WO2016035830A1 - Fluorine-containing highly-branched polymer, and biomolecule adsorption-suppressing surface - Google Patents

Abstract

[Problem] To provide a material with which it is possible to easily form a surface capable of suppressing the adsorption of biomolecules such as proteins on various substrates such as plastics by a coating method such as spin coating with which it is possible to produce a thin film in a short time. [Solution] A fluorine-containing highly-branched polymer obtained by polymerizing a polymerizable compound that contains at least a monomer A having two or more radical polymerizable double bonds in the molecule and a monomer B having a fluoroalkyl group and at least one radical polymerizable double bond in the molecule, polymerization taking place in the presence of 5-200 mol% of a polymerization initiator C relative to the number of moles of the monomer A, wherein the fluorine-containing highly-branched polymer has an oxyalkylene site at the end of the molecule.

Description

Fluorine-containing hyperbranched polymer and biomolecule adsorption inhibiting surface

The present invention relates to a novel fluorine-containing highly branched polymer and a biomolecule adsorption-suppressing surface (membrane) formed using the fluorine-containing highly branched polymer.

In recent years, polymer (polymer) materials have been increasingly used in many fields. Accordingly, the characteristics of the surface and interface of the polymer material as well as the polymer properties as a matrix are important in the polymer material according to each field. In particular, in recent years, medical materials using various polymer materials have been studied, such as blood filters, artificial kidney membranes, plasma separation membranes, catheters, artificial lung membranes, artificial blood vessels, adhesion prevention membranes, artificial membranes. Expected to be used on skin. In this case, since a synthetic material that is a foreign substance for a living body is used in contact with in vivo tissue or blood, the medical material is required to have biocompatibility.

On the other hand, there is a problem that biological components such as proteins and cells are adsorbed on the surface of a substrate such as an instrument or material to be used. For example, mainly in the medical field, if a small amount of protein is measured and analyzed, such as proteome analysis, if there are many adsorbed components, protein analysis cannot be performed accurately, but the protein may be substantially lost. There is a risk of it. In addition, problems such as reduction of useful proteins during extracorporeal circulation such as an artificial kidney, formation of a thrombus due to adhesion / aggregation of platelets, and coagulation of blood due to adsorption of coagulation-related proteins such as fibrinogen occur. Also in the food field, problems such as quality degradation due to the adsorption of biological components to the product container and problems such as blockage and deterioration of the pipeline due to the adsorption of biological components to the pipeline during the production process occur.

Generally, it is known that a hydrophilic polymer has bioaffinity with respect to a biomolecule and has an effect of suppressing nonspecific adsorption of the biomolecule. Biocompatible polymers that suppress nonspecific adsorption of cells and protein components include polyethylene glycol (PEG) or polyethylene oxide (PEO), polyvinyl pyrrolidone (PVP), poly (2-hydroxyethyl methacrylate) (PHEMA), poly Nonionic polymers such as (2-methoxyethyl acrylate) (PMEA) and amphoteric polymers having both positively and negatively charged functional groups in one molecule such as phosphobetaine, sulfobetaine, carboxybetaine, etc. .

For example, Patent Document 1 discloses a technique in which a solution obtained by diluting PEO having a thiol group at one end is coated on a gold-deposited glass substrate and used as a polymer material on the surface for nonspecific adsorption of DNA on a biochip. It is disclosed.

Further, in Non-Patent Document 1, a PMMA blend film in which PMEA is segregated to the surface by spin coating a polymer blend solution of PMEA and polymethylmethacrylate (PMMA) on a substrate, and performing solvent drying and heat treatment. Techniques for making are disclosed.

JP 2004-279204 A

When PEO having a thiol group at one end described in Patent Document 1 is coated on a gold-deposited glass substrate, it is necessary to immerse the substrate in the solution for a long time. An efficient manufacturing method has been a problem.

In addition, in the method described in Non-Patent Document 1, since a polymer blend solution of PMEA and PMMA is spin-coated on a substrate and heat treatment takes several hours to one day, it is inefficient production as in Patent Document 1. The method was a challenge.

As a result of intensive studies to achieve the above object, the present inventors have found that a fluorine-containing highly branched polymer having a fluoroalkyl group and an oxyalkylene moiety at the molecular end, and a resin blend containing a thermoplastic resin are spin-coating and the like. It has been found that a surface capable of easily suppressing the adsorption of biomolecules such as proteins can be easily formed on various substrates such as plastics by a coating method capable of producing a thin film in a short time. Completed.

That is, the present invention provides, as a first aspect, a monomer A having two or more radical polymerizable double bonds in the molecule, and a monomer B having a fluoroalkyl group and at least one radical polymerizable double bond in the molecule. Is a fluorine-containing highly branched polymer obtained by polymerizing a polymerizable compound containing at least 5 to 200 mol% of the polymerization initiator in the presence of a polymerization initiator C with respect to the number of moles of the monomer A. Relates to a fluorine-containing highly branched polymer having an oxyalkylene moiety represented by the formula [1].

(Wherein R ¹ represents an alkyl group having 1 to 6 carbon atoms, L ¹ represents an alkylene group having 2 to 6 carbon atoms, and n represents an integer of 1 to 60).
As a second aspect, the present invention relates to the fluorine-containing highly branched polymer according to the first aspect, wherein n is an integer of 1 to 30.
As a third aspect, the present invention relates to the fluorine-containing highly branched polymer according to the first aspect or the second aspect, in which the oxyalkylene moiety is bonded to the molecular end via a fragment of the polymerization initiator C.
As a 4th viewpoint, the said monomer A is a compound which has any one or both of a vinyl group or a (meth) acryl group, The fluorine-containing highly branched as described in any one of a 1st viewpoint thru | or a 3rd viewpoint Relates to polymers.
As a 5th viewpoint, the said monomer A is related with the fluorine-containing highly branched polymer as described in a 4th viewpoint which is a divinyl compound or a di (meth) acrylate compound.
As a sixth aspect, the present invention relates to the fluorine-containing highly branched polymer according to the fifth aspect, in which the monomer A is divinylbenzene.
As a seventh aspect, the monomer B is a compound having at least one of a vinyl group and a (meth) acryl group, and the fluorine-containing high content according to any one of the first aspect to the sixth aspect. Relates to branched polymers.
As an eighth aspect, the present invention relates to the fluorine-containing highly branched polymer according to the seventh aspect, in which the monomer B is a compound represented by the formula [2].

(In the formula, R ² represents a hydrogen atom or a methyl group, and R ³ represents a C 2-12 fluoroalkyl group which may be substituted with a hydroxy group.)
As a ninth aspect, the present invention relates to the fluorine-containing highly branched polymer according to any one of the first aspect to the eighth aspect, in which the polymerization initiator C is an azo polymerization initiator.
As a tenth aspect, the present invention relates to a varnish containing the fluorine-containing highly branched polymer according to any one of the first to ninth aspects.
As an 11th viewpoint, it is related with the thin film which has the biomolecule adsorption | suction suppression ability produced from the fluorine-containing hyperbranched polymer as described in any one of a 1st viewpoint thru | or a 9th viewpoint.
As a twelfth aspect, the present invention relates to a resin blend containing (a) the fluorine-containing highly branched polymer according to any one of the first to ninth aspects, and (b) a thermoplastic resin.
As a 13th viewpoint, it is related with the biomolecule adsorption | suction suppression film | membrane produced from the resin blend as described in a 12th viewpoint.
As a fourteenth aspect, polymerization comprising at least a monomer A having two or more radical polymerizable double bonds in the molecule and a monomer B having at least one radical polymerizable double bond in the molecule A carboxy group-containing fluorine-containing highly branched polymer obtained by polymerizing a functional compound in the presence of a polymerization initiator having a carboxy group in the molecule of 5 to 200 mol% relative to the number of moles of the monomer A, or The method for producing a fluorine-containing hyperbranched polymer according to any one of the first aspect to the ninth aspect, characterized by reacting a carboxy group activator with a compound represented by the formula [3]. About.

(Wherein R ¹ represents an alkyl group having 1 to 6 carbon atoms, L ¹ represents an alkylene group having 2 to 6 carbon atoms, and n represents an integer of 1 to 60).
As a fifteenth aspect, the present invention relates to the manufacturing method according to the fourteenth aspect, wherein n is an integer of 1 to 30.
As a sixteenth aspect, there is provided a method for producing a thin film having a biomolecule adsorption inhibiting ability produced from the fluorine-containing highly branched polymer according to any one of the first aspect to the ninth aspect,
Inhibition of biomolecule adsorption, including a step of applying a liquid containing the fluorine-containing hyperbranched polymer in a solvent on a substrate by spin coating to form a coating film, and a step of drying the coating film and removing the solvent The present invention relates to a method for manufacturing a thin film having a function.
As a seventeenth aspect, a method for producing a biomolecule adsorption-suppressing membrane produced from the resin blend described in the twelfth aspect,
Production of a biomolecule adsorption inhibiting film comprising a step of applying a liquid containing the resin blend in a solvent on a substrate by a spin coating method to form a coating film, and a step of drying the coating film and removing the solvent. Regarding the method.

