CN102634033B - Dextran base amphipathic nature block polymer preparation method - Google Patents
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Abstract
The present invention relates to dextran base amphipathic nature block polymer and preparation method.In described dextran base amphipathic nature block polymer, hydrophilic segment is dextran, and hydrophobic segment is polyamino acid class or polyester.Dextran base amphipathic nature block polymer is obtained by reacting by the high click that lives with end group azide polyamino acid or end group azide polyester respectively by end alkynyl radical dextran.Wherein, dextran segment preferred number average molecular weight is the dextran of 6000-60000; Polyamino acid segment preferred number average molecular weight is poly-(γ-phenmethyl-Pidolidone ester), poly-(β-benzyl-L-aspartate ester), poly-(ε-carbobenzoxy-(Cbz)-1B) of 3000-10000, poly-(O-benzyl-L-serine), poly-(L-Phe), poly-(ALANINE), poly-(L-Leu); Polyester segment preferred number average molecular weight is poly-(6-caprolactone), the poly(lactic acid) of 3000-10000.
Description
Technical field
The present invention relates to a kind of dextran base amphipathic nature block polymer and preparation method.
Background technology
Malignant tumour is becoming one of most serious disease threatening human health.At present, in the treatment of cancer, chemotherapy remains one of main means, and the key improving chemotherapy effect is inducing tumor cell programmed death, i.e. apoptosis.Because current the used specificity of small molecule chemotherapeutic medicine to cancer cells is poor, lack tumor-selective, each position of health can be distributed to blood, not only increase the economical load of patient, more seriously to human normal tissue and organ, there is toxic side effect.In addition, in medication process, cancer cells easily produces multidrug resistance, cause most of antitumor drug and unlike expection effective.In order to address these problems, antitumor drug and pharmaceutical carrier can be combined, change the water-soluble and stability of medicine, medicine is discharged, to play drug effect better with suitable concentration and speed by modes such as diffusion, infiltrations in vivo.Common pharmaceutical carrier organic and/or inorganic materials nanoparticle, branch-shape polymer, liposome, polymer nano hydrogel and polymer micelle etc.
Polymer nano micelle is by the aggregate with nucleocapsid structure of the amphipathic multipolymer nano-scale that spontaneous assembling is formed in water with hydrophilic segment and hydrophobic segment.Amphipathic copolymer self-assembled micelle has the following advantages as pharmaceutical carrier: (1) polymer micelle has obvious nucleocapsid structure, in self assembling process, hydrophobic block forms the kernel of micella, and hydrophilic block then forms the shell of micella around micelle inner core.Obvious nucleocapsid structure can effectively improve the water-soluble of medicine.(2) polymer micelle carrier can strengthen the stability of medicine in blood circulation, prolong drug cycling time in vivo.(3) size of polymer micelle is controlled, and suitable size is conducive to the gathering of carrier at tumor tissues, realizes its passive target to tumor tissues, improves the bioavailability of medicine, reduces the toxic side effect of medicine.Therefore, amphipathic copolymer self-assembled micelle has a good application prospect.
At present, in the research of the amphipathic multipolymer as pharmaceutical carrier, the kind of hydrophobic segment is more, and as aliphatic polyester, polyamino acid benzyl ester, polyoxytrimethylene etc., and hydrophilic segment majority selects polyoxyethylene glycol (PEG).PEG has good wetting ability and biocompatibility, toxicity is low, can avoid the identification of human body reticuloendothelial system, and the material be modified can be protected not by immune destruction, increases medicine cycling time in vivo.But the active group that can react in PEG molecule is only confined to terminal hydroxy group, be unfavorable for modifying micellar shell, as connected target group imparting carrier micelle active targeting or being cross-linked again micellar surface, micella stablized.Given this, the hydrophilic segment finding performance more excellent seems very important.
Dextran (Dextran), also known as dextran, a kind of water-soluble natural polysaccharide, can be degraded to dextran monomer in vivo, nontoxic, harmless.Dextran has the good function such as bio-compatibility, non-immunogenicity, anti-protein adsorption of similar PEG, is conducive to carrier and circulates for a long time in vivo.Dextran has the feature of " long circulating " and " stealth " of similar PEG when applying as pharmaceutical carrier, can reduce absorbing proteins in blood, and protection medicine is not destroyed.Dextran has the branched structure of 5%, containing the hydroxyl that can be functionalized in a large number in molecular structure, is easy to very much other target groups or fluorescence molecule to be bonded in dextran by the reactivity of hydroxyl.At present, utilize the hydroxyl synthesizing amphipathic graft copolymer research of dextran widely, as Biomaterials (Vol.30, p1363 ~ 1371,2009) a kind of polycaprolactone-g-dextran amphipathic graft copolymer is disclosed, it can form micella in aqueous, and can be effective as pharmaceutical carrier.To compare the structure more clear and definite of graft copolymer, segmented copolymer, and utilize the terminal aldehyde group of dextran to synthesize research also rare report based on the amphipathic nature block polymer of dextran.
For the deficiencies in the prior art, the present invention relates to dextran base amphipathic nature block polymer and preparation method.Preparation method provided by the invention is efficiently simple, the amphipathic nature block polymer obtained has good biological degradability, biocompatibility, be easy to the dextran shell of chemically modified in addition, can by further functionalization, medicine cycling time is in vivo significantly improved as pharmaceutical carrier, be conducive to the performance improving and improve medicine, realize the long time constant release of medicine.
