CN104559209B - Method for improving hydrophily and flexibility of polypeptide membrane by polycarbamate and polyethylene glycol - Google Patents
Method for improving hydrophily and flexibility of polypeptide membrane by polycarbamate and polyethylene glycol Download PDFInfo
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- CN104559209B CN104559209B CN201510002738.6A CN201510002738A CN104559209B CN 104559209 B CN104559209 B CN 104559209B CN 201510002738 A CN201510002738 A CN 201510002738A CN 104559209 B CN104559209 B CN 104559209B
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Abstract
The invention discloses a method for improving the hydrophily and flexibility of a polypeptide film by polycarbamate and polyethylene glycol. The method comprises the following steps: (1) adding diisocyanate, polytetrahydrofuran, a catalyst and a solvent into a reactor, adding butanediol to react for a period, and adding 3-hydroxypropionic acid to react to obtain carboxyl-terminated polycarbamate; (2) adding the carboxyl-terminated polycarbamate, a solvent, a condensing agent and polypeptide homopolymer into a reactor, and stirring to react for 3-4 days to obtain a polypeptide-polycarbamate copolymer; (3) adding the carboxyl-terminated polycarbamate, a solvent, a condensing agent and amino-terminated methoxy polyethylene glycol into a reactor, and reacting for 2-3 days to obtain a polyethylene glycol-polycarbamate copolymer; (4) adding the polypeptide-polycarbamate copolymer, the polyethylene glycol-polycarbamate copolymer and a solvent into a reactor, mixing for a period, forming a film by a tape casting method, and drying to obtain the target object. The preparation process is simple, and the hydrophily and flexibility of the modified film can be greatly improved.
Description
Technical field
The present invention relates to a kind of method that polyurethanes improves poly- peptide film hydrophilic and compliance with Polyethylene Glycol, belong to
In field of polymer film preparing technology.
Background technology
Poly- peptide is a kind of biomaterial with good biocompatibility and biodegradability, and poly- peptide film can be used as people
Make skin etc., but poly- peptide film is more stiff, lack hydrophilic, thus limiting its application to a certain extent.Polyurethanes
There is preferable biocompatibility and biodegradability, softer.Polyethylene Glycol has preferable biocompatibility and biology
Degradability, softer and there is preferable hydrophilic.First polyurethanes segment is introduced poly- peptide segment and poly- second respectively
Glycol segment forms poly- peptide-polyurethane block copolymers and polyethylene glycol urethane block copolymers, then
Again two kinds of copolymers being mixed to form the blend with the preferable compatibility, modified poly- peptide film being obtained, thus drastically increasing
The hydrophilic of poly- peptide film and compliance.With polyurethanes and Polyethylene Glycol, poly- peptide film hydrophilic and compliance are carried out at present
There is not been reported for improved research.
Content of the invention
It is an object of the invention to provide one kind is simple to operate and effect is preferably entered to poly- peptide film hydrophilic and compliance
The improved method of row.Its technical scheme is:
A kind of polyurethanes and Polyethylene Glycol improve poly- peptide film hydrophilic and compliance method it is characterised in that:
In Modified Membrane, the molecular weight of poly- peptide segment is 80000～90000, and the molecular weight of polyurethanes segment is 4000～6000,
The molecular weight of Polyethylene Glycol segment is 7000～8000；Its method of modifying adopts following steps:
1) contain the synthesis of the polyurethanes of end-cooh group: add diisocyanate in dry reactor, gather
Oxolane ether glycol, catalysts and solvents, under inert atmosphere, after 40～50 DEG C of stirring reactions 40～50 minutes, add 1,
4- butanediol reacts 10～15 minutes, adds 3- hydracrylic acid and reacts 5～10 minutes, and terminating reaction obtains object；
2) synthesis of poly- peptide-polyurethane block copolymers: add in dry reactor containing end-cooh group
Polyurethanes, solvent, condensing agent and poly- peptide homopolymer, under inert atmosphere, after 20～30 DEG C of stirring reactions 3～4 days
Terminating reaction, by filtering, dialysing, be dried, obtains object, and wherein, poly- peptide homopolymer adopts poly- (r- benzyl-l- paddy ammonia
Acid esters), poly- (r- ethyl-l- glutamate) or poly- (r- methyl-l- glutamate)；
3) synthesis of polyethylene glycol urethane block copolymers: add in dry reactor and contain end-cooh
The polyurethanes of group, solvent, condensing agent and amino-terminated poly glycol monomethyl ether, under inert atmosphere, in 25～35
DEG C stirring reaction terminating reaction after 2～3 days, by filtering, dialysis, is dried, obtains object；
4) preparation of polyurethanes and poly ethyldiol modified poly- peptide film: add poly- peptide-poly- in dry reactor
Urethane block copolymers, polyethylene glycol urethane block copolymers and solvent, under inert atmosphere, in 40～
After 50 DEG C are stirred mixing 30～40 minutes, with the tape casting film forming and dry, obtain object.
