CN105646891B - A kind of amphipathic ternary molecular brush polymer and its vermiform unimolecular micelle constructed - Google Patents
A kind of amphipathic ternary molecular brush polymer and its vermiform unimolecular micelle constructed Download PDFInfo
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- CN105646891B CN105646891B CN201610144709.8A CN201610144709A CN105646891B CN 105646891 B CN105646891 B CN 105646891B CN 201610144709 A CN201610144709 A CN 201610144709A CN 105646891 B CN105646891 B CN 105646891B
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- polymer
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- vermiform
- alkynyl
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- 229920000642 polymer Polymers 0.000 title claims abstract description 113
- 239000000693 micelle Substances 0.000 title claims abstract description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 40
- 229920002521 macromolecule Polymers 0.000 claims abstract description 19
- 238000004132 cross linking Methods 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000000502 dialysis Methods 0.000 claims abstract description 7
- 238000007334 copolymerization reaction Methods 0.000 claims abstract description 3
- 239000008367 deionised water Substances 0.000 claims abstract description 3
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 3
- -1 Azidoethyl Chemical group 0.000 claims description 43
- 238000006116 polymerization reaction Methods 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 18
- 229920002125 Sokalan® Polymers 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 239000004584 polyacrylic acid Substances 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 7
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 7
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 5
- 229920002319 Poly(methyl acrylate) Polymers 0.000 claims description 5
- 239000004793 Polystyrene Substances 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 229940114081 cinnamate Drugs 0.000 claims description 5
- 229920003213 poly(N-isopropyl acrylamide) Polymers 0.000 claims description 5
- 229920002454 poly(glycidyl methacrylate) polymer Polymers 0.000 claims description 5
- 229920000058 polyacrylate Polymers 0.000 claims description 5
- 229920001610 polycaprolactone Polymers 0.000 claims description 5
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 claims description 5
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- 239000001856 Ethyl cellulose Substances 0.000 claims description 3
- 229920002873 Polyethylenimine Polymers 0.000 claims description 3
- 229920001249 ethyl cellulose Polymers 0.000 claims description 3
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 3
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 3
- 229920002239 polyacrylonitrile Polymers 0.000 claims description 3
- 239000004632 polycaprolactone Substances 0.000 claims description 3
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 3
- 229920002223 polystyrene Polymers 0.000 claims description 3
- 150000001336 alkenes Chemical class 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000011943 nanocatalyst Substances 0.000 claims description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 claims 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims 1
- 229960000583 acetic acid Drugs 0.000 claims 1
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 239000000835 fiber Substances 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 16
- 238000001338 self-assembly Methods 0.000 abstract description 8
- 230000008859 change Effects 0.000 abstract description 5
- 239000002243 precursor Substances 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 description 15
- 238000000034 method Methods 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 11
- 230000002209 hydrophobic effect Effects 0.000 description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 238000007306 functionalization reaction Methods 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 239000005266 side chain polymer Substances 0.000 description 7
- 101710141544 Allatotropin-related peptide Proteins 0.000 description 6
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000010560 atom transfer radical polymerization reaction Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- UKODFQOELJFMII-UHFFFAOYSA-N pentamethyldiethylenetriamine Chemical compound CN(C)CCN(C)CCN(C)C UKODFQOELJFMII-UHFFFAOYSA-N 0.000 description 6
- 229920000578 graft copolymer Polymers 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical group C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 4
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical group [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000003999 initiator Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229920002189 poly(glycerol 1-O-monomethacrylate) polymer Polymers 0.000 description 4
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000010526 radical polymerization reaction Methods 0.000 description 3
- WOGITNXCNOTRLK-UHFFFAOYSA-N 3-phenylprop-2-enoyl chloride Chemical class ClC(=O)C=CC1=CC=CC=C1 WOGITNXCNOTRLK-UHFFFAOYSA-N 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical class CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- GCSVCUMDOQKEMT-UHFFFAOYSA-N butan-1-amine;hydrofluoride Chemical compound [H+].[F-].CCCCN GCSVCUMDOQKEMT-UHFFFAOYSA-N 0.000 description 2
- 238000003763 carbonization Methods 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229920000457 chlorinated polyvinyl chloride Polymers 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical class CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 description 2
- 239000004519 grease Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000002088 nanocapsule Substances 0.000 description 2
- NIZKVZYBUGUDTI-UHFFFAOYSA-N pent-3-ynoic acid Chemical compound CC#CCC(O)=O NIZKVZYBUGUDTI-UHFFFAOYSA-N 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 229920002689 polyvinyl acetate Polymers 0.000 description 2
- 239000011118 polyvinyl acetate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 230000004043 responsiveness Effects 0.000 description 2
- 235000019187 sodium-L-ascorbate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical class [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 235000019082 Osmanthus Nutrition 0.000 description 1
- 241000333181 Osmanthus Species 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 238000012661 block copolymerization Methods 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical class CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000004146 energy storage Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 238000010550 living polymerization reaction Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- QATBRNFTOCXULG-UHFFFAOYSA-N n'-[2-(methylamino)ethyl]ethane-1,2-diamine Chemical compound CNCCNCCN QATBRNFTOCXULG-UHFFFAOYSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical class CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000010148 water-pollination Effects 0.000 description 1
