CN104804195A - Mussel-adhered and cytomembrane antifouling double-bionic multi-armed PEG and preparation method thereof - Google Patents
Mussel-adhered and cytomembrane antifouling double-bionic multi-armed PEG and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a catechol Mytilopsis-adhered and amphion-like extracellular membrane structured double-bionic modified multi-armed PEG as shown in the general structural formula (I) and a preparation method thereof. By a simple direct coating mode such as dispensing, spraying, dip-coating or spin-coating, etc. of the PEG, a multi-armed polyethylene glycol flexible chain and amphion-like extracellular membrane structured double anti-biopollution surface is constructed on the surface of various polydopamine-mediated base materials. Due to a branching structure and multiple modifiable ends of the bionic modified multi-armed PEG, it brings the possibility to prepare a functional polymer with multiple functional groups and regulable proportion. As the polydopamine with ultrastrong adhesion is used as a mediation layer, a compact and stable double anti-biopollution coating can still be formed on the surface of almost any base materials on the condition that content of catechol in the multifunctional multi-armed PEG is limited.
Description
Technical field
The present invention relates to the preparation method of the adhesion of a kind of mussel and the two bionical multi-arm PEG of cytolemma anti-soil and use it for the application that various substrate surface builds stable against biological contamination coating, belonging to the process for modifying surface field of biological medical polymer material.
Background technology
In the last few years, the series of problems such as thrombus, inflammation, infection caused due to biological pollutants such as protein, cell, bacteriums seriously limits the clinical application of various biomaterial, therefore, the effective biological pollution problem solving biomaterial surface is vital.At present, the structure on conventional simple stable against biological contamination surface mainly carries out surface modification to existing bio-medical material, namely basad material surface is coated with the coating of antifouling effect, realizes stable against biological contamination (Y. Arima by control inerface
et al.
adv. Polym. Sci. 2012, 247,167; R. Yang,
et al.
soft Matter 2012, 8,31; S. R. Meyers,
et al.
chem. Rev. 2012, 112,1615.).
In the molecule of numerous structure anti-pollution layers, polyoxyethylene glycol (PEG) receives much concern.Because it has large volume-exclusion effect, flexible PEG chain can free movement, effectively stops the direct surface in contacts of biological pollutant such as protein; Superpower hydration layer can be formed simultaneously, suppress the generation of protein adsorption and sex change in simplified reaction, and then the series of problems that suppression causes thus (M. Heuberger,
et al.
biophys. J. 2005, 88,495.).But, the stable against biological contamination effect of PEG and its be closely-related in the coverage density of substrate surface, directly traditional strand PEG is fixed to material surface and is difficult to reach higher surface coverage.This just makes the research utilizing multi-arm PEG to carry out surface modification get more and more.Multi-arm PEG has plurality of advantages, and first the structure of its branching can realize high surface density, effectively improves the stable against biological contamination ability of coating; Secondly, multiple end group provides more reaction site and carries out modification to it, makes its multifunction.
Phosphorylcholine is the terminal hydrophilic group of composition cytolemma elementary cell, in okioplast film, account for critical role.Phosphorylcholine is simultaneously with positive and negative two kinds of electric charges, and this zwitter-ion group can form very firmly hydration layer with water molecules; Surface can be enriched to by Spontaneous migration in water surrounding, form the surface of imitating cell outer-layer membrane structure.The structure being similar to extracellular tunic with Phosphorylcholine amphoteric ion polymer is analogized to the mechanism realizing stable against biological contamination, and sulphonic acid betaine and carboxylic acid beet alkali ampholytic ionic group also can realize the antifouling effect of imitating cell outer-layer membrane structure.Separately there are some researches show, Phosphorylcholine and PEG have in anti-protein absorption and platelet adhesion reaction synergistic effect (M. Tanaka,
et al.
tetrahedron Lett. 2009,
50, 4092; Y. Iwasaki,
et al.
biomaterials 2003,
24, 3599.), therefore be expected at zwitter-ion groups such as the introducing of multi-arm PEG end Phosphorylcholine, sulphonic acid betaine and carboxylic acid trimethyl-glycines the surface obtaining a kind of antibiosis pollution effects brilliance.