The method that a kind of described polyurethanes improves poly- peptide film hydrophilic and compliance with Polyethylene Glycol, step 1)
In, diisocyanate adopts 2,4 toluene diisocyanate, and the difference of diisocyanate and the molal quantity of glycol is 0.001～
0.08；Catalyst adopts dibutyl tin laurate, and addition is the 3 of diisocyanate and PTMG gross weight
～5 ‰；Solvent adopts dimethylformamide, and reactant solution concentration is 5～15 g:100 ml.
The method that a kind of described polyurethanes improves poly- peptide film hydrophilic and compliance with Polyethylene Glycol, step 2)
In, condensing agent adoptsn ,n ’- dicyclohexylcarbodiimide,n ,n ’- DIC or 3- ethyl -1-(3-
Dimethylaminopropyl) carbodiimide, solvent adopts dimethylformamide, and reactant solution concentration is 5～15 g:100 ml.
The method that a kind of described polyurethanes improves poly- peptide film hydrophilic and compliance with Polyethylene Glycol, step 2)
In, polyurethanes is 6～15:1 with the mol ratio of poly- peptide homopolymer；Condensing agent is 1.06 with the mol ratio of poly- peptide homopolymer
～1.8:1.
The method that a kind of described polyurethanes improves poly- peptide film hydrophilic and compliance with Polyethylene Glycol, step 3)
In, condensing agent adoptsn ,n ’- dicyclohexylcarbodiimide,n ,n ’- DIC or 3- ethyl -1-(3-
Dimethylaminopropyl) carbodiimide, solvent adopts dimethylformamide, and reactant solution concentration is 5～15 g:100 ml.
The method that a kind of described polyurethanes improves poly- peptide film hydrophilic and compliance with Polyethylene Glycol, step 3)
In, polyurethanes is 3～8:1 with the mol ratio of poly glycol monomethyl ether；Condensing agent and poly glycol monomethyl ether mole
Than for 1.08～1.8:1.
The method that a kind of described polyurethanes improves poly- peptide film hydrophilic and compliance with Polyethylene Glycol, step 4)
In, mass percent in Modified Membrane for the polyethylene glycol urethane block copolymers is 1～4%, and solvent adopts 1,2-
Dichloroethanes or vinyl trichloride, mixture solution concentration is 25～35 g:100 ml.
Compared with prior art, its advantage is the present invention:
1. the method that the polyurethanes described in improves poly- peptide film hydrophilic and compliance with Polyethylene Glycol, using progressively
Addition polymerization, amidation process and blending three kinds of means, simple to operate, be easy to grasp；
2. the poly- peptide Modified Membrane hydrophilic described in is greatly improved with compliance.