The fluorine-containing hyperbranched polymer having an oxyalkylene moiety having an effect of suppressing the adsorption of biomolecules at the molecular end of the present invention is obtained by using a varnish containing the polymer, a resin blend containing the polymer, etc. A film can be easily formed by coating, and a surface capable of suppressing the adsorption of biomolecules such as proteins can be produced on a substrate in a short time.
In addition, the fluorine-containing highly branched polymer having an oxyalkylene moiety at the molecular end of the present invention has a branched structure, so that it has less entanglement between molecules compared to a linear polymer and exhibits fine particle behavior. . In addition, the fluorine-containing highly branched polymer whose surface energy has been reduced by the fluoroalkyl group is easy to move to the surface side, which is a free interface such as air, in the thermoplastic resin used as the matrix, and gives activity to the resin surface. It's easy to do. Accordingly, when a molded body such as a film is produced from a resin blend containing a fluorine-containing highly branched polymer having an oxyalkylene moiety at the molecular end of the present invention and the above thermoplastic resin, the finely divided fluorine-containing highly branched polymer is used as an interface. It can easily move to (film surface), and a molded body (film) in which the abundance of the fluorine-containing highly branched polymer is increased on the surface can be formed. That is, from the resin blend in which a thermoplastic resin or the like is blended with a fluorine-containing highly branched polymer having an oxyalkylene moiety at the molecular end of the present invention, a molded product whose surface is a surface capable of suppressing adsorption of biomolecules such as proteins ( Film) and the like.

FIG. 1 is a diagram showing a ¹ H NMR spectrum of a fluorine-containing highly branched polymer 1 having a carboxy group at the terminal. FIG. 2 is a diagram showing a ¹³ C NMR spectrum of fluorine-containing hyperbranched polymer 1 having a carboxy group at the terminal. FIG. 3 is a diagram showing IR spectra of the fluorine-containing highly branched polymer 1 having a carboxy group at the terminal and the fluorine-containing highly branched polymer 2 having a tri (ethylene oxide) moiety at the terminal. FIG. 4 is a diagram showing a ¹ H NMR spectrum of fluorine-containing highly branched polymer 2 having a tri (ethylene oxide) moiety at the terminal. FIG. 5 shows the results of surface composition analysis of fluorine-containing highly branched polymer 2 / PMMA blend film having a tri (ethylene oxide) moiety at the terminal by angle-resolved X-ray photoelectron spectroscopy (XPS) measurement (fluorine atom and carbon atom relative to photoelectron emission angle θ). _Is a diagram showing the photoelectron intensity ratio I _F1s / I _C1s ) (heat treatment temperature; (a) room temperature, (b) 150 ° C.). FIG. 6 is a graph showing changes in water contact angle with time in a fluorine-containing highly branched polymer 2 / PMMA blend film having a tri (ethylene oxide) portion at the terminal and a fluorine-containing highly branched polymer 1 / PMMA blend film having a carboxyl group at the terminal. It is. FIG. 7 is a diagram showing the observation results of a fluorescein isocyanate-labeled bovine serum albumin (BSA) adsorbed on a fluorine-containing hyperbranched polymer 2 / PMMA blend membrane having a tri (ethylene oxide) moiety at the terminal and a PMMA membrane with a fluorescence microscope ( BSA / phosphate buffered saline (PBS) solution concentrations: 10 μg / mL, 50 μg / mL, 100 μg / mL.) FIG. 8 is a plot of the values obtained by quantifying the brightness of the photographs in the fluorescence micrographs (FIG. 7) obtained in Example 4 and Comparative Example 2 against the BSA concentration. . FIG. 9 is a diagram showing IR spectra of fluorine-containing highly branched polymers 3 and 4 each having an oligo (ethylene oxide) portion at the terminal, and fluorine-containing highly branched polymer 5 having a poly (ethylene oxide) portion at the terminal. FIG. 10 is a diagram showing a ¹ H NMR spectrum of fluorine-containing highly branched polymer 3 having an oligo (ethylene oxide) moiety at the terminal. FIG. 11 is a diagram showing a ¹ H NMR spectrum of fluorine-containing highly branched polymer 4 having an oligo (ethylene oxide) moiety at the terminal. FIG. 12 is a diagram showing a ¹ H NMR spectrum of fluorine-containing hyperbranched polymer 5 having a poly (ethylene oxide) moiety at the terminal. FIG. 13 shows the results of surface composition analysis (photoelectron emission) of the fluorine-containing highly branched polymer 3 / PMMA blend film, the fluorine-containing highly branched polymer 4 / PMMA blend film, and the fluorine-containing highly branched polymer 5 / PMMA blend film by angle-resolved XPS measurement. It is a figure which shows the photoelectron intensity ratio _IF1s / _IC1s ) of the fluorine atom and the carbon atom with respect to angle (theta). FIG. 14 is a graph showing changes in the water contact angle with time in a fluorine-containing highly branched polymer 3 / PMMA blend film, a fluorine-containing highly branched polymer 4 / PMMA blend film, and a fluorine-containing highly branched polymer 5 / PMMA blend film. FIG. 15 shows a fluorescence microscope for fluorescein isocyanate-labeled BSA adsorption on fluorine-containing highly branched polymer 3 / PMMA blend membrane, fluorine-containing highly branched polymer 4 / PMMA blend membrane, fluorine-containing highly branched polymer 5 / PMMA blend membrane, and PMMA membrane. (BSA / PBS solution concentration: 5 μg / mL, 20 μg / mL, 50 μg / mL). FIG. 16 plots the values obtained by quantifying the luminance of the photographs in the fluorescence micrographs obtained in Examples 14 to 16 and Comparative Example 3 (FIG. 15) against the BSA concentration. FIG. FIG. 17 shows a fluorine-containing highly branched polymer 3 / PMMA blend film, a fluorine-containing highly branched polymer 4 / PMMA blend film, a fluorine-containing highly branched polymer 5 / PMMA blend film, a fluorine-containing highly branched polymer 1 / PMMA blend film, and a PMMA film. 2 is a scanning electron microscope (SEM) image of platelets adhered on a PET film. FIG. 18 is a graph plotting the number of platelets adhered to each membrane and the classification of the degree of activation in Examples 17 to 19 and Comparative Examples 4 to 6.

<Fluorine-containing highly branched polymer>
The fluorine-containing highly branched polymer of the present invention comprises a monomer A having two or more radical polymerizable double bonds in the molecule, and a monomer B having a fluoroalkyl group and at least one radical polymerizable double bond in the molecule. Is a fluorine-containing highly branched polymer obtained by polymerizing a polymerizable compound containing at least 5 to 200 mol% of the polymerization initiator in the presence of a polymerization initiator C with respect to the number of moles of the monomer A. Is a polymer having an oxyalkylene moiety represented by the formula [1].
The fluorine-containing hyperbranched polymer is a so-called initiator fragment incorporation (IFIRP) type hyperbranched polymer, and has a fragment of the polymerization initiator C used for polymerization at the terminal. Preferably, the oxyalkylene moiety represented by the formula [1] is bonded to the molecular end via a fragment of the polymerization initiator C.
Further, the fluorine-containing hyperbranched polymer may be copolymerized with a polyfunctional monomer and / or a monofunctional monomer, which do not belong to the monomer A and the monomer B described below, as necessary, as long as the effects of the present invention are not impaired. .

[Monomer A]
In the present invention, the monomer A having two or more radically polymerizable double bonds in the molecule preferably has at least one of either a vinyl group or a (meth) acryl group, and particularly a divinyl compound or di ( A meth) acrylate compound is preferred.
In the present invention, the (meth) acrylate compound refers to both an acrylate compound and a methacrylate compound. For example, (meth) acrylic acid refers to acrylic acid and methacrylic acid.

Examples of the monomer A having two or more radical polymerizable double bonds in the molecule include the compounds shown in the following (A1) to (A5).

(A1) Vinyl hydrocarbons:
(A1-1) Aliphatic vinyl hydrocarbons; isoprene, butadiene, 3-methyl-1,2-butadiene, 2,3-dimethyl-1,3-butadiene, 1,2-polybutadiene, pentadiene, hexadiene, octadiene etc.
(A1-2) Alicyclic vinyl hydrocarbons; cyclopentadiene, cyclohexadiene, cyclooctadiene, norbornadiene and the like.
(A1-3) Aromatic vinyl hydrocarbons; divinylbenzene, divinyltoluene, divinylxylene, trivinylbenzene, divinylbiphenyl, divinylnaphthalene, divinylfluorene, divinylcarbazole, divinylpyridine and the like.

(A2) Vinyl ester, allyl ester, vinyl ether, allyl ether and vinyl ketone:
(A2-1) Vinyl ester; divinyl adipate, divinyl maleate, divinyl phthalate, divinyl isophthalate, divinyl itaconate, vinyl (meth) acrylate and the like.
(A2-2) Allyl ester: diallyl maleate, diallyl phthalate, diallyl isophthalate, diallyl adipate, allyl (meth) acrylate, etc.
(A2-3) Vinyl ether; divinyl ether, diethylene glycol divinyl ether, triethylene glycol divinyl ether and the like.
(A2-4) Allyl ether; diallyl ether, diallyloxyethane, triallyloxyethane, tetraallyloxyethane, tetraallyloxypropane, tetraallyloxybutane, tetramethallyloxyethane and the like.
(A2-5) Vinyl ketone; divinyl ketone, diallyl ketone and the like.

(A3) (Meth) acrylic acid ester:
Ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, nonaethylene glycol di (meth) acrylate, trimethylene glycol di (meth) acrylate , Propylene glycol di (meth) acrylate, dipropylene glycol di (meth) acrylate, tripropylene glycol di (meth) acrylate, tetramethylene glycol di (meth) acrylate, neopentyl glycol di (meth) acrylate, 1,6-hexane Diol di (meth) acrylate, 2-methyl-1,8-octanediol di (meth) acrylate, 1,9-nonanediol di (meth) acrylate, 1,10 Decanediol di (meth) acrylate, trimethylolpropane tri (meth) acrylate, ditrimethylolpropane tetra (meth) acrylate, 2-hydroxy-1-acryloyloxy-3-methacryloyloxypropane, 2-hydroxy-1,3-di (Meth) acryloyloxypropane, glycerin = tri (meth) acrylate, pentaerythritol tetra (meth) acrylate, dioxane glycol di (meth) acrylate, tricyclo [5.2.1.0 ^2,6 ] decandimethanol di (meta ) Acrylate, 1,3-adamantanediol di (meth) acrylate, 1,3-adamantane dimethanol di (meth) acrylate, 9,9-bis [4- (2- (meth) acryloyloxyethoxy) phenyl] fluoro Len, bis [2- (meth) acryloylthioethyl] sulfide, bis [4- (meth) acryloylthiophenyl] sulfide, alkoxy titanium tri (meth) acrylate, isophorone urethane di (meth) acrylate, aliphatic urethane di (meth) Acrylate, aromatic urethane di (meth) acrylate, etc.

