CN106866883A - A kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino - Google Patents
A kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino Download PDFInfo
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Abstract
The present invention is a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino, including：Phosphoryl choline polymer of the synthesis containing amino；Phosphoryl choline polymer containing amino is dissolved in polar solvent, polymer solution is obtained.Then, under nitrogen protection, the polymer solution is heated to 20 DEG C~50 DEG C, then to 3,4 4-dihydroxy benzaldehydes are added in polymer solution, is grafted with amino reaction using aldehyde radical under the conditions of insulated and stirred.Again with after sodium borohydride reduction, hemodialysis reaction product, finally, by the product freeze-drying after dialysis, you can obtain double Biomimetic Polymers.Preparation method of the invention is simple, mild condition, grafting rate is controllable, adjacent two phenolic hydroxyl groups have the adhesive attraction of imitative bivalves attachment proteins dopamine, Phosphorylcholine has the antifouling property of imitating cell outer-layer membrane structure, the polymer has dual bionical feature, is expected to be had broad application prospects in material surface modification field.
Description
【Technical field】
The invention belongs to material surface science and biological medical polymer material technical field, and in particular to one kind is based on aldehyde
The method that double Biomimetic Polymers are synthesized with amino for base.
【Background technology】
Material is used for easy non-specific adsorption albumen, activating complement molecule and immune system when in organism, so as to cause
Blood coagulation, immune and inflammatory reaction, so that its performance is significantly reduced, or even failure.This is because Biocompatibility is poor
Reason, thus, Study on biocompatibility has turned into the matter of utmost importance in biomaterial research field.Material surface is material and life
The medium of object contact, electric charge, parent/hydrophobicity, chemical composition, the pattern on surface etc. are interfaces between influence material and organism
The key factor of interaction, is the principal element for determining whether Biocompatibility is excellent.Therefore, material surface is improved
Biocompatibility is the key for solving this problem in science.The material of good biocompatibility is incorporated into material surface modifying is
Improve the interaction between material and organism, improve the simple and effective approach of Biocompatibility.Material surface
It is an eternal theme in biomaterial research field that biocompatibility is modified, with important academic significance and it is huge should
Use prospect.
In recent years, the endothelial cell with good blood compatibility, albumin, heparin and polyethylene glycol are incorporated into material
Surface, can be obviously improved its biocompatibility, particularly significantly improve its blood compatibility.But, these methods are still deposited
In some problems.For example：Endothelial cell is poor with the interaction of material surface, and anti-blood impact capacity is not good, easy to fall off.In vain
Albumen, in material surface competitive Adsorption, causes absorption in the albumin content reduction of material surface with activity in vivo component, or even
Denaturation.Heparin facile hydrolysis, causes its activity to be decreased obviously, so that the complication such as induction bleeding, thrombopenia.Fiercely exhaling
During suction, polyethylene glycol is oxidized because of superoxide anion and hydrogen peroxide, and also there is different degrees of biological pollution on its surface.
Phosphorylcholine (phosphorylcholine, PC) is the terminal hydrophyllic group for constituting cell membrane elementary cell lecithin, is
Outer layer functional group in extracellular tunic, simultaneous with positive and negative xenogenesis electric charge, ability and hydrophily with stronger combination water
Can, the surface of this structure and composition interacts with physiological environment and will not only adsorb and depositing proteins, will not also trigger
Platelet activation, cause the adverse reactions such as blood coagulation, with good biocompatibility.Research in recent years shows, using phosphinylidyne
Choline group and its polymer build in material surface has imitating cell outer-layer membrane structure, can significantly improve the blood phase of material
Capacitive.
Physics is coated including dip-coating, spin coating and mode etc. drop coating, because it has process is simple, easy to operate and mild condition
Advantage, be to build the promising approach that imitating cell outer-layer membrane structure obtains superior bio compatibility surface.However, Phosphorylcholine base
The hydrophily of group is stronger, and physics is coated in the phosphoryl choline polymer coating of material surface and is easily sent out in complicated physiological environment
Raw dissolving, degraded, or even come off.It is then desired to cross-linking or covalent bond group is incorporated into phosphoryl choline polymer, pass through
Chemical reaction is by polymer coating crosslinking or covalent bonding in material surface.This undoubtedly increased this kind of phosphoryl choline polymer
Synthesis and application also cause the tediously long complexity of processing procedure of the technology to the difficulty of surface requirements.Therefore, in the urgent need to research is opened
Hair uses simple, widely applicable surface modifying method.