One of the object of the invention is to provide amphipathic dextran based medicine carrier, and its hydrophilic chain is dextran, and hydrophobic chain is polyamino acid or polyester.The number-average molecular weight scope of described dextran is 6000-60000, and the number-average molecular weight scope of polyamino acid is 3000-10000, and the number-average molecular weight scope of polyester is 3000-10000.Described polyamino acid comprises poly-(γ-phenmethyl-Pidolidone ester), poly-(β-benzyl-L-aspartate ester), poly-(ε-carbobenzoxy-(Cbz)-1B), poly-(O-benzyl-L-serine), poly-(L-Phe), poly-(ALANINE), poly-(L-Leu); Described polyester comprises poly(lactic acid), poly-(6-caprolactone).
Two of the object of the invention is to provide the preparation method of dextran base amphipathic nature block polymer.The preparation method of dextran-b-polyamino acid and dextran-b-polyester amphiphilic block polymer, step and reaction conditions as follows:
(1) preparation of end alkynyl radical dextran
Dextran is dissolved in the acetic acid/sodium acetate buffer of pH=5, propargylamine and sodium cyanoborohydride is added successively under whipped state, wherein, the mol ratio of described dextran, propargylamine, sodium cyanoborohydride is react 96h under 1: 10: 10,50 DEG C of agitation conditions.After reaction terminates, reaction product to be dialysed 96h with 3500Da dialysis tubing, continue to change water to remove water miscible small-molecule substance.By product freeze-drying after dialysis, obtain end alkynyl radical dextran.
(2) preparation of end group azide polyamino acid benzyl ester
Carboxylic acid anhydride in amino acid-N-is dissolved in anhydrous DMF, under stirrer whipped state, adds nitrine propylamine, wherein, nitrine propylamine and carboxylic acid anhydride in amino acid-N-mole ratio be 1: 30 ~ 70.72h is reacted under 25 DEG C of agitation conditions.After reaction terminates, with the ether sedimentation of 10 times of reaction solution volumes, filter, washing is precipitated thing.25 DEG C of vacuum-drying 24h, namely obtain the polyamino acid benzyl ester of end group azide.
(3) preparation of end group azide polyester
A. the preparation of differing molecular weight polyester
Be dissolved in toluene by aliphatic cyclic monomer, add stannous octoate and Virahol, the mol ratio of cyclic monomer, stannous octoate is 1: 1000, and the mol ratio of cyclic monomer and Virahol is react 24h under 1: 20 ~ 70,120 DEG C of stirrers stir.After reaction terminates, with the ether sedimentation of 10 times of reaction solution volumes, filter, washing is precipitated thing, and 25 DEG C of vacuum-drying 24h, obtain the polyester of different number-average molecular weight.
B. the preparation of methyl sulphonyl polyester
Dissolved by polyester anhydrous methylene chloride, stirrer adds triethylamine under stirring, and then slowly drip Methanesulfonyl chloride with dropping funnel, wherein, the mol ratio of described polyester, triethylamine, Methanesulfonyl chloride is 1: 10: 10.Under condition of ice bath, Keep agitation reaction 24h.After reaction terminates, with the ether sedimentation of 10 times of reaction solution volumes, filter, washing is precipitated thing, and 25 DEG C of vacuum-drying 24h, namely obtain methyl sulphonyl polyester.
C. the preparation of end group azide polyester
The methyl sulphonyl polyester tetrahydrofuran (THF) obtained by b dissolves, and then adds sodiumazide, and wherein, described methyl sulphonyl polyester, the mol ratio of sodiumazide are 1: 10.40 DEG C of Keep agitation reaction 24h.After reaction terminates, with the ether sedimentation of 10 times of reaction solution volumes, filter, washing is precipitated thing, 25 DEG C of vacuum-drying 24h, namely obtains end group azide polyester.
(4) preparation of dextran base Amphipathilic block polymer
A. the preparation of dextran-b-polyamino acid Amphipathilic block polymer
Be dissolved in dimethyl sulfoxide (DMSO) by end alkynyl radical dextran and end group azide polyamino acid, stirrer adds part pentamethyl-diethylenetriamine under stirring, and then uses liquefied ammonia freeze thawing three times, adds cuprous bromide when second time freeze thawing.Wherein, the mol ratio of dextran, azide polyamino acid, pentamethyl-diethylenetriamine, cuprous bromide is 1.5: 1: 1.5: 1.5.After freeze thawing terminates, 40 DEG C of click react 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance.By product freeze-drying after dialysis, obtain dextran-b-polyamino acid benzyl ester amphipathic nature block polymer.
B. the preparation of dextran-b-polyester amphipathic nature block polymer
Be dissolved in dimethyl sulfoxide (DMSO) by end alkynyl radical dextran and end group azide polyester, stirrer adds part pentamethyl-diethylenetriamine under stirring, and then uses liquefied ammonia freeze thawing three times, adds cuprous bromide when second time freeze thawing.Wherein, the mol ratio of dextran, azide polyester, pentamethyl-diethylenetriamine, cuprous bromide is 1.5: 1: 1.5: 1.5.After freeze thawing terminates, 40 DEG C of click react 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance.By product freeze-drying after dialysis, obtain dextran-b-polyester amphipathic nature block polymer.
Compared with prior art, the present invention is to have the dextran of good biocompatibility for hydrophilic chain, compare and PEG, dextran has the branched structure of 5%, containing the hydroxyl that can be functionalized in a large number in molecular structure, be easy to very much other target groups or fluorescence molecule to be bonded in dextran by the reactivity of hydroxyl, be conducive to preparing multi-functional antitumor carrier.The segmented copolymer obtained not only has good biological degradability, biocompatibility and molecular weight controllability, and is easy to the dextran shell of chemically modified in addition.
Accompanying drawing explanation
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of end alkynyl radical dextran in deuterated dimethyl sulfoxide that the embodiment of the present invention 1 obtains.
