CN104292455A - Thermosensitive copolymer as well as synthesis method and hydrogel system of thermosensitive copolymer - Google Patents
Thermosensitive copolymer as well as synthesis method and hydrogel system of thermosensitive copolymer Download PDFInfo
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Abstract
The invention discloses a thermosensitive copolymer as well as a synthesis method and a hydrogel system of the thermosensitive copolymer. The thermosensitive copolymer refers to a polyethylene glycol-poly(alanine-valine) block copolymer, wherein the poly(alanine-valine) is taken as a hydrophobic chain segment, while polyethylene glycol monomethyl ether is taken as a hydrophilic chain segment; in the hydrophobic chain segment poly(alanine-valine), the content of the alanine is 15.2-23.5wt% and the content of the valine is 76.5-84.8wt%; in the copolymer, the content of the hydrophilic chain segment polyethylene glycol monomethyl ether is 45.0-55.0wt%, and the content of the hydrophobic chain segment poly(alanine-valine) is 45.0-55.0wt%. The polypeptide-polyether hydrogel disclosed by the invention is composed of two amino acid components so that the hydrogen-bond interaction in the hydrogel can be weakened; the strength of the hydrogen-bond of the beta-folded chain can be regulated and controlled by regulating the composition of the alanine and the valine in the polypeptide, and therefore, the polypeptide hydrogel having good reversible thermal transformation behavior can be obtained.
Description
Technical field
The invention belongs to stimuli responsive field of material technology, particularly a kind of Thermo-sensitive multipolymer and synthetic method thereof and aquogel system.
Background technology
Stimulus responsive polymers refers to that polymkeric substance can experience conformational change thus it be made to a class environment sensitive shaped material of response when the ambient conditionss such as temperature, PH, photoelectromagnetism change.And as one of them temperature sensing polymer, along with temperature raises, aqueous solutions of polymers experience sol-gel transition.Like this, medicine or cell can mix when aqueous polymer solution viscosity is lower, and along with temperature change is at target location original position formation gel, thus be applied as drug delivery system or cell growth substrate afterwards.
In temperature-sensitive hydrogel material containing polypeptide fraction, amino acid whose secondary structure and nanoassemble play Main Function in material property.Can by regulation and control as transition temperature, gel modulus, critical gel strength, the parameters such as degradation property, reach the object that design has the Novel warm sensitivity aquogel system of special biomedical applications.
As temperature-sensitive hydrogel, the amphipathic nature polyalcohol containing polypeptide fraction has following advantage or feature: first, and aqueous solutions of polymers is at room temperature liquid, and viscosity is little; Secondly, because polypeptide secondary structure interacts, can there is sol-gel transition in the aqueous solution of multipolymer low concentration, and in drug controlled release field, application is more flexible; Again, after the mixture of medicine and polymers soln is injected in vivo in liquid form, cavity shape different in body can be adapted to, be not easy migration, be conducive to the fixed point release of medicine; Finally, the temperature-sensitive hydrogel containing polypeptide fraction can be become the small molecules such as amino acid by enzymolysis in human body, is easily absorbed, and harmless.
Byeongmoon Jeong, the people such as J Soft Matter, 4,2383-2387 (2008), Biomacromolecules, 14, it is the amphipathic multipolymer of poly-polypeptide-polyethers that hydrophobic chain segment and polyoxyethylene glycol form for hydrophilic segment that 3256-3266 (2013) reports with polylalanine, its certain density aqueous solution is flowable liquid state when low temperature, starts to form hydrogel time between 30 ~ 35 DEG C, has suitable sol-gel transition temperature.
But the polypeptide temperature-sensitive hydrogel hydrogen bond action of single amino acid component is too strong, and the reversibility of gel is often poor, especially when amino acid segment is long, be difficult to after gel formation revert to colloidal sol at low temperatures, be difficult to reach the object recycled.Therefore, development has good reversible Thermo-sensitive polypeptide hydrogel and has important using value.
Summary of the invention
The object of the invention is to the problem of the polypeptide temperature-sensitive hydrogel reversibility difference overcoming existing single amino acid component, a kind of Novel warm sensitivity multipolymer of being made up of L-Ala and α-amino-isovaleric acid two seed amino acid and aquogel system thereof are provided, HYDROGEN BOND INTENSITY in multipolymer between polypeptide chain by forming to regulate and control, thus can obtain the temperature-sensitive hydrogel with good reversibility.
