CN113861403A - 一种纳米材料及其制备方法和应用 - Google Patents
一种纳米材料及其制备方法和应用 Download PDFInfo
- Publication number
- CN113861403A CN113861403A CN202111182445.2A CN202111182445A CN113861403A CN 113861403 A CN113861403 A CN 113861403A CN 202111182445 A CN202111182445 A CN 202111182445A CN 113861403 A CN113861403 A CN 113861403A
- Authority
- CN
- China
- Prior art keywords
- compound
- amino
- group
- nanomaterial
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002086 nanomaterial Substances 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- 229920000587 hyperbranched polymer Polymers 0.000 claims abstract description 45
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 34
- 239000000126 substance Substances 0.000 claims abstract description 20
- 125000003277 amino group Chemical group 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 7
- 239000002105 nanoparticle Substances 0.000 claims abstract description 5
- -1 small molecule organic compound Chemical class 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 26
- 239000002202 Polyethylene glycol Substances 0.000 claims description 23
- 229920001223 polyethylene glycol Polymers 0.000 claims description 23
- 125000006239 protecting group Chemical group 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- GJOWSEBTWQNKPC-UHFFFAOYSA-N 3-methyloxiran-2-ol Chemical compound CC1OC1O GJOWSEBTWQNKPC-UHFFFAOYSA-N 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- 239000000178 monomer Substances 0.000 claims description 12
- 238000006116 polymerization reaction Methods 0.000 claims description 12
- 229920001519 homopolymer Polymers 0.000 claims description 11
- 239000002245 particle Substances 0.000 claims description 10
- 239000002994 raw material Substances 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 7
- 229920001400 block copolymer Polymers 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 7
- 229920005604 random copolymer Polymers 0.000 claims description 7
- 238000007142 ring opening reaction Methods 0.000 claims description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 230000000379 polymerizing effect Effects 0.000 claims description 5
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000003700 epoxy group Chemical group 0.000 claims description 4
- 229920001184 polypeptide Polymers 0.000 claims description 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 4
- CPRMKOQKXYSDML-UHFFFAOYSA-M rubidium hydroxide Chemical compound [OH-].[Rb+] CPRMKOQKXYSDML-UHFFFAOYSA-M 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 235000021122 unsaturated fatty acids Nutrition 0.000 claims description 4
- 150000004670 unsaturated fatty acids Chemical class 0.000 claims description 4
- VYDIEMYCPRLABB-UHFFFAOYSA-N 2-methyl-2-(oxiran-2-yl)butan-1-ol Chemical compound CCC(C)(CO)C1CO1 VYDIEMYCPRLABB-UHFFFAOYSA-N 0.000 claims description 3
- FMSOMPFGGXYNKV-UHFFFAOYSA-N 2-methyl-2-(oxiran-2-yl)propan-1-ol Chemical compound OCC(C)(C)C1CO1 FMSOMPFGGXYNKV-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims description 3
- 229940002612 prodrug Drugs 0.000 claims description 3
- 239000000651 prodrug Substances 0.000 claims description 3
