CN117143346A - Preparation method of anti-fouling antibacterial modified polymer on surface of cornea shaping mirror - Google Patents
Preparation method of anti-fouling antibacterial modified polymer on surface of cornea shaping mirror Download PDFInfo
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- 238000007493 shaping process Methods 0.000 title claims abstract description 47
- 210000004087 cornea Anatomy 0.000 title claims abstract description 46
- 229920000642 polymer Polymers 0.000 title claims abstract description 44
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 41
- 230000003373 anti-fouling effect Effects 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical group CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000006087 Silane Coupling Agent Substances 0.000 claims abstract description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 15
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- 238000012986 modification Methods 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 11
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- 230000001678 irradiating effect Effects 0.000 claims description 8
- KTALPKYXQZGAEG-UHFFFAOYSA-N 2-propan-2-ylthioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC(C(C)C)=CC=C3SC2=C1 KTALPKYXQZGAEG-UHFFFAOYSA-N 0.000 claims description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 4
- 238000002390 rotary evaporation Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 230000010355 oscillation Effects 0.000 claims description 2
- 241000894006 Bacteria Species 0.000 abstract description 31
- 230000006870 function Effects 0.000 abstract description 13
- 229920002845 Poly(methacrylic acid) Polymers 0.000 abstract description 10
- 108090000623 proteins and genes Proteins 0.000 abstract description 9
- 102000004169 proteins and genes Human genes 0.000 abstract description 9
- 230000003115 biocidal effect Effects 0.000 abstract description 4
- 238000002715 modification method Methods 0.000 abstract description 4
- 230000001105 regulatory effect Effects 0.000 abstract description 4
- 230000001276 controlling effect Effects 0.000 abstract description 2
- 229920000656 polylysine Polymers 0.000 abstract description 2
- QKPKBBFSFQAMIY-UHFFFAOYSA-N 2-ethenyl-4,4-dimethyl-1,3-oxazol-5-one Chemical compound CC1(C)N=C(C=C)OC1=O QKPKBBFSFQAMIY-UHFFFAOYSA-N 0.000 abstract 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 abstract 1
- ILOJFJBXXANEQW-UHFFFAOYSA-N aminooxy(phenyl)borinic acid Chemical compound NOB(O)C1=CC=CC=C1 ILOJFJBXXANEQW-UHFFFAOYSA-N 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 51
- 230000001580 bacterial effect Effects 0.000 description 16
- 239000010410 layer Substances 0.000 description 15
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 12
- 230000010069 protein adhesion Effects 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 8
- 230000001954 sterilising effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 6
- 238000004659 sterilization and disinfection Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000036571 hydration Effects 0.000 description 4
- 238000006703 hydration reaction Methods 0.000 description 4
- 230000004379 myopia Effects 0.000 description 4
- 208000001491 myopia Diseases 0.000 description 4
- 208000035143 Bacterial infection Diseases 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000008055 phosphate buffer solution Substances 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000010065 bacterial adhesion Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 230000004438 eyesight Effects 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000001860 Eye Infections Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000037358 bacterial metabolism Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 239000007822 coupling agent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
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- 230000001419 dependent effect Effects 0.000 description 1
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- 230000007613 environmental effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 208000011323 eye infectious disease Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
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- 239000000203 mixture Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
Classifications
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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
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
- C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
- C08G81/024—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G
- C08G81/028—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G containing polyamide sequences
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
-
- G—PHYSICS
- G02—OPTICS
- G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
- G02C7/00—Optical parts
- G02C7/02—Lenses; Lens systems ; Methods of designing lenses
- G02C7/04—Contact lenses for the eyes
- G02C7/049—Contact lenses having special fitting or structural features achieved by special materials or material structures
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2300/00—Characterised by the use of unspecified polymers
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- General Chemical & Material Sciences (AREA)
- Treatments Of Macromolecular Shaped Articles (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
The invention relates to a preparation method of a modified polymer for resisting dirt and bacteria on the surface of a cornea shaping lens. A preparation method of a cornea shaping mirror surface anti-fouling and antibacterial modified polymer, wherein polymer molecules are grafted by poly (2-vinyl-4, 4-dimethyl-2-oxazolin-5-one) (PVDMA) inserted with poly (lysine) (LYS) and Poly (PMAA) inserted with amino phenylboronic acid (NBA); the poly (2-vinyl-4, 4-dimethyl-2-oxazoline-5-ketone) is also inserted with a silane coupling agent, wherein the silane coupling agent is 3-aminopropyl triethoxysilane (APTES), has two functions of regulating and controlling the antibiosis and resisting protein, solves the problem of quick consumption of the antibiosis agent, can respond according to the ocular surface microenvironment, and has simple modification method operation.