Recently, Messersmith seminars in the U.S. are by imitative bivalves (Mussel) attachment proteins composition dopamine
(Dopamine) combined with PEG, assigned water-soluble polymer in the excellent adhesion property of material surface, obtained with good anti-
The stable coatings of biological pollution.DOPA amine groups in the coating are gone back in addition to various non-covalent bond effects such as pi-pi accumulation
Oxidizable polymerization forms adhesiveness poly-dopamine (PDA), can be resistance to including the various base materials generation including metal, glass and plastics
The strong adhesive attraction of water.Additionally, dopamine coating can be grafted with biological function by Michael's addition or schiff base reaction
Molecule.The surface modification method of this imitative bivalves adhesion can make up current physics coating and have to pass through complicated chemical treatment
The limitation of stable coatings can be obtained, simplifies the condition and process of material surface modifying.
Changed with the double Biomimetic Polymers containing cellulosa film component Phosphorylcholine and bivalves attachment proteins composition dopamine
Property material surface, the dopamine side base in polymer can be adhered the multiple material to including including polytetrafluoroethylene (PTFE) from the aqueous solution
Surface, Phosphorylcholine side base then automatically forms imitating cell outer-layer membrane structure in coating surface, significantly improves the life of base material
Thing compatibility.The technology provides the possibility for being worth exploration for the biocompatibility of graphene oxide.However, DOPA amine monomers
In phenolic hydroxyl group be radical polymerization polymerization inhibitor, thus protection phenolic hydroxyl group is the necessary process of this kind of monomer polymerization, is also many
The difficult point of bar amine polymer synthesis.Therefore, dopamine to be grafted to the phosphinylidyne courage containing carboxyl using amino and carboxyl reaction
On alkali polymer, the protection process of phenolic hydroxyl group can be omitted.But the grafting of dopamine in double Biomimetic Polymers prepared by this method
Rate is only 4% so that the polymer coating adhesion is relatively low easy to fall off.Although having synthesized dopamine with active ester monomer approach to contain
Amount double Biomimetic Polymers high and controllable, but active ester monomer needs are in water-less environment preparation, and also its separating-purifying is extremely
It is difficult.
【The content of the invention】
The technical problems to be solved by the invention are for above-mentioned the deficiencies in the prior art, there is provided one kind based on aldehyde radical with
The method that amino is synthesized double Biomimetic Polymers.Preparation method of the invention is simple, mild condition, and grafting rate is controllable, and adjacent two
Phenolic hydroxyl group has the adhesive attraction of imitative bivalves attachment proteins dopamine, and Phosphorylcholine has the pollution resistance of imitating cell outer-layer membrane structure
Can, the polymer has dual bionical feature, is expected to be had broad application prospects in material surface modification field.
In order to solve the above technical problems, the technical solution adopted by the present invention is：
A kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino, is comprised the following steps：
Step one, under nitrogen protection, by the vinyl monomer containing Phosphorylcholine group and the vinyl containing amino
Monomer carries out Raolical polymerizable in the presence of initiator, the vinyl monomer containing Phosphorylcholine group and contains amino
Vinyl monomer mol ratio be 3:7~9:1；After reaction terminates, concentration of reaction solution is dialysed with bag filter；Finally, will dialyse
Sample freeze-drying afterwards, obtains the phosphoryl choline polymer containing amino；
Step 2, the phosphoryl choline polymer containing amino described in step one is dissolved in polar solvent, is polymerized
Thing solution；Then, under nitrogen protection, the polymer solution is heated to 20 DEG C~50 DEG C, then in polymer solution
3,4- 4-dihydroxy benzaldehydes are added, the mole of 3,4- 4-dihydroxy benzaldehydes is amino in the phosphoryl choline polymer containing amino
The 10%~120% of mole；It is grafted with amino reaction using aldehyde radical under the conditions of insulated and stirred；Again with sodium borohydride also
After original, with bag filter in the aqueous hydrochloric acid solution that pH value is 3~4 hemodialysis reaction product, it is finally, the product after dialysis is cold
It is lyophilized dry, you can to obtain double Biomimetic Polymers.
