CN106032405B - Temperature- and pH-sensitivity block copolymer and its synthetic method and aquogel system - Google Patents
Temperature- and pH-sensitivity block copolymer and its synthetic method and aquogel system Download PDFInfo
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- CN106032405B CN106032405B CN201610345388.8A CN201610345388A CN106032405B CN 106032405 B CN106032405 B CN 106032405B CN 201610345388 A CN201610345388 A CN 201610345388A CN 106032405 B CN106032405 B CN 106032405B
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
- C08G69/08—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino-carboxylic acids
- C08G69/14—Lactams
- C08G69/16—Preparatory processes
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/48—Polymers modified by chemical after-treatment
Abstract
The invention discloses a kind of temperature- and pH-sensitivity block copolymer and its synthetic method and aquogel systems, it is the poly- valine triblock copolymer of polyethylene glycol polylysine constituted as hydrophobic chain segment, using poly glycol monomethyl ether as hydrophilic segment using the poly- valine of polylysine, wherein, the content of lysine is 22~34wt% in the poly- valine of hydrophobic chain segment polylysine, and the content of valine is 66~78wt%.The content of hydrophilic segment poly glycol monomethyl ether is 47~57wt% in the block copolymer, and the content of the poly- valine of hydrophobic chain segment polylysine is 43~53wt%.The invention discloses a kind of temperature- and pH-sensitivity aquogel systems to have good biocompatibility and degradability, has larger application value in technical field of biological material.
Description
Technical field
The invention belongs to technical field of biological materials, and in particular to a kind of temperature- and pH-sensitivity block copolymer and its
Synthetic method and aquogel system.
Background technology
Hydrogel can be applied successfully in technical field of biological material, be mainly attributed to the three-dimensional crosslinked network of itself.Cross-linked network
The structure ingredient of network and the inherent structure of itself and mechanical performance play the physical property of gel, biological characteristics in crucial work
With.Polyaminoacid hydrogel not only has the advantage of the aqueous moisturizing of conventional gel as a kind of supramolecular hydrogel, simultaneously as
The diversity of amino acid classes, building-up process, self assembling process can be manipulated accurately, and can be used for designing and preparing into good fixed
The material of justice.Relative to the aquogel system built as source using natural material, polyaminoacid material is not influencing material biology
In the case of chemical characteristic, there is preferably operability in terms of the mechanical property for adjusting material.
The formation of polyaminoacid hydrogel is in addition to system related with the close and distant water balance of material itself, also with polyaminoacid segment
Secondary structure have a direct relation, the difference of secondary structure can significantly affect the self assembly patterns of polymer.Therefore, can pass through
Hydrophobe segment balance, chain segment molecular weight and length, block topological structure, the amino acid classes etc. for adjusting copolymer, to design
Material with specific secondary structure and self assembly form prepares the polyaminoacid hydrogel with specific functionality, reaches control
The purpose of gel transition temperature processed, gel modulus, degradation cycle.
The polyaminoacid hydrogel of Thermo-sensitive with sol-gel transition is flowable sol solution at room temperature,
Its viscosity is relatively low to enter human body by injection, lesion of going directly.This administering mode is simple, safety, patient is along strong by property.When
Be loaded with drug polyaminoacid hydrogel enter human body isoreactivity tissue after, under the stimulation of human body temperature, colloidal sol can be sent out
Life is mutually deformed into gel, is trapped in human body injection position, it is not easy to migration.Further, it is also possible to according to other environment in human body because
The difference of element is accurately responded, and the Targeting delivery of drug and repairing and treating or even gel rubber system to specific organization are conducive to
Itself plays therapeutic effect as anti-inflammation drugs.The natural amino acid small molecule that hydrogel releases in degradation process is by human body
It absorbs or decomposes, metabolite has no toxic side effect to organism, and non-immunogenicity shows good biocompatibility and biology
Safety.