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 claims description 2
- ZOOPONUAQQEUQX-UHFFFAOYSA-N 5-amino-2,2-dimethylpentan-1-ol Chemical compound OCC(C)(C)CCCN ZOOPONUAQQEUQX-UHFFFAOYSA-N 0.000 claims description 2
- LQGKDMHENBFVRC-UHFFFAOYSA-N 5-aminopentan-1-ol Chemical compound NCCCCCO LQGKDMHENBFVRC-UHFFFAOYSA-N 0.000 claims description 2
- SUTWPJHCRAITLU-UHFFFAOYSA-N 6-aminohexan-1-ol Chemical compound NCCCCCCO SUTWPJHCRAITLU-UHFFFAOYSA-N 0.000 claims description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 claims description 2
- 239000004793 Polystyrene Substances 0.000 claims description 2
- 150000008065 acid anhydrides Chemical class 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims description 2
- 238000010539 anionic addition polymerization reaction Methods 0.000 claims description 2
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 2
- 239000000920 calcium hydroxide Substances 0.000 claims description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 150000008282 halocarbons Chemical group 0.000 claims description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 2
- 150000002596 lactones Chemical class 0.000 claims description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 2
- 229920000573 polyethylene Polymers 0.000 claims description 2
- 239000004626 polylactic acid Substances 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 2
- 229920002223 polystyrene Polymers 0.000 claims description 2
- 238000007127 saponification reaction Methods 0.000 claims description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
- 239000012279 sodium borohydride Substances 0.000 claims description 2
- UUCCCPNEFXQJEL-UHFFFAOYSA-L strontium dihydroxide Chemical compound [OH-].[OH-].[Sr+2] UUCCCPNEFXQJEL-UHFFFAOYSA-L 0.000 claims description 2
- 229910001866 strontium hydroxide Inorganic materials 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 150000003384 small molecules Chemical class 0.000 claims 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
- HUFRMAUWIZDZIJ-UHFFFAOYSA-N 2-hydroxyhexano-6-lactone Chemical compound OC1CCCCOC1=O HUFRMAUWIZDZIJ-UHFFFAOYSA-N 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 9
- 230000006870 function Effects 0.000 abstract description 7
- 230000007547 defect Effects 0.000 abstract description 4
- 229920002521 macromolecule Polymers 0.000 abstract description 3
- 206010028980 Neoplasm Diseases 0.000 abstract description 2
- 230000004888 barrier function Effects 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000004071 biological effect Effects 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 150000002894 organic compounds Chemical class 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 16
- 239000007788 liquid Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 229920006150 hyperbranched polyester Polymers 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 239000010931 gold Substances 0.000 description 7
- 229910052737 gold Inorganic materials 0.000 description 7
- 238000011068 loading method Methods 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000002390 rotary evaporation Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 5