(A4) Vinyl compound having a polyalkylene glycol chain:
Polyethylene glycol (molecular weight: 200, 300, 400, 600, 1000, etc.) di (meth) acrylate, polypropylene glycol (molecular weight: 400, 500, 700, etc.) di (meth) acrylate, polytetramethylene glycol (molecular weight: 650, etc.) Di (meth) acrylate, ethylene oxide-added polypropylene glycol (molecular weight: 700, etc.), di (meth) acrylate, etc.

(A5) Nitrogen-containing vinyl compound:
Diallylamine, diallyl isocyanurate, diallyl cyanurate, methylenebis (meth) acrylamide, bismaleimide and the like.

These monomers A may be used alone or in combination of two or more.

Among these, preferred are the above-mentioned aromatic vinyl hydrocarbons of the group (A1-3), vinyl esters, allyl esters, vinyl ethers, allyl ethers and vinyl ketones of the group (A2), (meth) acrylic of the group (A3). Acid esters, vinyl compounds having a polyalkylene glycol chain of group (A4), and nitrogen-containing vinyl compounds of group (A5), more preferably aromatic vinyl hydrocarbons of group (A1-3) above , (A3) group (meth) acrylic acid ester. Among these, divinylbenzene and ethylene glycol di (meth) acrylate are particularly preferable from the viewpoint of dispersibility in the thermoplastic resin described later.

[Monomer B]
In the present invention, the monomer B having a fluoroalkyl group and at least one radical polymerizable double bond in the molecule preferably has at least one of either a vinyl group or a (meth) acryl group.
For example, the monomer B includes a compound represented by the above formula [2], and a more preferred specific example includes a compound represented by the following formula [4].

(Wherein R ² represents the same meaning as defined in Formula [2], X represents a hydrogen atom or a fluorine atom, m represents 1 or 2, and p represents an integer of 0 to 5).

Examples of such a monomer B include 2,2,2-trifluoroethyl (meth) acrylate, 2,2,3,3,3-pentafluoropropyl (meth) acrylate, and 2- (perfluorobutyl) ethyl. (Meth) acrylate, 2- (perfluorohexyl) ethyl (meth) acrylate, 2- (perfluorooctyl) ethyl (meth) acrylate, 2- (perfluorodecyl) ethyl (meth) acrylate, 2- (perfluoro- 3-methylbutyl) ethyl (meth) acrylate, 2- (perfluoro-5-methylhexyl) ethyl (meth) acrylate, 2- (perfluoro-7-methyloctyl) ethyl (meth) acrylate, 1H, 1H, 3H- Tetrafluoropropyl (meth) acrylate, 1H, 1H, 5H-Octaf Olopentyl (meth) acrylate, 1H, 1H, 7H-dodecafluoroheptyl (meth) acrylate, 1H, 1H, 9H-hexadecafluorononyl (meth) acrylate, 1H-1- (trifluoromethyl) trifluoroethyl (meth) Acrylate, 1H, 1H, 3H-hexafluorobutyl (meth) acrylate, 3-perfluorobutyl-2-hydroxypropyl (meth) acrylate, 3-perfluorohexyl-2-hydroxypropyl (meth) acrylate, 3-perfluoro Octyl-2-hydroxypropyl (meth) acrylate, 3- (perfluoro-3-methylbutyl) -2-hydroxypropyl (meth) acrylate, 3- (perfluoro-5-methylhexyl) -2-hydroxypropyl (meth) Acryle DOO, 3- (perfluoro-7-methyl-octyl) -2-hydroxypropyl (meth) acrylate.

In the present invention, the amount of monomer B used is more preferably 5 to 300 mol%, particularly 10 to 150 mol%, based on the number of moles of monomer A used, from the viewpoint of reactivity and surface modification effect. Is preferably used in an amount of 20 to 100 mol%.

[Polymerization initiator C]
As the polymerization initiator C, an azo polymerization initiator is preferably used. Examples of the azo polymerization initiator include compounds shown in the following (1) to (5).
(1) Azonitrile compound:
2,2′-azobisisobutyronitrile, 2,2′-azobis (2-methylbutyronitrile), 2,2′-azobis (2,4-dimethylvaleronitrile), 1,1′-azobis ( 1-cyclohexanecarbonitrile), 2,2′-azobis (4-methoxy-2,4-dimethylvaleronitrile), 2- (carbamoylazo) isobutyronitrile and the like;
(2) Azoamide compound:
2,2′-azobis {2-methyl-N- [1,1-bis (hydroxymethyl) -2-hydroxyethyl] propionamide}, 2,2′-azobis {2-methyl-N- [2- ( 1-hydroxybutyl)] propionamide}, 2,2′-azobis [2-methyl-N- (2-hydroxyethyl) propionamide], 2,2′-azobis [N- (2-propenyl) -2- Methylpropionamide], 2,2′-azobis (N-butyl-2-methylpropionamide), 2,2′-azobis (N-cyclohexyl-2-methylpropionamide) and the like;
(3) Cyclic azoamidine compound:
2,2′-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 2,2′-azobis [2- (2-imidazolin-2-yl) propane] disulfate dihydrate, 2,2′-azobis [2- [1- (2-hydroxyethyl) -2-imidazolin-2-yl] propane] dihydrochloride, 2,2′-azobis [2- (2-imidazolin-2-yl) Propane], 2,2′-azobis (1-imino-1-pyrrolidino-2-methylpropane) dihydrochloride, etc .;
(4) Azoamidine compound:
2,2′-azobis (2-methylpropionamidine) dihydrochloride, 2,2′-azobis [N- (2-carboxyethyl) -2-methylpropionamidine] tetrahydrate, etc .;
(5) Other:
Dimethyl 2,2′-azobisisobutyrate, 4,4′-azobis (4-cyanovaleric acid), 2,2′-azobis (2,4,4-trimethylpentane), 1,1′-azobis (1-acetoxy- 1-phenylethane), dimethyl 1,1′-azobis (1-cyclohexanecarboxylate) and the like.

The azo polymerization initiators may be used alone or in combination of two or more.
Among these azo-based polymerization initiators, 4,4′-azobis (4- (4) -azobis (4- (4-azobenzene)) is used from the viewpoint of easy introduction of the oxyalkylene moiety represented by the formula [1] in the fluorine-containing highly branched polymer of the present invention described later. Cyanovaleric acid), 2,2′-azobis [N- (2-carboxyethyl) -2-methylpropionamidine] tetrahydrate, and the like are preferable.

The polymerization initiator C is used in an amount of 5 to 200 mol%, preferably 20 to 200 mol%, more preferably 20 to 100 mol%, based on the number of moles of the monomer A. used.

[Other monomers]
The polymerizable compound used in the present invention may contain other monomers that do not belong to the monomer A and the monomer B as long as the effects of the present invention are not impaired.
The other monomer is not particularly limited as long as it is a monomer having one radical polymerizable double bond in the molecule, but is preferably a vinyl compound or a (meth) acrylate compound.

[Oxyalkylene moiety]
Examples of the alkyl group having 1 to 6 carbon atoms represented by R ¹ in the formula [1] include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, and a sec-butyl group. Tert-butyl group, n-pentyl group, isoamyl group, neopentyl group, tert-amyl group, sec-isoamyl group, cyclopentyl group, n-hexyl group, cyclohexyl group and the like. Among these, an alkyl group having 1 to 4 carbon atoms is preferable, a methyl group, an ethyl group, an n-propyl group, and an n-butyl group are particularly preferable, and a methyl group and an ethyl group are more preferable.
Examples of the alkylene group having 2 to 6 carbon atoms represented by L ¹ include, for example, an ethylene group, trimethylene group, methylethylene group, tetramethylene group, 1-methyltrimethylene group, pentamethylene group, 2,2-dimethyl group. A trimethylene group, a hexamethylene group, etc. are mentioned. Among these, an ethylene group is preferable from the viewpoint of the biomolecule adsorption inhibiting effect.

[Polymerization method of polymerizable compound]
As a polymerization method for polymerizing the polymerizable compound containing at least the monomer A and the monomer B in the presence of a predetermined amount of the polymerization initiator C with respect to the monomer A, known methods such as solution polymerization and dispersion polymerization are used. , Precipitation polymerization, bulk polymerization and the like, among which solution polymerization or precipitation polymerization is preferable. In particular, it is preferable to carry out the reaction by solution polymerization in an organic solvent from the viewpoint of molecular weight control.

Examples of the organic solvent used at this time include aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene, and tetralin; aliphatic or alicyclic hydrocarbons such as n-hexane, n-heptane, mineral spirit, and cyclohexane; Halides such as methyl chloride, methyl bromide, methyl iodide, dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, perchloroethylene, orthodichlorobenzene; ethyl acetate, butyl acetate, methoxybutyl acetate, methyl cellosolve acetate, ethyl cellosolve Esters or ester ethers such as acetate and propylene glycol monomethyl ether acetate; diethyl ether, tetrahydrofuran, 1,4-dioxane, methyl cellosolve, ethyl cellosolve, butyl cell Ethers such as sorb and propylene glycol monomethyl ether; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, di-n-butyl ketone and cyclohexanone; methanol, ethanol, n-propanol, 2-propanol, n-butanol and 2-butanol , Tert-butyl alcohol, 2-ethylhexyl alcohol, benzyl alcohol, ethylene glycol and other alcohols; N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone and other amides; dimethyl sulfoxide, etc. Sulfoxides, and a mixed solvent of two or more of these.

