Method for hydrophilically processing substrate and hydrophilically modified substrate

Abstract

To provide a simple method for hydrophilically processing a substrate which can homogeneously expressing hydrophilicity rapidly under a mild condition while suppressing a substrate deterioration on heat and a hydrophilically modified substrate which keeps a contact angle with water sufficiently low.SOLUTION: A method for hydrophilically processing a substrate of this invention is to give hydrophilicity by forming a hydrophilic coating layer through a step of preparing a mixed aqueous solution containing a water-soluble electrolyte, a sulfobetaine high polymer electrolyte salt, and catechol a mine salt to deposit the mixed aqueous solution on the surface of a substrate with the result that free sulfobetaine high polymer and / or its electrolyte salt and free catechol amine and an adhesive substance such as its oxidant and / or cyclization product are deposited on the surface of a substrate while adsorbing, making reaction, coupling, interacting, and physically adsorbing with each other. This method enables a reduction of the contact angle by at least 10° below a substrate to be hydrophilicized to obtain a hydrophilically modified substrate with an improved hydrophilicity.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a hydrophilization treatment method for modifying the surface of a substrate made of a non-hydrophilic material into a hydrophilic surface that is compatible with water, an aqueous composition, and an aqueous suspension, and to a hydrophilic modified substrate thus modified. [Background technology]

[0002] Substrates made of hydrophilic materials have excellent properties such as antifouling, antifogging, biocompatibility, antithrombogenicity, and anti-protein adsorption. As disclosed in Non-Patent Document 1, they have a high affinity for water molecules, and when water adheres to the surface of the substrate, non-hydrophilic substances such as proteins are hardly adsorbed.

[0003] On the other hand, in order to improve the hydrophilicity of a substrate made of a material with relatively low hydrophilicity, it is important to subject the substrate to a hydrophilization treatment. A substrate surface that has been subjected to a hydrophilization treatment such as a dry treatment or a wet treatment for chemical surface modification can have an increased surface affinity with water, an aqueous composition, or an aqueous suspension.

[0004] Dry treatment of substrates made of materials with relatively low hydrophilicity involves subjecting the substrate surface to treatments such as plasma discharge, corona discharge, ultraviolet irradiation, excimer UV irradiation, electron beam irradiation, and radiation irradiation to generate hydrophilic polar functional groups such as hydroxyl groups, thereby making the substrate hydrophilic simply and quickly. However, these polar functional groups are highly active and are quickly altered and deteriorated by chemical reactions with moisture, etc., making it difficult to maintain hydrophilicity for a long period of time.

[0005] In addition, wet treatment is a method of imparting hydrophilicity to a substrate surface by adsorbing, reacting or bonding a hydrophilic group-containing compound as a hydrophilizing agent, and unlike dry treatment, hydrophilicity is maintained for a long period of time without decreasing by selecting a low-activity hydrophilic group-containing compound as the hydrophilizing agent. As an example of wet treatment, Non-Patent Document 2 discloses a hydrophilization treatment method using a sulfobetaine polymer, which is a zwitterion, as a hydrophilizing agent. According to this method, a sulfobetaine polymer having a hydrophilic group is adsorbed or chemically bonded to the substrate surface by electrostatic interaction or the like, thereby imparting excellent hydrophilicity to the substrate surface.

[0006] However, sulfobetaine polymers are insoluble in water, which is supposed to be a good solvent for polar substances, at relatively low temperatures such as room temperature, and therefore it is necessary to convert the sulfobetaine polymer into an aqueous solution in order to perform a homogeneous hydrophilic treatment on the surface of a substrate. Even if the sulfobetaine polymer is dissolved in water while heating it to convert it into an aqueous solution, and the hydrophilic treatment is performed on the surface of a substrate while the aqueous solution is still heated, it induces deterioration of the substrate when applied to the surface of a substrate made of a material with low heat resistance.

[0007] In addition, since the sulfobetaine polymer hardly bonds or adsorbs to the surface of a substrate made of a non-hydrophilic material such as polyethylene, it is difficult to impart sufficient hydrophilicity to the substrate.

[0008] As a method for hydrophilizing the surface of a non-hydrophilic substrate, Patent Document 1 discloses that the surface of a substrate that has been similarly dry pretreated to generate polar functional groups in advance is wet-treated so that a hydrophilizing agent is adsorbed, reacted or bonded to the polar functional groups to impart hydrophilicity to the substrate surface. This pretreatment requires direct treatment while appropriately securing the distance between the electrode of corona discharge or the light source of excimer UV irradiation and the substrate surface, but it is difficult to apply to uneven substrates such as multi-well culture plates or the inner walls of tubes. Furthermore, plasma treatment, which must be performed under vacuum, is difficult to secure a sufficient degree of vacuum for large substrates.

[0009] As a method for hydrophilizing the surface of a substrate without dry pretreatment, Non-Patent Document 3 discloses forming a layer of polydopamine, which is one of adhesive compounds, and adsorbing hyaluronic acid, a hydrophilizing agent, on the surface of the layer to give hydrophilicity to the substrate. However, according to this method, although the contact angle of the substrate after hydrophilization is reduced by about 10° compared to before hydrophilization, it is still only hydrophilized to about 100°. Therefore, in order to give biocompatibility, antithrombogenicity, protein non-adsorption, etc. to the substrate, it has been required to hydrophilize the water contact angle to about 20° or less. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] JP 2021-161208 A [Non-patent literature]

[0011] [Non-Patent Document 1] M. Tanaka, et al., “The roles of water molecules at the biointerface of medical polymers”, Polym. J., 2013, 45, 701-710. [Non-Patent Document 2] M. Tanaka, et al., “Synthesis and structures of zwitterionic polymers to induce electrostatic interaction with PDMS surface treated by air-plasma”, Arkivoc., 2018, 330-343. [Non-Patent Document 3] P. Xue, et al., “Surface modification of poly(dimethylsiloxane) with polydopamine and hyaluronic acid to enhance hemocompatibility for potential applications in medical implants or devices”, ACS Appl. Mater. Interfaces, 2017, 9, 33632-33644. Summary of the Invention [Problem to be solved by the invention]

[0012] The present invention has been made to solve the above-mentioned problems, and aims to provide a simple method for hydrophilizing a substrate, which can rapidly and uniformly develop hydrophilicity under mild conditions while suppressing deterioration of the substrate due to heat, and a hydrophilic modified substrate in which the contact angle with water is maintained sufficiently low. [Means for solving the problem]

[0013] The method for hydrophilizing a substrate of the present invention, which has been made to achieve the above-mentioned object, comprises a preparation step of preparing a mixed aqueous solution containing a water-soluble electrolyte, a free sulfobetaine polymer and / or an electrolyte salt thereof, and a free catecholamine and / or a salt thereof, and a hydrophilization step of applying the mixed aqueous solution to the surface of the substrate, so that the free sulfobetaine polymer and / or the electrolyte salt thereof and an adhesive substance containing at least one selected from the free catecholamine and salt thereof, any of their oxidized products and / or cyclized products, and any of their condensates, multimers, polymers, associations and / or aggregates are deposited on the surface of the substrate while adsorbing, reacting, bonding, interacting and / or physically adsorbing to each other, thereby forming a hydrophilic coating layer and imparting hydrophilicity.

[0014] In this method for hydrophilizing a substrate, the free catecholamine is preferably at least any compound selected from the group consisting of dopamine, L-3,4-dihydroxyphenylalanine, norepinephrine, and epinephrine.

[0015] In this method for hydrophilizing a substrate, the oxidized product and / or the cyclized product may be at least any catecholamine derivative selected from 4-(2-aminoethyl)-1,2-benzoquinone, 5,6-dihydroxyindoline, 5,6-dihydroxy-3H-indole, and 5,6-dihydroxyindole.