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical group CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
- 239000000693 micelle Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- PEUKZUNHDBBJQH-UHFFFAOYSA-N (3-methyloxolan-3-yl)methanol Chemical group OCC1(C)CCOC1 PEUKZUNHDBBJQH-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 230000004791 biological behavior Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960004488 linolenic acid Drugs 0.000 description 2
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- KRHOKZHVSQKTJI-BJBXXJATSA-N (1S,3R,8R,9S,11R)-2,2-dichloro-3,7,7,11-tetramethyl-10-oxatetracyclo[6.5.0.01,3.09,11]tridecane Chemical group CC1(C)CCC[C@@]2(C)C(Cl)(Cl)[C@]22CC[C@@](C)(O3)[C@@H]3[C@@H]21 KRHOKZHVSQKTJI-BJBXXJATSA-N 0.000 description 1
- LFKLPJRVSHJZPL-UHFFFAOYSA-N 1,2:7,8-diepoxyoctane Chemical group C1OC1CCCCC1CO1 LFKLPJRVSHJZPL-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OBOHMJWDFPBPKD-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-4-methoxybenzene Chemical group C1=CC(OC)=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 OBOHMJWDFPBPKD-UHFFFAOYSA-N 0.000 description 1
- PTBDIHRZYDMNKB-UHFFFAOYSA-N 2,2-Bis(hydroxymethyl)propionic acid Chemical compound OCC(C)(CO)C(O)=O PTBDIHRZYDMNKB-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- HYQXNCDBSALQLB-UHFFFAOYSA-N 9-bromo-9-phenylfluorene Chemical group C12=CC=CC=C2C2=CC=CC=C2C1(Br)C1=CC=CC=C1 HYQXNCDBSALQLB-UHFFFAOYSA-N 0.000 description 1
- GXBYFVGCMPJVJX-UHFFFAOYSA-N Epoxybutene Chemical group C=CC1CO1 GXBYFVGCMPJVJX-UHFFFAOYSA-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
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- NZHXEWZGTQSYJM-UHFFFAOYSA-N [bromo(diphenyl)methyl]benzene Chemical group C=1C=CC=CC=1C(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 NZHXEWZGTQSYJM-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical group 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- ABSOMGPQFXJESQ-UHFFFAOYSA-M cesium;hydroxide;hydrate Chemical compound O.[OH-].[Cs+] ABSOMGPQFXJESQ-UHFFFAOYSA-M 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 150000002343 gold Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 125000005481 linolenic acid group Chemical group 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000006068 polycondensation reaction Methods 0.000 description 1
- 239000000580 polymer-drug conjugate Substances 0.000 description 1
- 229920006389 polyphenyl polymer Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/3311—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group
- C08G65/3318—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group heterocyclic
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/26—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds
- C08G65/2618—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds the other compounds containing nitrogen
- C08G65/2621—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds the other compounds containing nitrogen containing amine groups
- C08G65/2624—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds the other compounds containing nitrogen containing amine groups containing aliphatic amine groups