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- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
- C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
- C08G81/024—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G
- C08G81/025—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G containing polyether sequences
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
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- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/06—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing polymers
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- C08F120/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
- C08F120/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
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- C08F120/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
- C08F120/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
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- C08F120/26—Esters containing oxygen in addition to the carboxy oxygen
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- C08F120/26—Esters containing oxygen in addition to the carboxy oxygen
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- 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
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- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
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- C08G65/3322—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof acyclic
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- C08J3/00—Processes of treating or compounding macromolecular substances
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- 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
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- C08G2650/28—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterised by the polymer type
- C08G2650/60—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterised by the polymer type containing acetylenic group
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Abstract
The invention belongs to self assembly polymeric material fields, and in particular to a kind of amphipathic ternary molecular brush polymer and its vermiform unimolecular micelle constructed.The polymer architecture general formula is A-g- (B-r-C-r-D), wherein g represents grafting, r represents random copolymerization, A is main polymer chain, and B is lipophilic polymer side chain, and C is the polymer side chain for having photo-crosslinking structure, D is hydrophilic macromolecule side chain, side chain B, C, D are randomly grafted on main chain A.The vermiform unimolecule nano-micelle is to remove n,N-Dimethylformamide by the way that deionized water is slowly added dropwise into the n,N-Dimethylformamide solution of above-mentioned amphiphilic polymer using dialysis and obtain.The vermiform unimolecular micelle structure that the present invention is prepared is novel, and can change the pattern and size of micella by changing the molecular weight of grafting rate and precursor polymer, has high controllability.
Description
Technical field
The invention belongs to self assembly polymeric material fields, and in particular to a kind of amphipathic ternary molecular brush polymer and its
The vermiform unimolecular micelle constructed.
Background technique
With the appearance of novel synthetic reaction technology (such as active free radical polymerization, click chemistry), by polymer system
The technology of standby functional nano micella also emerges in multitude.As most common one of the method for preparing micella, self-assembly method can be with
Simply by regulating and controlling the composition of block copolymer, each section weight ratio, length of chain etc. controls the shape of micella, greatly
Small and performance.
Currently, block copolymerization and graft copolymer are usually polymolecular micella by the micella that self assembly is prepared.
Traditional polymolecular micella plays very big effect really in terms of solubilized drug, and once by the great attention of people.But
Traditional polymolecular micella is a dynamic balance structure, and structure can change with the change of external environment.When poly-
When closing the concentration of object lower than CMC, micella can de-assembly.In addition, pH in blood circulation system, temperature, ionic strength, high shear force
Etc. factors also influence whether the stability of micella.These factors can all cause drug to be released too early, to lessen the curative effect.
In order to improve the stability of carrier, following two method is usually taken in people: 1) polymolecular micella is crosslinked,
Locking structure；2) replace polymolecular micella with unimolecular micelle.
However, carrying out the structure latches of carrier after containing drug, chemical crosslink technique would generally introduce toxic small point
Sub- crosslinking agent, photo-crosslinking rule can make to be contained to go bad in internal drug again.Therefore, diversified stable unimolecule is prepared
Micella is more preferably to select.
Other than stable structure, unimolecular micelle has bigger specific surface area, higher drugloading rate, smaller grain
Diameter, and can be by the molecular size range of precursor polymer, the size and form of the micella prepared needed for structure control.
Currently, most unimolecular micelle is prepared by dendritic amphiphilic polymer.But prepare branch
Type polymer process is extremely cumbersome, has seriously affected its application.And amphiphilic polymer preparation process is relatively easy, and can
With by the grafting rate for adjusting polymer, hydrophobe ratio, chain length etc. adjusts the pattern of obtained micella, size, tool
There is good controllability.
However, the research about graft copolymer most of at present, to prepare based on polymolecular micella/capsule, such as patent
The acid sensitive Nano capsule of CN103289099A report being prepared by graft copolymer, 103059312 A of patent CN report
A kind of multichannel PH responsiveness prepared by lotion self-assembly method Nano capsule, 104645908 A of patent CN report
The photo-crosslinking type nanometer wax phase change energy storage capsule in road, if do not locked further to capsule structure, they exist be easy by
The problem of external environment influences and disintegrates.
Summary of the invention
To solve the shortcomings and deficiencies of the prior art, the primary purpose of the present invention is that providing a kind of amphipathic ternary
Molecular brush polymer.
Another object of the present invention is to provide the synthetic methods of above-mentioned amphipathic ternary molecular brush polymer.
A further object of the present invention is to provide the vermiforms being prepared by above-mentioned amphipathic ternary molecular brush polymer
Unimolecular micelle.The vermiform unimolecular micelle has core-shell structure, and kernel is made of hydrophobic high polymer, and outer layer is hydrophily height
Polymers.