[0016] In this method for hydrophilizing a substrate, the hydrophilic coating layer preferably contains polycatecholamine.

[0017] This method for hydrophilizing a substrate does not subject the substrate to be hydrophilized to at least any dry surface modification treatment selected from plasma discharge, corona discharge, ultraviolet irradiation, excimer UV irradiation, electron beam irradiation, and radiation irradiation, nor any wet surface modification treatment selected from alkaline solution immersion, acidic solution immersion, and micro-nano bubble solution immersion.

[0018] In the method for hydrophilizing a substrate, the substrate to be hydrophilized may be subjected to at least any one of dry surface modification treatments selected from plasma discharge, corona discharge, ultraviolet irradiation, excimer UV irradiation, electron beam irradiation, and radiation irradiation, and / or any one of wet surface modification treatments selected from immersion in an alkaline solution, immersion in an acidic solution, and immersion in a micro-nano bubble solution.

[0019] This method for hydrophilizing a substrate involves adjusting the mixed aqueous solution to a pH of 8 to 11, for example.

[0020] In this method for hydrophilizing a substrate, for example, the mixed aqueous solution is prepared so that the weight ratio of the free sulfobetaine polymer and its electrolyte salt to the free catecholamine and its salt is 0.01 to 10.

[0021] In this method for hydrophilizing a substrate, the mixed aqueous solution is preferably prepared so as to contain 0.1 to 26 w / w% of the water-soluble electrolyte, 0.1 to 10 w / w% of the free sulfobetaine polymer and / or its electrolyte salt, and 0.1 to 10 w / w% of the catecholamine and / or its salt.

[0022] In this method for hydrophilizing a substrate, the water-soluble electrolyte is at least one selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, sodium bromide, potassium bromide, and sodium iodide.

[0023] In this method for hydrophilizing a substrate, the substrate is made of at least one material selected from the group consisting of rubber, resin, glass, metal, and ceramics.

[0024] In this method for hydrophilizing a substrate, the rubber is at least one selected from the group consisting of silicone rubber, fluororubber, ethylene-propylene binary copolymer rubber, ethylene-propylene-diene ternary copolymer rubber, urethane rubber, acrylic rubber, ethylene vinyl acetate rubber, chlorosulfonated polyethylene rubber, chlorinated polyethylene rubber, epichlorohydrin rubber, polysulfide rubber, butyl rubber, butadiene rubber, styrene butadiene rubber, chloroprene rubber, nitrile rubber, isoprene rubber, and natural rubber, and the resin is silicone resin, polyvinyl chloride, polyethylene, polypropylene, polystyrene, acrylonitrile-butadiene-styrene resin, (meth)acrylic resin, polyvinyl alcohol, polyamide, polyethylene terephthalate, polybutylene terephthalate, urethane resin, polycarbonate, nylon, polyether ether ketone, polylactic acid, styrene-based thermoplastic resin, polypropylene ... It is preferable that the ceramic is at least one selected from the group consisting of elastomers, olefin-based thermoplastic elastomers, ester-based thermoplastic elastomers, amide-based thermoplastic elastomers, dynamically crosslinked thermoplastic elastomers, fluorine-based thermoplastic elastomers, polyphenylene sulfide, cycloolefin polymers, cycloolefin copolymers, polyphenylsulfone, and polyoxymethylene, that the glass is at least one selected from the group consisting of quartz glass, borosilicate glass, and soda-lime glass, that the metal is at least one selected from the group consisting of stainless steel, iron, aluminum, titanium, silver, copper, gold, cobalt, chromium, molybdenum, nickel, tungsten, platinum, and alloys of any of these, and that the ceramic is at least one selected from the group consisting of alumina, zirconia, aluminum nitride, silicon carbide, silicon nitride, steatite, and hydroxyapatite.

[0025] In this method for hydrophilizing a substrate, the substrate may be formed from at least any low heat resistant material selected from the group consisting of the urethane rubber, the polyvinyl chloride, the polyethylene, the styrene-based thermoplastic elastomer, the olefin-based thermoplastic elastomer, the ester-based thermoplastic elastomer, the amide-based thermoplastic elastomer, the dynamically crosslinked thermoplastic elastomer, the fluorine-based thermoplastic elastomer, the urethane resin, and the (meth)acrylic resin.

[0026] The method for hydrophilizing a substrate is characterized in that the free sulfobetaine polymer is represented by the following chemical formula (1): [ka] (In formula (1), R 1 is a hydrogen atom or a methyl group, and n1 and n2 are numbers from 2 to 6), and / or the following chemical formula (2): [ka] (In formula (2), R 2 is a hydrogen atom or a methyl group, n3, n5, n6 and n8 are numbers from 2 to 6, and n4 a and n7 a are all 0 or n4 a and n7 a is 1, n4 b and n7 b is a number from 1 to 3), or a polymer composed only of repeating units having a sulfobetaine group represented by the above chemical formula (1) and / or (2) and a repeating unit having a sulfobetaine group represented by the following chemical formula (3): [ka] (In formula (3), R 3 is a hydrogen atom or a methyl group, n9 is a number from 2 to 6, n10 is a number from 0 to 1, R 4 is any active functional group selected from an azide group, a sulfo group, an alkoxysilyl group, and a hydroxyl group), and / or a repeating unit having an active functional group represented by the following chemical formula (4): [ka] (In formula (4), R 5 is a hydrogen atom or a methyl group, R 6 is any functional group selected from a carboxyl group, a carboxymethyl group, an ethylene glycol group or an ethylene glycol oligomer, an acryl group and a methacryl group), may be a random copolymer, a block copolymer, an alternating copolymer, or a graft copolymer.

[0027] In this method for hydrophilizing a substrate, the molecular weight of the free sulfobetaine polymer is preferably at least 30,000.

[0028] The method for hydrophilizing the substrate comprises, for example, applying the mixed aqueous solution at 1 to 30°C.

[0029] This method for hydrophilizing a substrate may include a step of desalting the water-soluble electrolyte, the sulfobetaine polymer electrolyte salt, and / or the catecholamine salt applied to the substrate by washing the substrate with water after the hydrophilization step.

[0030] In order to achieve the above object, the hydrophilically modified substrate of the present invention comprises a hydrophilic coating layer formed on the surface of the substrate, in which a free sulfobetaine polymer and / or an electrolyte salt thereof and an adhesive substance containing at least one selected from the group consisting of the free catecholamine and a salt thereof, an oxidized product and / or a cyclized product thereof, and a condensate, multimer, polymer, association and / or aggregate thereof are mutually adsorbed, reacted, bonded, interacted and / or physically adsorbed and deposited on the surface of the substrate, and the hydrophilic coating layer has a contact angle reduced by at least 10° compared to the surface of the substrate, thereby improving hydrophilicity.

[0031] The hydrophilically modified substrate may be one in which the surface of the hydrophilic coating layer is a desalting surface. Effect of the Invention

[0032] The method for hydrophilizing a substrate of the present invention involves applying to the substrate a mixed aqueous solution containing a water-soluble electrolyte, a free sulfobetaine polymer and / or an electrolyte salt thereof, and a free catecholamine and / or a salt thereof, so that the adhesive compound strongly adheres to the substrate surface to form an excellent hydrophilic coating layer on the substrate surface, thereby significantly reducing the contact angle of water compared to the surface of the substrate before the hydrophilization treatment, and thereby maintaining high hydrophilicity.

[0033] The free sulfobetaine polymer and / or sulfobetaine polyelectrolyte salt and adhesive compounds such as free catecholamines and / or their oxidized products, cyclized products, and polymers thereof are deposited on the surface of a substrate while being mutually adsorbed, reacted, bonded, interacted, and / or physically adsorbed, thereby forming a hydrophilic coating layer on the surface of the substrate, and the surface of the substrate can be hydrophilized by the sulfobetaine structure in the free sulfobetaine polymer and / or sulfobetaine polyelectrolyte salt exposed to the surface of the layer.