Specific embodiment
Embodiment 1
1) contain the synthesis of the polyurethanes of end-cooh group
5.5 grams of 2,4 toluene diisocyanates, 17 grams of PTMG (molecular weight are added in dry reactor
For 1000), add 350 ml solvent dimethylformamides, separately add the di lauric dibutyl of above-mentioned reactant gross weight 3 ‰
Stannum, under inert atmosphere, after 40 DEG C of stirring reactions 40 minutes, adds 0.8 gram of BDO to react 10 minutes, adds 1.2
Gram 3- hydracrylic acid reacts 5 minutes, and terminating reaction obtains object；
2) synthesis of poly- peptide-polyurethane block copolymers
Add 16 grams poly- (r- benzyl-l- glutamate) (molecular weight be 80000) in dry reactor and 9 grams contain
The polyurethanes of end-cooh group, adds 300 ml dimethylformamides, adds 0.045 gramn ,n ’- two hexamethylenes
Base carbodiimide, under inert atmosphere, terminating reaction after 20 DEG C of stirring reactions 3 days, by filtering, dialysis, it is dried, obtain target
Thing；
3) synthesis of polyethylene glycol urethane block copolymers
Add 4 grams of amino-terminated poly glycol monomethyl ethers (molecular weight is 7000) in dry reactor and 9 grams contain
The polyurethanes of end-cooh group, adds 180 ml dimethylformamides, adds 0.131 gramn ,n ’- two hexamethylenes
Base carbodiimide, under inert atmosphere, terminating reaction after 25 DEG C of stirring reactions 2 days, by filtering, dialysis, it is dried, obtain target
Thing；
4) preparation of polyurethanes and poly ethyldiol modified poly- peptide film
12 grams of poly- peptide-polyurethane block copolymers and 46 ml 1,2- dichloroethanes are added in dry reactor
Solvent, another addition accounts for the polyethylene glycol urethane block copolymers of Modified Membrane gross weight 1%, under inert atmosphere, in 40
DEG C stirring mixing 30 minutes, use the tape casting film forming, in 50 DEG C of vacuum drying ovens be dried, obtain object.
After tested: the hydrophilic rate of object of the present invention and elongation at break are respectively than improve 10.6% He before modified
12.4%.
Embodiment 2
1) contain the synthesis of the polyurethanes of end-cooh group
6.05 grams of 2,4 toluene diisocyanates, 19 grams of PTMG (molecules are added in dry reactor
Measure as 1000), add 353 ml solvent dimethylformamides, separately add tin dilaurate two fourth of above-mentioned reactant gross weight 4 ‰
Ji Xi, under inert atmosphere, after 45 DEG C of stirring reactions 45 minutes, adds 0.88 gram of BDO to react 12 minutes, adds
1.3 grams of 3- hydracrylic acids react 7 minutes, and terminating reaction obtains object；
2) synthesis of poly- peptide-polyurethane block copolymers
Add 16.5 grams poly- (r- ethyl-l- glutamate) (molecular weight be 85000) in dry reactor and 9 grams contain
The polyurethanes of end-cooh group, adds 310 ml dimethylformamides, adds 0.027 gramn ,n ’- diisopropyl
Base carbodiimide, under inert atmosphere, terminating reaction after 25 DEG C of stirring reactions 4 days, by filtering, dialysis, it is dried, obtain target
Thing；
3) synthesis of polyethylene glycol urethane block copolymers
4.5 grams of amino-terminated poly glycol monomethyl ethers (molecular weight is 7500) and 9.5 grams are added in dry reactor
Polyurethanes containing end-cooh group, adds 185 ml dimethylformamides, adds 0.091 gramn ,n ’- two
Diisopropylcarbodiimide, under inert atmosphere, terminating reaction after 28 DEG C of stirring reactions 3 days, by filtering, dialysis, it is dried, obtain
Object；
4) preparation of polyurethanes and poly ethyldiol modified poly- peptide film
12.3 grams of poly- peptide-polyurethane block copolymers and 45 ml 1,1,2- trichlorines are added in dry reactor
Ethane solvent, another addition accounts for the polyethylene glycol urethane block copolymers of Modified Membrane gross weight 2%, under inert atmosphere,
In 45 DEG C of stirring mixing 35 minutes, use the tape casting film forming, be dried in 50 DEG C of vacuum drying ovens, obtain object.
After tested: the hydrophilic rate of object of the present invention and elongation at break are respectively than improve 11.8% He before modified
13.6%.
