CN116284548B - Phosphorylcholine tetrapolymer with multiple self-turnover function, and preparation method and application thereof - Google Patents
Phosphorylcholine tetrapolymer with multiple self-turnover function, and preparation method and application thereof Download PDFInfo
- Publication number
- CN116284548B CN116284548B CN202310589903.7A CN202310589903A CN116284548B CN 116284548 B CN116284548 B CN 116284548B CN 202310589903 A CN202310589903 A CN 202310589903A CN 116284548 B CN116284548 B CN 116284548B
- Authority
- CN
- China
- Prior art keywords
- phosphorylcholine
- tetrapolymer
- methacrylate
- multiple self
- hydrophilic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229950004354 phosphorylcholine Drugs 0.000 title claims abstract description 55
- 229920006029 tetra-polymer Polymers 0.000 title claims abstract description 42
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 239000012620 biological material Substances 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 25
- ZSZRUEAFVQITHH-UHFFFAOYSA-N 2-(2-methylprop-2-enoyloxy)ethyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CC(=C)C(=O)OCCOP([O-])(=O)OCC[N+](C)(C)C ZSZRUEAFVQITHH-UHFFFAOYSA-N 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 24
- 239000011541 reaction mixture Substances 0.000 claims description 15
- NQSLZEHVGKWKAY-UHFFFAOYSA-N 6-methylheptyl 2-methylprop-2-enoate Chemical compound CC(C)CCCCCOC(=O)C(C)=C NQSLZEHVGKWKAY-UHFFFAOYSA-N 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims description 13
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 13
- 239000008367 deionised water Substances 0.000 claims description 9
- 229910021641 deionized water Inorganic materials 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 3
- OXJGJKIURHREKH-UHFFFAOYSA-O CC(=C)C(=O)OCCP(=O)=C(O)C[N+](C)(C)C Chemical compound CC(=C)C(=O)OCCP(=O)=C(O)C[N+](C)(C)C OXJGJKIURHREKH-UHFFFAOYSA-O 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- 125000001165 hydrophobic group Chemical group 0.000 abstract description 14
- 229920000642 polymer Polymers 0.000 abstract description 10
- 230000003993 interaction Effects 0.000 abstract description 2
- YHHSONZFOIEMCP-UHFFFAOYSA-N 2-(trimethylazaniumyl)ethyl hydrogen phosphate Chemical compound C[N+](C)(C)CCOP(O)([O-])=O YHHSONZFOIEMCP-UHFFFAOYSA-N 0.000 description 47
- 229920001577 copolymer Polymers 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- 230000002209 hydrophobic effect Effects 0.000 description 16
- 210000003813 thumb Anatomy 0.000 description 15
- 230000000694 effects Effects 0.000 description 12
- 239000000463 material Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 7
- 239000000693 micelle Substances 0.000 description 7
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 239000000178 monomer Substances 0.000 description 5
- 150000003904 phospholipids Chemical group 0.000 description 5
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical group CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- -1 alkyl methacrylate Chemical compound 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000003999 initiator Substances 0.000 description 3
- 238000000053 physical method Methods 0.000 description 3
- XDLMVUHYZWKMMD-UHFFFAOYSA-N 3-trimethoxysilylpropyl 2-methylprop-2-enoate Chemical compound CO[Si](OC)(OC)CCCOC(=O)C(C)=C XDLMVUHYZWKMMD-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000007348 radical reaction Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229920000536 2-Acrylamido-2-methylpropane sulfonic acid Polymers 0.000 description 1
- XHZPRMZZQOIPDS-UHFFFAOYSA-N 2-Methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(C)(C)NC(=O)C=C XHZPRMZZQOIPDS-UHFFFAOYSA-N 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- DNSSXCNMYWINJB-UHFFFAOYSA-O OCC[N+](C)(C)C#P=O.CC(=C)C(=O)OCCP(=O)=C(O)C[N+](C)(C)C Chemical compound OCC[N+](C)(C)C#P=O.CC(=C)C(=O)OCCP(=O)=C(O)C[N+](C)(C)C DNSSXCNMYWINJB-UHFFFAOYSA-O 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- DBPBBEWGTZWSRJ-UHFFFAOYSA-N [4-(2-methylprop-2-enoyloxy)-1-(trimethylazaniumyl)butan-2-yl] hydrogen phosphate Chemical compound CC(=C)C(=O)OCCC(C[N+](C)(C)C)OP(O)([O-])=O DBPBBEWGTZWSRJ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- NKSJNEHGWDZZQF-UHFFFAOYSA-N ethenyl(trimethoxy)silane Chemical compound CO[Si](OC)(OC)C=C NKSJNEHGWDZZQF-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- JYVHOGDBFNJNMR-UHFFFAOYSA-N hexane;hydrate Chemical compound O.CCCCCC JYVHOGDBFNJNMR-UHFFFAOYSA-N 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/12—Esters of monohydric alcohols or phenols
- C08F220/14—Methyl esters, e.g. methyl (meth)acrylate
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention belongs to the technical field of functional high molecular polymers, and discloses a phosphorylcholine quadripolymer with multiple self-turnover functions, and a preparation method and application thereof. The molecular structural formula of the phosphorylcholine tetrapolymer is shown as follows:n is more than or equal to 6 and less than or equal to 9. The four different types of hydrophilic and hydrophobic groups are simultaneously present in the side chain of the tetrapolymer, namely a charged extremely hydrophilic group, an extremely hydrophobic group, a general hydrophilic group and a general hydrophobic group, and the selection of the different types of hydrophilic and hydrophobic groups balances the performance of the tetrapolymer, so that the tetrapolymer can self-turn in different environments, has accessible diversity and interaction accuracy, and has good biocompatibility. The method is simple in process, green and environment-friendly, and can be applied to the field of biological materials.
