A kind of amphipathic ternary molecular brush polymer and the vermiform unimolecular micelle of constructing thereof
Technical field
The invention belongs to self assembly polymeric material field, be specifically related to the polymerization of a kind of amphipathic ternary molecular brushThing and the vermiform unimolecular micelle of constructing thereof.
Background technology
Along with the appearance of novel synthetic reaction technology (as active free radical polymerization, click chemistry etc.), pass throughThe technology that polymer is prepared functional nano micella also emerges in multitude. As the modal method of preparing micellaOne of, self-assembly method can pass through composition, the each several part weight ratio of regulation and control block copolymer simply,The length of chain etc. is controlled shape, size and the performance of micella.
At present, the micella that block copolymerization and graft copolymer prepare by self assembly is generally polymolecularMicella. Traditional polymolecular micella really plays very large effect aspect solubilize drugs, and is once being subject to peopleGreat attention. But traditional polymolecular micella is a dynamic balance structure, and its structure can be along with the external worldThe change of environment and changing. When the concentration of polymer is during lower than CMC, micella can de-assembly. In addition,PH in blood circulation system, temperature, ionic strength, the factors such as high shear force also can have influence on the stable of micellaProperty. These factors, all can cause medicine to be released too early, thereby lessen the curative effect.
In order to improve the stability of carrier, people take following two kinds of methods conventionally: 1) polymolecular micella is enteredRow is crosslinked, latch-up structure; 2) replace polymolecular micella with unimolecular micelle.
But, after bag medicine carrying thing, carrying out the structure locking of carrier, chemical crosslink technique can be introduced poisonous conventionallyLittle molecule crosslinked dose, photo-crosslinking rule can make again to be wrapped that to be loaded in inner medicine rotten. Therefore, preparation is manyThe stable unimolecular micelle of sample is better selection.
Except Stability Analysis of Structures, unimolecular micelle has larger specific area, higher medicine carrying amount, moreLittle particle diameter, and can be by the molecular size range of precursor polymer, the micella of the required preparation of structure controlSize and geometric.
At present, most unimolecular micelle is all to prepare by dendritic amphipathic nature polyalcohol. But systemStandby dendritic polymer process is extremely loaded down with trivial details, has had a strong impact on its application. And prepared by amphipathic nature polyalcoholJourney is relatively simple, and can be by the percent grafting of telomerized polymer, close and distant water ratio, and chain lengths etc. are adjustedThe pattern of the micella that joint obtains, size, has good controllability.
But, most of research about graft copolymer at present, to prepare polymolecular micella/capsule as main,As the acid-sensitive type Nano capsule being prepared by graft copolymer of patent CN103289099A report, patentCN103059312A report pass through a kind of multichannel PH response that emulsion self-assembly method preparesNano capsule, the photo-crosslinking type nanometer wax phase change energy storage capsule of patent CN104645908A report, ifCapsule structure is not further locked, they all exist be easily affected by the external environment and occur disintegrate problem.
Summary of the invention
For solving the shortcoming and defect part of prior art, primary and foremost purpose of the present invention is to provide a kind of amphiphilicProperty ternary molecular brush polymer.
Another object of the present invention is to provide the synthetic method of above-mentioned amphipathic ternary molecular brush polymer.
A further object of the present invention is to provide wriggling of being prepared by above-mentioned amphipathic ternary molecular brush polymerWorm shape unimolecular micelle. This vermiform unimolecular micelle has nucleocapsid structure, and kernel is made up of hydrophobic high polymer,Skin is hydrophily high polymer.