[0034] This hydrophilization method makes it possible to omit the steps of performing a dry surface modification treatment such as plasma treatment and a wet surface modification treatment such as immersion in an alkaline solution in advance to generate polar functional groups on the surface of the substrate. In addition, the hydrophilization can be performed uniformly even on areas that are difficult to perform dry surface modification treatment, such as the inner walls of tubes and the recesses of multi-well culture plates.

[0035] Furthermore, when the mixed aqueous solution is applied to a substrate surface that has previously been subjected to a dry surface modification treatment and / or a wet surface modification treatment, the polar functional groups generated on the substrate surface and the adhesive compound strongly adsorb, react, bond, interact and / or physically adsorb to each other, making it possible to form a hydrophilic coating layer that is less likely to peel off from the substrate surface compared to the case where the dry surface modification treatment and the wet surface modification treatment are omitted.

[0036] According to this hydrophilic treatment method, since no heating is required in the series of steps, it is possible to perform hydrophilic treatment on the surface of a substrate without deteriorating not only substrates made of heat-resistant materials but also substrates made of low-heat-resistant materials such as polyvinyl chloride and polyethylene.

[0037] According to this hydrophilization treatment method, by adjusting the weight ratio of the free sulfobetaine polymer and its electrolyte salt to the free catecholamine and its salt in the mixed aqueous solution, the amount of the free sulfobetaine polymer and / or its electrolyte salt exposed to the hydrophilic coating layer increases or decreases according to the weight ratio, and the degree of hydrophilicity can be adjusted, so that the contact angle of the hydrophilic coating layer surface with water can be appropriately controlled.

[0038] The hydrophilically modified substrate of the present invention has free sulfobetaine polymer and / or sulfobetaine polymer electrolyte salt exposed on the surface of the hydrophilic coating layer formed on the substrate surface, and therefore has a contact angle with water that is at least 10° smaller than that of the substrate before hydrophilization treatment, and exhibits excellent hydrophilicity with a contact angle of approximately 20° or less.

[0039] When the surface of the hydrophilic coating layer of this hydrophilically modified substrate is washed with an electrolyte washing liquid such as physiological saline or with water, only the excess electrolyte remaining on the surface, the free sulfobetaine polymer and / or sulfobetaine polyelectrolyte salt not contained in the hydrophilic coating layer, and the adhesive compound are removed, but the free sulfobetaine polymer and / or sulfobetaine polyelectrolyte salt in the hydrophilic coating layer are not washed away, and the low contact angle and excellent hydrophilicity of the hydrophilic coating layer are maintained. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0040] Hereinafter, embodiments for carrying out the present invention will be described in detail, but the scope of the present invention is not limited to these embodiments.

[0041] A preferred embodiment of the hydrophilization treatment method of the present invention includes a preparation step of dissolving a water-soluble electrolyte, a free sulfobetaine polymer, and a salt of a catecholamine such as dopamine hydrochloride to prepare a mixed aqueous solution; a hydrophilization step of applying the mixed aqueous solution to a substrate made of a low heat-resistant material by immersion or the like at room temperature, so that the free sulfobetaine polymer and / or the sulfobetaine polymer electrolyte salt, and the adhesive compound containing free catecholamine and / or its oxidized product or cyclized product, as well as their multimers, polymers, associations, and / or aggregates, such as polydopamine, are deposited on the surface of the substrate while adsorbing, reacting, bonding, interacting, and / or physically adsorbing to each other, thereby forming a hydrophilic coating layer and imparting hydrophilicity; and a washing step of washing with physiological saline and then with ion-exchanged water to obtain a hydrophilic modified substrate.

[0042] Free sulfobetaine polymers aggregate and disperse in cold water, remaining almost completely insoluble and suspended in water. Therefore, in order to dissolve free sulfobetaine polymers in water, it is necessary to carry out the process at a temperature above the upper critical solution temperature (UCST), which is higher than room temperature, and heating to about 55°C or higher is required to almost completely dissolve the polymer.

[0043] In the process of preparing this mixed aqueous solution, the free sulfobetaine polymer is dissolved in water together with a water-soluble electrolyte, whereby an ionic bond is formed between the sulfobetaine structure and the water-soluble electrolyte or an interaction with the hydrate of the water-soluble electrolyte salt occurs, and the sulfobetaine structures within or between the molecules are ionic dissociated to generate a sulfobetaine polymer electrolyte salt without heating. This salt has a lower UCST than the free sulfobetaine polymer, and is almost completely dissolved without agglomeration even at relatively low temperatures such as room temperature.

[0044] When the mixed aqueous solution is applied to the surface of a substrate, for example, dopamine hydrochloride as a catecholamine becomes free dopamine, and at least a part of it is oxidized or cyclized to become catecholamine derivatives such as 4-(2-aminoethyl)-1,2-benzoquinone, 5,6-dihydroxyindoline, 5,6-dihydroxyindole, etc. Furthermore, at least a part of the free catecholamine and / or catecholamine derivative becomes polydopamine such as multimers as shown in chemical formulas (5) and (6), polymers as shown in chemical formulas (7) and (8), condensates as shown in chemical formula (9), and / or associations as shown in chemical formula (10) by covalent bonds or intermolecular interactions. [ka] (In formula (6), p1 is a number of 0 or 1; in formula (7), p2 to p4 are numbers of 0 or more constituting polydopamine (excluding the case where p2 to p4 are all 0); in formula (8), p5 is a number of 1 or more constituting polydopamine and p6 is a number of 0 or 1; in formula (9), p7 is a number of 1 or more constituting polydopamine; and in formula (10), p8 is a number of 1 or more constituting polydopamine.)

[0045] The polycatecholamine may be, for example, any combination of a multimer, a polymer, a condensate, and an association, or a complex structure of multimers, polymers, condensates, and associations.

[0046] These compounds, as adhesive compounds, adhere to the surface of a substrate by adsorption such as physical adsorption or chemical adsorption, binding such as covalent bonding, or interaction such as intermolecular interaction with the surface of the substrate.

[0047] A hydrophilic coating layer containing the sulfobetaine polyelectrolyte salt and the adhesive compound is formed on the substrate surface by depositing the sulfobetaine polyelectrolyte salt and the adhesive compound on the substrate surface while adsorbing to each other physically or chemically (preferably chemically), reacting with each other, bonding with each other such as ionic or covalent bonds, interacting with each other such as entanglement or intermolecular interactions, and / or physically adsorbing. Since the sulfobetaine polyelectrolyte salt is exposed on the surface of the hydrophilic coating layer, the surface of the hydrophilic coating layer has a water contact angle at least 10° lower than that of the substrate surface before the hydrophilization step, and exhibits excellent hydrophilicity with a contact angle of about 20° or less.

[0048] When free catecholamine is included in the formation of a hydrophilic coating layer, the amount of sulfobetaine polyelectrolyte salt exposed on the layer surface varies depending on the weight ratio of sulfobetaine polyelectrolyte salt to free catecholamine, and the higher the weight ratio, the more the contact angle can be reduced and the more hydrophilic the layer can be.

[0049] The adsorption or interaction between the sulfobetaine polyelectrolyte salt and the adhesive compound in the hydrophilic coating layer is stronger than the interaction between the sulfobetaine polyelectrolyte salt and water or a water-soluble electrolyte. Therefore, even if the surface of the hydrophilic coating layer is washed with an electrolyte washing liquid such as water, e.g., ion-exchanged water, or physiological saline after forming the hydrophilic coating layer on the surface of the substrate, the free sulfobetaine polymer and / or sulfobetaine polyelectrolyte salt exposed on the surface of the hydrophilic coating layer is hardly washed away, and the hydrophilicity of the substrate is stably maintained. On the other hand, the excess water-soluble electrolyte salt, the free sulfobetaine polymer and / or sulfobetaine polyelectrolyte salt not contained in the hydrophilic coating layer, and the adhesive compound are washed away.

