CN103992451B - A kind of diblock copolymer possessing sugar, temperature, the triple sensitivity of pH and preparation method thereof - Google Patents
A kind of diblock copolymer possessing sugar, temperature, the triple sensitivity of pH and preparation method thereof Download PDFInfo
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- CN103992451B CN103992451B CN201410198944.4A CN201410198944A CN103992451B CN 103992451 B CN103992451 B CN 103992451B CN 201410198944 A CN201410198944 A CN 201410198944A CN 103992451 B CN103992451 B CN 103992451B
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Abstract
The invention belongs to macromolecular material and biomedical engineering field, be specifically related to diblock copolymer of a kind of sugar, temperature, the triple sensitivity of pH and preparation method thereof. The method key step is as follows: ATRP initiator, ABIB cause borate ester and DMAEMA to generate diblock copolymer, are prepared for Ad-PpBDEMA-DMAEMA diblock copolymer. Product structure of the present invention is linear, and synthesis step is simple, and molecular size is controlled, possesses sugar, temperature, the triple response of pH, can be used for the multiple intellectual material fields such as drug delivery, genophore, memory cell switch.
Description
Technical field
The present invention relates to a kind of diblock copolymer possessing sugar, temperature, the triple sensitivity of pH and preparation method thereof.
Background technology
Compared to the more single stimuli responsive system of research, exploitation has dual and multiple stimulation response system and scientific research and practical application has the meaning of even more important effect. First, have multiple response polymeric system can Study system release dynamics, these systems independently can must regulate each respondent behavior for different stimulations, as can be strengthened or weaken drug release simultaneously. Secondly, organism has the stimuli responsive behavior of complexity, and this kind of research is to diabetes, and the research of the diseases such as cancer is of great advantage. The polymer drug conveying material with multiple response can form the micelle of different shape under different stimulated or cause the decomposition of micelle, namely utilizes the self assembly of micelle to realize the controllable release of medicine.
Diabetes are a kind of metabolic diseases being feature with hyperglycemia. Hyperglycemia then makes due to defect of insulin secretion and biological agent is impaired causes, various tissue can be caused, particularly eye, kidney, heart, blood vessel, neural chronic lesion, dysfunction, reducing blood glucose is the main method treating diabetes at present, traditional injection and drug administration need doctor and patient strictly to control the consumption of medicine, and long-time use also can make patient produce drug resistance and cause Diabetic liver injury of kidney. So, find a kind of sugar response medicine carrier particularly important for the treatment of diabetes. This sugar Response System can realize the controllable release of medicine, and phenylboric acid and derivant thereof have sugar response. There is two states in aqueous in phenyl boronic acid derivative, electronegative tetrahedral structure can form stable borate ester structure with glucose complexation, it is dissolved in water, and the phenylboric acid of neutral trihedral structure and glucose form the circulus of instability. By changing pH, and the concentration of glucose in solutions realizes the purpose of phenylboric acid system sustained-release administration. This method can be convenient and safe intelligently at the site of disease selectivity release medicine that blood sugar concentration is high, reaches the purpose of efficiently treatment.
Summary of the invention
The purpose of the present invention couple is in that to provide a kind of diblock copolymer possessing sugar, temperature, the triple sensitivity of pH and preparation method thereof.
A kind of diblock copolymer possessing sugar, temperature, the triple sensitivity of pH provided by the invention, its structure is shown below:
Wherein m is 48-80, n is 54-90.
The preparation method of the diblock copolymer with sugar, temperature, the triple sensitivity of pH provided by the present invention, comprises the following steps:
(1) under nitrogen protection, ABIB initiator, cuprous bromide, ATRP part PMDETA and PpBDEMA monomer are dissolved in methyl phenyl ethers anisole with mol ratio 1:1.2:1.2:60-100, stir 18-60 hour at 85-95 DEG C, obtain Ad-PpBDEMA polymer I:
(2) under nitrogen protection; macromole evocating agent Ad-PpBDEMA, cuprous bromide and DMAEMA monomer are dissolved in dry DMF with mol ratio 1:1.2:60-100; react 50-70 minute at 38-42 DEG C; concentration removes after mantoquita precipitation in normal hexane again; dialyse 42-50 hour and remove DMF lyophilizing removing water, obtain linear polymerAd-PpBDEMA-DMAEMA:
Wherein m is 48-80, n is 54-90.
The method have the advantages that
1) sugar response polymer drug delivering material provided by the present invention has sugar response functional group, and its special hydrophobic segment structure is provided that in aqueous phase self assembly power, forms nano-particle.
2) sugar response polymer drug delivering material itself provided by the present invention and sugar respond after little molecule phenylboric acid sugar ester and become the polymer of double-hydrophilic and be respectively provided with good biocompatibility. After polymer provided by the invention and sugar response, phenylboric acid comes off and sugar forms little molecular complex from polymer, and thus phenylboric acid just can excrete with internal metabolism, has good biocompatibility.
3) present invention has sugar, temperature, the triple response of pH, better can must be used for drug release, chemical sensor and polymer and the field such as separate.
Detailed description of the invention
Elaborate by the examples below: the present embodiment is carried out under premised on technical solution of the present invention, give detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to the embodiment of subordinate.