Description
Technical Field
The invention relates to the field of surface modification of cornea shaping mirrors, in particular to a preparation method of an anti-fouling antibacterial modified polymer on the surface of a cornea shaping mirror.
Background
At present, myopia has become a main cause of global vision impairment, and related myopia prevention and control means are also layered endlessly. The cornea shaping lens (also called OK lens) is a hard contact lens with reverse geometric structure and can effectively control 50% of myopia increment.
In recent years, as myopia gradually becomes lower in age and worse, cornea shaping lenses are widely used, but in clinical application, complications appear more in the wearing process of patients. Because the lens contacts the ocular surface for a long period of time, bacterial infection and protein adhesion are extremely easy to be caused. Among them, pseudomonas aeruginosa is one of the main pathogens causing eye infection during wearing, seriously affecting the vision health and quality of life of hundreds of millions of people, and even blinding. And secondly, the cornea surface is covered with a thin tear film which contains various substances such as lipid, protein and the like, so that protein precipitation of the lens is easy to form, the air permeability and comfort of the lens are reduced, the risk of ocular inflammation is increased, the normal service life of the lens is shortened, the shaping effect is influenced and the like.
Aiming at the problem, a corresponding cornea shaping mirror surface sterilization and protein adhesion resistance modification method exists at present. However, the methods have the disadvantages of complicated operation steps, high technical requirements, low preparation success rate and certain defects in practical application. Meanwhile, how to regulate and control the two functions of antibiosis and protein resistance and prevent the rapid consumption of the antibacterial agent is also a great difficulty in the surface antibiosis and antifouling modification process of the cornea shaping mirror.
Disclosure of Invention
The invention provides a preparation method of a cornea shaping mirror surface anti-fouling and antibacterial modified polymer, which has two functions of regulating and controlling antibacterial and anti-protein, solves the problem of rapid consumption of antibacterial agents, and can respond according to ocular surface microenvironment, and the modification method is simple to operate.
A preparation method of a cornea shaping mirror surface anti-fouling antibacterial modified polymer comprises the following steps:
(1) After carboxyl activation is carried out on MAA, the MAA and NBA are stirred and reacted for 12-24 hours in 5-10mL of acetonitrile; wherein, the mole ratio of MAA to NBA is 1-5: 1, wherein the mass of MAA and NBA is 0.2-1 g and 0.324g respectively;
(2) After acetonitrile is removed by rotary evaporation, dissolving the product in 1-10 mL of N, N-Dimethylformamide (DMF), adding MAA again, and uniformly mixing to obtain a MAA-NBA solution; the ratio of the amount of MAA to the molar amount of NBA in step (1) is 1 to 15:1, a step of;
(3) Adding 0.5-10ml of the MAA-NBA solution obtained in the step (2) into 1-10 ml of 2-Isopropyl Thioxanthone (ITX) DMF solution with the solute mass fraction of 10% -20%, and irradiating under ultraviolet light to polymerize the solution and generate a PMAA-NBA polymer with an active end;
(4) Adding 0.2-5 mL of DMF solution of VDMA with the solute volume fraction of 10% -20%, and irradiating under ultraviolet light to form covalent bond connection between the VDMA and the PMAA-NBA active end to obtain PVDMA-PMAA-NBA solution;
(5) Adding 1-10 mL of PBS solution with mass concentration of 100-500 mg/mL LYS into the PVDMA-PMAA-NBA solution obtained in the step 4, and carrying out oscillation reaction for 24-72 h to obtain PVDMA-PMAA-NBA-LYS solution;
(6) And (3) dropwise adding a NaOH solution into the PVDMA-PMAA-NBA-LYS solution obtained in the step (5) to adjust the pH to be alkaline, then adding APTES as a silane coupling agent, wherein the volume fraction of the APTES in the solution is 5% -20%, and reacting for 0.5-10 hours to obtain the PVDMA-PMAA-NBA-LYS-APTES solution, namely the anti-fouling and antibacterial modified polymer for the surface of the cornea shaping mirror.