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 lipophile macromoleculeSide chain, C is the polymer side chain of tool photo-crosslinking structure, D is hydrophilic macromolecule side chain; Lipophile macromoleculeThe polymer side chain C of side chain B, tool photo-crosslinking structure and hydrophilic macromolecule side chain D are randomly grafted on masterOn chain A;
The degree of polymerization of described main polymer chain A is 100~1000, and the degree of polymerization of lipophile polymer side chain B is50~120, the degree of polymerization of the polymer side chain C of tool photo-crosslinking structure is 50~100, hydrophilic macromolecule side chainThe degree of polymerization of D is 100~150; The percent grafting of lipophile polymer side chain B is 1~10%, tool photo-crosslinking knotThe percent grafting of the polymer side chain C of structure is 10~19%, and the percent grafting of hydrophilic macromolecule side chain D is40~70%;
The polymer that forms described main polymer chain A can be azido poly (glycidyl methacrylate) P(GMA-N3), azido ethyl cellulose (EC-N3), alkynyl ethyl cellulose (EC-C ≡ CH), foldedNitrogen base polyvinyl alcohol P (VA-N3), alkynyl polyvinyl alcohol P (VA-C ≡ CH), alkynyl polymethylacrylic acid hydroxylEthyl ester P (HEMA-C ≡ CH), alkynyl PHEMA P (HEA-C ≡ CH), the poly-methyl-prop of alkynylOlefin(e) acid hydroxypropyl acrylate (PHPMA-C ≡ CH), azido polymethylacrylic acid hydroxypropyl acrylate (PHPMA-N3), alkynesBased polyacrylic acid hydroxypropyl acrylate (PHPA-C ≡ CH) and azido polyacrylic acid hydroxypropyl acrylate (PHPA-N3) oneKind;
The polymer that forms described lipophile polymer side chain B is that end is the butyl polyacrylate of alkynyl(PnBA-C ≡ CH), the polyacrylic acid tert-butyl ester (PtBA-C ≡ CH), PMA (PMA-C ≡CH), polymethyl methacrylate (PMMA-C ≡ CH), polycaprolactone (PCL-C ≡ CH), polyphenyl secondAlkene (PS-C ≡ CH), polyacrylonitrile (PAN-C ≡ CH), polylactide (PLA-C ≡ CH) and poly-vinegarOne in vinyl acetate (PVAc-C ≡ CH), or the end butyl polyacrylate (PnBA-that is azidoN3) and the polyacrylic acid tert-butyl ester (PtBA-N3) in one;
The polymer that forms the polymer side chain C of described tool photo-crosslinking structure is that end is the poly-methyl-prop of alkynylOlefin(e) acid cinnamoyl ethyl ester (PCEMA-C ≡ CH), polyacrylic acid cinnamoyl ethyl ester (PCEA-C ≡ CH)And one in polyvinyl cinnamate (PVC-C ≡ CH), or the end poly-methyl-prop that is azidoOlefin(e) acid cinnamoyl ethyl ester (PCEMA-N3), polyacrylic acid cinnamoyl ethyl ester (PCEA-N3) and poly-secondEnol cinnamate (PVC-N3) in one;
The polymer that forms described hydrophilic macromolecule side chain D is that end is the polyethylene glycol (MPEG-C of alkynyl≡ CH), NIPA (PNIPAM-C ≡ CH) and polymine (PEI-C ≡ CH)In one, or the end polyethylene glycol (MPEG-N that is azido3) and poly-(N-isopropyl acrylamideAmine) (PNIPAM-N3) in one;
Above-mentioned amphipathic ternary molecular brush polymer can be synthetic by methods such as living polymerization and some chemistry, and it closesOne-tenth method specifically comprises the following steps:
(1) synthetic main chain, then main chain is carried out to functionalization, obtain functionalization trunk polymer;
(2) synthetic side chain is introduced functional group simultaneously or the side chain after synthetic is carried out to merit in building-up processEnergyization, obtains hydrophilic macromolecule side chain polymer, lipophile polymer side chain polymer and tool photo-crosslinking knotThe polymer side chain polymer of structure;
(3) by functionalization trunk polymer, hydrophilic macromolecule side chain polymer, lipophile polymer side chainThe polymer side chain mixed with polymers of polymer and tool photo-crosslinking structure is carried out a step and " is folded under catalyst existsNitrogen-alkynyl " click chemistry reaction, obtain amphipathic three-component grafted polymer.