[0050] Although a preferred embodiment of the present invention has been described above, other materials and qualities may also be used.

[0051] Specifically, the free catecholamine may be at least one selected from L-3,4-dihydroxyphenylalanine, norepinephrine, and epinephrine, in addition to dopamine. Since the free catecholamine is highly reactive, stable salts such as hydrochloride, hydrobromide, and hydroiodide may be used as raw materials in the step of preparing the mixed aqueous solution.

[0052] In the mixed aqueous solution, as the weight ratio of the free sulfobetaine polymer and its electrolyte salt to the free catecholamine and its salt increases, the amount of the free sulfobetaine polymer and its salt exposed to the surface of the hydrophilic coating layer increases, and the hydrophilicity of the substrate can be improved. The ratio is preferably 0.01 to 10 by weight, more preferably 0.1 to 5, and even more preferably 0.5 to 3. If the ratio is less than 0.01, the hydrophilic effect due to the addition of the sulfobetaine polymer and its electrolyte salt is almost lost, and if it exceeds 10, the possibility of aggregation due to only the sulfobetaine polymer and its electrolyte salt increases.

[0053] The free catecholamine and its salt in the mixed aqueous solution are dissolved preferably to 0.001 to 30 w / w%, more preferably to 0.01 to 20 w / w%, and even more preferably to 0.1 to 10 w / w%. If the concentration is less than 0.001 w / w%, there will be insufficient adhesive components and the mixture will not be able to adhere to the substrate, and if the concentration is more than 30 w / w%, there will be too much insoluble matter.

[0054] The oxidation and / or cyclization of free catecholamine and / or its salt, as well as the multimerization, polymerization, association and aggregation reactions, depend on the pH of the mixed aqueous solution, and in order to rapidly proceed with the reactions, the pH is preferably 8.0 to 11.0, more preferably 8.0 to 10.0, and even more preferably 8.0 to 9.0. If the pH is more acidic than neutral, no chemical reaction occurs, and if the pH is strongly alkaline at 11 or more, there is a concern that the compound may be decomposed.

[0055] The solvent of the mixed aqueous solution may be water such as ultrapure water, ion-exchanged water, distilled water, or RO water. In order to stably proceed with the reaction, it is necessary to keep the pH of the mixed aqueous solution constant, so a buffer solution is preferable. The buffer solution is not particularly limited, but is preferably a trishydroxymethylaminomethane hydrochloride buffer solution, a tris-glycine buffer solution, a tris-hydrochloric acid buffer solution, a tris-EDTA buffer solution, a tris-acetate-EDTA buffer solution, an EDTA-sodium hydroxide buffer solution, a phosphate buffer solution, or an ammonium chloride buffer solution.

[0056] The sulfobetaine polymer may be a polymer consisting only of repeating units having a sulfobetaine structure in the side chain represented by the above chemical formula (1) and / or (2), and more preferably, a polymer represented by the following chemical formula (11) or (12): [ka] (In formulas (11) and (12), m1 and m2 are any positive numbers for forming a sulfobetaine polymer, m3 a and m4 a are all 0 or m3 a and m4 a is 1 in m3 b and m4 b Examples of the homopolymer include those represented by 1) to 3).

[0057] The free sulfobetaine polymer has, for example, an ammonium group, preferably a quaternary ammonium group, and a sulfonate group in a side chain extending from the main chain of the repeating unit. Although the polymer having the repeating units represented by the above chemical formula (1) and / or (2) has been shown, the free sulfobetaine polymer may also be a polymer having repeating units represented by the above chemical formula (1) and / or (2) and the above chemical formula (3) and / or (4).

[0058] In the sulfobetaine polymer, the repeating main chain having repeating units is, for example, a poly(meth)acrylic skeleton. (Meth)acrylic includes acryl and methacryl. More specifically, the poly(meth)acrylic skeleton is a poly(meth)acrylamide copolymer skeleton and / or a poly(meth)acrylate polymer skeleton such as poly(meth)acrylic acid ester. Among them, those having a poly(meth)acrylamide copolymer skeleton are preferred.

[0059] In the side chain of the sulfobetaine polymer, the sulfobetaine structure and the repeating main chain are connected by an alkylene chain (-(CH2) n1、n3又はn5 -; n1, n3 or n5 is a number from 2 to 6), a polyethylene glycol chain (-O-(CH2-CH2-O) n4b -;n4 b is a number of 1 to 3), an ester bond, an amide bond, an ether bond, or a combination of these may be used for bonding.

[0060] In the sulfobetaine structure, the ammonium group and the sulfonate group are connected by an alkylene chain (-(CH2) n2、n6又はn8 -; n2, n6 or n8 is a number from 2 to 6) or a polyethylene glycol chain (-O-(CH2-CH2-O) n7b -;n7 b is a number from 1 to 3), or a combination thereof.

[0061] The sulfobetaine structure is preferably one in which the ammonium group is located in the middle of the side chain and the sulfonate group is located at the end of the side chain, but may also be one in which the sulfonate group is located in the middle of the side chain and the ammonium group is located at the end of the side chain.

[0062] The sulfobetaine polymer may be at least any one of a random copolymer, a block copolymer, an alternating copolymer and a graft copolymer having a repeating unit having a sulfobetaine structure in a side chain represented by the chemical formula (1) and / or (2) represented by the chemical formula (1) and / or (2) represented by the chemical formula (3) having an active functional group selected from an azide group, a sulfo group, an alkoxysilyl group and a hydroxyl group in a side chain, and / or a repeating unit having a polar functional group such as a carboxyl group or a functional group selected from a carboxymethyl group, an ethylene glycol group or an ethylene glycol oligomer, an acryl group and a methacryl group in a side chain, as represented by the chemical formula (4), instead of a polymer consisting only of a repeating unit having a sulfobetaine structure in a side chain represented by the chemical formula (1) and / or (2). Specific examples of the copolymer include those represented by the chemical formulas (13) and (14) below. [ka] (In formulas (13) and (14), R 7 , R 8 , R 10 and R 11 is a hydrogen atom or a methyl group, R 9 is an active functional group selected from an azide group, a sulfo group, an alkoxysilyl group, and a hydroxyl group; R 12 is any functional group selected from a carboxyl group, a carboxymethyl group, an ethylene glycol group or an ethylene glycol oligomer, an acryl group, and a methacryl group; m5, m8, m11, and m14 are positive numbers for forming a sulfobetaine polymer; m6, m7, m9, m12, and m13 are numbers from 2 to 6; and m10 is a number from 0 to 1).

[0063] In the copolymer represented by chemical formula (13), among the active functional groups, the azide group is decomposed by light or heat to generate a nitrene group, which can form a covalent bond by reacting with the surface functional group of the substrate or by ring expansion. The alkoxysilyl group can form a covalent bond, which is a silyl ether bond, by condensation reaction with a functional group on the substrate, such as a hydroxyl group.

[0064] In addition, instead of the repeating unit having an active functional group in the side chain in the copolymer represented by chemical formula (13), the side chain may be an aromatic hydrocarbon ring group such as phenyl or naphthyl, a non-aromatic heterocyclic group such as piperazinyl, pyrrelidinyl, pyrazolyl, or morpholinyl, an aromatic heterocyclic group such as pyridyl, pyrazolyl, imidazolyl, triazolyl, pyrazinyl, or triazolyl, a linear, branched, and / or cyclic, saturated, and / or unsaturated hydrocarbon group such as methyl, ethyl, vinyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclobutyl, n-pentyl, isopentyl, neopentyl, cyclopentyl, n-hexyl, or cyclohexyl, or benzyl or phenethyl, an amide group (-CO-N(R 13 )-;R 13 The active functional group may be any single spacer group selected from the group consisting of an alkyl group having 1 to 6 carbon atoms or a phenyl group, and an ester group (-CO-O-), or a composite spacer group consisting of at least any of them in combination.