Description
Technical Field
The invention belongs to the technical field of functional high molecular polymers, and particularly relates to a phosphorylcholine quadripolymer with multiple self-turnover functions, and a preparation method and application thereof.
Background
Monomers and polymers thereof having a phospholipid group are greatly favored in the field of biomaterials as novel biomaterials. Wherein the side chain contains phosphorylcholine 2-Methacryloyloxyethyl Phosphorylcholine (MPC), has similar properties to the outer layer of human cell membrane, and is a monomer most suitable for simulating the phospholipid polar group of cell membrane.
Researchers believe that the material biocompatibility can be remarkably increased by copolymerizing alkyl methacrylate and MPC to obtain MPC polymer and modifying the outer layer structure of the imitated cell membrane on the surface of the material. And these materials have amphiphilicity: a very hydrophilic phospholipid group and a hydrophobic alkyl group. When these MPC polymers are dissolved in a suitable solvent and physically coated on the surface of a material, the material will have good biocompatibility and exhibit desirable interactions with biological tissues.
Thus, a number of patents have made a number of structural changes to MPC monomers and derivatives thereof, and patent CN100563716C, "biocompatible monodisperse nano-polymer carrier and method for preparing and loading the same," an amphiphilic block MPC copolymer was prepared by a polymerization process wherein the hydrophobic segment is n-Butyl Methacrylate (BMA). Then preparing nano polymer micelle by using the amphiphilic MPC copolymer through a solvent volatilization method to obtain a monodisperse nano polymer drug-carrying system with good biocompatibility. Patent CN111467571A 'multifunctional cardiovascular coating material with super-hydrophilicity and preparation method thereof' the preparation method comprises the steps of preparing MPC multipolymer with super-hydrophilicity by free radical polymerization of 2-methacryloxyethyl phosphorylcholine, vinyl trimethoxy silane, 2-acrylamido-2-methylpropanesulfonic acid, maleimide-tri (ethylene glycol) -propionic acid and the like under the action of an initiator, and then uniformly mixing the MPC multipolymer with chitosan quaternary ammonium salt, thus obtaining the material with super-hydrophilicity and good biocompatibility. Korean patent KR1020130012877 "copolymer containing phosphono group and method for preparing and using the same" copolymerization of 2-acryloyloxyethyl Methyl Phosphorylcholine (MPC) monomer and hydrophobic monomer methacrylate ester with addition of a suitable initiator to synthesize a random amphiphilic MPC polymer, and further coating the MPC random copolymer on a medical device to prepare a medical device having amphiphilicity and good biocompatibility. However, the biological material has complex conditions of extremely hydrophilia, general hydrophilia, hydrophobicity, extremely hydrophobicity and the like in the actual use environment, and the MPC copolymer prepared by the above patent is difficult to meet the use requirement and is greatly limited in the actual use, so that the development of the MPC copolymer which can meet the actual use of various environments and has good biocompatibility has important significance.
Disclosure of Invention
The invention aims to solve the defects and the shortcomings of the prior art, and the primary aim is to provide a phosphorylcholine quadripolymer with multiple self-inversions.