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/333—Polymers modified by chemical after-treatment with organic compounds containing nitrogen
- C08G65/33303—Polymers modified by chemical after-treatment with organic compounds containing nitrogen containing amino group
- C08G65/33306—Polymers modified by chemical after-treatment with organic compounds containing nitrogen containing amino group acyclic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/333—Polymers modified by chemical after-treatment with organic compounds containing nitrogen
- C08G65/33396—Polymers modified by chemical after-treatment with organic compounds containing nitrogen having oxygen in addition to nitrogen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/337—Polymers modified by chemical after-treatment with organic compounds containing other elements
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2650/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G2650/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterized by the type of post-polymerisation functionalisation
- C08G2650/04—End-capping
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polyethers (AREA)
Abstract
本发明提供一种纳米材料及其制备方法和应用,涉及生物医用材料领域。该纳米材料包括一端是氨基、另一端是羟基的化合物,所述化合物的羟基端连接有超支化聚合物。在该化合物的氨基端可以用来连接功能性物质,如小分子有机化合物、高分子化合物、纳米颗粒、生物大分子等,克服了现有技术中超支化聚合物不能连接其他功能性物质,无法实现载体功能进一步提升的缺陷。在不改变其原有的生物学活性功能的情况下,改善其它特性使之对人体有益。本发明提供的纳米材料为纳米级别,尺寸小,能够较好地穿过人体的生理屏障,对人体安全性高。此外,本发明提供的纳米材料作为载药材料在治疗肿瘤和其它疾病上都存在广阔的应用前景。
Description
技术领域
本发明涉及生物医用材料领域,具体涉及一种纳米材料及其制备方法和应用。
背景技术
1988年Kim和Wenster首次提出超支化聚合物的概念并制备出可溶的超支化聚苯,此后,由于超支化聚合物的独特性质以及优于树形聚合物的实用性,得到人们的广泛关注。由于具有高度支化的结构,超支化聚合物难以结晶,也无链缠结,因而溶解性能大大提高,大量的末端基团可以通过化学改性赋予超支化聚合物新的物理化学性能。
近年来超支化聚合物在生物医用材料领域的应用越来越广泛,基于超支化聚合物的药物载体的构建尤其受到关注。根据载药方式的不同,可以细分为五种类型:聚合物-药物复合物、单分子胶束、多分子胶束、环境响应性胶束、聚合物-药物缀合物。然而现有技术中提供的超支化聚合物作为药物载体仍存在局限性。例如中国专利文献CN103169977A公开了一种超支化聚合物纳米药物载体,包括多个纳米胶束,每个纳米胶束包括由改性的端羟基超支化聚酯形成的内核和连接于内核表面的由聚乙二醇单甲醚形成的多个支臂,改性的端羟基超支化聚酯为马来酸酐开环与端羟基超支化聚酯连接形成的多羧基超支化聚酯。又如中国专利文献CN101474411A公开了一种新型两亲性超支化聚酯为载体的抗肿瘤前药,两亲性超支化聚酯的亲水段为聚乙二醇或聚乙二醇单甲醚,亲油段为一种基于二羟甲基丙酸及羟基乙酸、乳酸的齐聚物或者他们的交替齐聚物而构筑的新型可生物降解超支化聚酯单元,抗肿瘤药物分子与两亲性超支化聚酯的亲油段以酯键或酰胺键连接。前述载体虽然具有良好的载药功能,但是不能连接其他功能性物质,无法实现载体功能的进一步提升。
发明内容
因此,本发明要解决的技术问题在于克服现有技术中超支化聚合物不能连接其他功能性物质,无法实现载体功能进一步提升的缺陷,从而提供一种纳米材料及其制备方法和应用。
为实现上述目的,本发明提供如下技术方案:
第一方面,本发明提供一种纳米材料,包括一端是氨基、另一端是羟基的化合物,所述化合物的羟基端连接有超支化聚合物。
进一步地,所述化合物的氨基端连接有功能性物质,所述功能性物质包括小分子有机化合物、高分子化合物、纳米颗粒、生物大分子中的至少一种,所述化合物的氨基端通过所述功能性物质含有的羧基、环氧基、磺酸基、卤代烃基、醛基、羟基、酰氯基、酸酐中的至少一种与之连接,优选的,所述功能性物质包括不饱和脂肪酸、羟基表面修饰纳米金颗粒、多肽、氨基酸、环氧烷烃中的至少一种。
进一步地,所述化合物为一端是氨基、另一端是羟基的小分子化合物或高分子化合物;
所述小分子化合物包括6-氨基-1-己醇、6-氨基-2-羟基甲基-n-1-己醇、5-氨基-1-戊醇、5-氨基-2,2-二甲基戊醇中的至少一种;
所述高分子化合物的高分子链为均聚物、随机共聚物或者嵌段共聚物,所述均聚物为聚乙烯、聚苯乙烯、聚乙二醇、聚甲基丙烯酸甲酯、聚乙酸内酯、聚乳酸、聚乙二醇单甲醚中的任意一种,所述随机共聚物是至少两种形成所述均聚物的小分子单体随机聚合而成的,所述嵌段共聚物是至少两种所述均聚物的嵌段连接而成的,所述高分子化合物的数均分子量为100~3000000,优选为500~50000。
进一步地,所述超支化聚合物是由小分子单体在所述化合物的羟基端聚合而成的均聚物、随机共聚物或嵌段共聚物,所述小分子单体包括环氧丙醇、甲基环氧丙醇、α-羟基-ε己内酯、3-乙基-3-羟甲基-环氧丁烷、3-甲基-3-羟甲基-环氧丁烷中的至少一种,所述超支化聚合物的数均分子量为100~3000000,优选为500~50000。
第二方面,本发明提供所述的纳米材料的制备方法,包括以下步骤:
(1)以一端是氨基、另一端是羟基的化合物为原料,使用保护基团保护所述化合物一端的氨基;
(2)通过小分子单体发生开环超支化聚合反应,在所述化合物的羟基端连接超支化聚合物;
(3)脱除所述保护基团,得到一端是氨基,另一端连接超支化聚合物的纳米材料。
进一步地,所述制备方法还包括:在步骤(3)所得纳米材料的氨基端连接功能性物质。