Fig. 2 is poly-(γ-phenmethyl-Pidolidone ester) the hydrogen nuclear magnetic resonance spectrogram in deuterated trifluoroacetic acid of the end group azide that the embodiment of the present invention 2 (1) obtains.
Fig. 3 is the infrared spectrum of poly-(γ-phenmethyl-Pidolidone ester) of the end group azide that the embodiment of the present invention 2 (1) obtains.
Fig. 4 is the dextran-poly-hydrogen nuclear magnetic resonance spectrogram of (γ-phenmethyl-Pidolidone ester) segmented copolymer in deuterated dimethyl sulfoxide that the embodiment of the present invention 11 obtains.
Fig. 5 is the infrared spectrum of dextran-poly-(γ-phenmethyl-Pidolidone ester) segmented copolymer that the embodiment of the present invention 11 obtains.
Embodiment
In order to further illustrate the present invention, following examples are described in detail dextran base amphipathic nature block polymer thing provided by the invention and preparation method thereof.
In following embodiment, reaction raw materials is to be buied from the market or conventionally obtains, product quality × 100% that reaction yield=actual product quality/theory obtained obtains.
Embodiment 1 ~ 3: the preparation of the end alkynyl radical dextran of different number-average molecular weight
Take that 5g number-average molecular weight is 6000 (0.00083mol), the dextran of 30000 (0.00017mol) and 60000 (0.000083mol) is dissolved in the buffered soln of acetic acid/sodium-acetate of pH=5 respectively, add 0.46g (0.0083mol), 0.09g (0.0017mol) and 0.046g (0.00083mol) propargylamine under agitation condition successively, then add the sodium cyanoborohydride of 0.52g (0.0083mol), 0.11g (0.0017mol) and 0.052g (0.00083mol) respectively.96h is reacted under 50 DEG C of stirrers stir.After reaction terminates, reaction product to be dialysed 96h with 3500Da dialysis tubing, continue to change water to remove water miscible small-molecule substance.By product freeze-drying after dialysis, obtain the end alkynyl radical dextran of different number-average molecular weight, result ginseng table 1.
The preparation of the end alkynyl radical dextran of the different number-average molecular weight of table 1
| Experiment numbers | Mn(g mol -1) | M 1(g) | M 2(g) | M 3(g) | Reaction yield (%) |
| 1 | 6000 | 5 | 0.46 | 0.52 | 91.3 |
| 2 | 30000 | 5 | 0.09 | 0.11 | 90.6 |
| 3 | 60000 | 5 | 0.046 | 0.052 | 90.2 |
In upper table, Mn is the number-average molecular weight of dextran, M
1for the quality of dextran, M
2for the quality of propargylamine, M
3for the quality of sodium cyanoborohydride.
Embodiment 4 ~ 6: the preparation of poly-(γ-phenmethyl-Pidolidone ester) of the end group azide of different number-average molecular weight
Carboxylic acid anhydride monomer in the γ-phenmethyl-Pidolidone ester-N-taking 3 parts of 2g, puts into 3 dry ampullas respectively, adds the anhydrous DMF of 40mL respectively and dissolved by monomer.Add 0.025g (0.00025mol) under agitation respectively, 0.015g (0.00015mol), 0.011g (0.00011mol) nitrine propylamine initiator, then stirring reaction 72h under 25 DEG C of conditions.After reaction terminates, by reaction solution 400mL ether sedimentation, filter, washing is precipitated thing.Vacuum-drying 24h under 25 DEG C of conditions, namely obtains poly-(γ-phenmethyl-Pidolidone ester) of the end group azide of 3 kinds of different number-average molecular weights.Result ginseng table 2.
Poly-(γ-phenmethyl-Pidolidone ester) of the end group azide of the different number-average molecular weight of table 2
| Experiment numbers | Mn(g mol -1) | Reaction yield (%) |
| 1 | 5793 | 90.5 |
| 2 | 9516 | 91.2 |
| 3 | 14334 | 91.6 |
In upper table, Mn is the number-average molecular weight of poly-(γ-phenmethyl-Pidolidone ester), by
1hNMR test obtains.
Embodiment 7 ~ 9: the preparation of poly-(β-benzyl-L-aspartate ester) of the end group azide of different number-average molecular weight
Take carboxylic acid anhydride monomer in 3 parts of 2g β-benzyl-L-aspartate ester-N-respectively, put into 3 dry ampullas respectively, add the anhydrous DMF of 40mL respectively and monomer is dissolved.Under agitation add 0.027g (0.00027mol) respectively, 0.016g (0.00016mol), 0.011g (0.00011mol) nitrine propylamine initiator, then stirring reaction 72h under 25 DEG C of conditions, after reaction terminates, by reaction solution 400mL ether sedimentation, filter, washing is precipitated thing, 25 DEG C of vacuum-drying 24h, namely obtain poly-(β-benzyl-L-aspartate ester) of the end group azide of 3 kinds of different number-average molecular weights, result ginseng table 3.
The preparation of poly-(β-benzyl-L-aspartate ester) of the end group azide of the different number-average molecular weight of table 3
| Experiment numbers | Mn(g mol -1) | Reaction yield (%) |
| 1 | 5429 | 89.7 |
| 2 | 8914 | 90.8 |
| 3 | 11365 | 91.4 |
In upper table, Mn is the number-average molecular weight of poly-(β-benzyl-L-aspartate ester), is tested obtaining by 1HNMR.