In step one, the vinyl monomer containing Phosphorylcholine group and the vinyl monomer containing amino are respectively methyl
Acrylyl oxy-ethyl Phosphorylcholine and 2- aminoethyl methacrylate hydrochlorides.
In step one, the initiator is azodiisobutyronitrile.
In step one, the polymerization solvent is ethanol and tetrahydrofuran mixed solution.
In step one, the temperature of Raolical polymerizable is 60 DEG C~80 DEG C, and the time is 12h~24h.
In step 2, polar solvent is water, methyl alcohol or ethanol.
In step 2, the time of graft reaction is 10h~24h.
In step 2, the consumption of sodium borohydride is 20%~200% of the phosphoryl choline polymer quality containing amino, instead
It is 2h~4h between seasonable.
Bag filter molecular cut off is 6000~8000.
The present invention compared with prior art, with advantages below：
Be dissolved in phosphoryl choline polymer containing amino in polar solvent by the present invention, obtains polymer solution.Then, exist
Under nitrogen protection, the polymer solution is heated to 20 DEG C~50 DEG C, then to adding 3,4- dihydroxy in polymer solution
Benzaldehyde, is grafted using aldehyde radical under the conditions of insulated and stirred with amino reaction.Again with sodium borohydride reduction after, use bag filter
The hemodialysis reaction product in the aqueous hydrochloric acid solution that pH value is 3~4, finally, by the product freeze-drying after dialysis, you can
To double Biomimetic Polymers.There was only two kinds compared to the method for preparing double Biomimetic Polymers at this stage, the first is to utilize active ester；
Second is that epoxy is prepared with amino open loop grafting dopamine.First method reactivity is also higher, higher to solvent requirement,
Reaction condition is more harsh；Second method reaction condition is fairly simple, but reactivity is relatively low, and grafting rate is not high.This hair
Bright preparation method is simple, mild condition, and grafting rate is controllable, and adjacent two phenolic hydroxyl group has the adhesion of imitative bivalves attachment proteins dopamine
Effect, Phosphorylcholine has the antifouling property of imitating cell outer-layer membrane structure, and the polymer has dual bionical feature, is expected to
Material surface modification field has broad application prospects.Preparation method of the invention is simple, mild condition, double bionical to obtain
Polymer provides a kind of new approach.The double Biomimetic Polymers prepared using the inventive method are implanted into material in vivo, organize
The fields such as engineering, medicament slow release and biology sensor have broad application prospects.
【Brief description of the drawings】
Fig. 1 is the synthetic route chart of double Biomimetic Polymers of the embodiment of the present invention 1.
Fig. 2 is the hydrogen nuclear magnetic spectrogram of double Biomimetic Polymers prepared by the embodiment of the present invention 1.
【Specific embodiment】
A kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino of the present invention, is comprised the following steps：
Step one, under nitrogen protection, by the vinyl monomer containing Phosphorylcholine group and the vinyl containing amino
Monomer carries out Raolical polymerizable in the presence of initiator,；After reaction terminates, concentration of reaction solution is dialysed with bag filter；Most
Afterwards, by the sample freeze-drying after dialysis, the phosphoryl choline polymer containing amino is obtained；
Wherein, the vinyl monomer containing Phosphorylcholine group and the vinyl monomer containing amino are respectively metering system
Acyloxyethyl Phosphorylcholine and 2- aminoethyl methacrylate hydrochlorides, the initiator are azodiisobutyronitrile, described poly-
It is ethanol and tetrahydrofuran mixed solution to close reaction dissolvent.Vinyl monomer containing Phosphorylcholine group and the second containing amino
The mol ratio of alkenyl monomer is 3:7~9:1.The temperature of Raolical polymerizable is 60 DEG C~80 DEG C, and the time is 12h~24h.