For solving the problems of the technologies described above, the present invention by the following technical solutions:
A kind of Thermo-sensitive multipolymer, be be hydrophobic chain segment with poly-(alanine-valine), polyethylene glycol-(alanine-valine) segmented copolymer that formed for hydrophilic segment with monomethyl ether polyoxyethylene glycol, wherein, in hydrophobic chain segment poly-(alanine-valine), the content of L-Ala is 15.2 ~ 23.5wt%, and the content of α-amino-isovaleric acid is 76.5 ~ 84.8wt%.
Further, in described multipolymer, the content of hydrophilic segment monomethyl ether polyoxyethylene glycol is 45.0 ~ 55.0wt%, and the content of hydrophobic chain segment poly-(alanine-valine) is 45.0 ~ 55.0wt%.
In order to reach better effect, further, in described multipolymer, the content of hydrophilic segment monomethyl ether polyoxyethylene glycol is 51.7 ~ 52.5wt%, and the content of hydrophobic chain segment poly-(alanine-valine) is 47.5 ~ 48.3wt%.
Further, the number-average molecular weight of described hydrophilic segment monomethyl ether polyoxyethylene glycol is 500 ~ 5000.
The number-average molecular weight of described hydrophilic segment monomethyl ether polyoxyethylene glycol is 1000-2000 further.
The present invention also provides a kind of synthetic method of Thermo-sensitive multipolymer, comprises the following steps:
S1: take following material in proportion:
Initiator: Amino End Group poly glycol monomethyl ether;
Solvent: trichloromethane/DMF mixed solvent;
Reaction raw materials: N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride monomer and N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride monomer;
S2: the initiator taken is added in the reaction vessel with magnetic agitation, and reaction vessel decompression is evacuated, pass into high-purity argon gas displacement system, so repeatedly several times every half an hour subsequently;
S3: the trichloromethane/DMF mixed solvent adding weighing in reaction vessel, makes Amino End Group poly glycol monomethyl ether dissolve, in mixed solvent, the volume ratio of trichloromethane and DMF is 2:1;
S4: after Amino End Group poly glycol monomethyl ether dissolves completely, add N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride and the N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride mix monomer of weighing, then reaction vessel is placed in the oil bath of certain temperature, makes mix monomer carry out ring-opening copolymerization reaction;
S5: the freezing ether of reaction product is carried out dissolution process, then filters, and be dried to constant weight in vacuum drying oven.
In the preparation method of above-mentioned Thermo-sensitive multipolymer, in described step S1, the weight fraction of each material is: Amino End Group poly glycol monomethyl ether 100, N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride monomer 23 ~ 35, N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride monomer 100 ~ 114.
In the preparation method of above-mentioned Thermo-sensitive multipolymer, when in described step S4, mix monomer carries out ring-opening copolymerization reaction, oil bath temperature is 30 ~ 60 DEG C.
In the preparation method of above-mentioned Thermo-sensitive multipolymer, in described step S4, mix monomer carries out the time of ring-opening copolymerization reaction is 16 ~ 36h.
Temperature-sensitive hydrogel system of the present invention, be prepared from by above-mentioned Thermo-sensitive multipolymer, in this temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer is 4 ~ 9wt%.
The invention has the beneficial effects as follows:
1, poly-polypeptide-polyethers hydrogel of the present invention has two seed amino acid components, hydrogen bond action in hydrogel can be weakened, there is good biocompatibility, biodegradable and syringeability, the intensity of the hydrogen bond of beta sheet chain can be regulated and controled by the composition regulating and controlling L-Ala and α-amino-isovaleric acid in poly-polypeptide, thus obtain the polypeptide hydrogel with good reversible thermal transition behavior, show through verification experimental verification, this temperature-sensitive hydrogel is after repeatedly heating and cooling, its sol-gel transition temperature variation is little, shows that it has good reversible heat deflection performance;
2, Thermo-sensitive polyethylene glycol-(alanine-valine) block copolymer hydrogel system of the present invention by poly-(alanine-valine) for hydrophobic segment and polyoxyethylene glycol are that the amphipathic multipolymer that hydrophilic segment forms forms, its certain density aqueous solution exists with flowable solation below room temperature or room temperature, viscosity is little, then gel state is become under human body temperature, therefore, the mixture of medicine and polymers soln can be injected in vivo in liquid form, in human body, mixing liquid is transformed into gel state, cavity shape different in body can be adapted to, be not easy migration, be conducive to the fixed point release of medicine, in drug controlled release field, application is more flexible.