Summary of the invention
Main purpose of the present invention is to provide a kind of can adhesion and the structure of cytolemma anti-soil pair bionical multi-arm PEG, this multi-arm PEG branching effectively can solve the low problem of coating density in the mussel of various material surface by spontaneous adhesion; The catechol group of peg moiety end, by the modes such as hydrophobic interaction, coordination, oxypolymerization and the almost spontaneous combination of various substrate surface, makes the polymeric coating of highly-hydrophilic be fixed up at material surface; The zwitter-ion group of part arm terminal graft, due to the hydratability that himself is superpower, coatingsurface can be enriched to by Spontaneous migration under water surrounding, form the surface being similar to cell outer-layer membrane structure, the basis of polyoxyethylene glycol is formed the second layer opposing barrier to biological pollutant, forms the surface of zwitter-ion and the dual stable against biological contamination of polyoxyethylene glycol; Part arm end also can grafting folic acid functional group, makes its greater functionality.
Another object of the present invention is to provide the preparation method of above-mentioned two bionical multi-arm PEG.
Implementation procedure of the present invention is as follows:
Polymkeric substance shown in general structure (I),
Wherein, m to be 1,1.5 or 2, n be 20 ~ 100 positive integer;
R
1~ R
4independently selected from the pyrocatechol base shown in structural formula (II), the Phosphorylcholine base shown in structural formula (III), sulphonic acid betaine base, carboxylic acid beet base, the folic acid shown in general structure (IV) derives small molecules group,
, a is the positive integer of 1 ~ 5;
X is the positive integer of 5 ~ 30, and y is the positive integer of 1 ~ 10, and z is the positive integer of 1 ~ 6, and wherein the molar content of x monomer is the molar content of 80% ~ 90%, y monomer is 10% ~ 20%;
。
Above-mentioned R
1~ R
4in functional group, group molar content 20 ~ 90% is pyrocatechol base, and 10 ~ 80% is Phosphorylcholine, sulphonic acid betaine or carboxylic acid beet base, and 0 ~ 15% derives small molecules group for folic acid.
The preparation method of the polymkeric substance shown in general structure (I): by amino or the hydroxyl of multi-arm PEG end, in the mode of amido linkage or ester bond by R
1~ R
4functional group small molecules or oligopolymer be grafted to its arm end.
The application of polymkeric substance shown in general structure (I) in preparation stable against biological contamination coating.Specifically, being polymkeric substance is dissolved in pH 7 ~ 8.5 aqueous solution or moisture organic solvent, being coated with dripping, spraying, dip-coating or spin coating mode make polymkeric substance in the coating being formed evenly coating by decorative material or tool face.
Need that the substrate surface of modification is first coated with dripping, spraying, dip-coating or spin coating mode apply poly-DA Mediated coating, then coated structure leads to the polymkeric substance shown in formula I, and described base material is glass, stainless steel, polyvinyl chloride, polycarbonate, polypropylene, tetrafluoroethylene, titanium dioxide, metal.In order to improve the stability of polymkeric substance at substrate surface, to the sheet base after coated polymer air mutually in heat treated 1 ~ 24 h in 90 ~ 150 ° of C temperature ranges, make the catechol group in polymer molecule oxidation cross-linked, form stable polymeric coating.Coating soaks 0.5 ~ 24 h in the water of room temperature to 90 ° C temperature range, the hydrophilic radical in polymer architecture is made to move orientation to coatingsurface, form imitating cell outer-layer membrane structure hydrophilic coating, make Static water contact angles within the scope of 30 ~ 52 °, protein adsorption reduces 70 ~ 98%, and bacterial adhesion reduces 90 ~ 99%.
Advantage of the present invention: 1) select the multi-arm PEG with branched structure as research object, imitate the several functions groups such as the zwitter-ion of cytolemma anti-soil, the imitative pyrocatechol of mussel adhesion, the folic acid of target at its arm terminal graft, prepare a series of function, the regulatable multi-arm PEG of ratio; 2) the two biomimetic modification multi-arm PEG coating formation polyoxyethylene glycol flexible chain of pyrocatechol and zwitter-ion and zwitter-ion imitating cell outer-layer membrane structure double barrier, produce significant inhibition to biological pollutant; 3) the poly-Dopamine HCL that will have a Ultrastrength adhesive performance, as mediation layer, in multi-functional multi-arm PEG when pyrocatechol restricted levels, still can form fine and close polymeric coating at almost any substrate surface.
Accompanying drawing explanation
Fig. 1 is eight arm PEG grafting Phosphorylcholine oligopolymer, pyrocatechol and the micromolecular synthesis path of folic acid;
Fig. 2 is that the 1H-NMR spectrogram of two biomimetic modification multi-arm PEG (is specially: (catechol)
6.5-g-PEG-g-(PMN)
1.5, solvent: D
2o);
Fig. 3 be two biomimetic modification multi-arm PEG before modified after the static contact angle figure on gold plaque surface;
Fig. 4 be two biomimetic modification multi-arm PEG before modified after the atomic force microscope 2D shape appearance figure on gold plaque surface;
Fig. 5 be two biomimetic modification multi-arm PEG before modified after the XPS spectrogram entirely on gold plaque surface;
Fig. 6 is two biomimetic modification multi-arm PEG rear gold plaque surface protein absorption SPR figure before modified;
Fig. 7 is two biomimetic modification multi-arm PEG rear gold plaque surface platelet adhesion reaction scanning electron microscope (SEM) photograph before modified;
Fig. 8 is two biomimetic modification multi-arm PEG rear gold plaque surface before modified
e.colibacterial adhesion shows fluorescent microscopy images.
Embodiment
The imitative mussel attachment proteins of synthesis and the two bionical multi-arm PEG of membrane structure comprise 4 steps:
1) Phosphorylcholine of reactive behavior, the preparation of the zwitter-ion oligopolymer such as sulphonic acid betaine or carboxylic acid trimethyl-glycine;
2) introduce containing zwitter-ion oligopolymer at multi-arm peg moiety arm end with amido linkage or ester bond mode;
3) by amide condensed or ester condensation reaction, the catechol group with adhesion function is introduced at multi-arm peg moiety arm end;
4) also folic acid functional molecular can be introduced at multi-arm peg moiety arm end with amido linkage or ester bond mode.By 1H NMR, GPC and UV-Vis, structural characterization is carried out to the two biomimetic modification multi-arm PEG obtained, determine the Grafting Content of each several part group.
Build poly-DA Mediated layer: be dissolved in by dopamine hydrochloride in the mixing solutions of pH 7 ~ 8.5 aqueous solution or the organic solvent such as water and ethanol, methyl alcohol, Virahol or tetrahydrofuran (THF), the blending ratio of water and organic solvent is 1/0 ~ 1/1, and concentration is 0.1 ~ 5 mg/mL.Be coated with by dripping, spraying, dip-coating or spin coating mode be coated to the common used material surfaces such as glass, stainless steel, polyvinyl chloride, polycarbonate, polypropylene, tetrafluoroethylene, titanium dioxide, metal, form stable poly-DA Mediated layer by the polyreaction of Dopamine HCL self.
Build the two biomimetic modification multi-arm PEG anti-pollution layer of mussel attachment proteins and cytolemma: two biomimetic modification multi-arm PEG of preparation are dissolved in pH 7 ~ 8.5 aqueous solution or water and ethanol, methyl alcohol, Virahol, tetrahydrofuran (THF), acetonitrile, dimethyl sulfoxide (DMSO) or N, in the mixed solvent of dinethylformamide etc., concentration is 0.5 ~ 5 mg/mL.By dip-coating, drip be coated with, the substrate surface of mode after poly-DA Mediated of spin coating or spraying evenly apply two biomimetic modification multi-arm PEG.Coating is heat treated 1 ~ 24 h in 90 ~ 150 ° of C temperature ranges, makes the catechol group in polymer molecule oxidation cross-linked, forms stable polymeric coating.After recovering room temperature, drip washing adheres to unstable polymer molecule to remove.Method in reference literature (S. Yang,
et al.J. Biomed. Mater. Res., Part A 2008,
84, 837; N. Hao,
et al.
j. Biomed. Mater. Res., Part A,
2014,
102, 2972.) and to be immersed in from room temperature 0.5 ~ 24 h to the water of 90 ° of C temperature ranges, hydrophilic regulation and control are carried out to coating, makes spontaneous the moving of zwitter-ion group in polymer architecture, form imitating cell outer-layer membrane structure hydrophilic coating.
Embodiment 1
Oligopolymer preparation method containing p-nitrophenyl oxygen formyl active ester group and Phosphorylcholine group is as follows: the preparation of reference literature method (K. Ishihara,
et al.
polym. J. 1990,
22, 355; T. Konno,
et al.
biomacromolecules 2004,
5, 342.) and 2-methylacryoyloxyethyl Phosphorylcholine (MPC) and p-nitrophenyl oxygen formyl (gathering) glycolmethacrylate (NPEM).By " starvation method " of bibliographical information (A .L. Lewis,
et al.
biomaterials 2000,
21, 1847.) and synthesize free radical randomcopolymer p (MPC-co-NPEM), be called for short PMN.Detailed process is as follows: in 250 mL three-necked bottles, adds 15 mL ethanol and 0.006 g 2,2'-Azobis(2,4-dimethylvaleronitrile) (ABVN), dress prolong, is heated to 65 ° of C and logical N
2oxygen in 30 min removing systems.Take 5.113 g MPC, 1.271 g NPEM and 0.058 g initiator 2,2'-Azobis(2,4-dimethylvaleronitrile) (ABVN) in 500 mL round-bottomed flasks, add 200 mL drying ethanols and 6 mL tetrahydrofuran (THF)s, proceed in constant pressure funnel after making it fully dissolve.Induction stirring, N
2under protection, the mixing solutions of monomer and initiator is added drop-wise in three-necked bottle, drips, change enclosed system into.React 24 h to stop.React that reaction solution is loaded molecular weight cut-off is in the dialysis tubing of 3500, carried out dialysis 2 days with pH 3-4 buffered soln.White solid is obtained after lyophilize.1H NMR test result show the molar content of MPC and NPEM be respectively 75% and 25%, GPC record the molecular weight (M of polymkeric substance
w) be about 5000 g/mol.
Embodiment 2
Oligopolymer preparation method containing p-nitrophenyl oxygen formyl active ester group and sulphonic acid betaine group is as follows: the free radical randomcopolymer p (SBMA-co-NPEM) having been synthesized 2-methylacryoyloxyethyl sulphonic acid betaine (SBMA) and p-nitrophenyl oxygen formyl (gathering) glycolmethacrylate (NPEM) by " starvation method ", is called for short PSN.Detailed process is as follows: in 250 mL three-necked bottles, adds 10 mL ethanol and 0.003 g 2,2'-Azobis(2,4-dimethylvaleronitrile) (ABVN), dress prolong, is heated to 65 ° of C and logical N
2oxygen in 30 min removing systems.Take 2.295 g SBMA, 0.636 g NPEM and 0.029 g initiator A BVN in 500 mL round-bottomed flasks, add 100 mL drying ethanols and 6 mL tetrahydrofuran (THF)s, proceed in constant pressure funnel after making it fully dissolve.Induction stirring, N
2under protection, the mixing solutions of monomer and initiator is added drop-wise in three-necked bottle, drips, change enclosed system into.React 24 h to stop.React that reaction solution is loaded molecular weight cut-off is in the dialysis tubing of 3500, carried out dialysis 2 days with pH 3-4 buffered soln.White solid is obtained after lyophilize.1H NMR test result show the molar content of SBMA and NPEM be respectively 81% and 19%, GPC record the molecular weight (M of polymkeric substance
w) be about 4500 g/mol.
Embodiment 3
The preparation method of eight arm peg moiety arm terminal graft Phosphorylcholine oligopolymer: take 0.500 g PEG-(NH
2)
8be dissolved in 50 mL round-bottomed flasks with 40 mL ethanol/TEA and 3 mL distilled water mixing solutionss (pH 6.5-7.0), immerse under being preheated to the oil bath magnetic agitation of 60 ° of C, by 0.376 g PMN polymkeric substance with after 20 mL dissolve with ethanol, be added drop-wise in three-necked bottle, drip, react 22 h.Be the small molecules of dialysis tubing except dereaction generation and the lower molecular weight (M of non-grafting of 12000 with molecular weight cut-off after stopped reaction
w~ 5000 g/mol) polymer P MN, the NaOH aqueous solution being about 9 with pH is that extracellular fluid dialysis to yellow is taken off (unreacted active ester group is hydrolyzed), then is transitioned into distilled water, and the specific conductivity to extracellular fluid dialysis is basically identical with distillation electrical conductivity of water.Namely lyophilize obtains eight arm PEG of part arm terminal graft PMN phosphoryl choline polymer.The 1H NMR of Fig. 2 confirms that PMN is successfully grafted to the part arm end of eight arm PEG, by the change of molecular weight that GPC before and after grafting PMN measures, calculate about 1.5 mol PMN and be grafted to 1 mol eight arm PEG arm end, then this polymkeric substance can be expressed as PEG-g-(PMN)
1.5-(NH
2)
6.5.
Embodiment 4
The preparation method of Fig. 1 eight arm peg moiety arm terminal graft catechol group (catechol) and folic acid (FA) molecule: in 50 mL three-necked bottles, take 3, (0. 039 g) for 4-dihydroxy-benzene propionic acid (DHPA), FA(0.022 g), HOBt(0.057 g) and triethylamine (0.054 g), disperseed under the methylene dichloride of 1:1 and DMF mixing solutions magnetic agitation by 3.5 mL volume ratios, logical N
2, ice-water bath priming reaction 1 h; Take HBTU(0.080 g) disperseed with 3 mL methylene dichloride after, proceed in three-necked bottle, continue logical N
2ice-water bath activates 2 h; Take PEG-g-(PMN) prepared by 0.4125 g embodiment 3
1.5-(NH
2)
6.5, be dissolved in the methylene dichloride and DMF mixing solutions that 20 mL volume ratios are 1:1, be added dropwise in three-necked bottle by dropping funnel, about 1 h adds.Continue logical N
2, ice-water bath reaction about 3 h.Recover room temperature reaction 24 h afterwards, before stopped reaction, add glacial acetic acid (2.0 mL) and make system be acid state (dripping below immersed in liquid level), in order to avoid cause the oxidation of catechol group in last handling process.Suction filtration removing solid impurity, instills filtrate in ether and precipitates ,-20 DEG C of hold over night.Incline supernatant liquor, load in 3500 dialysis tubings after precipitation is dissolved with 30 mL methylene dichloride, successively with ethanol, ethanol/pH=2-3 mixing solutions, pH=2-3 buffered soln for dialysis medium removing impurity, namely lyophilize obtains 8 arm PEG of the two biomimetic modification of pyrocatechol, Phosphorylcholine and folic acid.1H NMR test result confirms that pyrocatechol and folic acid are successfully grafted to eight arm PEG ends; GPC result shows that the molecular weight of this pair of biomimetic modification eight arm PEG is 22000 g/mol; Measured the working curve of DHPA and folic acid under the ultraviolet light absorption angle value at 280 nm and 360 nm places and the same terms by UV-Vis, calculate 1 mol PEG-g-(PMN)
1.5-(NH
2)
6.5upper grafting 5.91 mol catechol and 0.47 mol FA, then this polymkeric substance can be expressed as (catechol)
6.0-g-PEG-g-(PMN)
1.5-(FA)
0.5.
Embodiment 5
The structure of poly-DA Mediated layer: be dissolved in by dopamine hydrochloride in Tris-HCl (pH 8.5) buffered soln, compound concentration is the solution of 2 mg/mL.Room temperature, air mutually in, by 2 × 2 cm
2gold plaque is immersed in 24 h in above-mentioned solution, makes Dopamine HCL spontaneous adhesion be aggregated to sheet primary surface.Use distilled water drip washing 5 times after taking out sheet base, after naturally drying, obtain poly-Dopamine HCL coating.Static contact angle is changed to 68.2 ± 2.0 ° (as shown in Figure 3) by 101.1 ± 0.5 ° of naked gold plaque; The sheet base AFM 2D shape appearance figure generation obviously change (as shown in Figure 4) that poly-Dopamine HCL is modified; Occur obvious N peak (as shown in Figure 5) during XPS composes entirely, these data all prove that gold plaque surface defines poly-Dopamine HCL coating.
Embodiment 6
The structure of pyrocatechol and the two bionical multi-arm PEG anti-pollution layer of Phosphorylcholine: the antifouling property preferably two bionical multi-arm PEG((catechol by preparation in embodiment 4)
6.5-g-PEG-g-(PMN)
1.5) to be dissolved in volume ratio be in the aqueous ethanolic solution of 1:1, is mixed with the polymers soln that concentration is 5 mg/mL; After it fully dissolves, pipette 40 μ L polymers solns with micropipet drip the poly-DA Mediated gold plaque primary surface being coated in preparation in embodiment 5 uniformly, cold wind dries up; Air mutually in, in 100 ° of C baking ovens, heat 12 h, make the catechol group in polymer architecture occur oxidation cross-linked fully; Recover room temperature, after drip washing sheet primary surface 5 times, modified sheet base is immersed in 30 min in 80 ° of C water, polymeric coating is occurred surface that regulation and control form surface enrichment hydrophilic radical.As Fig. 3 shows, pyrocatechol and the two bionical multi-arm PEG((catechol of Phosphorylcholine)
6.5-g-PEG-g-(PMN)
1.5) gold plaque static contact angle after coating is reduced to 47.0 ± 1.0 ° further; The shape characteristic (Fig. 4) that size is larger is there is in AFM 2D height map; In Fig. 5 there is Phosphorylcholine P peak in entirely composing in corresponding XPS, and all the two biomimetic modification multi-arm PEG of sufficient proof is successfully fixed to the gold plaque primary surface of poly-DA Mediated.
Embodiment 7
Two biomimetic modification multi-arm PEG surfaces anti-protein absorption property is evaluated: by (catechol) of preparation in embodiment 6
6.5-g-PEG-g-(PMN)
1.5modified gold plaque base is installed on Reichert SR7500DC surface plasma body resonant vibration instrument.Take PBS7.4 as moving phase, under the flow velocity of 50 μ L/min, flow through surface plasma resonance instrument (SPR) chip surface, under 25 ° of C, obtain stable baseline.Under identical flow velocity, inject PBS7.4 solution 10 min of 1 mg/mL BSA or Fg, switch back PBS7.4 buffered soln afterwards, identical flow velocity undershoot is washed surface and is washed off by unstable for absorption protein, is drawn the protein quality of surface adsorption by the change calculations comparing PBS7.4 baseline before and after injection protein soln.Two bionical multi-arm PEG (catechol)
6.5-g-PEG-g-(PMN)
1.5before and after modification gold plaque, SPR adsorption curve such as Fig. 6 of BSA and Fg shows, compared with naked gold surface, the adsorptive capacity of modified surface to BSA is reduced to 98.7%, is reduced to 75.1% to the adsorptive capacity of Fg, shows significant anti-protein adsorption effect.
Embodiment 8
Two biomimetic modification multi-arm PEG surfaces antiplatelet adhesion property is evaluated: with preparation (catechol) in embodiment 6
6.5-g-PEG-g-(PMN)
1.5gold plaque base after modifying, carry out platelet attachment experiment to the gold plaque of blank, to be coated with poly-Dopamine HCL and poly-DA Mediated two biomimetic modification multi-arm PEG, result as shown in Figure 7.The blank gold plaque surface adhesion of SEM shooting has a large amount of thrombocytes, and thrombocyte occurs assemble and obvious deformation occurs; The thrombocyte amount that the modified gold plaque of poly-Dopamine HCL adheres to occurs obviously to reduce, and pattern is regular; The thrombocyte that gold surface after two biomimetic modification multi-arm PEG modifies almost does not adhere to.There is significant inhibition on surface after this result illustrates pyrocatechol and the two biomimetic modification of Phosphorylcholine to thrombocyte.