Step 2, the phosphoryl choline polymer containing amino described in step one is dissolved in polar solvent, is polymerized
Thing solution.Then, under nitrogen protection, the polymer solution is heated to 20 DEG C~50 DEG C, then in polymer solution
3,4- 4-dihydroxy benzaldehydes are added, is grafted with amino reaction using aldehyde radical under the conditions of insulated and stirred.Reaction is used after terminating
Bag filter hemodialysis reaction product in the aqueous hydrochloric acid solution that pH value is 3~4, finally, by the product freeze-drying after dialysis,
Can obtain double Biomimetic Polymers.
Wherein, polar solvent is water, methyl alcohol or ethanol.The mole of 3,4- 4-dihydroxy benzaldehydes is the phosphorus containing amino
The 10%~120% of amino mole in phatidylcholine polymer.The time of graft reaction is 10h~24h.The consumption of sodium borohydride
It is 0.1g~1g when phosphoryl choline polymer 0.5g () containing amino that the reaction time is 2h~4h.Bag filter molecular cut off
It is 6000~8000.
With reference to the accompanying drawings and examples, technical scheme is described in further detail.
Embodiment 1
The present embodiment is comprised the following steps：
Step one, weigh 8mmol 2- methacryloxyethyls Phosphorylcholines and 2mmol 2- aminoethyl metering systems
Acid esters hydrochloride, dissolves well mixed, by 0.1mmol azodiisobutyronitriles tetrahydrochysene furan with ethanol and tetrahydrofuran mixed solvent
Dissolving of muttering obtains initiator solution, in N2Protection, under 70 DEG C of stirring conditions, in three-necked bottle add monomer mixed solution, in advance
After hot 30min, initiator solution is added to continue to react 24h, after reaction terminates, concentration of reaction solution is 6000 with molecular cut off
The bag filter dialysis of~8000D；Finally, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain the phosphorus containing amino
Phatidylcholine polymer；Nuclear-magnetism test result shows that the molar content of amino is about 18% in the polymer；
Step 2, the phosphoryl choline polymer containing amino described in 0.5g steps one is dissolved in 20mL methyl alcohol and is gathered
Polymer solution, in N2Protection, under 30 DEG C of stirring conditions, to the polymer solution is added in three-necked bottle, preheats 30min, then add
Enter 0.15g 3,4- 4-dihydroxy benzaldehydes, insulated and stirred reaction 12h.Then 0.3gNaBH is added4Reduction 3h, reaction terminates
Afterwards, concentration of reaction solution, is dialysed with the bag filter that molecular cut off is 6000~8000D in the aqueous hydrochloric acid solution that pH value is 3~4
Reaction solution after concentration, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain double Biomimetic Polymers.
With 400MHz NMRs with D2O tests the manufactured in the present embodiment pair of proton magnetic of Biomimetic Polymers for solvent
(see Fig. 2), has no appearance at 5ppm~6.5ppm, shows do not have residual monomer in resulting polymers, and successfully synthesize this
Polymer, with 3.28ppm at as-N+(CH3)3Characteristic peak, is methylene and pendant methyl on main chain at 0.9ppm~2.2ppm
Peak is more in this pair of Biomimetic Polymers for the peak of the phenyl ring in DOPA amine groups calculates polymer composition at 6.8ppm~7.2ppm
The molar content of bar amine groups is about 16%.
Embodiment 2
The present embodiment is comprised the following steps：
Step one, weigh 7mmol 2- methacryloxyethyls Phosphorylcholines and 3mmol 2- aminoethyl metering systems
Acid esters hydrochloride, dissolves well mixed, by 0.1mmol azodiisobutyronitriles tetrahydrochysene furan with ethanol and tetrahydrofuran mixed solvent
Dissolving of muttering obtains initiator solution, in N2Protection, under 60 DEG C of stirring conditions, in three-necked bottle add monomer mixed solution, in advance
After hot 30min, initiator solution is added to continue to react 24h, after reaction terminates, concentration of reaction solution is 6000 with molecular cut off
The bag filter dialysis of~8000D；Finally, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain the phosphorus containing amino
Phatidylcholine polymer；Nuclear-magnetism test result shows that the molar content of amino is about 28% in the polymer；
Step 2, the phosphoryl choline polymer containing amino described in 0.5g steps one is dissolved in 20mL ethanol and is gathered
Polymer solution, in N2Protection, under 25 DEG C of stirring conditions, to the polymer solution is added in three-necked bottle, preheats 30min, then add
Enter 0.2g 3,4- 4-dihydroxy benzaldehydes, insulated and stirred reaction 15h.Then 0.1gNaBH is added4Reduction 4h, after reaction terminates,
Concentration of reaction solution, is dialysed dense with the bag filter that molecular cut off is 6000~8000D in the aqueous hydrochloric acid solution that pH value is 3~4
Reaction solution after contracting, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain double Biomimetic Polymers.
Embodiment 3
The present embodiment is comprised the following steps：
Step one, weigh 6mmol 2- methacryloxyethyls Phosphorylcholines and 4mmol 2- aminoethyl metering systems
Acid esters hydrochloride, dissolves well mixed, by 0.1mmol azodiisobutyronitriles tetrahydrochysene furan with ethanol and tetrahydrofuran mixed solvent
Dissolving of muttering obtains initiator solution, in N2Protection, under 80 DEG C of stirring conditions, in three-necked bottle add monomer mixed solution, in advance
After hot 30min, initiator solution is added to continue to react 24h, after reaction terminates, concentration of reaction solution is 6000 with molecular cut off
The bag filter dialysis of~8000D；Finally, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain the phosphorus containing amino
Phatidylcholine polymer；Nuclear-magnetism test result shows that the molar content of amino is about 39% in the polymer；
Step 2, the phosphoryl choline polymer containing amino described in 0.5g steps one is dissolved in 20mL distilled water obtains
Polymer solution, in N2Protection, under 20 DEG C of stirring conditions, to the polymer solution is added in three-necked bottle, preheats 30min, then
Add 0.4g 3,4- 4-dihydroxy benzaldehydes, insulated and stirred reaction 24h.Then 1gNaBH is added4Reductase 12 h, after reaction terminates,
Concentration of reaction solution, is dialysed dense with the bag filter that molecular cut off is 6000~8000D in the aqueous hydrochloric acid solution that pH value is 3~4
Reaction solution after contracting, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain double Biomimetic Polymers.
Embodiment 4
The present embodiment is comprised the following steps：
Step one, weigh 9mmol 2- methacryloxyethyls Phosphorylcholines and 1mmol 2- aminoethyl metering systems
Acid esters hydrochloride, dissolves well mixed, by 0.1mmol azodiisobutyronitriles tetrahydrochysene furan with ethanol and tetrahydrofuran mixed solvent
Dissolving of muttering obtains initiator solution, in N2Protection, under 65 DEG C of stirring conditions, in three-necked bottle add monomer mixed solution, in advance
After hot 30min, initiator solution is added to continue to react 24h, after reaction terminates, concentration of reaction solution is 6000 with molecular cut off
The bag filter dialysis of~8000D；Finally, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain the phosphorus containing amino
Phatidylcholine polymer；Nuclear-magnetism test result shows that the molar content of amino is about 9% in the polymer；
Step 2, the phosphoryl choline polymer containing amino described in 0.5g steps one is dissolved in 20mL methyl alcohol and is gathered
Polymer solution, in N2Protection, under 40 DEG C of stirring conditions, to the polymer solution is added in three-necked bottle, preheats 30min, then add
Enter 0.2g 3,4- 4-dihydroxy benzaldehydes, insulated and stirred reaction 15h.Then 0.4gNaBH is added4Reduction 3h, after reaction terminates,
Concentration of reaction solution, is dialysed dense with the bag filter that molecular cut off is 6000~8000D in the aqueous hydrochloric acid solution that pH value is 3~4
Reaction solution after contracting, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain double Biomimetic Polymers.