Embodiment 10 ~ 12: the preparation of poly-(ε-carbobenzoxy-(Cbz)-1B) of the end group azide of different number-average molecular weight
Take carboxylic acid anhydride monomer in 3 parts of 2g ε-carbobenzoxy-(Cbz)-1B-N-respectively, put into 3 dry ampullas respectively, add the anhydrous DMF of 40mL respectively and monomer is dissolved.Under agitation add 0.022g (0.00022mol) respectively, 0.013g (0.00013mol), 0.01g (0.0001mol) nitrine propylamine initiator, then reacts solution to 72h under 25 DEG C of stirrer agitation conditions, after reaction terminates, by reaction solution 400mL ether sedimentation, filter, washing is precipitated thing, dry 24h under 25 DEG C of vacuum conditions, namely obtain poly-(ε-carbobenzoxy-(Cbz)-1B) of 3 kinds of different number-average molecular weights, result ginseng table 4.
The preparation of poly-(ε-carbobenzoxy-(Cbz)-1B) of the end group azide of the different number-average molecular weight of table 4
| Experiment numbers | Mn(g mol-1) | Reaction yield (%) |
| 1 | 6911 | 89.7 |
| 2 | 11365 | 90.8 |
| 3 | 17129 | 91.4 |
In upper table, Mn is the number-average molecular weight of poly-(ε-carbobenzoxy-(Cbz)-1B), is tested obtaining by 1HNMR.
Embodiment 13 ~ 15: the preparation of poly-(the O-benzyl-L-serine) of the end group azide of different number-average molecular weight
Take carboxylic acid anhydride monomer in 3 parts of 2gL-Serine-N-respectively, put into 3 dry ampullas respectively, add the anhydrous DMF of 40mL respectively and monomer is dissolved.Under agitation add 0.03g (0.00032mol) respectively, 0.018g (0.00018mol), 0.013g (0.00013mol) nitrine propylamine initiator, then solution is reacted 72h under 25 DEG C of stirrer agitation conditions, after reaction terminates, by reaction solution 400mL ether sedimentation, filter, washing is precipitated thing, dry 24h under 25 DEG C of vacuum conditions, namely obtains poly-(the O-benzyl-L-serine) of 3 kinds of different number-average molecular weights.Result ginseng table 5.
The preparation of poly-(the 0-benzyl-L-serine) of the different number-average molecular weight of table 5
| Experiment numbers | Mn(g mol -1) | Reaction yield (%) |
| 1 | 4701 | 88.9 |
| 2 | 7710 | 89.7 |
| 3 | 11604 | 90.4 |
In upper table, Mn is the number-average molecular weight of poly-(O-benzyl-L-serine), by
1hNMR test obtains.
Embodiment 16 ~ 18: the preparation of poly-(L-Phe) of the end group azide of different number-average molecular weight
Take carboxylic acid anhydride monomer in 3 parts of 2gL-phenylalanine-N-respectively, put into 3 dry ampullas respectively, add the anhydrous DMF of 40mL respectively and monomer is dissolved.Under agitation add 0.035g (0.00035mol) respectively, 0.021g (0.00021mol), 0.015g (0.00015mol) nitrine propylamine initiator, then solution is reacted 72h under 25 DEG C of stirrer agitation conditions, after reaction terminates, by reaction solution 400mL ether sedimentation, filter, washing is precipitated thing, dry 24h under 25 DEG C of vacuum conditions, namely obtains poly-(L-Phe) of 3 kinds of different number-average molecular weights.Result ginseng table 6.
The preparation of poly-(L-Phe) of the different number-average molecular weight of table 6
| Experiment numbers | Mn(g mol -1) | Reaction yield (%) |
| 1 | 4215 | 88.7 |
| 2 | 7008 | 90.2 |
| 3 | 10095 | 91.5 |
In upper table, Mn is the number-average molecular weight of poly-(L-Phe), by
1hNMR test obtains.
Embodiment 19 ~ 21: the preparation of poly-(ALANINE) of the end group azide of different number-average molecular weight
Take carboxylic acid anhydride monomer in 3 parts of 2gL-L-Ala-N-respectively, put into 3 dry ampullas respectively, add the anhydrous DMF of 40mL respectively and monomer is dissolved.Under agitation add 0.058g (0.00025mol) respectively, 0.035g (0.00035mol), 0.025g (0.00013mol) nitrine propylamine initiator, then reacts 72h under 25 DEG C of agitation conditions.After reaction terminates, by reaction solution 400mL ether sedimentation, filter, washing is precipitated thing, dry 24h under 25 DEG C of vacuum conditions, namely obtains poly-(ALANINE) of 3 kinds of different number-average molecular weights.Result ginseng table 7.
The preparation of poly-(ALANINE) of the different number-average molecular weight of table 7
| Experiment numbers | Mn(g mol -1) | Reaction yield (%) |
| 1 | 2087 | 87.6 |
| 2 | 5779 | 90.3 |
| 3 | 8619 | 90.8 |
In upper table, Mn is the number-average molecular weight of poly-(ALANINE), is tested obtaining by 1HNMR.
Embodiment 22 ~ 24: the preparation of poly-(L-Leu) of the end group azide of different number-average molecular weight
Take carboxylic acid anhydride monomer in 3 parts of 2gL-leucine-N-respectively, put into 3 dry ampullas respectively, add the anhydrous DMF of 40mL respectively and monomer is dissolved.Under agitation add 0.042g (0.00042mol) respectively, 0.025g (0.00025mol), 0.014g (0.00014mol) nitrine propylamine initiator, then stirring reaction 72h under 25 DEG C of conditions, after reaction terminates, by reaction solution 400mL ether sedimentation, filter, washing is precipitated thing, dry 24h under 25 DEG C of vacuum conditions, namely obtains poly-(L-Leu) of 3 kinds of different number-average molecular weights.Result ginseng table 8.
