Polymer compound

Abstract

Provided is a novel biocompatible polymer.　This polymer compound has a chain ether structure in a side chain and has a specific branched structure in this chain ether structure.

Description

polymer compounds 【0001】 This invention relates to polymer compounds and the like that exhibit biocompatibility. This application claims priority based on Japanese Patent Application No. 2024-213889, filed in Japan on December 6, 2024, and incorporates the contents of thereunder. 【0002】 Generally, when biological components such as blood come into contact with the surface of various artificial materials, the material surface is recognized as a foreign substance, leading to nonspecific adsorption, denaturation, and multilayer adsorption of proteins from biological tissues to the material surface. As a result, activation of the coagulation system, complement system, platelet system, etc. For this reason, it is desirable to impart biocompatibility to the surface of medical devices used in contact with living organisms, or biological materials such as tissues, cells, and blood extracted from living organisms, in order to prevent the device from being recognized as a foreign substance and causing a foreign substance reaction with biological components during use. 【0003】 As a means of imparting biocompatibility to the surface of various medical devices, biocompatible materials have been artificially synthesized and applied to the surface of medical devices to impart biocompatibility to the surface. Known biocompatible materials include polymer compositions containing polymer compounds such as 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, polyethylene glycol (PEG), poly(2-methoxyethyl acrylate) (PMEA), and polyalkoxyalkyl (meth)acrylamide. By using these biocompatible materials to constitute the parts of the medical device surface that come into contact with biological components such as blood, it is possible to prevent the medical device surface from being recognized as a foreign substance, and as a result, it is possible to suppress the activation of the coagulation system, complement system, platelet system, etc. 【0004】MPC polymers are a type of betaine that maintains electrical neutrality in the biological environment. They are produced by bonding the phospholipid polar groups that cover the cell membranes of living organisms to polymerizable groups such as vinyl groups via ester bonds, and then polymerizing these polymerizable groups. They have a structure in which phospholipid polar groups are bonded as side chains to an alkyl chain (main chain). In other words, MPC polymers are polymers that exhibit biocompatibility by having a structure that mimics the substances that make up living organisms. By constructing the surface of medical devices with MPC polymers, a structure similar to the molecular structure of cell membranes is formed on the surface, thereby suppressing platelet adhesion and exhibiting excellent antithrombotic properties. 【0005】 In contrast, PEG is a type of chain-like ether structure - (C ２ H ４ It is a polymer whose repeating unit is -O)- and is known to have excellent biocompatibility despite having a structure that is not similar to the substances that make up living organisms. Furthermore, PMEA has a (meth)acrylic skeleton that corresponds to a structure in which the side chain portion is linked to the carbon chain main chain by an ester bond, and the constituent unit of PEG is -(C ２ H ４ It is known that a structure incorporating a side chain with -O)- as the main structure exhibits biocompatibility, and is widely used as a material to impart biocompatibility to the surface of pathways that carry blood and other fluids. 【0006】 Furthermore, Patent Document 1 describes a polymer having a structure in which (meth)acrylamide repeating units differs from the above-mentioned PMEA in that the structure of the part corresponding to the linker that connects the side chains is different, and it is described that due to its appropriate hydrophilicity, it is possible to suppress the activation of the coagulation system, complement system, platelet system, etc., and exhibits excellent blood affinity. 【0007】In addition, for example, Patent Document 2 discloses a polymer in which a side chain having a chain ether structure or a cyclic ether structure is provided for a vinyl ether skeleton having an ether bond as a linker for the main chain. Patent Document 3 discloses a biodegradable polymer in which a side chain having a chain ether structure or the like is bonded to a main chain having a carbonate bond or the like via an alkylene group, an ether bond, a thioether bond or the like as a linker. Patent Document 4 discloses a polymer in which the density of introducing a side chain containing a chain ether structure into various main chains is changed when compared with the above PMEA. Patent Document 5 describes polymers having different numbers of repetitions of the chain ether structure contained in each side chain when compared with the above PMEA, and each of them is described as exhibiting biocompatibility. 【0008】 In addition, Patent Document 6 describes a polymer obtained by modifying the structure of the -(C ２ H ４ -O)- moiety, which is a chain ether structure introduced into the side chain, based on the above PMEA as a basic structure. That is, in PMEA, when the chain ether structure represented by the structural formula of (C ２ H ４ -O) is generalized to (C ｎ H ２ｎ -O), it is described that a predetermined biocompatibility is exhibited in the range of n = 3 to 6, and the degree of hydrophilicity / hydrophobicity of the polymer particularly changes according to the n value, and it is described that a structure corresponding to the use of the polymer can be selected. 【0009】 In addition, Patent Document 7 describes a polymer obtained by polymerizing an olefin containing an ether bond or the like, and having a biocompatibility in which the chain ether structure contained in the side chain portion is bonded to the main chain via an alkylene group as a linker. 【0010】 As described above, in addition to MPC polymers and the like in which a structure imitating a substance constituting a living body is provided as a side chain for the main chain of a synthetic polymer, -(C ２ H ４It has been revealed that polymers incorporating chain-like ether structures, such as -O), as side chains in various forms exhibit biocompatibility similar to that of biologically derived substances. Thus, regarding the mechanism by which biocompatibility is expressed even in polymers with structures completely different from those of biologically derived substances, it has been revealed that when these polymers are hydrated, they can commonly contain water molecules in a state called "freezing-bound water" (intermediate water). This has been used as a clue to explore the mechanism by which biocompatibility is expressed. 【0011】 For example, Non-Patent Literature 1 describes that near the surface of the above-mentioned PMEA that is saturated with water, there is intermediate water that generates latent heat transfer due to the ordering / disordering of water molecules even in sub-zero temperature ranges. It has been revealed that such intermediate water can be observed not only in the above-mentioned polymer but also in various bio-derived substances, and is thought to play an important role in the expression of biocompatibility. 【0012】 Japanese Patent Publication No. 2004-357826, Japanese Patent Publication No. 2014-47347, Japanese Patent Publication No. 2014-161675, Japanese Patent Publication No. 2014-105221, International Publication No. 2004 / 087228, Japanese Patent Publication No. 2017-82174, Japanese Patent Publication No. 2024-12222 【0013】 Tanaka, M. et al. , Journal of Biomaterials Science Polymer Edition, 2010, 21, p. 1849-1863 【0014】 As described above, even if the material is not a living organism, it is possible to construct polymers that can contain intermediate water by introducing structures such as chain-like ethers that contribute to the formation of intermediate water into the main chain of various polymers, thereby enabling the expression of biocompatibility. On the other hand, because the mechanism by which each of the above-mentioned polymers contains intermediate water has not been fully elucidated, the relationship between the specific structure of the chain-like ether introduced, particularly for the purpose of forming intermediate water, and the properties exhibited by that structure can only be clarified by evaluating polymers that have been actually synthesized. 【0015】 On the other hand, as described above, while there is a need to impart biocompatibility to the surface of various medical devices, there is also a need for these medical devices to possess various properties other than biocompatibility, depending on their intended use. Therefore, it is hoped that a new polymer capable of exhibiting various functions along with biocompatibility will be obtained to meet this need. Accordingly, the object of the present invention is to provide a novel polymer exhibiting biocompatibility. 