Coating film-forming composition containing a phosphate group-containing polymer

Abstract

The present invention provides: a composition for coating film formation which includes a phosphate-group-containing polymer, the composition being capable of forming a film on a substrate through a simple process, the film being capable of retaining the film performance in a water-containing solvent environment; and a coating film which is a cured object obtained from the composition.　The composition for coating film formation comprises: a hydroxylated polymer (P) which contains phosphate-group-derived hydroxy groups as the only hydroxy groups; a polycarbodiimide (C) containing the structure represented by formula (c-1); and a solvent.

Description

[Technical Field]

[0001] The present invention relates to a coating film-forming composition containing a phosphate group-containing polymer, and a coating film that is a cured product of the composition. [Background technology]

[0002] Phosphate group-containing polymers are used for a variety of purposes. One of their uses is as a biocompatible coating material. Patent Document 1 discloses an ion complex material containing a phosphate group-containing polymer. Patent Document 2 discloses an aqueous metallic paint composition using a phosphate group-containing polymer. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2014 / 196650 [Patent Document 2] Special Publication No. 2010-505969 Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention aims to provide a coating film-forming composition containing a phosphate group-containing polymer, which can be formed into a film on a substrate or the like by a simple process and can maintain film performance such as the ability to inhibit adhesion of biological materials and to hydrophilize the surface in a solvent environment containing water, and a coating film that is a cured product of the composition. [Means for solving the problem]

[0005] The present invention encompasses the following.

[0006] [1] a polymer (P) containing hydroxy groups, wherein the hydroxy groups are derived solely from phosphate groups; The following formula (c-1): [ka] A polycarbodiimide (C) having a structure represented by the formula: A coating film-forming composition comprising:

[0007] [2] The polymer (P) is represented by formula (a) or formula (a-1): [ka] [In formula (a), U a1 and U a2 each independently represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms; U a1 and U a2 at least one of which is a hydrogen atom, and in formula (a-1), A represents an alkali metal.

[0008] [3] The polymer (P) is represented by the formula (1): [ka] [In the formula, R 11 represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and X 1 represents an alkylene group having 1 to 5 carbon atoms, n1 represents an integer of 1 to 10, T 1 represents a group of the formula (a) or (a-1).

[0009] [4] The coating film-forming composition according to any one of [1] to [3], wherein the polycarbodiimide (C) contains a hydrophilic group.

[0010] [5] The hydrophilic group is represented by the following formula (I): [ka] (In the formula, R 1 represents an alkyl group having 1 to 5 carbon atoms, and R 2 represents a hydrogen atom or a methyl group, while R 2 If there are multiple R 2 may be the same or different, and m represents an integer of 1 to 30.

[0011] [6] 6. The coating film-forming composition according to claim 1, which is used to form a coating film having an ability to inhibit adhesion of biological substances.

[0012] [7] The coating film-forming composition according to [6], wherein the biological material is a biopolymer.

[0013] [8] [1] to [7] A coating film which is a cured product of a coating film of the coating film-forming composition according to any one of the above items.

[0014] [9] [1] to [7] A method for producing a coating film, comprising a step of applying the coating film-forming composition according to any one of the above items to a substrate. [Effects of the Invention]

[0015] The coating film-forming composition containing the phosphate group-containing polymer of the present invention has storage stability even when it contains water as a solvent, and further, the coating film formed from the composition has excellent durability against solvents including water. The coating film formed from the composition of the present invention has the ability to inhibit adhesion of biopolymers as a cured film without elution even in water. In particular, it has excellent adhesion inhibition ability for biopolymers. [Brief explanation of the drawings]

[0016] [Figure 1]The results of a protein adhesion test (QCM-D measurement) on QCM sensors that were surface-treated with the coating film-forming compositions of Example 1 and Comparative Examples 1 and 2, as evaluated in Test Example 1, are shown in a graph of the time dependence of mass per unit area. [Figure 2] The results of a DNA adhesion test (QCM-D measurement) on QCM sensors that had been surface-treated with the coating film-forming compositions of Example 1 and Comparative Examples 1 and 2, as evaluated in Test Example 2, are shown in a graph of the time dependence of mass per unit area. [Figure 3] The results of a protein adhesion test (QCM-D measurement) on a QCM sensor surface-treated with the coating film-forming composition of Example 2, evaluated in Test Example 4, are shown in a graph of the time dependence of mass per unit area. DETAILED DESCRIPTION OF THE INVENTION

[0017] <Coating film-forming composition> The phosphate group-containing polymer of the present invention is characterized in that it is a polymer (P) containing hydroxy groups, in which the hydroxy groups are derived solely from phosphate groups.

[0018] Although compositions containing copolymers obtained by polymerizing a monomer containing a phosphate group with a monomer containing a hydroxy group other than a phosphate group are already known, the hydroxy groups possessed by the phosphate group-containing polymer of the present invention are solely derived from phosphate groups. The hydroxy groups derived from phosphate groups cause crosslinking reactions between the phosphate group-containing polymers via polycarbodiimide (C), which will be described in detail below, resulting in a coating film with excellent durability (water resistance) against aqueous solvents and the like.

[0019] The coating film-forming composition of the present invention comprises the polymer (P) and The following formula (c-1): [ka] A polycarbodiimide (C) having a structure represented by the formula: The solvent and the polycarbodiimide (C) will be described later.

[0020] The polymer (P) is represented by formula (a) or formula (a-1): [ka] [In formula (a), U a1 and U a2 each independently represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms; U a1 and U a2 At least one of the groups represented by the formula (a-1) is a hydrogen atom. In the formula (a-1), A represents an alkali metal.

[0021] It is preferable that the structure represented by the formula (a) or (a-1) is present in a side chain of the polymer main chain.

[0022] It is preferable that the structure represented by the formula (a) or (a-1) is contained in the repeating unit structure of the polymer.

[0023] Examples of the alkyl group having 1 to 5 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, an s-butyl group, a t-butyl group, an n-pentyl group, a 1-methylbutyl group, a 2-methylbutyl group, a 3-methylbutyl group, a 1,1-dimethylpropyl group, a 1,2-dimethylpropyl group, a 2,2-dimethylpropyl group, and a 1-ethylpropyl group. a1 and U a2 is preferably a methyl group or an ethyl group.

[0024] The alkali metals include lithium, sodium, potassium, rubidium, cesium and francium, with sodium or potassium being preferred.

[0025] Examples of the polymer (P) include polymers of the following compounds. Specific examples of the compound include acid phosphooxyethyl methacrylate, vinyl phosphonic acid, acid phosphooxyethyl acrylate, 3-chloro-2-acid phosphooxypropyl methacrylate, acid phosphooxypropyl methacrylate, acid phosphooxymethyl methacrylate, acid phosphooxypolyoxyethylene glycol monomethacrylate, and acid phosphooxypolyoxypropylene glycol monomethacrylate. Commercially available products may also be used. Examples of commercially available products include Hosmer M (manufactured by Unichemical Co., Ltd.) and PPM-5P (manufactured by Toho Chemical Co., Ltd.).

[0026] The polymer (P) is represented by the formula (1): [ka] [In the formula, R 11 represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and X 1 represents an alkylene group having 1 to 5 carbon atoms, n1 represents an integer of 1 to 10, T 1 represents a group of the formula (a) or (a-1).

[0027] The alkyl group having 1 to 5 carbon atoms is the same as that described above. 11 is preferably a hydrogen atom or a methyl group. Examples of the alkylene group having 1 to 5 carbon atoms include a methylene group, an ethylene group, a propylene group, a trimethylene group, a tetramethylene group, a 1-methylpropylene group, a 2-methylpropylene group, a dimethylethylene group, an ethylethylene group, a pentamethylene group, a 1-methyl-tetramethylene group, a 2-methyl-tetramethylene group, a 1,1-dimethyl-trimethylene group, a 1,2-dimethyl-trimethylene group, a 2,2-dimethyl-trimethylene group, and a 1-ethyl-trimethylene group. 1 is preferably selected from an ethylene group and a propylene group. As n1, an integer of 1 to 6 is preferred.

[0028] The polymer (P) is represented by the formula (1-1): [ka] [In the formula, R 11 , X 1 , n1 and T 1 is the same as that of the formula (1) above] by a known method.

[0029] Furthermore, the polymer (P) according to the present invention may be copolymerized with any monomer within the range that does not impair the desired performance of the coating film of the present invention. In addition, even in the optional monomer, the hydroxy group is only derived from a phosphate group. Examples of such monomers include those represented by formula (2-1) or (3-1): [ka] [In the formula, R 12 and R 13 each independently represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms; X 2 and X 3 each independently represents an alkylene group having 1 to 5 carbon atoms; T 2 is expressed by the following formula (b): [ka] (In the formula, U b1 , U b2 and U b3 each independently represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms; An - represents an anion selected from the group consisting of a halide ion, an inorganic acid ion, a hydroxide ion, and an isothiocyanate ion. represents a group of T 3represents an alkyl group having 1 to 18 carbon atoms, a cyclic hydrocarbon group having 3 to 10 carbon atoms, an aryl group having 6 to 10 carbon atoms, an aralkyl group having 7 to 14 carbon atoms, or an aryloxyalkyl group having 7 to 14 carbon atoms.

[0030] Specific examples of the compound of the above formula (2-1) include dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, dimethylaminopropyl (meth)acrylate, 2-(t-butylamino)ethyl (meth)acrylate, and methacryloylcholine chloride. Specific examples of the compound (3-1) above include linear or branched alkyl esters of (meth)acrylic acid such as butyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, lauryl (meth)acrylate, and stearyl (meth)acrylate; cyclic alkyl esters of (meth)acrylic acid such as cyclohexyl (meth)acrylate and isobornyl (meth)acrylate; and aralkyl esters of (meth)acrylic acid such as benzyl (meth)acrylate and phenethyl (meth)acrylate.

[0031] Examples of other optional monomers include (meth)acrylate compounds having two or more functional groups, such as ethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, propylene glycol di(meth)acrylate, bis(methacryloyloxymethyl)phosphate, bis[2-(methacryloyloxy)ethyl]phosphate, bis[2-(methacryloyloxy)propyl]phosphate, and phosphinylidyne tris(oxy-2,1-ethanediyl)triacrylate. Copolymerization of such optional monomers may cause a portion of the polymer (P) to partially form three-dimensional crosslinks. The proportion of the optional monomer in the polymer (P) is 0 mol % to 50 mol %.

[0032] The weight-average molecular weight of the polymer (P) of the present invention may be several thousand to several million, preferably 5,000 to 5,000,000. It is more preferably 10,000 to 2,000,000. The weight-average molecular weight can be measured, for example, by gel filtration chromatography, as described in the Examples. Furthermore, when the polymer (P) is a copolymer, the copolymer may be any of a random copolymer, a block copolymer, and a graft copolymer. The copolymerization reaction for producing the copolymer is not particularly limited, and known synthesis methods in solution, such as radical polymerization, ionic polymerization, photopolymerization, macromer polymerization, and emulsion polymerization, can be used. The coating film-forming composition of the present invention may contain any one of the polymers (P) alone, or may contain a mixture of multiple polymers (P) in varying ratios, depending on the intended application.

[0033] <Solvent> The solvent contained in the coating film-forming composition of the present invention includes water, phosphate buffered saline (PBS), and alcohol. Examples of the alcohol include alcohols having 2 to 6 carbon atoms, such as ethanol, propanol, isopropanol, 1-butanol, 2-butanol, isobutanol, t-butanol, 1-pentanol, 2-pentanol, 3-pentanol, 1-heptanol, 2-heptanol, 2,2-dimethyl-1-propanol (neopentyl alcohol), 2-methyl-1-propanol, 2-methyl-1-butanol, 2-methyl-2-butanol (t-amyl alcohol), 3-methyl-1-butanol, 3-methyl-3-pentanol, cyclopentanol, 1-hexanol, 2-hexanol, 3-hexanol, and 2,3- Examples of the solvent include dimethyl-2-butanol, 3,3-dimethyl-1-butanol, 3,3-dimethyl-2-butanol, 2-ethyl-1-butanol, 2-methyl-1-pentanol, 2-methyl-2-pentanol, 2-methyl-3-pentanol, 3-methyl-1-pentanol, 3-methyl-2-pentanol, 3-methyl-3-pentanol, 4-methyl-1-pentanol, 4-methyl-2-pentanol, 4-methyl-3-pentanol, and cyclohexanol. These solvents may be used alone or in combination, but are preferably selected from water, PBS, and ethanol from the viewpoint of the solubility of the phosphoric acid-containing polymer.

[0034] A pH adjuster may be included to adjust the ion balance in the coating film-forming composition of the present invention. For example, this may be achieved by adding a pH adjuster to a composition containing the copolymer and a solvent to adjust the pH of the composition to 3.5 to 8.5, more preferably 4.0 to 8.0. The type and amount of pH adjuster to be used are appropriately selected depending on the concentration of the copolymer and the ratio of its anions to its cations. Examples of pH adjusters include organic amines such as ammonia, diethanolamine, pyridine, N-methyl-D-glucamine, and tris(hydroxymethyl)aminomethane; alkali metal hydroxides such as potassium hydroxide and sodium hydroxide; alkali metal halides such as potassium chloride and sodium chloride; inorganic acids or alkali metal salts thereof such as sulfuric acid, phosphoric acid, hydrochloric acid, and carbonic acid; quaternary ammonium cations such as choline; and mixtures thereof (e.g., buffer solutions such as phosphate-buffered saline). Among these, inorganic acids such as sulfuric acid, phosphoric acid, hydrochloric acid, and carbonic acid are preferred.

[0035] <Polycarbodiimide (C)> The polycarbodiimide (C) of the present invention is represented by the following formula (c-1): [ka] It includes a structure represented by:

[0036] The reaction between the phosphate group-containing polymer (polymer (P)) of the present invention and the polycarbodiimide (C) is believed to proceed according to the following reaction formula: The crosslinking reaction between the phosphate group-containing polymers is believed to proceed according to this reaction formula.

[0037] [ka]

[0038] The polycarbodiimide (C) of the present invention may be a polycarbodiimide compound derived from an aliphatic diisocyanate compound having at least one primary isocyanate group, The polycarbodiimide compound may have a structure in which all ends are blocked with an organic compound having a functional group that reacts with an isocyanate group.

[0039] For example, the aliphatic diisocyanate compound having at least one primary isocyanate group may be at least one selected from the group consisting of chain aliphatic isocyanate compounds such as ethylene diisocyanate, tetramethylene diisocyanate, hexamethylene diisocyanate, and 2,2,4-trimethylhexamethylene diisocyanate; cyclic aliphatic diisocyanate compounds such as isophorone diisocyanate, 1,3-bis(isocyanatomethyl)cyclohexane, and norbornane diisocyanate; and aliphatic diisocyanate compounds having an aromatic ring such as xylylene diisocyanate.

[0040] The polycarbodiimide (C) of the present invention may be, for example, an isocyanate-terminated polycarbodiimide having at least two carbodiimide groups represented by the formula (c-1) in the molecule, which is obtained by a condensation reaction accompanied by decarbonation of an aliphatic diisocyanate compound having at least one primary isocyanate group, or may be a polycarbodiimide having a structure in which the terminals are blocked with an organic compound having a functional group reactive with an isocyanate group.

[0041] The functional group of the organic compound may be at least one selected from a hydroxy group, an amino group, an isocyanate group, an epoxy group, and a carboxy group.

[0042] Examples of the organic compound include organic compounds having a hydroxy group such as polyethylene glycol monomethyl ether, polyethylene glycol monoethyl ether, polypropylene glycol monomethyl ether, polypropylene glycol monoethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, tetraethylene glycol monomethyl ether, tetraethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, ethyl alcohol, propyl alcohol, butyl alcohol, pentyl alcohol, hexyl alcohol, octyl alcohol, and dodecyl alcohol; methylamine, ethylamine, propylamine, butylamine, pentylamine, hexylamine, octylamine, dodecylamine, diethylamine, dipropylamine, dibutylamine, and cyclohexylamine. Organic compounds having an amino group such as adamantanamine, allylamine, polyoxyethylene laurylamine, polyoxymethylenestearylamine, aniline, diphenylamine, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, N-phenyl-3-aminopropyltrimethoxysilane, 2,2-difluoroamine, fluorobenzylamine, trifluoroethylamine, [[4-(trifluoromethyl)cyclohexyl]methyl]amine, and their derivatives; organic compounds having an isocyanate group such as butyl isocyanate, pentyl isocyanate, hexyl isocyanate, octyl isocyanate, dodecyl isocyanate, cyclohexyl isocyanate, 1-adamantyl isocyanate, 3-isocyanatopropyltriethoxysilane, 2-isocyanatoethyl acrylate, benzyl isocyanate, 2-phenylethyl isocyanate, and their derivatives;Examples of organic compounds having an epoxy group include 1,2-epoxyheptane, 1,2-epoxyhexane, 1,2-epoxydecane, 1,2-epoxy-5-hexene, ethyl glycidyl ether, 2-ethylhexyl glycidyl ether, glycidyl lauryl ether, allyl glycidyl ether, diethoxy(3-glycidyloxypropyl)methylsilane, 3-[2-(perfluorohexyl)ethoxy]-1,2-epoxypropane, and derivatives thereof; and organic compounds having a carboxy group, such as acetic acid, ethanoic acid, propionic acid, butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, cyclohexanecarboxylic acid, adamantaneacetic acid, phenylacetic acid, benzoic acid, undecenoic acid, and derivatives thereof.

[0043] The organic compound may further have a hydrophilic group in addition to the functional group.

[0044] The polycarbodiimide (C) preferably contains a hydrophilic group.

[0045] The hydrophilic group is represented by the following formula (I): [ka] (In the formula, R 1 represents an alkyl group having 1 to 5 carbon atoms, and R 2 represents a hydrogen atom or a methyl group, while R 2 If there are multiple R 2 may be the same or different, and m represents an integer of 1 to 30. The alkyl group having 1 to 5 carbon atoms is as described above.

[0046] Examples of organic compounds having a hydrophilic group, particularly a hydrophilic group represented by the above formula (I), together with a functional group reactive with an isocyanate group include polyethylene glycol monomethyl ether (MPEG), tetraethylene glycol monomethyl ether (MTEG), etc. These may be used alone or in combination of two or more. By capping the terminals of an isocyanate-terminated polycarbodiimide with such an organic compound, a polycarbodiimide (C) having a hydrophilic group represented by the above formula (I) introduced therein can be obtained.

[0047] As the polycarbodiimide (C), the polycarbodiimide compound described in WO 2018 / 194102 can be used. Other details of the polycarbodiimide compound of the present invention are in accordance with the contents described in WO 2018 / 194102.

[0048] The polycarbodiimide (C) may be a commercially available product, such as "Carbodilite V-02," "Carbodilite V-02-L2," "Carbodilite V-04," "Carbodilite E-01," or "Carbodilite E-02" (all of which are product names manufactured by Nisshinbo Chemical Inc.).

[0049] <Coating film and coating film manufacturing method> To form the coating film of the present invention, the coating film-forming composition is applied to at least a portion of the surface of a base such as a substrate. The application method is not particularly limited, and conventional application methods such as spin coating, dip coating, and solvent casting can be used.

[0050] The shape of the substrate is not particularly limited, and any shape such as a flat plate, a curved surface, or an uneven surface can be used.

[0051] The drying step of the coating film according to the present invention is carried out in the atmosphere or under vacuum, preferably at a temperature within the range of −200° C. to 200° C. The drying step removes the solvent from the coating film-forming composition and also causes a crosslinking reaction to form a cured product, thereby adhering the coating film to the substrate.

[0052] The coating film can be formed by drying at room temperature (10°C to 35°C, e.g., 25°C), but to form the coating film more quickly, drying at, for example, 40°C to 50°C may also be used. A drying process at extremely low to low temperatures (around -200°C to -30°C) using the freeze-drying method may also be used. Freeze-drying is also called vacuum freeze-drying, and is a method in which the material to be dried is cooled with a refrigerant and the solvent is removed by sublimation in a vacuum. Common refrigerants used in freeze-drying include a mixture of dry ice and methanol (-78°C) and liquid nitrogen (-196°C).

[0053] If the drying temperature is lower than -200°C, an uncommon refrigerant must be used, resulting in a lack of versatility, and drying takes a long time due to solvent sublimation, resulting in low efficiency. If the drying temperature is higher than 200°C, the ionic bond reaction on the coating film surface will proceed too much, causing the surface to lose its hydrophilicity and failing to exhibit the ability to inhibit adhesion of biological materials. A more preferred drying temperature is 10°C to 180°C, and even more preferred is 25°C to 150°C. This drying process allows the phosphate group-containing polymers of the present invention to undergo a crosslinking reaction via the polycarbodiimide compound, for example, as shown in the above reaction formula, to become a cured product, thereby forming a coating film.

[0054] The coating film of the present invention has durability against the above-mentioned <solvents> in addition to water. In particular, since the coating film of the present invention has durability (water resistance) against water, it is effective when used in a situation where it is constantly exposed to a solvent containing water.

[0055] After drying, the coating film is preferably washed with running water or ultrasonically with one or more solvents selected from water and an aqueous solution containing an electrolyte to remove impurities, unreacted monomers, etc. remaining on the coating film and to adjust the ion balance of the polymer in the film. The aqueous solution containing water and an electrolyte may be heated, for example, to a temperature in the range of 40°C to 95°C. Preferred aqueous solutions containing electrolytes include PBS, saline (containing only sodium chloride), Dulbecco's phosphate-buffered saline, Tris-buffered saline, HEPES-buffered saline, and Veronal-buffered saline, with PBS being particularly preferred. After adhesion, the coating film remains firmly attached to the substrate without elution even when washed with water, PBS, alcohol, etc. Even if biological materials adhere to the formed coating film, they can be easily removed by subsequent washing with water, etc., and the substrate surface on which the coating film of the present invention is formed has the ability to inhibit adhesion of biological materials.

[0056] The coating film of the present invention has a thickness of 10 to 1000 Å, more preferably 10 to 500 Å, and most preferably 20 to 400 Å.

[0057] Examples of the material for the substrate include glass, a metal-containing compound or a metalloid-containing compound, or a resin, with glass or a resin being preferred from the viewpoint of versatility. Examples of the metal-containing compound or the metalloid-containing compound include ceramics, which are sintered bodies whose basic component is a metal oxide and which are sintered by heat treatment at high temperatures, inorganic solid materials such as molded bodies of inorganic compounds such as semiconductors like silicon, metal oxides or metalloid oxides (silicon oxide, alumina, etc.), metal carbides or metalloid carbides, metal nitrides or metalloid nitrides (silicon nitride, etc.), and metal borides or metalloid borides, aluminum, nickel titanium, and stainless steel (SUS304, SUS316, SUS316L, etc.).

[0058] The resin may be a natural resin or a derivative thereof, or a synthetic resin. Preferred examples of natural resins or derivatives thereof include cellulose, cellulose triacetate (CTA), nitrocellulose (NC), and cellulose with immobilized dextran sulfate. Preferred examples of synthetic resins include polyacrylonitrile (PAN), polyimide (PI), polyester polymer alloy (PEPA), polystyrene (PS), polysulfone (PSF), polyethylene terephthalate (PET), polymethyl methacrylate (PMMA), polyvinyl alcohol (PVA), polyurethane (PU), ethylene vinyl alcohol (EVAL), polyethylene (PE), polyester, polypropylene (PP), polyvinylidene fluoride (PVDF), polyethersulfone (PES), polycarbonate (PC), cycloolefin polymer (COP), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), ultra-high molecular weight polyethylene (UHPE), polydimethylsiloxane (PDMS), acrylonitrile-butadiene-styrene resin (ABS), and Teflon (registered trademark).

[0059] The coating film of the present invention is preferably a coating film that has the ability to inhibit adhesion of biological materials.

[0060] <Biomaterials> In the present invention, biological materials include proteins, sugars, viruses, nucleic acids, and cells, or combinations thereof.

[0061] The proteins include fibrinogen, bovine serum albumin (BSA), human albumin, various globulins, β-lipoprotein, various antibodies (IgG, IgA, IgM), peroxidase, various complements, various lectins, fibronectin, lysozyme, von Willebrand factor (vWF), serum γ-globulin, pepsin, ovalbumin, insulin, histone, ribonuclease, collagen, cytochrome c, For example, sugars include glucose, galactose, mannose, fructose, heparin, hyaluronic acid, For example, nucleic acids include deoxyribonucleic acid (DNA), ribonucleic acid (RNA), The cells include fibroblasts, bone marrow cells, B lymphocytes, T lymphocytes, neutrophils, erythrocytes, platelets, macrophages, monocytes, bone cells, pericytes, dendritic cells, keratinocytes, adipocytes, mesenchymal cells, epithelial cells, epidermal cells, endothelial cells, vascular endothelial cells, hepatocytes, chondrocytes, cumulus cells, nervous system cells, glial cells, neurons, oligodendrocytes, microglia, astrocytes, cardiac cells, esophageal cells, muscle cells (e.g., smooth muscle cells or skeletal muscle cells), pancreatic beta cells, melanocytes, hematopoietic progenitor cells, mononuclear cells, embryonic stem cells (ES cells), embryonic tumor cells, embryonic germ stem cells, and artificial Examples of such cells include pluripotent stem cells (iPS cells), neural stem cells, hematopoietic stem cells, mesenchymal stem cells, hepatic stem cells, pancreatic stem cells, muscle stem cells, germline stem cells, intestinal stem cells, cancer stem cells, hair follicle stem cells, and various cell lines (e.g., HCT116, Huh7, HEK293 (human embryonic kidney cells), HeLa (human cervical cancer cell line), HepG2 (human liver cancer cell line), UT7 / TPO (human leukemia cell line), CHO (Chinese hamster ovary cell line), MDCK, MDBK, BHK, C-33A, HT-29, AE-1, 3D9, Ns0 / 1, Jurkat, NIH3T3, PC12, S2, Sf9, Sf21, High Five, and Vero).

[0062] Among these, the coating film of the present invention has excellent adhesion-inhibiting properties against sugars, proteins, and nucleic acids, which are so-called biopolymers.

[0063] In the present invention, the term "having the ability to inhibit protein adhesion" refers to a relative mass per unit area (%) (mass per unit area (ng / cm) in the examples) when compared to when there is no coating film, as determined by QCM-D measurement performed by the method described in the examples. 2 ) / (mass per unit area without coating film (ng / cm 2 ))) is 50% or less, preferably 30% or less, and more preferably 20% or less; In the present invention, having the ability to suppress cell adhesion means that the relative absorbance (WST O.D.450nm) (%) ((absorbance (WST O.D.450nm) in the example) / (absorbance (WST O.D.450nm) in the comparative example)) when compared with the case without a coating film by a fluorescence microscope performed by the method described in International Publication No. 2016 / 093293 is 50% or less, preferably 30% or less, more preferably 20% or less.

[0064] It is preferable that the biological substance is selected from proteins or nucleic acids.

Example

[0065] Hereinafter, the present invention will be described in more detail based on synthesis examples, examples, test examples, etc., but the present invention is not limited thereto.

[0066] The weight average molecular weight of the copolymer shown in the following synthesis example is the measurement result by Gel Filtration Chromatography (hereinafter abbreviated as GFC) or Gel Permeation Chromatography (hereinafter abbreviated as GPC). The measurement conditions are as follows.

[0067] <GFC measurement conditions> · Apparatus: Prominence (manufactured by Shimadzu Corporation) · GFC column: TSKgel GMPWXL (7.8mm I.D. × 30cm) × 2 - 3 columns · Flow rate: 1.0 mL / min · Eluent: Aqueous solution containing an ionic substance or a mixed solution of EtOH · Column temperature: 40°C · Detector: RI · Injection concentration: Polymer solid content 0.05 - 0.5 mass% · Injection volume: 100 uL · Calibration curve: Third - order approximation curve · Standard sample: Polyethylene oxide (manufactured by Agilent) × 10 types <Measurement method of raw material composition> The concentration (mass%) of each phosphorus-containing compound in a raw material containing phosphorus-containing compounds is measured by: 31 The absolute concentration (absolute mass %) of each phosphorus-containing compound contained in the raw material was calculated using the following standard substances.

[0068] (Measurement conditions) Mode: Inverse gate decoupling mode (quantitative mode) ·Equipment: Varian 400MHz Solvent: CD3OD (deuterated methanol) (30% by weight) Rotation speed: 0Hz Data points: 64000 Flip angle: 90° Waiting time: 70 seconds Number of times: 16, n=4 Standard substance: Trimethyl phosphate + DO (prepared 75% TMP solution)

[0069] <Synthesis Example 1> 10 g of acid phosphooxyethyl methacrylate (product name: Hosmer M, manufactured by Unichemical Co., Ltd.; non-volatile content at 100°C for 1 hour: 91.8%; mixture of acid phosphooxyethyl methacrylate (44.2% by mass), bis[2-(methacryloyloxy)ethyl]phosphate (28.6% by mass), and other substances (27.2% by mass) was cooled with water and neutralized by adding 11.49 g of 5 mol / L aqueous sodium hydroxide solution (5N) (manufactured by Kanto Chemical Co., Ltd.) dropwise while stirring, maintaining the temperature below 35°C. 18.72 g of purified water was added, and 0.05 g of 2,2'-azobis(N-(2-carboxyethyl)-2-methylpropionamidine) n-hydrate (product name: VA-057, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was added and fully dissolved at below 35°C. Further, 10.79 g of ethanol was added and thoroughly stirred to obtain a homogeneous mixture. The resulting mixture was then transferred to a three-neck flask via a dropping pump. Separately, 68.86 g of pure water was added to a three-neck flask equipped with a condenser, and the mixture was heated to the reflux temperature while being sparged with nitrogen. While maintaining this condition, the mixture was added dropwise to boiling pure water over 0.5 hours using a dropping pump connected to a Teflon tube. After the dropwise addition, the mixture was heated and stirred for 4 hours while maintaining the above environment. After 4 hours, the mixture was cooled to obtain 119.91 g of a varnish containing polymer (P-1) with a solids content of approximately 9.26% by mass. The weight-average molecular weight of the resulting liquid was approximately 290,000 in GFC.

[0070] <Synthesis Example 2> 6.02 g of acid phosphooxy polypropylene glycol monomethacrylate (average propylene oxide addition mole number: 5) (product name: PPM-5P, manufactured by Toho Chemical Industry Co., Ltd., absolute mass % (purity): 97.3 mass%), 2.54 g of approximately 80% aqueous solution of methacryloylcholine chloride (manufactured by Tokyo Chemical Industry Co., Ltd.), 4.15 g of butyl methacrylate (manufactured by Tokyo Chemical Industry Co., Ltd.), 48.7 g of ethanol (manufactured by Junsei Chemical Co., Ltd.), and 32.3 mg of dimethyl-1,1'-azobis(1-cyclohexanecarboxylate) (product name: VE-073, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were added to a four-neck flask equipped with a condenser and stirred uniformly to prepare a mixed solution. The atmosphere inside the flask was replaced with nitrogen, and the temperature was raised to the reflux temperature while stirring. The mixture was heated and stirred while maintaining the above environment for 24 hours, yielding a polymer (P-2)-containing varnish with a solids content of approximately 19.9 mass%. The weight average molecular weight of the obtained liquid in GFC was about 150,000.

[0071] Example 1 To 4 g of the varnish containing the polymer (P-1) obtained in Synthesis Example 1 above, 0.38 g of 1 mol / L hydrochloric acid (1N) (Kanto Chemical Co., Inc.) and 13.9 g of pure water were added and thoroughly stirred. 0.18 g of Carbodilite V-02 (Nisshinbo Chemical Inc., solids content approximately 40% by mass) was added and stirred until homogenous. 17.81 g of ethanol was then added and thoroughly stirred to prepare a coating film-forming composition. The pH was 7.5. The resulting coating film-forming composition was spin-coated at 1500 rpm for 60 seconds onto a commercially available silicon wafer for semiconductor evaluation and dried in an oven at 70°C for 24 hours. The wafer was then thoroughly washed with PBS and pure water to obtain a silicon wafer with a coating film formed thereon. The thickness of the coating film on the silicon wafer was measured using an optical interference film thickness meter and found to be 171 Å.

[0072] <Example 2> To 2 g of the varnish containing the polymer (P-2) obtained in Synthesis Example 2, 11.58 g of ethanol, 21.35 g of pure water, and 5.26 g of 1N aqueous ammonia (Kanto Chemical Co., Ltd.) were added and thoroughly stirred. To this solution, 1.50 g of a solution prepared by diluting Carbodilite V-02 (Nisshinbo Chemical Co., Ltd., solids content approximately 40% by mass) 10 times with pure water was added and thoroughly stirred to prepare a coating film-forming composition. The pH was 9.9. The resulting coating film-forming composition was spin-coated onto an HMDS-treated silicon wafer at 1500 rpm / 60 sec and dried at 50°C for 3 hours. The wafer was then thoroughly washed with PBS and pure water and dried at 70°C for 1 hour to obtain a coating film on the HMDS-treated silicon wafer. The thickness of the coating film on the HMDS-treated silicon wafer was measured using a spectroscopic ellipsometer and found to be 227 Å.

[0073] <Comparative Example 1> To 4 g of the varnish containing the polymer (P) obtained in Synthesis Example 1 above, 0.38 g of 1 mol / L hydrochloric acid (1N) (Kanto Chemical Co., Inc.) and 14.57 g of pure water were added and thoroughly stirred. Then, 17.81 g of ethanol was added and thoroughly stirred to prepare a coating film-forming composition. The pH was 7.5. The resulting coating film-forming composition was spin-coated at 1500 rpm for 60 seconds onto a commercially available silicon wafer for semiconductor evaluation, and then dried in an oven at 70°C for 24 hours. The wafer was then thoroughly washed with PBS and pure water to obtain a silicon wafer with a coating film formed thereon. The thickness of the coating film on the silicon wafer was measured using an optical interference film thickness meter and found to be 26 Å.

[0074] <Comparative Example 2> 1 g of a commercially available silicone coating agent, Siliconize L-25 (manufactured by Fuji Systems Co., Ltd.), was added to 50 g of pure water and thoroughly stirred. The resulting coating film-forming composition was spin-coated at 1500 rpm for 60 seconds onto a commercially available silicon wafer for semiconductor evaluation, and then dried in an oven at 150°C for 0.5 hours. The wafer was then thoroughly washed with PBS and pure water to obtain a silicon wafer with a coating film formed thereon.

[0075] [Test Example 1] <Preparation of QCM Sensor (PS)>[[]END]] A crystal oscillator (Q-Sense, QSX304, manufactured by Biolin Scientific) vapor-deposited with Au was cleaned using a UV / ozone cleaning device (UV253E, manufactured by Filgen Co., Ltd.) for 3 minutes, and immediately immersed in a solution prepared by dissolving 0.0772 g of 2-aminoethanethiol (manufactured by Tokyo Chemical Industry Co., Ltd.) in 1000 mL of ethanol for 24 hours. After cleaning the sensor surface with ethanol, it was air-dried, and a varnish prepared by dissolving 1.00 g of polystyrene (manufactured by Aldrich) in 99.00 g of toluene was spin-coated on the sensor side at 3500 rpm for 30 seconds and dried at 120 °C for 1 minute to obtain a QCM sensor (PS).

[0076] <Preparation of Surface-Treated QCM Sensor>[[]END]] The coating film-forming compositions of Example 1, Example 2 and Comparative Example 1 were spin-coated on the QCM sensor (PS) at 3500 rpm for 30 seconds and baked in an oven at 70 °C for 24 hours as a drying process. Then, as a cleaning process, the uncured coating film-forming composition remaining in excess was washed twice each with PBS and ultrapure water, and further, each sensor was immersed in PBS and washed with ultrasonic waves for 5 minutes to obtain surface-treated QCM sensors with the coating film-forming compositions of Example 1, Example 2 and Comparative Example 1. The coating film-forming composition of Comparative Example 2 was used to obtain a surface-treated QCM sensor in the same manner except that it was baked at 150 °C for 30 minutes in the drying process.

[0077] <Protein Attachment Test; QCM-D Measurement>[[]END]] Each QCM sensor surface-treated with the coating film-forming compositions of Example 1 and Comparative Examples 1 and 2 was attached to a dissipative crystal oscillator microbalance QCM-D (E4, Q-Sense, manufactured by Biolin Scientific), and PBS was flowed until a stable baseline with a frequency change of 1 Hz or less per hour was established. Next, PBS was flowed for about 10 minutes with the frequency of the stable baseline set to 0 Hz. Subsequently, a solution obtained by diluting γ-globulin derived from human blood (manufactured by Aldrich) at 100 μg / mL with PBS was flowed for about 30 minutes, and then the shift (Δf) in the adsorption-induced frequency of the 9th overtone after flowing PBS again for about 20 minutes was read. As a control, a PS sensor without a coating film was also subjected to the same test. Using Q-Tools (manufactured by Q-Sense, Biolin Scientific) for analysis, the shift (Δf) in the adsorption-induced frequency, which is the shift (Δf) in the adsorption-induced frequency explained by the Sauerbrey equation, was converted to the mass per unit area (ng / cm 2 ), and the amount of protein adsorption was shown in Table 1, and a graph of the time dependence of the mass per unit area is shown in FIG. 1. The surface-treated QCM sensor (Example 1) with the coating film-forming composition according to the present invention showed a significantly lower protein adsorption amount compared to the surface-treated QCM sensors (Comparative Examples 1 and 2) with the coating film-forming compositions of the comparative examples and the PS sensor without a coating film.

[0078] [Table 1] q

[0079] [Test Example 2] [DNA Adhesion Test; QCM-D Measurement] Each QCM sensor surface-treated with the coating film-forming compositions of Example 1, Comparative Example 1, and Comparative Example 2, prepared by the same method as in Test Example 1, was attached to a dissipation-type crystal oscillator microbalance QCM-D (E4, Q-Sense, manufactured by Biolin Scientific), and PBS was flowed until a stable baseline with a frequency change of 1 Hz or less per hour was established. Next, PBS was flowed for about 10 minutes with the frequency of the stable baseline set to 0 Hz. Subsequently, a solution of sodium deoxyribonucleic acid human placenta-derived (manufactured by Aldrich) diluted with PBS at 100 μg / mL was flowed for about 30 minutes, and then the shift (Δf) of the adsorption-induced frequency of the 9th overtone after flowing PBS again for about 20 minutes was read. As a control, a PS sensor without a coating film was also subjected to the same test. Using Q-Tools (manufactured by Q-Sense, Biolin Scientific) for analysis, the shift (Δf) of the adsorption-induced frequency, which is the shift (Δf) of the adsorption-induced frequency explained by the Sauerbrey equation, was converted to the mass per unit area (ng / cm 2 ), and the DNA adhesion amount was shown in Table 2, and a graph of the time dependence of the mass per unit area was shown in Figure 2. The QCM sensor surface-treated with the coating film-forming composition according to the present invention (Example 1) showed a significantly lower DNA adhesion amount compared to the QCM sensors surface-treated with the coating film-forming compositions of the comparative examples (Comparative Example 1 and Comparative Example 2) and the PS sensor without a coating film.

[0080] [Table 2] [[ID=A]]

[0081] [Test Example 3] [DNA Adsorption Inhibition Test; Fluorescence Intensity Measurement] The coating film-forming composition of Example 1 and the coating film-forming composition of Comparative Example 1 were placed in 1.5 mL polypropylene (PP) tubes (Thermo Fisher Scientific) at 150 μL per tube, and the entire volume was dried at 50°C. After thorough washing with pure water, 1.5 mL PP tubes with coating films were obtained. Human genomic DNA (TAKARA BIO INC.) was then prepared at 2 ng / μL using 10 mM Tris-EDTA buffer (pH 7.4) (Fujifilm Wako Pure Chemical Industries, Ltd.) supplemented with 0.1 M NaCl, and 100 μL was placed in the 1.5 mL PP tubes with coating films. As a control, human genomic DNA was similarly placed in a 1.5 mL PP tube without a coating film (uncoated tube). Each tube was stored at 40°C for 7 days. After storage, the human genomic DNA solution was recovered, and 5 μL of the DNA solution was placed on a black polystyrene microplate (Corning) and 95 μL of QuantiFluor® ONE dsDNA System (Promega) was added. DNA concentrations were calculated by measuring Ex. 504 nm and Em. 531 nm using an Enspire multimode plate reader (PerkinElmer).

[0082] As a result of this test, the concentration of human genomic DNA remaining in each tube without adhering to the tube after storage is shown in Table 3.

[0083] [Table 3]

[0084] [Test Example 4] <Protein adhesion test; QCM-D measurement> A QCM sensor surface-treated with the coating film-forming composition of Example 2, prepared in the same manner as in Test Example 1, was attached to a dissipative quartz crystal microbalance QCM-D (E4, Q-Sense, Biolin Scientific), and PBS was allowed to flow for 100 hours. Next, PBS was allowed to flow for approximately 10 minutes, with the stable baseline frequency set to 0 Hz. Subsequently, a solution of γ-globulin derived from human blood (Aldrich) diluted with PBS at 100 μg / mL was allowed to flow for approximately 30 minutes, and then PBS was allowed to flow again for approximately 20 minutes, after which the adsorption-induced frequency shift (Δf) of the 9th overtone was read. A PS sensor without a coating film was also subjected to the same test as a control. For analysis, the adsorption-induced frequency shift (Δf) was calculated using Q-Tools (Q-Sense, Biolin Scientific) and expressed as the mass per unit area (ng / cm) of the adsorption-induced frequency shift (Δf) as explained by the Sauerbrey equation. 2 The amount of protein adhesion, converted into mass per unit area, is shown in Table 4, and a graph of the time dependence of mass per unit area is shown in Figure 3. The QCM sensor surface-treated with the coating film-forming composition according to the present invention (Example 2) showed a significantly lower amount of protein adhesion than the PS sensor without a coating film.

[0085] [Table 4] [Industrial Applicability]

[0086] According to the present invention, by using a coating film-forming composition containing the phosphate group-containing polymer of the present invention, it is possible to provide a coating film that is excellent in durability against solvents including water, a coating film that has the ability to inhibit adhesion of biological substances, and a coating film that has excellent ability to inhibit adhesion of proteins and nucleic acids.

Claims

1. a polymer (P) containing hydroxy groups, wherein the hydroxy groups are derived solely from phosphate groups; The following formula (c-1): 【Chemistry 1】 A polycarbodiimide (C) having a structure represented by the formula: a solvent, and the polymer (P) is a polymer represented by the following formula (1): 【Chemistry 2】 [In the formula, R 11 represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, X 1 represents an alkylene group having 1 to 5 carbon atoms, n1 represents an integer of 1 to 10, and T 1 represents a group represented by the following formula (a) or formula (a-1): 【Transformation 3】 (in formula (a), U a1 and U a2 each independently represent a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, at least one of U a1 and U a2 is a hydrogen atom, and in formula (a-1), A represents an alkali metal).

2. The coating film-forming composition according to claim 1 , wherein the polycarbodiimide (C) contains a hydrophilic group.

3. The hydrophilic group is represented by the following formula (I): 【Chemistry 4】 (In the formula, R １ represents an alkyl group having 1 to 5 carbon atoms, and R ２ represents a hydrogen atom or a methyl group, and R ２ When there are multiple R ２ may be the same or different, and m represents an integer of 1 to 30.

4. The coating film-forming composition according to any one of claims 1 to 3, which is used to form a coating film having an ability to inhibit adhesion of biological substances.

5. The coating film-forming composition according to claim 4 , wherein the biological material is a biopolymer.

6. A coating film which is a cured product of a coating film of the coating film-forming composition according to any one of claims 1 to 5.

7. A method for producing a coating film, comprising a step of applying the coating film-forming composition according to any one of claims 1 to 5 to a substrate.

Images