Accompanying drawing explanation
The viscosity comparison diagram of temperature-sensitive hydrogel system when 10 DEG C and 37 DEG C of Fig. 1 to be P1 concentration be 8wt%.
Fig. 2 is the sol-gel transition phasor of the temperature-sensitive hydrogel system of different concns of the present invention.
Embodiment
In order to make object of the present invention, technical scheme and advantage clearly understand, below knot and drawings and Examples, be further elaborated to the present invention.Should be appreciated that specific embodiment described herein only in order to explain the present invention, be not intended to limit the present invention.
Embodiment 1
A kind of Thermo-sensitive multipolymer, be be hydrophobic chain segment with poly-(alanine-valine), polyethylene glycol-(alanine-valine) segmented copolymer that formed for hydrophilic segment with monomethyl ether polyoxyethylene glycol, wherein, in hydrophobic chain segment poly-(alanine-valine), the content of L-Ala is 23.5wt%, and the content of α-amino-isovaleric acid is 76.5wt%.
Further, in described multipolymer, the content of hydrophilic segment monomethyl ether polyoxyethylene glycol is 52.5wt%, and the content of hydrophobic chain segment poly-(alanine-valine) is 47.5wt%.
Described in the present embodiment, the number-average molecular weight of hydrophilic segment monomethyl ether polyoxyethylene glycol is 1000.
Further, the number-average molecular weight of described hydrophilic segment monomethyl ether polyoxyethylene glycol can also be 500,2000,3000,4000 or 5000.
The synthetic method of the Thermo-sensitive multipolymer of the present embodiment comprises the following steps:
S1: take material in proportion, comprises following material:
Initiator: Amino End Group poly glycol monomethyl ether: number-average molecular weight is 1000, quality is 1.00g;
Solvent: trichloromethane/DMF mixed solvent: 6ml, wherein, trichloromethane/DMF volume ratio is 2:1;
Reaction raw materials: N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride monomer 0.35g and N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride monomer 1.00g;
S2: the initiator taken is added in the reaction vessel with magnetic agitation, and reaction vessel decompression is evacuated, pass into high-purity argon gas displacement system, so repeatedly several times every half an hour subsequently;
S3: the trichloromethane/DMF mixed solvent adding weighing in reaction vessel, makes Amino End Group poly glycol monomethyl ether dissolve;
S4: after Amino End Group poly glycol monomethyl ether dissolves completely, add N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride and the N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride mix monomer of weighing, then reaction vessel is placed in the oil bath of 40 DEG C, makes mix monomer carry out ring-opening copolymerization reaction;
S5: after question response carries out 24h, carries out dissolution process by the freezing ether of reaction product, then filters, and be dried to constant weight in vacuum drying oven.
By above-mentioned steps, obtain Thermo-sensitive copolymer p 1.
Further, when in step S4, mix monomer carries out ring-opening copolymerization reaction, oil bath temperature can also be: 30 DEG C, 35 DEG C, 40 DEG C, 45 DEG C, 50 DEG C, 55 DEG C, 60 DEG C.
Further, the reaction times that in step S4, mix monomer carries out ring-opening copolymerization reaction can also be: 16h, 20h, 24h, 28h, 32h, 36h.
The temperature-sensitive hydrogel system of the present embodiment is prepared from by Thermo-sensitive multipolymer, and in this temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer is 4wt%.
Further, in described temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer can also be: 6wt%, 7wt%, 8wt%, 9wt%.
Embodiment 2
A kind of Thermo-sensitive multipolymer, be be hydrophobic chain segment with poly-(alanine-valine), polyethylene glycol-(alanine-valine) segmented copolymer that formed for hydrophilic segment with monomethyl ether polyoxyethylene glycol, wherein, in hydrophobic chain segment poly-(alanine-valine), the content of L-Ala is 15.2wt%, and the content of α-amino-isovaleric acid is 84.8wt%.
