JP6645971B2 - Fluorine-containing hyperbranched polymer and biomolecule adsorption suppressing surface - Google Patents

Description

  The present invention relates to a novel fluorine-containing hyperbranched polymer and a surface (membrane) for suppressing adsorption of biomolecules formed using the fluorine-containing hyperbranched polymer.

  BACKGROUND ART In recent years, polymer (polymer) materials have been increasingly used in various fields. Accordingly, the properties of the matrix as well as the properties of its surface and interface have become important in the polymer materials according to the respective fields. Particularly, in recent years, medical materials using various polymer materials have been studied, and blood filters, artificial kidney membranes, plasma separation membranes, catheters, artificial lung membranes, artificial blood vessels, adhesion prevention membranes, artificial membranes, etc. It is expected to be used for skin and the like. In this case, since the synthetic material which is a foreign substance to the living body is used in contact with the tissue or blood in the living body, 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 base material such as instruments and materials to be used. For example, mainly in the medical field, when measuring and analyzing a small amount of protein such as proteome analysis, if there are many adsorbed components, not only can the protein analysis not be performed accurately, but also the protein is substantially lost. There is a possibility that it will end up. In addition, problems such as a decrease in useful proteins during extracorporeal circulation such as an artificial kidney, formation of a thrombus due to adhesion and aggregation of platelets, and coagulation of blood due to adsorption of a coagulation-related protein such as fibrinogen occur. In the food field as well, there are problems such as deterioration in quality due to adsorption of biological components to product containers, and problems such as blockage and deterioration of pipelines due to adsorption of biological components to pipelines during the production process.

  In general, it is known that a polymer having hydrophilicity has biocompatibility with biomolecules and has an effect of suppressing nonspecific adsorption of biomolecules. Biocompatible polymers that suppress nonspecific adsorption of cells and protein components include polyethylene glycol (PEG) or polyethylene oxide (PEO), polyvinylpyrrolidone (PVP), poly (2-hydroxyethyl methacrylate) (PHEMA), 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, and carboxybetaine are exemplified. .

  For example, Patent Literature 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 of a biochip for nonspecific adsorption of DNA. It has been disclosed.

  In Non-Patent Document 1, a polymer blend solution of PMEA and polymethyl methacrylate (PMMA) is spin-coated on a substrate, and solvent drying and heat treatment are performed to form a PMMA blend film in which PMEA is segregated on the surface. A fabrication technique is disclosed.

JP 2004-279204 A

Phys. Chem. Chem. Phys. , 13, 4928-4934 (2011).

  The PEO having a thiol group at one end described in Patent Literature 1 needs to be immersed in the solution for a long time when coated on a gold-deposited glass substrate, and is not suitable for producing an adsorption suppression surface. An efficient manufacturing method has been a problem.

  Further, in the method described in Non-Patent Document 1, heat treatment requires several hours to one day after spin-coating a polymer blend solution of PMEA and PMMA on a substrate. The method was the challenge.

  The present inventors have conducted intensive studies to achieve the above object, and as a result, a resin blend containing a fluoroalkyl group and a fluorinated hyperbranched polymer having an oxyalkylene moiety at a molecular terminal, and a resin blend containing a thermoplastic resin have been spin-coated and the like It has been found that a coating method that can produce a thin film in a short time can easily form a surface capable of suppressing the adsorption of biomolecules such as proteins on various substrates such as plastics. Completed.

That is, the present invention provides, as a first aspect, a monomer A having two or more radically polymerizable double bonds in a molecule and a monomer B having a fluoroalkyl group and at least one radically polymerizable double bond in a molecule. And a polymerizable compound containing at least 5 to 200 mol% of a polymerization initiator C with respect to the number of moles of the monomer A, and a fluorine-containing hyperbranched polymer obtained by polymerizing the polymerizable compound. And a fluorinated hyperbranched polymer having an oxyalkylene moiety represented by Formula [1].
(In the formula, 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 hyperbranched 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 hyperbranched polymer according to the first aspect or the second aspect, wherein the oxyalkylene moiety is bonded to a molecular terminal of the polymerization initiator C via a fragment thereof.
As a fourth aspect, the fluorinated hyperbranch according to any one of the first to third aspects, wherein the monomer A is a compound having one or both of a vinyl group and a (meth) acryl group. For polymers.
As a fifth aspect, the present invention relates to the fluorine-containing hyperbranched polymer according to the fourth aspect, wherein the monomer A is a divinyl compound or a di (meth) acrylate compound.
As a sixth aspect, the present invention relates to the fluorinated hyperbranched polymer according to the fifth aspect, wherein 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 to sixth aspects. Related to branched polymers.
As an eighth aspect, the present invention relates to the fluorine-containing hyperbranched polymer according to the seventh aspect, 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 fluoroalkyl group having 2 to 12 carbon atoms which may be substituted with a hydroxy group.)
As a ninth aspect, the present invention relates to the fluorinated hyperbranched polymer according to any one of the first to eighth aspects, wherein the polymerization initiator C is an azo-based polymerization initiator.
As a tenth aspect, the present invention relates to a varnish containing the fluorinated hyperbranched polymer according to any one of the first to ninth aspects.
As an eleventh aspect, the present invention relates to a thin film having a biomolecule adsorption suppressing ability, which is produced from the fluorinated hyperbranched polymer according to any one of the first to ninth aspects.
As a twelfth aspect, the present invention relates to a resin blend containing (a) the fluorinated hyperbranched polymer according to any one of the first to ninth aspects, and (b) a thermoplastic resin.
As a thirteenth aspect, the present invention relates to a biomolecule adsorption suppressing film produced from the resin blend according to the twelfth aspect.
As a fourteenth aspect, a polymerization including at least a monomer A having two or more radically polymerizable double bonds in a molecule and a monomer B having a fluoroalkyl group and at least one radically polymerizable double bond in a molecule Group-containing fluorinated hyperbranched polymer obtained by polymerizing an acidic compound in the presence of a polymerization initiator having a carboxy group in the molecule of 5 to 200 mol% based on 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 to ninth aspects, wherein the activated carboxy group is reacted with a compound represented by the formula [3]. About.
(In the formula, 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, a method for producing a thin film having a biomolecule adsorption-suppressing ability, which is produced from the fluorine-containing hyperbranched polymer according to any one of the first to ninth aspects,
A step of applying a liquid containing the fluorinated hyperbranched polymer in a solvent onto a substrate by a spin coating method to form a coating film, and a step of drying the coating film and removing the solvent to suppress biomolecule adsorption. The present invention relates to a method for producing a thin film having a function.
As a seventeenth aspect, there is provided a method for producing a biomolecule adsorption suppression membrane produced from the resin blend according to the twelfth aspect,
Production of a biomolecule adsorption suppressing film, comprising a step of applying a liquid containing the resin blend in a solvent to a substrate by a spin coating method to form a coating film, and a step of drying the coating film and removing the solvent. About the method.