The present invention also provides the purposes of above-mentioned vermiform unimolecular micelle.
The object of the invention is achieved through the following technical solutions:
A kind of amphipathic ternary molecular brush polymer has following general formula: A-g- (B-r-C-r-D)；
Wherein, g represents grafting, and r represents random copolymerization, and A is main polymer chain, and B is lipophilic polymer side chain, and C is tool
The polymer side chain of photo-crosslinking structure, D are hydrophilic macromolecule side chain；Lipophilic polymer side chain B, the height for having photo-crosslinking structure
Molecular side chain C and hydrophilic macromolecule side chain D are randomly grafted on main chain A；
The degree of polymerization of the main polymer chain A is 100~1000, the degree of polymerization of lipophilic polymer side chain B is 50~
120, the degree of polymerization for having the polymer side chain C of photo-crosslinking structure is 50~100, and the degree of polymerization of hydrophilic macromolecule side chain D is 100
~150；The grafting rate of lipophilic polymer side chain B is 1~10%, and the grafting rate for having the polymer side chain C of photo-crosslinking structure is
The grafting rate of 10~19%, hydrophilic macromolecule side chain D are 40~70%；
The polymer for forming the main polymer chain A can be azido poly (glycidyl methacrylate) P (GMA-
N3), Azidoethyl cellulose (EC-N3), alkynyl ethyl cellulose (EC-C ≡ CH), azido polyvinyl alcohol P (VA-N3), alkynes
Base polyvinyl alcohol P (VA-C ≡ CH), alkynyl poly hydroxy ethyl acrylate P (HEMA-C ≡ CH), alkynyl hydroxyethyl acrylate P
(HEA-C ≡ CH), alkynyl polyhydroxypropyl methaciylate (PHPMA-C ≡ CH), azido polyhydroxypropyl methaciylate
(PHPMA-N3), alkynyl polyhydroxypropyl acrylate (PHPA-C ≡ CH) and azido polyhydroxypropyl acrylate (PHPA-N3) one
Kind；
The polymer for forming the lipophilic polymer side chain B is butyl polyacrylate (PnBA-C ≡ that end is alkynyl
CH), the polyacrylic acid tert-butyl ester (PtBA-C ≡ CH), polymethyl acrylate (PMA-C ≡ CH), polymethyl methacrylate (PMMA-
C ≡ CH), polycaprolactone (PCL-C ≡ CH), polystyrene (PS-C ≡ CH), polyacrylonitrile (PAN-C ≡ CH), polylactide
One of (PLA-C ≡ CH) and polyvinyl acetate (PVAc-C ≡ CH) or end are the butyl polyacrylate of azido
(PnBA-N3) and the polyacrylic acid tert-butyl ester (PtBA-N3One of)；
Form it is described tool photo-crosslinking structure polymer side chain C polymer be end be alkynyl polymethylacrylic acid meat
Osmanthus acyl group ethyl ester (PCEMA-C ≡ CH), polyacrylic acid cinnamoyl ethyl ester (PCEA-C ≡ CH) and polyvinyl cinnamate
One of (PVC-C ≡ CH) or end are the polymethylacrylic acid cinnamoyl ethyl ester (PCEMA-N of azido3), poly- third
Olefin(e) acid cinnamoyl ethyl ester (PCEA-N3) and polyvinyl cinnamate (PVC-N3One of)；
Form the hydrophilic macromolecule side chain D polymer be end be alkynyl polyethylene glycol (MPEG-C ≡ CH),
One of poly(N-isopropylacrylamide) (PNIPAM-C ≡ CH) and polyethyleneimine (PEI-C ≡ CH) or end are
Polyethylene glycol (the MPEG-N of azido3) and poly(N-isopropylacrylamide) (PNIPAM-N3One of)；
Above-mentioned amphipathic ternary molecular brush polymer can pass through the synthesis of the methods of living polymerization and point chemistry, synthetic method
Specifically includes the following steps:
(1) main chain is synthesized, then functionalization is carried out to main chain, obtains functionalization trunk polymer；
(2) side chain is synthesized, introduce functional group simultaneously in the synthesis process or functionalization is carried out to the side chain after synthesis, is obtained
To hydrophilic macromolecule side chain polymer, lipophilic polymer side chain polymer and the polymer side chain polymerization for having photo-crosslinking structure
Object；
(3) by functionalization trunk polymer, hydrophilic macromolecule side chain polymer, lipophilic polymer side chain polymer and
Have the polymer side chain mixed with polymers of photo-crosslinking structure, carries out a step " nitrine-alkynyl " click chemistry in the presence of a catalyst
Reaction, obtains amphipathic three-component grafted polymer.