【0016】 (1) A polymer having a side chain portion represented by the following formula 1, [However, L in the formula is a linker that connects the side chains to the polymer main chain, and R １ R is a divalent saturated hydrocarbon group containing a linear or branched carbon chain having 2 to 6 carbon atoms, ２ R is a monovalent hydrocarbon group having 6 or fewer carbon atoms, which may have a hydrogen atom or an ether bond. １ A polymer in which at least one hydrogen atom bonded to a carbon atom is replaced by a structure represented by the following formula 2. [However, R in the formula ３ R is a divalent saturated hydrocarbon group comprising a linear or branched carbon chain having 0 to 5 carbon atoms, wherein the number of carbon atoms (C) between the oxygen atom (O) and the linker (L) in formula 2 is 2 to 6, ４ (1) The polymer is a hydrogen atom or a monovalent hydrocarbon group having 6 or fewer carbon atoms which may have an ether bond. (2) The polymer is hydrated and, when hydrated, releases or absorbs latent heat due to the ordering / disordering of water molecules in a temperature range below the freezing point. (3) The above R １ and R ３(4) The polymer having six or fewer carbon atoms. (5) The polymer having one hydrogen atom substituted with the structure of formula 2. (6) The polymer having a carbon chain whose main chain is mainly composed of carbon atoms. (7) The polymer having a linker which is an alkylene group, an ether bond, a thioether bond, an ester bond, an amide bond, a urethane bond, or a urea bond. (8) A polymer composition containing the polymer. (9) The polymer composition used to coat at least a portion of a surface that is used in contact with a biological substance. 【0017】 The polymer compound according to the present invention exhibits biocompatibility and, in particular, hydrophobic properties compared to PMEA, etc., enabling the formation of stable coatings on the surfaces of various substrates. It can be used not only on surfaces where biocompatibility is required, such as surfaces used in contact with biological substances, but also as a material for constituting surfaces for selectively adhering to and recovering various proteins and cells, as well as as an antifouling material. 【0018】 Synthesized DiMEA １ This chart shows the results of the 1H NMR measurement. １ This chart shows the results of the 1H NMR measurement. １ This chart shows the results of 1H NMR measurements. This graph shows the contact angle of water on the surface of a PP substrate coated with PDiMEA and PMEA, and on the surface of an untreated PP substrate. These are photographs showing the surface condition of a substrate coated with PDiMEA and PMEA, and the substrate after being immersed in water. This graph shows the density of platelets adhering to substrates with various polymer surfaces. This graph shows the absorbance at 405 nm in solutions taken from the surfaces of various polymers in contact with PPP. This graph shows the amount of plasma protein adsorbed from PPP onto each polymer. 【0019】In hydrophobic polymers, which exhibit hydrophobicity due to their weak interaction with water molecules, a clear interface is maintained between the polymer and the aqueous phase at the interface where the hydrophobic polymer contacts the aqueous phase, as virtually no interaction occurs between the polymer molecules and water molecules. On the other hand, when a hydrophilic polymer is brought into equilibrium with the aqueous phase, it is known that a complex interfacial structure (hydration structure) is formed due to hydration reactions between the polymer molecules and water molecules. It is thought that various polymers are classified as hydrophobic or hydrophilic depending on whether or not they interact with the aqueous phase (water molecules). 【0020】 It is known that within the hydration structure formed in the hydrophilic polymer in equilibrium with the aqueous phase described above, there exist water molecules that are generally strongly constrained by polymer molecules and cannot undergo phenomena such as solidification / melting inherent to water molecules when subjected to temperature histories such as heating or cooling. Water molecules in this state are generally called "nonfreeze water." Furthermore, it is known that on the outer shell of this nonfreeze water, there exist water molecules in a state called "free water," which are weakly constrained by cohesive forces with the water molecules constituting the nonfreeze water, but can undergo solidification / melting similar to the single-phase aqueous phase. 【0021】 On the other hand, for example, it has been confirmed that within the hydrated structure of polymers described in Patent Documents 1 to 7, etc., which are hydrated with the aqueous phase, there are water molecules that behave differently from the nonfreezing water and free water described above. In other words, when the polymers described in Patent Documents 1 to 7, etc., are hydrated and subjected to temperature changes in the range of -100°C to 0°C, latent heat transfer is observed, which is thought to be due to the phase transformation of water molecules into ordered / disordered. 【0022】The latent heat of water molecules observed in the range of -100°C to 0°C, which is thought to be due to the order / disorder phase transformation, is difficult to consider as originating from the above-mentioned nonfreezing water or free water. It is thought to suggest the existence of water molecules in a state different from that of nonfreezing water or free water, and these water molecules in this state are defined as "intermediate water." This "intermediate water," defined by the occurrence of order / disorder phase transformation in the range of -100°C to 0°C, is also observed in various substances that make up living organisms. Furthermore, in synthetic polymers, it has been observed that the interaction between the polymer and biomolecules such as proteins and cells changes depending on the intermediate water content in the hydrated synthetic polymer, and that biocompatibility is expressed (see Patent Documents 1 to 7, etc.). 【0023】 The mechanism by which water molecules in the state defined as intermediate water are generated in polymers having a predetermined structure, such as those described in Patent Documents 1 to 7, is not yet clear. However, it is thought that a predetermined amount of water molecules are in a state where they can become ordered or disordered below freezing point due to the influence of antifreeze water that is strongly constrained by the polymer molecules, or from polymers that exist across the antifreeze water. In other words, it is presumed that the mechanism by which intermediate water is contained in a hydrated polymer is due to a predetermined interaction between the polymer and water molecules, which is indirectly caused by the polymer's hydrophilicity. 【0024】 Furthermore, due to the mechanism described above, it is believed that in polymers with particularly high biocompatibility, such as PEG and MPC polymers, when brought into contact with an aqueous phase, biocompatibility is exhibited, and as a result of high-density bonding of water molecules around the molecular chains of the polymer, the bonds between polymer molecules become difficult to maintain, leading to the emergence of water-soluble polymer characteristics. 【0025】 For water-soluble polymers exhibiting biocompatibility, polymers such as PMEA have relatively low hydrophilicity in their polymer backbone, and the constituent unit of PEG is -(C ２ H ４It is believed that by having structures such as -O- in the side chain portion relative to the main chain, hydration necessary for the formation of intermediate water occurs in the side chain portion, while the bonds between polymer molecules are maintained as a whole, resulting in water insolubility. 【0026】 As described above, when using polymers that contain water molecules in an intermediate water state through hydration and exhibit biocompatibility to coat the surface of medical devices, it is desirable that the polymers used in the coating exhibit high water insolubility, and that the coating film remains stable even when in prolonged contact with aqueous solutions containing blood, etc., particularly from the viewpoint of enabling stable use over long periods. On the other hand, as explained above, the formation of intermediate water is due to the hydrophilicity exhibited by the polymers, etc., so there is a trade-off between the expression of biocompatibility and the expression of high water insolubility, and it is necessary to design polymers that can achieve both. 【0027】 When forming polymers that exhibit biocompatibility but are water-insoluble, a common method is to introduce a structure that contributes to the formation of intermediate water as a side chain portion to a predetermined water-insoluble polymer backbone. This is mainly because, in polymer production, the polymer backbone is formed by polymerization between predetermined monomer molecules, making it difficult to introduce both hydrophobic structures and structures that contribute to the formation of intermediate water into the polymer backbone exposed to the polymerization reaction. 【0028】 Therefore, when forming polymers that are particularly water-insoluble but exhibit biocompatibility, it is common to use monomer molecules in which a structure that contributes to the generation of intermediate water has been introduced into a monomer structure capable of forming a water-insoluble polymer main chain by polymerization, and then polymerize this molecule. The structure of the polymer main chain selected in this case can be determined by considering the expected degree of hydrophobicity and other physical properties, within a range where the generation of intermediate water by the introduced structure is not inhibited. 