Embodiment 3
1) contain the synthesis of the polyurethanes of end-cooh group
6.6 grams of 2,4 toluene diisocyanates, 21 grams of PTMG (molecular weight are added in dry reactor
For 1000), add 360 ml solvent dimethylformamides, separately add the di lauric dibutyl of above-mentioned reactant gross weight 5 ‰
Stannum, under inert atmosphere, after 50 DEG C of stirring reactions 50 minutes, adds 0.92 gram of BDO to react 15 minutes, adds
1.84 grams of 3- hydracrylic acids react 10 minutes, and terminating reaction obtains object；
2) synthesis of poly- peptide-polyurethane block copolymers
Add 16.8 grams poly- (r- methyl-l- glutamate) (molecular weight be 90000) in dry reactor and 9.9 grams contain
There is the polyurethanes of end-cooh group, add 315 ml dimethylformamides, add 0.046 gram of 3- ethyl -1-(3-
Dimethylaminopropyl) carbodiimide, under inert atmosphere, terminating reaction after 30 DEG C of stirring reactions 3 days, by filtering, dialysis, dry
Dry, obtain object；
3) synthesis of polyethylene glycol urethane block copolymers
4.8 grams of amino-terminated poly glycol monomethyl ethers (molecular weight is 8000) and 9.6 grams are added in dry reactor
Polyurethanes containing end-cooh group, adds 188 ml dimethylformamides, adds 0.135 gram of 3- ethyl -1-
(3- dimethylaminopropyl) carbodiimide, under inert atmosphere, terminating reaction after 35 DEG C of stirring reactions 2 days, by filtering, dialysis,
It is dried, obtain object；
4) preparation of polyurethanes and poly ethyldiol modified poly- peptide film
13 grams of poly- peptide-polyurethane block copolymers and 45.5 ml 1,2- bis- chloroethene is added in dry reactor
Alkane solvents, another addition accounts for the polyethylene glycol urethane block copolymers of Modified Membrane gross weight 4%, under inert atmosphere, in
50 DEG C of stirrings mix 40 minutes, use the tape casting film forming, be dried, obtain object in 50 DEG C of vacuum drying ovens.
After tested: the hydrophilic rate of object of the present invention and elongation at break are respectively than improve 12.7% He before modified
14.5%.
Claims (7)
1. a kind of polyurethanes and Polyethylene Glycol improve poly- peptide film hydrophilic and compliance method it is characterised in that: change
Property film in the molecular weight of poly- peptide segment be 80000～90000, the molecular weight of polyurethanes segment is 4000～6000, gathers
The molecular weight of ethylene glycol segment is 7000～8000；Its method of modifying adopts following steps:
1) contain the synthesis of the polyurethanes of end-cooh group: add diisocyanate, poly- tetrahydrochysene in dry reactor
Furan ether glycol, catalysts and solvents, under inert atmosphere, after 40～50 DEG C of stirring reactions 40～50 minutes, add Isosorbide-5-Nitrae-fourth
Glycol reacts 10～15 minutes, adds 3- hydracrylic acid and reacts 5～10 minutes, and terminating reaction obtains object；
2) synthesis of poly- peptide-polyurethane block copolymers: add poly- containing end-cooh group in dry reactor
Carbamate, solvent, condensing agent and poly- peptide homopolymer, under inert atmosphere, terminate after 20～30 DEG C of stirring reactions 3～4 days
Reaction, by filtering, dialysing, be dried, obtains object, and wherein, poly- peptide homopolymer adopts poly- (γ-benzyl-l- glutamic acid
Ester), poly- (γ-ethyl-l- glutamate) or poly- (γ-methyl-l- glutamate)；
3) synthesis of polyethylene glycol urethane block copolymers: add in dry reactor containing end-cooh group
Polyurethanes, solvent, condensing agent and amino-terminated poly glycol monomethyl ether, under inert atmosphere, stir in 25～35 DEG C
Mix terminating reaction after reaction 2～3 days, by filtering, dialysis, be dried, obtain object；
4) preparation of polyurethanes and poly ethyldiol modified poly- peptide film: add poly- peptide-poly- amino in dry reactor
Formate-blocked copolymer, polyethylene glycol urethane block copolymers and solvent, under inert atmosphere, in 40～50 DEG C
After stirring mixing 30～40 minutes, with the tape casting film forming and dry, obtain object.