The method that main chain is synthesized described in step (1) is free radical polymerization, controllable free-radical polymerisation and anionic polymerisation
One of；
Functionalization described in step (1) is that alkynyl or azido group are introduced on each unit of main chain；
Functionalization trunk polymer described in step (1) can be azido poly (glycidyl methacrylate) P
(GMA-N3), Azidoethyl cellulose (EC-N3), alkynyl ethyl cellulose (EC-C ≡ CH), azido polyvinyl alcohol P (VA-
N3), alkynyl polyvinyl alcohol P (VA-C ≡ CH), alkynyl poly hydroxy ethyl acrylate P (HEMA-C ≡ CH), alkynyl polyacrylic acid
Hydroxyl ethyl ester P (HEA-C ≡ CH), alkynyl polyhydroxypropyl methaciylate (PHPMA-C ≡ CH), azido polymethylacrylic acid hydroxypropyl
Ester (PHPMA-N3), alkynyl polyhydroxypropyl acrylate (PHPA-C ≡ CH) and azido polyhydroxypropyl acrylate (PHPA-N3) one
Kind；
The method that side chain is synthesized described in step (2) is free radical polymerization, controllable free-radical polymerisation and anionic polymerisation
One of；
Hydrophilic macromolecule side chain polymer described in step (2) is polyethylene glycol (the MPEG-C ≡ that end is alkynyl
CH), one of poly(N-isopropylacrylamide) (PNIPAM-C ≡ CH) and polyethyleneimine (PEI-C ≡ CH), or end
End is the polyethylene glycol (MPEG-N of azido3) and poly(N-isopropylacrylamide) (PNIPAM-N3One of)；
Lipophilicity polymer side chain polymer described in step (2) is the butyl polyacrylate (PnBA-C that end is alkynyl
≡ CH), the polyacrylic acid tert-butyl ester (PtBA-C ≡ CH), polymethyl acrylate (PMA-C ≡ CH), polymethyl methacrylate
(PMMA-C ≡ CH), polycaprolactone (PCL-C ≡ CH), polystyrene (PS-C ≡ CH), polyacrylonitrile (PAN-C ≡ CH), poly- third
One of lactide (PLA-C ≡ CH) and polyvinyl acetate (PVAc-C ≡ CH) or end are the polyacrylic acid of azido
Butyl ester (PnBA-N3) and the polyacrylic acid tert-butyl ester (PtBA-N3One of)；
The polymer side chain polymer of tool photo-crosslinking structure described in step (2) is the polymethyl that end is alkynyl
Sour cinnamoyl ethyl ester (PCEMA-C ≡ CH), polyacrylic acid cinnamoyl ethyl ester (PCEA-C ≡ CH) and polyvinyl alcohol cinnamic acid
One of ester (PVC-C ≡ CH) or end are the polymethylacrylic acid cinnamoyl ethyl ester (PCEMA-N of azido3), it is poly-
Acrylic acid cinnamoyl ethyl ester (PCEA-N3) and polyvinyl cinnamate (PVC-N3One of)；
Introducing functional group and functionalization described in step (2) are that alkynyl or azido are introduced on the end of side chain
Group；
Catalyst described in step (3) is one of following combination: copper sulphate and ascorbic acid, cuprous bromide and five
Methyl diethylenetriamine or cuprous bromide and 2,2'- bipyridyl；The mass ratio of the copper sulphate and ascorbic acid is preferably 1:
2。
A kind of vermiform unimolecular micelle, length are 20~300nm, and width is 15~35nm.It is that deionized water is slow
It is added dropwise in the n,N dimethylformamide solution of the amphipathic ternary molecular brush polymer, removes N, N- using dialysis
Dimethylformamide obtains, specific steps are as follows: the above-mentioned amphipathic high grafting density polymer of ternary of 1~10 mass parts is dissolved in 1
In~50 mass parts n,N-Dimethylformamide, then 50~500 mass parts water are slowly dropped to above-mentioned amphipathic ternary molecule
In the n,N-Dimethylformamide of brush polymer, n,N dimethylformamide finally is removed to water dialysis and obtains vermiform unimolecule
Micella.
Due to grafting rate height, mutually exclusive between side chain, the amphipathic high grafting density polymer of ternary is without the low grafting of the image of Buddha
The polymer molecule brush of rate is the same, shrinks bending, forms stable polymolecular micella with other interaction of molecules, can only pass through
The interaction of intramolecular is formed using hydrophobic side chain B and C as core, and hydrophilic side-chains D is the vermiform unimolecular micelle of hat.It should
The side chain PtBA of polymer is further hydrolyzed, and PAA can be become.PAA has PH responsiveness.Self assembly in acid condition,
PAA and PCEMA is shunk because hydrophobic, therefore, can be in assembling by inside drug encapsulation to unimolecular micelle, when around ring
When border is in alkalinity, due to the deprotonation of PAA, contains and Medicine small molecule is released slowly inside unimolecular micelle.
The vermiform unimolecular micelle can apply to the fields such as pharmaceutical carrier, nano-reactor or nanocatalyst.
Compared with prior art, the present invention has the following advantages and beneficial effects:
(1) the vermiform unimolecular micelle that this technology obtains, structure novel.
(2) morphology and size of vermiform unimolecule nano-micelle can be controlled by adjusting backbone length with side chain lengths
System, improves the controllability of micella appearance and size.