【0029】Conventionally, polymer main chains in which the formation of intermediate water has been confirmed by introducing structures such as chain-like ethers that contribute to the formation of intermediate water into the side chain portion include, for example, (meth)acrylic structures (Patent Documents 4-6), (meth)acrylamide structures (Patent Document 1), vinyl ether structures (Patent Document 2), and polyolefin structures (Patent Document 7). Furthermore, in base polymer main chains composed of alkylene groups linked by carbonate bonds, ester bonds, amide bonds, urethane bonds, or urea bonds, the formation of intermediate water has also been confirmed by introducing structures such as chain-like ethers into the side chain portion (Patent Document 3). 【0030】 In this specification, polymers that do not exhibit water solubility among polymers that form hydration with water molecules may be specifically referred to as hydrateable polymers. Furthermore, in this specification, when a polymer is described as non-water soluble or not exhibiting water solubility, it means that the polymer substantially has no solubility in the aqueous phase, and for example, that it has sufficient solubility resistance to prevent the coating from dissolving and disappearing into the aqueous phase during the period of use of a medical device, etc., whose surface is composed of a coating made of such polymer. 【0031】 Furthermore, in this specification, the terms "polymer" and "polymer" shall be used interchangeably to refer to compounds (molecules) having a structure composed of repeating monomer units. In addition, an aggregate comprising such polymer compounds may be referred to as a polymer composition, and a polymer composition may include polymer molecules with different microstructures and molecular weights, as well as organic solvents capable of dissolving such polymer molecules. 【0032】 Furthermore, in the polymer (polymer), the repeating units that constitute the polymer may be referred to as monomer units. In addition, the term "polymer" shall be used to refer not only to polymers but also to macromolecules, such as proteins and nucleic acids, which are composed of many atoms bonded together by covalent bonds. Furthermore, the term "chain ether structure" shall be used to mean a structure in which one or more unit structures are linked together, in which at least one end of a divalent saturated hydrocarbon group containing a linear or branched carbon chain is replaced by an ether bond (-O-). 【0033】 Furthermore, in this invention, "biocompatibility" refers to the characteristic of being less likely to be recognized as a foreign substance when in contact with biological substances or substances derived from biological materials. Specifically, for example, it means that it does not cause complement activation or platelet activation and is minimally invasive or non-invasive to tissues. The "biocompatibility" aspect also includes the "blood compatibility" aspect. "Blood compatibility" means that it does not induce blood coagulation mainly caused by platelet adhesion or activation. 【0034】 Furthermore, when referring to a surface used in contact with biological substances, it means a surface that comes into contact with, or is formed or used in the event of contact with, living organisms, intracellular tissues, tissues extracted from living organisms, cells extracted from living organisms or cultured after extraction, tissues obtained by culturing such cells, blood, or other substances that have activity as part of life's activities. 【0035】 The inventors conducted various studies on polymers that exhibit biocompatibility and are water-insoluble. They discovered that by introducing a chain-like ether structure into the side chain portion of various polymer main chains via a linker portion, and by introducing a predetermined branching structure within the chain-like ether structure, they were able to maintain biocompatibility while producing changes in properties such as increased hydrophobicity compared to cases where the branching is not introduced. This led to the present invention. 【0036】 In other words, for example, in the PMEA mentioned above, the side chain portion is such that the linker (L) portion is an ester bond, and the carbon chain R included in the linear ether structure is such that the linker (L) portion is an ester bond. １ (-CH ２ -CH ２ -), structure of the tip of the side chain (R ２ This corresponds to a structure in which the methyl group is located. 【0037】 In contrast to the side chain structure in PMEA, etc., the polymer compound according to the present invention has a carbon chain R that constitutes the chain-like ether structure. １The present invention is characterized by having a structure in which at least one hydrogen atom bonded to a carbon atom contained in the material is replaced with a structure represented by the following formula 2. 【0038】 【0039】 However, R in equation 2 ３ R is a divalent saturated hydrocarbon group comprising a linear or branched carbon chain having 0 to 5 carbon atoms, wherein the number of carbon atoms (C) between the oxygen atom (O) and the linker (L) in formula 2 is 2 to 6. ４ This is a hydrogen atom or a monovalent hydrocarbon group having 6 or fewer carbon atoms, which may have an ether bond. In other words, the polymer compound according to the present invention, for example, when the above PMEA is used as a reference, contains carbon chains (-CH) in the chain-like ether structure of its side chain portion. ２ -CH ２ By introducing branching (-), this corresponds to a structure in which a side chain having multiple tip portions (-OR) is introduced. 【0040】 Chain ether structure included in the structure described in Formula 1 above [R １ -O] is the R １ ga-CH ２ -CH ２ -In this case, the structure corresponds to the constituent unit of PEG, which has excellent biocompatibility. Furthermore, in a polymer obtained by introducing the structure described in Formula 1 above into the side chain portion, R １ It has been confirmed that when the number of carbon atoms in the ether is between 2 and 6, it effectively contains intermediate water when hydrated (Patent Document 6, etc.), and this chain-like ether structure is considered to be a suitable structure for generating water molecules in an intermediate water state through hydration. 【0041】Although the mechanism by which the chain-like ether structure contributes to the formation of intermediate water is not clear, the present invention has revealed that even when a predetermined branching is introduced into the chain-like ether structure, as shown in the following examples, and the side chain portion that is linked to the polymer main chain by a single linker (L) has multiple terminal structures (-OR), the contribution to the formation of intermediate water is maintained. In other words, even when the chain-like ether structure has a predetermined branching, the structure can be understood as a form of chain-like ether structure in that it contributes to the formation of intermediate water. 【0042】 Furthermore, it is presumed that introducing branching into the chain-like ether structure, which changes (increases) the number of carbon atoms per unit side chain, improves the hydrophobicity of the side chain portion, thereby increasing the overall hydrophobicity of the polymer. 【0043】 The coating obtained by applying a composition containing the polymer compound according to the present invention to various resin substrates, etc., exhibits biocompatibility and is water-insoluble. In particular, it is less prone to morphological changes such as uneven film thickness even when in contact with an aqueous phase for a long period of time, making it preferably usable for imparting biocompatibility to the surface of medical devices and the like. 【0044】 In comparison with the present invention, when a film is formed on the surface of a resin substrate such as PET (polyethylene terephthalate) or PP (polypropylene) using the above-mentioned PMEA, which corresponds to a structure in which a branch-free structure within the chain-like ether structure is introduced as a side chain to the acrylic skeleton, if the film is in contact with the aqueous phase for a long period of time, it is observed that the film thickness of the PMEA-composed film on the surface of the resin substrate becomes non-uniform, and a spotted pattern containing minute, hill-like protrusions is generated, resulting in what is known as dewetting. This phenomenon is thought to be the result of the PMEA agglomerating because the surface tension of the PMEA prevails in the balance between the surface energy present between the PMEA and PET, etc. 【0045】The coating formed on the surface of various substrates using the polymer compound according to the present invention exhibits high adhesion to the PMEA and the like, and maintains its shape stably even when in contact with the aqueous phase for a long period of time. It can be preferably used to impart biocompatibility to the surface of medical devices such as cardiopulmonary bypass machines, which are expected to be used continuously for long periods of time. 【0046】 On the other hand, the polymer compound according to the present invention exhibits hydrophobic properties compared to PMEA, which reduces the surface energy generated at the interface with resin substrates and the like. As a result, it is considered that film non-uniformity is less likely to occur. 