Further, the MAA carboxyl groups in step 1 are activated as: after dissolution of MAA in acetonitrile, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) was added in a molar ratio of 1:1, stirring and reacting for 2-6 h at room temperature.
Further, in the steps 3 and 4, the ultraviolet irradiation time is 3-10 min.
Further, the reaction conditions in step 6 are: and (3) reacting at room temperature in a dark place and oscillating.
Further, the alkalinity in step 6 is ph=8.5.
Further, the method comprises the steps of: taking 3-10 mL PVDMA-PMAA-NBA-LYS-APTES solution, namely the multifunctional cornea shaping mirror surface anti-fouling and antibacterial modified polymer for cornea shaping mirror surface anti-fouling and antibacterial modification, and soaking the OK mirror in the solution for 2-4 h at room temperature to finish the cornea shaping mirror surface modification.
The invention has the beneficial effects that:
1. in the technical scheme, the contradiction between the simultaneous actions of the two strategies of resisting and killing is skillfully avoided by constructing the double-layer polymer molecular brush in the solution, and the double-layer polymer molecular brush has higher efficient protein adhesion resistance and long-acting antibacterial property compared with the traditional anti-killing combined polymer surface.
2. In the present solution, the polymer molecules are designed to have pH responsiveness. When bacterial infection occurs on the ocular surface, acidic substances generated by bacterial metabolism can cause a local environmental pH drop, the outer PMAA chains collapse in response, NBA captures bacteria and LYS is exposed to kill bacteria; after the bacteria are eliminated, the pH value is increased, the PMAA layer is restored to an expanded state, the killed bacteria are effectively desorbed, and the function of resisting protein adhesion is performed under normal physiological conditions. Compared with the traditional monolayer polymer surface, the intelligent response type polymer molecule can adjust the self behavior according to the change of the ocular surface microenvironment as required, and no additional human assistance is needed.
3. In the technical scheme, the PMAA super hydrophilic layer forms a compact hydration layer which can effectively prevent protein adhesion. Meanwhile, the inserted NBA can selectively capture harmful pathogenic bacteria such as pseudomonas aeruginosa and the like without damaging normal bacterial flora of eyes.
4. In the technical scheme, the bactericidal substance adopts natural biological metabolic product polylysine, has good biocompatibility and strong bactericidal performance, is a nutritional bacteriostat, and cannot damage corneal epithelial cells; meanwhile, under normal physiological conditions, the upper layer PMAA can effectively isolate LYS from other substances, avoid excessive consumption of LYS, ensure the long-acting antibacterial performance of the modified lens, and no additional bactericidal substances are needed in the use process.
5. In the technical scheme, the silane coupling agent is added to keep the reactive groups, so that convenience is provided for subsequent application on the surface of the OK mirror. The selected coupling agent APTES can be connected with PVDMA through the amino at one end, and the other end is hydrolyzed into silanol to react with the hydroxyl in the OK mirror to generate a covalent bond, so that the ordered arrangement of polymer molecules and the grafting stability on the surface of the OK mirror are ensured. The modification method is simple.
Drawings
FIG. 1 is a schematic diagram of the molecular structure of a polymer used in the preparation method of the anti-fouling and antibacterial modified polymer for the surface of a cornea shaping lens;
FIG. 2 is a schematic view of the surface modification structure of the cornea shaping lens according to the present invention;
FIG. 3 is a FTIR chart of example 1 of the present invention;
FIG. 4 (a) is a schematic diagram showing the anti-protein adhesion performance test of OK samples, and (b) is a schematic diagram showing the anti-protein adhesion performance test of OK-PVDMA-PMAA-NBA-LYS;
FIG. 5 (a) is a photograph representative of Pseudomonas aeruginosa in an OK sample in vitro antibacterial test, and (b) is a photograph representative of Pseudomonas aeruginosa in an OK-PVDMA-PMAA-NBA-LYS sample in vitro antibacterial test;
FIG. 6 (a) is a representative SEM photograph of Pseudomonas aeruginosa in OK sample in vitro bacterial capture experiments, (b) is a representative SEM photograph of Pseudomonas aeruginosa in OK-PVDMA-PMAA sample in vitro bacterial capture experiments, and (c) is a representative SEM photograph of Pseudomonas aeruginosa in OK-PVDMA-PMAA-NBA sample in vitro bacterial capture experiments.
Detailed Description
In order to further describe the technical means and effects adopted by the present invention for achieving the intended purpose, the following detailed description will refer to the specific implementation, structure, characteristics and effects according to the present invention with reference to the accompanying drawings and preferred embodiments.
Example 1
A preparation method of a cornea shaping mirror surface anti-fouling antibacterial modified polymer comprises the following steps:
1) To 5mL of analytically pure acetonitrile solution, 0.485g of EDC and 0.2g of MAA were added in a molar ratio of 1:1, reacting for 2 hours to finish the activation of MAA carboxyl; stirring and reacting with NBA in 5mL of acetonitrile for 12h; wherein, the molar ratio of MAA to NBA is 1:1, and the mass of MAA and NBA is 0.2g and 0.324g respectively;
2) After acetonitrile was removed by rotary evaporation, the product was dissolved in 1mL of N, N-Dimethylformamide (DMF), MAA was added again, and mixed well to give MAA-NBA solution; the ratio of the amount of MAA to the molar amount of NBA in step (1) is 1:1, a step of;
3) Taking 0.5mL of the MAA-NBA solution obtained in the step (2), adding 1mL of 2-Isopropyl Thioxanthone (ITX) DMF solution with the solute mass fraction of 10%, and irradiating under ultraviolet light to polymerize the solution and generate a PMAA-NBA polymer with an active end; the ultraviolet irradiation time is 3min;
4) Adding 0.2mL of DMF solution of VDMA with the solute volume fraction of 10%, and irradiating under ultraviolet light to form covalent bond connection between the VDMA and the active end of PMAA-NBA to obtain PVDMA-PMAA-NBA solution; the ultraviolet irradiation time is 3min;
5) Adding 1mL of LYS PBS solution with the mass concentration of 100mg/mL into the PVDMA-PMAA-NBA solution obtained in the step 4, and carrying out shake reaction for 24 hours to obtain PVDMA-PMAA-NBA-LYS solution;
6) Dropwise adding a NaOH solution into the PVDMA-PMAA-NBA-LYS solution obtained in the step (5) to adjust the pH to be alkaline, wherein the pH=8.5 is adopted in the embodiment, then APTES is added as a silane coupling agent, the volume fraction of the APTES in the solution is 5%, and the reaction is carried out for 0.5h under the following reaction conditions: reacting at room temperature in a dark place, and oscillating; obtaining PVDMA-PMAA-NBA-LYS-APTES solution, namely the anti-fouling and antibacterial modified polymer on the surface of the cornea shaping mirror.
The method for modifying the surface of the cornea shaping mirror by anti-fouling and antibacterial comprises the following steps:
3mL PVDMA-PMAA-NBA-LYS-APTES solution is taken, and the OK mirror is soaked in the solution for 2 hours at room temperature, so that the surface modification of the cornea shaping mirror can be completed.
As shown in the FTIR results of FIG. 3, OK-PVDMA-PMAA-NBA-LYS-APTES samples were at 1665cm -1 The c=n characteristic peak appears at the position, which indicates that the VDMA monomer is successfully grafted to the surface of the OK mirror; at 1530cm -1 The N-H characteristic peak appears, which indicates that the NBA and LYS monomers are successfully grafted on the surface of the OK mirror; 2400-3500 cm -1 An O-H characteristic peak appears at this point, indicating successful grafting of MAA monomer to the OK mirror surface.
OK mirror protein adhesion resistance test after cornea shaping mirror surface anti-fouling antibacterial modified polymer treatment
In order to study the protein adhesion resistance of the OK mirror treated by the anti-fouling and antibacterial modified polymer on the surface of the cornea shaping mirror, the surface adhesion area of the original OK mirror (OK) and the OK mirror (OK-PVDMA-PMAA-NBA-LYS) which is subjected to the solution modification are respectively tested when the OK mirror and the protein are incubated together. The samples were immersed in an equal amount of Bovine Serum Albumin (BSA) at a concentration of 50. Mu.g/mL and incubated at 37℃for 2h in the absence of light. As shown in FIG. 4, the surface of the OK-PVDMA-PMAA-NBA-LYS sample is not found to have fluorescence shown by the protein, and the anti-protein adhesion effect of the sample is remarkable compared with the original OK mirror.