(3) vermiform unimolecule nano-micelle will not because of its concentration, the effect of the other factors such as shearing force and disintegrate.Solution
When being lower than critical micelle concentration, or in ionic strength, the effect of the factors such as high shear force is lower to be solved certainly traditional polymolecular micella
The problem of body.
Detailed description of the invention
Fig. 1 is the core for the ternary brush polymer P GMA-g- (PtBA-r-PCEMA-r-MPEG) being prepared in embodiment 1
Magnetic chart, Fig. 1 illustrate that side chain PtBA, PCEMA, MPEG are successfully grafted on main chain.
Fig. 2 is the poly- of the ternary brush polymer P GMA-g- (PtBA-r-PCEMA-r-MPEG) being prepared in embodiment 1
The pattern of object chain under an atomic force microscope is closed, Fig. 2 can be seen that the polymer molecular chain has vermiform pattern, illustrate side chain
Grafting density is big, and steric hindrance is larger, so that the main chain of polymer, which can not crimp, obtains vermiform pattern.
Specific embodiment
Below with reference to embodiment and attached drawing, the present invention is described in further detail, but embodiments of the present invention are unlimited
In this.
Embodiment 1
A kind of high grafting density polymer of amphipathic ternary, is prepared by the following steps to obtain:
(1)P(GMA-N3) main chain synthesis
By the mass ratio of the material, take 1 part of 2- isobutyl bromide mono methoxy ethyl ester initiator, 700 parts of Glycidyl methacrylates sweet
Grease (GMA), 600 parts of diphenyl ether, 1 part of CuBr and 1 part of N, N, N', N', N "-pentamethyl-diethylenetriamine (PMDETA), in nitrogen
The lower 30 DEG C of progress ATRP of gas shielded react 3 hours, obtain the poly (glycidyl methacrylate) that the degree of polymerization (DP) is 260
(PGMA)。
By the mass ratio of the material, 1 part of PGMA (DP=260), 1000 parts of NaN are taken3, 130000 parts of dimethylformamides (DMF)
And 6 parts of AlCl3, reacted 24 hours at 50 DEG C, obtain P (GMA-N3), as main chain.
The synthesis of (2) three kinds of side chains
The synthesis of hydrophilic macromolecule side chain: the mass ratio of the material is pressed, 1 part of mono methoxy polyethylene glycol (Mn=5000), 3 are taken
Part 2-propynyl acetic acid, 4 parts of 4-dimethylaminopyridine (DMAP), 6 parts of 1- (3- dimethylaminopropyl) -3- ethyls carbonizations two are sub-
Amine hydrochlorate (EDCHCl) and 500 parts of methylene chloride, 30 DEG C are reacted 24 hours, obtain MPEG-C ≡ CH (DP=114).
The synthesis of lipophilic polymer side chain: the mass ratio of the material is pressed, 1 part of trimethyl silicane propargyl -2- bromine isobutyl ester is taken to draw
Send out agent, 80 parts of tert-butyl acrylates (tBA), 120 parts of toluene, 1 part of CuBr and 1 part of N, N, N', N', N "-pentamethyl divinyl three
Amine (PMDETA), 80 DEG C of progress ATRP react 6 hours under nitrogen protection, obtain the PtBA-C ≡ that trimethyl silicane alkynyl is end
C-TMS.By the mass ratio of the material, 1 part of PtBA-C ≡ C-TMS polymer is taken, is dissolved in 5000 tetrahydrofurans, adds 4 part four
Butyl ammonium fluoride hydrolyzes for 24 hours at room temperature, after sloughing trimethyl silicane group, obtains the PtBA-C ≡ C-TMS that DP is 85.
Have the synthesis of the polymer side chain of photo-crosslinking structure: pressing the mass ratio of the material, take 1 part of trimethyl silicane propargyl -2- bromine
Isobutyl ester initiator, 60 parts of hydroxyethyl methacrylates (HEMA), 100 parts of methanol, 1 part of CuCl and 1 part of 2,2'- bipyridyl,
The lower 50 DEG C of progress ATRP reaction of nitrogen protection obtains the PHEMA-C ≡ CH-TMS that the degree of polymerization (DP) is 120.Take 100 parts of PHEMA-
C ≡ CH-TMS, 200 parts of cinnamoyl chlorides and 300 parts of anhydrous pyridines carry out acylation reaction under room temperature, obtain PCEMA-C ≡ CH-
TMS.1 part of PCEMA-C ≡ CH-TMS polymer is taken again, is dissolved in 5000 tetrahydrofurans, is added 4 parts of tetrabutyl ammonium fluorides,
It hydrolyzes at room temperature for 24 hours, after sloughing trimethyl silicane group, obtains the PCEMA-C ≡ CH that DP is 65.
(3) synthesis of the high grafting density polymer P GMA-g- (PtBA-r-PCEMA-r-MPEG) of amphipathic ternary
By the mass ratio of the material, 1 part of P (GMA-N is taken3), 200 parts of MPEG-C ≡ CH of part, 46 parts of PtBA-C ≡ CH, 5 parts
PCEMA-C ≡ CH is dissolved in 1000 parts of dimethylformamides (DMF), adds 1 part of CuSO4And 2 parts of sodium ascorbates, it is anti-at 30 DEG C
It answers 3 days, obtains the high grafting density polymer P GMA-g- (PtBA-r-PCEMA-r-MPEG) of amphipathic ternary.