The preparation of poly-(L-Leu) of the different number-average molecular weight of table 8
| Experiment numbers | Mn(g mol -1) | Reaction yield (%) |
| 1 | 3264 | 89.5 |
| 2 | 5410 | 90.1 |
| 3 | 9704 | 91.4 |
In upper table, Mn is the number-average molecular weight of poly-(L-Leu), by
1hNMR test obtains.
Embodiment 25 ~ 26: the preparation of poly-(6-caprolactone) of the end group azide of different number-average molecular weight
(1) 6-caprolactone of 2 parts of 10g is taken respectively, dissolve with 50mL toluene respectively, then 0.012g (0.0002mol) and 0.006g (0.0001mol) Virahol is added under agitation respectively, 0.028g (0.000069mol) and 0.028g (0.000069mol) stannous octoate, stirring reaction three days in 120 DEG C of oil baths.After reaction terminates, carry out sedimentation with 500mL ether, filter, washing is precipitated thing, dry 24h under 25 DEG C of vacuum conditions, namely obtains poly-(6-caprolactone) of 2 kinds of different number-average molecular weights.
(2) take respectively poly-(6-caprolactone) that 2g number-average molecular weight is 4219 and 8550, put into two dry ampullas respectively, dissolve with 40mL anhydrous methylene chloride respectively, 0.66mL, 0.33mL triethylamine and 0.54g (0.0047mol), 0.27g (0.0023mol) Methanesulfonyl chloride is added respectively under the condition stirred, then Methanesulfonyl chloride is added in dropping funnel, slowly Methanesulfonyl chloride is instilled reaction solution, then stirring reaction 24h under condition of ice bath.After reaction terminates, by the ether sedimentation of reaction solution 400mL, filter, washing is precipitated thing, dry 24h under 25 DEG C of vacuum conditions, namely obtains methyl sulphonyl poly-(6-caprolactone).
(3) take respectively poly-(6-caprolactone) that the above-mentioned one end of 2 parts of 0.5g is Methanesulfonyl chloride, dissolve with 20mL tetrahydrofuran (THF) respectively, then 0.077g (0.0012mol), 0.038g (0.00058mol) sodiumazide is added respectively, then stirring reaction 24h at 40 DEG C.After reaction terminates, by reaction solution 200mL ether sedimentation, filter, washing is precipitated thing, dry 24h under 25 DEG C of vacuum conditions, namely obtains poly-(6-caprolactone) of end group azide.Result ginseng table 9.
Poly-(6-caprolactone) of the different number-average molecular weight of table 9
In upper table, Mn
1for the number-average molecular weight of the first step reaction product poly-(6-caprolactone), the productive rate that reaction yield 1 is reacted for the first step; The productive rate that reaction yield 2 is reacted for second step, reaction yield 3 is the productive rate of three-step reaction.
Embodiment 27 ~ 28: the preparation of the poly(lactic acid) of the end group azide of different number-average molecular weight
(1) rac-Lactide of 2 parts of 5g is taken, dissolve with 50mL toluene respectively, then 0.012g (0.0002mol) and 0.006g (0.0001mol) Virahol is added under agitation respectively, 0.028g (0.000069mol) and 0.028g (0.000069mol) stannous octoate, stirring reaction three days in 120 DEG C of oil baths.After reaction terminates, carry out sedimentation with 500mL ether, filter, washing is precipitated thing, and dry 24h under 25 DEG C of vacuum conditions, namely obtains the poly(lactic acid) of 3 kinds of different number-average molecular weights.
(2) number-average molecular weight taking 2 parts of 2g is respectively the poly(lactic acid) of 4219 and 8550, put into two dry ampullas respectively, dissolve with 40mL methylene dichloride respectively, add 0.66mL, 0.33mL triethylamine and 0.54g (0.0047mol), 0.27g (0.0023mol) Methanesulfonyl chloride under agitation respectively, then Methanesulfonyl chloride is added in dropping funnel, slowly Methanesulfonyl chloride is instilled reaction solution, then stirring reaction 24h in ice bath.After reaction terminates, by the ether sedimentation of reaction solution 400mL, filter, washing is precipitated thing, and dry 24h under 25 DEG C of vacuum conditions, namely obtains sulfonyloxy methyl base polylactic acid.
(3) the sulfonyloxy methyl base polylactic acid in 2 parts of 0.5g (2) is taken respectively; dissolve with 20mL tetrahydrofuran (THF) respectively; then 0.077g (0.0012mol) and 0.038g (0.00058mol) sodiumazide is added, then stirring reaction 24h at 40 DEG C.After reaction terminates, by reaction solution 200mL ether sedimentation, filter, washing is precipitated thing, dry 24h under 25 DEG C of vacuum conditions, namely obtains end group azide poly(lactic acid).Result ginseng table 10.
The poly(lactic acid) of the different number-average molecular weight of table 10
In upper table, Mn
1for the number-average molecular weight of the first step reaction product poly(lactic acid), the productive rate that reaction yield 1 is reacted for the first step; The productive rate that reaction yield 2 is reacted for second step, reaction yield 3 is the productive rate of three-step reaction.
Embodiment 29 ~ 31: the preparation of poly-(γ-phenmethyl-Pidolidone ester) segmented copolymer of dextran-b-
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 6000, the number-average molecular weight adding embodiment 4 ~ 6 preparation is respectively 5793, 9516, poly-(γ-phenmethyl-Pidolidone ester) 0.19g (0.0000333mol) of the end group azide of 14334, 0.32g (0.0000333mol), 0.48g (0.0000333mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively when second time freeze thawing, 7.2mg, 7.2mg cuprous bromide.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(γ-phenmethyl-Pidolidone ester) segmented copolymer of dextran-b-.Result ginseng table 11.