It is another object of the present invention to provide a method for preparing the above-mentioned phosphorylcholine tetrapolymer with multiple self-inversions. The method takes 2-methacryloyloxyethyl phosphorylcholine, isooctyl methacrylate, oligomeric ethylene glycol methacrylate and methyl methacrylate as raw materials, and synthesizes a tetrapolymer through free radical reaction under the action of an initiator, so that the phosphorylcholine tetrapolymer with side chains containing 4 different hydrophilic and hydrophobic types is obtained.
It is a further object of the present invention to provide the use of the above-described phosphorylcholine tetrapolymer with multiple self-inversions.
The aim of the invention is achieved by the following technical scheme:
a phosphorylcholine quadripolymer with multiple self-inversions has the following molecular structural formula:
，6≤n≤9。
the preparation method of the phosphorylcholine quadripolymer with multiple self-turnover comprises the steps of mixing 2-methacryloyloxyethyl phosphorylcholine, isooctyl methacrylate, oligomeric ethylene glycol methacrylate, methyl methacrylate, azodiisobutyronitrile and a solvent, blowing the solution by using dry nitrogen, stirring and reacting at 60-80 ℃, cooling the reaction mixture to room temperature, then placing the reaction mixture into n-hexane to precipitate out a white thick matter, filtering and washing the white thick matter for multiple times by using deionized water and n-hexane, and drying the white thick matter overnight at 40-50 ℃.
Preferably, the total volume ratio of the oligoethylene glycol methacrylate to the methyl methacrylate is (1-4): 1; the mass ratio of the 2-methacryloyloxyethyl phosphorylcholine to the azobisisobutyronitrile is (100-500) 1;
preferably, the reaction time is 5-7 hours; the stirring speed is 400-600 rpm/min.
Preferably, the molar ratio of the 2-methacryloyloxyethyl phosphorylcholine, the isooctyl methacrylate, the oligomeric ethylene glycol methacrylate and the methyl methacrylate is 1 (2-14): (5-10): (8-14).
The application of the phosphorylcholine quadripolymer with multiple self-inversions in the field of biological materials.
The phosphocholine tetrapolymer side chain copolymer with multiple self-turnover is formed by copolymerizing 2-methacryloyloxyethyl phosphocholine with extremely hydrophilic charges, extremely hydrophobic isooctyl methacrylate, generally hydrophilic oligomeric ethylene glycol methacrylate and generally hydrophobic methyl methacrylate. The 2-methacryloyloxyethyl phosphorylcholine with extremely hydrophilic charge can reduce the aggregation tendency of the tetrapolymer and has good biocompatibility. Isooctyl methacrylate and methyl methacrylate are capable of modulating the structural distribution of the tetrapolymer in the oil phase; the oligomeric ethylene glycol methacrylate can regulate the overall hydrophilicity and promote the formation of hydrogen bond chains.
The four groups with different polarities, namely an extremely hydrophilic group, an extremely hydrophobic group, a general hydrophilic group and a general hydrophobic group, exist on the side chain of the four-component copolymer of the phosphorylcholine to form a four-component polymer micelle, and the extremely hydrophilic group of the phosphorylcholine is exposed to contact with the extremely hydrophilic environment in the extremely hydrophilic environment; in a very hydrophobic environment, isooctyl very hydrophobic groups are exposed to contact with the very hydrophobic environment; in a general hydrophilic environment, exposing the general hydrophilic group of the oligomeric ethylene glycol to contact with the general hydrophilic environment; in a generally hydrophobic environment, methyl groups are exposed to the generally hydrophobic environment.
When the phosphorylcholine tetrapolymer is further coated on the surface of the biological material by using a physical method or chemical modification, the modified biological material is in different environments, and the microstructure distribution of four polar groups on the surface of the modified biological material can be changed. In a very hydrophilic environment, the thermodynamic effect minimizes the effect of the very hydrophilic groups on the surface of the modified biological material on water, and the very hydrophilic groups are exposed to contact with water; in the extremely hydrophobic environment, the thermodynamic effect minimizes the effect of extremely hydrophobic groups on the surface of the modified biological material and oil, the extremely hydrophobic groups are exposed to contact with the oil, the general hydrophilic environment and the general hydrophobic environment are the same, the prepared modified biological material has access diversity to different environments, and meanwhile, the application of the multi-self-turnover phosphorylcholine tetrapolymer and the microstructure thereof can meet the application characteristic requirements of the biological material.
Compared with the prior art, the invention has the following beneficial effects:
the microstructure of the phosphorylcholine tetrapolymer is favorable for the tetrapolymer to access different environments, and is suitable for complex use environments. In different environments, the microstructure of 4 groups with different polarities can be changed, and in a very hydrophilic environment, the thermodynamic effect exposes the very hydrophilic groups to contact with water; in very hydrophobic environments, thermodynamic effects expose hydrophobic groups to oil contact, and generally hydrophilic environments and generally hydrophobic environments are the same.