Embodiment 5
The present embodiment is comprised the following steps：
Step one, weigh 5mmol 2- methacryloxyethyls Phosphorylcholines and 5mmol 2- aminoethyl metering systems
Acid esters hydrochloride, dissolves well mixed, by 0.1mmol azodiisobutyronitriles tetrahydrochysene furan with ethanol and tetrahydrofuran mixed solvent
Dissolving of muttering obtains initiator solution, in N2Protection, under 75 DEG C of stirring conditions, in three-necked bottle add monomer mixed solution, in advance
After hot 30min, initiator solution is added to continue to react 24h, after reaction terminates, concentration of reaction solution is 6000 with molecular cut off
The bag filter dialysis of~8000D；Finally, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain the phosphorus containing amino
Phatidylcholine polymer；Nuclear-magnetism test result shows that the molar content of amino is about 48% in the polymer；
Step 2, the phosphoryl choline polymer containing amino described in 0.5g steps one is dissolved in 20mL ethanol and is gathered
Polymer solution, in N2Protection, under 50 DEG C of stirring conditions, to the polymer solution is added in three-necked bottle, preheats 30min, then add
Enter 0.5g 3,4- 4-dihydroxy benzaldehydes, insulated and stirred reaction 10h.Then 0.8gNaBH is added4Reductase 12 .4h, reaction terminates
Afterwards, concentration of reaction solution, is dialysed with the bag filter that molecular cut off is 6000~8000D in the aqueous hydrochloric acid solution that pH value is 3~4
Reaction solution after concentration, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain double Biomimetic Polymers.
Embodiment 6
The present embodiment is comprised the following steps：
Step one, weigh 4mmol 2- methacryloxyethyls Phosphorylcholines and 6mmol 2- aminoethyl metering systems
Acid esters hydrochloride, dissolves well mixed, by 0.1mmol azodiisobutyronitriles tetrahydrochysene furan with ethanol and tetrahydrofuran mixed solvent
Dissolving of muttering obtains initiator solution, in N2Protection, under 70 DEG C of stirring conditions, in three-necked bottle add monomer mixed solution, in advance
After hot 30min, initiator solution is added to continue to react 24h, after reaction terminates, concentration of reaction solution is 6000 with molecular cut off
The bag filter dialysis of~8000D；Finally, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain the phosphorus containing amino
Phatidylcholine polymer；Nuclear-magnetism test result shows that the molar content of amino is about 59% in the polymer；
Step 2, the phosphoryl choline polymer containing amino described in 0.5g steps one is dissolved in 20mL distilled water obtains
Polymer solution, in N2Protection, under 35 DEG C of stirring conditions, to the polymer solution is added in three-necked bottle, preheats 30min, then
Add 0.7g 3,4- 4-dihydroxy benzaldehydes, insulated and stirred reaction 14h.Then 0.9gNaBH is added4Reductase 12 .1h, reaction knot
Shu Hou, concentration of reaction solution is saturating in the aqueous hydrochloric acid solution that pH value is 3~4 with the bag filter that molecular cut off is 6000~8000D
Reaction solution after analysis concentration, by the freeze-drying at -50 DEG C of the sample after dialysis, you can obtain double Biomimetic Polymers.
Embodiment 7
The present embodiment is comprised the following steps：
Step one, weigh 3mmol 2- methacryloxyethyls Phosphorylcholines and 7mmol 2- aminoethyl metering systems
Acid esters hydrochloride, dissolves well mixed, by 0.1mmol azodiisobutyronitriles tetrahydrochysene furan with ethanol and tetrahydrofuran mixed solvent
Dissolving of muttering obtains initiator solution, in N2Protection, under 76 DEG C of stirring conditions, in three-necked bottle add monomer mixed solution, in advance
After hot 30min, initiator solution is added to continue to react 24h, after reaction terminates, concentration of reaction solution is 6000 with molecular cut off
The bag filter dialysis of~8000D；Finally, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain the phosphorus containing amino
Phatidylcholine polymer；Nuclear-magnetism test result shows that the molar content of amino is about 71% in the polymer；
Step 2, the phosphoryl choline polymer containing amino described in 0.5g steps one is dissolved in 20mL methyl alcohol and is gathered
Polymer solution, in N2Protection, under 45 DEG C of stirring conditions, to the polymer solution is added in three-necked bottle, preheats 30min, then add
Enter 0.6g 3,4- 4-dihydroxy benzaldehydes, insulated and stirred reaction 19h.Then 0.7gNaBH is added4Reduction 3h, after reaction terminates,
Concentration of reaction solution, is dialysed dense with the bag filter that molecular cut off is 6000~8000D in the aqueous hydrochloric acid solution that pH value is 3~4
Reaction solution after contracting, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain double Biomimetic Polymers.
Embodiment 8
The present embodiment is comprised the following steps：
Step one, weigh 4.5mmol 2- methacryloxyethyls Phosphorylcholines and 5.5mmol 2- aminoethyl methyl
Acrylate hydrochloride, dissolves well mixed with ethanol and tetrahydrofuran mixed solvent, and 0.1mmol azodiisobutyronitriles are used into four
The dissolving of hydrogen furans obtains initiator solution, in N2Protection, under 68 DEG C of stirring conditions, to being added in three-necked bottle, the mixing of monomer is molten
Liquid, after preheating 30min, adds initiator solution to continue to react 24h, and after reaction terminates, concentration of reaction solution is with molecular cut off
The bag filter dialysis of 6000~8000D；Finally, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain containing amino
Phosphoryl choline polymer；Nuclear-magnetism test result shows that the molar content of amino is about 56% in the polymer；
Step 2, the phosphoryl choline polymer containing amino described in 0.5g steps one is dissolved in 20mL methyl alcohol and is gathered
Polymer solution, in N2Protection, under 32 DEG C of stirring conditions, to the polymer solution is added in three-necked bottle, preheats 30min, then add
Enter 0.7g 3,4- 4-dihydroxy benzaldehydes, insulated and stirred reaction 11h.Then 0.2gNaBH is added4Reduction 3.5h, reaction terminates
Afterwards, concentration of reaction solution, is dialysed with the bag filter that molecular cut off is 6000~8000D in the aqueous hydrochloric acid solution that pH value is 3~4
Reaction solution after concentration, by the sample freeze-drying at -50 DEG C after dialysis, you can obtain double Biomimetic Polymers.
The above, is only presently preferred embodiments of the present invention, and any limitation is not done to the present invention, every according to invention skill
Any simple modification, change and equivalent structure change that art is substantially made to above example, still fall within the technology of the present invention
In the protection domain of scheme.
Claims (9)
1. a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino, it is characterised in that comprise the following steps：
Step one, under nitrogen protection, by the vinyl monomer containing Phosphorylcholine group and the vinyl monomer containing amino
Raolical polymerizable is carried out in the presence of initiator, the vinyl monomer containing Phosphorylcholine group and the second containing amino
The mol ratio of alkenyl monomer is (3:7)~(9:1)；After reaction terminates, concentration of reaction solution is dialysed with bag filter；Finally, will dialyse
Sample freeze-drying afterwards, obtains the phosphoryl choline polymer containing amino；
Step 2, the phosphoryl choline polymer containing amino described in step one is dissolved in polar solvent, obtains polymer molten
Liquid；Then, under nitrogen protection, the polymer solution is heated to 20 DEG C~50 DEG C, is then added in polymer solution
3,4- 4-dihydroxy benzaldehydes, the mole of 3,4- 4-dihydroxy benzaldehydes is amino mole in the phosphoryl choline polymer containing amino
The 10%~120% of amount；It is grafted with amino reaction using aldehyde radical under the conditions of insulated and stirred；Sodium borohydride reduction is used again
Afterwards, with bag filter in the aqueous hydrochloric acid solution that pH value is 3~4 hemodialysis reaction product, finally, by after dialysis product freezing
Dry, you can obtain double Biomimetic Polymers.