2. a kind of polyurethanes according to claim 1 and Polyethylene Glycol improve poly- peptide film hydrophilic and compliance
Method it is characterised in that: in step 1), diisocyanate adopts 2,4 toluene diisocyanate, diisocyanate and glycol
The difference of molal quantity is 0.001～0.08；Catalyst adopts dibutyl tin laurate, and addition is diisocyanate and poly- tetrahydrochysene
3～the 5 ‰ of furan ether glycol gross weight；Solvent adopts dimethylformamide, and reactant solution concentration is 5～15 g:100 ml.
3. a kind of polyurethanes according to claim 1 and Polyethylene Glycol improve poly- peptide film hydrophilic and compliance
Method it is characterised in that: step 2) in, condensing agent adopts n, n '-dicyclohexylcarbodiimide, n, and n '-diisopropyl carbon two is sub-
Amine or 3- ethyl -1-(3- dimethylaminopropyl) carbodiimide, solvent adopts dimethylformamide, and reactant solution concentration is 5～
15 g:100 ml.
4. a kind of polyurethanes according to claim 1 and Polyethylene Glycol improve poly- peptide film hydrophilic and compliance
Method it is characterised in that: step 2) in, the mol ratio of polyurethanes and poly- peptide homopolymer is 6～15:1；Condensing agent with poly-
The mol ratio of peptide homopolymer is 1.06～1.8:1.
5. a kind of polyurethanes according to claim 1 and Polyethylene Glycol improve poly- peptide film hydrophilic and compliance
Method it is characterised in that: in step 3), condensing agent adopts n, n '-dicyclohexylcarbodiimide, n, and n '-diisopropyl carbon two is sub-
Amine or 3- ethyl -1-(3- dimethylaminopropyl) carbodiimide, solvent adopts dimethylformamide, and reactant solution concentration is 5～
15 g:100 ml.
6. a kind of polyurethanes according to claim 1 and Polyethylene Glycol improve poly- peptide film hydrophilic and compliance
Method it is characterised in that: in step 3), the mol ratio of polyurethanes and poly glycol monomethyl ether is 3～8:1；Condensing agent
Mol ratio with poly glycol monomethyl ether is 1.08～1.8:1.
7. a kind of polyurethanes according to claim 1 and Polyethylene Glycol improve poly- peptide film hydrophilic and compliance
Method it is characterised in that: in step 4), percent mass in Modified Membrane for the polyethylene glycol urethane block copolymers
For 1～4%, solvent adopts 1,2- dichloroethanes or vinyl trichloride to ratio, and mixture solution concentration is 25～35 g:100
ml.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510002738.6A CN104559209B (en) | 2015-01-05 | 2015-01-05 | Method for improving hydrophily and flexibility of polypeptide membrane by polycarbamate and polyethylene glycol |
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| CN201510002738.6A CN104559209B (en) | 2015-01-05 | 2015-01-05 | Method for improving hydrophily and flexibility of polypeptide membrane by polycarbamate and polyethylene glycol |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102181061B (en) * | 2011-03-20 | 2012-09-12 | 山东理工大学 | Polyurethane-polypeptide graft copolymer and preparation method thereof |
| CN103834180B (en) * | 2014-03-04 | 2016-02-24 | 山东理工大学 | A kind of method that polycaprolactone and polypropylene glycol improve poly-peptide film kindliness |
| CN103788607B (en) * | 2014-03-07 | 2015-08-26 | 山东理工大学 | A kind of PPDO and aqueous polyurethane improve the poly-hydrophilic method of peptide film |
| CN103819908B (en) * | 2014-03-14 | 2016-04-06 | 山东理工大学 | A kind of method that PPDO and urethane improve poly-peptide film kindliness |
| CN103819909B (en) * | 2014-03-14 | 2015-12-02 | 山东理工大学 | A kind of PPDO and urethane improve the method for poly-peptide film kindliness |
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