【0047】 The polymer compound according to the present invention is characterized by including a side chain structure containing a chain-like ether represented by formula (1) above, wherein at least one hydrogen atom contained in the chain-like ether is substituted by formula (2) above. In formula (1) above, L is a linker that connects the side chain to the polymer main chain, and R １ R is a divalent saturated hydrocarbon group containing a linear or branched carbon chain having 2 to 6 carbon atoms. ２ This represents a monovalent hydrocarbon group having 6 or fewer carbon atoms, which may have a hydrogen atom or an ether bond. The term "hydrocarbon group which may have an ether bond" includes forms in which the two carbon atoms constituting the hydrocarbon group are bonded via an ether bond (-O-), such as an ethyl group (-CH₂). ２ -CH ３ In contrast to, -CH ２ -O-CH ３ This means that the group may contain the group represented by [the symbol]. Furthermore, the ether bond contained in each hydrocarbon group is not limited to one, but may contain multiple ether bonds. 【0048】 R １ By setting the number of carbon atoms in to 2 or 3, a side chain structure suitable for efficiently generating intermediate water when hydrated can be formed. On the other hand, by setting the number of carbon atoms to 4 to 6, hydrophobicity improves with increasing carbon number, and the water-insoluble properties of the polymer compound can be improved. Also, R ２ If it does not have an ether bond, R２ R is based on the case of a hydrogen atom. ２ Increasing the number of carbon atoms in improves hydrophobicity, which can improve the water-insoluble properties of the polymer compound. On the other hand, R ２ If the polymer compound contains an ether bond, the ether bond forms a new chain-like ether structure with the oxygen atom (O) described in formula (1) above, which can improve the amount of intermediate water that the polymer compound can contain. 【0049】 In the above equation (2), R in the equation ３ R is a divalent saturated hydrocarbon group containing a linear or branched carbon chain having 0 to 5 carbon atoms, wherein the number of carbon atoms (C) between the oxygen atom (O) and the linker (L) in formula 2 is 2 to 6. ３ If we set the number of carbon atoms in formula (2) to 0, then the oxygen atoms in formula (1) are R １ By directly bonding to the carbon atoms contained in, a side chain having multiple leading ends (-OR) is formed. ３ By setting the number of carbon atoms contained in to 1 to 5, and the number of carbon atoms (C) between the oxygen atom (O) and the linker (L) in formula 2 to 6, it is considered that the introduced structural part of formula (2) also has a chain-like ether structure and contributes to the formation of intermediate water. 【0050】 Also, especially R ３ When using a linear saturated hydrocarbon group, R ３ (CH ２ ) ｍ (where m is an integer from 0 to 5) This can be expressed as: R ４ R in equation (1) is ２ Similarly, the properties of the polymer compound change depending on the number of carbon atoms and the presence or absence of ether bonds, so the structure of the polymer compound can be determined according to its intended use. In the polymer compound according to the present invention, R is formed within a single side chain portion. ２ and R ４ The structure of R may be the same. ２ and R ４ The structures may be different. 【0051】 R is replaced by the structure shown in formula (2) above. １ The number of hydrogen atoms bonded to the carbon atom in R may be one or multiple. １ The two hydrogen atoms bonded to a single carbon atom contained in may be substituted by the structure shown in formula (2), and R １ It is also possible to substitute the hydrogen atoms of different carbon atoms contained in the formula with the structures shown in formula (2). 【0052】 Furthermore, the polymer compound according to the present invention may have any side chain structure having the structure shown in formulas (1) and (2) above, for example, the above R １ ~R ４ In addition to homopolymers consisting of monomer units having the same structure, R may be different from each other within the range of formulas (1) and (2) above. １ ~R ４ This can be a polymer compound containing a side chain having the following properties: 【0053】 Furthermore, the polymer compound according to the present invention may contain side chain structures other than the side chain structure represented by formula (1) substituted by formula (2), within the range in which intermediate water can be generated when hydrated. For example, by introducing a side chain containing a chain-like ether that does not have branching due to the absence of substitution by formula (2), the hydrophilicity of the polymer compound as a whole can be increased. Alternatively, by introducing alkyl groups or the like that that do not contain chain-like ether structures as side chains, the hydrophobicity of the polymer compound as a whole can be increased. 【0054】 As described above, polymer compounds having side chain portions with mutually different structures can be synthesized by copolymerizing a polymer while mixing monomers constituting the desired side chain in a predetermined ratio. Furthermore, the side chain portions with mutually different structures may be randomly introduced into the polymer compound, or they may form block copolymers containing groups with identical structures. 【0055】In the polymer compound according to the present invention, it is desirable that the ratio of the side chain structure represented by the above formula (1) substituted by the above formula (2) is 51 mol% or more with respect to the total number of repeating units constituting the polymer compound. In particular, when the ratio is 70 mol% or more, or 90 mol% or more, 95 mol% or more, or when the polymer compound has substantially only the side chain structure represented by the above formula (1) substituted by the above formula (2), it is possible to exhibit good characteristics. 【0056】 The above divalent saturated hydrocarbon group (R １ ) is a divalent saturated hydrocarbon group containing a linear or branched carbon chain having 2 to 6 carbon atoms. As an example thereof, a linear or branched carbon chain having 2 to 6 carbon atoms, -CH ２ CH ２ -, -CH(CH ３ ) -, -CH ２ CH ２ CH ２ -, -CH(CH ３ )CH ２ -, -CH ２ (CH ２ ) ２ CH ２ -, -CH(CH ３ )CH ２ CH ２ -, -CH ２ (CH)(CH ３ )CH ２ -, -CH(CH ３ )CH(CH ３ ) -, -CH ２ (CH ２ ) ３ CH ２ -, -CH(CH ３ )(CH ２ ) ２ ​​​​​​​​​​​​​​​​​​​​A divalent saturated hydrocarbon group selected from the group consisting of -, etc., can be used. 【0057】 In formula (1), a saturated hydrocarbon group (R １ ) and the said R １ It is thought that the ether bond attached to the ether forms a chain-like ether structure, and that the presence of this chain-like ether structure generates intermediate water when hydrated, thereby exhibiting biocompatibility. In addition, the R that constitutes the tip of the side chain ２ By further incorporating ether bonds within the structure, it is possible to create a chain-like ether structure in which multiple units are linked together. 【0058】 Also, R in equation (1) ２ In addition to selecting a hydrogen atom, other monovalent hydrocarbon groups with six or fewer carbon atoms include, for example, methyl (CH4). ３ ), ethyl (-CH ２ CH ３ ), propyl (-(CH ２ ) ２ CH ３ ), i-propyl (-CH(CH ３ ) ２ ), n-butyl (-(CH ２ ) ３ CH ３ ), i-butyl (-CH ２ CH (CH ３ ) ２ ), tert-butyl (-C(CH ３ ) ３ ), n-pentyl(-(CH ２ ) ４ CH ３ ), neopentyl (-CH ２ C (CH ３ ) ３ ), isoamyl (-(CH ２ ) ２ CH (CH ３ ) ２ ), tert-amil (-C (CH ３ ) ２ CH ２ CH ３ ), n-hexyl (-(CH ２ ) ３ CH ３), and i-hexyl (-(CH ２ ) ３ CH (CH ３ ) ２ Examples of hydrocarbon groups selected from the group consisting of ) include, in particular, -CH ３ ,-CH ２ CH ３ ,-(CH ２ ) ２ CH ３ ,-(CH ２ ) ３ CH ３ ,-(CH ２ ) ４ CH ３ ,-(CH ２ ) ５ CH ３ These can be used. Furthermore, by having an ether bond inside the monovalent hydrocarbon group, a chain-like ether structure that contributes to the formation of intermediate water can be constructed. 【0059】 The structure of the polymer backbone constituting the polymer compound according to the present invention can be selected and used without particular restriction, as long as it does not significantly inhibit the generation of intermediate water caused by the side chain structure specified by formulas (1) and (2) above. The polymer compound according to the present invention can be obtained by introducing the side chain structure specified by formulas (1) and (2) above as a linker, with the crosslinking group determined in relation to the structure of the polymer backbone being used. 【0060】 As the structure of the polymer main chain and linker constituting the polymer compound according to the present invention, for example, polyethylene ((C ２ H ４ ) ｎ In polymers in which a linear ether structure is introduced into the side chain portion, using the structure of (meth)acrylic as the base and using (meth)acrylic structures equivalent to a structure in which the side chain portion is linked by ester bonds, (meth)acrylamide structures equivalent to a structure in which the side chain portion is linked by amide bonds, vinyl ether structures equivalent to a structure in which the side chain portion is linked by ether bonds, and polyolefin structures equivalent to a structure in which the side chain portion is linked by alkylene groups as the polymer main chain and linker, it is known that when hydrated, water molecules in an intermediate water state are contained. 