A kind of vermiform unimolecule nano-micelle is obtained using solution self-assembly method, and preparation method includes the following steps:
In mass ratio, 1 part of amphipathic high grafting density polymer of ternary is taken to be dissolved in 10 parts of n,N-Dimethylformamide,
Under 30 DEG C of magnetic agitation 1000rpm, 30 parts of deionized waters are slowly dropped in polymer solution with peristaltic pump, be added dropwise after
Continuous stirring 30 minutes is then transferred in bag filter to water two days removing DMF of dialysis, that is, obtaining with PCEMA, PtBA is core, MPEG
For the vermiform unimolecular micelle of hat.
Embodiment 2
Preparation method and raw material composition are with embodiment 1, only to the three-component grafted polymer of amphipathic vermiform of embodiment 1
Backbone length be adjusted, various sizes of nano-micelle can be made.The length of three kinds of main chains is shown in Table 1.
Influence of 1 backbone length of table to unimolecular micelle length
As can be seen from Table 1, by changing the length of main chain, the vermiform unimolecule nanometre glue of different length can be prepared
Beam.
Embodiment 3
Preparation method and raw material are adjusted the hydrophobe side chain mass ratio of polymer, probe into hydrophobe with embodiment 1
Influence of the side chain mass ratio to micella stability, the results are shown in Table 2.Here, hydrophobic side chains are PCEMA and PtBA.
Influence of the 2 hydrophobe side chain mass ratio of table to micella stability
As can be seen from Table 2, when hydrophobic side chain is greater than the 60% of total side chain quality, polymer starts that reality can not be passed through
The method for applying example 1 obtains stable unimolecular micelle, thus Precipitation.
Embodiment 4
Preparation method and raw material are adjusted the volume ratio of PCEMA and PtBA, probe into PCEMA and PtBA with embodiment 1
Influence of the volume ratio to micelle inner core phase structure, the results are shown in Table 3.
Influence of the volume ratio of table 3 PCEMA and PtBA to micelle inner core phase structure
As can be seen from Table 3, when PCEMA volume accounts for the 12.5% of PCEMA and PtBA total volume, micelle inner core has body
The globular micelle (BCC) of heart cubic array；When PCEMA volume fraction reaches 30%, micelle inner core has two-dimentional Hexagonal packing
Shape structure (HEX)；When PCEMA volume fraction reaches 50%, layer structure (LAM).
Embodiment 5
A kind of high grafting density polymer of amphipathic ternary, is prepared by the following steps to obtain:
(1)P(GMA-N3) main chain synthesis
By the mass ratio of the material, take 1 part of 2- isobutyl bromide mono methoxy ethyl ester initiator, 700 parts of Glycidyl methacrylates sweet
Grease (GMA), 600 parts of diphenyl ether, 1 part of CuBr and 1 part of N, N, N', N', N "-pentamethyl-diethylenetriamine (PMDETA), in nitrogen
The lower 30 DEG C of progress ATRP of gas shielded react 3 hours, obtain the poly (glycidyl methacrylate) that the degree of polymerization (DP) is 260
(PGMA)。
By the mass ratio of the material, 1 part of PGMA (DP=260), 1000 parts of NaN are taken3, 130000 parts of dimethylformamides (DMF)
And 6 parts of AlCl3, reacted 24 hours at 50 DEG C, obtain P (GMA-N3), as main chain.
The synthesis of (2) three kinds of side chains
The synthesis of hydrophilic macromolecule side chain: the mass ratio of the material is pressed, 1 part of mono methoxy polyethylene glycol (Mn=5000), 3 are taken
Part 2-propynyl acetic acid, 4 parts of 4-dimethylaminopyridine (DMAP), 6 parts of 1- (3- dimethylaminopropyl) -3- ethyls carbonizations two are sub-
Amine hydrochlorate (EDC.HCl) and 500 parts of methylene chloride, 30 DEG C are reacted 24 hours, obtain MPEG-C ≡ CH (DP=114).
The synthesis of lipophilic polymer side chain: the mass ratio of the material is pressed, 1 part of trimethyl silicane propargyl -2- bromine isobutyl ester is taken to draw
Send out agent, 80 parts of n-butyl acrylates (nBA), 100 parts of toluene, 1 part of CuBr and 1 part of N, N, N', N', N "-pentamethyl divinyl three
Amine (PMDETA), 80 DEG C of progress ATRP react 6 hours under nitrogen protection, obtain the PBA-C ≡ that trimethyl silicane alkynyl is end
C-TMS.By the mass ratio of the material, 1 part of PnBA-C ≡ C-TMS polymer is taken, is dissolved in 5000 tetrahydrofurans, adds 4 part four
Butyl ammonium fluoride hydrolyzes for 24 hours at room temperature, after sloughing trimethyl silicane group, obtains the PnBA-C ≡ C-TMS that DP is 85.