[0065] There is no limitation on the molar ratio of the repeating units having a sulfobetaine structure in the side chain represented by the chemical formula (1) and / or (2) to the repeating units represented by the chemical formula (3) and / or (4).

[0066] The homopolymer consisting of only repeating units having a sulfobetaine structure in the side chain, represented by chemical formula (1), is synthesized as follows. Specifically, the homopolymer represented by the above chemical formula (11) is taken as an example.

[0067] Dimethylaminopropyl methacrylamide is reacted with propane sultone to synthesize methacrylamidepropyl sulfobetaine, which is a sulfobetaine structure-containing monomer for forming a repeating unit as represented by chemical formula (1).

[0068] By polymerizing this sulfobetaine structure-containing monomer, a homopolymer represented by the above chemical formula (11) can be obtained.

[0069] Although a homopolymer has been shown as an example of the sulfobetaine polymer, it may be at least any one of a random copolymer, a block copolymer, an alternating copolymer, and a graft copolymer having a repeating unit represented by the chemical formula (1) and a repeating unit represented by the chemical formula (2).

[0070] Taking the sulfobetaine polymer represented by the above chemical formulas (13) and (14) as an example, it can be synthesized as follows. Specifically, it can be synthesized as follows: [ka] (in the formulae (15) and (16), m15 to m18 are positive numbers for forming a sulfobetaine polymer) will be taken as an example for explanation.

[0071] The amino group of 4-aminobenzoic acid is diazotized, azidized, and further converted into an acid chloride, and then reacted with mono-protected piperidine in which one of the amino groups of piperidine is protected with a protecting group to obtain amidation, and then the protecting group is removed to obtain mono-p-azidobenzoic acid piperazine amide. Methacrylic acid chloride and 6-aminocaproic acid are amidated, and further amidated with the free amino group of the mono-p-azidobenzoic acid piperazine amide to synthesize an active functional group-containing comonomer for forming a repeating unit as represented by chemical formula (3). The sulfobetaine structure-containing monomer and the active functional group-containing monomer are copolymerized to obtain a copolymer represented by chemical formula (15).

[0072] The copolymer represented by the chemical formula (16) can be obtained by copolymerizing the sulfobetaine structure-containing monomer with methacrylic acid.

[0073] The molecular weight and molecular weight distribution of the polymer consisting only of repeating units having a sulfobetaine structure in a side chain represented by the chemical formula (1) and / or (2) and the copolymer having repeating units represented by the chemical formula (1) and / or (2) and repeating units represented by the chemical formula (3) or (4) are not particularly limited, but the molecular weight, for example, the number average molecular weight or weight average molecular weight, is preferably 30,000 to 600,000, more preferably 50,000 to 150,000, and even more preferably 50,000 to 100,000.

[0074] The free sulfobetaine polymer and its salt in the mixed aqueous solution are dissolved preferably at 0.01 to 10 w / w%, more preferably at 0.05 to 5 w / w%, and even more preferably at 0.1 to 1 w / w%. If the concentration is less than 0.01, the hydrophilizing effect is not exhibited, and if it exceeds 10, the insoluble content becomes large.

[0075] A water-soluble electrolyte is used to dissolve the sulfobetaine polymer to form the sulfobetaine polyelectrolyte salt.

[0076] By dissolving a free sulfobetaine polymer in a predetermined concentration in the mixed aqueous solution so that the water-soluble electrolyte is at a certain concentration or more in the mixed aqueous solution, the water-soluble electrolyte and the sulfobetaine structure in the free sulfobetaine polymer are ionic bonded to each other, the intramolecular ion pair is dissociated, and a sulfobetaine polyelectrolyte salt is formed. By ionic bonding between the sulfobetaine structure and the water-soluble electrolyte in the aqueous solution, hydration occurs with almost no aggregation due to ionic bonds between the sulfobetaine structures within or between molecules, and the sulfobetaine polyelectrolyte salt dissolves with almost no aggregation even at a relatively low temperature such as room temperature.

[0077] In the mixed aqueous solution, the water-soluble electrolyte is preferably prepared at 0.1 to 26 w / w%, more preferably at 0.1 to 10 w / w%, and even more preferably at 0.1 to 1 w / w%. If the concentration is less than 0.1 w / w%, the amount of sulfobetaine polymer that becomes the sulfobetaine polymer electrolyte salt decreases, and if the concentration is more than 26 w / w%, the salt precipitates at room temperature.

[0078] The water-soluble electrolyte is preferably sodium chloride, potassium chloride, calcium chloride, sodium bromide, potassium bromide, or sodium iodide, more preferably sodium chloride, potassium chloride, or calcium chloride, and even more preferably sodium chloride, which is inexpensive and has safety in the body and low cytotoxicity.

[0079] The temperature at which the mixed aqueous solution is applied to the substrate is preferably about room temperature, for example, 1 to 30° C., more preferably 10 to 25° C., and even more preferably 20 to 25° C. If the temperature is below 10° C., there is an increased risk of precipitation of the sulfobetaine polymer, and if the temperature is above 30° C., the substrate made of a material with low heat resistance will deteriorate due to deformation, discoloration, etc.

[0080] In the hydrophilization step, when the mixed aqueous solution is applied to the surface of the substrate, the sulfobetaine polymer electrolyte salt does not aggregate even at a relatively low temperature, so that the substrate surface can be homogeneously hydrophilized without causing unevenness even if a method performed at room temperature, such as spray coating or spin coating, is used instead of immersion. Methods for applying the mixed aqueous solution include, but are not limited to, coating, spraying, screen printing, flexographic printing, inkjet printing, and gravure printing.

[0081] The material of the substrate may be, for example, at least one material selected from low heat resistant materials such as urethane rubber, polyethylene, polyvinyl chloride, styrene-based thermoplastic elastomers, olefin-based thermoplastic elastomers, ester-based thermoplastic elastomers, amide-based thermoplastic elastomers, dynamically crosslinked thermoplastic elastomers, fluorine-based thermoplastic elastomers, urethane resins, and (meth)acrylic resins, as well as highly heat resistant rubbers such as silicone rubber, resins such as silicone resins, glass, metals, and ceramics.

[0082] Examples of the rubber include silicone rubber, fluororubber, ethylene-propylene binary copolymer rubber, ethylene-propylene-diene ternary copolymer rubber, urethane rubber, acrylic rubber, ethylene vinyl acetate rubber, chlorosulfonated polyethylene rubber, chlorinated polyethylene rubber, epichlorohydrin rubber, polysulfide rubber, butyl rubber, butadiene rubber, styrene butadiene rubber, chloroprene rubber, nitrile rubber, isoprene rubber, and natural rubber.

[0083] Examples of the resin include silicone resin, polypropylene, polystyrene, acrylonitrile-butadiene-styrene resin, (meth)acrylic resin, polyvinyl alcohol, polyamide, polyethylene terephthalate, polybutylene terephthalate, urethane resin, polycarbonate, nylon, polyether ether ketone, polylactic acid, polyphenylene sulfide, polyphenylsulfone, cycloolefin polymer, cycloolefin copolymer, and polyoxymethylene.

[0084] Examples of the glass include quartz glass, borosilicate glass, and soda-lime glass.

[0085] Examples of the metal include stainless steel, iron, aluminum, titanium, silver, copper, gold, cobalt, chromium, molybdenum, nickel, tungsten, and platinum, as well as alloys of any of these metals.

[0086] Examples of the ceramics include alumina, zirconia, aluminum nitride, silicon carbide, silicon nitride, steatite, and hydroxyapatite.

[0087] During the hydrophilization step, the adhesive compound generally adheres strongly to the substrate surface and is deposited, so that a hydrophilic coating layer can be formed on the substrate surface without carrying out dry surface modification treatments such as plasma discharge, corona discharge, ultraviolet irradiation, excimer UV irradiation, electron beam irradiation, and radiation irradiation, and wet surface modification treatments such as immersion in an alkaline solution, immersion in an acidic solution, and immersion in a micro-nano bubble solution, prior to the hydrophilization step.

[0088] In addition, the substrate surface may be subjected to a dry surface modification treatment and / or a wet surface modification treatment in advance to generate polar functional groups, which can then be reacted with an adhesive compound to strengthen the adhesion between the substrate surface and the hydrophilic coating layer, making it difficult to peel off from the substrate surface.

[0089] By washing the hydrophilized substrate with an electrolyte washing solution, it is possible to remove excess free sulfobetaine polymer and / or sulfobetaine polymer electrolyte salt remaining on the substrate surface without adsorbing, reacting or bonding. The electrolyte washing solution is not particularly limited, but is preferably physiological saline, a buffer solution, Ringer's solution or other salt aqueous solution. Washing with this washing solution may be omitted.

[0090] By washing the hydrophilized substrate with water, it is possible to remove excess electrolytes contained on the surface of the hydrophilic coating layer, free sulfobetaine polymers and / or sulfobetaine polymer electrolyte salts remaining without mutual adsorption, reaction, binding, interaction and / or physical adsorption, and adhesive compounds such as free catecholamines and / or their oxidized or cyclized products. The water used for washing is not particularly limited, but is preferably ultrapure water, ion-exchanged water, distilled water, or RO water. Note that washing with water may be performed after washing with an electrolyte washing solution, or the washing step may be omitted.

[0091] The hydrophilically modified substrate of the present invention is a hydrophilic coating layer formed by depositing a sulfobetaine polyelectrolyte salt and an adhesive compound such as a free catecholamine and / or its oxidized or cyclized form on the surface of a low heat-resistant resin substrate while the sulfobetaine polyelectrolyte salt is adsorbed, reacted, bonded, interacted, and / or physically adsorbed to each other, and then desalting the resulting hydrophilic coating layer has a contact angle that is at least 10° lower than that of the surface of the substrate to be hydrophilized, thereby improving hydrophilicity, and further exhibiting excellent hydrophilicity with a contact angle of 20° or less.

[0092] When this hydrophilized substrate is applied to a medical device used in a living body, such as a vascular catheter, even if it comes into contact with blood or body fluids containing a large amount of water-soluble electrolytes, the free sulfobetaine polymer and / or sulfobetaine polymer electrolyte salt exposed on the surface of the hydrophilic coating layer is not washed away because it is strongly adsorbed or interacts with the adhesive compound contained in the hydrophilic coating layer, and therefore the hydrophilicity is maintained for a long period of time.

[0093] This hydrophilically modified substrate has a hydrophilic surface and is endowed with antifouling properties, biocompatibility, antithrombogenicity, and anti-protein adsorption properties, and is therefore used, for example, in medical devices such as vascular catheters and bio-experimental devices such as cell culture vessels; and since it is endowed with antifogging properties, it is used, for example, in automobile window glass, etc. EXAMPLES

[0094] Examples for applying the present invention and comparative examples to which the present invention is not applied will be described in detail below.

[0095] (Synthesis example: Synthesis of sulfobetaine polymer [chemical formula (11)]) (1) Synthesis of methacrylamide propyl sulfobetaine [ka] Dimethylaminopropyl methacrylamide (1.70 g, 10 mmol) and dehydrated acetone (120 mL) were placed in a three-neck flask (300 mL) and stirred at room temperature. A solution of 1.83 g (15 mmol) of 1,3-propane sultone in dehydrated acetone (20 mL) was added dropwise and stirred at room temperature for 48 hours. Acetone was removed by distillation, and the resulting solid was washed with acetone (20 mL). The resulting solid was dissolved in methanol, hydroquinone was added, and the solvent was removed by distillation. The solid was taken out and dried under reduced pressure to obtain a colorless solid methacrylamidepropyl sulfobetaine in a 98% yield. m / z: 293 (M+H + ) and the structure was supported. (2) Polymerization to sulfobetaine polymer [chemical formula (11)] [ka] In a 25 mL eggplant flask, 1.46 g (5 mmol) of methacrylamide propyl sulfobetaine, 11.4 mg of ammonium persulfate, and 5 mL of water were placed, and the flask was covered with aluminum foil to form a homogeneous solution. The eggplant flask was immersed in an oil bath at 50°C for 48 hours to polymerize. After the reaction, 5 mL of water was added and stirred, and the solution was poured into 200 mL of methanol. The resulting precipitate was filtered, washed with methanol, and dried under reduced pressure to obtain a white solid sulfobetaine polymer [chemical formula (11)] in a yield of 92%. Measurement by gel permeation chromatography (Shodex OHpak SB-802.5 HQ and SB-806M HQ; both manufactured by Showa Denko K.K.) revealed a number average molecular weight of 94,000 in terms of polystyrene, supporting the structure.

[0096] The sulfobetaine polymer obtained in the synthesis example was dissolved according to the following preparation example, and the resulting mixed aqueous solution was used to prepare a hydrophilic modified substrate according to the following example. The contact angle of water was measured to evaluate the hydrophilicity of the hydrophilic modified substrate.

[0097] (Preparation Example 1) 0.6 g of the sulfobetaine polymer obtained in the synthesis example, 0.2 g of dopamine hydrochloride (Sigma Aldrich), and 0.9 g of sodium chloride were dissolved in 100 g of 10 mM trishydroxymethylaminomethane hydrochloride buffer (pH 8.5) (Cosmo Bio Co., Ltd.) to prepare a mixed aqueous solution containing 0.6 w / w% of the sulfobetaine polymer, 0.2 w / w% of dopamine hydrochloride, and 0.9 w / w% of sodium chloride, and having a weight ratio of the sulfobetaine polymer to dopamine hydrochloride of 3.0.

[0098] Example 1 Using the mixed aqueous solution prepared in Preparation Example 1, various substrates were subjected to hydrophilic treatment as follows. First, a silicone rubber sheet (LSR7050, manufactured by Momentive Corp., thickness 30 μm) was used as the substrate. The surface of the substrate was wiped with cotton containing denatured ethanol (Neoethanol PIP, manufactured by Taishin Chemical Co., Ltd.), and the substrate was immersed in the mixed aqueous solution prepared in Preparation Example 1, left to stand overnight at 20°C while immersed, and then pulled out, thereby performing hydrophilic treatment on the substrate. The substrate after hydrophilic treatment was immersed in physiological saline for 1 minute, then pulled out, then immersed in ion-exchanged water for 1 minute, then pulled out, and further immersed in another ion-exchanged water for 1 minute, then pulled out, thereby washing the substrate after hydrophilic treatment. The washed substrate was dried with an air blower to obtain a modified substrate.

[0099] (Examples 2 to 9) The various modified substrates of Examples 2 to 9 were obtained in the same manner as in Example 1, except that a rigid polyvinyl chloride resin sheet (Standard Test Piece Co., Ltd.: rigid PVC (clear)), a flexible polyvinyl chloride resin sheet (Uemura Co., Ltd.: flexible PVC sheet t0.3 mm), a polystyrene plate (AS ONE Co., Ltd.: Aznol sterilized petri dish, laser processed to form a plate), a cycloolefin polymer sheet (Zeon Japan Co., Ltd.: ZF16-188), a stainless steel plate (SUS304, Nicola Co., Ltd.: 20 μm thick foil), a titanium alloy plate (64 titanium, Standard Test Piece Co., Ltd.: no product name), an alumina plate (Tokyo Glass Instruments Co., Ltd.: alumina square material), and a glass plate (Matsunami Glass Co., Ltd.: borosilicate cover glass 18 mm square) were used as the substrate.

[0100] Comparative Preparation Example 1 A mixed suspension was prepared in the same manner as in Preparation Example 1, except that sodium chloride was not used.

[0101] (Comparative Preparation Example 2) A mixed aqueous solution was prepared in the same manner as in Preparation Example 1, except that the sulfobetaine polymer was not used.

[0102] (Comparative Example 1-1) A modified base material was obtained in the same manner as in Example 1, except that the mixed suspension prepared in Comparative Preparation 1 was used instead of the mixed aqueous solution prepared in Preparation Example 1.

[0103] (Comparative Example 1-2) A modified base material was obtained in the same manner as in Example 1, except that the mixed aqueous solution prepared in Comparative Preparation 2 was used instead of the mixed aqueous solution prepared in Preparation Example 1.

[0104] (Comparative Example 1-3) A modified substrate was obtained in the same manner as in Example 1, except that the modified substrate obtained in Comparative Example 1-2 was immersed in a 0.1 w / w % solution of sulfobetaine polymer in physiological saline.

[0105] (Comparative Examples 2-1, 3-1, and 4-9) Various modified base materials of Comparative Examples 2-1, 3-1, and 4-9 were obtained in the same manner as in Examples 2 to 9, except that the mixed suspension prepared in Comparative Preparation 1 was used instead of the mixed aqueous solution prepared in Preparation Example 1.

[0106] (Comparative Examples 2-2 and 3-2) Various modified substrates of Comparative Examples 2-2 and 3-2 were obtained in the same manner as in Examples 2 and 3, except that the substrate was immersed in the mixed suspension prepared in Comparative Example 1 and left to stand overnight at 80°C while still immersed.

[0107] (Contact angle measurement) 1.0 μL of ion-exchanged water was dropped onto the surface of the modified substrate obtained in Examples 1 to 9 and Comparative Examples 1-1 to 1-3, 2-1 to 2-2, 3-1 to 3-2, and 4 to 9, and the contact angle of the droplet was measured at random at 5 points on each sample 10 seconds after the drop using a contact angle meter (Drop Master, manufactured by Kyowa Interface Science Co., Ltd.), and the average value was calculated. In addition, the contact angle was measured in the same manner for the substrate before the hydrophilization treatment as a blank. The results are shown in Table 1.

[0108] [Table 1]

[0109] (Evaluation of hydrophilicity of modified substrate) The hydrophilicity of the modified substrates was evaluated by comparing the contact angles shown in Table 1 with each other as shown below.

[0110] The modified substrates obtained in Examples 1 to 9 all had a contact angle that was 10° or more lower than that of the blank, and was less than 20°, regardless of the material of the substrate. This shows that the hydrophilicity of the substrate was greatly improved by applying a mixed aqueous solution containing a sulfobetaine polymer electrolyte salt and dopamine hydrochloride to the substrate surface to form a hydrophilic coating layer on the substrate surface.

[0111] The contact angles of water for the modified substrates obtained in Examples 1 to 9 were all about 30° to about 50° lower than those of the modified substrates obtained in Comparative Examples 1-1, 2-1, 3-1, and 4 to 9 in which sodium chloride was not used in the mixed aqueous solution. This shows that when a mixed aqueous solution containing a sulfobetaine polymer electrolyte salt is used in the hydrophilization treatment step at room temperature, it is possible to impart higher hydrophilicity to the substrate than when a mixed suspension containing a free sulfobetaine polymer is used.

[0112] The contact angle could not be measured for the modified substrates obtained in Comparative Examples 2-2 and 3-2 because the substrates became cloudy and deteriorated due to deformation. This shows that the hydrophilization treatment method using a mixed aqueous solution in which sulfobetaine polymer electrolyte salt is dissolved even at room temperature can impart high hydrophilicity to substrates made of low heat-resistant materials such as polyvinyl chloride resin without causing deterioration due to heat.

[0113] The contact angle of the modified substrate obtained in Example 1 was about 50° lower than that of the substrate obtained in Comparative Example 1-2, which did not use the sulfobetaine polymer. This indicates that in the hydrophilization treatment of the substrate, the sulfobetaine polymer exposed on the surface of the hydrophilic coating layer formed on the substrate surface after the treatment significantly reduced the contact angle and imparted high hydrophilicity to the substrate.

[0114] The contact angle of the modified substrate obtained in Example 1 was about 40° lower than the contact angle of the substrate obtained in Comparative Example 1-3, in which the modified substrate obtained in Comparative Example 1-2 was immersed in a sulfobetaine polymer physiological saline solution. This shows that a hydrophilic coating layer exhibiting excellent hydrophilicity cannot be formed unless the sulfobetaine polymer electrolyte salt and the adhesive compound are mutually adsorbed, reacted, bonded, interacted, and / or physically adsorbed when the mixed aqueous solution is applied.

[0115] Next, in order to confirm the difference in the contact angle of the hydrophilic modified substrate due to the difference in the ratio of sulfobetaine polymer electrolyte salt to dopamine hydrochloride in the mixed aqueous solution, the contact angles of the modified substrate obtained in Example 1 and the modified substrates obtained in the following Examples 10 to 12 were measured.

[0116] (Preparation Examples 2 to 4) Various mixed aqueous solutions were prepared in the same manner as in Preparation Example 1, except that 0.1 g, 0.2 g, and 0.4 g of the sulfobetaine polymer were used, respectively, and the sulfobetaine polymer was dissolved at 0.1, 0.2, and 0.4 (w / w or w / v)%, and the weight ratio of the sulfobetaine polymer to dopamine hydrochloride was 0.5, 1.0, and 2.0, respectively.

[0117] (Examples 10 to 12) Hydrophilically modified substrates of Examples 10 to 12 were obtained in the same manner as in Example 1, except that the mixed aqueous solutions obtained in Preparation Examples 2 to 4 were used, respectively.

[0118] (Evaluation of hydrophilicity based on the weight ratio of sulfobetaine polymer and dopamine hydrochloride) The water contact angles of the modified substrates obtained in Examples 1 and 10 to 12 were measured in the same manner as described above. The results are shown in Table 2.

[0119] [Table 2]

[0120] As is clear from Table 2, when the weight ratio exceeded 0.5 and reached approximately 1.0, the contact angle fell below 20°, and when the weight ratio of the sulfobetaine polymer to the dopamine hydrochloride in the mixed aqueous solution was further increased, the contact angle decreased. This shows that by increasing the weight ratio of the sulfobetaine polymer, the amount of the sulfobetaine polymer exposed in the hydrophilic coating layer increases, and hydrophilicity can be further enhanced.

[0121] From the above results, it was confirmed that the method of the present invention provides a simple method for hydrophilizing a substrate, which can rapidly and uniformly develop hydrophilicity under mild conditions while suppressing deterioration of the substrate due to heat, and a hydrophilic modified substrate in which the contact angle with water is maintained sufficiently low. [Industrial Applicability]

[0122] The method for hydrophilizing a substrate of the present invention and the hydrophilically modified substrate obtained by the treatment are used in medical devices such as vascular catheters that require hydrophilicity to be maintained for a long period of time, bio-experimental devices such as cell culture vessels and microchannel chips, daily necessities such as automobile window glass and eyeglass lenses, and various optical components such as optical lenses.

Claims

1. A preparation step of preparing a mixed aqueous solution containing a water-soluble electrolyte, a free sulfobetaine polymer and / or an electrolyte salt thereof, and a free catecholamine and / or a salt thereof; a hydrophilization step of applying the mixed aqueous solution to a surface of a substrate, and depositing the free sulfobetaine polymer and / or electrolyte salt thereof and the adhesive substance containing at least one selected from the free catecholamine and salt thereof, oxidized form and / or cyclized form of any of them, and condensation product, multimer, polymer, association product and / or aggregate of any of them on the surface of the substrate while adsorbing, reacting, bonding, interacting and / or physically adsorbing to each other, thereby forming a hydrophilic coating layer and imparting hydrophilicity to the surface of the substrate; A method for hydrophilizing a substrate, comprising:

2. 2. The method for hydrophilizing a substrate according to claim 1, wherein the free catecholamine is at least any one of compounds selected from the group consisting of dopamine, L-3,4-dihydroxyphenylalanine, norepinephrine and epinephrine.

3. 2. The method for hydrophilizing a substrate according to claim 1, wherein the oxidized product and / or the cyclized product is at least any one of catecholamine derivatives selected from 4-(2-aminoethyl)-1,2-benzoquinone, 5,6-dihydroxyindoline, 5,6-dihydroxy-3H-indole, and 5,6-dihydroxyindole.

4. 2. The method for hydrophilizing a substrate according to claim 1, wherein the hydrophilic coating layer contains a polycatecholamine.

5. 2. The method for hydrophilizing a substrate according to claim 1, wherein the substrate to be hydrophilized is not subjected to at least any dry surface modification treatment selected from plasma discharge, corona discharge, ultraviolet irradiation, excimer UV irradiation, electron beam irradiation, and radiation irradiation, and is not subjected to any wet surface modification treatment selected from alkaline solution immersion, acidic solution immersion, and micro-nano bubble solution immersion.

6. 2. The method for hydrophilizing a substrate according to claim 1, wherein the substrate to be hydrophilized is subjected to at least any one of dry surface modification treatments selected from plasma discharge, corona discharge, ultraviolet irradiation, excimer UV irradiation, electron beam irradiation, and radiation irradiation, and / or any one of wet surface modification treatments selected from alkaline solution immersion, acidic solution immersion, and micro-nano bubble solution immersion.

7. 2. The method for hydrophilizing a substrate according to claim 1, wherein the mixed aqueous solution is adjusted to a pH of 8 to 11.

8. 2. The method for hydrophilizing a substrate according to claim 1, wherein the mixed aqueous solution is prepared so that the weight ratio of the free sulfobetaine polymer and its electrolyte salt to the free catecholamine and its salt is 0.01 to 10.

9. 2. The method for hydrophilizing a substrate according to claim 1, wherein the mixed aqueous solution is prepared to contain 0.1 to 26 w / w % of the water-soluble electrolyte, 0.01 to 10 w / w % of the free sulfobetaine polymer and / or electrolyte salt thereof, and 0.001 to 30 w / w % of the free catecholamine and / or salt thereof.

10. 2. The method for hydrophilizing a substrate according to claim 1, wherein the water-soluble electrolyte is at least one selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, sodium bromide, potassium bromide, and sodium iodide.

11. 2. The method for hydrophilizing a substrate according to claim 1, wherein the substrate is made of at least one material selected from the group consisting of rubber, resin, glass, metal and ceramics.

12. The rubber is at least one selected from the group consisting of silicone rubber, fluororubber, ethylene-propylene binary copolymer rubber, ethylene-propylene-diene ternary copolymer rubber, urethane rubber, acrylic rubber, ethylene vinyl acetate rubber, chlorosulfonated polyethylene rubber, chlorinated polyethylene rubber, epichlorohydrin rubber, polysulfide rubber, butyl rubber, butadiene rubber, styrene butadiene rubber, chloroprene rubber, nitrile rubber, isoprene rubber, and natural rubber, and the resin is silicone resin, polyvinyl chloride, polyethylene, polypropylene, polystyrene, acrylonitrile-butadiene-styrene resin, (meth)acrylic resin, polyvinyl alcohol, polyamide, polyethylene terephthalate, polybutylene terephthalate, urethane resin, polycarbonate, nylon, polyether ether ketone, polylactic acid, styrene-based thermoplastic elastomer, olefin-based thermoplastic 12. The method for hydrophilizing a substrate according to claim 11, wherein the ceramic is at least one selected from the group consisting of elastomers, ester-based thermoplastic elastomers, amide-based thermoplastic elastomers, dynamically crosslinked thermoplastic elastomers, fluorine-based thermoplastic elastomers, polyphenylene sulfide, polyphenylsulfone, cycloolefin polymers, cycloolefin copolymers, and polyoxymethylene; the glass is at least one selected from the group consisting of quartz glass, borosilicate glass, and soda-lime glass; the metal is at least one selected from the group consisting of stainless steel, iron, aluminum, titanium, silver, copper, gold, cobalt, chromium, molybdenum, nickel, tungsten, platinum, and alloys thereof; and the ceramic is at least one selected from the group consisting of alumina, zirconia, aluminum nitride, silicon carbide, silicon nitride, steatite, and hydroxyapatite.

13. 13. The method for hydrophilizing a substrate according to claim 12, wherein the substrate is formed from at least any low heat-resistant material selected from the group consisting of the urethane rubber, the polyvinyl chloride, the polyethylene, the urethane resin, the styrene-based thermoplastic elastomer, the olefin-based thermoplastic elastomer, the ester-based thermoplastic elastomer, the amide-based thermoplastic elastomer, the dynamically crosslinked thermoplastic elastomer, the fluorine-based thermoplastic elastomer, and the (meth)acrylic resin.

14. The free sulfobetaine polymer is represented by the following chemical formula (1): [Formula 1] (In formula (1), R １ is a hydrogen atom or a methyl group, and n1 and n2 are numbers from 2 to 6), and / or the following chemical formula (2): [Case 2] (In formula (2), R ２ is a hydrogen atom or a methyl group, n3, n5, n6 and n8 are numbers from 2 to 6, and n4 ａ and n7 ａ are all 0 or n4 ａ and n7 ａ is 1, n4 ｂ and n7 ｂ is a number from 1 to 3), or a polymer composed only of repeating units having a sulfobetaine group represented by the above chemical formula (1) and / or (2) and a repeating unit having a sulfobetaine group represented by the following chemical formula (3): [C3] (In formula (3), R ３ is a hydrogen atom or a methyl group, n9 is a number from 2 to 6, n10 is a number from 0 to 1, R ４ is any active functional group selected from an azide group, a sulfo group, an alkoxysilyl group, and a hydroxyl group), and / or a repeating unit having an active functional group represented by the following chemical formula (4): [C4] (In formula (4), R 5 is a hydrogen atom or a methyl group, R 6is any functional group selected from a carboxyl group, an ethylene glycol group or an ethylene glycol oligomer, an acrylic group, and a methacrylic group), which is a random copolymer, a block copolymer, an alternating copolymer, or a graft copolymer with a repeating unit represented by the following formula (I):

15. 2. The method for hydrophilizing a substrate according to claim 1, wherein the molecular weight of the free sulfobetaine polymer is at least 30,000.

16. 2. The method for hydrophilizing a substrate according to claim 1, wherein the mixed aqueous solution is applied at a temperature of 1 to 30°C.

17. 2. The method for hydrophilizing a substrate according to claim 1, further comprising a step of desalting the water-soluble electrolyte, the sulfobetaine polymer electrolyte salt, and / or the catecholamine salt applied to the substrate by washing the substrate with water after the hydrophilization step.

18. A hydrophilic modified substrate, characterized in that a hydrophilic coating layer is formed on the surface of the substrate, in which a free sulfobetaine polymer and / or an electrolyte salt thereof and an adhesive substance containing at least one selected from the group consisting of the free catecholamine and its salt, oxidized form and / or cyclized form of any of them, and condensation product, multimer, polymer, association product and / or aggregate of any of them are mutually adsorbed, reacted, bonded, interacted and / or physically adsorbed and deposited on the surface of the substrate, and the hydrophilic coating layer has a contact angle reduced by at least 10° compared to the surface of the substrate, thereby improving hydrophilicity.

19. 20. The hydrophilically modified substrate according to claim 18, wherein the surface of the hydrophilic coating layer is a desalting surface.

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