【0061】 Furthermore, the density of side chain structures introduced to the polymer backbone is not particularly limited. In addition to structures in which one side chain is introduced for every two carbon atoms constituting the polymer backbone, such as the (meth)acrylic structure produced by vinyl polymerization, structures with a reduced density of introduced side chains can also be obtained by ring-opening polymerization of monomers having various cyclic structures. Moreover, polymer backbones can be used in which alkylene groups, in which hydrogen atoms are substituted with groups containing chain-like ether structures, are bonded by carbonate bonds, ester bonds, amide bonds, urethane bonds, urea bonds, etc. 【0062】 The number-average molecular weight of the polymer compound according to the present invention is preferably in the range of 10,000 to 500,000, and more preferably in the range of 30,000 to 100,000. The polymer compound according to the present invention generates a hydrated structure composed of nonfreezing water, intermediate water, etc., through hydration, and exhibits a predetermined hydrophilicity. By setting the number-average molecular weight to 10,000 or more, or 30,000 or more, good water resistance can be imparted. Furthermore, by setting the number-average molecular weight to 500,000 or less, or 100,000 or less, fluidity can be ensured when the polymer compound according to the present invention is applied to a substrate surface by means of coating or other means. In addition, setting the molecular weight distribution (Mw / Mn) in the range of 1.0 to 2.5, more preferably in the range of 1.0 to 1.5, is desirable in that it can prevent variations in various properties. 【0063】 The polymer compound according to the present invention can be used as a composition mixed with other polymer compounds, filler components, solvents, dispersion media, etc., depending on its intended use. In particular, a coating composition can be prepared by dissolving the polymer compound in a suitable solvent, and this can be used by coating the surface of various substrates using methods such as coating, spraying, or dipping. This coating can be performed, for example, by applying the coating composition to the surface of various substrates on which biocompatibility is to be imparted, and then removing the solvent by evaporation or other means. 【0064】In coating compositions obtained by dissolving the polymer compound according to the present invention in various solvents, additives such as antibacterial agents, radical scavengers, peroxide decomposers, antioxidants, ultraviolet absorbers, heat stabilizers, plasticizers, flame retardants, and antistatic agents can be mixed and used depending on the purpose of the coating, as long as they do not significantly impair the biocompatibility and other properties. 【0065】 Furthermore, after coating the surfaces of various components using the coating composition, the durability of the coating film can be improved by using various crosslinking agents or by crosslinking polymer molecules in the coating film using energy irradiation such as electron beams. 【0066】 The polymer compounds according to the present invention can be used by those skilled in the art by appropriately synthesizing them using conventionally known methods, using materials that can be purchased or synthesized by those skilled in the art. Generally, the polymer according to the present invention can be synthesized by synthesizing a compound into which a structure for forming a side chain of a predetermined structure is introduced, and then using this as a monomer to cause polymerization between monomers. 【0067】 For example, when the main chain is a (meth)acrylic skeleton and a side chain of a predetermined structure is introduced using an ester bond as a linker (L), the polymer according to the present invention can be synthesized by polymerizing (meth)acrylic acid, which has the portion to be the side chain introduced in advance, by appropriate means. Alternatively, for example, when the main chain structure is a polycarbonate skeleton, the polymer according to the present invention can also be synthesized by introducing the portion to be the side chain into a cyclic compound having an appropriate structure in advance and then performing ring-opening polymerization using this as a monomer under appropriate conditions. 【0068】The thickness of the coating film containing the polymer according to the present invention, which is applied to the surface of various substrates, can be set to a range of, for example, several nm to 1 mm, depending on the application in which the substrate is used, thereby creating a coating film that exhibits good biocompatibility. Furthermore, by taking advantage of the high adhesion of the polymer according to the present invention to various substrates, it is also possible to use a coating composition containing the polymer according to the present invention as a so-called primer, and to laminate various polymers onto the surface of the coating film. 【0069】 Furthermore, when bringing a surface coated with the polymer according to the present invention into contact with biological substances such as blood, it is preferable to pre-hydrate the polymer portion containing a structure that contributes to the inclusion of intermediate water by pre-watering the surface. The polymer composition containing the polymer according to the present invention only needs to coat at least a portion of the surface used in contact with biological tissues, cells, blood, etc., and can be used as a coating composition for coating the surface of a substrate that makes up a medical device, etc. 【0070】 In this specification, a medical device is a device used in contact with living organisms, intracellular tissues, cells, blood, etc., and means, for example, a device used for the purpose of not impairing the physiological activity exhibited by such intracellular tissues or blood. Such medical devices naturally include, for example, a form in which they are placed inside a living organism, a form in which they are used in contact with intracellular tissues or blood with the intracellular tissue exposed, a form in which they are used in contact with intracellular tissues such as bone tissue while implanted in such tissues, and a form in which they are used in contact with blood, which is an intracellular component taken outside the body, as an extracorporeal circulation medical material. 【0071】 Furthermore, in this specification, when referring to a surface used in contact with a biological substance, it includes surfaces that come into contact with, or are formed or used in anticipation of coming into contact with, a living organism 【0072】The material and shape of the components constituting medical devices, etc., that are coated with the coating composition according to the present invention are not particularly limited and may be porous bodies, fibers, nonwoven fabrics, particles, films, sheets, tubes, hollow fibers, powders, etc. Examples of materials include natural polymers such as brocade and hemp, synthetic polymers such as nylon, polyester, polyacrylonitrile, polyolefin, halogenated polyolefin, polyurethane, polyamide, polycarbonate, polysulfone, polyethersulfone, poly(meth)acrylate, ethylene-vinyl alcohol copolymer, butadiene-acrylonitrile copolymer, or mixtures thereof. In particular, the coating composition containing the polymer compound according to the present invention can be used even on surfaces where it is difficult to ensure adhesion with polymer materials, such as metals, ceramics, glass, and composite materials thereof. 【0073】 The coating composition according to the present invention can be used in medical devices that come into contact with biological tissues or blood. It is desirable that it be used on at least a portion, preferably almost all, of the surface of medical devices that come into contact with biological tissues or blood, such as implantable artificial organs and treatment devices, extracorporeal circulation artificial organs, and catheters (cardiovascular catheters such as angiography catheters, guidewires, and PTCA catheters, digestive catheters such as gastric tubes, gastrointestinal catheters, and esophageal tubes, and urological catheters such as tubes, urethral catheters, and ureteral catheters). 【0074】 Furthermore, the invention may also be used for an artificial lung of the hollow fiber membrane external blood perfusion type, in which a large number of porous hollow fiber membranes for gas exchange are housed in a housing, blood flows on the outer surface of the hollow fiber membranes, and oxygen-containing gas flows inside the hollow fiber membranes, wherein the outer surface or outer layer of the hollow fiber membranes is coated with the coating composition according to the present invention. Alternatively, the invention may also be used for a dialysis apparatus having a dialysis circuit including at least one dialysis fluid container filled with dialysis fluid and at least one drainage container for collecting the dialysis fluid, and a fluid delivery means for delivering the dialysis fluid starting from the dialysis fluid container or ending at the drainage container, wherein at least a portion of the surface in contact with blood is coated with the coating composition according to the present invention. 【0075】 Furthermore, the coating composition according to the present invention may be used to construct various diagnostic chips by taking advantage of the selective adsorption properties of a surface having a predetermined amount of intermediate water to proteins, cells, etc., and coating it onto the surface of a substrate or particles that come into contact with an aqueous solution containing various proteins, cells, etc. 