Further, in described multipolymer, the content of hydrophilic segment monomethyl ether polyoxyethylene glycol is 45.0wt%, and the content of hydrophobic chain segment poly-(alanine-valine) is 55.0wt%.
Further, the number-average molecular weight of described hydrophilic segment monomethyl ether polyoxyethylene glycol is 1500.
The synthetic method of the present embodiment Thermo-sensitive multipolymer is identical with embodiment 1.
The temperature-sensitive hydrogel system of the present embodiment is prepared from by Thermo-sensitive multipolymer, and in this temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer is 5wt%.
Embodiment 3
A kind of Thermo-sensitive multipolymer, be be hydrophobic chain segment with poly-(alanine-valine), polyethylene glycol-(alanine-valine) segmented copolymer that formed for hydrophilic segment with monomethyl ether polyoxyethylene glycol, wherein, in hydrophobic chain segment poly-(alanine-valine), the content of L-Ala is 19wt%, and the content of α-amino-isovaleric acid is 81wt%.
Further, in described multipolymer, the content of hydrophilic segment monomethyl ether polyoxyethylene glycol is 55.0wt%, and the content of hydrophobic chain segment poly-(alanine-valine) is 45.0wt%.
Further, the number-average molecular weight of described hydrophilic segment monomethyl ether polyoxyethylene glycol is 5000.
The synthetic method of the present embodiment Thermo-sensitive multipolymer is identical with embodiment 1.
The temperature-sensitive hydrogel system of the present embodiment is prepared from by Thermo-sensitive multipolymer, and in this temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer is 7.5wt%.
Embodiment 4
A kind of Thermo-sensitive multipolymer, be be hydrophobic chain segment with poly-(alanine-valine), polyethylene glycol-(alanine-valine) segmented copolymer that formed for hydrophilic segment with monomethyl ether polyoxyethylene glycol, wherein, in hydrophobic chain segment poly-(alanine-valine), the content of L-Ala is 21wt%, and the content of α-amino-isovaleric acid is 79wt%.
Further, in described multipolymer, the content of hydrophilic segment monomethyl ether polyoxyethylene glycol is 51.7wt%, and the content of hydrophobic chain segment poly-(alanine-valine) is 48.3wt%.
Further, the number-average molecular weight of described hydrophilic segment monomethyl ether polyoxyethylene glycol is 3000.
The synthetic method of the present embodiment Thermo-sensitive multipolymer is identical with embodiment 1.
The temperature-sensitive hydrogel system of the present embodiment is prepared from by Thermo-sensitive multipolymer, and in this temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer is 9wt%.
Embodiment 5
A kind of Thermo-sensitive multipolymer, be be hydrophobic chain segment with poly-(alanine-valine), polyethylene glycol-(alanine-valine) segmented copolymer that formed for hydrophilic segment with monomethyl ether polyoxyethylene glycol, wherein, in hydrophobic chain segment poly-(alanine-valine), the content of L-Ala is 17wt%, and the content of α-amino-isovaleric acid is 83wt%.
Further, in described multipolymer, the content of hydrophilic segment monomethyl ether polyoxyethylene glycol is 52.1wt%, and the content of hydrophobic chain segment poly-(alanine-valine) is 47.9wt%.
Further, the number-average molecular weight of described hydrophilic segment monomethyl ether polyoxyethylene glycol is 3500.
The synthetic method of the present embodiment Thermo-sensitive multipolymer is identical with embodiment 1.
The temperature-sensitive hydrogel system of the present embodiment is prepared from by Thermo-sensitive multipolymer, and in this temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer is 9wt%.
Embodiment 6
A kind of Thermo-sensitive multipolymer, its component is identical with embodiment 1.
The synthetic method of the Thermo-sensitive multipolymer of the present embodiment comprises the following steps:
S1: take material in proportion, comprises following material:
Initiator: Amino End Group poly glycol monomethyl ether: number-average molecular weight is 1000, quality is 1.00g;
Solvent: trichloromethane/DMF mixed solvent: 6ml, wherein, the volume ratio of trichloromethane/DMF is 2:1;
Reaction raw materials: N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride monomer 0.23g and N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride monomer 1.14g;
S2: the initiator taken is added in the reaction vessel with magnetic agitation, and reaction vessel decompression is evacuated, pass into high-purity argon gas displacement system, so repeatedly several times every half an hour subsequently;
S3: the trichloromethane/DMF mixed solvent adding weighing in reaction vessel, makes Amino End Group poly glycol monomethyl ether dissolve;
S4: after Amino End Group poly glycol monomethyl ether dissolves completely, add N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride and the N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride mix monomer of weighing, then reaction vessel is placed in the oil bath of 30 DEG C, makes mix monomer carry out ring-opening copolymerization reaction;
S5: after question response carries out time 24h, carries out dissolution process by the freezing ether of reaction product, then filters, and be dried to constant weight in vacuum drying oven.
By above-mentioned steps, obtain Thermo-sensitive copolymer p 2.
Further, when in described step S4, mix monomer carries out ring-opening copolymerization reaction, oil bath temperature can also be: 30 DEG C, 35 DEG C, 40 DEG C, 45 DEG C, 50 DEG C, 55 DEG C, 60 DEG C.
Further, the reaction times that in described step S4, mix monomer carries out ring-opening copolymerization reaction can also be: 1h, 8h, 16h, 24h, 36h, 48h.
The temperature-sensitive hydrogel system of the present embodiment is prepared from by Thermo-sensitive multipolymer, and in this temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer is 4wt%.
Further, in described temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer can also be: 6wt%, 7wt%, 8wt%, 9wt%.
Embodiment 7
A kind of Thermo-sensitive multipolymer, its component is identical with embodiment 2.
The synthetic method step of the Thermo-sensitive multipolymer of the present embodiment is identical with embodiment 6, difference is: reaction raw materials: N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride monomer is 0.29g, N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride monomer 1.07g.
The temperature-sensitive hydrogel system preparation method of the present embodiment is identical with embodiment 6.
Experimental verification: below by the performance of experimental verification temperature-sensitive hydrogel system of the present invention.
Observe the viscosity B coefficent of temperature-sensitive hydrogel system between 10 ~ 80 DEG C that Thermo-sensitive copolymer p 1 concentration is 8wt%, as shown in Figure 1,10 DEG C time, temperature-sensitive hydrogel system is flowable liquids, and is converted into gel 37 DEG C time.
The Thermo-sensitive copolymer p 1 that Example 1 is obtained and the Thermo-sensitive copolymer p 2 that embodiment 6 obtains, P1, P2 are configured to respectively the temperature-sensitive hydrogel system that concentration is 4wt%, 6wt%, 8wt%, 9wt%, and measure its sol-gel thermal transition behavior respectively, obtain its sol-gel transition phasor, as shown in Figure 2.As seen from the figure, when P1, P2 concentration is 8wt%, two kinds of temperature-sensitive hydrogel systems are flowable liquid below room temperature or room temperature, then exist with stable gel state when human body temperature.
Choose P1, P2 respectively and be configured to the temperature-sensitive hydrogel system that concentration is 8wt%, be repeatedly elevated temperature three times, the sol-gel transition temperature obtained is as shown in the table respectively.
| ? | For the first time | For the second time | For the third time |
| P18wt% temperature-sensitive hydrogel system | 32℃ | 33℃ | 31℃ |
| P28wt% temperature-sensitive hydrogel system | 35℃ | 34℃ | 33℃ |
Above table illustrates that temperature-sensitive hydrogel in the present invention is after repeatedly heating and cooling, and its sol-gel transition temperature variation is little, shows that gained hydrogel has good reversible heat deflection performance.
Those of ordinary skill in the art will appreciate that, embodiment described here is to help reader understanding's principle of the present invention, should be understood to that protection scope of the present invention is not limited to so special statement and embodiment.Those of ordinary skill in the art can make various other various concrete distortion and combination of not departing from essence of the present invention according to these technology enlightenment disclosed by the invention, and these distortion and combination are still in protection scope of the present invention.
Claims (10)
1. a Thermo-sensitive multipolymer, it is characterized in that, be hydrophobic chain segment with poly-(alanine-valine), polyethylene glycol-(alanine-valine) segmented copolymer that formed for hydrophilic segment with monomethyl ether polyoxyethylene glycol, wherein, in hydrophobic chain segment poly-(alanine-valine), the content of L-Ala is 15.2 ~ 23.5wt%, and the content of α-amino-isovaleric acid is 76.5 ~ 84.8wt%.
2. a kind of Thermo-sensitive multipolymer according to claim 1, it is characterized in that, in described multipolymer, the content of hydrophilic segment monomethyl ether polyoxyethylene glycol is 45.0 ~ 55.0wt%, and the content of hydrophobic chain segment poly-(alanine-valine) is 45.0 ~ 55.0wt%.
3. a kind of Thermo-sensitive multipolymer according to claim 2, it is characterized in that, in described multipolymer, the content of hydrophilic segment monomethyl ether polyoxyethylene glycol is 51.7 ~ 52.5wt%, and the content of hydrophobic chain segment poly-(alanine-valine) is 47.5 ~ 48.3wt%.
4. Thermo-sensitive multipolymer according to claim 1, is characterized in that, the number-average molecular weight of described hydrophilic segment monomethyl ether polyoxyethylene glycol is 500 ~ 5000.
5. Thermo-sensitive multipolymer according to claim 4, is characterized in that, the number-average molecular weight of described hydrophilic segment monomethyl ether polyoxyethylene glycol is 1000 ~ 2000.
6. a synthetic method for the Thermo-sensitive multipolymer described in any one of Claims 1 to 5 claim, is characterized in that, comprise the following steps:
S1: take following material in proportion:
Initiator: Amino End Group poly glycol monomethyl ether;
Solvent: trichloromethane/DMF mixed solvent;
Reaction raw materials: N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride monomer and N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride monomer;
S2: the initiator taken is added in the reaction vessel with magnetic agitation, and reaction vessel decompression is evacuated, pass into high-purity argon gas displacement system every half an hour subsequently, 3 ~ 5 times so repeatedly;
S3: the trichloromethane/DMF mixed solvent adding weighing in reaction vessel, makes Amino End Group poly glycol monomethyl ether dissolve;
S4: after Amino End Group poly glycol monomethyl ether dissolves completely, add N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride and the N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride mix monomer of weighing, then reaction vessel is placed in the oil bath of certain temperature, makes mix monomer carry out ring-opening copolymerization reaction;
S5: the freezing ether of reaction product is carried out dissolution process, then filters, and be dried to constant weight in vacuum drying oven.
7. the synthetic method of Thermo-sensitive multipolymer according to claim 6, is characterized in that: in described S1, the weight fraction of each material is: Amino End Group poly glycol monomethyl ether 100, N-carboxyl-alpha-amino group-ALANINE ring inner-acid anhydride monomer 23 ~ 35, N-carboxyl-alpha-amino group-Valine ring inner-acid anhydride monomer 100 ~ 114.
8. the synthetic method of Thermo-sensitive multipolymer according to claim 6, is characterized in that: when in described S4, mix monomer carries out ring-opening copolymerization reaction, oil bath temperature is 30 ~ 60 DEG C.
9. the synthetic method of Thermo-sensitive multipolymer according to claim 6, is characterized in that: in described S4, mix monomer carries out the reaction times of ring-opening copolymerization reaction is 16 ~ 36h.
10. a temperature-sensitive hydrogel system, is characterized in that: the Thermo-sensitive multipolymer any one of Claims 1 to 5 described in claim is prepared from, and in this temperature-sensitive hydrogel system, the concentration of Thermo-sensitive multipolymer is 4 ~ 9wt%.
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| CN106397793A (en) * | 2016-09-18 | 2017-02-15 | 中国医学科学院生物医学工程研究所 | L-alanine and L-glutamic acid-5-benzyl ester polypeptide copolymer hydrogel and application thereof |
| CN107652453A (en) * | 2017-09-26 | 2018-02-02 | 天津工业大学 | It is grafted temperature sensitive injection aquagel of RGD small peptides and its preparation method and application |
| CN110183648A (en) * | 2019-05-28 | 2019-08-30 | 电子科技大学 | A kind of Thermo-sensitive copolymer and its synthetic method and the reversible Self-Assembled comprising the copolymer |
| CN110240700A (en) * | 2019-06-12 | 2019-09-17 | 电子科技大学 | A kind of Thermo-sensitive copolymer and its synthetic method and reversible Self-Assembled system |
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