Access modification segment or group are adjusted altogether usually in order to increase the hydrophily of system on polyaminoacid segment
The close and distant water balance of polymers builds gel network.Modification segment is generally high molecular polymer or chain alkyl, and modification group is main
For short chain units or stimulating responsive functional group, single or multiple stimulation response water gel can be built.Chitosan graft
Polyethylene glycol alanine is a kind of typical pH and temperature Dual Sensitive polymer (Journal of materials
chemistry 2011,21(14):5484-5491), the sol-gel transition temperature of the polymer rises with the raising of pH
Height can form firm gel in affected part, keep less viscous collosol state under neutral ph, can be used for noting under the action of acid pH
Penetrate the diseases such as treatment gastric ulcer.
Based on the Thermo-sensitive polyaminoacid hydrogel of multiple responsive type drug load, organizational project application etc. weight
Application value is wanted, the present invention is quasi- using polyethylene glycol, poly- valine, polylysine as component, by regulating and controlling composition and block structure,
Build the polyaminoacid hydrogel answered with pH, temperature double-bang firecracker.
Invention content
The purpose of the present invention is being based on polyethers, polylysine, poly- valine, a kind of temperature- and pH-sensitivity block is provided
Copolymer and its synthetic method and aquogel system.
To achieve the above object, the present invention uses following technical scheme：
A kind of temperature- and pH-sensitivity block copolymer is using the poly- valine of polylysine-as hydrophobic chain segment, with poly-
Glycol monoethyl ether is polyethylene glycol lysine-poly- valine triblock copolymer that hydrophilic segment is constituted, wherein is dredged
The content of lysine is 22~34wt% in aqueous segment polylysine-poly- valine, and the content of valine is 66~78wt%.
Further, the content of hydrophilic segment poly glycol monomethyl ether is 47~57wt% in the block copolymer, is dredged
The content of aqueous segment polylysine-poly- valine is 43~53wt%.
In order to reach better effect, further, hydrophilic segment poly glycol monomethyl ether in the block copolymer
Content is 49~54wt%, and the content of hydrophobic chain segment polylysine-poly- valine is 46~51wt%.
Further, the number-average molecular weight of the hydrophilic segment poly glycol monomethyl ether is 500~5000, preferably
1000-2000。
Also a kind of synthetic method of temperature- and pH-sensitivity block copolymer of the present invention, includes the following steps：
S1：Following material is weighed in proportion：
Initiator：Amino End Group poly glycol monomethyl ether；
Solvent：Chloroform/n,N-Dimethylformamide mixed solvent；
Reaction raw materials：N- carboxyls-alpha-amido-L benzyloxycarbonyl group lysine ring inner-acid anhydride monomers and N- carboxyls-alpha-amido-L-
Valine ring inner-acid anhydride monomer；
S2：The initiator weighed is added in the reaction vessel with magnetic agitation, and reaction vessel decompression is pumped into very
Sky, it is then each to be passed through within X hours high-purity argon gas displacement system, repeatedly several times；
S3：Chloroform/n,N-Dimethylformamide mixed solvent of weighing is added into reaction vessel, keeps Amino End Group poly-
Glycol monoethyl ether dissolves, in the mixed solvent, and the volume ratio of chloroform and n,N-Dimethylformamide is 2：1；
S4：After Amino End Group poly glycol monomethyl ether is completely dissolved, N- carboxyls-alpha-amido-L- benzyloxy carbonyls of weighing are added
Reaction vessel, is then placed in the oil bath of certain temperature by base lysine ring inner-acid anhydride monomer, so that mix monomer is carried out open loop poly-
Close reaction；
S5：N- carboxyl-alpha-amido-Valine ring the inner-acid anhydrides of weighing are added into reaction vessel, continue open loop
Polymerisation；
S6：The reaction product of S5 is subjected to dissolution/precipitation processing, is then filtered, and is dried to constant weight in vacuum drying oven,
Obtain the poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer.
S7：Following material is weighed in proportion：
Reactant：The poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer obtained by S6 and bromine
Change hydroacetic acid solution；
Solvent：Trifluoroacetic acid；
S8：The poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer is added anti-with stirrer
It answers in container, trifluoroacetic acid is added, open stirring, make the poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymerization
Object is completely dissolved.
S9：Ice bath reaction condition is set, hydrogen bromide acetic acid solution is added into reaction vessel, carries out deprotection reaction；
S10：Reaction product obtained by S9 is subjected to dissolution process with frost ether, is then filtered, and done in vacuum drying oven
It is dry to constant weight, obtain the poly- valine triblock copolymer of poly glycol monomethyl ether-polylysine-.
In the synthetic method of above-mentioned temperature- and pH-sensitivity block copolymer, the parts by weight of each material in the S1
For：1 part of Amino End Group poly glycol monomethyl ether, N- carboxyls -0.612 part of alpha-amido-L benzyloxycarbonyl group lysine ring inner-acid anhydrides monomer,
1.001 parts of N- carboxyl-alpha-amido-Valine ring inner-acid anhydrides monomer.
In the synthetic method of above-mentioned temperature- and pH-sensitivity block copolymer, the parts by weight of each material in the S7
For：The poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer 1 part, 2 parts of hydrogen bromide acetic acid solution.
In the synthetic method of above-mentioned temperature- and pH-sensitivity block copolymer, mix monomer is opened in described S4, S5
When cyclopolymerization is reacted, oil bath temperature is 20~40 DEG C, preferably 25~35 DEG C, further preferably 25~30 DEG C..
In the synthetic method of above-mentioned temperature- and pH-sensitivity block copolymer, mix monomer is opened in described S4, S5
When cyclopolymerization is reacted, the reaction time is 12~36h, preferably 16~36h, further preferably 20~for 24 hours.
When carrying out deprotection reaction in the synthetic method of above-mentioned temperature- and pH-sensitivity block copolymer, in the S9,
Reaction time is 4~7h, preferably 6h.
The temperature- and pH-sensitivity aquogel system of the present invention, by above-mentioned temperature- and pH-sensitivity block copolymer system
It is standby to form, a concentration of the 1 of temperature and pH Dual Sensitive block copolymers in the temperature- and pH-sensitivity aquogel system~
10wt%, preferably 3~6wt%.
In the present invention, the synthesis of polyethylene glycol lysine-poly- valine triblock copolymer is according to " amido " machine
Reason, using Amino End Group poly glycol monomethyl ether as initiator, causes N- carboxyls-alpha-amido-L under conditions of not needing catalyst
Ring-opening polymerisation occurs for benzyloxycarbonyl group lysine ring inner-acid anhydride, N- carboxyl-alpha-amido-Valine ring inner-acid anhydride monomers, is made poly-
The poly- benzyloxycarbonyl group lysine of glycol monoethyl ether-- poly- valine copolymer, it is further poly- to obtained poly glycol monomethyl ether-
Benzyloxycarbonyl group lysine-poly- valine copolymer systems carry out deprotection reaction, slough lysine segment and glutamic acid chain respectively
The last acquisition poly- valine copolymer of poly glycol monomethyl ether-polylysine-of benzyloxycarbonyl protecting group group in section.
The beneficial effects of the invention are as follows：
1, the hydrogel in the present invention has the characteristic of pH, temperature sensitive, within the scope of wider pH (such as pH 3~
Between 8) all show the temperature sensitive transformation performance of good sol-gel, and transition temperature is near human body temperature, so that this is solidifying
It can be applied under glue pH environment different in human body.
2, the sol-gel transition temperature of the hydrogel in the present invention is increased with the reduction of pH, is had certain pH and is rung
The function of answering.
3, temperature- and pH-sensitivity aquogel system provided by the invention has good biocompatibility in general
And degradability, there is larger application value in technical field of biological material.
Description of the drawings
Fig. 1 is the sol-gel transition phasor of 1 various concentration temperature- and pH-sensitivity aquogel system of embodiment；
Fig. 2 is that 1 a concentration of 5wt% temperature- and pH-sensitivities water gel of embodiment ties up to gel turn under condition of different pH
Become phasor.
Specific implementation mode
In order to make the purpose , technical scheme and advantage of the present invention be clearer, below knot and drawings and examples, it is right
The present invention is further elaborated.It should be appreciated that described herein, specific examples are only used to explain the present invention, not
For limiting the present invention.
Embodiment 1
A kind of temperature- and pH-sensitivity block copolymer is using the poly- valine of polylysine-as hydrophobic chain segment, with poly-
Glycol monoethyl ether (mPEG) is polyethylene glycol lysine-poly- valine triblock copolymer that hydrophilic segment is constituted,
In, the content of lysine is 27wt% in hydrophobic chain segment polylysine-poly- valine, and the content of valine is 73wt%.
Further, the content of hydrophilic segment poly glycol monomethyl ether is 51wt%, hydrophobicity in aforesaid block copolymer
The content of segment polylysine-poly- valine is 49wt%.
The number-average molecular weight of the aforementioned hydrophilic segment poly glycol monomethyl ether of the present embodiment is 1000.
Further, the number-average molecular weight of aforementioned hydrophilic segment poly glycol monomethyl ether can also be 500,2000 or
5000。
The synthetic method of the temperature- and pH-sensitivity block copolymer of the present embodiment includes the following steps：
S1：Following material is weighed in proportion：
Initiator：Amino End Group poly glycol monomethyl ether, number-average molecular weight 1000, quality 1.00g；
Solvent：Chloroform/n,N-Dimethylformamide mixed solvent 6ml, wherein chloroform and N, N- dimethyl methyls
The volume ratio of amide is 2：1；
Reaction raw materials：N- carboxyls-alpha-amido-L benzyloxycarbonyl group lysine ring inner-acid anhydride monomer 0.612g, N- carboxyls-α-ammonia
Base-Valine ring inner-acid anhydride monomer 1.001g；
S2：The initiator weighed is added in the reaction vessel with magnetic agitation, and reaction vessel decompression is pumped into very
Sky is then passed through high-purity argon gas every half an hour and replaces system, repeatedly several times；
S3：Chloroform/n,N-Dimethylformamide mixed solvent of weighing is added into reaction vessel, keeps Amino End Group poly-
Glycol monoethyl ether dissolves；
S4：After Amino End Group poly glycol monomethyl ether is completely dissolved, N- carboxyls-alpha-amido-L- benzyloxy carbonyls of weighing are added
Reaction vessel, is then placed in 25 DEG C of oil bath by base lysine ring inner-acid anhydride monomer, so that mix monomer is carried out ring-opening polymerisation anti-
It answers；
S5：After reaction carries out for 24 hours, it is added into reaction vessel in the N- carboxyl-alpha-amido-Valine rings of weighing sour
Acid anhydride continues ring-opening polymerization；
S6：After reaction carries out for 24 hours, the reaction product of S5 is subjected to dissolution/precipitation processing, is then filtered, and in vacuum
It is dried to constant weight in baking oven, obtains the poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer.
S7：Following material is weighed in proportion：
Reactant：The poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer 1 g obtained by S6, and
The hydrogen bromide acetic acid solution 2ml of concentration 33%；
Solvent：Trifluoroacetic acid 10ml；
S8：The poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer is added anti-with stirrer
It answers in container, trifluoroacetic acid is added, open stirring, make the poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymerization
Object is completely dissolved.
S9：Ice bath reaction condition is set, hydrogen bromide acetic acid solution is added into reaction vessel, carries out deprotection reaction；
S10：After reaction carries out 6h, reaction product obtained by S9 is subjected to dissolution process with frost ether, is then filtered, and
It is dried to constant weight in vacuum drying oven, obtains the poly- valine triblock copolymer of poly glycol monomethyl ether-polylysine-.
Further, when mix monomer carries out ring-opening polymerization in described S4, S5, oil bath temperature can also be：20℃、
30℃、35℃、40℃。
Further, in described S4, S5 mix monomer carry out ring-opening polymerization when, the reaction time can also be 12h,
16h、36h、48h。
Further, when carrying out deprotection reaction in the S9, the reaction time can also be 4h, 5h, 7h.
The temperature- and pH-sensitivity aquogel system of the present embodiment, is prepared by temperature- and pH-sensitivity block copolymer
It forms, a concentration of 5wt% of temperature and pH Dual Sensitive block copolymers in the temperature- and pH-sensitivity aquogel system.
Further, temperature and pH Dual Sensitive block copolymers in the temperature- and pH-sensitivity aquogel system
It is a concentration of：1wt%, 3wt%, 6wt%, 10wt%.
Embodiment 2
A kind of temperature- and pH-sensitivity block copolymer is using the poly- valine of polylysine-as hydrophobic chain segment, with poly-
Glycol monoethyl ether (mPEG) is polyethylene glycol lysine-poly- valine triblock copolymer that hydrophilic segment is constituted,
In, the content of lysine is 34wt% in hydrophobic chain segment polylysine-poly- valine, and the content of valine is 66wt%.
Further, the content of hydrophilic segment poly glycol monomethyl ether is 57wt%, hydrophobicity in aforesaid block copolymer
The content of segment polylysine-poly- valine is 43wt%.
Further, the number-average molecular weight of aforementioned hydrophilic segment poly glycol monomethyl ether is 3500.
The synthetic method of the temperature- and pH-sensitivity block copolymer of the present embodiment is same as Example 1.
The temperature- and pH-sensitivity aquogel system of the present embodiment, is prepared by temperature- and pH-sensitivity block copolymer
It forms, a concentration of 4wt% of temperature and pH Dual Sensitive block copolymers in the temperature- and pH-sensitivity aquogel system.
Embodiment 3
A kind of temperature- and pH-sensitivity block copolymer is using the poly- valine of polylysine-as hydrophobic chain segment, with poly-
Glycol monoethyl ether (mPEG) is polyethylene glycol lysine-poly- valine triblock copolymer that hydrophilic segment is constituted,
In, the content of lysine is 22wt% in hydrophobic chain segment polylysine-poly- valine, and the content of valine is 78wt%.
Further, the content of hydrophilic segment poly glycol monomethyl ether is 47wt%, hydrophobicity in aforesaid block copolymer
The content of segment polylysine-poly- valine is 53wt%.
Further, the number-average molecular weight of aforementioned hydrophilic segment poly glycol monomethyl ether is 3000.
The synthetic method of the temperature- and pH-sensitivity block copolymer of the present embodiment is same as Example 1.
The temperature- and pH-sensitivity aquogel system of the present embodiment, is prepared by temperature- and pH-sensitivity block copolymer
It forms, a concentration of 9wt% of temperature and pH Dual Sensitive block copolymers in the temperature- and pH-sensitivity aquogel system.
Embodiment 4
A kind of temperature- and pH-sensitivity block copolymer is using the poly- valine of polylysine-as hydrophobic chain segment, with poly-
Glycol monoethyl ether (mPEG) is polyethylene glycol lysine-poly- valine triblock copolymer that hydrophilic segment is constituted,
In, the content of lysine is 30wt% in hydrophobic chain segment polylysine-poly- valine, and the content of valine is 70wt%.
Further, the content of hydrophilic segment poly glycol monomethyl ether is 53wt%, hydrophobicity in aforesaid block copolymer
The content of segment polylysine-poly- valine is 46wt%.
Further, the number-average molecular weight of aforementioned hydrophilic segment poly glycol monomethyl ether is 5000.
The synthetic method of the temperature- and pH-sensitivity block copolymer of the present embodiment is same as Example 1.
The temperature- and pH-sensitivity aquogel system of the present embodiment, is prepared by temperature- and pH-sensitivity block copolymer
It forms, a concentration of 7.5wt% of temperature and pH Dual Sensitive block copolymers in the temperature- and pH-sensitivity aquogel system.
Embodiment 5
A kind of temperature- and pH-sensitivity block copolymer is using the poly- valine of polylysine-as hydrophobic chain segment, with poly-
Glycol monoethyl ether (mPEG) is polyethylene glycol lysine-poly- valine triblock copolymer that hydrophilic segment is constituted,
In, the content of lysine is 25wt% in hydrophobic chain segment polylysine-poly- valine, and the content of valine is 75wt%.
Further, the content of hydrophilic segment poly glycol monomethyl ether is 49wt%, hydrophobicity in aforesaid block copolymer
The content of segment polylysine-poly- valine is 51wt%.
Further, the number-average molecular weight of aforementioned hydrophilic segment poly glycol monomethyl ether is 1500.
The synthetic method of the temperature- and pH-sensitivity block copolymer of the present embodiment is same as Example 1.
The temperature- and pH-sensitivity aquogel system of the present embodiment, is prepared by temperature- and pH-sensitivity block copolymer
It forms, a concentration of 3wt% of temperature and pH Dual Sensitive block copolymers in the temperature- and pH-sensitivity aquogel system.
Embodiment 6
A kind of temperature- and pH-sensitivity block copolymer, component are same as Example 1.
The synthetic method of the temperature- and pH-sensitivity block copolymer of the present embodiment includes the following steps：
S1：Following material is weighed in proportion：
Initiator：Amino End Group poly glycol monomethyl ether, number-average molecular weight 1000, quality 1.00g；
Solvent：Chloroform/n,N-Dimethylformamide mixed solvent 6ml, wherein chloroform and N, N- dimethyl methyls
The volume ratio of amide is 2：1；
Reaction raw materials：N- carboxyls-alpha-amido-L benzyloxycarbonyl group lysine ring inner-acid anhydride monomer 0.612g, N- carboxyls-α-ammonia
Base-Valine ring inner-acid anhydride monomer 1.001g；
S2：The initiator weighed is added in the reaction vessel with magnetic agitation, and reaction vessel decompression is pumped into very
Sky is then passed through high-purity argon gas every half an hour and replaces system, repeatedly several times；
S3：Chloroform/n,N-Dimethylformamide mixed solvent of weighing is added into reaction vessel, keeps Amino End Group poly-
Glycol monoethyl ether dissolves；
S4：After Amino End Group poly glycol monomethyl ether is completely dissolved, N- carboxyls-alpha-amido-L- benzyloxy carbonyls of weighing are added
Reaction vessel, is then placed in 35 DEG C of oil bath by base lysine ring inner-acid anhydride monomer, so that mix monomer is carried out ring-opening polymerisation anti-
It answers；
S5：After reaction carries out 16h, it is added into reaction vessel in the N- carboxyl-alpha-amido-Valine rings of weighing sour
Acid anhydride continues ring-opening polymerization；
S6：After reaction carries out 16h, the reaction product of S5 is subjected to dissolution/precipitation processing, is then filtered, and in vacuum
It is dried to constant weight in baking oven, obtains the poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer.
S7：Following material is weighed in proportion：
Reactant：The poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer 1 g obtained by S6, and
The hydrogen bromide acetic acid solution 2ml of concentration 33%；
Solvent：Trifluoroacetic acid 10ml；
S8：The poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer is added anti-with stirrer
It answers in container, trifluoroacetic acid is added, open stirring, make the poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymerization
Object is completely dissolved.
S9：Ice bath reaction condition is set, hydrogen bromide acetic acid solution is added into reaction vessel, carries out deprotection reaction；
S10：After reaction carries out 4h, reaction product obtained by S9 is subjected to dissolution process with frost ether, is then filtered, and
It is dried to constant weight in vacuum drying oven, obtains the poly- valine triblock copolymer of poly glycol monomethyl ether-polylysine-.
Further, when mix monomer carries out ring-opening polymerization in described S4, S5, oil bath temperature can also be：20℃、
25℃、30℃、40℃。
Further, in described S4, S5 mix monomer carry out ring-opening polymerization when, the reaction time can also be 12h,
20h、24h、36h。
Further, when carrying out deprotection reaction in the S9, the reaction time can also be 5h, 6h, 7h.
The temperature- and pH-sensitivity aquogel system of the present embodiment, is prepared by temperature- and pH-sensitivity block copolymer
It forms, a concentration of 5wt% of temperature and pH Dual Sensitive block copolymers in the temperature- and pH-sensitivity aquogel system.
Further, temperature and pH Dual Sensitive block copolymers in the temperature- and pH-sensitivity aquogel system
It is a concentration of：1wt%, 3wt%, 6wt%, 10wt%.
Experimental verification：Below by the performance of the temperature- and pH-sensitivity aquogel system of the experimental verification present invention.
Example 1 be made temperature- and pH-sensitivity block copolymer be raw material, configuration concentration 3wt%, 4wt%,
The temperature- and pH-sensitivity aquogel system of 5wt%, 6wt%, and its sol-gel thermal transition behavior is measured respectively, it obtains
Sol-gel transition phasor, as shown in Figure 1.As can be seen from Figure, when temperature- and pH-sensitivity block copolymer is a concentration of
When 5wt%, 6wt%, it is flowable liquid that two kinds of temperature- and pH-sensitivity water gels, which tie up to room temperature or room temperature or less, and
Then exist with stable gel state in human body temperature.
A concentration of 5wt% temperature- and pH-sensitivities aquogel system made from Example 1, and measured respectively in pH value
The sol-gel transition behavior in the sections 3-8.5, obtains sol-gel transition phasor, as shown in Figure 2.As can be seen from Figure,
When it is 3-8.5 ranges that temperature- and pH-sensitivity water gel, which ties up to pH value, temperature- and pH-sensitivity water gel ties up to
It is flowable liquid below room temperature or room temperature, and then exists with stable gel state in human body temperature.
Those of ordinary skill in the art will understand that the embodiments described herein, which is to help reader, understands this hair
Bright principle, it should be understood that protection scope of the present invention is not limited to such specific embodiments and embodiments.This field
Those of ordinary skill can make according to the technical disclosures disclosed by the invention various does not depart from the other each of essence of the invention
The specific variations and combinations of kind, these variations and combinations are still within the scope of the present invention.
Claims (10)
1. a kind of temperature- and pH-sensitivity block copolymer, it is characterised in that：It is using the poly- valine of polylysine-as hydrophobicity
Segment, the polyethylene glycol lysine-poly- valine triblock copolymer constituted as hydrophilic segment using poly glycol monomethyl ether
Object, wherein the content of lysine is 22~34wt% in hydrophobic chain segment polylysine-poly- valine, and the content of valine is
66~78wt%.
2. temperature- and pH-sensitivity block copolymer according to claim 1, it is characterised in that：The block copolymer
The content of middle hydrophilic segment poly glycol monomethyl ether is 47~57wt%, the content of hydrophobic chain segment polylysine-poly- valine
It is 43~53wt%.
3. temperature- and pH-sensitivity block copolymer according to claim 1, it is characterised in that：The hydrophilic segment
The number-average molecular weight of poly glycol monomethyl ether is 500~5000.