【0076】 Furthermore, by applying the coating composition according to the present invention, the surface composed of the polymer compound according to the present invention can be preferably used as a cell culture support capable of adhering and maintaining cells in a desirable form. In other words, the cell culture support whose surface is composed of the polymer compound according to the present invention is not particularly limited as long as it contains cells that adhere to and live on a substrate, including epidermal cells, gastrointestinal epithelial cells such as vascular endothelial cells, oral endothelial cells, esophageal epithelial cells, gastric epithelial cells, and intestinal epithelial cells, respiratory epithelial cells such as nasal mucosal epithelial cells, tracheal epithelial cells, and alveolar epithelial cells, exocrine gland cells such as sweat gland cells, sebaceous gland cells, apocrine gland cells, and mammary gland cells, salivary gland epithelial cells, lacrimal gland cells, pancreatic islet cells, adrenal medullary cells, adrenal cortical cells, and pineal gland cells. It can be applied to cell cultures of endocrine gland cells such as pituitary cells and thyroid cells, visceral parenchymal cells such as hepatocytes, renal epithelial cells, pancreatic cells and adrenal cells, sensory organ cells such as taste bud cells, olfactory epithelial cells and hair cells, nerve cells, glial cells such as astrocytes and Schwann cells, muscle cells such as cardiomyocytes, skeletal muscle cells and smooth muscle cells, mesenchymal cells such as fibroblasts, stromal cells, connective tissue cells, chondrocytes and osteoblasts, thymic epithelial cells, uterine epithelial cells, ovarian follicular cells, fallopian tube epithelial cells, seminiferous tubule epithelial cells, and Leydig cells. 【0077】Furthermore, the cell culture support whose surface is composed of the polymer compound according to the present invention can be used for culturing various types of stem cells, including pluripotent stem cells such as embryonic stem cells (ES cells), induced pluripotent stem cells (iPS cells), embryonic tumor cells (EC cells), embryonic germ cells (EG cells), nuclear transfer ES cells, somatic cell-derived ES cells, hematopoietic stem cells, bone marrow-derived mesenchymal stem cells, adipose tissue-derived mesenchymal stem cells, other stromal-derived stem cells, tissue stem cells such as Muse cells and neural stem cells, pluripotent stem cells, and progenitor cells in various tissues such as liver, pancreas, adipose tissue, bone tissue, and cartilage tissue. In stem cell culture using the cell culture support whose surface is composed of the polymer compound according to the present invention, differentiation is promoted or inhibited depending on the characteristics of the cultured stem cells, due to the ability to adhere and maintain cells in a desirable morphology, etc., thus enabling cell culture in accordance with the purpose of culture. The present invention will be described in more detail below using examples, but the present invention is not limited to these examples. 【0078】 1. Synthesis of Poly(1,3-dimethoxy-2-propyl acrylate)(PDiMEA) The polymer compound shown in formula (3) (Poly(1,3-dimethoxy-2-propyl acrylate)(PDiMEA)) was synthesized and evaluated by the method described below. 【0079】 In formula (1), the above PDiMEA is R １ to C ２ H ４ , R ２ CH ３ And in equation (2), R ３ CH ２ , R ４ CH ３ This corresponds to a structure like this. 【0080】 For comparison, we also synthesized and used Poly(2-methoxyethyl acrylate) (PMEA) (Formula (4)), a polymer that has been widely used to exhibit biocompatibility, according to standard methods. 【0081】 【0082】 Compared to PMEA, the above-mentioned PDiMEA has a branched structure originating from the carbon atoms in the chain-like ether structure within the side chain of PMEA, and corresponds to a structure in which two methoxy groups are introduced at the end of the side chain. 【0083】 (Synthesis of 1,3-dimethoxy-2-propyl acrylate (DiMEA)) DiMEA, to be used as a monomer, was synthesized by reacting acryloyl chloride with 1,3-dimethoxy-2-propanol according to the scheme below. 【0084】 【0085】 In a 1 L three-necked flask, triethylamine (28.90 g, 286 mmol), approximately 400 mL of diethyl ether, a small amount of N,N-dimethyl-4-aminopyridine as a catalyst, and 1,3-dimethoxy-2-propanol (26.40 g, 220 mmol) were added and the system was stirred under a nitrogen atmosphere, then cooled in an ice bath. While the system was cooled, acryloyl chloride (20.64 g, 228 mmol) was added dropwise over 30 minutes using a dropping funnel. After confirming that there was no heat generation after the addition, the ice bath was removed, and the reaction was completed by stirring at room temperature for 4 hours. 【0086】 From the above reaction solution, the precipitated triethylamine hydrochloride was removed by suction filtration. After drying the filtrate in an evaporator, a small amount of water was added to remove unreacted acryloyl chloride. Further dehydration was performed by adding an excess amount of hexane and magnesium sulfate. After removing the magnesium sulfate from the dehydrated solution by suction filtration, triethylamine was removed using alumina base and an alumina column. Finally, distillation was performed, with the first distillate taken at 40°C and the final distillate at 50°C. The substance obtained by distillation was... １ DiMEA was confirmed to have been synthesized by 1H NMR measurement (20.92 g, 120 mmol, yield 54.5%). 【0087】 Figure 1 shows the DiMEA obtained above. １The results of the 1H NMR measurements are shown below. The NMR measurements for the monomers and polymers shown below were performed using an NMR analyzer (JEOL 500MHz JNM-ECX, manufactured by JEOL Ltd.). １ H-NMR measurement and １３ ¹³C-NMR measurements were performed. The chemical shift was based on CDCl3 (1H: 7.26 ppm, 13C: 77.1 ppm). 【0088】 (Synthesis of PDiMEA by polymerization of DiMEA) The target PDiMEA was synthesized by polymerizing the DiMEA obtained above. In this example, in order to achieve a degree of polymerization and polydispersity comparable to that of the comparative PMEA, the synthesis was carried out by reversible addition-cleavage chain transfer polymerization (RAFT), a type of living polymerization, as described below. DDMAT-DiMe was synthesized as a RAFT agent for polymerizing DiMEA according to the following scheme. 【0089】 【0090】 In a round-bottom flask, 0.508 g, 1.39 mmol of 2-(dodecylthiocarbonothio)-2-methylpropanoic acid (DDMAT) was mixed with 1 mL, 12.7 mmol of oxalyl chloride. Then, one drop of the polar aprotic solvent N,N-dimethylformamide (DMF) was added to accelerate the SN2 reaction of the nucleophile, replacing the OH group with a chlorine atom. After 30 minutes, the impurities, oxalyl chloride and DMF, were removed using a vacuum pump. 【0091】 Subsequently, 1,3-dimethoxy-2-propanol (0.201 g, 1.67 mmol) was added and the mixture was allowed to react overnight at room temperature. A hexane:acetone = 4:1 mixture was added to the reaction solution, and the target product (rf = 0.5) was recovered by silica gel column chromatography. The solvent was removed using an evaporator to obtain DDMAT-DiMe (0.584 g, 1.25 mmol, yield 90%) as an orange viscous substance. Figure 2 shows the DDMAT-DiMe synthesized above. １ The results of the 1H NMR measurement are shown. 【0092】DiMEA was polymerized using the DDMAT-DiMe synthesized above as a RAFT agent according to the following scheme. 【0093】 【0094】 Using a Schlenk tube, DDMAT-DiMe, DiMEA, and AIBN were mixed in a molar ratio of 1:475:0.5 (weight ratio of 17.6 mg:3.12 g:3.05 mg), and toluene (5.95 mL) was added to prepare a solution with a DiMEA concentration of 2 mol / L. After removing oxygen from the tube by freeze-degassing with liquid nitrogen, the Schlenk tube was immersed in a 65°C oil bath and a polymerization reaction was initiated (1.5 hours) while stirring with a stirrer. The reaction was then stopped by rapid cooling with liquid nitrogen. The monomer reaction conversion rate, as measured by 1H NMR, was approximately 80%. 【0095】 The polymerization product was purified by precipitation using THF and hexane on the contents of the Schlenk tube, and then dried to obtain a yellow, transparent, viscous PDiMEA. Figure 3 shows the results of 1H NMR measurement of the obtained PDiMEA. In addition, the number-average molecular weight (M) of the synthesized PDiMEA was determined by GPC measurement. ｎ The calculated values ​​were 49,000 and the polyvariance index (PDI) was 1.23. 【0096】 2. Solubility Test of PDiMEA in Various Solvents: Approximately 3-5 mg of the PDiMEA synthesized above was taken into small vials, and 3 mL of water and various organic solvents were added to each vial. The solubility in each solvent was then investigated by leaving the samples at room temperature for 24 hours. For comparison, the solubility in each solvent was also investigated using the same method for PMEA obtained by polymerization using a conventional method (Mn = 36700, PDI = 1.17). 【0097】 Table 1 shows the solubility of PDiMEA and PMEA in various solvents. In Table 1, "Soluble" indicates that the entire 3-5 mg sample was dissolved in the solvent, while "Insoluble" indicates that the sample remained undissolved in the solvent. 