The invention synthesizes the phosphorylcholine quadripolymer through the free radical reaction to obtain the quadripolymer with 4 groups with different polarities on the side chains, and the preparation method is simple, has strong practicability, low cost of raw materials, abundant and easily obtained sources and easy popularization.
The phosphorylcholine quadripolymer prepared by the method can be further coated on the surface of a biological material in a physical method or a chemical modification way, so that the modified biological material has access diversity and good biocompatibility.
Drawings
FIG. 1 is a schematic diagram of the synthesis of a phosphorylcholine tetrapolymer according to the present invention;
FIG. 2 is an infrared spectrum of 2-methacryloyloxyethyl phosphorylcholine, isooctyl methacrylate, oligoethylene glycol methacrylate and tetrapolymer of example 1;
FIG. 3 is a nuclear magnetic resonance spectrum of the phosphorylcholine tetrapolymer of example 1;
FIG. 4 is a water contact angle test of the phosphorylcholine tetrapolymer of example 2 and the phosphorylcholine-containing bipolymer of comparative example 1;
FIG. 5 is an optical image of the dispersibility of the phosphorylcholine tetrapolymer of example 3 and the phosphorylcholine-containing bipolymer of comparative example 2, and a schematic view of a bilayer of human skin phospholipids;
FIG. 6 is a schematic view of the microstructure principle of phosphorylcholine tetrapolymer.
Detailed Description
The present invention is further illustrated below in conjunction with specific examples, but should not be construed as limiting the invention. The technical means used in the examples are conventional means well known to those skilled in the art unless otherwise indicated. Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present invention are those conventional in the art.
Example 1
FIG. 1 is a schematic diagram of the synthesis of a phosphocholine tetrapolymer with multiple self-inversions according to the present invention, prepared as follows:
2-methacryloyloxyethyl phosphorylcholine (0.5 mmol,0.148 g), isooctyl methacrylate (3.0 mmol,0.588 g), oligoethylene glycol methacrylate (4.0 mmol,1.600g, average molecular weight 400), methyl methacrylate (7 mmol,0.700 g) and 3mL absolute ethanol were weighed into a thumb bottle and the resulting solution was slowly purged with dry nitrogen for 10min. Then, the thumb flask was transferred to an oil bath at 80℃and then 0.001g of Azobisisobutyronitrile (AIBN) was weighed and dissolved in 1mL of absolute ethanol, and slowly dropped into the thumb flask to react with stirring for 4 hours. After the reaction, the reaction mixture is cooled to room temperature, the reaction mixture is put into normal hexane for precipitation, the product is filtered and washed with deionized water and normal hexane for a plurality of times, and the phosphorylcholine tetrapolymer of white thick matter is obtained, the structural formula of which is ，n=6。
FIG. 2 is an infrared spectrum of 2-methacryloyloxyethyl phosphorylcholine, isooctyl methacrylate, oligoethylene glycol methacrylate and tetrapolymer of example 1. FIG. 3 is a nuclear magnetic resonance spectrum of the phosphorylcholine tetrapolymer of example 1. As can be seen from fig. 2, in the tetrapolymer,1020-1200cm -1 an infrared absorption peak of C-O-C appears at 1380cm -1 And 1460cm -1 where-CH appears 3 Is 2900-3000cm -1 where-N (CH) 3 ) Indicating successful preparation of the phosphorylcholine tetrapolymer.
Example 2
The preparation method of the phosphorylcholine quadripolymer with multiple self-inversions comprises the following steps:
2-methacryloyloxyethyl phosphorylcholine (0.5 mmol,0.148 g), isooctyl methacrylate (3.0 mmol,0.588 g), oligoethylene glycol methacrylate (4.0 mmol,1.600g, average molecular weight 400), methyl methacrylate (5 mmol,0.500 g) and 3mL absolute ethanol were weighed into a thumb bottle and the resulting solution was slowly purged with dry nitrogen for 10min. Then, the thumb flask was transferred to an oil bath at 80℃and then 0.001g of Azobisisobutyronitrile (AIBN) was weighed and dissolved in 1mL of absolute ethanol, and slowly dropped into the thumb flask to react with stirring for 4 hours. After the completion of the reaction, the reaction mixture was cooled to room temperature, the reaction mixture was precipitated in n-hexane, the product was filtered, and washed with deionized water and n-hexane several times to obtain a phosphorylcholine tetrapolymer as a white thick substance having the same structural formula as in example 1.
Comparative example 1
A preparation method of the phosphorylcholine-containing binary copolymer comprises the following steps: 2-methacryloyloxyethyl phosphorylcholine (1 mmol, 0.292 g) and 3- (methacryloyloxy) propyl trimethoxysilane (2 mmol,0.746 g) and 3mL of absolute ethanol were weighed into a thumb flask and the resulting solution was slowly blown with dry nitrogen for 10min. Then transferring the thumb bottle into an oil bath at 80 ℃, then weighing 0.001g of Azodiisobutyronitrile (AIBN) to be dissolved in 1mL of absolute ethyl alcohol, slowly dripping the solution into the thumb bottle, stirring and reacting for 4 hours, cooling the reaction mixture to room temperature after the reaction is finished, putting the reaction mixture into deionized water for precipitation, filtering the product, and washing the product with deionized water for a plurality of times to prepare the phosphorylcholine-containing binary copolymer.
Fig. 4 is a graph showing water contact angle measurements of the tetrapolymer (a) of example 2 and the bipolymer (B) of comparative example 1. Cutting 8 pieces of 1X 1cm dry A4 paper, putting 5 pieces of A4 paper into the ethanol solution of the quadripolymer prepared in the example 2 to be soaked and coated for 0.5h, putting 3 pieces of A4 paper into the ethanol solution of the bipolymer prepared in the comparative example 1 to be soaked and coated for 0.5h, clamping the paper out of forceps, putting the paper on the surface of a glass sheet, and drying the paper in an oven at 50 ℃ for 12h. Soaking four pieces of dried A4 paper coated with the tetrapolymer in water, ethanol, acetone and n-hexane solution for 5min respectively, and drying at 50deg.C for 6h; two pieces of dried A4 paper coated with the binary copolymer are respectively soaked in water and acetone solution for 5min and then are placed in a glass sheet surface oven for drying at 50 ℃ for 6h. The 8 dried samples were tested for water contact angle, respectively, and the two samples numbered (1) in fig. 4 were not subjected to the solution soaking treatment, and the same sample was randomly averaged for 5 point measurements. As can be seen from fig. 4, the water contact angle of the A4 coated with the tetrapolymer after the aqueous solution treatment was 55 °, the water contact angle after the acetone solution treatment was 125 °, and the water contact angle was changed more than that of the A4 paper without the solution treatment was 115 °; the water contact angle of the A4 coated with the binary copolymer after being treated by the aqueous solution is 87 degrees, the water contact angle of the A4 coated with the binary copolymer after being treated by the acetone solution is 110 degrees, and the water contact angle is 108 degrees compared with the water contact angle of the A4 paper which is not treated by the solution, so that the water contact angle is less changed. When the phosphorylcholine tetrapolymer is further coated on the surface of a material by using a physical method, the modified material is in different environments, and the microstructure distribution of four polar groups on the surface of the modified material can be changed. In a hydrophilic environment, the thermodynamic effect minimizes the effect of hydrophilic groups on the surface of the modified biological material on water, and the polar hydrophilic groups are exposed to contact with water; in a hydrophobic environment, thermodynamic action minimizes the action of hydrophobic groups on the surface of the modified biomaterial with oil, and the hydrophobic groups are exposed to contact with the oil.
Example 3
The preparation method of the phosphorylcholine quadripolymer with multiple self-inversions comprises the following steps:
2-methacryloyloxyethyl phosphorylcholine (0.5 mmol,0.148 g), isooctyl methacrylate (2.0 mmol,0.397 g), oligoethylene glycol methacrylate (2.5 mmol,1.000 g), methyl methacrylate (5 mmol,0.500 g) and 3mL absolute ethanol were weighed into a thumb bottle and the resulting solution was slowly blown with dry nitrogen for 10min. Then, the thumb flask was transferred to an oil bath at 80℃and then 0.001g of Azobisisobutyronitrile (AIBN) was weighed and dissolved in 1mL of absolute ethanol, and slowly dropped into the thumb flask to react with stirring for 4 hours. After the completion of the reaction, the reaction mixture was cooled to room temperature, the reaction mixture was precipitated in n-hexane, the product was filtered, and washed with deionized water and n-hexane several times to obtain a phosphorylcholine tetrapolymer as a white thick substance having the same structural formula as in example 1.
Comparative example 2
2-methacryloyloxyethyl phosphorylcholine (1 mmol, 0.298 g) and 3- (methacryloyloxy) propyltrimethoxysilane (1.5 mmol,0.600 g) and 3mL absolute ethanol were weighed into a thumb flask and the resulting solution was slowly blown with dry nitrogen for 10min. Then, the thumb flask was transferred to an oil bath at 80℃and then 0.001g of Azobisisobutyronitrile (AIBN) was weighed and dissolved in 1mL of absolute ethanol, and slowly dropped into the thumb flask to react with stirring for 4 hours. After the completion, the reaction mixture was cooled to room temperature, the reaction mixture was precipitated in deionized water, the product was filtered, and washed with deionized water several times to obtain a white thick phosphorylcholine-containing copolymer.
FIG. 5 is a dispersion photomicrograph of the phosphorylcholine tetrapolymer (B) of example 3 and the phosphorylcholine-containing bipolymer (A) of comparative example 2, wherein (C) is a schematic view of a phospholipid bilayer of human skin. 2 beakers of the same specification were taken, and the same volume of n-hexane, water and chloroform were sequentially added, respectively. Respectively adding red dye with the same mass into ethanol solution containing phosphorylcholine binary copolymer and phosphorylcholine quaternary copolymer, stirring for half an hour, respectively taking the same volume of the dyed binary copolymer and the quaternary copolymer into the beaker, and standing. As can be seen from fig. 5, after three minutes of standing, the phosphorylcholine tetrapolymer had passed through the n-hexane layer to the water layer and half an hour later to the chloroform layer, and all had good dispersibility; the phosphorylcholine-containing binary copolymer reached the aqueous layer only in a very small amount after half an hour, and failed to reach the chloroform layer through the aqueous layer. The microstructure of four polar groups on the surface of the phosphorylcholine quadripolymer micelle prepared by the invention can be automatically turned when the phosphorylcholine quadripolymer micelle is in different environments. In a hydrophilic environment, the thermodynamic effect minimizes the effect of hydrophilic groups on the surface of the phosphorylcholine quadripolymer micelle and water, and the hydrophilic groups are exposed to contact with water; in the extremely hydrophobic environment, the thermodynamic effect minimizes the effect of extremely hydrophobic groups on the surface of the phosphorylcholine quadripolymer micelle and oil, and the hydrophobic groups are exposed to contact with the oil, so that the phosphorylcholine quadripolymer micelle has better and faster access diversity than the prior phosphorylcholine-containing dipolymer, as shown in the schematic diagram of the microstructure principle of the phosphorylcholine quadripolymer in fig. 6.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (4)
1. A phosphorylcholine tetrapolymer with multiple self-inversions, which is characterized by the following molecular structural formula:
，6≤n≤9；
wherein the molar ratio of the 2-methacryloyloxyethyl phosphorylcholine to the isooctyl methacrylate to the methyl methacrylate is 1 (2-14): 5-10): 8-14.
2. The method for preparing the phosphorylcholine tetrapolymer with multiple self-inversions according to claim 1, wherein the method is characterized in that 2-methacryloxyethyl phosphorylcholine, isooctyl methacrylate, oligomeric ethylene glycol methacrylate, methyl methacrylate, azodiisobutyronitrile and a solvent are mixed, the solution is blown by dry nitrogen, the reaction mixture is stirred at 60-80 ℃ for reaction, the reaction mixture is cooled to room temperature, then the reaction mixture is placed into n-hexane for precipitation to separate out white thick matters, the white thick matters are filtered and washed for multiple times by deionized water and n-hexane, and the white thick matters are dried overnight at 40-50 ℃ to obtain the phosphorylcholine tetrapolymer with multiple self-inversions;
the solvent is methanol, ethanol or glycol, and the total volume ratio of the volume of the solvent to the total volume of isooctyl methacrylate, oligomeric ethylene glycol methacrylate and methyl methacrylate is (1-4): 1; the mass ratio of the 2-methacryloyloxyethyl phosphorylcholine to the azobisisobutyronitrile is (100-500) 1; the molar ratio of the 2-methacryloyloxyethyl phosphorylcholine to the isooctyl methacrylate to the methyl methacrylate is 1 (2-14), 5-10 and 8-14.
3. The method for preparing the phosphorylcholine tetrapolymer with multiple self-inversions according to claim 2, wherein the reaction time is 5-7 hours; the stirring speed is 400-600 rpm/min.
4. Use of the phosphorylcholine tetrapolymer with multiple self-inversions according to claim 1 in the field of biological materials.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310589903.7A CN116284548B (en) | 2023-05-24 | 2023-05-24 | Phosphorylcholine tetrapolymer with multiple self-turnover function, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310589903.7A CN116284548B (en) | 2023-05-24 | 2023-05-24 | Phosphorylcholine tetrapolymer with multiple self-turnover function, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116284548A CN116284548A (en) | 2023-06-23 |
| CN116284548B true CN116284548B (en) | 2023-08-11 |
Family
ID=86820789
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310589903.7A Active CN116284548B (en) | 2023-05-24 | 2023-05-24 | Phosphorylcholine tetrapolymer with multiple self-turnover function, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116284548B (en) |
Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07268038A (en) * | 1994-03-31 | 1995-10-17 | Nippon Oil & Fats Co Ltd | Copolymer with phosphorylcholine group or its derivative group, its production, and antithrombotic material |
| WO1999026637A1 (en) * | 1997-11-26 | 1999-06-03 | Nof Corporation | Ophthalmic preparation and ophthalmic composition |
| JP2003040942A (en) * | 2001-05-22 | 2003-02-13 | Shiseido Co Ltd | Phosphorylcholine group-containing polymer and method for producing the same |
| CN1587347A (en) * | 2004-08-05 | 2005-03-02 | 复旦大学 | Electrochemical luminous composite material capable of resisting biological pollution and its preparing method and use |
| JP2007204432A (en) * | 2006-02-02 | 2007-08-16 | Shiseido Co Ltd | Solubilized cosmetic |
| CN102887976A (en) * | 2011-07-21 | 2013-01-23 | 西北大学 | Imitation mussel attachment protein and cell membrane structure copolymer and preparation method and application thereof |
| CN104610516A (en) * | 2015-01-12 | 2015-05-13 | 西北大学 | Functional polymer containing phosphorylcholine and PEG and method for forming anti-pollution coating with functional polymer |
| WO2016064006A1 (en) * | 2014-10-23 | 2016-04-28 | 주식회사 케이씨아이 | Polymer containing phosphorylcholine, and cosmetic composition containing same |
| KR20160047893A (en) * | 2014-10-23 | 2016-05-03 | 주식회사 케이씨아이 | Polymers containing phosphorylcholine-like groups, and their cosmetic Formulations |
| JP2016194054A (en) * | 2015-03-31 | 2016-11-17 | 東ソー株式会社 | Block copolymer |
| CN106380542A (en) * | 2016-08-27 | 2017-02-08 | 西安科技大学 | Preparation method of photocurable phosphorylcholine polymer |
| CN107110841A (en) * | 2015-02-19 | 2017-08-29 | 国立大学法人京都工艺纤维大学 | Suppress the method for protein absorption |
| CN107249652A (en) * | 2015-07-27 | 2017-10-13 | Jsr株式会社 | The manufacture method and medical equipment of medical equipment |
| WO2017209222A1 (en) * | 2016-05-31 | 2017-12-07 | 京セラ株式会社 | Method for producing medical device |
| WO2018056344A1 (en) * | 2016-09-22 | 2018-03-29 | 日油株式会社 | Two pack type coating agent for medical devices |
| WO2022054743A1 (en) * | 2020-09-10 | 2022-03-17 | 京セラ株式会社 | Method for forming graft layer, method for producing composite, and treatment liquid for forming graft layer |
| CN114259421A (en) * | 2022-01-29 | 2022-04-01 | 江苏奥洁生物科技有限公司 | Daily chemical raw material based on phosphorylcholine polymer and preparation method thereof |
-
2023
- 2023-05-24 CN CN202310589903.7A patent/CN116284548B/en active Active
Patent Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07268038A (en) * | 1994-03-31 | 1995-10-17 | Nippon Oil & Fats Co Ltd | Copolymer with phosphorylcholine group or its derivative group, its production, and antithrombotic material |
| WO1999026637A1 (en) * | 1997-11-26 | 1999-06-03 | Nof Corporation | Ophthalmic preparation and ophthalmic composition |
| JP2003040942A (en) * | 2001-05-22 | 2003-02-13 | Shiseido Co Ltd | Phosphorylcholine group-containing polymer and method for producing the same |
| CN1587347A (en) * | 2004-08-05 | 2005-03-02 | 复旦大学 | Electrochemical luminous composite material capable of resisting biological pollution and its preparing method and use |
| JP2007204432A (en) * | 2006-02-02 | 2007-08-16 | Shiseido Co Ltd | Solubilized cosmetic |
| CN102887976A (en) * | 2011-07-21 | 2013-01-23 | 西北大学 | Imitation mussel attachment protein and cell membrane structure copolymer and preparation method and application thereof |