进一步地,步骤(1)中,所述保护基团包括苄氧羰基、叔丁氧羰基、烯丙氧羰基、甲氧羰基、乙氧羰基、三甲基硅乙氧羰基、邻苯二甲酰基、对甲苯磺酰基、三氟乙酰基、邻硝基苯磺酰基、对硝基苯磺酰基、三苯甲基、2,4-二甲氧基苄基、对甲氧基苄基、苄基中的至少一种;
步骤(3)中,脱除所述保护基团的方法包括催化氢解、酸解裂解、皂化、高温脱除、强碱脱除中的至少一种;脱除所述保护基团的试剂包括乙酸、盐酸、溴化氢、氢氧化钾、硼氢化钠、三氟乙酸、三氟化硼二乙醚中的至少一种。
进一步地,步骤(2)中,所述开环超支化聚合反应是在强碱、溶剂、加热条件下发生的阴离子聚合反应,其中,所述强碱包括氢氧化钠、氢氧化钾、氢氧化铷、氢氧化锂、氢氧化铯、氢氧化钙、氢氧化锶中的至少一种;所述溶剂包括甲苯、苯甲醚、苯、乙苯、二甲苯中的至少一种;加热温度为20~300℃,优选为90℃。
第三方面,本发明提供所述的纳米材料或者所述的制备方法得到的纳米材料在制备药物载体中的应用。
第四方面,本发明提供一种前体药物,包括所述的纳米材料或者所述的制备方法得到的纳米材料,以及负载在所述纳米材料上的药物。
本发明技术方案,具有如下优点:
1.本发明提供的纳米材料,包括一端是氨基、另一端是羟基的化合物,该化合物的羟基端连接有超支化聚合物。在该化合物的氨基端可以用来连接功能性物质,如小分子有机化合物、高分子化合物、纳米颗粒、生物大分子等,克服了现有技术中超支化聚合物不能连接其他功能性物质,无法实现载体功能进一步提升的缺陷。氨基端可以连接的功能性物质有多种,例如多肽,可以降低其免疫原性,增强水溶性,显著延长其在生物体内的半衰期等;又如纳米金颗粒,增强其在体内的颗粒分散性和生物相容性,改善其在体内的稳定性。此外还有很多能在氨基端连接的化合物或材料,凡是能够与化合物的氨基反应从而与之相连的功能性物质均可,在不改变其原有的生物学活性功能的情况下,改善其它特性使之对人体有益。本发明提供的纳米材料为纳米级别,尺寸小,能够较好地穿过人体的生理屏障,对人体安全性高。此外,本发明提供的纳米材料作为载药材料在治疗肿瘤和其它疾病上都存在广阔的应用前景,例如通过与超支化聚合物的枝状结构连接来载药。
2.本发明提供的纳米材料中超支化聚合物是由小分子单体在化合物的羟基端聚合而成的均聚物、随机共聚物或嵌段共聚物,其中,小分子单体包括环氧丙醇、甲基环氧丙醇、α-羟基-ε己内酯、3-乙基-3-羟甲基-环氧丁烷、3-甲基-3-羟甲基-环氧丁烷中的至少一种。由于该超支化聚合物引入大量羟基,使得本发明提供的纳米材料是多羟基结构,当纳米材料进入生物环境中,由于其大的比表面积和高的吸附活性,表面会吸附大量蛋白,形成蛋白冠,这层蛋白冠不仅会影响蛋白质本身的结构和生物功能,同时也会改变纳米材料的生物学行为。研究表明纳米材料亲水性增加可以导致一些蛋白质的吸附面积降低,蛋白冠缩小,多羟基的结构亲水性能优异,这有助于阻止蛋白冠的产生,减少其对纳米材料的生物学行为的影响。同时该纳米材料由于其超支化结构与多羟基末端官能团,具有良好的柔性和生物相容性,无毒副作用,能够提供良好的体内游动性能和分布性能。
3.本发明提供的纳米材料的制备方法,以一端是氨基、另一端是羟基的化合物为原料,使用保护基团保护化合物一端的氨基;通过小分子单体发生开环超支化聚合反应在化合物的羟基端连接超支化聚合物;脱除保护基团,得到一端是氨基,另一端连接超支化聚合物的纳米材料。
本发明制备纳米材料的原料化合物端基分别为氨基和羟基,两端基均可以引发单体开环缩聚形成超支化聚合物,聚合反应后氨基无法保留,无法进一步加以利用。大部分氨基保护基团在室温条件下,中性、弱酸及弱碱的溶液中是稳定的,然而超支化聚合反应需要应用强碱使羟基呈现去质子化状态,且聚合反应过程需要持续高温,强碱和高温这样的反应环境对氨基保护基团的保护机制具有很大的挑战性。
本发明使用苄氧羰基(Cbz)、叔丁氧羰基(Boc)、烯丙氧羰基(Alloc)、甲氧羰基、乙氧羰基、三甲基硅乙氧羰基(Teoc)、邻苯二甲酰基(Pht)、对甲苯磺酰基(Tos)、三氟乙酰基(Tfa)、邻(对)硝基苯磺酰基(Ns)、三苯甲基(Trt)、2,4-二甲氧基苄基(DMB)、对甲氧基苄基(PMB)、苄基(Bn)等氨基保护基团,在聚合反应过程中稳定保护氨基,克服了反应过程中氨基保护基团在强碱高温条件下失活的障碍,使化合物的氨基端在聚合反应过程中保持其生物特性,不会引发聚合,反应后脱除保护基团,得到了一端是氨基、另一端是超支化聚合物结构的纳米材料。该化合物的氨基端能连接含有其他官能基团的化合物或材料,通过这种方式合成了一种新结构、新特性的纳米材料。
附图说明
为了更清楚地说明本发明具体实施方式或现有技术中的技术方案,下面将对具体实施方式或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图是本发明的一些实施方式,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
图1是本发明实施例1提供的纳米材料的化学结构式;
图2是本发明实施例1提供的纳米材料的合成路线图。
具体实施方式
提供下述实施例是为了更好地进一步理解本发明,并不局限于所述最佳实施方式,不对本发明的内容和保护范围构成限制,任何人在本发明的启示下或是将本发明与其他现有技术的特征进行组合而得出的任何与本发明相同或相近似的产品,均落在本发明的保护范围之内。
本发明实施例中使用的原料来源如表1所示,仪器来源如表2所示。
表1原料来源
表2仪器来源
设备名称 | 规格型号 | 产地 |
旋蒸仪 | EV311-V | 北京莱伯泰科仪器股份有限公司 |
真空干燥箱 | DZF-6053 | 上海-恒科学仪器公司 |
高速离心机 | TGL-16 | 北京市永光明医疗仪器有限公司 |
干燥箱 | DHG-9070A | 上海-恒科学仪器公司 |
磁力搅拌器 | SY20-2 | 上海司乐仪器有限公司 |
手套箱 | IGBS1200 | 北京艾普有限公司 |
实施例中未注明具体实验步骤或条件者,按照本领域内的文献所描述的常规实验步骤的操作或条件即可进行。所用原料或仪器,均为可以通过市购获得的常规产品,包括但不限于本申请实施例中采用的原料或仪器。
实施例1
本实施例提供一种纳米材料,其结构式如式(I)所示:
其中,n=22,环氧丙醇数量约为30(结构式中环氧丙醇形成的超支化结构未完全示出)。
上述纳米材料的合成路线如下:
步骤(a):使用保护基团R保护氨基聚乙二醇羟基的端氨基;
步骤(b):端氨基被保护基团R保护的聚乙二醇的端羟基与环氧丙醇发生超支化聚合反应,得到一端氨基被保护基团R保护,另一端羟基连接超支化聚合物的聚乙二醇;
步骤(c):一端氨基被保护基团R保护,另一端羟基连接超支化聚合物的聚乙二醇脱除保护基团R,得到一端是氨基,另一端羟基连接超支化聚合物的聚乙二醇;
步骤(d):基团X与一端是氨基,另一端羟基连接超支化聚合物的聚乙二醇的端氨基反应,得到一端连接功能基团X,另一端羟基连接超支化聚合物的聚乙二醇。
如式(I)所示纳米材料的制备方法如下:
第一步:将1000分子量的氨基聚乙二醇羟基(NH2-PEG-OH,500mg,0.5mmol)加入到含有二氯甲烷(超干,4mL)的真空反应管中,滴入三乙胺(150μL,1.07mmol),氮气鼓泡除去溶液中的氧,在冰水浴下磁力搅拌,转速650r/min。将三苯基氯甲烷(420mg,1.5mmol)溶解在二氯甲烷(超干,2mL)中,逐滴加入到反应管中,撤下冰水浴,在室温条件下继续搅拌2.5h,转速650r/min。反应结束后,旋蒸除去二氯甲烷,得到油状液体,先用甲苯(2mL)溶解过滤除掉三乙胺盐,再滴入冷的乙醚(45mL)中,冷冻离心得到沉淀,除掉多余的三苯基氯甲烷,在真空烘干箱中室温5h,得到434.56mg的油状液体,分子量为1242,充氮气低温储存。