Have the synthesis of the polymer side chain of photo-crosslinking structure: pressing the mass ratio of the material, take 1 part of trimethyl silicane propargyl -2- bromine
Isobutyl ester initiator, 60 parts of hydroxyethyl methacrylates (HEMA), 100 parts of methanol, 1 part of CuCl and 1 part of 2,2'- bipyridyl,
The lower 50 DEG C of progress ATRP reaction of nitrogen protection obtains the PHEMA-C ≡ CH-TMS that the degree of polymerization (DP) is 120.Take 100 parts of PHEMA-
C ≡ CH-TMS, 200 parts of cinnamoyl chlorides and 300 parts of anhydrous pyridines carry out acylation reaction under room temperature, obtain PCEMA-C ≡ CH-
TMS.1 part of PCEMA-C ≡ CH-TMS polymer is taken again, is dissolved in 5000 tetrahydrofurans, is added 4 parts of tetrabutyl ammonium fluorides,
It hydrolyzes at room temperature for 24 hours, after sloughing trimethyl silicane group, obtains the PCEMA-C ≡ CH that DP is 65.
(3) synthesis of the high grafting density polymer P GMA-g- (PnBA-r-PCEMA-r-MPEG) of amphipathic ternary
By the mass ratio of the material, 1 part of P (GMA-N is taken3), 200 parts of MPEG-C ≡ CH of part, 46 parts of PnBA-C ≡ CH, 5 parts
PCEMA-C ≡ CH is dissolved in 1000 parts of dimethylformamides (DMF), adds 1 part of CuSO4And 2 parts of sodium ascorbates, it is anti-at 30 DEG C
It answers 3 days, obtains the high grafting density polymer P GMA-g- (PnBA-r-PCEMA-r-MPEG) of amphipathic ternary.
A kind of vermiform unimolecule nano-micelle is obtained using solution self-assembly method, and preparation method includes the following steps:
In mass ratio, 1 part of amphipathic high grafting density polymer of ternary is taken to be dissolved in 10 parts of n,N-Dimethylformamide,
Under 30 DEG C of magnetic agitation 1000rpm, 30 parts of deionized waters are slowly dropped in polymer solution with peristaltic pump, be added dropwise after
Continuous stirring 30 minutes is then transferred in bag filter to water two days removing DMF of dialysis, that is, obtaining with PCEMA, PnBA is core, MPEG
For the vermiform unimolecular micelle of hat.
Embodiment 6
Preparation method and raw material are only adjusted the degree of polymerization of hydrophilic macromolecule side chain with embodiment 5, probe into hydrophilic
Influence of the degree of polymerization of property polymer side chain to the diameter of vermiform unimolecular micelle, the results are shown in Table 5.
Influence of the degree of polymerization of 5 hydrophilic side-chains of table to the diameter of vermiform unimolecular micelle
By table 5 as it can be seen that the degree of polymerization of hydrophilic macromolecule side chain is bigger, the diameter of vermiform unimolecular micelle is also bigger.
Embodiment 7
Preparation method and raw material are the same as embodiment 5, MPEG, PCEMA and PnBA of every kind of amphipathic ternary molecular brush polymer
The grafting rate of side chain is respectively 70%, 8%, 12%, is only adjusted to the degree of polymerization of lipophilic polymer side chain, probes into oleophylic
Influence of the degree of polymerization of property polymer side chain to the hydrophobic nuclear diameter of vermiform unimolecular micelle, the results are shown in Table 6.
Influence of the degree of polymerization of the lipophilic side chain of table 6 to the hydrophobic nuclear diameter of vermiform unimolecular micelle
By table 6 as it can be seen that the degree of polymerization of lipophilic polymer side chain is bigger, the hydrophobic nuclear diameter of vermiform unimolecular micelle is also got over
Greatly.
Embodiment 8
Preparation method and raw material are adjusted the hydrophobe side chain mass ratio of polymer, probe into hydrophobe with embodiment 5
Influence of the side chain mass ratio to micella stability, the results are shown in Table 7.Here, hydrophobic side chains are PCEMA and PnBA.
Influence of the 7 hydrophobe side chain mass ratio of table to micella stability
As shown in Table 7, when hydrophobic side chain is greater than the 50% of total side chain quality, polymer starts that embodiment can not be passed through
5 method obtains stable unimolecular micelle, thus Precipitation.