【0098】As shown in Table 1, the solubility behavior of the PDiMEA synthesized above in various solvents was found to be generally similar to that of PMEA. In particular, PDiMEA did not dissolve in pure water and was shown to be insoluble, similar to PMEA. On the other hand, while PMEA is insoluble in ethanol, PDiMEA is soluble in ethanol, indicating that ethanol, which has minimal adverse effects on the human body, can be used as a solvent when applying it to surfaces of medical devices, etc. 【0099】 【0100】 3. Evaluation of the Hydration State of PDiMEA The state of water molecules contained in saturated PDiMEA was evaluated using the method described below. The PDiMEA synthesized above was saturated and brought to a stable hydration state by immersing it in phosphate buffer (PBS(-)) for one week. For comparison, PMEA was also saturated using the same method. 35 mg each of the saturated PDiMEA and PMEA were placed in a sealed aluminum measuring cell, sealed using an electric sample sealer, and the mass of the measuring cell was measured. 【0101】 Using a measurement cell containing the hydrated polymer as a sample, the heat transfer to each hydrated polymer in the range of -100 to 50°C was evaluated using a DSC measuring device (SII Nanotechnologies Corporation, EXSTAR X-DSC7000). The measurement was performed by lowering the temperature from 30°C to -100°C at a rate of -5°C / min with a nitrogen gas flow rate of 150 mL / min, holding at -100°C for 5 minutes, and then raising the temperature to 50°C at a rate of 5°C / min. The glass transition temperature was also evaluated during this heating process. 【0102】 After performing the above measurements, a small hole was made in the seal of the measurement cell, and the cell was left in a vacuum at 110°C for three days to remove moisture from inside the measurement cell. The mass of the measurement cell was then measured, and the amount of mass reduction due to moisture removal was considered to be the amount of moisture contained in each polymer. 【0103】Based on the DSC measurement results obtained above, the amount of water molecules that underwent this ordering was calculated using the latent heat of solidification of water (J / mol) from the area (J) of the exothermic peak observed in the temperature range below -20°C due to the latent heat (exothermic) associated with the ordering of water molecules in a supercooled state, and this was defined as the intermediate water amount. 【0104】 Furthermore, the area (J) of the endothermic peak observed in the temperature range of -20°C to 0°C during the sample heating process is considered to be due to the melting of intermediate water and free water. Therefore, the amount of free water was calculated by subtracting the area (J) of the exothermic peak observed in the temperature range below -20°C from this area, and assuming that this amount corresponds to the melting of free water, and similarly using the latent heat of solidification of water (J / mol). In addition, the amount of nonfreezing water, which does not undergo latent heat transfer due to phase transformation, etc., in the range of -100 to 50°C, was obtained by subtracting the amounts of intermediate water and free water from the amount of water removed by the vacuum drying process. 【0105】 The DSC measurements described above revealed that in PMEA, a peak originating from intermediate water was observed around -40 to -30°C during the heating process from -100°C. On the other hand, in PDiMEA, a peak originating from intermediate water was mainly observed around -40 to -30°C during the cooling process to -100°C, and a peak originating from intermediate water was also observed in the same temperature range during the heating process, confirming that hydrated PDiMEA contains intermediate water. Furthermore, it is presumed that the mechanism by which the peak originating from intermediate water is observed during the cooling or heating process, depending on the polymer structure, is related to differences in the mobility of the molecular structure (or parts thereof) that interact with water molecules in the intermediate water state. 【0106】Table 2 shows the hydration state of PDiMEA and PMEA evaluated by the method described above. As shown in Table 2, it was observed that PDiMEA had a lower water content per unit mass (saturation water content) compared to PMEA, and consequently, the amount of free water and intermediate water also decreased. On the other hand, when converted to the number of monomer units constituting PDiMEA and PMEA, the amount of intermediate water was equivalent for both, suggesting that the number of water molecules in the intermediate water state present in a single side chain portion did not change significantly. As shown in Table 2, the presence of intermediate water in hydrated PDiMEA suggests that even when branching is introduced within the chain-like ether structure, which is thought to contribute to the formation of intermediate water, there is no significant change in the ability to form intermediate water. 【0107】 【0108】 Table 2 shows the glass transition temperature (T) of each saturated polymer. ｇ，ｗｅｔ ) Along with the glass transition temperature (T) of each polymer in its dry state obtained by DSC measurement, ｇ，ｄｒｙ The results are also shown. In PMEA, the glass transition temperature shows a relatively large change due to water content, whereas in PDiMEA, the amount of change in this temperature is observed to be small. 【0109】 4. Evaluation of Surface Properties of PDiMEA Using the method described below, PDiMEA (Mn = 49,000 g / mol, PDI = 1.21), synthesized in the same manner as described above, was used to coat the surfaces of various resin substrates, and their surface properties were evaluated. PDiMEA was dissolved by adding methanol to prepare a 1.0 (wt / vol%) polymer solution. For comparison, methanol solutions were similarly prepared for PMEA (Mn = 36,700 g / mol, PDI = 1.17) and PMPC (Mn = approximately 500,000 g / mol) which was made water-insoluble by copolymerizing MPC with butyl methacrylate (BMA). An ethanol solution of polybutyl acrylate (PBA) (Mn = 36,000 g / mol, PDI = 1.04) was also prepared. 【0110】Hydrophilized PET and PP films, treated with nitrogen plasma, were shaped into 14 mm diameter circles, washed with methanol, and dried. 40 μL of each polymer solution was then dropped onto a spin coater, and spin-coated under the following conditions: 500 rpm (5 s), 2000 rpm (10 s), SLOPE (5 s), 4000 rpm (5 s), SLOPE (4 s). After standing for 15 minutes, the spin-coating was repeated, and the substrates were then left to stand in a 25°C incubator to produce polymer-coated substrates. Verification using an XPS apparatus showed that the fabricated polymer-coated substrates contained nitrogen around 400 eV, derived from the PET and PP substrates. １Ｓ The disappearance of the peak confirmed that the substrate surface was coated with each polymer. 【0111】 Figure 4 shows the water contact angles on PP substrate surfaces coated with PDiMEA and PMEA, and on an untreated PP substrate surface. The water contact angle was measured using the θ / 2 method with a fully automated contact angle meter (Drop Master, DMo-501SA, Kyowa Interface Science Co., Ltd.), and the contact angle was measured 30 seconds after droplet placement. As shown in Figure 4, it was demonstrated that coating with PDiMEA or PMEA reduces the water contact angle and makes the substrate surface hydrophilic. Furthermore, it was shown that the surface of PDiMEA is slightly more hydrophobic than that of PMEA. 【0112】 5. Evaluation of the coating stability of PDiMEA Based on the above, the surface condition of the coated substrate obtained by coating a PP substrate with polymer solutions of PDiMEA and PMEA was observed using a digital microscope (VHX-900F, manufactured by KEYENCE) to evaluate the stability of the coating film in a hydrated state. This was done by observing the surface condition after coating and the surface condition after immersing the substrate in water for 24 hours. 【0113】Figure 5 shows the surface state of the coated substrate after coating and after immersion in water. As shown in Figure 5, in the substrate coated with PMEA on a PP substrate, a speckled pattern of several tens of micrometers in size appeared after immersion in water, suggesting that the flow of hydrated PMEA in water caused non-uniformity in the coating film. On the other hand, in the substrate coated with PDiMEA on a PP substrate, no significant change in the surface state was observed before and after immersion in water, suggesting that a stable coating film was formed. 【0114】 As described above, the difference in the stability of the coating film when immersed in water, depending on the polymer structure, is attributed to differences in the interfacial energy between the substrate PP and PDiMEA / PMEA. It was inferred that when the interfacial energy is high, polymer aggregation within the coating film is more likely to occur. Furthermore, it was inferred that PDiMEA exhibits good adhesion to PP and other materials with low polarity. 【0115】 6. Evaluation of Biocompatibility of PDiMEA The platelet adhesion frequency on surfaces coated with polymers such as PDiMEA was evaluated using the method described below. It has been shown that when blood comes into contact with a surface that does not exhibit biocompatibility, the surface is recognized as a foreign substance, leading to nonspecific adsorption, denaturation, and multilayer adsorption of proteins in biological tissue, which in turn activates platelets and causes platelet adhesion. Therefore, by evaluating the platelet adhesion frequency to various surfaces, it is possible to evaluate the biocompatibility exhibited by those surfaces. 