2. a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino according to claim 1, its feature
It is that in step one, the vinyl monomer containing Phosphorylcholine group and the vinyl monomer containing amino are respectively methyl-prop
Alkene acyloxyethyl Phosphorylcholine and 2- aminoethyl methacrylate hydrochlorides.
3. a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino according to claim 1, its feature
It is that in step one, the initiator is azodiisobutyronitrile.
4. a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino according to claim 1, its feature
It is that in step one, the polymerization solvent is ethanol and tetrahydrofuran mixed solution.
5. a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino according to claim 1, its feature
It is that in step one, the temperature of Raolical polymerizable is 60 DEG C~80 DEG C, and the time is 12h~24h.
6. a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino according to claim 1, its feature
It is that in step 2, polar solvent is water, methyl alcohol or ethanol.
7. a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino according to claim 1, its feature
It is that in step 2, the time of graft reaction is 10h~24h.
8. a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino according to claim 1, its feature
It is that in step 2, the consumption of sodium borohydride is 20%~200% of the phosphoryl choline polymer quality containing amino, reaction
Time is 2h~4h.
9. a kind of method that double Biomimetic Polymers are synthesized based on aldehyde radical and amino according to claim 1, its feature
It is that bag filter molecular cut off is 6000~8000.
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| CN108715644A (en) * | 2018-06-14 | 2018-10-30 | 西安科技大学 | A kind of preparation method of aldehyde radical and amino phosphoryl choline polymer bionic adhesion coating |
| CN108721704A (en) * | 2018-07-05 | 2018-11-02 | 四川大学 | It is a kind of to have both anticalciumization and the difunctional long-acting slow-release angiocarpy coating material and preparation method thereof of anti-proliferate |
| CN108939173A (en) * | 2018-07-05 | 2018-12-07 | 四川大学 | It is a kind of to have both anti-inflammatory and situ catalytic NO sustained release difunctional cardiovascular coating material and preparation method thereof |
| CN111793399A (en) * | 2020-07-21 | 2020-10-20 | 西安科技大学 | Preparation method of two phosphorylcholine coatings containing catechol, amino and carboxyl |
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| CN105670022A (en) * | 2016-02-25 | 2016-06-15 | 西安科技大学 | Preparation method of phosphorylcholine bionic coating |
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| CN108715644A (en) * | 2018-06-14 | 2018-10-30 | 西安科技大学 | A kind of preparation method of aldehyde radical and amino phosphoryl choline polymer bionic adhesion coating |
| CN108715644B (en) * | 2018-06-14 | 2021-07-30 | 西安科技大学 | Preparation method of aldehyde group and aminophosphorylcholine polymer bionic adhesion coating |
| CN108721704A (en) * | 2018-07-05 | 2018-11-02 | 四川大学 | It is a kind of to have both anticalciumization and the difunctional long-acting slow-release angiocarpy coating material and preparation method thereof of anti-proliferate |
| CN108939173A (en) * | 2018-07-05 | 2018-12-07 | 四川大学 | It is a kind of to have both anti-inflammatory and situ catalytic NO sustained release difunctional cardiovascular coating material and preparation method thereof |
| CN108721704B (en) * | 2018-07-05 | 2020-03-10 | 四川大学 | Long-acting sustained-release cardiovascular coating material with dual functions of calcification resistance and hyperplasia resistance and preparation method thereof |
| CN108939173B (en) * | 2018-07-05 | 2020-04-21 | 四川大学 | Bifunctional cardiovascular coating material with anti-inflammatory and in-situ catalytic NO sustained release functions and preparation method thereof |
| CN111793399A (en) * | 2020-07-21 | 2020-10-20 | 西安科技大学 | Preparation method of two phosphorylcholine coatings containing catechol, amino and carboxyl |
| CN113683787A (en) * | 2021-08-04 | 2021-11-23 | 华中科技大学同济医学院附属协和医院 | Hydrogel material with secondary crosslinking characteristic and preparation method and application thereof |
| CN113683787B (en) * | 2021-08-04 | 2023-07-21 | 华中科技大学同济医学院附属协和医院 | Hydrogel material with secondary crosslinking characteristic and preparation method and application thereof |
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