OK mirror sterilization function test after cornea shaping mirror surface anti-fouling antibacterial modified polymer treatment
Gram negative bacteria Pseudomonas aeruginosa was selected as a representative test bacteria. The bacterial strain was grown in liquid medium at 37℃for 12h, then the bacteria were collected by centrifugation (3000 rpm,6 min) and washed three times with phosphate buffered saline. Redispersing the obtained bacteria in phosphate buffer solution, and regulating bacteria concentration by enzyme-labeled instrument to obtain 10 8 CFU•mL -1 Is a bacterial liquid.
And (3) dripping 10 mu L of bacteria on the surface of a sample (OK, OK-PVDMA-PMAA-NBA-LYS), co-culturing for 4 hours at 37 ℃, adding 3mL of phosphate buffer solution PBS, and performing ultrasonic treatment for 4 minutes to desorb bacteria adhered on the surface of the lens into the PBS. Bacterial-containing PBS was gradient diluted and plated, and after incubation at 37℃for 16h, photographed counts were performed.
As shown in FIG. 5, the agar plates of the original OK mirror sample are full of bacteria, which shows that the bacteria on the surface of the sample can be stored, and the agar plates of the OK-PVDMA-PMAA-NBA-LYS sample have no bacterial colony, because LYS kills all bacteria in the co-culture process, the sterilization rate can reach 99.9%.
OK mirror bacterial catching function test after cornea shaping mirror surface anti-pollution antibacterial modified polymer treatment
Gram negative bacteria Pseudomonas aeruginosa was selected as a representative test bacteria. The bacterial strain was grown in liquid medium at 37℃for 12h, then the bacteria were collected by centrifugation (3000 rpm,6 min) and washed three times with phosphate buffered saline. Redispersing the obtained bacteria in phosphate buffer solution, and regulating bacteria concentration by enzyme-labeled instrument to obtain 10 8 CFU.mL-1 bacterial liquid.
All the articles, samples (OK, OK-PVDMA-PMAA-NBA) were sterilized prior to the antimicrobial test. The samples are respectively immersed into the same amount of bacterial liquid, after the bacterial liquid is cultured for 6 hours at 37 ℃, the bacterial liquid is sucked away, the samples are washed by phosphate buffer saline PBS and ultrapure water, and then a proper amount of 4% tissue cell fixing liquid is added to fix the bacterial form for 3 hours. After the fixation, 30%, 50%, 70%, 90% and 100% gradient concentration alcohol was used for dehydration, and the sample was left to stand for 10min in each gradient, and then dried under vacuum, and the number of bacteria adhering to the surface of the sample was observed by a Scanning Electron Microscope (SEM).
As shown in FIG. 6, the OK-PVDMA-PMAA surface has no bacterial adhesion compared with the original OK mirror film, because the adhesion of bacteria on the sample is mostly dependent on partial proteins on the surface, so that the compact hydration layer formed by PMAA can prevent the adhesion of the bacteria while preventing the adhesion of the proteins; the surface bacterial adhesion quantity of OK-PVDMA-PMAA-NBA is obviously increased, which shows that NBA can effectively capture pseudomonas aeruginosa.
According to the analysis of the detection results of the OK mirror protein adhesion resistance test and the OK mirror sterilization function test, the PMAA protein adhesion resistance test shows that the effect is remarkable, LYS can effectively kill bacteria, and the two functions are combined organically through upper and lower layers. According to the analysis of the detection result of the OK mirror bacteria capturing function test, the NBA can effectively capture pseudomonas aeruginosa, increase the mutual contact between bacteria and sterilizing substances, and further improve the sterilizing effect of the molecular brush.