Embodiment 9
Preparation method and raw material composition only change the lipophilicity of the amphipathic ternary molecular brush of embodiment 5 with embodiment 5
The composition of polymer side chain, the preparation method and PtBA of PnBA, PCL, PMA, PS that the lipophilic polymer side chain degree of polymerization is 85
It prepares similar, is prepared by common ARTP.MPEG, PCEMA and oleophylic of every kind of amphipathic ternary molecular brush polymer
The grafting rate of property polymer side chain is respectively 70%, 8%, 12%.Lipophilic polymer side chain structure is probed into mutually to tie intramolecular
The influence of structure.The experimental results showed that the unimolecule assembled with the ternary brush that PnBA, PCL, PMA are lipophilic polymer side chain
Micella, internal phase structure is roughly the same, the unimolecular micelle that the ternary brush with PS for lipophilic polymer side chain is prepared,
Inside mutually separates unobvious.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (3)
1. a kind of vermiform unimolecular micelle, which is characterized in that the vermiform unimolecular micelle length is 20~300nm, wide
Degree is 15~35nm；The vermiform unimolecular micelle is deionized water to be slowly added dropwise to amphipathic ternary molecular brush polymer
N,N-Dimethylformamide solution in, using dialysis remove n,N-Dimethylformamide obtain；
The amphipathic ternary molecular brush polymer has following general formula: A-g- (B-r-C-r-D)；
Wherein, g represents grafting, and r represents random copolymerization, and A is main polymer chain, and B is lipophilic polymer side chain, and C is that tool light is handed over
It is coupled the polymer side chain of structure, D is hydrophilic macromolecule side chain；Lipophilic polymer side chain B, the macromolecule for having photo-crosslinking structure
Side chain C and hydrophilic macromolecule side chain D are randomly grafted on main chain A；
The polymer for forming the main polymer chain A is azido poly (glycidyl methacrylate), Azidoethyl fiber
Element, alkynyl ethyl cellulose, azido polyvinyl alcohol, alkynyl polyvinyl alcohol, alkynyl poly hydroxy ethyl acrylate, alkynyl poly- third
Olefin(e) acid hydroxyl ethyl ester, alkynyl polyhydroxypropyl methaciylate, azido polyhydroxypropyl methaciylate, alkynyl polyacrylic acid hydroxypropyl
One kind of ester, azido polyhydroxypropyl acrylate；
The polymer for forming the lipophilic polymer side chain B is the tertiary fourth of butyl polyacrylate, polyacrylic acid that end is alkynyl
Ester, polymethyl acrylate, polymethyl methacrylate, polycaprolactone, polystyrene, polyacrylonitrile, polylactide and poly-vinegar acid
One of vinyl acetate or end are one of butyl polyacrylate and polyacrylic acid tert-butyl ester of azido；
Form it is described tool photo-crosslinking structure polymer side chain C polymer be end be alkynyl polymethylacrylic acid cinnamoyl
One of base ethyl ester, polyacrylic acid cinnamoyl ethyl ester and polyvinyl cinnamate or end are the poly- first of azido
One of base acrylic acid cinnamoyl ethyl ester, polyacrylic acid cinnamoyl ethyl ester and polyvinyl cinnamate；
Form the hydrophilic macromolecule side chain D polymer be end be alkynyl polyethylene glycol, poly- (N- isopropyl acrylamide
Amine) and one of polyethyleneimine or end be in the polyethylene glycol and poly(N-isopropylacrylamide) of azido
It is a kind of；
The degree of polymerization of the main polymer chain A is 100~1000, and the degree of polymerization of lipophilic polymer side chain B is 50~120, tool
The degree of polymerization of the polymer side chain C of photo-crosslinking structure is 50~100, and the degree of polymerization of hydrophilic macromolecule side chain D is 100~150；
The grafting rate of lipophilic polymer side chain B be 1~10%, have photo-crosslinking structure polymer side chain C grafting rate be 10~
The grafting rate of 19%, hydrophilic macromolecule side chain D are 40~70%.
2. vermiform unimolecular micelle according to claim 1, which is characterized in that the vermiform unimolecular micelle passes through
Following steps are prepared: the high grafting density polymer of the amphipathic ternary of 1~10 mass parts is dissolved in 1~50 mass parts N, N- bis-
In methylformamide, then 50~500 mass parts water droplets are added to the N of above-mentioned amphipathic ternary molecular brush polymer, N- dimethyl
In formamide, n,N-Dimethylformamide finally is removed to water dialysis and obtains vermiform unimolecular micelle.
3. vermiform unimolecular micelle described in claim 1 is in pharmaceutical carrier, nano-reactor or nano-catalyst field
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| CN102911370A (en) * | 2012-10-23 | 2013-02-06 | 中科院广州化学有限公司 | Amphiphilic ternary polymer brush and nano capsule |
| CN103059312A (en) * | 2012-12-12 | 2013-04-24 | 中科院广州化学有限公司 | Amphipathic ternary molecular brush polymer constructed multichannel nanocapsule |
| CN103289099A (en) * | 2013-06-07 | 2013-09-11 | 中科院广州化学有限公司 | Amphiphilic acid-sensitive ternary molecular brush polymer constructed acid-sensitive nanocapsule |
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| CN102911370A (en) * | 2012-10-23 | 2013-02-06 | 中科院广州化学有限公司 | Amphiphilic ternary polymer brush and nano capsule |
| CN103059312A (en) * | 2012-12-12 | 2013-04-24 | 中科院广州化学有限公司 | Amphipathic ternary molecular brush polymer constructed multichannel nanocapsule |
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