第二步:将第一步得到的油状液体(200mg,0.16mmol)溶解在装有苯(超干,2mL)的真空反应管中,加入氢氧化铯一水合物(27mg,0.16mmol),在90℃油浴下搅拌3h,转速700r/min。连接冷阱,使用真空泵抽除苯,后关闭真空泵,保持反应管内真空环境。将除水后的环氧丙醇(0.52ml,0.45mmol)用针筒转移至反应管中,在90℃油浴下反应搅拌24h,转速700r/min。反应结束后,加入过量甲醇和酸性氧化铝,震荡摇晃几下,过滤除掉酸性氧化铝,旋蒸除掉甲醇,得到油状液体。干法上样过凝胶层析柱,先用洗脱剂甲醇:二氯甲烷=1:7(v/v)洗脱掉极性相对较小的杂质,再用洗脱剂甲醇:二氯甲烷=1:2(v/v)洗脱反应后应得到的产物,旋蒸得到油状液体330mg,分子量为3256,洗脱剂全部为甲醇时洗脱掉的是极性强的杂质。
第三步:将第二步得到的油状液体(330mg)用乙酸(2mL)溶解在真空反应管中,再滴加50μL的水,在氮气状态下油浴60℃加热搅拌2h,转速600r/min,反应结束后大量甲醇稀释,旋蒸除去甲醇和乙酸,将旋蒸后的液体滴入冷的乙醚(40mL)中,冷冻离心得到沉淀,在真空烘干箱中室温烘24h,得到油状液体294mg,产物分子量为3013,储存备用。
第四步:将5-降冰片烯-exo-2,3-二羧酸酐(10g,60.9mmol)和γ-氨基丁酸(6.595g,63.97mmol)加入甲苯(200mL)中,在140℃油浴下分水蒸馏,磁力搅拌转速700r/min,反应24h。反应结束后拆卸反应装置,旋蒸除去甲苯,得到粉末状固体。干法上样,使用正己烷:乙酸乙酯=1:1(v/v)的洗脱剂过凝胶层析柱,旋蒸除去洗脱剂后得到12.48g的粉末状固体。
第五步:将第四步得到的粉末状固体(3g,12mmol)加入到二氯甲烷(300mL)中,再陆续加入1-乙基-碳酰二亚胺盐酸盐(EDC,3.461g,18mmol)、4-二甲氨基吡啶(DMAP,0.147g,1.2mmol),先搅拌10min,转速600r/min,再加入N-羟基琥珀酰亚胺(NHS,2.072g,18mmol),在室温条件下搅拌20h,转速600r/min。反应结束后,旋蒸除去二氯甲烷,得到粉末状固体。干法上样,使用正己烷:乙酸乙酯=1:1(v/v)的洗脱剂过凝胶层析柱,旋蒸除去洗脱剂得到2.05g的粉末状固体,充氮气低温储存。
第六步:将第三步得到的油状液体(75mg)用二氧六环(超干,1mL)溶解加入真空反应管中,冻干除水,保持真空状态。用N,N-二甲基甲酰胺(超干,1mL)溶解第五步得到的粉末状固体(15mg),在溶液里加入三乙胺(10μL),微量4-二甲氨基吡啶,通过针筒转移进真空反应管中,室温条件下搅拌5h,转速650r/min。反应结束后,连接冷阱,使用真空泵抽除N,N-二甲基甲酰胺,后关闭真空泵。干法上样,用甲醇:二氯甲烷=1:1(v/v)的洗脱剂过凝胶层析柱,旋蒸后用0.5mL的甲醇溶解滴入冷的乙醚(20mL)中,冷冻离心得到沉淀,在真空烘干箱中室温烘24h,得到油状液体40mg,产物的分子量为3264。
实施例2
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于将实施例1中第三步的三苯基氯甲烷替换为4-甲氧基三苯甲基氯。
实施例3
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于将实施例1中第三步的三苯基氯甲烷替换为9-溴-9-苯基芴。
实施例4
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于将实施例1中第三步的三苯基氯甲烷替换为溴三苯基甲烷。
实施例5
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于将实施例1中第二步的环氧丙醇替换为甲基环氧丙醇,制得产物的数均分子量为3895,结构式如式(II)所示:
其中,n=22,甲基环氧丙醇数量约为35(结构式中甲基环氧丙醇形成的超支化结构未完全示出)。
实施例6
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于将实施例1中第二步的环氧丙醇替换为3-甲基-3-羟甲基-环氧丁烷,制得产物的数均分子量为4350,结构式如式(III)所示:
其中,n=22,3-甲基-3-羟甲基-环氧丁烷数量约为35(结构式中3-甲基-3-羟甲基-环氧丁烷形成的超支化结构未完全示出)。
实施例7
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于将实施例1中第一步的氨基聚乙二醇羟基替换为氨基聚苯乙烯羟基,制得产物的数均分子量为3680,结构式如式(IV)所示:
其中,n=20,环氧丙醇数量约为35(结构式中环氧丙醇形成的超支化结构未完全示出)。
实施例8
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于将实施例1中第一步的氨基聚乙二醇羟基替换为6-氨基-2-羟基甲基-n-1-己醇,制得产物的数均分子量为3089,结构式如式(V)所示:
其中,环氧丙醇数量约为50(结构式中环氧丙醇形成的超支化结构未完全示出)。
实施例9
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于省去第四步和第五步,并将实施例1第六步中加入的第五步得到的粉末状固体替换为亚麻酸,制得产物的数均分子量为2450,结构式如式(VI)所示:
其中,n=22,环氧丙醇数量约为20(结构式中环氧丙醇形成的超支化结构未完全示出)。
实施例10
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于省去第四步和第五步,并将实施例1第六步中加入的第五步得到的粉末状固体替换为油酸,制得产物的数均分子量为2780,结构式如式(VII)所示:
实施例11
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于省去第四步和第五步,并将实施例1第六步中加入的第五步得到的粉末状固体替换为花生四烯酸,制得产物的数均分子量为3045,结构式如式(VIII)所示:
实施例9中的亚麻酸、实施例10中的油酸和本实施例中的花生四烯酸皆为不饱和脂肪酸。不饱和脂肪酸是人体不可缺少的,末端羧基与连接超支化聚合物的聚乙二醇的端氨基反应,增强其亲水性与在体内分布性能。
实施例12
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于省去第四步和第五步,并将实施例1第六步中加入的第五步得到的粉末状固体替换为羧基修饰的纳米金粒子溶液,纳米金粒子表面的羧基与连接超支化聚合物的聚乙二醇的端氨基反应,得到表面被超支化聚合物修饰的纳米金粒子。修饰纳米金颗粒,增强其在体内的颗粒分散性和生物相容性,改善其在体内的稳定性。
实施例13
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于省去第四步和第五步,并将实施例1第六步中加入的第五步得到的粉末状固体替换为谷氨酸,制得产物的结构式如式(IX)所示:
谷氨酸两端的羧基分别与连接超支化聚合物的聚乙二醇的端氨基反应,也可以使用保护基团保护特定位置的羧基,修饰氨基酸。
实施例14
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于省去第四步和第五步,并将实施例1第六步中加入的第五步得到的粉末状固体替换为天冬氨酸组装好的肽链(先用烯丙基保护特定位置的天冬氨酸侧链羧基,肽链组装好后再脱除烯丙基),肽链上的羧基与连接超支化聚合物的聚乙二醇的端氨基反应,制得产物的结构式如式(X)所示:
修饰多肽,改善其生物特性,可以降低其免疫原性,增强水溶性,显著延长其在生物体内的半衰期等。
实施例15
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于省去第四步和第五步,并将实施例1第六步中加入的第五步得到的粉末状固体替换为环氧丁烯,制得产物的结构式如式(XI)所示:
环氧基与连接超支化聚合物的聚乙二醇的端氨基反应,使端基由原来的氨基变为双键,改变端基官能团,使其能对其他功能性材料进行修饰。
实施例16
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于省去第四步和第五步,并将实施例1第六步中加入的第五步得到的粉末状固体替换为环氧十二烷,制得产物的结构式如式(XII)所示:
环氧基与连接超支化聚合物的聚乙二醇的端氨基反应,使聚乙二醇主链延长十二个碳原子。端氨基连接此类环氧烷烃,能改变其空间位阻。
实施例17
本实施例提供一种纳米材料,其制备方法参照实施例1,不同之处仅在于省去第四步和第五步,并将实施例1第六步中加入的第五步得到的粉末状固体替换为1,2,7,8-二环氧辛烷,制得产物的结构式如式(XIII)所示:
双环氧基分别与连接超支化聚合物的聚乙二醇的端氨基反应,得到具有对称结构的超支化聚合物,增强其生物相容性与亲水性。
显然,上述实施例仅仅是为清楚地说明所作的举例,而并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。
Claims (10)
1.一种纳米材料,其特征在于,包括一端是氨基、另一端是羟基的化合物,所述化合物的羟基端连接有超支化聚合物。
2.根据权利要求1所述的纳米材料,其特征在于,所述化合物的氨基端连接有功能性物质,所述功能性物质包括小分子有机化合物、高分子化合物、纳米颗粒、生物大分子中的至少一种,所述化合物的氨基端通过所述功能性物质含有的羧基、环氧基、磺酸基、卤代烃基、醛基、羟基、酰氯基、酸酐中的至少一种与之连接,优选的,所述功能性物质包括不饱和脂肪酸、羟基表面修饰纳米金颗粒、多肽、氨基酸、环氧烷烃中的至少一种。
3.根据权利要求1所述的纳米材料,其特征在于,所述化合物为一端是氨基、另一端是羟基的小分子化合物或高分子化合物;
所述小分子化合物包括6-氨基-1-己醇、6-氨基-2-羟基甲基-n-1-己醇、5-氨基-1-戊醇、5-氨基-2,2-二甲基戊醇中的至少一种;
所述高分子化合物的高分子链为均聚物、随机共聚物或者嵌段共聚物,所述均聚物为聚乙烯、聚苯乙烯、聚乙二醇、聚甲基丙烯酸甲酯、聚乙酸内酯、聚乳酸、聚乙二醇单甲醚中的任意一种,所述随机共聚物是至少两种形成所述均聚物的小分子单体随机聚合而成的,所述嵌段共聚物是至少两种所述均聚物的嵌段连接而成的,所述高分子化合物的数均分子量为100~3000000,优选为500~50000。
4.根据权利要求1所述的纳米材料,其特征在于,所述超支化聚合物是由小分子单体在所述化合物的羟基端聚合而成的均聚物、随机共聚物或嵌段共聚物,所述小分子单体包括环氧丙醇、甲基环氧丙醇、α-羟基-ε己内酯、3-乙基-3-羟甲基-环氧丁烷、3-甲基-3-羟甲基-环氧丁烷中的至少一种,所述超支化聚合物的数均分子量为100~3000000,优选为500~50000。
5.权利要求1~4任一项所述的纳米材料的制备方法,其特征在于,包括以下步骤:
(1)以一端是氨基、另一端是羟基的化合物为原料,使用保护基团保护所述化合物一端的氨基;
(2)通过小分子单体发生开环超支化聚合反应,在所述化合物的羟基端连接超支化聚合物;
(3)脱除所述保护基团,得到一端是氨基,另一端连接超支化聚合物的纳米材料。
6.根据权利要求5所述的纳米材料的制备方法,其特征在于,还包括:在步骤(3)所得纳米材料的氨基端连接功能性物质。
7.根据权利要求5所述的纳米材料的制备方法,其特征在于,步骤(1)中,所述保护基团包括苄氧羰基、叔丁氧羰基、烯丙氧羰基、甲氧羰基、乙氧羰基、三甲基硅乙氧羰基、邻苯二甲酰基、对甲苯磺酰基、三氟乙酰基、邻硝基苯磺酰基、对硝基苯磺酰基、三苯甲基、2,4-二甲氧基苄基、对甲氧基苄基、苄基中的至少一种;
步骤(3)中,脱除所述保护基团的方法包括催化氢解、酸解裂解、皂化、高温脱除、强碱脱除中的至少一种;脱除所述保护基团的试剂包括乙酸、盐酸、溴化氢、氢氧化钾、硼氢化钠、三氟乙酸、三氟化硼二乙醚中的至少一种。
8.根据权利要求5所述的纳米材料的制备方法,其特征在于,步骤(2)中,所述开环超支化聚合反应是在强碱、溶剂、加热条件下发生的阴离子聚合反应,其中,所述强碱包括氢氧化钠、氢氧化钾、氢氧化铷、氢氧化锂、氢氧化铯、氢氧化钙、氢氧化锶中的至少一种;所述溶剂包括甲苯、苯甲醚、苯、乙苯、二甲苯中的至少一种;加热温度为20~300℃,优选为90℃。
9.权利要求1~4任一项所述的纳米材料或者权利要求5~8任一项所述的制备方法得到的纳米材料在制备药物载体中的应用。
10.一种前体药物,其特征在于,包括权利要求1~4任一项所述的纳米材料或者权利要求5~8任一项所述的制备方法得到的纳米材料,以及负载在所述纳米材料上的药物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111182445.2A CN113861403B (zh) | 2021-10-11 | 2021-10-11 | 一种纳米材料及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111182445.2A CN113861403B (zh) | 2021-10-11 | 2021-10-11 | 一种纳米材料及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113861403A true CN113861403A (zh) | 2021-12-31 |
CN113861403B CN113861403B (zh) | 2024-01-26 |
Family
ID=78998961
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111182445.2A Active CN113861403B (zh) | 2021-10-11 | 2021-10-11 | 一种纳米材料及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113861403B (zh) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010144044A (ja) * | 2008-12-18 | 2010-07-01 | Lion Corp | 有効成分保持体 |