Of these, aromatic hydrocarbons, halides, esters, ester ethers, ethers, ketones, alcohols, amides and the like are preferable, and benzene, toluene, xylene, ortho are particularly preferable. Dichlorobenzene, ethyl acetate, butyl acetate, propylene glycol monomethyl ether acetate, propylene glycol monomethyl ether, tetrahydrofuran, 1,4-dioxane, methyl ethyl ketone, methyl isobutyl ketone, methanol, ethanol, n-propanol, 2-propanol, n-butanol, 2-butanol, tert-butyl alcohol, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone and the like.

When the polymerization reaction is performed in the presence of an organic solvent, the mass of the organic solvent relative to 1 part by mass of the monomer A is usually 5 to 120 parts by mass, preferably 10 to 110 parts by mass.
The polymerization reaction is carried out under normal pressure, under pressure and under pressure, or under reduced pressure, and is preferably carried out under normal pressure in view of simplicity of the apparatus and operation. Further, preferably carried out in an atmosphere of inert gas such as N _2.
The polymerization temperature is arbitrary as long as it is not higher than the boiling point of the reaction mixture, but is preferably 50 to 200 ° C., more preferably 80 to 150 ° C., more preferably 80 to 130 ° C. from the viewpoint of polymerization efficiency and molecular weight control. More preferred.
The reaction time varies depending on the reaction temperature, the types and ratios of the monomer A, the monomer B and the polymerization initiator C, the type of polymerization solvent, etc., but cannot be defined unconditionally, but is preferably 30 to 720 minutes, more preferably Is 40 to 540 minutes.
After completion of the polymerization reaction, the obtained fluorine-containing hyperbranched polymer is collected by an arbitrary method, and post-treatment such as washing is performed as necessary. Examples of a method for recovering the polymer from the reaction solution include a method such as reprecipitation.

The weight average molecular weight (Mw) of the fluorine-containing highly branched polymer of the present invention measured by gel permeation chromatography in terms of polystyrene is 1,000 to 400,000, preferably 2,000 to 200,000, more preferably. It is 2,000 to 100,000, more preferably 2,000 to 50,000.

<Method for producing fluorine-containing highly branched polymer>
The fluorine-containing highly branched polymer of the present invention has an oxyalkylene moiety represented by the above formula [1] at the molecular end.
The introduction of the oxyalkylene moiety involves introduction of a carboxy group-containing fluorine-containing highly branched polymer, which can be said to be a precursor of the fluorine-containing highly branched polymer, or an activated product thereof, and a compound represented by the above formula [3] It is obtained by reacting with an alkyl ether).
This production method is also an object of the present invention.

The carboxy group-containing fluorine-containing highly branched polymer includes a monomer A having two or more radical polymerizable double bonds in the molecule, and a monomer having a fluoroalkyl group and at least one radical polymerizable double bond in the molecule. A polymer obtained by polymerizing a polymerizable compound containing at least B in the presence of a polymerization initiator having a carboxy group in a molecule of 5 to 200 mol% based on the number of moles of the monomer A.
The carboxy group activated product is a polymer obtained by reacting the carboxy group-containing fluorine-containing hyperbranched polymer with a known active esterifying agent to partially or fully convert the carboxy group into an active ester. It is. Examples of the known active esterifying agent include nitrophenol, pentafluorophenol, N-hydroxysuccinimide and the like.

The carboxy group-containing fluorine-containing highly branched polymer can be produced using the method described in the above-mentioned [Polymerization method of polymerizable compound], and the monomer A and monomer B include the above [monomer A] [monomer B] and the polymerization initiator having a carboxy group such as 4,4′-azobis (4-cyanovaleric acid) among the above-mentioned [polymerization initiator C]. An initiator can be suitably used. In addition to monomer A and monomer B, the above-mentioned [other monomers] may be used in combination as a polymerizable compound.

When the carboxy group-activated fluorine-containing highly branched polymer is used, the carboxy group-containing fluorine-containing highly branched polymer and the known active esterifying agent are reacted in a solvent capable of dissolving these compounds. Then, an active esterifying agent is bonded to part or all of the carboxy groups of the fluorine-containing hyperbranched polymer to obtain a carboxy group activated product. As said solvent, the solvent used for the above-mentioned [polymerization method of a polymeric compound] can be mentioned, for example.
In the above reaction, the amount of the active esterifying agent used is, for example, 0.1 to 10 mol times the amount of carboxy groups of the carboxy group-containing fluorine-containing highly branched polymer. By changing the amount of the active esterifying agent used, the ratio of the activated carboxy group to the total carboxy group can be adjusted.
The above reaction is carried out under normal pressure, under pressure and under pressure, or under reduced pressure, and is preferably carried out under normal pressure in view of simplicity of the apparatus and operation. Further, preferably carried out in an atmosphere of inert gas such as N _2.
At this time, the reaction temperature is desirably −80 to 200 ° C., preferably 0 to 100 ° C., more preferably 10 to 50 ° C., and the reaction time is 0.1 to 48 hours, preferably 0.2 to 40 ° C. It is desirable to do it in time.
After completion of the reaction, the obtained carboxy group active form is recovered by an arbitrary method, and after-treatment such as washing is performed as necessary, and used in the subsequent steps. Examples of the method for recovering from the reaction solution include methods such as reprecipitation.

The reaction of the carboxy group-containing fluorine-containing highly branched polymer or the activated carboxy group thereof with the compound represented by the above formula [3] is carried out in a solvent capable of dissolving these compounds in the presence of a known condensing agent. Will be implemented. As the solvent, for example, the solvent used in the above-mentioned [Polymerization method of polymerizable compound] can be used.

In the compound represented by the above formula [3], examples of R ¹ and L ¹ in the formula include the groups shown in the above-mentioned [oxyalkylene moiety].
Although it does not specifically limit as a compound represented by the said Formula [3], In particular, it is preferable that it is a compound in which n represents an integer greater than or equal to 3. In addition, from the viewpoint of the characteristics of the resulting fluorine-containing highly branched polymer, a compound in which n represents an integer of 45 or less is preferable. Further, a compound in which n represents an integer of 5 to 45, a compound in which n represents an integer of 10 to 45, a compound in which n represents an integer of 5 to 30 or a compound in which n represents an integer of 10 to 30 It is preferable that
Examples of the compound represented by the formula [3] include ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, diethylene glycol monobutyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, tetraethylene glycol monomethyl ether, heptaethylene glycol monomethyl. Ether, hexaethylene glycol monomethyl ether, nonaethylene glycol monomethyl ether, dodecaethylene glycol monoethyl ether, tridecaethylene glycol monomethyl ether, tetradecaethylene glycol monomethyl ether, polyethylene glycol monomethyl ether, dipropylene glycol monomethyl ether, tripropylene glycol Methyl ether, hepta propylene glycol monomethyl ether, tri (tetramethylene glycol) monomethyl ether, nona (tetramethylene glycol) monomethyl ether, poly (tetramethylene glycol) monomethyl ether, and the like. Among these, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, hexaethylene glycol monomethyl ether, dodecaethylene glycol monomethyl ether, polyethylene glycol monomethyl ether, and the like can be suitably used.

Examples of the known condensing agent include N, N′-dicyclohexylcarbodiimide (DCC), N, N′-diisopropylcarbodiimide (DIC), and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC) hydrochloride. Carbodiimides such as N, N′-carbonyldiimidazole, dimesityl ammonium pentafluorobenzenesulfonate and the like. When carbodiimides such as DCC are used, a catalytic amount of 4-dimethylaminopyridine (DMAP) is preferably used in combination.
The above reaction is carried out under normal pressure, under pressure and under pressure, or under reduced pressure, and is preferably carried out under normal pressure in view of simplicity of the apparatus and operation. Further, preferably carried out in an atmosphere of inert gas such as N _2.
At this time, the reaction temperature is desirably −80 to 200 ° C., preferably 0 to 100 ° C., more preferably 10 to 50 ° C., and the reaction time is 0.1 to 48 hours, preferably 0.2 to 40 ° C. It is desirable to do it in time.
After completion of the above reaction, the obtained hyperbranched polymer (fluorine-containing hyperbranched polymer having an oxyalkylene moiety represented by the formula [1] at the molecular end) is recovered by any method, and washed as necessary. Perform post-processing. Examples of a method for recovering the polymer from the reaction solution include a method such as reprecipitation.

<Method for producing varnish and thin film containing fluorine-containing highly branched polymer>
As a specific method for forming a thin film (thin film having a biomolecule adsorption-inhibiting action) produced from the fluorine-containing highly branched polymer of the present invention, first, a fluorine-containing highly branched polymer is dissolved or dispersed in a solvent, Form (film forming material), and the varnish is cast-coated on a substrate, spin coating method, blade coating method, dip coating method, roll coating method, bar coating method, die coating method, spray coating method, ink jet method, printing The film is applied by a method (eg, letterpress, intaglio, planographic, screen printing, etc.), and then dried by a hot plate or oven to form a film.
Among these coating methods, the spin coating method is preferable. In the case of using the spin coating method, since it can be applied in a single time, even a highly volatile solution can be used, and there is an advantage that highly uniform application can be performed.

The solvent used in the form of the varnish is not particularly limited as long as it dissolves the fluorine-containing highly branched polymer. For example, methanol, acetone, tetrahydrofuran (THF), toluene, N, N-dimethylformamide (DMF), cyclohexanone. Propylene glycol monomethyl ether (PGME), propylene glycol monomethyl ether acetate (PGMEA), propylene glycol monoethyl ether, ethyl lactate, diethylene glycol monoethyl ether, butyl cellosolve, γ-butyrolactone, and the like. These solvents may be used alone, or two or more kinds of solvents may be mixed.
The concentration in which the solvent is dissolved or dispersed is arbitrary, but the concentration of the fluorine-containing highly branched polymer is 0.01 to 90% by mass with respect to the total mass (total mass) of the fluorine-containing highly branched polymer and the solvent. The amount is preferably 0.05 to 50% by mass, more preferably 0.1 to 20% by mass.

The thickness of the thin film made of the fluorine-containing highly branched polymer is not particularly limited, but is usually 0.005 to 50 μm, preferably 0.01 to 20 μm.

<Resin blend containing fluorine-containing highly branched polymer>
The present invention also relates to a resin blend comprising the aforementioned (a) fluorine-containing highly branched polymer, and (b) a thermoplastic resin.

[Thermoplastic resin]
The thermoplastic resin contained in the resin blend of the present invention is not particularly limited. For example, PE (polyethylene), PP (polypropylene), EVA (ethylene-vinyl acetate copolymer), EEA (ethylene-ethyl acrylate copolymer) Polyolefin resins such as PS (polystyrene), HIPS (high impact polystyrene), AS (acrylonitrile-styrene copolymer), ABS (acrylonitrile-butadiene-styrene copolymer), MS (methyl methacrylate-styrene copolymer) Polycarbonate resin; Polyvinyl resin; Polyamide resin; (Meth) acrylic resin such as PMMA (polymethyl methacrylate); PET (polyethylene terephthalate), polybutylene terephthalate, polyester Polyester resins such as lennaphthalate, polybutylene naphthalate, PLA (polylactic acid), poly-3-hydroxybutyric acid, polycaprolactone, polybutylene succinate, polyethylene succinate / adipate; polyphenylene ether resin; modified polyphenylene ether resin; polyacetal resin Polysulfone resin, polyphenylene sulfide resin, polyvinyl alcohol resin, polyglycolic acid, modified starch, cellulose acetate, cellulose triacetate, chitin, chitosan, lignin and the like.
Among them, a polystyrene resin or a (meth) acrylic resin is preferable, and a polystyrene resin or a polymethyl methacrylate resin is particularly preferable.

In the above resin blend, the blending amount of the fluorine-containing highly branched polymer with respect to the thermoplastic resin is preferably 0.01 to 50% by mass, and particularly preferably 0.1 to 40% by mass.

<Biomolecule adsorption suppression film prepared from resin blend and formation method thereof>
The resin blend of the present invention is obtained by dissolving or dispersing the resin blend in a solvent to form a varnish (film-forming material), and applying (coating) the varnish on a base material. Can form a molded body.
The coating method on the substrate includes a cast coating method, a spin coating method, a blade coating method, a dip coating method, a roll coating method, a bar coating method, a die coating method, a spray coating method, an ink jet method, a printing method (a relief plate, an intaglio plate). Lithographic printing, screen printing, etc.) can be selected as appropriate, and since it can be applied in a short time, it can be used even in a highly volatile solution, and it has the advantage of being able to perform highly uniform coating. It is desirable to use a coating method. It is preferable that the resin blend is filtered in advance using a filter having a pore diameter of about 0.2 μm in advance and then applied to the coating.

The solvent used in the form of the varnish is not particularly limited as long as it dissolves the resin blend. Specific examples of these solvents include those described in <Method for producing varnish and thin film containing fluorine-containing hyperbranched polymer>. Examples of the solvent are the same.
The solid content in the varnish is, for example, 0.01 to 50% by mass, 0.05 to 30% by mass, or 0.1 to 20% by mass. Here, the solid content is obtained by removing the solvent component from all components of the varnish.

Examples of the base material include silicon / silicon dioxide coated substrates, silicon wafers, silicon nitride substrates, glass substrates, ITO substrates, plastic substrates (polyimide, polycarbonate, polymethacrylate, polystyrene, polyester, polyolefin, epoxy, melamine, Acetyl cellulose, ABS, AS, norbornene resin, etc.), metal, wood, paper, glass, slate and the like. The shape of these base materials may be a plate shape, a film shape, or a three-dimensional molded body.

After application, if necessary, it is then dried with a hot plate or oven to remove the solvent. The drying temperature and drying time at this time can be appropriately selected from room temperature (approximately 25 ° C.) to 400 ° C., 10 seconds to 48 hours, depending on the solvent used.

The coating film from which the solvent has been removed may be subsequently subjected to annealing of the obtained coating film in a polar medium atmosphere, so-called “solvent annealing”.
As used herein, the term “solvent annealing” refers to solvent vapor treatment and refers to exposure to air containing solvent vapor in a sealed container at room temperature or higher. Solvent annealing generally can change the surface state of the film, and in the present invention, the abundance of the fluorine-containing highly branched polymer on the film surface can be further increased.
In the present invention, examples of the polar medium (solvent used for solvent annealing) include alcohols such as methanol and ethanol, with methanol being preferred.
Further, the temperature during annealing and the annealing time (time for exposure to solvent vapor) are not particularly limited, but can be appropriately selected from, for example, room temperature (approximately 25 ° C.) to the boiling point of the solvent used, 10 seconds to 48 hours.

The film thickness by coating is usually 0.005 to 50 μm, preferably 0.01 to 20 μm after drying and, if necessary, subsequent solvent annealing.

EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated more concretely, this invention is not limited to the following Example.
In the examples, the apparatus and conditions used for sample preparation and physical property analysis are as follows.

(1) ¹ H NMR spectrum apparatus: JNM-ECA700 (manufacturing example 1) manufactured by JEOL Ltd.
JNM-ECP400 (Example 1, 5-7) manufactured by JEOL Ltd.
Solvent: CDCl ₃ (Production Example 1, Example 1)
(CD ₃ ) ₂ C (═O) (Examples 5 to 7)
Criteria: CHCl ₃ (7.26 ppm) (Production Example 1)
Tetramethylsilane (0.00 ppm) (Example 1)
(CH ₃ ) ₂ C (═O) (2.10 ppm) (Examples 5 to 7)
(2) ¹³ C NMR spectrum apparatus: AVANCE (registered trademark) III 600 manufactured by BRUKER
Solvent: CDCl ₃
Reference peak: CDCl ₃ (77.0 ppm)
(3) Gel permeation chromatography (GPC)
Equipment: HLC-8220GPC manufactured by Tosoh Corporation
Column: Shodex (registered trademark) GPC KF-804L, KF-805L manufactured by Showa Denko K.K.
Column temperature: 40 ° C
Solvent: Tetrahydrofuran Detector: RI
(4) IR spectrum device: FT / IR-620 manufactured by JASCO Corporation
Measurement conditions: KBr tablet method, room temperature, under air Resolution: 4 cm ^-1
(5) Spin coater equipment: 1H-D7 manufactured by Mikasa Co., Ltd.
(6) Dryer Equipment: ISUZU-SVK-10S manufactured by Isuzu Manufacturing Co., Ltd.
(7) X-ray photoelectron spectroscopy (XPS)
Equipment: ESCA 5800 manufactured by ULVAC-PHI Co., Ltd.
Measurement conditions: 14.0 kV, 14 mA
Neutralization conditions: bias (V) 6.00
Extractor (V) 30
X = 24.5
Y: Change according to angle (8) Contact angle Device: DropMaster 500 manufactured by Kyowa Interface Science Co., Ltd.
(9) Fluorescence microscope Device: Keyence Co., Ltd. Standard type Biozero fluorescence microscope BZ-8100 series Filter: BZ filter TRITC
Exposure time: 2.5 seconds Excitation wavelength: 494 nm
Absorption wavelength: 520 nm
(10) Scanning electron microscope (SEM) observation apparatus: SS-550 manufactured by Shimadzu Corporation
Acceleration voltage: 15 kV
Magnification: × 1500

Abbreviations represent the following meanings.
DVB: Divinylbenzene [DVB-960, manufactured by Nippon Steel & Sumikin Chemical Co., Ltd.]
C6FA: 2- (perfluorohexyl) ethyl acrylate [FAAC-6 manufactured by Unimatec Co., Ltd.]
ACVA: 4,4′-azobis (4-cyanovaleric acid) [Wako Pure Chemical Industries, Ltd. V-501]
TEGME: Triethylene glycol monoethyl ether [manufactured by Tokyo Chemical Industry Co., Ltd.]
HEGMME: Hexaethylene glycol monomethyl ether [manufactured by Tokyo Chemical Industry Co., Ltd.]
12EGME: Polyethylene glycol monomethyl ether [manufactured by Aldrich, product number: 202487, number average molecular weight: 550]
45EGME: Polyethylene glycol monomethyl ether [manufactured by Aldrich, product number: 202509 number average molecular weight: ˜2,000]
DCC: N, N′-dicyclohexylcarbodiimide [manufactured by Tokyo Chemical Industry Co., Ltd.]
DIC: N, N′-diisopropylcarbodiimide [manufactured by Tokyo Chemical Industry Co., Ltd.]
DMAP: 4- (dimethylamino) pyridine [manufactured by Kanto Chemical Co., Inc.]
PMMA: Polymethyl methacrylate [manufactured by Polymer Source, weight average molecular weight: 315,000]
EGME: ethylene glycol monomethyl ether IPE: diisopropyl ether THF: tetrahydrofuran