Embodiment 1:
1) 0.03g (0.1mmol) ABIB initiator, 0.0208g (0.12mmol) ATRP part PMDETA and 2.73g (10mmol) PpBDEMA monomer are dissolved in 2.5ml methyl phenyl ethers anisole, freezing pumping cycle three times, to the logical nitrogen of system during last freezing, add 1.12mg (0.1mmol) cuprous bromide, the logical nitrogen of deoxygenation is at 90 DEG C, stir 40 hours, concentration precipitates after removing mantoquita in the mixed liquor of normal hexane and ether, obtains Ad-PpBDEMA polymer I:
2) under nitrogen protection; macromole evocating agent 2.738g (0.1mmol) Ad-100PpBDEMA, 1.194g (12mmol) cuprous bromide and 1.5721g (10mmol) DMAEMA monomer are dissolved in dry DMF; react four hours at 40 DEG C; concentration removes after mantoquita precipitation in normal hexane again; dialyse 48 hours and remove DMF lyophilizing removing water, obtain linear polymer II (Ad-PpBDEMA-DMAEMA).
Embodiment 2:
1) 0.03g (0.1mmol) ABIB initiator, 0.0208g (0.12mmol) ATRP part PMDETA and 2.184g (8mmol) PpBDEMA monomer are dissolved in 2.5ml methyl phenyl ethers anisole, freezing pumping cycle three times, to the logical nitrogen of system during last freezing, add 1.12mg (0.1mmol) cuprous bromide, the logical nitrogen of deoxygenation is at 90 DEG C, stir 40 hours, concentration precipitates after removing mantoquita in the mixed liquor of normal hexane and ether, obtains Ad-PpBDEMA polymer I;
2) with embodiment 1 step 2).
Embodiment 3
1) 0.03g (0.1mmol) ABIB initiator, 0.0208g (0.12mmol) ATRP part PMDETA and 1.638g (6mmol) PpBDEMA monomer are dissolved in 2.5ml methyl phenyl ethers anisole, freezing pumping cycle three times, to the logical nitrogen of system during last freezing, add 1.12mg (0.1mmol) cuprous bromide, the logical nitrogen of deoxygenation is at 90 DEG C, stir 40 hours, concentration precipitates after removing mantoquita in the mixed liquor of normal hexane and ether, obtains Ad-PpBDEMA polymer I;
2) with embodiment 1 step 2).
Claims (2)
1. the diblock copolymer possessing sugar, temperature, the triple response of pH, it is characterised in that structural formula is as follows:
Wherein m is 48-80, n is 54-90.
2. the preparation method of the diblock copolymer possessing sugar, temperature, the triple response of pH as claimed in claim 1, it is characterised in that specifically comprise the following steps that
(1) under nitrogen protection; by ABIB initiator, cuprous bromide, ATRP part PMDETA and PpBDEMA monomer with mol ratio 1:1.2:1.2:(60-100) it is dissolved in methyl phenyl ethers anisole; stir 18-60 hour at 85-95 DEG C, obtain Ad-PpBDEMA polymer I:
Polymer I
(2) under nitrogen protection; macromole evocating agent Ad-PpBDEMA, cuprous bromide and DMAEMA monomer are dissolved in dry DMF with mol ratio 1:1.2:60-100; react 50-70 minute at 38-42 DEG C; concentration precipitates after removing mantoquita in normal hexane; dialyse 42-50 hour; removing DMF, lyophilizing removes water, obtains linear polymerAd-PpBDEMA-DMAEMA:
Polymer II
Wherein m is 48-80, n is 54-90.
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| CN201410198944.4A CN103992451B (en) | 2014-05-13 | 2014-05-13 | A kind of diblock copolymer possessing sugar, temperature, the triple sensitivity of pH and preparation method thereof |
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| CN201410198944.4A CN103992451B (en) | 2014-05-13 | 2014-05-13 | A kind of diblock copolymer possessing sugar, temperature, the triple sensitivity of pH and preparation method thereof |
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| CN103992451B true CN103992451B (en) | 2016-06-15 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1334830A (en) * | 1998-12-29 | 2002-02-06 | B·F·谷德里奇公司 | Hydrophilic ampholytic polymer |
| CN101348570A (en) * | 2008-09-03 | 2009-01-21 | 东华理工大学 | Preparation of star copolymer self-assembled nano micelle |
| CN101503497A (en) * | 2009-03-02 | 2009-08-12 | 江南大学 | Preparation of star type block acid sensitive nano micelle |
| CN102212178A (en) * | 2011-04-11 | 2011-10-12 | 同济大学 | Pentablock copolymer with temperature and pH dual sensitivity, and preparation method and application thereof |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1334830A (en) * | 1998-12-29 | 2002-02-06 | B·F·谷德里奇公司 | Hydrophilic ampholytic polymer |
| CN101348570A (en) * | 2008-09-03 | 2009-01-21 | 东华理工大学 | Preparation of star copolymer self-assembled nano micelle |
| CN101503497A (en) * | 2009-03-02 | 2009-08-12 | 江南大学 | Preparation of star type block acid sensitive nano micelle |
| CN102212178A (en) * | 2011-04-11 | 2011-10-12 | 同济大学 | Pentablock copolymer with temperature and pH dual sensitivity, and preparation method and application thereof |
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Granted publication date: 20160615 Termination date: 20190513 |