CN109384937A (zh) * | 2018-09-30 | 2019-02-26 | 广州医科大学 | 二氢卟吩修饰的超支化聚缩水甘油醚衍生物及其制备方法和用途 |
CN112694608A (zh) * | 2019-10-23 | 2021-04-23 | 厦门赛诺邦格生物科技股份有限公司 | 一种六臂聚乙二醇衍生物、制备方法及修饰的生物相关物质 |
-
2021
- 2021-10-11 CN CN202111182445.2A patent/CN113861403B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010144044A (ja) * | 2008-12-18 | 2010-07-01 | Lion Corp | 有効成分保持体 |
CN109384937A (zh) * | 2018-09-30 | 2019-02-26 | 广州医科大学 | 二氢卟吩修饰的超支化聚缩水甘油醚衍生物及其制备方法和用途 |
CN112694608A (zh) * | 2019-10-23 | 2021-04-23 | 厦门赛诺邦格生物科技股份有限公司 | 一种六臂聚乙二醇衍生物、制备方法及修饰的生物相关物质 |
Non-Patent Citations (2)
Title |
---|
刘鹰翔: "《药物合成反应》", 31 August 2017 * |
陈莉等: "单氨基末端超支化聚甘油的可控合成", 《天津工业大学学报》 * |
Also Published As
Publication number | Publication date |
---|---|
CN113861403B (zh) | 2024-01-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Liarou et al. | Smart polymersomes and hydrogels from polypeptide-based polymer systems through α-amino acid N-carboxyanhydride ring-opening polymerization. From chemistry to biomedical applications | |
Zhao et al. | A review of polypeptide-based polymersomes | |
US9821078B2 (en) | Branched amphipathic block polymer and molecular aggregate and drug delivery system using same | |
KR100972264B1 (ko) | 알파 토코페롤에 의하여 관능화된 폴리아미노산 및 특히치료용을 위한 이의 용도 | |
KR100431491B1 (ko) | 유기용매에 용해가능한 폴리(알킬렌 옥사이드)-폴리(파라-디옥산온)의 생분해성 블록공중합체, 및 이를 포함하는 약물 전달체 조성물 | |
Li et al. | Short and simple peptide-based pH-sensitive hydrogel for antitumor drug delivery | |
JP5933889B2 (ja) | 新規なポリ(エチレンオキサイド)−ブロックーポリ(エステル)ブロック共重合体 | |
KR20040029359A (ko) | 약물 전달을 위한 양친매성 별모양 거대분자 | |
KR100527291B1 (ko) | 약물 전달체용 양이온기-함유 양친성 블록 공중합체 및그의 음이온성 약물과의 복합체 | |
ES2391691T3 (es) | Copolímeros de injerto como sistemas de suministro de fármacos | |
AU2016374669A1 (en) | Biodegradable amphiphilic polymer, polymer vesicle prepared therefrom and use in preparing target therapeutic medicine for lung cancer | |
CN109627449B (zh) | Peg化树枝状大分子药物载体及其制备方法 | |
Gu et al. | Reverse micelles based on biocompatible β-cyclodextrin conjugated polyethylene glycol block polylactide for protein delivery | |
KR20040021760A (ko) | 약물 담지능력이 우수한 블록 공중합체 미셀 조성물 | |
Choe et al. | Self-assembled polypeptide and polypeptide hybrid vesicles: from synthesis to application | |
CN1698899A (zh) | 以壳聚糖或其衍生物作为药物载体的新型药物组合物 | |
JP2001515522A (ja) | ポリマーキャリア | |
CN100389140C (zh) | 由聚肽-b-聚四氢呋喃-b-聚肽三嵌段共聚物制备纳米及微米级自组装体的方法 | |
CN107998405A (zh) | 新型包含难溶性药物的no供体型聚合胶束组合物的制备方法及应用 | |
Feng et al. | Y-shaped folic acid-conjugated PEG-PCL copolymeric micelles for delivery of curcumin | |
CN113861403A (zh) | 一种纳米材料及其制备方法和应用 | |
Zhu et al. | Synthesis and characterization of biodegradable amphiphilic triblock copolymers methoxy-poly (ethylene glycol)-b-poly (L-lysine)-b-poly (L-lactic acid) | |
Gao et al. | Hydrotropic polymer-based paclitaxel-loaded self-assembled nanoparticles: preparation and biological evaluation | |
CN107296790B (zh) | 一种基于聚磷酸酯的混合载药胶束及其制备方法和一种主动靶向基团修饰的混合载药胶束 | |
Zhao et al. | Star-shaped polycaprolactone-polyethyleneglycol copolymer micelle-like nanoparticles for picropodophyllin delivery |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |