing sugars thereof, polymers of single or mixed polysaccharides, and the like, and the polysaccharides may refer to three or more saccharides.
- the monosaccharides include, for example, mannose, glucose, arabinose, fructose, galactose, and the like;
- Examples of the disaccharide include sucrose, trehalose, maltose, lactose, cellobiose, gentiobiose, isomaltose, melibose, and the like;
- the sugar alcohol includes mannitol, sorbitol, xylitol, erythritol, maltitol, and the like;
- Examples of the polysaccharide include, but are not limited to, raffinose, dextran, starch, hydroxyethyl starch, cyclodextrin, cellulose, hetastarch, and oligosaccharide.
- the “pH-adjusting agent” may be Tris, glycine, histidine, glutamate, succinate, phosphate, acetate, aspartate or a combination thereof
- the “surfactant” may be sodium lauryl sulfate, dioctyl Sodium sulfosuccinate, dioctyl sodium sulfonate, chenodeoxycholic acid, N-lauroyl sarcosine sodium salt, lithium dodecyl sulfate, 1-octanesulfonic acid sodium salt, sodium cholate hydrate, sodium deoxycholate, glycoside Deoxycholic acid sodium salt, benzalkonium chloride, Triton X-100, Triton X-114, lauromacrogol 400, polyoxyl 40 stearate, polysorbate 20, 40, 60, 65 and 80 or a combination thereof, but is not limited thereto.
- the “chelating agent” may be citric acid, polyphenolic acid, EDTA, DTPA, EDDHA, or a combination thereof, but is not limited thereto.
- the “inorganic salt” refers to a salt of a monovalent or divalent metal, and may be NaCl, KCl, MgCl 2 , CaCl 2 , MgSO 4 , CaSO 4 , CaCO 3 , MgCO 3 , or the like, but is not limited thereto.
- the second chamber is 5 to 15 mM Tris, 5 to 15 mM histidine, 50 to 90 mM NaCl, 2 to 8% sucrose (w/v), 0.5 to 1.5 mM MgCl 2 , 0.005 to 0.05% (w/v) PS-80, 0.05 to 0.15 mM EDTA, and 0.1 to 1.0% ethanol (v/v), and the pH may be 7.0 to 8.0.
- the second chamber is a PBS buffer, for example, PH 7.0 to pH 8.0, 2.0 to 3.5 mM KCl, 1.0 to 2.5 mM KH 2 PO 4 , 125 to 145 mM NaCl, and a solution comprising 7.5 to 9.5 mM Na 2 HPO 4 .
- the "chamber” is suitable for containing a material of nanoparticles or a solvent containing the same, and includes glass, plastic, paper, pack, etc., but is not limited thereto.
- Preparation Example 1 Preparation of first chamber composition containing dioTETA/mPEG-PLA-tocopherol (2k-1.7k)/PLANa (1.7k) and formation of nanoparticles
- dioTETA 1,6-dioleoyl triethylenetetramide
- mPEG-PLA-tocopherol monomethoxypolyethylene glycol-polylactide-tocopherol copolymer
- PLANa sodium polylactate
- A195 buffer (10 mM Tris, 10 mM histidine, 75 mM NaCl, 5% sucrose (w/v), 1 mM MgCl 2 , 0.02% (w/v) PS-80, 0.1 mM EDTA, 0.5% ethanol (v/v) v), pH 7.4) was prepared by counting VQAd CMV Luc virus (ViraQuest, Lot #: 33088) in the form dispensed to 1x10 10 VP.
- Nanoparticles were formed by mixing the first chamber composition and the second chamber composition by vortexing for 10 to 15 seconds immediately before use.
- MDA-MB435 cells with low CAR expression suitable for evaluating the virus delivery efficiency were prepared.
- the nanoparticles of Examples 1 to 4 were formed by mixing the first chamber composition and the second chamber composition immediately before intracellular injection, and the cells were dispensed in an amount corresponding to 500 moi based on the virus. After additional incubation for 15 to 24 hours, luciferin was added to the cells to measure the amount of luciferase expressed.
- a virus naked Ad; Ad
- Preparation Example 2 Preparation of first chamber composition containing (dioTETA)/mPEG-PLA(2k-1.7k)/PLANa(1.7k) and formation of nanoparticles
- dioTETA 20 mg in 1 ml of 20 mM sodium acetate buffer (pH 4.6), 10 mg of monomethoxypolyethylene glycol-polylactide copolymer (mPEG-PLA) (2k-1.7k) in 1 ml of water, and PLANa (1.7k)
- mPEG-PLA monomethoxypolyethylene glycol-polylactide copolymer
- PLANa 1.7k
- Nanoparticles were formed by mixing the first chamber composition and the second chamber composition by vortexing for 10 to 15 seconds immediately before use.
- Nanoparticles corresponding to Examples 6 or 8 were formed by mixing the first chamber composition and the second chamber composition immediately before intracellular injection, and were dispensed into cells in an amount corresponding to 250 ng mRNA in 96 wells. After additional incubation for 6 hours, the amount of luciferase expressed by adding luciferin to the cells was measured.
- a commercial reagent, TransIT ® -mRNA Kit (Mirus Bio) was used. The results are shown in FIG. 4 . As a result, it was observed that the nanoparticles of the experimental example showed a similar level of intracellular delivery efficiency as the control.
- Nanoparticles prepared with the kit have higher intracellular delivery efficiency just before administration due to the stability of the nanoparticles
- HepG2 cells were prepared and the intracellular delivery efficiency was compared as an accelerated test.
- Nanoparticles corresponding to Example 6 were formed by mixing the first chamber composition and the second chamber composition immediately before intracellular injection, and were dispensed into cells in an amount corresponding to 250 ng mRNA in 96 wells.
- nanoparticles prepared in the same manner and nanoparticles prepared using L3K, which is usually used as a transfection agent, stored at 42° C. for 1 hour were used, and the same was dispensed into cells.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Nanotechnology (AREA)
- Genetics & Genomics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims (8)
- 양친성 블록 공중합체, 양이온성 화합물 및 폴리락트산염을 포함하는 제1 챔버; 및핵산, 폴리펩티드, 바이러스 또는 이들의 조합으로부터 선택된 유효성분을 포함하는 제2 챔버;를 포함하는,나노입자 조성물 제조용 키트.
- 제1항에 있어서, 세포 내 유효성분을 전달하는 나노입자를 형성하기 위한 것인, 나노입자 조성물 제조용 키트.
- 제1항에 있어서, 상기 제1 챔버 및 제2 챔버로 이루어진 군 중에서 선택된 하나 이상은 추가의 용매를 더 포함하는 것인, 나노입자 조성물 제조용 키트.
- 제3항에 있어서, 상기 용매는 수성 용매, 수혼화성 용매 또는 이의 혼합물인, 나노입자 조성물 제조용 키트.
- 제1항에 있어서, 상기 제2 챔버는 pH 조절제, 무기염, 당류, 계면활성제, 킬레이트제 또는 이들의 조합을 더 포함하는 것인, 나노입자 조성물 제조용 키트.
- 제1항에 있어서, 상기 양친성 블록 공중합체의 양은 상기 양이온성 화합물 1 중량부를 기준으로 0.01 내지 50 중량부인, 나노입자 조성물 제조용 키트.
- 제1항에 있어서, 상기 폴리락트산염의 양은 상기 양이온성 화합물 1 중량부를 기준으로 0.1 내지 100 중량부인, 나노입자 조성물 제조용 키트.
- 제1항에 있어서, 상기 제1 챔버에서 상기 양친성 블록 공중합체, 양이온성 화합물, 및 폴리락트산염의 혼합물은, 혼합 후 친수성 필터로 1회 이상 여과된 것인, 나노입자 조성물 제조용 키트.
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2020407348A AU2020407348A1 (en) | 2019-12-20 | 2020-12-16 | Kit for preparing nanoparticle composition for drug delivery, comprising polylactic acid salt |
JP2022538147A JP2023508313A (ja) | 2019-12-20 | 2020-12-16 | ポリ乳酸塩を含む薬物送達用ナノ粒子組成物製造用キット |
EP20901243.4A EP4079298A4 (en) | 2019-12-20 | 2020-12-16 | KIT FOR PRODUCING A NANOPARTICLE COMPOSITION FOR ACTIVE DELIVERY WITH POLYLACTIC ACID SALT |
CA3162374A CA3162374A1 (en) | 2019-12-20 | 2020-12-16 | Kit for preparing nanoparticle composition for drug delivery, comprising polylactic acid salt |
BR112022012118A BR112022012118A2 (pt) | 2019-12-20 | 2020-12-16 | Kit para preparar uma composição de nanopartículas |
CN202080096831.7A CN115135310A (zh) | 2019-12-20 | 2020-12-16 | 用于制备包含聚乳酸盐的药物递送用纳米颗粒组合物的试剂盒 |
US17/787,156 US20230039124A1 (en) | 2019-12-20 | 2020-12-16 | Kit for preparing nanoparticle composition for drug delivery, comprising polylactic acid salt |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20190171528 | 2019-12-20 | ||
KR10-2019-0171528 | 2019-12-20 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021125805A1 true WO2021125805A1 (ko) | 2021-06-24 |
Family
ID=76477867
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2020/018480 WO2021125805A1 (ko) | 2019-12-20 | 2020-12-16 | 폴리락트산염을 포함하는 약물전달용 나노입자 조성물 제조용 키트 |
Country Status (9)
Country | Link |
---|---|
US (1) | US20230039124A1 (ko) |
EP (1) | EP4079298A4 (ko) |
JP (1) | JP2023508313A (ko) |
KR (1) | KR102650691B1 (ko) |
CN (1) | CN115135310A (ko) |
AU (1) | AU2020407348A1 (ko) |
BR (1) | BR112022012118A2 (ko) |
CA (1) | CA3162374A1 (ko) |
WO (1) | WO2021125805A1 (ko) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20230072453A (ko) | 2021-11-17 | 2023-05-24 | 주식회사 엘지생활건강 | 구형 물질을 포함하는 두피 또는 모발용 조성물 |
KR20240035317A (ko) * | 2022-09-08 | 2024-03-15 | 주식회사 삼양홀딩스 | 약물 함유 나노입자 제조용 키트 및 약물전달용 나노입자 조성물 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05111524A (ja) * | 1991-10-23 | 1993-05-07 | Maeda Sangyo Kk | 医療用キツト製品 |
JP2002542341A (ja) * | 1999-04-20 | 2002-12-10 | ザ ユニバーシティ オブ ブリティッシュ コロンビア | カチオン性peg脂質および使用方法。 |
KR20040021760A (ko) * | 2002-09-04 | 2004-03-11 | 학교법인 포항공과대학교 | 약물 담지능력이 우수한 블록 공중합체 미셀 조성물 |
WO2018220553A1 (en) * | 2017-05-30 | 2018-12-06 | Glaxosmithkline Biologicals Sa | Methods for manufacturing a liposome encapsulated rna |
KR20190127277A (ko) * | 2018-05-04 | 2019-11-13 | 주식회사 삼양바이오팜 | mRNA 전달용 고분자 나노입자 조성물 및 그 제조방법 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2018003096A (es) * | 2015-09-15 | 2018-05-11 | Samyang Biopharmaceuticals | Composicion farmaceutica que contiene farmaco anionico, y metodo de preparacion para la misma. |
-
2020
- 2020-12-16 WO PCT/KR2020/018480 patent/WO2021125805A1/ko unknown
- 2020-12-16 EP EP20901243.4A patent/EP4079298A4/en active Pending
- 2020-12-16 CA CA3162374A patent/CA3162374A1/en active Pending
- 2020-12-16 AU AU2020407348A patent/AU2020407348A1/en active Pending
- 2020-12-16 JP JP2022538147A patent/JP2023508313A/ja active Pending
- 2020-12-16 KR KR1020200176143A patent/KR102650691B1/ko active IP Right Grant
- 2020-12-16 CN CN202080096831.7A patent/CN115135310A/zh active Pending
- 2020-12-16 US US17/787,156 patent/US20230039124A1/en active Pending
- 2020-12-16 BR BR112022012118A patent/BR112022012118A2/pt unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05111524A (ja) * | 1991-10-23 | 1993-05-07 | Maeda Sangyo Kk | 医療用キツト製品 |
JP2002542341A (ja) * | 1999-04-20 | 2002-12-10 | ザ ユニバーシティ オブ ブリティッシュ コロンビア | カチオン性peg脂質および使用方法。 |
KR20040021760A (ko) * | 2002-09-04 | 2004-03-11 | 학교법인 포항공과대학교 | 약물 담지능력이 우수한 블록 공중합체 미셀 조성물 |
WO2018220553A1 (en) * | 2017-05-30 | 2018-12-06 | Glaxosmithkline Biologicals Sa | Methods for manufacturing a liposome encapsulated rna |
KR20190127277A (ko) * | 2018-05-04 | 2019-11-13 | 주식회사 삼양바이오팜 | mRNA 전달용 고분자 나노입자 조성물 및 그 제조방법 |
Non-Patent Citations (3)
Title |
---|
DE PAULA DBENTLEY MVMAHATO RI: "Hydrophobization and bioconjugation for enhanced siRNA delivery and targeting", RNA, vol. 13, 2007, pages 431 - 56 |
GARY DJPURI NWON YY: "Polymer-based siRNA delivery: Perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery", J CONTROL RELEASE, vol. 121, 2007, pages 64 - 73, XP022179907, DOI: 10.1016/j.jconrel.2007.05.021 |
See also references of EP4079298A4 |
Also Published As
Publication number | Publication date |
---|---|
CA3162374A1 (en) | 2021-06-24 |
AU2020407348A1 (en) | 2022-07-14 |
EP4079298A1 (en) | 2022-10-26 |
JP2023508313A (ja) | 2023-03-02 |
US20230039124A1 (en) | 2023-02-09 |
KR20210081256A (ko) | 2021-07-01 |
CN115135310A (zh) | 2022-09-30 |
KR102650691B1 (ko) | 2024-03-25 |
EP4079298A4 (en) | 2024-01-17 |
BR112022012118A2 (pt) | 2022-08-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2013256008B2 (en) | Lipid-based drug carriers for rapid penetration through mucus linings | |
WO2021125805A1 (ko) | 폴리락트산염을 포함하는 약물전달용 나노입자 조성물 제조용 키트 | |
WO2019212288A1 (ko) | Messenger rna 전달용 고분자 나노입자 조성물 및 그 제조방법 | |
US20180250409A1 (en) | Pharmaceutical composition containing anionic drug, and preparation method therefor | |
WO2020032581A1 (ko) | 바이러스 전달용 고분자 나노입자 조성물 및 그의 제조방법 | |
WO2022231374A1 (ko) | 약물을 함유하고 양친성 고분자를 포함하지 않는 나노입자 제조용 키트 | |
WO2024053862A1 (ko) | 약물 함유 나노입자 제조용 키트 및 약물전달용 나노입자 조성물 | |
WO2021101265A1 (ko) | 약물전달용 나노입자 조성물 제조용 키트 | |
WO2019098691A9 (ko) | 음이온성 약물 함유 약제학적 조성물의 동결건조 조성물 및 방법 | |
US20190328903A1 (en) | Polymer nanoparticle composition for plasmid dna delivery, and preparation method therefor | |
WO2019093802A2 (ko) | 음이온성 약물 전달용 지질 나노입자의 동결건조 조성물 및 방법 | |
WO2023121388A1 (ko) | 약물의 폐 전달용 나노입자 조성물 | |
WO2021091272A1 (ko) | 면역유도용 고분자 나노입자 조성물 및 그 제조방법 | |
KR20230096312A (ko) | 약물 전달용 지질 및 이를 포함하는 나노입자, 및 이 나노입자를 포함하는 약물 전달용 조성물 | |
KR20220149400A (ko) | 이황화 결합을 갖는 양이온성 지질을 사용하여 약물을 전달하기 위한 나노입자 조성물 및 그 제조방법 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 20901243 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 3162374 Country of ref document: CA |
|
ENP | Entry into the national phase |
Ref document number: 2022538147 Country of ref document: JP Kind code of ref document: A |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112022012118 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 2020407348 Country of ref document: AU Date of ref document: 20201216 Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2020901243 Country of ref document: EP Effective date: 20220720 |
|
ENP | Entry into the national phase |
Ref document number: 112022012118 Country of ref document: BR Kind code of ref document: A2 Effective date: 20220617 |