【0116】The evaluation was performed on PET substrates coated with various polymers as described above, as well as on untreated PET substrates. The platelet suspension samples were prepared by uniformly mixing human whole blood (containing 3.2% sodium citrate) collected in the United States within four days of collection. The mixture was then centrifuged at 400 rcf (1500 rpm) for 5 minutes, and the supernatant, containing the plasma components, was collected to obtain platelet-rich plasma (PRP). The remaining blood was centrifuged at 2500 rcf (4000 rpm) for 10 minutes, and the supernatant was collected to obtain platelet-poor plasma (PPP). The platelet concentration in the PRP was measured using a hemocytometer, and the seeding density on the substrate was determined to be 4 × 10⁶. ７ cells / cm ２ PRP was diluted with PPP to prepare the solution. 【0117】 Each substrate was dropped with 200 μL of PBS(-) and held for 1 hour to thoroughly hydrate the surface of each substrate. After removing the PBS(-), the platelet suspension (200 μL) prepared above was seeded and incubated at 37°C for 1 hour. The suspension was then removed, the substrates were washed twice with PBS(-), and the platelets were fixed by immersion in PBS(-) containing 1% glutaraldehyde at room temperature for 2 hours. After fixation, the substrates were washed by immersion in PBS(-) for 10 minutes, in a PBS(-):pure water = 1:1 solution for 8 minutes, and in pure water for 8 minutes. 【0118】 After washing the substrates and air-drying them for several days, SEM observation was performed on five locations on each substrate at a magnification of 1200x. The number of platelets adhering to each field of view and their activity level were evaluated based on their shape. The activity level of the adhered platelets was classified into three types: Type I, where the degree of activation was low and the platelets maintained a circular shape similar to that in blood; Type II, where the degree of activation was moderate and pseudopod formation was observed; and Type III, where the degree of activation was high and the platelets were extended. 【0119】Figure 6 shows a graph of the density of platelets adhering to each substrate. As shown in Figure 6, the frequency of platelet adhesion to the surface of PDiMEA was suppressed to the same extent as PMEA and PMPC, which produce intermediate water through hydration, and showed a significant difference compared to PET and PBA surfaces, which do not produce intermediate water. Furthermore, most of the platelets adhering to the surface of PDiMEA maintained their circular shape (Type I), demonstrating good biocompatibility. 【0120】 The degree of exposure of the fibrinogen γ' chain on the surface of each substrate used above was evaluated when it came into contact with PPP, using the method described below. Fibrinogen is a scaffold protein that provides adhesion for platelets, and it is known to expose the γ' chain, which is the platelet adhesion site, by undergoing a structural change through foreign body reaction. By evaluating this degree of exposure, it is possible to assess the biocompatibility exhibited by the substrate surface, etc. 【0121】 The evaluation was performed using 96-well tissue culture polystyrene (TCPS) plates (IWAKI, AGC Technoglass Co., Ltd.) on which 15 μL of a solution containing each polymer at 0.2 wt / vol% was dropped and allowed to stand at 25°C for 3 days to form a polymer cast film at the bottom of the wells. 【0122】Each well was then thoroughly hydrated by adding 50 μL of PBS(-) and holding for 1 hour. After removing the PBS(-), the PPP prepared above (50 μL) was seeded and incubated at 37°C for 1 hour. After removing the PPP, the wells were washed five times with PBS(-), and 50 μL of primary antibody (Mouse monoclonal IgG1, anti FNG γ' chain antibody (Santa Cruz Biotechnology)) diluted 200-fold with Blocking One was added and incubated at 37°C for 2 hours. Subsequently, the wells were washed five times with PBS(-), and 50 μL of secondary antibody (Goat monoclonal IgG1, anti-mouse antibody, HRP labeled (Biorad)) diluted 1000-fold with Blocking One diluted 50-fold was added and incubated at 37°C for 2 hours. Subsequently, the solution was washed five times with PBS(-), 200 μL of 1 mg / mL ABTS solution was added dropwise, and the mixture was reacted at room temperature for 10 minutes. The solution was then transferred to another TCPS96well plate, and the degree of γ' chain exposure was evaluated by measuring the absorbance at 405 nm using a microplate reader (iMark Microplate Reader, BIO-RAD). 【0123】 Figure 7 shows the absorbance at 405 nm for solutions taken from wells containing each polymer. As shown in Figure 7, the exposure of the fibrinogen γ' chain on the surface of PDiMEA in contact with PPP was suppressed to the same extent as PMEA and PMPC, which produce intermediate water through hydration, and was significantly lower than that of PET and PBA surfaces, which do not produce intermediate water. As shown in Figure 7, it was inferred that the suppression of fibrinogen γ' chain exposure reduces the frequency of platelet adhesion as shown in Figure 6. 【0124】 The amount of plasma protein adsorbed from the PPP onto the surface of each substrate used above, upon contact with the PPP, was evaluated using the Micro BCA method. In the Micro BCA method, Cu was used under alkaline conditions. ２＋ Cu is produced when it is reduced by protein. ＋This method quantifies proteins by utilizing the fact that it coordinates with Bicinchoninic Acid (BCA) and produces a purple color. 【0125】 In a TCPS96 well plate in which a polymer cast film was formed at the bottom of the wells as described above, 50 μL of PBS(-) was dropped into each well and held for 1 hour to thoroughly hydrate the surface of each polymer. After the PBS(-) was removed, 50 μL of the PPP prepared above was seeded and incubated at 37°C for 1 hour. After removing the PPP and drying, 30 μL of a 0.1 N NaOH aqueous solution containing 5% sodium dodecyl sulfate (SDS) was dropped and incubated at 37°C for 2 hours to detach the plasma proteins adsorbed on the substrate and transfer them into the aqueous solution. 【0126】 After diluting the above aqueous solution by adding 120 μL of PBS(-), 150 μL of a BCA solution, prepared by mixing solution A:solution B:solution C in a ratio of 25:24:1, was added dropwise. After incubation at 37°C for 2 hours, 150 μL of each solution was transferred to another TCPS96well plate, and the absorbance at 570 nm was measured using a microplate reader. The amount of protein adsorbed by PPP upon contact with each polymer was calculated by converting the obtained absorbance to protein concentration. 【0127】 Figure 8 shows the amount of plasma protein adsorbed onto each polymer from the PPP. As shown in Figure 7, the amount of plasma protein adsorbed onto the surface of PDiMEA in contact with PPP was suppressed to the same extent as PMEA and PMPC, which generate intermediate water through hydration, and was significantly lower than that of PET and PBA surfaces, which do not generate intermediate water. 【0128】 The polymer according to the present invention exhibits high biocompatibility and can form stable coating films on various substrates. Therefore, it is desirable to impart biocompatibility to surfaces such as those of medical devices, and it can be preferably used as a material for forming surfaces that come into contact with biological materials.

Claims

1. A polymer having a structure represented by the following formula 1 in a side chain portion, [wherein, L in the formula is a linker for connecting the side chain to the polymer main chain, and R １ is a divalent saturated hydrocarbon group containing a linear or branched carbon chain having 2 to 6 carbon atoms, and R ２ is a hydrogen atom or a monovalent hydrocarbon group having 6 or less carbon atoms which may have an ether bond. ] At least one of the hydrogen atoms bonded to the carbon atoms contained in the R １ is substituted with a structure represented by the following formula 2. [wherein, R ３ is a divalent saturated hydrocarbon group containing a linear or branched carbon chain having 0 to 5 carbon atoms, the number of carbon atoms (C) existing between the oxygen atom (O) in formula 2 and the above linker (L) is 2 to 6, and R ４ is a hydrogen atom or a monovalent hydrocarbon group having 6 or less carbon atoms which may have an ether bond. ] 2. The polymer according to claim 1, characterized in that the polymer is hydrated and, when hydrated, releases or absorbs latent heat due to the ordering / disordering of water molecules in a temperature range below the freezing point.

3. The above R １ and R ３ The polymer according to claim 1, characterized in that the number of carbon atoms contained therein is 6 or less.

4. The polymer according to claim 1, characterized in that it has one hydrogen atom substituted with the structure of formula 2 above.

5. The polymer according to any one of claims 1 to 4, characterized in that the main chain consists of carbon chains composed mainly of carbon atoms.

6. The polymer according to any one of claims 1 to 4, characterized in that the linker is an alkylene group, an ether bond, a thioether bond, an ester bond, an amide bond, a urethane bond, or a urea bond.

7. A polymer composition characterized by comprising the polymer described in any one of claims 1 to 4.

8. The polymer composition according to claim 7, characterized in that it is used to coat at least a portion of a surface that is used in contact with a biological substance.

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