[Production Example 1] Production of fluorine-containing hyperbranched polymer 1 having a carboxy group at the terminal Charge 325 g of EGME into a 1 L reaction flask, pour nitrogen for 5 minutes with stirring, and heat until the internal liquid is refluxed (approximately 125 ° C). did.
In a separate 500 mL reaction flask was charged 6.5 g (50 mmol) of DVB as monomer A, 10.5 g (25 mmol) of C6FA as monomer B, 14.0 g (50 mmol) of ACVA as initiator, and 325 g of EGME, and nitrogen was added while stirring. Pour nitrogen replacement.
The contents were dropped into the EGME refluxed in the 1 L reaction flask from the above 500 mL reaction flask charged with DVB, C6FA and ACVA using a dropping pump over 1 hour. After completion of dropping, the mixture was further stirred for 1 hour.
Next, after 553 g of EGME was distilled off from the reaction solution using a rotary evaporator, the residue was added to 650 g of IPE to precipitate the polymer in a slurry state. The slurry was filtered under reduced pressure to obtain a white powdery crude product. This crude product was redissolved in 50 g of THF and added again to 650 g of IPE to reprecipitate the polymer. Further, the above series of operations (vacuum filtration-redissolved in THF-reprecipitation with IPE) was repeated and purified once more. Finally, the obtained precipitate was filtered under reduced pressure and dried under vacuum to obtain 13.8 g of the desired product (fluorinated highly branched polymer 1 having a carboxy group at the terminal) as a white powder.
The ¹ H NMR spectrum of the obtained fluorine-containing highly branched polymer 1 having a carboxy group at the terminal is shown in FIG. 1, and the ¹³ C NMR spectrum is shown in FIG. The unit structure composition (molar ratio) of the fluorine-containing highly branched polymer 1 having a carboxy group at the terminal shown in the following structural formula, calculated from ¹³ C NMR spectrum, is DVB unit [A]: C6FA unit [B]: ACVA unit [ C] = 1.0: 0.7: 0.5. Moreover, the weight average molecular weight Mw measured by polystyrene conversion by GPC of this polymer was 9,500, and dispersion degree: Mw (weight average molecular weight) / Mn (number average molecular weight) was 2.4.

In the formula, a black dot represents a coupling end.

[Example 1] Production of fluorine-containing hyperbranched polymer 2 having a tri (ethylene oxide) moiety at its end 38 mg (5) of fluorine-containing highly branched polymer 1 having a carboxyl group at its end obtained in Production Example 1 in a 25 mL three-necked flask 0.1 μmol), TEGMEE 16 mg (97 μmol), DMAP 7 mg (57 μmol) as a catalyst, DCC 21 mg (100 μmol) as a condensing agent, and 2.7 mg of THF dehydrated in advance with CaH ₂ . This solution was stirred and reacted at room temperature (approximately 20 ° C.) for 24 hours under a nitrogen atmosphere. The precipitated dicyclohexylurea (DCU) was removed by filtration. THF was distilled off under reduced pressure, and the resulting residue was dissolved in chloroform. Next, this solution was washed three times with an aqueous hydrochloric acid solution having a pH of 5 to remove DMAP. Furthermore, after washing twice with distilled water, it was dried over anhydrous sodium sulfate, and chloroform was distilled off under reduced pressure. The residue was washed 3 times with diethyl ether to obtain 9 mg of a white viscous target product (fluorinated highly branched polymer 2 having a tri (ethylene oxide) moiety at the end).
FIG. 3 shows the IR spectrum of the fluorine-containing highly branched polymer 2 having a tri (ethylene oxide) moiety at the terminal, and FIG. 4 shows the ¹ H NMR spectrum. FIG. 3 also shows the IR spectrum of the fluorine-containing highly branched polymer 1 having a carboxy group at the terminal. In the IR spectrum, no broad peak derived from the OH stretching vibration of carboxylic acid was observed in the vicinity of 2800 to 2500 cm ⁻¹ , so that tri (ethylene oxide) sites were present on almost all terminal carboxy groups of the fluorine-containing highly branched polymer 1. It was confirmed that was introduced.

[Example 5] Production of fluorine-containing highly branched polymer 3 having an oligo (ethylene oxide) moiety at the end (number of repeating units of ethylene oxide n = 6) A carboxy group was added to the end obtained in Production Example 1 in a 25 mL three-necked flask. Fluorine-containing highly branched polymer 1 200 mg (21 μmol), HEGMME 120 mg (0.40 mmol), DMAP 27 mg (0.22 mmol) as a catalyst, DIC 60 mg (0.48 mmol) as a condensing agent, and THF 1.3 g previously dehydrated with CaH ₂ were charged. It is. This solution was stirred and reacted at room temperature (approximately 20 ° C.) for 120 hours under a nitrogen atmosphere. Precipitated diisopropyl urea (DIU) was removed by filtration. THF was distilled off under reduced pressure, and the resulting residue was dissolved in chloroform. Next, this solution was washed three times with an aqueous hydrochloric acid solution having a pH of 5 to remove DMAP. Furthermore, after washing twice with distilled water, it was dried over anhydrous sodium sulfate, and chloroform was distilled off under reduced pressure. The residue was dissolved in ethanol, and the remaining unreacted HEGMME was removed by dialysis against ethanol, and the white viscous target product (fluorine-containing highly branched polymer 3 having an oligo (ethylene oxide) moiety at the terminal ( n = 6)) 99 mg was obtained.
FIG. 9 shows the IR spectrum of the fluorine-containing highly branched polymer 3 (n = 6) having an oligo (ethylene oxide) moiety at the terminal, and FIG. 10 shows the ¹ H NMR spectrum. In the IR spectrum, almost no broad peak derived from the OH stretching vibration of carboxylic acid was observed in the vicinity of 2800-2500 cm ⁻¹ , so an oligo (ethylene oxide) moiety was introduced into the terminal carboxy group of fluorine-containing hyperbranched polymer 1. It has been confirmed.

[Example 6] Production of fluorine-containing hyperbranched polymer 4 having an oligo (ethylene oxide) moiety at the end (the number of repeating units of ethylene oxide n = 12) A carboxy group was added to the end obtained in Production Example 1 in a 25 mL three-necked flask. Fluorine-containing highly branched polymer 1 having 500 mg (53 μmol), 12EGME870 mg (1.6 mmol), DMAP 91 mg (0.75 mmol), DIC 200 mg (1.6 mmol) as a condensing agent, and THF 6 previously distilled in the presence of Na / benzophenone. 2 g was charged. This solution was stirred and reacted at room temperature (approximately 20 ° C.) for 24 hours under a nitrogen atmosphere. The precipitated diisopropyl urea (DIU) was removed by filtration, and THF was distilled off under reduced pressure. The obtained residue is dissolved in ethanol, and DMAP and the remaining unreacted 12EGME are removed by dialysis against ethanol to obtain a white viscous target product (fluorine-containing product having an oligo (ethylene oxide) part at the end) 570 mg of hyperbranched polymer 4 (n = 12) was obtained.
FIG. 9 shows the IR spectrum of the fluorine-containing highly branched polymer 4 (n = 12) having an oligo (ethylene oxide) moiety at the terminal, and FIG. 11 shows the ¹ H NMR spectrum. In the IR spectrum, almost no broad peak derived from the OH stretching vibration of carboxylic acid was observed in the vicinity of 2800-2500 cm ⁻¹ , so an oligo (ethylene oxide) moiety was introduced into the terminal carboxy group of fluorine-containing hyperbranched polymer 1. It has been confirmed.

[Example 7] Production of fluorine-containing hyperbranched polymer 5 having a poly (ethylene oxide) moiety at the end (number of repeating units of ethylene oxide n = 45) A carboxy group at the end obtained in Production Example 1 was added to a 25 mL three-necked flask. Fluorine-containing highly branched polymer 1 350 mg (37 μmol), 45 EGME 2.2 g (1.1 mmol), DMAP 70 mg (0.57 mmol), DIC 150 mg (1.2 mmol) as a condensing agent, and previously distilled in the presence of Na / benzophenone 9.5 g of THF was charged. This solution was stirred and reacted at room temperature (approximately 20 ° C.) for 120 hours under a nitrogen atmosphere. The precipitated diisopropyl urea (DIU) was removed by filtration, and THF was distilled off under reduced pressure. The obtained residue was dissolved in ethanol, and DMAP and the remaining unreacted 45EGME were removed by dialysis against ethanol, and the target product of white powder (fluorine-containing high content having a poly (ethylene oxide) part at the end) was obtained. 740 mg of branched polymer 5 (n = 45)) was obtained.
FIG. 9 shows the IR spectrum of the fluorine-containing highly branched polymer 5 (n = 45) having a poly (ethylene oxide) moiety at the terminal, and FIG. 12 shows the ¹ H NMR spectrum. In the IR spectrum, a broad peak derived from the OH stretching vibration of carboxylic acid was hardly observed in the vicinity of 2800-2500 cm ⁻¹ , so a poly (ethylene oxide) site was introduced into the terminal carboxy group of fluorine-containing hyperbranched polymer 1. It has been confirmed.

[Example 2] Preparation of a fluorine-containing highly branched polymer 2 / PMMA blend film having a tri (ethylene oxide) moiety at the terminal and a fluorine-containing highly branched polymer 2 having a tri (ethylene oxide) moiety at the terminal and PMMA obtained in Example 1 Were mixed at a mass ratio of 5:95. This mixture was dissolved in THF so as to have a concentration of 2% by mass and filtered to prepare a varnish. This varnish was spin-coated (3,000 rpm, 60 seconds) on a silicon wafer to form a blend film.
After film formation, heat treatment was performed under vacuum at room temperature (approximately 20 ° C.) or 150 ° C. for 24 hours. The film thickness estimated from ellipsometry measurement was 100 nm.
Angle-resolved XPS measurement was performed on each of the obtained films to evaluate the surface composition of the films. The photoelectron intensity ratio (I _F1s / I _C1s ) of fluorine and carbon with respect to the sine (sin θ) of the photoelectron emission angle in each blend film is shown in FIG. 5 (heat treatment temperature; FIG. 5 (a) room temperature, (b) 150 ° C. ). In any film, I _F1s / I _C1s increased as sin θ decreased. The smaller the value of sin θ, the shallower the analysis depth, that is, near the surface. That is, even if the fluorine-containing highly branched polymer 2 has a hydrophilic tri (ethylene oxide) moiety at the end, it has fluorine with low surface free energy, and therefore can be concentrated near the surface of the blend film with PMMA. confirmed.

[Example 8] Preparation of fluorine-containing highly branched polymer 3 (n = 6) / PMMA blend film having an oligo (ethylene oxide) moiety at the end Oligo at the end obtained in Example 5 in place of fluorine-containing highly branched polymer 2 A blend film was prepared in the same manner as in Example 2 except that the fluorine-containing highly branched polymer 3 (n = 6) having an (ethylene oxide) part was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum, and the same evaluation was performed.
The film thickness estimated from the ellipsometric measurement of the obtained blend film was 200 nm. FIG. 13 shows the photoelectron intensity ratio (I _F1s / I _C1s ) of fluorine and carbon with respect to the sine of the photoelectron emission angle (sin θ).

[Example 9] Preparation of fluorine-containing hyperbranched polymer 4 (n = 12) / PMMA blend film having an oligo (ethylene oxide) moiety at the end Oligo at the end obtained in Example 6 in place of fluorine-containing highly branched polymer 2 A blend film was prepared in the same manner as in Example 2 except that the fluorine-containing highly branched polymer 4 (n = 12) having an (ethylene oxide) part was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum, and the same evaluation was performed.
The film thickness estimated from the ellipsometric measurement of the obtained blend film was 200 nm. Further, the photoelectron intensity ratio (I _F1s / I _C1s ) of fluorine and carbon with respect to the sine of the photoelectron emission angle (sin θ) is also shown in FIG.

[Example 10] Preparation of fluorine-containing highly branched polymer 5 (n = 45) / PMMA blend film having a poly (ethylene oxide) moiety at the terminal A blend film was prepared in the same manner as in Example 2 except that the fluorine-containing highly branched polymer 5 (n = 45) having an (ethylene oxide) part was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum, and the same evaluation was performed.
The film thickness estimated from the ellipsometric measurement of the obtained blend film was 200 nm. Further, the photoelectron intensity ratio (I _F1s / I _C1s ) of fluorine and carbon with respect to the sine of the photoelectron emission angle (sin θ) is also shown in FIG.

As shown in FIG. 13, in any film, I _F1s / I _C1s increased as sin θ decreased. That is, fluorine in the vicinity of the surface regardless of the chain length (n = 6, 12, 45) of the terminal hydrophilic portion (oligo (ethylene oxide) portion or poly (ethylene oxide) portion) of the fluorine-containing highly branched polymers 3, 4, 5 It was confirmed that the fraction was almost the same. From this, it was confirmed that the hyperbranched polymers 3, 4, and 5 having fluorine having a low surface free energy are concentrated near the surface of the blend film with PMMA even though they have a hydrophilic portion at the terminal.

[Example 3] Surface structure rearrangement of fluorine-containing highly branched polymer 2 / PMMA blend film having tri (ethylene oxide) moiety at the terminal Example 2 Fluorine-containing highly branched polymer 2 having a tri (ethylene oxide) moiety at the terminal prepared in Example 2 / PMMA blend membrane was heat treated at 150 ° C. under vacuum for 24 hours.
In order to evaluate the change in the surface structure of the membrane when it comes into contact with water, measurement of the change in contact angle with time using a 1 μL ultrapure water (millQ water) probe at room temperature (approximately 20 ° C.) in the atmosphere (60 Seconds). The results are shown in FIG.

[Comparative Example 1] Surface structure reorganization of fluorine-containing highly branched polymer 1 / PMMA blend film having carboxy group at the terminal, except that fluorine-containing highly branched polymer 1 having a carboxyl group at the terminal obtained in Production Example 1 was used In the same manner as in Example 2, a fluorine-containing highly branched polymer 1 / PMMA blend film was produced. This film was heat-treated in the same manner as in Example 3 and evaluated. The results are also shown in FIG.

As shown in FIG. 6, in the fluorine-containing highly branched polymer 1 / PMMA blend film having a carboxy group at the terminal, only a monotonous decrease in contact angle with water due to evaporation of water droplets was observed. On the other hand, on the blend film of fluorine-containing highly branched polymer 2 having a tri (ethylene oxide) portion at the end and PMMA, an exponential decrease in contact angle was observed within a few seconds after the water droplet was dropped. This is known to be caused by surface structure reorganization accompanying water contact. From this result, it was confirmed that the terminal tri (ethylene oxide) part of the fluorine-containing hyperbranched polymer 2 concentrated on the surface in the blend film appeared at the water interface with contact with water.

[Example 11] Surface structure rearrangement of fluorine-containing hyperbranched polymer 3 (n = 6) / PMMA blend film having an oligo (ethylene oxide) moiety at the end. For the blend film obtained in Example 8, Example 3 and The same heat treatment was performed and evaluated. The results are shown in FIG.

[Example 12] Surface structure rearrangement of fluorine-containing hyperbranched polymer 4 (n = 12) / PMMA blend film having an oligo (ethylene oxide) moiety at the end. For the blend film obtained in Example 9, Example 3 and The same heat treatment was performed and evaluated. The results are also shown in FIG.

[Example 13] Surface structure rearrangement of fluorine-containing hyperbranched polymer 5 (n = 45) / PMMA blend film having a poly (ethylene oxide) portion at the end. For the blend film obtained in Example 10, Example 3 and The same heat treatment was performed and evaluated. The results are also shown in FIG.

As shown in FIG. 14, in the fluorine-containing highly branched polymer 4 (n = 12) / PMMA blend film having an oligo (ethylene oxide) part at the terminal, the contact angle derived from the reorganization of the film surface within a few seconds after dropping the water droplet. A slight exponential decrease in water contact angle was observed, followed by a monotonic decrease in water contact angle due to water droplet evaporation. On the other hand, in the fluorine-containing hyperbranched polymer 3 (n = 6) / PMMA blend film having an oligo (ethylene oxide) portion at the terminal, the former is not clearly observed, and the contact angle with water due to the evaporation of water droplets. Only a monotonic decrease was observed. Furthermore, in the fluorine-containing hyperbranched polymer 5 (n = 45) / PMMA blend film having a poly (ethylene oxide) part at the terminal, the contact angle with water significantly decreased with the passage of time after the water droplet was dropped. From this result, the terminal oligo (ethylene oxide) part or poly (ethylene oxide) part of the fluorine-containing hyperbranched polymer concentrated on the surface in the blend film appears at the water interface upon contact with water, and the extent is It was confirmed that it was different depending on the chain length (number of repeating units n).

[Example 4] Protein adsorption behavior of fluorine-containing highly branched polymer 2 / PMMA blend film A fluorine-containing highly branched polymer 2 / PMMA blend film was prepared in the same manner as in Example 2 except that the silicon wafer was changed to a cover glass. did. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The membrane was washed with ultrapure water and placed at the bottom of a 24-well plate. Next, the membrane was immersed in ultrapure water for 24 hours, and then washed with phosphate buffered saline (PBS). This membrane was immersed in fluorescein isocyanate-labeled bovine serum albumin (BSA) [manufactured by ELASTIN PRODUCTS COMPANY] / PBS prepared at 10 μg / mL, 50 μg / mL, and 100 μg / mL at 37 ° C. for 1 hour. Thereafter, each membrane was washed with PBS and observed under a fluorescence microscope in PBS to evaluate the adsorption behavior of bovine serum albumin on the membrane. FIG. 7 shows the obtained fluorescence micrograph, and FIG. 8 shows a graph plotting the luminance of this image with the hybrid cell count function [Software by Keyence Corporation] and plotting it against the concentration of bovine serum albumin.

Comparative Example 2 Protein Adsorption Behavior of PMMA Film A PMMA film was produced in the same manner as in Example 2 except that the fluorine-containing highly branched polymer 2 was not added and the silicon wafer was changed to a cover glass. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The operation was performed in the same manner as in Example 4 except that this membrane was used. The results are also shown in FIGS.

As shown in FIGS. 7 and 8, it was revealed that the fluorescence intensity resulting from the adsorption of albumin in the blend film of the present invention was weaker than that in the PMMA film. From this, it was confirmed that the adsorption of albumin was suppressed on the surface of the blend film of the present invention.

[Example 14] Protein adsorption behavior of fluorine-containing hyperbranched polymer 3 (n = 6) / PMMA blend film having an oligo (ethylene oxide) moiety at the terminal end obtained in Example 5 instead of fluorine-containing hyperbranched polymer 2 A blend film was prepared in the same manner as in Example 2 except that the fluorine-containing highly branched polymer 3 (n = 6) having an oligo (ethylene oxide) portion was used and the silicon wafer was changed to a cover glass. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The membrane was washed with ultrapure water and placed at the bottom of a 24-well plate. Next, the membrane was immersed in ultrapure water for 24 hours, and then washed with phosphate buffered saline (PBS). This membrane was immersed in fluorescein isocyanate-labeled bovine serum albumin (BSA) [ELASTIN PRODUCTS COMPANY] / PBS prepared at 5 μg / mL, 20 μg / mL, and 50 μg / mL at 37 ° C. for 1 hour. Thereafter, each membrane was washed with PBS and observed under a fluorescence microscope in PBS to evaluate the adsorption behavior of bovine serum albumin on the membrane. FIG. 15 shows the obtained fluorescence micrograph, and FIG. 16 shows a graph in which the brightness of this image is digitized using the hybrid cell count function [Keyence Co., Ltd. software] and plotted against the bovine serum albumin concentration.

[Example 15] Protein adsorption behavior of fluorine-containing hyperbranched polymer 4 (n = 12) / PMMA blend film having an oligo (ethylene oxide) moiety at the terminal end obtained in Example 6 instead of fluorine-containing hyperbranched polymer 2 A blend film was prepared in the same manner as in Example 2 except that fluorine-containing highly branched polymer 4 (n = 12) having an oligo (ethylene oxide) portion was used and the silicon wafer was changed to a cover glass. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The operation was performed in the same manner as in Example 14 except that this membrane was used. The results are shown in FIGS. 15 and 16 together.

[Example 16] Protein adsorption behavior of fluorine-containing hyperbranched polymer 5 (n = 45) / PMMA blend film having a poly (ethylene oxide) moiety at the terminal end obtained in Example 7 in place of fluorine-containing hyperbranched polymer 2 A blend film was prepared in the same manner as in Example 2 except that the fluorine-containing highly branched polymer 5 (n = 45) having a poly (ethylene oxide) portion was used and the silicon wafer was changed to a cover glass. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The operation was performed in the same manner as in Example 14 except that this membrane was used. The results are shown in FIGS. 15 and 16 together.

Comparative Example 3 Protein Adsorption Behavior of PMMA Film A PMMA film was produced in the same manner as in Example 2 except that the fluorine-containing highly branched polymer 2 was not added and the silicon wafer was changed to a cover glass. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The operation was performed in the same manner as in Example 14 except that this membrane was used. The results are shown in FIGS. 15 and 16 together.

As shown in FIGS. 15 and 16, the fluorescence intensity resulting from the adsorption of albumin in the blend film of the present invention is weaker than that in the PMMA film, and the adsorption of albumin is suppressed on the surface of the blend film of the present invention. Was confirmed. In particular, it became clear that it was most remarkable in the fluorine-containing highly branched polymer 4 (n = 12) / PMMA blend film. Comparing the results of the fluorine-containing highly branched polymer 3 (n = 6) / PMMA blend film and the fluorine-containing highly branched polymer 4 (n = 12) / PMMA blend film, the film increases as the chain length of oligo (ethylene oxide) increases. When the adsorption of albumin on the surface was suppressed and the chain length became longer and n = 45, albumin was adsorbed on the membrane surface. This is presumably because a part of the fluorine-containing highly branched polymer 5 was dissolved by immersion in water for a long time.

[Example 17] Platelet adhesion behavior of fluorine-containing hyperbranched polymer 3 (n = 6) / PMMA blend film having an oligo (ethylene oxide) moiety at the terminal end obtained in Example 5 instead of fluorine-containing hyperbranched polymer 2 A blend film was prepared in the same manner as in Example 2 except that fluorine-containing highly branched polymer 3 (n = 6) having an oligo (ethylene oxide) part was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
This membrane was immersed in phosphate buffered saline (PBS) at room temperature (approximately 20 ° C.) for 12 hours. On this membrane, platelet-rich plasma prepared by diluting platelet-rich plasma prepared from normal human whole blood with poor platelet plasma was mounted and allowed to stand at 37 ° C. for 1 hour. The membrane was washed with PBS and then immersed in a 1% by mass glutaraldehyde / PBS solution at 37 ° C. for 2 hours to immobilize the adherent platelets on the membrane. The membrane was washed with PBS and sterilized water, dried, and then evaluated for platelet adhesion to the membrane by SEM observation. The obtained SEM image is shown in FIG. 17, and the result of classifying the number of adhered platelets and the degree of activation thereof is shown in FIG. The activation degree was in accordance with the following criteria.
[Activity classification criteria]
Category I: Round platelets Category II: Platelets with partially developed pseudopod formation and flattening Category III: Platelets with pseudopod formation and flattening (fully activated)

[Example 18] Platelet adhesion behavior of fluorine-containing highly branched polymer 4 (n = 12) / PMMA blend film having an oligo (ethylene oxide) moiety at the terminal end obtained in Example 6 instead of fluorine-containing highly branched polymer 2 A blend film was prepared in the same manner as in Example 2 except that fluorine-containing highly branched polymer 4 (n = 12) having an oligo (ethylene oxide) part was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The operation was performed in the same manner as in Example 17 except that this membrane was used. The results are also shown in FIGS.

[Example 19] Platelet adhesion behavior of fluorine-containing hyperbranched polymer 5 (n = 45) / PMMA blend film having a poly (ethylene oxide) moiety at the terminal end obtained in Example 7 in place of fluorine-containing hyperbranched polymer 2 A blend film was prepared in the same manner as in Example 2 except that fluorine-containing highly branched polymer 5 (n = 45) having a poly (ethylene oxide) portion was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The operation was performed in the same manner as in Example 17 except that this membrane was used. The results are also shown in FIGS.

Comparative Example 4 Platelet Adhesion Behavior of Fluorine-containing Highly Branched Polymer 1 / PMMA Blend Film Having Carboxy Groups at Terminals Fluorine-containing Highly Carboxy Groups Having Terminal Carboxy Groups Obtained in Production Example 1 Instead of Fluorine-containing Hyperbranched Polymer 2 A blend film was prepared in the same manner as in Example 2 except that the branched polymer 1 was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The operation was performed in the same manner as in Example 17 except that this membrane was used. The results are also shown in FIGS.

[Comparative Example 5] Platelet adhesion behavior of PMMA film A PMMA film was prepared in the same manner as in Example 2 except that the fluorine-containing highly branched polymer 2 was not added. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The operation was performed in the same manner as in Example 17 except that this membrane was used. The results are also shown in FIGS.

[Comparative Example 6] Platelet adhesion behavior of PET film The same operation as in Example 17 was carried out except that a PET film [manufactured by Teijin DuPont Films Ltd.] was used. The results are also shown in FIGS.

As shown in FIGS. 17 and 18, in the fluorine-containing highly branched polymer 1 / PMMA blend film, platelets adhered and activated as much as or more than the PET film, whereas in the blend film of the present invention, It was confirmed that the platelet adhesion number was extremely small. From this, it is clear that platelet adhesion was suppressed by the effect of introducing the oligo (ethylene oxide) part. In particular, in the fluorine-containing highly branched polymer 4 (n = 12) / PMMA blend film and the fluorine-containing highly branched polymer 5 (n = 45), not only the platelet adhesion number is remarkably reduced, but also the formation and flattening of false feet. Did not progress much.

Claims (17)

1. A polymerizable compound comprising at least a monomer A having two or more radical polymerizable double bonds in the molecule and a monomer B having at least one radical polymerizable double bond in the molecule; A fluorine-containing highly branched polymer obtained by polymerizing in the presence of 5 to 200 mol% of a polymerization initiator C based on the number of moles of monomer A, and having an oxy group represented by the formula [1] at its molecular end A fluorine-containing highly branched polymer having an alkylene moiety.
   

   

   (Wherein R ¹ represents an alkyl group having 1 to 6 carbon atoms, L ¹ represents an alkylene group having 2 to 6 carbon atoms, and n represents an integer of 1 to 60).
2. The fluorine-containing highly branched polymer according to claim 1, wherein n is an integer of 1 to 30.
3. The fluorine-containing hyperbranched polymer according to claim 1 or 2, wherein the oxyalkylene moiety is bonded to the molecular end via a fragment of the polymerization initiator C.
4. The fluorine-containing highly branched polymer according to any one of claims 1 to 3, wherein the monomer A is a compound having one or both of a vinyl group and a (meth) acryl group.
5. The fluorine-containing highly branched polymer according to claim 4, wherein the monomer A is a divinyl compound or a di (meth) acrylate compound.
6. The fluorine-containing highly branched polymer according to claim 5, wherein the monomer A is divinylbenzene.
7. The fluorine-containing highly branched polymer according to any one of claims 1 to 6, wherein the monomer B is a compound having at least one of either a vinyl group or a (meth) acryl group.
8. The fluorine-containing highly branched polymer according to claim 7, wherein the monomer B is a compound represented by the formula [2].
   

   

   (In the formula, R ² represents a hydrogen atom or a methyl group, and R ³ represents a C 2-12 fluoroalkyl group which may be substituted with a hydroxy group.)
9. The fluorine-containing highly branched polymer according to any one of claims 1 to 8, wherein the polymerization initiator C is an azo polymerization initiator.
10. A varnish containing the fluorine-containing highly branched polymer according to any one of claims 1 to 9.
11. The thin film which has the biomolecule adsorption | suction suppression ability produced from the fluorine-containing hyperbranched polymer as described in any one of Claims 1 thru | or 9.
12. (A) A resin blend comprising the fluorine-containing highly branched polymer according to any one of claims 1 to 9 and (b) a thermoplastic resin.
13. A biomolecule adsorption inhibiting film produced from the resin blend according to claim 12.
14. A polymerizable compound comprising at least a monomer A having two or more radical polymerizable double bonds in the molecule and a monomer B having at least one radical polymerizable double bond in the molecule; Carboxy group-containing fluorine-containing highly branched polymer obtained by polymerizing in the presence of a polymerization initiator having a carboxy group in the molecule of 5 to 200 mol% relative to the number of moles of monomer A, or an activated product of the carboxy group And the compound represented by the formula [3] is reacted. The method for producing a fluorine-containing highly branched polymer according to any one of claims 1 to 9.
    

    

    (Wherein R ¹ represents an alkyl group having 1 to 6 carbon atoms, L ¹ represents an alkylene group having 2 to 6 carbon atoms, and n represents an integer of 1 to 60).
15. The manufacturing method according to claim 14, wherein n is an integer of 1 to 30.
16. A method for producing a thin film having a biomolecule adsorption inhibiting ability produced from the fluorine-containing highly branched polymer according to any one of claims 1 to 9,
    Inhibition of biomolecule adsorption, including a step of applying a liquid containing the fluorine-containing hyperbranched polymer in a solvent on a substrate by spin coating to form a coating film, and a step of drying the coating film and removing the solvent For producing a thin film having a function.
17. A method for producing a biomolecule adsorption-suppressing membrane produced from the resin blend according to claim 12,
    Production of a biomolecule adsorption inhibiting film comprising a step of applying a liquid containing the resin blend in a solvent on a substrate by a spin coating method to form a coating film, and a step of drying the coating film and removing the solvent. Method.

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