4. the synthesis side of the temperature- and pH-sensitivity block copolymer described in a kind of any one of claims 1 to 3 claim
Method, it is characterised in that：Include the following steps：
S1：Following material is weighed in proportion：
Initiator：Amino End Group poly glycol monomethyl ether；
Solvent：Chloroform/n,N-Dimethylformamide mixed solvent；
Reaction raw materials：N- carboxyls-alpha-amido-L benzyloxycarbonyl group lysine ring inner-acid anhydride monomers and N- carboxyls-alpha-amido-L- figured silk fabrics ammonia
Sour ring inner-acid anhydride monomer；
S2：The initiator weighed is added in the reaction vessel with magnetic agitation, and reaction vessel decompression is evacuated, with
Afterwards every half an hour be passed through high-purity argon gas replace system, 3~5 times repeatedly；
S3：Chloroform/n,N-Dimethylformamide mixed solvent of weighing is added into reaction vessel, makes the poly- second of Amino End Group two
Alcohol monomethyl ether dissolves；
S4：After Amino End Group poly glycol monomethyl ether is completely dissolved, N- carboxyls-alpha-amido-L- benzyloxycarbonyl groups that weighing is added rely
Reaction vessel, is then placed in the oil bath of certain temperature by propylhomoserin ring inner-acid anhydride monomer, so that mix monomer is carried out ring-opening polymerisation anti-
It answers；
S5：N- carboxyl-alpha-amido-Valine ring the inner-acid anhydrides of weighing are added into reaction vessel, continue ring-opening polymerisation
Reaction；
S6：The reaction product of S5 is subjected to dissolution/precipitation processing, is then filtered, and is dried to constant weight in vacuum drying oven, is obtained poly-
The poly- benzyloxycarbonyl group lysine of glycol monoethyl ether-- poly- valine copolymer；
S7：Following material is weighed in proportion：
Reactant：The poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer obtained by S6 and hydrogen bromide
Acetic acid solution；
Solvent：Trifluoroacetic acid；
S8：The reaction with stirrer is added in the poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer to hold
In device, trifluoroacetic acid is added, opens stirring, keeps the poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer complete
Fully dissolved；
S9：Ice bath reaction condition is set, hydrogen bromide acetic acid solution is added into reaction vessel, carries out deprotection reaction；
S10：Reaction product obtained by S9 is subjected to dissolution process with frost ether, is then filtered, and dried extremely in vacuum drying oven
Constant weight obtains the poly- valine triblock copolymer of poly glycol monomethyl ether-polylysine-.
5. the synthetic method of temperature- and pH-sensitivity block copolymer according to claim 4, it is characterised in that：It is described
The parts by weight of each material are in S1：1 part of Amino End Group poly glycol monomethyl ether, N- carboxyls-alpha-amido-L benzyloxycarbonyl group lysines
0.612 part of ring inner-acid anhydride monomer, 1.001 parts of N- carboxyl-alpha-amido-Valine ring inner-acid anhydrides monomer.
6. the synthetic method of temperature- and pH-sensitivity block copolymer according to claim 4, it is characterised in that：It is described
The parts by weight of each material are in S7：The poly- benzyloxycarbonyl group lysine of poly glycol monomethyl ether-- poly- valine copolymer 1 part, bromination
2 parts of hydroacetic acid solution.
7. the synthetic method of temperature- and pH-sensitivity block copolymer according to claim 4, it is characterised in that：It is described
When mix monomer carries out ring-opening polymerization in S4, S5, oil bath temperature is 20~40 DEG C.
8. the synthetic method of temperature- and pH-sensitivity block copolymer according to claim 4, it is characterised in that：It is described
When mix monomer carries out ring-opening polymerization in S4, S5, the reaction time is 12~36h.
9. the synthetic method of temperature- and pH-sensitivity block copolymer according to claim 4, it is characterised in that：It is described
When carrying out deprotection reaction in S9, the reaction time is 4~7h.
10. a kind of temperature- and pH-sensitivity aquogel system, it is characterised in that：It is wanted by any one of claims 1 to 3 right
The temperature- and pH-sensitivity block copolymer is asked to be prepared, temperature in the temperature- and pH-sensitivity aquogel system
With a concentration of 1~10wt% of pH Dual Sensitive block copolymers.
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| CN102964591A (en) * | 2012-11-27 | 2013-03-13 | 中国科学院长春应用化学研究所 | Preparation method of polyamino acid segmented copolymer and polyamino acid segmented copolymer hydrogel |
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