Specifically, in the technical scheme, the multifunctional cornea shaping lens surface anti-fouling and antibacterial modified polymer for cornea shaping lens surface anti-fouling and antibacterial modification is synthesized by selecting corresponding substances, adjusting raw material formulas, optimizing production process and the like, and when the multifunctional cornea shaping lens surface anti-fouling and antibacterial modified polymer is used, the surface modification can be completed by only immersing the lens in the solution for 2 hours, so that the multifunctional cornea shaping lens surface anti-fouling and antibacterial modified polymer is rapid in reaction, simple to operate and high in practical value. In the scheme, the pH responsive polymer molecular brush is constructed to realize organic combination of multiple functions, and the selected PMAA super-hydrophilic layer can form a compact hydration layer in the subsequent application process, so that the adhesion of proteins is effectively resisted; meanwhile, under the condition that the bacterial quantity is too small and the pH value of the ocular surface is not changed, the hydration layer can also prevent partial bacteria from adhering, so that a great difficulty in the wearing process of the cornea shaping lens is solved, the protein deposition on the surface of the lens can be effectively reduced, the service life of the cornea shaping lens is prolonged, and the cornea shaping lens has higher practical value. In addition, NBA inserted in the outer layer can selectively capture harmful bacteria such as pseudomonas aeruginosa and is insensitive to normal flora of the ocular surface such as staphylococcus aureus, so that the ecological environment of the eyes is not disturbed.
Example 2
A preparation method of a cornea shaping mirror surface anti-fouling antibacterial modified polymer comprises the following steps:
1) To 10mL of analytically pure acetonitrile solution were added 0.97g of EDC, 0.4g of MAA in a molar ratio of 1:1, reacting for 6 hours to complete the activation of MAA carboxyl; stirring and reacting with NBA in 10mL of acetonitrile for 24h; wherein, the molar ratio of MAA to NBA is 5:1, and the mass of MAA and NBA is 1g and 0.324g respectively;
2) After acetonitrile is removed by rotary evaporation, the product is dissolved in 10mL of N, N-Dimethylformamide (DMF), MAA is added again, and the mixture is uniformly mixed to obtain MAA-NBA solution; the ratio of the amount of MAA to the molar amount of NBA in step (1) was 15:1, a step of;
3) Taking 10mL of the MAA-NBA solution obtained in the step (2), adding 10mL of 2-Isopropyl Thioxanthone (ITX) DMF solution with the solute mass fraction of 20%, and irradiating under ultraviolet light to polymerize the solution and generate a PMAA-NBA polymer with an active end; the ultraviolet irradiation time is 10min;
4) Adding 5mL of DMF solution of VDMA with the solute volume fraction of 20%, and irradiating under ultraviolet light to form covalent bond connection between the VDMA and the active end of PMAA-NBA to obtain PVDMA-PMAA-NBA solution; the ultraviolet irradiation time is 10min;
5) Adding 10mL of LYS PBS solution with the mass concentration of 500mg/mL into the PVDMA-PMAA-NBA solution obtained in the step 4, and carrying out shake reaction for 72h to obtain PVDMA-PMAA-NBA-LYS solution;
6) Dropwise adding a NAOH solution into the PVDMA-PMAA-NBA-LYS solution obtained in the step (5) to adjust the pH to be alkaline, wherein the pH=8.5 is adopted in the embodiment, then APTES is added as a silane coupling agent, the volume fraction of the APTES in the solution is 20%, and the reaction is carried out for 10 hours under the following conditions: reacting at room temperature in a dark place, and oscillating; obtaining PVDMA-PMAA-NBA-LYS-APTES solution, namely the anti-fouling and antibacterial modified polymer on the surface of the cornea shaping mirror.
The method for modifying the surface of the cornea shaping mirror by anti-fouling and antibacterial comprises the following steps:
10mL PVDMA-PMAA-NBA-LYS-APTES solution is taken, and the OK mirror is soaked for 4 hours under the room temperature condition, so that the surface modification of the cornea shaping mirror can be completed.