Embodiment 9
Two biomimetic modification multi-arm PEG surfaces anti-bacterial attachment performance evaluation: with the two biomimetic modification multi-arm PEG (catechol) of preparation in embodiment 6
6.5-g-PEG-g-(PMN)
1.5gold plaque base after modifying, it is 5 × 10 that gold plaque that is blank, that be coated with two biomimetic modification multi-arm PEG of poly-Dopamine HCL and poly-DA Mediated is immersed in concentration
7cells/mL Gram-E. coli (
e.coli) PBS solution in, cultivate 24 h under 37 ° of C, saturated humidity.After taking out sheet base, with PBS drip washing 5 times, wash away and adhere to unstable bacterium.Sheet primary surface drips the PBS solution of 30 μ L 2 μ L/mL Syto 9, and dark at room temperature dyes 20 min, and inverted fluorescence microscope observations as shown in Figure 8.Blank gold plaque surface is almost covered completely by bacterium; The amount of bacteria that the modified gold plaque of poly-Dopamine HCL adheres to occurs obviously to reduce; The bacterium that gold surface after two biomimetic modification multi-arm PEG modifies almost does not adhere to, reaches 99% to the anti-adhesion rate of bacterium.
Claims (9)
1. the polymkeric substance shown in general structure (I),
Wherein, m to be 1,1.5 or 2, n be 20 ~ 100 positive integer;
R
1~ R
4independently selected from the pyrocatechol base shown in structural formula (II), the Phosphorylcholine base shown in structural formula (III), sulphonic acid betaine base, carboxylic acid beet base, the folic acid shown in general structure (IV) derives small molecules group,
, a is the positive integer of 1 ~ 5;
X is the positive integer of 5 ~ 30, and y is the positive integer of 1 ~ 10, and z is the positive integer of 1 ~ 6, and wherein the molar content of x monomer is the molar content of 80% ~ 90%, y monomer is 10% ~ 20%;
。
2. polymkeric substance according to claim 1, is characterized in that: R
1~ R
4in functional group, group molar content 20 ~ 90% is pyrocatechol base, and 10 ~ 80% is Phosphorylcholine, sulphonic acid betaine or carboxylic acid beet base, and 0 ~ 15% derives small molecules group for folic acid.
3. the preparation method of polymkeric substance described in claim 1, is characterized in that: by amino or the hydroxyl of multi-arm PEG end, in the mode of amido linkage or ester bond by R
1~ R
4functional group small molecules or oligopolymer be grafted to its arm end.
4. the application of polymkeric substance described in claim 1 in preparation stable against biological contamination coating.
5. apply according to claim 4, it is characterized in that: polymkeric substance is dissolved in pH 7 ~ 8.5 aqueous solution or moisture organic solvent, being coated with dripping, spraying, dip-coating or spin coating mode make polymkeric substance in the coating being formed evenly coating by decorative material or tool face.
6. apply according to claim 4, it is characterized in that: need that the substrate surface of modification is first coated with dripping, spraying, dip-coating or spin coating mode apply poly-DA Mediated coating, then coated structure leads to the polymkeric substance shown in formula I.
7. apply according to claim 6, it is characterized in that: described base material is glass, stainless steel, polyvinyl chloride, polycarbonate, polypropylene, tetrafluoroethylene, titanium dioxide, metal.
8. apply according to claim 4, it is characterized in that: in order to improve the stability of polymkeric substance at substrate surface, to the sheet base after coated polymer air mutually in heat treated 1 ~ 24 h in 90 ~ 150 ° of C temperature ranges, make the catechol group in polymer molecule oxidation cross-linked, form stable polymeric coating.
9. apply according to claim 4, it is characterized in that: coating soaks 0.5 ~ 24 h in the water of room temperature to 90 ° C temperature range, the hydrophilic radical in polymer architecture is made to move orientation to coatingsurface, form imitating cell outer-layer membrane structure hydrophilic coating, make Static water contact angles within the scope of 30 ~ 52 °, protein adsorption reduces 70 ~ 98%, and bacterial adhesion reduces 90 ~ 99%.
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| CN115721786A (en) * | 2022-11-18 | 2023-03-03 | 杰美特涂层科技(厦门)有限公司 | Functional medical coating and preparation method thereof |
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