The method of the synthetic main chain described in step (1) be radical polymerization, controllable free-radical polymerisation and cloudy fromOne in sub-polymerization;
Functionalization described in step (1) is to introduce alkynyl or azido group on each unit of main chain;
Functionalization trunk polymer described in step (1) can be azido polymethyl acid glycidylEster P (GMA-N3), azido ethyl cellulose (EC-N3), alkynyl ethyl cellulose (EC-C ≡ CH),Azido polyvinyl alcohol P (VA-N3), alkynyl polyvinyl alcohol P (VA-C ≡ CH), alkynyl polymethylacrylic acidHydroxyl ethyl ester P (HEMA-C ≡ CH), alkynyl PHEMA P (HEA-C ≡ CH), the poly-methyl-prop of alkynylOlefin(e) acid hydroxypropyl acrylate (PHPMA-C ≡ CH), azido polymethylacrylic acid hydroxypropyl acrylate (PHPMA-N3), alkynesBased polyacrylic acid hydroxypropyl acrylate (PHPA-C ≡ CH) and azido polyacrylic acid hydroxypropyl acrylate (PHPA-N3) oneKind;
The method of the synthetic side chain described in step (2) be radical polymerization, controllable free-radical polymerisation and cloudy fromOne in sub-polymerization;
Hydrophilic macromolecule side chain polymer described in step (2) is that end is the polyethylene glycol of alkynyl(MPEG-C ≡ CH), NIPA (PNIPAM-C ≡ CH) and polymineOne in (PEI-C ≡ CH), or the end polyethylene glycol (MPEG-N that is azido3) and poly-(N-N-isopropylacrylamide) (PNIPAM-N3) in one;
Lipophile polymer side chain polymer described in step (2) is that end is the butyl polyacrylate of alkynyl(PnBA-C ≡ CH), the polyacrylic acid tert-butyl ester (PtBA-C ≡ CH), PMA (PMA-C ≡CH), polymethyl methacrylate (PMMA-C ≡ CH), polycaprolactone (PCL-C ≡ CH), polyphenyl secondAlkene (PS-C ≡ CH), polyacrylonitrile (PAN-C ≡ CH), polylactide (PLA-C ≡ CH) and poly-vinegarOne in vinyl acetate (PVAc-C ≡ CH), or the end butyl polyacrylate that is azido(PnBA-N3) and the polyacrylic acid tert-butyl ester (PtBA-N3) in one;
The polymer side chain polymer of the tool photo-crosslinking structure described in step (2) is that end is the poly-first of alkynylBase acrylic acid cinnamoyl ethyl ester (PCEMA-C ≡ CH), polyacrylic acid cinnamoyl ethyl ester (PCEA-C≡ CH) and polyvinyl cinnamate (PVC-C ≡ CH) in one, or end to be azido poly-Methacrylic acid cinnamoyl ethyl ester (PCEMA-N3), polyacrylic acid cinnamoyl ethyl ester (PCEA-N3)And polyvinyl cinnamate (PVC-N3) in one;
Introducing functional group described in step (2) and functionalization be on the end of side chain, introduce alkynyl orAzido group;
Catalyst described in step (3) is the one in following combination: copper sulphate and ascorbic acid, brominationCuprous and pentamethyl-diethylenetriamine or cuprous bromide and 2,2'-bipyridyl; Described copper sulphate and ascorbic acidMass ratio be preferably 1:2.
A kind of vermiform unimolecular micelle, length is 20~300nm, width is 15~35nm. By deionizationWater slowly drops in the DMF solution of described amphipathic ternary molecular brush polymer, thenRemove DMF through dialysis and obtain, concrete steps are: by above-mentioned amphipathic 1~10 mass partsThe high grafting density polymer of ternary is dissolved in 1~50 mass parts DMF, then by 50~500 matterAmount part water is slowly added drop-wise in the DMF of above-mentioned amphipathic ternary molecular brush polymer, lastTo water, dialysis is removed DMF and is obtained vermiform unimolecular micelle.
Because percent grafting is high, the mutual eliminating between side chain, the high grafting density polymer of amphipathic ternary cannot look likeThe polymer molecule brush of low percent grafting is the same, shrinks bendingly, forms stable many with other interaction of moleculesMolecule micella, can only be by intramolecular interaction, forms taking hydrophobic side chain B and C as core hydrophilySide chain D is the vermiform unimolecular micelle of hat. The side chain PtBA of this polymer, can through further hydrolysisBecome PAA. PAA has PH response. Self assembly under acid condition, PAA and PCEMA are because dredgingShrinking appears in water, therefore, can in assembling, drug encapsulation be arrived to unimolecular micelle inside, works as surrounding environmentWhile being alkalescence, due to the deprotonation of PAA, bag is loaded in unimolecular micelle inside to Medicine small molecule quilt slowlyDischarge.
Described vermiform unimolecular micelle can be applied to pharmaceutical carrier, nano-reactor or nanocatalyst etc.Field.
Compared with prior art, the present invention has the following advantages and beneficial effect:
(1) the vermiform unimolecular micelle that this technology obtains, novel structure.
(2) pattern of vermiform unimolecule nano-micelle and size can be by regulating backbone length and side chain lengthsControl, improved the controllability of micella appearance and size.
(3) vermiform unimolecule nano-micelle can be because of its concentration, the effect of other factors such as shearing force andDisintegrate. Solve traditional polymolecular micella when lower than critical micelle concentration, or in ionic strength, high shear forceEtc. the problem that occurs under factor effect to disintegrate.
Brief description of the drawings
Fig. 1 is the ternary brush polymer preparing in embodiment 1The nuclear-magnetism figure of PGMA-g-(PtBA-r-PCEMA-r-MPEG), Fig. 1 has illustrated side chainPtBA, PCEMA, MPEG has successfully been grafted on main chain.
Fig. 2 is the ternary brush polymer preparing in embodiment 1The pattern of the polymer chain of PGMA-g-(PtBA-r-PCEMA-r-MPEG) under AFM, Fig. 2Can find out that this polymer molecular chain has vermiform pattern, illustrate that side chain graft density is large, steric hindrance is larger,The main chain that makes polymer cannot be curling and obtains vermiform pattern.
Detailed description of the invention
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but enforcement side of the present inventionFormula is not limited to this.
Embodiment 1
The high grafting density polymer of a kind of amphipathic ternary, is prepared by following steps:
(1)P(GMA-N3) main chain synthetic
Press amount of substance ratio, get 1 part of 2-isobutyl bromide mono methoxy ethyl ester initator, 700 parts of methacrylic acidsEthylene oxidic ester (GMA), 600 parts of diphenyl ether, 1 part of CuBr and 1 part of N, N, N', N', N " pentamethyl twoEthene triamine (PMDETA), under nitrogen protection, 30 DEG C are carried out ATRP reaction 3 hours, obtain the degree of polymerization(DP) be 260 poly (glycidyl methacrylate) (PGMA).
Press amount of substance ratio, get 1 part of PGMA (DP=260), 1000 parts of NaN3, 130000 parts of diformazansBase formamide (DMF) and 6 parts of AlCl3, at 50 DEG C, react 24 hours, obtain P (GMA-N3), doFor main chain.
Synthesizing of (2) three kinds of side chains
Synthesizing of hydrophilic macromolecule side chain: press amount of substance ratio, get 1 part of mono methoxy polyethylene glycol(Mn=5000), 3 parts of 2-propynyl acetic acid, 4 parts of DMAPs (DMAP), 6 parts of 1-(3-bis-Methylamino propyl group)-3-ethyl-carbodiimide hydrochloride (EDCHCl) and 500 parts of carrene, 30 DEG CReact 24 hours, obtain MPEG-C ≡ CH (DP=114).
Synthesizing of lipophile polymer side chain: press amount of substance ratio, get 1 part of trimethyl silicane propargyl-2-bromine differentButyl ester initator, 80 parts of tert-butyl acrylates (tBA), 120 parts of toluene, 1 part of CuBr and 1 partN, N, N', N', N " pentamethyl-diethylenetriamine (PMDETA), under nitrogen protection 80 DEG C to carry out ATRP anti-Answer 6 hours, obtaining trimethyl silicane alkynyl is the PtBA-C ≡ C-TMS of end. Press amount of substance ratio, get 1Part PtBA-C ≡ C-TMS polymer, is dissolved in 5000 oxolanes, then adds 4 parts of tetrabutyls to fluoridizeAmmonium, is hydrolyzed 24h under room temperature, sloughs after trimethyl silicane group, obtains DP and be 85 PtBA-C ≡ C-TMS.
Synthesizing of the polymer side chain of tool photo-crosslinking structure: press amount of substance ratio, get 1 part of trimethyl silicane alkynes thirdBase-2-bromine isobutyl ester initator, 60 parts of hydroxyethyl methacrylates (HEMA), 100 parts of methyl alcohol, 1 part of CuClAnd 1 part 2,2'-bipyridyl, under nitrogen protection, 50 DEG C are carried out ATRP reaction, obtain the degree of polymerization (DP) to be120 PHEMA-C ≡ CH-TMS. Get 100 parts of PHEMA-C ≡ CH-TMS, 200 parts of cinnamoyl chloridesAnd 300 parts of anhydrous pyridines, under normal temperature, carry out acylation reaction, obtain PCEMA-C ≡ CH-TMS. Get again 1Part PCEMA-C ≡ CH-TMS polymer, is dissolved in 5000 oxolanes, then adds 4 parts of tetrabutylsAmmonium fluoride, is hydrolyzed 24h under room temperature, sloughs after trimethyl silicane group, obtains DP and be 65 PCEMA-C ≡CH。
(3) closing of amphipathic ternary high grafting density polymer P GMA-g-(PtBA-r-PCEMA-r-MPEG)Become
Press amount of substance ratio, get 1 part of P (GMA-N3), part 200 parts of MPEG-C ≡ CH, 46 parts of PtBA-C≡ CH, 5 parts of PCEMA-C ≡ CH are dissolved in 1000 parts of dimethyl formamides (DMF), then add 1 partCuSO4And 2 parts of sodium ascorbates, react 3 days at 30 DEG C, obtain the high grafting density polymerization of amphipathic ternaryThing PGMA-g-(PtBA-r-PCEMA-r-MPEG).
A kind of vermiform unimolecule nano-micelle adopts solution self-assembly method to make, and its preparation method comprises followingStep:
In mass ratio, get 1 part of high grafting density polymer of amphipathic ternary and be dissolved in 10 parts of N, N-dimethyl formylIn amine, under 30 DEG C of magnetic agitation 1000rpm, 30 parts of deionized waters are slowly added drop-wise to polymerization with peristaltic pumpIn thing solution, dropwise and continue to stir 30 minutes, then transfer in bag filter water is dialysed and removed for two daysDMF, obtains with PCEMA, and PtBA is core, and MPEG is the vermiform unimolecular micelle of hat.
Embodiment 2
Preparation method and raw material form all with embodiment 1, only three-component grafted to the amphipathic vermiform of embodiment 1The backbone length of polymer regulates, and can make the nano-micelle of different size. The length of three kinds of main chainsIn table 1.
The impact of table 1 backbone length on unimolecular micelle length
As can be seen from Table 1, by changing the length of main chain, can prepare the vermiform unimolecule of different lengthNano-micelle.
Embodiment 3
Preparation method and raw material, with embodiment 1, are adjusted the close hydrophobic side chain mass ratio of polymer, probe intoThe impact of parent's hydrophobic side chain mass ratio on micella stability, result is as shown in table 2. At this, hydrophobic side chainsFor PCEMA and PtBA.
The impact of the close hydrophobic side chain mass ratio of table 2 on micella stability
As can be seen from Table 2, hydrophobic side chain be greater than total side chain quality 60% time, polymer starts nothingMethod obtains stable unimolecular micelle by the method for embodiment 1, thus Precipitation.
Embodiment 4
Preparation method and raw material, with embodiment 1, are adjusted the volume ratio of PCEMA and PtBA, probe intoThe impact of the volume ratio of PCEMA and PtBA on micella kernel phase structure, result is as shown in table 3.
The impact of the volume ratio of table 3PCEMA and PtBA on micella kernel phase structure
As can be seen from Table 3, when PCEMA volume account for PCEMA and PtBA cumulative volume 12.5% time,Micella kernel has the globular micelle (BCC) that body-centered cubic is arranged; When PCEMA volume fraction reaches 30%,Micella kernel has the shape structure (HEX) of two-dimentional Hexagonal packing; When PCEMA volume fraction reaches 50%, layerShape structure (LAM).
Embodiment 5
The high grafting density polymer of a kind of amphipathic ternary, is prepared by following steps:
(1)P(GMA-N3) main chain synthetic
Press amount of substance ratio, get 1 part of 2-isobutyl bromide mono methoxy ethyl ester initator, 700 parts of methacrylic acidsEthylene oxidic ester (GMA), 600 parts of diphenyl ether, 1 part of CuBr and 1 part of N, N, N', N', N " pentamethyl twoEthene triamine (PMDETA), under nitrogen protection, 30 DEG C are carried out ATRP reaction 3 hours, obtain the degree of polymerization(DP) be 260 poly (glycidyl methacrylate) (PGMA).
Press amount of substance ratio, get 1 part of PGMA (DP=260), 1000 parts of NaN3, 130000 parts of diformazansBase formamide (DMF) and 6 parts of AlCl3, at 50 DEG C, react 24 hours, obtain P (GMA-N3), doFor main chain.
Synthesizing of (2) three kinds of side chains
Synthesizing of hydrophilic macromolecule side chain: press amount of substance ratio, get 1 part of mono methoxy polyethylene glycol(Mn=5000), 3 parts of 2-propynyl acetic acid, 4 parts of DMAPs (DMAP), 6 parts of 1-(3-bis-Methylamino propyl group)-3-ethyl-carbodiimide hydrochloride (EDC.HCl) and 500 parts of carrene, 30 DEG CReact 24 hours, obtain MPEG-C ≡ CH (DP=114).
Synthesizing of lipophile polymer side chain: press amount of substance ratio, get 1 part of trimethyl silicane propargyl-2-bromine differentButyl ester initator, 80 parts of n-butyl acrylates (nBA), 100 parts of toluene, 1 part of CuBr and 1 partN, " pentamethyl-diethylenetriamine (PMDETA), under nitrogen protection, 80 DEG C are carried out ATRP for N, N', N', NReact 6 hours, obtaining trimethyl silicane alkynyl is the PBA-C ≡ C-TMS of end. Press amount of substance ratio, get1 part of PnBA-C ≡ C-TMS polymer, is dissolved in 5000 oxolanes, then adds 4 parts of tetrabutyl fluorineChange ammonium, under room temperature, be hydrolyzed 24h, slough after trimethyl silicane group, obtain DP and be 85 PnBA-C ≡ C-TMS.
Synthesizing of the polymer side chain of tool photo-crosslinking structure: press amount of substance ratio, get 1 part of trimethyl silicane alkynes thirdBase-2-bromine isobutyl ester initator, 60 parts of hydroxyethyl methacrylates (HEMA), 100 parts of methyl alcohol, 1 part of CuClAnd 1 part 2,2'-bipyridyl, under nitrogen protection, 50 DEG C are carried out ATRP reaction, obtain the degree of polymerization (DP) to be120 PHEMA-C ≡ CH-TMS. Get 100 parts of PHEMA-C ≡ CH-TMS, 200 parts of cinnamoyl chloridesAnd 300 parts of anhydrous pyridines, under normal temperature, carry out acylation reaction, obtain PCEMA-C ≡ CH-TMS. Get again 1Part PCEMA-C ≡ CH-TMS polymer, is dissolved in 5000 oxolanes, then adds 4 parts of tetrabutylsAmmonium fluoride, is hydrolyzed 24h under room temperature, sloughs after trimethyl silicane group, obtains DP and be 65 PCEMA-C ≡CH。
(3) the high grafting density polymer P of amphipathic ternary GMA-g-(PnBA-r-PCEMA-r-MPEG)Synthetic
Press amount of substance ratio, get 1 part of P (GMA-N3), part 200 parts of MPEG-C ≡ CH, 46 parts of PnBA-C≡ CH, 5 parts of PCEMA-C ≡ CH are dissolved in 1000 parts of dimethyl formamides (DMF), then add 1 partCuSO4And 2 parts of sodium ascorbates, react 3 days at 30 DEG C, obtain the high grafting density polymerization of amphipathic ternaryThing PGMA-g-(PnBA-r-PCEMA-r-MPEG).
A kind of vermiform unimolecule nano-micelle adopts solution self-assembly method to make, and its preparation method comprises followingStep:
In mass ratio, get 1 part of high grafting density polymer of amphipathic ternary and be dissolved in 10 parts of N, N-dimethyl formylIn amine, under 30 DEG C of magnetic agitation 1000rpm, 30 parts of deionized waters are slowly added drop-wise to polymerization with peristaltic pumpIn thing solution, dropwise and continue to stir 30 minutes, then transfer in bag filter water is dialysed and removed for two daysDMF, obtains with PCEMA, and PnBA is core, and MPEG is the vermiform unimolecular micelle of hat.
Embodiment 6
Preparation method and raw material, with embodiment 5, are only adjusted the degree of polymerization of hydrophilic macromolecule side chain, visitThe impact of the diameter of the degree of polymerization of studying carefully hydrophilic macromolecule side chain on vermiform unimolecular micelle, result is as table 5Shown in.
The impact of the diameter of the degree of polymerization of table 5 hydrophilic side-chains on vermiform unimolecular micelle
From table 5, the degree of polymerization of hydrophilic macromolecule side chain is larger, the diameter of vermiform unimolecular micelleAlso larger.
Embodiment 7
Preparation method and raw material be with embodiment 5, the MPEG of every kind of amphipathic ternary molecular brush polymer,The percent grafting of PCEMA and PnBA side chain is respectively 70%, 8%, 12%, only to lipophile polymer side chainThe degree of polymerization adjust, the degree of polymerization of probing into lipophile polymer side chain is hydrophobic to vermiform unimolecular micelleThe impact of nuclear diameter, result is as shown in table 6.
The impact of the degree of polymerization of table 6 lipophile side chain on vermiform unimolecular micelle hydrophobic core diameter
From table 6, the degree of polymerization of lipophile polymer side chain is larger, vermiform unimolecular micelle hydrophobic coreDiameter is also larger.
Embodiment 8
Preparation method and raw material, with embodiment 5, are adjusted the close hydrophobic side chain mass ratio of polymer, probe intoThe impact of parent's hydrophobic side chain mass ratio on micella stability, result is as shown in table 7. At this, hydrophobic side chainsFor PCEMA and PnBA.
The impact of the close hydrophobic side chain mass ratio of table 7 on micella stability
As shown in Table 7, hydrophobic side chain be greater than total side chain quality 50% time, polymer starts to lead toThe method of crossing embodiment 5 obtains stable unimolecular micelle, thus Precipitation.
Embodiment 9
Preparation method and raw material form all with embodiment 5, only changes the amphipathic ternary molecular brush of embodiment 5The composition of lipophile polymer side chain, PnBA, PCL that the lipophile polymer side chain degree of polymerization is 85, PMA,Prepared by the preparation method of PS and PtBA similar, is to be prepared by conventional ARTP. Every kind amphipathic threeUnit MPEG, the PCEMA of molecular brush polymer and the percent grafting of lipophile polymer side chain be respectively 70%,8%, 12%. Probe into the impact of lipophile polymer side chain structure on phase structure in molecule. Experimental result showsThe unimolecular micelle obtaining as the ternary brush assembling of lipophile polymer side chain taking PnBA, PCL, PMA,Its inner phase structure is roughly the same, and the ternary taking PS as lipophile polymer side chain is brushed the unimolecule preparingMicella, inside is separated not obvious.
Above-described embodiment is preferably embodiment of the present invention, but embodiments of the present invention are not subject to above-mentioned realityExecute routine restriction, other any do not deviate from the change done under Spirit Essence of the present invention and principle, modification,Substitute, combine, simplify, all should be equivalent substitute mode, within being included in protection scope of the present invention.