According to the present invention, a fluorine-containing hyperbranched polymer having an oxyalkylene moiety having an effect of suppressing the adsorption of a biomolecule at a molecular terminal is spin-coated using a varnish containing the polymer or a resin blend containing the polymer. A film can be easily formed by coating, and a surface capable of suppressing adsorption of biomolecules such as proteins on a substrate in a short time can be produced.
In addition, since the fluorine-containing hyperbranched polymer having an oxyalkylene moiety at the molecular terminal of the present invention has a positively introduced branched structure, it has less entanglement between molecules than linear polymers and exhibits a fine particle behavior. . Furthermore, the fluorine-containing hyperbranched polymer whose surface energy is reduced by the fluoroalkyl group makes it easy for air and other substances to move to the surface side, which is a free interface, in the thermoplastic resin used as the matrix, and imparts activity to the resin surface It's easy to do. Therefore, when producing a molded article such as a film from a resin blend containing the above-mentioned thermoplastic resin and a fluorine-containing hyperbranched polymer having an oxyalkylene site at the molecular terminal of the present invention, the finely divided fluorine-containing hyperbranched polymer in the form of an interface (A membrane surface), and a molded article (membrane) in which the amount of the fluorine-containing hyperbranched polymer is increased on the surface can be formed. That is, from a resin blend of the present invention in which a thermoplastic resin or the like is blended with a fluorine-containing hyperbranched polymer having an oxyalkylene site at a molecular terminal, a molded body whose surface is a surface capable of suppressing adsorption of biomolecules such as proteins ( Film) can be formed.

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

<Fluorine-containing hyperbranched polymer>
The fluorinated hyperbranched polymer of the present invention comprises a monomer A having two or more radically polymerizable double bonds in a molecule and a monomer B having a fluoroalkyl group and at least one radically polymerizable double bond in a molecule. And a polymerizable compound containing at least 5 to 200 mol% of a polymerization initiator C with respect to the number of moles of the monomer A, and a fluorine-containing hyperbranched polymer obtained by polymerizing the polymerizable compound. And a polymer having an oxyalkylene moiety represented by the formula [1].
The fluorinated 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 its terminal. Preferably, the oxyalkylene moiety represented by the formula [1] is bonded to a molecular terminal of the polymerization initiator C via a fragment of the polymerization initiator C.
Furthermore, as long as the effect of the present invention is not impaired, the fluorine-containing hyperbranched polymer may be copolymerized with a polyfunctional monomer and / or a monofunctional monomer that does not belong to the monomers A and B described below. .

[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 a vinyl group and a (meth) acryl group, and particularly a divinyl compound or a di ( It is preferably a meth) acrylate compound.
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 radically polymerizable double bonds in the molecule include the following compounds (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 esters; divinyl adipate, divinyl maleate, divinyl phthalate, divinyl isophthalate, divinyl itaconate, vinyl (meth) acrylate and the like.
(A2-2) Allyl esters: diallyl maleate, diallyl phthalate, diallyl isophthalate, diallyl adipate, allyl (meth) acrylate and the like.
(A2-3) Vinyl ethers: 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, ditrimethylolpropanetetra (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 ] decanedimethanol di (meth) ) 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, alkoxytitanium tri (meth) acrylate, isophorone urethane di (meth) acrylate, aliphatic urethane di (meth) Acrylate, aromatic urethane di (meth) acrylate and the like.

(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 and the like.

(A5) Nitrogen-containing vinyl compound:
Diallylamine, diallyl isocyanurate, diallyl cyanurate, methylene bis (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), and (meth) acrylic groups of the group (A3). Acid esters, vinyl compounds having a polyalkylene glycol chain of the group (A4), and nitrogen-containing vinyl compounds of the group (A5), more preferably the aromatic vinyl hydrocarbons of the above group (A1-3) , (A3) group (meth) acrylates. Among these, divinylbenzene and ethylene glycol di (meth) acrylate are particularly preferable from the viewpoint of dispersibility in a 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 a vinyl group and a (meth) acryl group.
For example, as the monomer B, a compound represented by the above formula [2] can be mentioned, and as a more preferable specific example, a compound represented by the following formula [4] can be mentioned.
(Wherein, R ² has the same meaning as defined in the above 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-octaflu Lopentyl (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) Ace relay 3- (perfluoro-7-methyl-octyl) -2-hydroxypropyl (meth) acrylate.

  In the present invention, the amount of the monomer B is more preferably 5 to 300 mol%, particularly preferably 10 to 150 mol%, based on the number of moles of the monomer A, 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, preferably, an azo-based polymerization initiator is used. Examples of the azo polymerization initiator include the following compounds (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 and the like;
(4) Azoamidine compound:
2,2′-azobis (2-methylpropionamidine) dihydrochloride, 2,2′-azobis [N- (2-carboxyethyl) -2-methylpropionamidine] tetrahydrate, and the like;
(5) Others:
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-based polymerization initiators may be used alone or in combination of two or more.
Among these azo-based polymerization initiators, 4,4′-azobis (4- (4,4 ′)-azobis (4-) is preferable 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 below. Preferred are cyanovaleric acid) and 2,2′-azobis [N- (2-carboxyethyl) -2-methylpropionamidine] tetrahydrate.

  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 include other monomers that do not belong to the monomers A and B as long as the effects of the present invention are not impaired.
The other monomer is not particularly limited as long as it has 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, and 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 an ethylene group, a trimethylene group, a methylethylene group, a tetramethylene group, a 1-methyltrimethylene group, a pentamethylene group, and a 2,2-dimethyl group. Examples include a trimethylene group and a hexamethylene group. Among these, an ethylene group is preferable from the viewpoint of a biomolecule adsorption suppression effect.

[Method of polymerizing polymerizable compound]
Known polymerization methods for polymerizing a 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, such as solution polymerization and dispersion polymerization , Precipitation polymerization, and bulk polymerization. Among them, solution polymerization or precipitation polymerization is preferable. In particular, from the viewpoint of controlling the molecular weight, it is preferable to carry out the reaction by solution polymerization in an organic solvent.

  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 Ester or ester ether such as acetate, propylene glycol monomethyl ether acetate; diethyl ether, tetrahydrofuran, 1,4-dioxane, methyl cellosolve, ethyl cellosolve, butyl cello Ethers such as rub 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 Alcohols such as tert-butyl alcohol, 2-ethylhexyl alcohol, benzyl alcohol and ethylene glycol; amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone; dimethyl sulfoxide and the like And a mixed solvent of two or more of these.

  Among these, preferred are aromatic hydrocarbons, halides, esters, ester ethers, ethers, ketones, alcohols, amides, and the like, and particularly preferred are benzene, toluene, xylene, and ortho. 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 above polymerization reaction is performed in the presence of an organic solvent, the mass of the organic solvent is usually 5 to 120 parts by mass, preferably 10 to 110 parts by mass with respect to 1 part by mass of the monomer A.
The polymerization reaction is carried out under normal pressure, under pressure or under reduced pressure, or under reduced pressure. Further, it is preferable to perform the treatment under an atmosphere of an inert gas such as N ₂ .
The polymerization temperature is optional as long as it is equal to or lower than the boiling point of the reaction mixture, but is preferably from 50 to 200 ° C, more preferably from 80 to 150 ° C, and from 80 to 130 ° C, from the viewpoint of polymerization efficiency and molecular weight control. More preferred.
The reaction time cannot be specified unequivocally because it varies depending on the reaction temperature, the type and ratio of the monomer A, the monomer B and the polymerization initiator C, the type of the polymerization solvent, and the like, but is preferably 30 to 720 minutes, more preferably. Is 40 to 540 minutes.
After the completion of the polymerization reaction, the obtained fluorine-containing hyperbranched polymer is recovered by an optional 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 fluorinated hyperbranched polymer of the present invention measured by gel permeation chromatography in terms of polystyrene is from 1,000 to 400,000, preferably from 2,000 to 200,000, more preferably from 2,000 to 200,000. It is 2,000 to 100,000, more preferably 2,000 to 50,000.

<Production method of fluorine-containing hyperbranched polymer>
The fluorinated hyperbranched polymer of the present invention has an oxyalkylene moiety represented by the above formula [1] at the molecular terminal.
The introduction of the oxyalkylene moiety is carried out by introducing a carboxy group-containing fluorinated hyperbranched polymer which can be said to be a precursor of the fluorinated hyperbranched polymer or a carboxyl group activated body thereof, and a compound represented by the above formula [3] (polyalkylene glycol mono- Alkyl ether).
This manufacturing method is also an object of the present invention.

The carboxy group-containing fluorinated hyperbranched polymer includes a monomer A having two or more radical polymerizable double bonds in a molecule and a monomer having a fluoroalkyl group and at least one radical polymerizable double bond in a molecule. B is 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 activated carboxy group is a polymer obtained by reacting the carboxy group-containing highly branched polymer containing carboxy group with a known active esterifying agent to partially or entirely activate the carboxy group. It is. Examples of the known active esterifying agent include nitrophenol, pentafluorophenol, N-hydroxysuccinimide and the like.

  The carboxy group-containing fluorine-containing hyperbranched polymer can be produced by the method described in the above-mentioned [Method for polymerizing polymerizable compound], and the above-mentioned [A] B] and monomers having a carboxy group such as 4,4′-azobis (4-cyanovaleric acid) among the above-mentioned polymerization initiators C as the polymerization initiator. Initiators can be suitably used. In addition to the monomers A and B, the above-mentioned [other monomers] may be used in combination as a polymerizable compound.

When using the activated carboxy group of the carboxy group-containing highly branched fluorinated polymer, the carboxy group-containing highly branched fluorinated polymer is reacted with the known active esterifying agent in a solvent capable of dissolving these compounds. Then, an active esterifying agent is bonded to a part or all of the carboxy groups of the fluorinated hyperbranched polymer to obtain an activated carboxy group. Examples of the solvent include the solvents used in the above-mentioned [method of polymerizing a polymerizable compound].
In the above-mentioned reaction, the amount of the active esterifying agent used is, for example, 0.1 to 10 times the molar amount of the carboxy group of the carboxy group-containing fluorinated hyperbranched polymer. By changing the amount of the active esterifying agent used, the ratio of the activated carboxy groups to all the carboxy groups can be adjusted.
The above reaction is carried out under normal pressure, under pressure or under reduced pressure, and is preferably carried out under normal pressure in view of simplicity of the apparatus and operation. Further, it is preferable to perform the treatment under an atmosphere of an inert gas such as N ₂ .
At this time, the reaction temperature is preferably −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 hours. It is desirable to perform in time.
After completion of the reaction, the obtained activated carboxy group is recovered by an optional method, and after-treatment such as washing is performed, if necessary, and used in the subsequent step. Examples of a method for recovering from the reaction solution include a method such as reprecipitation.

  The reaction between the carboxy group-containing fluorine-containing hyperbranched polymer or its activated carboxy group and the compound represented by the 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 [Method of polymerizing polymerizable compound] can be used.

In the compound represented by the above formula [3], as R ¹ and L ¹ in the formula, the groups represented by the aforementioned [oxyalkylene moiety] can be exemplified.
The compound represented by the formula [3] is not particularly limited, but is preferably a compound in which n represents an integer of 3 or more. Further, from the viewpoint of the properties of the obtained fluorine-containing hyperbranched polymer, it is preferable that n is an integer of 45 or less. Further, a compound in which n is an integer of 5 to 45, a compound in which n is an integer in the range of 10 to 45, a compound in which n is an integer of 5 to 30 or a compound in which n is an integer of 10 to 30 It is preferred 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, and 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 them, 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 preferably used.

Examples of the known condensing agent include N, N′-dicyclohexylcarbodiimide (DCC), N, N′-diisopropylcarbodiimide (DIC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC) hydrochloride And the like, N, N'-carbonyldiimidazole, dimesitylammonium pentafluorobenzenesulfonate and the like. When using carbodiimides such as DCC, it is preferable to use a catalytic amount of 4-dimethylaminopyridine (DMAP) in combination.
The above reaction is carried out under normal pressure, under pressure or under reduced pressure, and is preferably carried out under normal pressure in view of simplicity of the apparatus and operation. Further, it is preferable to perform the treatment under an atmosphere of an inert gas such as N ₂ .
At this time, the reaction temperature is preferably −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 hours. It is desirable to perform in time.
After the completion of the above reaction, the obtained hyperbranched polymer (fluorinated hyperbranched polymer having an oxyalkylene moiety represented by the above formula [1] at the molecular terminal) is recovered by any method, and if necessary, washed or the like. 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 hyperbranched polymer>
As a specific method for forming a thin film (a thin film having a biomolecule adsorption suppressing action) produced from the fluorinated hyperbranched polymer of the present invention, first, the fluorinated hyperbranched polymer is dissolved or dispersed in a solvent to prepare a varnish. In the form (film forming material), the varnish is cast on a substrate by 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, and printing. It is applied by a method such as letterpress, intaglio, lithographic, or screen printing, and then dried on a hot plate or oven to form a film.
Among these coating methods, spin coating is preferred. In the case of using the spin coating method, since the coating can be performed in a single time, there is an advantage that a highly volatile solution can be used and the coating can be performed with high uniformity.

The solvent used in the form of the varnish may be any solvent that dissolves the above-mentioned fluorine-containing hyperbranched polymer, and examples thereof include methanol, acetone, tetrahydrofuran (THF), toluene, N, N-dimethylformamide (DMF), and 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 solvents may be mixed.
The concentration of the fluorinated hyperbranched polymer is 0.01 to 90% by mass based on the total mass (total mass) of the fluorinated hyperbranched polymer and the solvent. , Preferably 0.05 to 50% by mass, more preferably 0.1 to 20% by mass.

  Although the thickness of the formed thin film made of the fluorine-containing hyperbranched polymer is not particularly limited, it is usually 0.005 to 50 μm, preferably 0.01 to 20 μm.

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

[Thermoplastic resin]
Although 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) PS (polystyrene), HIPS (high impact polystyrene), AS (acrylonitrile-styrene copolymer), ABS (acrylonitrile-butadiene-styrene copolymer), MS (methyl methacrylate-styrene copolymer) Polycarbonate resin; Polyvinyl chloride resin; Polyamide resin; Polyimide resin; (Meth) acrylic resin such as PMMA (Polymethyl methacrylate); PET (Polyethylene terephthalate), Polybutylene terephthalate, Polyethylene resin 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;
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 hyperbranched 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 produced from resin blend and method for forming the same>
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 to form a biomolecule adsorption suppressing film. Can form a molded article.
The coating method on the base material 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 inkjet method, and a printing method (letter plate, intaglio plate). , Lithography, screen printing, etc.) can be appropriately selected. Among them, spin-coating can be used because it can be applied even in a highly volatile solution because it can be applied in a short time, and spin-coating can be performed with high uniformity. It is desirable to use a coating method. It is preferable that the resin blend is filtered using a filter having a pore diameter of about 0.2 μm or the like in advance, and then subjected to coating.

The solvent used in the form of the varnish may be any solvent capable of dissolving the resin blend, and specific examples of these solvents are described in the above <Method for producing varnish and thin film containing fluorine-containing hyperbranched polymer>. And the same solvents as those described above.
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 a value obtained by removing the solvent component from all components of the varnish.

  Examples of the substrate include a silicon / silicon dioxide-coated substrate, a silicon wafer, a silicon nitride substrate, a glass substrate, an ITO substrate, and a plastic substrate (polyimide, polycarbonate, polymethacrylate, polystyrene, polyester, polyolefin, epoxy, melamine, triamine, etc.). Acetylcellulose, ABS, AS, norbornene-based resin, etc.), metal, wood, paper, glass, slate and the like. The shape of these substrates may be plate-like, film-like or three-dimensionally formed.

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

The coating film from which the solvent has been removed may be subjected to annealing of the obtained coating film in an atmosphere of a polar medium, that is, 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 at room temperature or higher in a closed vessel. The solvent annealing can generally change the surface state of the film, and in the present invention, the amount of the fluorine-containing hyperbranched 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, and among them, methanol is preferable.
The annealing temperature and annealing time (exposure time to the solvent vapor) are not particularly limited, but may be appropriately selected from, for example, room temperature (about 25 ° C.) to the boiling point of the solvent used, and 10 seconds to 48 hours.

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

Hereinafter, the present invention will be described more specifically with reference to Examples, but the present invention is not limited to the following Examples.
In the examples, the devices and conditions used for sample preparation and physical property analysis are as follows.

(1) ¹ H NMR spectrum Apparatus: JNM-ECA700 manufactured by JEOL Ltd. (Production Example 1)
JNM-ECP400 manufactured by JEOL Ltd. (Examples 1, 5 to 7)
Solvent: CDCl ₃ (Production Example 1, Example 1)
_{(CD 3) 2 C (=} O) ( Example 5-7)
Standard: CHCl ₃ (7.26 ppm) (Production Example 1)
Tetramethylsilane (0.00 ppm) (Example 1)
_{(CH 3) 2 C (=} O) (2.10ppm) ( Example 5-7)
(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)
Apparatus: Tosoh Corporation HLC-8220GPC
Column: Showex (registered trademark) GPC KF-804L, KF-805L manufactured by Showa Denko KK
Column temperature: 40 ° C
Solvent: tetrahydrofuran Detector: RI
(4) IR spectrum Apparatus: FT / IR-620 manufactured by JASCO Corporation
Measurement conditions: KBr tablet method, room temperature, under air Resolution: 4 cm ^-1
(5) Spin coater: 1H-D7 manufactured by Mikasa Corporation
(6) Dryer device: ISUZU-SVK-10S manufactured by Isuzu Corporation
(7) X-ray photoelectron spectroscopy (XPS)
Apparatus: ESCA 5800 manufactured by ULVAC-PHI, Inc.
Measurement conditions: 14.0 kV, 14 mA
Neutralization condition: 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 Apparatus: Keyence Corporation 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

The abbreviations have 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) [V-501, Wako Pure Chemical Industries, Ltd.]
TEGMEE: 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 [Kanto Chemical Co., Ltd.]
PMMA: Polymethyl methacrylate [Weight average molecular weight: 315,000, manufactured by Polymer Source Co.]
EGME: ethylene glycol monomethyl ether IPE: diisopropyl ether THF: tetrahydrofuran

[Production Example 1] Production of fluorinated hyperbranched polymer 1 having a carboxy group at the end 325 g of EGME was charged into a 1 L reaction flask, and nitrogen was poured for 5 minutes with stirring, and the mixture was heated until the internal solution was refluxed (about 125 ° C). did.
Another 500 mL reaction flask was charged with 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 an initiator, and 325 g of EGME. Pour nitrogen was performed.
The contents were dropped into the refluxed EGME 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 the completion of the dropwise addition, the mixture was further stirred for 1 hour.
Next, 553 g of EGME was distilled off from the reaction solution using a rotary evaporator, and the residue was added to 650 g of IPE to precipitate a polymer in a slurry state. This slurry was filtered under reduced pressure to obtain a white powder as a 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 (reduced pressure filtration-redissolved in THF-reprecipitation with IPE) was repeated once and purified. Finally, the obtained precipitate was filtered under reduced pressure and dried under vacuum to obtain 13.8 g of the target substance (fluorine-containing highly branched polymer 1 having a carboxy group at a terminal) as a white powder.
The ¹ H NMR spectrum and the ¹³ C NMR spectrum of the obtained fluorine-containing hyperbranched polymer 1 having a carboxy group at the terminal are shown in FIG. 1 and FIG. 2, respectively. The unit structural composition (molar ratio) of the fluorine-containing hyperbranched polymer 1 having a carboxy group at the terminal represented by the following structural formula, calculated from the ¹³ C NMR spectrum, is as follows: DVB unit [A]: C6FA unit [B]: ACVA unit [ C] = 1.0: 0.7: 0.5. The weight average molecular weight Mw of the polymer measured in terms of polystyrene by GPC was 9,500, and the degree of dispersion: Mw (weight average molecular weight) / Mn (number average molecular weight) was 2.4.

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

Example 1 Production of Fluorine-Containing Hyperbranched Polymer 2 Having Tri (ethylene oxide) Portion at the Terminal In a 25 mL three-necked flask, 38 mg (5) of the fluorinated hyperbranched polymer having a carboxy group at the terminal obtained in Production Example 1 was added. 0.1 μmol), 16 mg (97 μmol) of TEGMEE, 7 mg (57 μmol) of DMAP as a catalyst, 21 mg (100 μmol) of DCC as a condensing agent, and 2.7 mg of THF previously dehydrated with CaH ₂ . This solution was stirred and reacted at room temperature (about 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 obtained residue was dissolved in chloroform. Next, this solution was washed three times with an aqueous hydrochloric acid solution of pH 5 to remove DMAP. Further, after washing twice with distilled water, drying was performed with anhydrous sodium sulfate, and chloroform was distilled off under reduced pressure. The residue was washed three times with diethyl ether to obtain 9 mg of a white viscous target substance (fluorinated hyperbranched polymer 2 having a tri (ethylene oxide) moiety at a terminal).
FIG. 3 shows the IR spectrum of the obtained fluorinated hyperbranched polymer 2 having a tri (ethylene oxide) moiety at the terminal, and FIG. 4 shows the ¹ H NMR spectrum thereof. FIG. 3 also shows the IR spectrum of the fluorinated hyperbranched polymer 1 having a carboxy group at the terminal. In the IR spectrum, a broad peak derived from the OH stretching vibration of the carboxylic acid was not observed around 2800 to 2500 cm ⁻¹ , so that a tri (ethylene oxide) site was added to almost all terminal carboxy groups of the fluorine-containing hyperbranched polymer 1. It was confirmed that was introduced.

Example 5 Production of Fluorine-Containing Hyperbranched Polymer 3 Having an Oligo (ethylene oxide) Portion at the Terminal (Number of Repeating Units of Ethylene Oxide n = 6) In a 25 mL three-necked flask, a carboxy group was added at the terminal obtained in Production Example 1 200 mg (21 μmol) of a fluorinated hyperbranched polymer having 1, 120 mg (0.40 mmol) of HEGMME, 27 mg (0.22 mmol) of DMAP as a catalyst, 60 mg (0.48 mmol) of DIC as a condensing agent, and 1.3 g of THF previously dehydrated with CaH _2. It is. This solution was stirred and reacted at room temperature (about 20 ° C.) for 120 hours under a nitrogen atmosphere. The precipitated diisopropyl urea (DIU) was removed by filtration. THF was distilled off under reduced pressure, and the obtained residue was dissolved in chloroform. Next, this solution was washed three times with an aqueous hydrochloric acid solution of pH 5 to remove DMAP. Further, after washing twice with distilled water, drying was performed with 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. The target substance was a white viscous substance (fluorinated hyperbranched polymer 3 having an oligo (ethylene oxide) moiety at the terminal ( n = 6)) 99 mg were obtained.
FIG. 9 shows the IR spectrum of the obtained fluorinated hyperbranched polymer 3 (n = 6) having an oligo (ethylene oxide) moiety at the terminal, and FIG. 10 shows the ¹ H NMR spectrum thereof. In the IR spectrum, a broad peak derived from the OH stretching vibration of the carboxylic acid was hardly observed around 2800 to 2500 cm ⁻¹ , and an oligo (ethylene oxide) moiety was introduced into the terminal carboxy group of the fluorine-containing hyperbranched polymer 1. It was confirmed that it was.

Example 6 Production of Fluorine-Containing Hyperbranched Polymer 4 Having an Oligo (Ethylene Oxide) Portion at the Terminal (Number of Repeating Units of Ethylene Oxide n = 12) In a 25 mL three-necked flask, a carboxy group was added at the terminal obtained in Production Example 1 Fluorine-containing hyperbranched polymer 1 having 500 mg (53 μmol), 12EGME 870 mg (1.6 mmol), DMAP 91 mg (0.75 mmol) as a catalyst, DIC 200 mg (1.6 mmol) as a condensing agent, and THF previously distilled in the presence of Na / benzophenone. 2 g were charged. This solution was stirred and reacted at room temperature (about 20 ° C.) for 24 hours under a nitrogen atmosphere. The precipitated diisopropylurea (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 substance (a fluorine-containing substance having an oligo (ethylene oxide) moiety at a terminal). 570 mg of hyperbranched polymer 4 (n = 12) was obtained.
FIG. 9 shows the IR spectrum and FIG. 11 shows the ¹ H NMR spectrum of the obtained fluorine-containing hyperbranched polymer 4 (n = 12) having an oligo (ethylene oxide) moiety at the terminal. In the IR spectrum, a broad peak derived from the OH stretching vibration of the carboxylic acid was hardly observed around 2800 to 2500 cm ⁻¹ , and an oligo (ethylene oxide) moiety was introduced into the terminal carboxy group of the fluorine-containing hyperbranched polymer 1. It was confirmed that it was.

Example 7 Production of Fluorine-Containing Hyperbranched Polymer 5 Having Poly (ethylene oxide) Portion at the Terminal (Number of Repeating Units of Ethylene Oxide n = 45) In a 25 mL three-necked flask, a carboxy group was added at the terminal obtained in Production Example 1 Fluorine-containing hyperbranched polymer 1 having 350 mg (37 μmol), 2.2 g (1.1 mmol) of 45EGME, 70 mg (0.57 mmol) of DMAP as a catalyst, 150 mg (1.2 mmol) of DIC 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 (about 20 ° C.) for 120 hours under a nitrogen atmosphere. The precipitated diisopropylurea (DIU) was removed by filtration, and THF was distilled off under reduced pressure. The obtained residue was dissolved in ethanol and dialyzed against ethanol to remove DMAP and the remaining unreacted 45EGME. Thus, the target substance (white powder containing poly (ethylene oxide) at the terminal) was removed. 740 mg of branched polymer 5 (n = 45) was obtained.
FIG. 9 shows the IR spectrum and ¹ H NMR spectrum of the obtained fluorinated hyperbranched polymer 5 (n = 45) having a poly (ethylene oxide) moiety at the terminal. In the IR spectrum, a broad peak derived from the OH stretching vibration of the carboxylic acid was hardly observed around 2800 to 2500 cm ⁻¹ , so that a poly (ethylene oxide) site was introduced into the terminal carboxy group of the fluorine-containing hyperbranched polymer 1. It was confirmed that it was.

Example 2 Preparation of Fluorinated Hyperbranched Polymer 2 / PMMA Blend Membrane Having Tri (ethylene Oxide) Portion at Terminal and Fluorinated Hyperbranched Polymer 2 Having Tri (ethylene oxide) Portion at 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 at room temperature (about 20 ° C.) or 150 ° C. for 24 hours under vacuum. The film thickness estimated from the 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. FIG. 5 shows the ratio of the photoelectron intensity of fluorine and carbon ( _IF1s / _IC1s ) to the sine (sin θ) of the photoelectron emission angle in each blend film (heat treatment temperature; FIG. 5 (a) room temperature, (b) 150 ° C.). ). In any of the films, _IF1s / _IC1s increased as sinθ decreased. The smaller the value of sin θ, the shallower the analysis depth, that is, the closer to the surface. That is, even if the fluorinated hyperbranched polymer 2 has a hydrophilic tri (ethylene oxide) moiety at the terminal, it has fluorine having a low surface free energy, so that it can be concentrated near the surface of the blend film with PMMA. confirmed.

Example 8 Preparation of Fluorinated Hyperbranched Polymer 3 (n = 6) / PMMA Blend Membrane Having Oligo (Ethylene Oxide) Portions at Terminals Oligo-terminal oligos obtained in Example 5 in place of fluorinated hyperbranched polymer 2 A blend film was produced in the same manner as in Example 2, except that the fluorine-containing hyperbranched 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 of the obtained blend film estimated by ellipsometry was 200 nm. FIG. 13 shows the photoelectron intensity ratio of fluorine and carbon ( _IF1s / _IC1s ) with respect to the sine (sin θ) of the photoelectron emission angle.

Example 9 Preparation of Fluorinated Hyperbranched Polymer 4 (n = 12) / PMMA Blend Membrane Having Oligo (Ethylene Oxide) Portion at Terminal Terminal Oligomeric terminal obtained in Example 6 in place of fluorinated hyperbranched polymer 2 A blend film was produced in the same manner as in Example 2, except that the fluorine-containing hyperbranched 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 of the obtained blend film estimated by ellipsometry was 200 nm. FIG. 13 also shows the photoelectron intensity ratio of fluorine and carbon ( _IF1s / _IC1s ) with respect to the sine (sin θ) of the photoelectron emission angle.

Example 10 Preparation of Fluorinated Hyperbranched Polymer 5 (n = 45) / PMMA Blend Membrane Having Poly (Ethylene Oxide) Portion at the Terminal Poly (terminal oxide) obtained in Example 7 in place of fluorinated hyperbranched polymer 2 A blend film was produced in the same manner as in Example 2, except that the fluorine-containing hyperbranched 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 of the obtained blend film estimated by ellipsometry was 200 nm. FIG. 13 also shows the photoelectron intensity ratio of fluorine and carbon ( _IF1s / _IC1s ) with respect to the sine (sin θ) of the photoelectron emission angle.

As shown in FIG. 13, in each of the films, _IF1s / _IC1s increased as sinθ decreased. That is, regardless of the chain length (n = 6, 12, 45) of the terminal hydrophilic site (oligo (ethylene oxide) portion or poly (ethylene oxide) portion) of the fluorine-containing hyperbranched polymers 3, 4, and 5, fluorine near the surface is not affected. It was confirmed that the fractions were almost the same. From this, it was confirmed that the highly branched polymers 3, 4 and 5 having fluorine with low surface free energy were concentrated near the surface of the blend film with PMMA even if they had a hydrophilic site at the terminal.

Example 3 Reorganization of Surface Structure of Fluorine-Containing Hyperbranched Polymer 2 / PMMA Blend Film Having Tri (ethylene Oxide) Portion at Terminal Terminal Fluorinated Hyperbranched Polymer 2 having Tri (ethylene oxide) Portion at Terminal Prepared in Example 2 The / PMMA blend film was subjected to a heat treatment at 150 ° C. for 24 hours under vacuum.
In order to evaluate the change in the surface structure when the film comes into contact with water, a change with time in the contact angle with respect to water (60 μm) was measured using 1 μL of ultrapure water (millQ water) at room temperature (about 20 ° C.) under air. Seconds). FIG. 6 shows the results.

Comparative Example 1 Rearrangement of Surface Structure of Fluorinated Hyperbranched Polymer Having a Carboxyl Group at the Terminal 1 / PMMA Blend Membrane Except that the fluorinated hyperbranched polymer 1 having a carboxy group at the terminal obtained in Production Example 1 was used. By operating in the same manner as in Example 2, a fluorine-containing hyperbranched 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 the contact angle with respect to water due to evaporation of water droplets was observed. On the other hand, on the blend film of PMMA and the fluorine-containing hyperbranched polymer 2 having a tri (ethylene oxide) moiety at the end, an exponential decrease in the contact angle was observed within a few seconds after the dropping of the water droplet. This is known to be due to surface structure rearrangement accompanying water contact. From this result, it was confirmed that the terminal tri (ethylene oxide) portion of the fluorinated hyperbranched polymer 2 concentrated on the surface of the blend film appeared at the water interface with contact with water.

Example 11 Surface Reorganization of Fluorine-Containing Hyperbranched Polymer 3 (n = 6) / PMMA Blend Film Having Oligo (Ethylene Oxide) Portion at the Terminal Similarly, heat treatment was performed and evaluated. FIG. 14 shows the results.

Example 12 Rearrangement of Surface Structure of Fluorinated Hyperbranched Polymer 4 (n = 12) / PMMA Blend Film Having Oligo (Ethylene Oxide) Portion at the Terminal The blend film obtained in Example 9 was compared with Example 3 Similarly, heat treatment was performed and evaluated. The results are also shown in FIG.

Example 13 Surface Reorganization of Fluorinated Hyperbranched Polymer 5 (n = 45) / PMMA Blend Film Having Poly (Ethylene Oxide) Portions at Ends The blend film obtained in Example 10 was compared with Examples 3 and Similarly, heat treatment was performed and evaluated. The results are also shown in FIG.

  As shown in FIG. 14, in the case of the fluorine-containing hyperbranched polymer 4 (n = 12) / PMMA blend film having an oligo (ethylene oxide) moiety at the terminal, a contact angle derived from the surface structure rearrangement of the film several seconds after the addition of the water droplet. An exponential decrease in was observed, albeit slightly, followed by a monotonic decrease in water contact angle due to evaporation of the water droplets. On the other hand, in the fluorinated hyperbranched polymer 3 (n = 6) / PMMA blend film having an oligo (ethylene oxide) moiety at the terminal, the former is not so clearly observed, and the contact angle with water almost derived from the evaporation of water droplets. Only a monotonic decrease in was observed. Furthermore, in the fluorinated hyperbranched polymer 5 (n = 45) / PMMA blend film having a poly (ethylene oxide) moiety at the terminal, the contact angle with water decreased remarkably with the lapse of time after the dropping of water drops. From this result, the terminal oligo (ethylene oxide) or poly (ethylene oxide) part of the fluorine-containing hyperbranched polymer concentrated on the surface of the blend membrane appears at the water interface with contact with water, and the degree of ethylene oxide It was confirmed that they differed depending on the chain length (number of repeating units n).

Example 4 Protein Adsorption Behavior of Fluorine-Containing Hyperbranched Polymer 2 / PMMA Blend Membrane A fluorine-containing hyperbranched 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 a fluorescein isocyanate-labeled bovine serum albumin (BSA) [ELASTIN PRODUCTS COMPANY] / PBS solution 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 by fluorescence microscopy 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 in which the brightness of this image was quantified using a hybrid cell counting function [Software manufactured by Keyence Corporation] and plotted 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 hyperbranched 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.
Except that this film was used, the same operation as in Example 4 was performed and evaluated. The results are shown in FIGS. 7 and 8.

  As shown in FIGS. 7 and 8, it became clear that the fluorescence intensity due to albumin adsorption in the blend film of the present invention was weaker than that in the PMMA film. This confirmed that adsorption of albumin on the surface of the blend film of the present invention was suppressed.

Example 14 Protein Adsorption Behavior of Fluorine-Containing Hyperbranched Polymer 3 (n = 6) / PMMA Blend Membrane Having Oligo (Ethylene Oxide) Portion at the Terminal The terminal obtained in Example 5 in place of fluorinated hyperbranched polymer 2 A blend film was prepared in the same manner as in Example 2, except that a fluorine-containing hyperbranched polymer 3 (n = 6) having an oligo (ethylene oxide) moiety 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 a fluorescein isocyanate-labeled bovine serum albumin (BSA) [Elastin Products Company] / PBS solution 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 by fluorescence microscopy 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 was quantified using a hybrid cell counting function [Software manufactured by Keyence Corporation] and plotted against the concentration of bovine serum albumin.

Example 15 Protein Adsorption Behavior of Fluorine-Containing Hyperbranched Polymer 4 (n = 12) / PMMA Blend Membrane Having Oligo (Ethylene Oxide) Portion at the Terminal Terminal obtained in Example 6 in place of fluorinated hyperbranched polymer 2 A fluorine-containing hyperbranched polymer 4 (n = 12) having an oligo (ethylene oxide) moiety was used, and a blend film was produced in the same manner as in Example 2 except that the silicon wafer was changed to a cover glass. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
Except that this film was used, the same operation as in Example 14 was performed and evaluated. The results are shown in FIGS. 15 and 16.

Example 16 Protein Adsorption Behavior of Fluorinated Hyperbranched Polymer 5 (n = 45) / PMMA Blend Membrane Having Poly (Ethylene Oxide) Portion at the Terminal End obtained in Example 7 in place of fluorinated hyperbranched polymer 2 A blend film was produced in the same manner as in Example 2, except that a fluorine-containing hyperbranched polymer 5 having a poly (ethylene oxide) part (n = 45) 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.
Except that this film was used, the same operation as in Example 14 was performed and evaluated. The results are shown in FIGS. 15 and 16.

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 hyperbranched 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.
Except that this film was used, the same operation as in Example 14 was performed and evaluated. The results are shown in FIGS. 15 and 16.

  As shown in FIGS. 15 and 16, the fluorescence intensity due to albumin adsorption in the blend film of the present invention is weaker than that in the PMMA film, and the adsorption of albumin on the surface of the blend film of the present invention is suppressed. Was confirmed. In particular, it became clear that the effect was most remarkable in the fluorine-containing hyperbranched polymer 4 (n = 12) / PMMA blend film. Comparing the results of the fluorinated hyperbranched polymer 3 (n = 6) / PMMA blend film and the fluorinated hyperbranched polymer 4 (n = 12) / PMMA blend film, the results show that as the chain length of the oligo (ethylene oxide) becomes longer, the film becomes longer. Albumin adsorption on the surface was suppressed, and its chain length was further increased. When n = 45, albumin was adsorbed on the membrane surface. This is presumed to be because a portion of the fluorine-containing hyperbranched polymer 5 was melted out by immersion in water for a long time.

Example 17 Platelet Adhesion Behavior of Fluorine-Containing Hyperbranched Polymer 3 (n = 6) / PMMA Blend Membrane Having Oligo (Ethylene Oxide) Portion at the Terminal End obtained in Example 5 in place of fluorinated hyperbranched polymer 2 A blend film was prepared in the same manner as in Example 2, except that a fluorine-containing hyperbranched polymer 3 (n = 6) having an oligo (ethylene oxide) moiety was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
The membrane was immersed in phosphate buffered saline (PBS) at room temperature (approximately 20 ° C.) for 12 hours. Platelet-rich plasma prepared by diluting platelet-rich plasma prepared from normal human whole blood with platelet-poor plasma was mounted on this membrane, 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 fix the adhered platelets on the membrane. The membrane was washed with PBS and sterile water, dried, and evaluated for platelet adhesion behavior to the membrane by SEM observation. FIG. 17 shows the obtained SEM images, and FIG. 18 shows the results of classification of the number of adhered platelets and the degree of activation thereof. The degree of activation conformed to the following criteria.
[Activation degree classification standard]
Class I: Circular platelets Class II: Platelets with partially advanced pseudopodium formation or flattening Class III: Platelets with advanced pseudopodium formation or flattening (fully activated)

Example 18 Platelet Adhesion Behavior of Fluorine-Containing Hyperbranched Polymer 4 (n = 12) / PMMA Blend Membrane Having Oligo (Ethylene Oxide) Portion at the Terminal End obtained in Example 6 in place of fluorinated hyperbranched polymer 2 A blend film was produced in the same manner as in Example 2, except that a fluorine-containing hyperbranched polymer 4 (n = 12) having an oligo (ethylene oxide) moiety was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
Except that this film was used, the same operation as in Example 17 was performed and evaluated. The results are shown in FIG. 17 and FIG.

Example 19 Platelet Adhesion Behavior of Fluorine-Containing Hyperbranched Polymer 5 (n = 45) / PMMA Blend Membrane Having Poly (Ethylene Oxide) Portion at the Terminal End obtained in Example 7 in place of fluorinated hyperbranched polymer 2 A blend film was produced in the same manner as in Example 2, except that a fluorine-containing hyperbranched polymer 5 (n = 45) having a poly (ethylene oxide) part was used. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
Except that this film was used, the same operation as in Example 17 was performed and evaluated. The results are shown in FIG. 17 and FIG.

Comparative Example 4 Platelet Adhesion Behavior of Fluorinated Hyperbranched Polymer Having a Carboxyl Group at the Terminal 1 / PMMA Blend Membrane A blend film was produced 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.
Except that this film was used, the same operation as in Example 17 was performed and evaluated. The results are shown in FIG. 17 and FIG.

Comparative Example 5 Platelet Adhesion Behavior of PMMA Membrane A PMMA membrane was produced in the same manner as in Example 2, except that fluorinated hyperbranched polymer 2 was not added. After film formation, heat treatment was performed at 150 ° C. for 24 hours under vacuum.
Except that this film was used, the same operation as in Example 17 was performed and evaluated. The results are shown in FIG. 17 and FIG.

Comparative Example 6 Platelet Adhesion Behavior of PET Membrane The operation was evaluated in the same manner as in Example 17, except that a PET film [manufactured by Teijin Dupont Film Co., Ltd.] was used. The results are shown in FIG. 17 and FIG.

  As shown in FIGS. 17 and 18, in the fluorinated hyperbranched polymer 1 / PMMA blend membrane, platelets adhered and activated more than or equal to the PET membrane. It was confirmed that the platelet adhesion number was extremely low. From this, it is clear that platelet adhesion was suppressed by the effect of introducing the oligo (ethylene oxide) moiety. In particular, the fluorinated hyperbranched polymer 4 (n = 12) / PMMA blend membrane and the fluorinated hyperbranched polymer 5 (n = 45) not only have extremely low platelet adhesion numbers, but also have pseudopodia formation and flattening. Did not progress very much.

Claims (15)

A polymerizable compound containing at least a monomer A having two or more radically polymerizable double bonds in the molecule and a monomer B represented by the formula [2] is added in an amount of 5 to 200 moles per mole of the monomer A. A fluorine-containing hyperbranched polymer obtained by polymerizing in the presence of mol% of a polymerization initiator C, which has an oxyalkylene moiety represented by the formula [1] at a molecular terminal.
(In the formula, 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.)
(In the formula, R ² represents a hydrogen atom or a methyl group, and R ³ represents a fluoroalkyl group having 2 to 12 carbon atoms which may be substituted with a hydroxy group.) The fluorinated hyperbranched polymer according to claim 1, wherein n is an integer of 1 to 30. The fluorinated hyperbranched polymer according to claim 1 or 2, wherein the oxyalkylene moiety is bonded to a molecular terminal of the polymerization initiator C via a fragment of the polymerization initiator C. The fluorine-containing hyperbranched 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. The fluorinated hyperbranched polymer according to claim 4, wherein the monomer A is a divinyl compound or a di (meth) acrylate compound. The fluorinated hyperbranched polymer according to claim 5, wherein the monomer A is divinylbenzene. The fluorinated hyperbranched polymer according to any one of claims 1 to 6 , wherein the polymerization initiator C is an azo-based polymerization initiator. A varnish containing the fluorine-containing hyperbranched polymer according to any one of claims 1 to 7 . A thin film having the ability to inhibit biomolecule adsorption produced from the fluorinated hyperbranched polymer according to any one of claims 1 to 7 . A resin blend comprising: (a) the fluorinated hyperbranched polymer according to any one of claims 1 to 7 ; and (b) a thermoplastic resin. A biomolecule adsorption suppressing film produced from the resin blend according to claim 10 . A polymerizable compound containing at least a monomer A having two or more radically polymerizable double bonds in the molecule and a monomer B represented by the formula [2] is added in an amount of 5 to 200 moles per mole of the monomer A. A carboxy group-containing highly branched polymer obtained by polymerizing in the presence of a polymerization initiator having a carboxy group in a molecule of mol%, or a carboxyl group-activated polymer thereof, and a compound represented by the formula [3] The method for producing a fluorine-containing hyperbranched polymer according to any one of claims 1 to 7 , wherein
(In the formula, R ² represents a hydrogen atom or a methyl group, and R ³ represents a fluoroalkyl group having 2 to 12 carbon atoms which may be substituted with a hydroxy group.)
(In the formula, 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.) The method according to claim 12 , wherein n is an integer of 1 to 30. A method for producing a thin film having a biomolecule adsorption suppressing ability, which is produced from the fluorinated hyperbranched polymer according to any one of claims 1 to 7 ,
A step of applying a liquid containing the fluorinated hyperbranched polymer in a solvent onto a substrate by a spin coating method to form a coating film, and a step of drying the coating film and removing the solvent to suppress biomolecule adsorption. A method for producing a thin film having a function. A method for producing a biomolecule adsorption suppression film produced from the resin blend according to claim 10 ,
Production of a biomolecule adsorption suppressing film, comprising a step of applying a liquid containing the resin blend in a solvent to 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.