Table 11 dextran-b-gathers (γ-phenmethyl-Pidolidone ester) segmented copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 5793 | 0.19 | 83.4 |
| 2 | 0.3 | 9516 | 0.32 | 83.1 |
| 3 | 0.3 | 14334 | 0.48 | 82.5 |
In upper table, Mn
1for the number-average molecular weight of poly-(γ-phenmethyl-Pidolidone ester), m
1for the quality of dextran, m
2for the quality of poly-(γ-phenmethyl-Pidolidone ester).
Embodiment 32 ~ 34: the preparation of dextran-b-poly-(β-benzyl-L-aspartate ester)
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 6000, the number-average molecular weight adding embodiment 7 ~ 9 preparation is respectively 5429, 8914, poly-(β-benzyl-L-aspartate ester) 0.18g (0.0000333mol) of the end group azide of 13424, 0.30g (0.0000333mol), 0.45g (0.0000333mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively when second time freeze thawing, 7.2mg, 7.2mg cuprous bromide.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(β-benzyl-L-aspartate ester) segmented copolymer of dextran-b-.Result ginseng table 12.
Table 12 dextran-b-gathers (β-benzyl-L-aspartate ester) segmented copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 5429 | 0.18 | 83.4 |
| 2 | 0.3 | 8914 | 0.30 | 83.1 |
| 3 | 0.3 | 13424 | 0.45 | 82.5 |
In upper table, Mn
1for the number-average molecular weight of poly-(β-benzyl-L-aspartate ester), m
1for the quality of dextran, m
2for the quality of poly-(β-benzyl-L-aspartate ester).Embodiment 35 ~ 37: the preparation of poly-(ε-carbobenzoxy-(Cbz)-1B) segmented copolymer of dextran-b-
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 6000, the number-average molecular weight adding embodiment 10 ~ 12 preparation is respectively 6911, 11365, poly-(ε-carbobenzoxy-(Cbz)-1B) 0.23g (0.0000333mol) of the end group azide of 17129, 0.38g (0.0000333mol), 0.57g (0.0000333mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively when second time freeze thawing, 7.2mg, 7.2mg cuprous bromide.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(ε-carbobenzoxy-(Cbz)-1B) segmented copolymer of dextran-b-.Result ginseng table 13.
Table 13 dextran-b-gathers (ε-carbobenzoxy-(Cbz)-1B) segmented copolymer
| Experiment numbers | M 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 6911 | 0.23 | 83.8 |
| 2 | 0.3 | 11365 | 0.38 | 84.3 |
| 3 | 0.3 | 17129 | 0.57 | 83.5 |
In upper table, Mn
1for the number-average molecular weight of poly-(ε-carbobenzoxy-(Cbz)-1B), m
1for the quality of dextran, m
2for the quality of poly-(ε-carbobenzoxy-(Cbz)-1B).
Embodiment 38 ~ 40: the preparation of poly-(the O-benzyl ester-Serine) segmented copolymer of dextran-b-
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 6000, the number-average molecular weight adding embodiment 13 ~ 15 preparation is respectively 4701, 7710, poly-(O-benzyl ester-Serine) 0.16g (0.0000333mol) of the end group azide of 11604, 0.26g (0.0000333mol), 0.39g (0.0000333mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively when second time freeze thawing, 7.2mg, 7.2mg cuprous bromide.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(the O-benzyl ester-Serine) segmented copolymer of dextran-b-.Result ginseng table 14.
Table 14 dextran-b-gathers (O-benzyl ester-Serine) segmented copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 4701 | 0.16 | 84.4 |
| 2 | 0.3 | 7710 | 0.26 | 83.7 |
| 3 | 0.3 | 11604 | 0.39 | 83.6 |
In upper table, Mn
1for the number-average molecular weight of poly-(O-benzyl ester-Serine), m
1for the quality of dextran, m
2for the quality of poly-(O-benzyl ester-Serine).
Embodiment 41 ~ 43: the preparation of poly-(L-Phe) segmented copolymer of dextran-b-
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 6000, the number-average molecular weight adding embodiment 16 ~ 18 preparation is respectively 4215, 7008, poly-(L-Phe) 0.14g (0.0000333mol) of the end group azide of 10095, 0.23g (0.0000333mol), 0.34g (0.0000333mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively when second time freeze thawing, 7.2mg, 7.2mg cuprous bromide.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(L-Phe) segmented copolymer of dextran-b-.Result ginseng table 15.
Table 15 gained dextran-b-gathers (L-Phe) segmented copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 4215 | 0.14 | 83.6 |
| 2 | 0.3 | 7008 | 0.23 | 84.8 |
| 3 | 0.3 | 10095 | 0.34 | 84.2 |
In upper table, Mn
1for the number-average molecular weight of poly-(L-Phe), m
1for the quality of dextran, m
2for the quality of poly-(L-Phe).
Embodiment 44 ~ 46: the preparation of poly-(ALANINE) segmented copolymer of dextran-b-
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 6000, the number-average molecular weight adding embodiment 19 ~ 21 preparation is respectively 2087,5779, poly-(ALANINE) 0.07g (0.0000333mol) of the end group azide of 8619,0.19g (0.0000333mol), 0.29g (0.0000333mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively, 7.2mg, 7.2mg cuprous bromide when second time freeze thawing.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(ALANINE) segmented copolymer of dextran-b-.Result ginseng table 16.
Table 16 dextran-b-gathers (ALANINE) segmented copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 2087 | 0.07 | 84.8 |
| 2 | 0.3 | 5779 | 0.19 | 83.5 |
| 3 | 0.3 | 8619 | 0.29 | 82.7 |
In upper table, Mn
1for the number-average molecular weight of poly-(ALANINE), m
1for the quality of dextran, m
2for the quality of poly-(ALANINE).
Embodiment 47 ~ 49: the preparation of poly-(L-Leu) segmented copolymer of dextran-b-
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 6000, the number-average molecular weight adding embodiment 22 ~ 24 preparation is respectively 3264,5410, poly-(L-Leu) 0.11g (0.0000333mol) of the end group azide of 9704,0.18g (0.0000333mol), 0.32g (0.0000333mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively, 7.2mg, 7.2mg cuprous bromide when second time freeze thawing.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(L-Leu) segmented copolymer of dextran-b-.Result ginseng table 17.
Table 17 dextran-b-gathers (L-Leu) segmented copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 3264 | 0.11 | 83.9 |
| 2 | 0.3 | 5410 | 0.18 | 83.5 |
| 3 | 0.3 | 9704 | 0.32 | 84.3 |
In upper table, Mn
1for the number-average molecular weight of poly-(L-Leu), m
1for the quality of dextran, m
2for the quality of poly-(L-Leu).
Embodiment 50 ~ 51: the preparation of poly-(6-caprolactone) segmented copolymer of dextran-b-
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 6000, the number-average molecular weight adding embodiment 25 ~ 26 preparation is respectively 4191, poly-(6-caprolactone) 0.18g (0.0000333mo1) of the end group azide of 8322,0.14g (0.0000333mo1), 0.28g (0.0000333mo1) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively when second time freeze thawing, 7.2mg, 7.2mg cuprous bromide.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(6-caprolactone) segmented copolymer of dextran-b-.Result ginseng table 18.
Table 18 dextran-b-gathers (6-caprolactone) segmented copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 4191 | 0.14 | 83.4 |
| 2 | 0.3 | 8322 | 0.28 | 83.1 |
In upper table, Mn
1for the number-average molecular weight of poly-(6-caprolactone), m
1for the quality of dextran, m
2for the quality of poly-(6-caprolactone).
Embodiment 52 ~ 53: the preparation of dextran-b-polylactic-acid block copolymer
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 6000, the number-average molecular weight adding embodiment 27 ~ 28 preparation is respectively 5429,8914, the poly(lactic acid) 0.18g (0.0000333mol) of the end group azide of 13424,0.30g (0.0000333mol), 0.45g (0.0000333mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively, 7.2mg, 7.2mg cuprous bromide when second time freeze thawing.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain dextran-b-polylactic-acid block copolymer.Result ginseng table 19.
Table 19 dextran-b-polylactic-acid block copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 4314 | 0.14 | 84.3 |
| 2 | 0.3 | 8928 | 0.30 | 83.5 |
In upper table, Mn
1for the number-average molecular weight of poly(lactic acid), m
1for the quality of dextran, m
2for the quality of poly(lactic acid).
Embodiment 54 ~ 56: the preparation of poly-(γ-phenmethyl-Pidolidone ester) segmented copolymer of dextran-b-
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 30000, the number-average molecular weight adding embodiment 2 preparation is respectively 5793, 9516, poly-(γ-phenmethyl-Pidolidone ester) 0.038g (0.000067mol) of the end group azide of 14334, 0.063g (0.0000067mol), 0.10g (0.0000067mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively when second time freeze thawing, 7.2mg, 7.2mg cuprous bromide.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(γ-phenmethyl-Pidolidone ester) segmented copolymer of dextran-b-.Result ginseng table 20.
Table 20 dextran-b-gathers (γ-phenmethyl-Pidolidone ester) segmented copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 5793 | 0.038 | 85.2 |
| 2 | 0.3 | 9516 | 0.063 | 84.5 |
| 3 | 0.3 | 14334 | 0.100 | 83.3 |
In upper table, Mn
1for the number-average molecular weight of poly-(γ-phenmethyl-Pidolidone ester), m
1for the quality of dextran, m
2for the quality of poly-(γ-phenmethyl-Pidolidone ester).
Embodiment 57 ~ 59: the preparation of poly-(γ-phenmethyl-Pidolidone ester) segmented copolymer of dextran-b-
The number-average molecular weight taking 3 parts of 0.3g embodiments 1 preparations is respectively the end alkynyl radical dextran of 60000, the number-average molecular weight adding embodiment 2 preparation is respectively 5793, 9516, poly-(γ-phenmethyl-Pidolidone ester) 0.019g (0.00000333mol) of the end group azide of 14334, 0.032g (0.00000333mol), 0.048g (0.00000333mol) puts into ampulla, use 30mL dmso solution, add 10 μ L sodium cyanoborohydride parts, then liquefied ammonia freeze thawing is used three times, 7.2mg is added respectively when second time freeze thawing, 7.2mg, 7.2mg cuprous bromide.After freeze thawing terminates, under 40 DEG C of agitation conditions, Click reacts 72h.After reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, namely obtain poly-(γ-phenmethyl-Pidolidone ester) segmented copolymer of dextran-b-.Result ginseng table 21.
Table 21 dextran-b-gathers (γ-phenmethyl-Pidolidone ester) segmented copolymer
| Experiment numbers | m 1(g) | Mn 1(g mol -1) | m 2(g) | Reaction yield (%) |
| 1 | 0.3 | 5793 | 0.019 | 85.8 |
| 2 | 0.3 | 9516 | 0.032 | 83.9 |
| 3 | 0.3 | 14334 | 0.048 | 84.7 |
In upper table, Mn
1for the number-average molecular weight of poly-(γ-phenmethyl-Pidolidone ester), m
1for the quality of dextran, m
2for the quality of poly-(γ-phenmethyl-Pidolidone ester).
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (3)
1. dextran base amphipathic nature block polymer, is characterized in that, in described dextran base amphipathic nature block polymer, hydrophilic segment is dextran, and hydrophobic segment is polyamino acid or aliphatic polyester; Dextran base amphipathic nature block polymer is obtained by reacting by highly active click with end group azide polyamino acid or end group azide polyester respectively by end alkynyl radical dextran; The number-average molecular weight scope of described dextran is 6000-60000, and the number-average molecular weight of polyamino acid segment is 3000-10000, and the number-average molecular weight of polyester segment is 3000-10000.
2. dextran base amphipathic nature block polymer as claimed in claim 1, it is characterized in that, described polyamino acid comprises poly-(γ-phenmethyl-Pidolidone ester), poly-(β-benzyl-L-aspartate ester), poly-(ε-carbobenzoxy-(Cbz)-1B), poly-(O-benzyl-L-serine), poly-(L-Phe), poly-(ALANINE), poly-(L-Leu); Described polyester comprises poly(lactic acid) and poly-(6-caprolactone).
3. the preparation method of dextran base amphipathic nature block polymer as claimed in claim 1, is characterized in that, step and reaction conditions as follows:
(1) preparation of end alkynyl radical dextran
Dextran is dissolved in the acetic acid/sodium acetate buffer of pH=5, propargylamine and sodium cyanoborohydride is added successively under whipped state, wherein, the mol ratio of described dextran, propargylamine, sodium cyanoborohydride is 1: 10: 10,50 DEG C of reaction 96h, after reaction terminates, reaction product to be dialysed 96h with 3500Da dialysis tubing, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, obtain end alkynyl radical dextran;
(2) preparation of end group azide polyamino acid
Carboxylic acid anhydride in amino acid-N-is dissolved in anhydrous N, in N--methylformamide, under stirrer whipped state, add nitrine propylamine, wherein, nitrine propylamine and carboxylic acid anhydride in amino acid-N-mole ratio be 1: 30 ~ 70,25 DEG C of stirring reaction 72h, after reaction terminates, with the ether sedimentation of 10 times of reaction solution volumes, filter, washing is precipitated thing, and 25 DEG C of vacuum-drying 24h, namely obtain the polyamino acid of end group azide;
(3) preparation of end group azide polyester
A. the preparation of differing molecular weight polyester
Aliphatic cyclic monomer is dissolved in toluene, add stannous octoate and Virahol, the mol ratio of cyclic monomer, stannous octoate is 1: 1000, and the mol ratio of cyclic monomer and Virahol is react 24h under 1: 20 ~ 70,120 DEG C of stirrers stir, after reaction terminates, with the ether sedimentation of 10 times of reaction solution volumes, filter, washing is precipitated thing, 25 DEG C of vacuum-drying 24h, obtain the polyester of different number-average molecular weight;
B. the preparation of methyl sulphonyl polyester
Dissolved by polyester anhydrous methylene chloride, stirrer adds triethylamine under stirring, and then slowly drips Methanesulfonyl chloride with dropping funnel, wherein, the mol ratio of described polyester, triethylamine, Methanesulfonyl chloride is 1: 10: 10, under condition of ice bath, Keep agitation reaction 24h, after reaction terminates, with the ether sedimentation of 10 times of reaction solution volumes, filter, washing is precipitated thing, 25 DEG C of vacuum-drying 24h, namely obtain methyl sulphonyl polyester;
C. the preparation of end group azide polyester
The methyl sulphonyl polyester tetrahydrofuran (THF) obtained by b dissolves, then sodiumazide is added, wherein, described methyl sulphonyl polyester, the mol ratio of sodiumazide are 1: 10,40 DEG C of Keep agitation reaction 24h, after reaction terminates, with the ether sedimentation of 10 times of reaction solution volumes, filter, washing is precipitated thing, 25 DEG C of vacuum-drying 24h, namely obtain end group azide polyester;
(4) preparation of dextran base Amphipathilic block polymer
A. the preparation of dextran-b-polyamino acid Amphipathilic block polymer
End alkynyl radical dextran and end group azide polyamino acid are dissolved in dimethyl sulfoxide (DMSO), stirrer adds part pentamethyl-diethylenetriamine under stirring, then liquefied ammonia freeze thawing is used three times, cuprous bromide is added when second time freeze thawing, wherein, dextran, azide polyamino acid, pentamethyl-diethylenetriamine, the mol ratio of cuprous bromide is 1.5: 1: 1.5: 1.5, after freeze thawing terminates, 40 DEG C of click react 72h, after reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, obtain dextran-b-polyamino acid amphipathic nature block polymer,
B. the preparation of dextran-b-polyester amphipathic nature block polymer
End alkynyl radical dextran and end group azide polyester are dissolved in dimethyl sulfoxide (DMSO), stirrer adds part pentamethyl-diethylenetriamine under stirring, then liquefied ammonia freeze thawing is used three times, cuprous bromide is added when second time freeze thawing, wherein, dextran, azide polyester, pentamethyl-diethylenetriamine, the mol ratio of cuprous bromide is 1.5: 1: 1.5: 1.5, after freeze thawing terminates, 40 DEG C are stirred lower click and react 72h, after reaction terminates, with 10000Da dialysis tubing dialysis 96h, continue to change water to remove water miscible small-molecule substance, by product freeze-drying after dialysis, obtain dextran-b-polyester amphipathic nature block polymer.
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