The OK mirror treated by the anti-fouling and antibacterial polymer solution on the surface of the cornea shaping mirror can realize good bacteria capturing, sterilization and protein adhesion resistance. Under normal physiological conditions, the surface of the lens has an anti-protein adhesion function, and protein adhesion can not occur on the surface of the lens after the modified OK mirror is co-cultured with the protein solution. When bacterial infection occurs on the ocular surface, the local pH is reduced, and the upper layer of the polymer molecular brush is subjected to responsive collapse, so that NBA capture bacteria are exposed, inner antibacterial substances kill bacteria, and the sterilization performance is good. When all the bacteria on the surface are killed, the pH value can be recovered to be normal, the upper layer of the molecular brush is recovered to be in an expanded state, and the killed bacteria are successfully desorbed and continue to play the function of resisting protein adhesion. The p H responsive outer layer regulates the self behavior, so that the reversible conversion of the anti-killing function is realized.
The present invention is not limited to the above embodiments, but is capable of modification and variation in detail, and other modifications and variations can be made by those skilled in the art without departing from the scope of the present invention.
Claims (6)
1. The preparation method of the anti-fouling and antibacterial modified polymer on the surface of the cornea shaping mirror is characterized by comprising the following steps:
(1) After carboxyl activation is carried out on MAA, the MAA and NBA are stirred and reacted for 12-24 hours in 5-10mL of acetonitrile; wherein, the mole ratio of MAA to NBA is 1-5: 1, wherein the mass of MAA and NBA is 0.2-1 g and 0.324g respectively;
(2) After acetonitrile is removed by rotary evaporation, dissolving the product in 1-10 mL of N, N-Dimethylformamide (DMF), adding MAA again, and uniformly mixing to obtain a MAA-NBA solution; the ratio of the amount of MAA to the molar amount of NBA in step (1) is 1 to 15:1, a step of;
(3) Adding 0.5-10ml of the MAA-NBA solution obtained in the step (2) into 1-10 ml of 2-Isopropyl Thioxanthone (ITX) DMF solution with the solute mass fraction of 10% -20%, and irradiating under ultraviolet light to polymerize the solution and generate a PMAA-NBA polymer with an active end;
(4) Adding 0.2-5 mL of DMF solution of VDMA with the solute volume fraction of 10% -20%, and irradiating under ultraviolet light to form covalent bond connection between the VDMA and the PMAA-NBA active end to obtain PVDMA-PMAA-NBA solution;
(5) Adding 1-10 mL of PBS solution with mass concentration of 100-500 mg/mL LYS into the PVDMA-PMAA-NBA solution obtained in the step 4, and carrying out oscillation reaction for 24-72 h to obtain PVDMA-PMAA-NBA-LYS solution;
(6) And (3) dropwise adding a NAOH solution into the PVDMA-PMAA-NBA-LYS solution obtained in the step (5) to adjust the pH to be alkaline, then adding APTES as a silane coupling agent, wherein the volume fraction of the APTES in the solution is 5% -20%, and reacting for 0.5-10 hours to obtain the PVDMA-PMAA-NBA-LYS-APTES solution, namely the anti-fouling and antibacterial modified polymer on the surface of the cornea shaping mirror.
2. The method for preparing the modified polymer for anti-fouling and antibacterial treatment of the surface of a cornea-shaped mirror according to claim 1, wherein the MAA carboxyl group in the step 1 is activated as follows: after dissolution of MAA in acetonitrile, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) was added in a molar ratio of 1:1, stirring and reacting for 2-6 h at room temperature.
3. The method for preparing the anti-fouling and antibacterial modified polymer on the surface of the cornea shaping mirror as set forth in claim 1, wherein in the steps 3 and 4, the ultraviolet irradiation time is 3-10 min.
4. The method for preparing the modified polymer for anti-fouling and antibacterial treatment of the surface of the cornea shaping lens according to claim 1, wherein the reaction conditions in the step 6 are as follows: and (3) reacting at room temperature in a dark place and oscillating.
5. The method for preparing the modified polymer for anti-fouling and antibacterial treatment of a surface of a cornea-shaping lens according to claim 1, wherein the alkalinity in the step 6 is ph=8.5.
6. A method for the anti-fouling and antibacterial modification of the surface of a cornea shaping lens using the solution of claim 1, comprising: and 3-10 mL PVDMA-PMAA-NBA-LYS-APTES solution, namely the anti-fouling and antibacterial modified polymer on the surface of the cornea shaping mirror, is taken, and the OK mirror is soaked in the solution for 2-4 hours at room temperature, so that the surface modification of the cornea shaping mirror can be completed.
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