| KR20160047893A (en) * | 2014-10-23 | 2016-05-03 | 주식회사 케이씨아이 | Polymers containing phosphorylcholine-like groups, and their cosmetic Formulations |
| WO2016064006A1 (en) * | 2014-10-23 | 2016-04-28 | 주식회사 케이씨아이 | Polymer containing phosphorylcholine, and cosmetic composition containing same |
| CN104610516A (en) * | 2015-01-12 | 2015-05-13 | 西北大学 | Functional polymer containing phosphorylcholine and PEG and method for forming anti-pollution coating with functional polymer |
| CN107110841A (en) * | 2015-02-19 | 2017-08-29 | 国立大学法人京都工艺纤维大学 | Suppress the method for protein absorption |
| JP2016194054A (en) * | 2015-03-31 | 2016-11-17 | 東ソー株式会社 | Block copolymer |
| CN107249652A (en) * | 2015-07-27 | 2017-10-13 | Jsr株式会社 | The manufacture method and medical equipment of medical equipment |
| WO2017209222A1 (en) * | 2016-05-31 | 2017-12-07 | 京セラ株式会社 | Method for producing medical device |
| CN106380542A (en) * | 2016-08-27 | 2017-02-08 | 西安科技大学 | Preparation method of photocurable phosphorylcholine polymer |
| WO2018056344A1 (en) * | 2016-09-22 | 2018-03-29 | 日油株式会社 | Two pack type coating agent for medical devices |
| WO2022054743A1 (en) * | 2020-09-10 | 2022-03-17 | 京セラ株式会社 | Method for forming graft layer, method for producing composite, and treatment liquid for forming graft layer |
| CN114259421A (en) * | 2022-01-29 | 2022-04-01 | 江苏奥洁生物科技有限公司 | Daily chemical raw material based on phosphorylcholine polymer and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116284548A (en) | 2023-06-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Xu et al. | Surface functionalization of polycaprolactone films via surface-initiated atom transfer radical polymerization for covalently coupling cell-adhesive biomolecules | |
| CN110804144B (en) | Cationic-zwitterionic block copolymers | |
| Ju et al. | pH/temperature-responsive behaviors of semi-IPN and comb-type graft hydrogels composed of alginate and poly (N-isopropylacrylamide) | |
| Hemmati et al. | pH responsive tragacanth gum and poly (methyl methacrylate-co-maleic anhydride)-g-poly (caprolactone) conetwork microgel for in vitro quercetin release | |
| CN112375191B (en) | Block copolymer, preparation method and application thereof | |
| JP2009518469A (en) | Flexible superabsorbent binder polymer composition | |
| CA2786141A1 (en) | Transparent bacterial cellulose nanocomposite hydrogels | |
| Huang et al. | Synthesis and characterization of polyacrylate modified by polysiloxane latexes and films | |
| Xia et al. | Cell attachment/detachment behavior on poly (N-isopropylacrylamide)-based microgel films: the effect of microgel structure and swelling ratio | |
| CN116284548B (en) | Phosphorylcholine tetrapolymer with multiple self-turnover function, and preparation method and application thereof | |
| Santos et al. | Temperature-responsive fibres of cellulose-based copolymers | |
| WO2020168188A1 (en) | Biocompatible polymeric coating containing therapeutic agents | |
| CN106496464B (en) | A kind of amphipathic network of UV light anti-fouling type and preparation method thereof | |
| GB2338958A (en) | Hyperbranched-graft hybrid copolymers from vinyl branching monomers and vinyl macromonomers | |
| Wei et al. | Preparation of thermosensitive hydrogels by means of tandem physical and chemical crosslinking | |
| CN108641092B (en) | Preparation method of supramolecular polymer composite micelle based on hydrogen bond | |
| CN111205485A (en) | Preparation method of reinforced modified carboxymethyl chitosan hydrogel | |
| CN111592653A (en) | Preparation method of topological elastomer with highly branched structure and low-modulus high elasticity | |
| Angiolini et al. | Hybrid organic–inorganic copolymers from oxohydroxoorganotin dimethacrylate and methyl methacrylate | |
| CN114702691B (en) | Ion-responsive and biological antifouling hydrogel as well as preparation method and application thereof | |
| CN111217968A (en) | Polyolefin triblock copolymer responding to multiple effects on environment and preparation method thereof | |
| CN116621872A (en) | Acryloxy (2-hydroxypropyl) phosphorylcholine and binary polymer thereof, preparation method and application | |
| CN113831178B (en) | Slow-release coated fertilizer and preparation method thereof | |
| CN113831740B (en) | Self-repairing organic silicon polymeric material and preparation method and application thereof | |
| JPH1017622A (en) | New copolymer and its production |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |