Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/14—Macromolecular materials
  • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/14—Macromolecular materials
  • A61L27/20—Polysaccharides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
  • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
  • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
  • C08F220/10—Esters
  • C08F220/22—Esters containing halogen
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
  • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
  • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
  • C08F220/10—Esters
  • C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
  • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
  • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
  • C08F220/10—Esters
  • C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
  • C08F220/28—Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
  • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
  • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
  • C08F220/52—Amides or imides
  • C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
  • C08F220/58—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing oxygen in addition to the carbonamido oxygen, e.g. N-methylolacrylamide, N-(meth)acryloylmorpholine
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
  • C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
  • C08L33/04—Homopolymers or copolymers of esters
  • C08L33/14—Homopolymers or copolymers of esters of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
  • C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
  • C08L33/24—Homopolymers or copolymers of amides or imides
  • C08L33/26—Homopolymers or copolymers of acrylamide or methacrylamide

Definitions

• the present invention relates to polymers, resin compositions, and medical materials.
• PET resin which is commonly used as a material for artificial blood vessels, tends to have platelet adhesion, and there has been a need to improve its biocompatibility.
• highly biocompatible resins include polymers whose main constituent units are hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate.
• Patent Document 1 Such polymers whose main constituent units are hydroxyalkyl (meth)acrylates and/or alkoxyalkyl (meth)acrylates have properties such as mechanical strength and elastic modulus that are similar to those of living tissues such as blood vessels. Therefore, attempts have been made to improve its properties by adjusting the chemical composition using copolymer components.
• Patent Document 1 describes the use of polyfunctional (meth)acrylate in combination with alkoxyalkyl (meth)acrylate.
• Patent Documents 2 to 6, etc. attempts have been made to obtain elastic polymers by host-guest reactions using cyclodextrins and the like.
• the purpose of the present invention is to improve the physical properties of a polymer whose main constituent unit is alkoxyalkyl (meth)acrylate, and to obtain a polymer that has physical properties extremely similar to biological constituent substances. .
• the present invention is a copolymer characterized in that its constituent units are hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate (A) and a monomer (B) having a host group.
• the copolymer may further have a monomer (C) having a guest group as a constituent unit.
• the above copolymer may have a structure in which the main chain penetrates through the host group.
• the present invention provides a resin composition that has an alkoxyalkyl (meth)acrylate (A) and a monomer (B) having a host group as structural units as a whole, and is a mixture of two or more types of polymers. It is also a thing.
• the resin composition may further include a monomer (C) having a guest group as a constituent unit.
• the resin composition may have a structure in which the main chain penetrates through the host group.
• the present invention also provides a medical material characterized by containing the above copolymer and/or the above resin composition.
• the above medical material can be used as an artificial blood vessel.
• the polymer and resin composition of the present invention have excellent biological safety and have physical properties extremely similar to biological materials such as blood vessels, making them suitable for use as medical materials.
• FIG. 3 is a diagram showing the results of platelet adhesion tests of Examples 1 to 4 and Comparative Examples 1 and 2.
• FIG. 3 is a diagram showing the results of platelet adhesion tests and contact angles of Examples 1 to 4 and Comparative Examples 1 and 2.
• FIG. 3 is a diagram showing the results of HUVEC adhesion tests of Examples 1 to 4 and Comparative Examples 1 and 2.
• FIG. 3 is a diagram showing the results of HUVEC adhesion tests of Examples 1 to 4 and Comparative Examples 1 and 2.
• 2 is a diagram showing physical properties of Examples 1 to 4 and Comparative Examples 1 and 2.
• FIG. It is a diagram showing the relationship between strain and stress of various materials described in Science, 2018, 359, 1509-1513.
• FIG. 7 is a diagram showing the relationship between strain and stress in Examples 5 to 7.
• FIG. 7 is a diagram showing the relationship between Young's modulus and toughness in Examples 5 to 7.
• (meth)acrylate means “methacrylate” or “acrylate.”
• Polymers whose main constituent units are alkoxyalkyl (meth)acrylates have excellent biocompatibility, but as mentioned above, their physical properties are inadequate, making them difficult to use as medical materials. Met.
• a polymer having a crosslinked structure using a polyfunctional (meth)acrylate does not have self-healing properties, although it can improve physical properties.
• the crosslinked chain formed by the host-guest group in the present invention has excellent self-repairing performance because even if the bond is once broken, it can be rebonded thereafter.
• a polymer in which the main chain penetrates through the host group tends to be a mobile crosslinked polymer, and thus tends to be a polymer suitable for use as a medical material.
• since it has crosslinked chains it has elasticity and toughness. This allows a resin composition to have physical properties close to those of biological materials such as blood vessels.
• platelets when used as an artificial blood vessel, platelets may adhere to the artificial blood vessel. Even when PET, which is a well-known material for artificial blood vessels, is used, some platelet adhesion occurs. Platelet adhesion is undesirable because it causes blood vessel clogging.
• HUVEC human umbilical vein endothelial cells
• the polymer of the present invention is also preferable in that it shows less adhesion of platelets and more adhesion of HUVEC.
• the polymer of the present invention has excellent properties not only from the viewpoint of physical properties but also from the viewpoint of biocompatibility.
• the polymer and resin composition of the present invention will be explained in detail.
• the present invention relates to a copolymer (No. 1 of the present invention) and a monomer (B) having a hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate (A) and a host group as a constituent unit as a whole, and two or more types of polymers.
• the resin composition (second invention) is characterized by being a mixture of agglomerates.
• the polymer of the present invention has both a host group and a guest group
• the polymer having the host group and the guest group It may also be a mixture of polymers with
• the copolymer or resin composition of the present invention For a host-guest reaction to occur, it is not important whether the host group and the guest group are present in the same polymer molecule; Even if they exist in the molecule, they have the same action and produce the same effect. Therefore, both of these copolymers (the first invention) and the resin composition containing the structural units necessary for the composition as a whole (the second invention) are covered by the invention. In addition, hereinafter, these may be collectively referred to as "the copolymer or resin composition of the present invention".
• the hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate (A) in the present invention is not particularly limited, but the hydroxyalkyl (meth)acrylate and/or having an alkoxyalkyl group having 2 to 20 carbon atoms is Preferred examples include alkoxyalkyl (meth)acrylates, more preferably hydroxyalkyl (meth)acrylates and/or alkoxyalkyl (meth)acrylates having an alkoxyalkyl group having 2 to 15 carbon atoms, and still more preferably having 2 to 15 carbon atoms.
• Examples include hydroxyalkyl (meth)acrylates and/or alkoxyalkyl (meth)acrylates having 8 alkoxyalkyl groups, particularly preferably hydroxyalkyl (meth)acrylates and/or alkoxyalkyl groups having 2 to 5 carbon atoms. Examples include alkoxyalkyl (meth)acrylates.
• hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate include compounds represented by the following general formula (1).
• CH 2 CR 1 -COO-R 2 -OR 3 (1)
• R 1 represents a hydrogen atom or a methyl group.
• R 2 represents an alkylene group having 1 to 10 carbon atoms.
• R 3 represents an alkyl group having 1 to 10 carbon atoms or H.
• R 2 is preferably an alkylene group having 1 to 5 carbon atoms, more preferably an alkylene group having 1 to 3 carbon atoms.
• R 3 is preferably an alkyl group having 1 to 5 carbon atoms or hydrogen, more preferably an alkyl group having 1 to 3 carbon atoms.
• alkoxyalkyl (meth)acrylate 2-hydroxyethyl (meth)acrylate and 2-hydroxypropyl (meth)acrylate are particularly preferred.
• those having a secondary hydroxyl group are preferable because they are not too strong and have an appropriate hydrogen bond compared to a primary hydroxyl group.
• Examples of such monomers include 2-hydroxypropyl (meth)acrylate and 2-hydroxybutyl (meth)acrylate.
• the alkoxyalkyl (meth)acrylates include, for example, methoxymethyl (meth)acrylate, methoxyethyl (meth)acrylate, ethoxypropyl (meth)acrylate, methoxybutyl (meth)acrylate, and ethoxymethyl (meth)acrylate.
• Preferred examples include acrylate, ethoxyethyl (meth)acrylate, ethoxypropyl (meth)acrylate, and ethoxybutyl (meth)acrylate.
• the monomer composition of the present invention may contain only one type of the above-mentioned alkoxyalkyl (meth)acrylate, or may contain two or more types.
• a monomer having an ether group may be used. Since such monomers can also form hydrogen bonds, the same effects as the above-mentioned hydroxyl group-containing monomers can be obtained.
• monomers having such an ether group include vinyl alkyl ether compounds, alkyl ether compounds of hydroxyalkyl (meth)acrylic acid, and the like.
• the copolymer or resin composition of the present invention has a host group.
• the host group is the following general formula (5)
• R 7 is the same or different and is a hydrogen atom, an acyl group having 2 to 50 carbon atoms, an alkyl group having 1 to 30 carbon atoms, or -CONHR 8 (R 8 is an alkyl group having 1 to 20 carbon atoms) x is an integer from 5 to 7)) It is preferable that the structure is represented by the following.
• the above structure is a monovalent group obtained by removing one hydrogen atom or hydroxyl group from a cyclodextrin derivative.
• the above-mentioned cyclodextrin is known as ⁇ -cyclodextrin, ⁇ -cyclodextrin, ⁇ -cyclodextrin, etc., but any of these may be used, or two or more of these may be used in combination. good.
• the expression cyclodextrin in this specification means at least one member selected from the group consisting of ⁇ -cyclodextrin, ⁇ -cyclodextrin, and ⁇ -cyclodextrin.
• R 7 may be hydrogen atoms, or some or all of R 7 may be an acyl group having 2 to 50 carbon atoms or an alkyl group having 1 to 30 carbon atoms. Alternatively, it may be substituted with -CONHR 8 (R 8 is an alkyl group having 1 to 20 carbon atoms).
• the copolymer and resin composition will have high hydrophilicity. Therefore, in applications where hydrophilicity is required, a polymer with many hydroxyl groups can be used. More specifically, it is preferable that 70% or more of R 7 be hydrogen atoms, and preferably 80% or more be hydrogen atoms. All of R 7 may be hydroxyl groups.
• R 7 group When the above R 7 group is substituted with a functional group other than a hydrogen atom, the cyclodextrin group becomes highly hydrophobic. Therefore, in applications requiring high hydrophobicity, it is preferable to substitute some or all of the hydroxyl groups. More specifically, it is preferable that 70% or more of the hydroxyl groups in R 7 be substituted, and it is preferable that 80% or more of the hydrogen atoms be substituted. All of R 7 may be substituted.
• the host group preferably has a structure in which 70% or more of the hydrogen atoms of hydroxyl groups out of the total number of hydroxyl groups present in one molecule of the cyclodextrin derivative are substituted with the hydrocarbon group or the like.
• the host group-containing polymerizable monomer can exhibit higher affinity for the hydrophobic polymerizable monomer.
• it is more preferable that 80% or more of the hydrogen atoms of the hydroxyl groups present in one molecule of the cyclodextrin derivative are substituted with the hydrocarbon group, etc. It is particularly preferred that 90% or more of the hydrogen atoms of the hydroxyl groups are substituted with the hydrocarbon group or the like.
• the host group preferably has a structure in which hydrogen atoms of 13 or more hydroxyl groups out of all the hydroxyl groups present in one molecule of the ⁇ -cyclodextrin derivative are substituted with the hydrocarbon group or the like.
• the host group-containing polymerizable monomer can exhibit higher affinity for the hydrophobic polymerizable monomer.
• the host group preferably has a structure in which hydrogen atoms of 13 or more hydroxyl groups out of all the hydroxyl groups present in one molecule of the ⁇ -cyclodextrin derivative are substituted with the hydrocarbon group or the like.
• the host group-containing polymerizable monomer can exhibit higher affinity for the hydrophobic polymerizable monomer. More preferably, the host group has hydrogen atoms of 17 or more hydroxyl groups out of all the hydroxyl groups present in one molecule of the ⁇ -cyclodextrin derivative being substituted with the hydrocarbon group, etc. It is particularly preferred that 19 or more hydrogen atoms of the hydroxyl groups are substituted with the hydrocarbon group or the like.
• the host group preferably has a structure in which hydrogen atoms of 17 or more hydroxyl groups out of all the hydroxyl groups present in one molecule of the ⁇ -cyclodextrin derivative are substituted with the hydrocarbon group or the like.
• the host group-containing polymerizable monomer can exhibit higher affinity for the hydrophobic polymerizable monomer.
• the cyclodextrin derivative for forming the host group at least one hydroxyl group possessed by the cyclodextrin is selected from the group consisting of a hydrocarbon group, an acyl group, and -CONHR (R is a methyl group or an ethyl group). It is preferable to have a structure substituted with at least one type of group.
• the host group-containing polymerizable monomer of the present invention exhibits high affinity for both hydrophilic polymerizable monomers and hydrophobic polymerizable monomers, for example.
• the host group-containing polymerizable monomer can be copolymerized with various polymerizable monomers.
• hydrocarbon group is not particularly limited.
• examples of the hydrocarbon group include an alkyl group, an alkenyl group, and an alkynyl group.
• the number of carbon atoms in the hydrocarbon group is not particularly limited. From the viewpoint that host group-containing polymerizable monomers exhibit higher affinity for both hydrophilic and hydrophobic polymerizable monomers and are more likely to form host-guest interactions, hydrocarbon groups The number of carbon atoms in is preferably 1 to 4.
• hydrocarbon groups having 1 to 4 carbon atoms include methyl, ethyl, propyl, and butyl groups.
• hydrocarbon group When the hydrocarbon group is a propyl group or a butyl group, it may be either linear or branched.
• the hydrocarbon group may have a substituent as long as the effects of the present invention are not impaired.
• acyl group examples include an acetyl group, propionyl group, and formyl group.
• the acyl group can also have a further substituent.
• the host group-containing polymerizable monomer exhibits higher affinity for both hydrophilic and hydrophobic polymerizable monomers, easily forms host-guest interactions, and has excellent toughness and strength.
• the acyl group is preferably an acetyl group from the viewpoint of making it easy to obtain a polymeric material with excellent toughness and strength.
• -CONHR (R is a methyl group or an ethyl group) is a methyl carbamate group or an ethyl carbamate group.
• -CONHR is Preferably it is an ethyl carbamate group.
• the host group-containing polymerizable monomer of the present invention can be used as a raw material for obtaining a polymer contained in a polymeric material.
• a polymer obtained using a host group-containing polymerizable monomer may have a structure in which molecules are crosslinked, for example, by reversible host-guest interaction.
• the structure of the host group-containing polymerizable monomer of the present invention is not particularly limited as long as it has the host group and is a polymerizable compound.
• polymerizability as used in this specification includes, for example, radical polymerization, ionic polymerization, polycondensation (condensation polymerization, condensation polymerization), addition condensation, living polymerization, living radical polymerization, and other conventionally known polymerization. It means that it has the property of undergoing various types of polymerization.
• Host group-containing polymerizable monomers can be subjected to radical polymerization or polycondensation (condensation polymerization, condensation polymerization) from the viewpoint of ease of synthesis and the ease of obtaining polymeric materials with excellent toughness and strength.
• radical polymerization or polycondensation condensation polymerization, condensation polymerization
• it is a certain compound.
• the type of host group-containing polymerizable monomer is not particularly limited as long as it has a host group and a functional group exhibiting polymerizability.
• Specific examples of functional groups exhibiting polymerizability include alkenyl groups, vinyl groups, etc., as well as -OH, -SH, -NH 2 , -COOH, -SO 3 H, -PO 4 H, isocyanate groups, and epoxy groups ( Examples include functional groups that are incorporated into resins by reaction, such as glycidyl groups.
• These polymerizable functional groups can be introduced into the cyclodextrin derivative by substituting hydrogen atoms of one or more hydroxyl groups of the cyclodextrin. As a result, a host group-containing polymerizable monomer having a functional group exhibiting polymerizability is formed.
• host group-containing polymerizable monomers can be classified into “host group-containing vinyl monomers” and “host group-containing non-vinyl monomers.” Below, they will be explained in order.
• the host group-containing polymerizable monomer is a host group-containing vinyl monomer
• the host group-containing vinyl monomer is a vinyl compound having a radical polymerizable functional group in addition to the host group. It is.
• host group-containing polymerizable monomer examples include vinyl-based polymerizable monomers to which the host group is bonded.
• the host group-containing vinyl monomer has the following general formula (h1)
• Ra represents a hydrogen atom or a methyl group
• R H represents the above-mentioned host group
• R 1 represents a hydroxyl group, a thiol group, or an alkoxy group which may have one or more substituents.
• a thioalkoxy group which may have one or more substituents
• an alkyl group which may have one or more substituents
• an amino group which may have one substituent
• 1 Represents a divalent group formed by removing one hydrogen atom from a monovalent group selected from the group consisting of an amide group, an aldehyde group, and a carboxyl group, which may have 5 substituents.
• the host group-containing polymerizable monomer has the following general formula (h2)
• Ra, R H and R 1 are each synonymous with Ra, R H and R 1 of formula (h1).
• Compounds represented by formula (h2) can be mentioned.
• the host group-containing polymerizable monomer has the following general formula (h3)
• Ra, R H and R 1 have the same meanings as Ra, R H and R 1 in formula (h1), respectively.
• n is 1 to 20, preferably 1 to 10, more preferably 1 to It is an integer of 5.
• Rb represents hydrogen or an alkyl group having 1 to 20 carbon atoms (preferably an alkyl group having 1 to 10 carbon atoms, more preferably an alkyl group having 1 to 6 carbon atoms).
• the host group R H in the host group-containing polymerizable monomers represented by formulas (h1), (h2), and (h3) is a monovalent group obtained by removing one hydroxyl group from a cyclodextrin derivative. This is an example of a certain case.
• the host group-containing polymerizable monomer can be one type alone of the compounds represented by formula (h1), formula (h2), and formula (h3), or can contain two or more types. I can do it.
• Ra in formula (h1), formula (h2), and formula (h3) may be the same or different from each other.
• R H in formulas (h1), formulas (h2), and formulas (h3), and R 1 in formulas (h1), formulas (h2), and formulas (h3) may be the same or different from each other.
• substituents include an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, an alkynyl group having 2 to 20 carbon atoms, a halogen atom, a carboxyl group, a carbonyl group, a sulfonyl group, a sulfone group, and a cyano group. Examples include groups.
• R 1 is a divalent group formed by removing one hydrogen atom from an amino group which may have one substituent, then the amino group The nitrogen atom of can be bonded to the carbon atom of the C ⁇ C double bond.
• R 1 is a divalent group formed by removing one hydrogen atom from an amide group which may have one substituent, then the amide group carbon atoms can be bonded to the carbon atoms of the C ⁇ C double bond.
• R 1 is a divalent group formed by removing one hydrogen atom from an aldehyde group
• the host group-containing polymerizable monomers represented by (h1) to (h3) are, for example, (meth)acrylic acid ester derivatives (i.e., R 1 is -COO-), (meth)acrylamide derivatives (i.e., R It is preferable that 1 is -CONH- or -CONR-, and R has the same meaning as the above-mentioned substituent. In this case, the polymerization reaction can proceed more easily, and the toughness and strength of the resulting polymer material can also be higher.
• (meth)acrylic in this specification refers to either acrylic or methacryl.
• R in -CONR- is, for example, preferably an alkyl group having 1 to 20 carbon atoms, more preferably an alkyl group having 1 to 10 carbon atoms, and particularly preferably an alkyl group having 1 to 6 carbon atoms.
• the host group-containing polymerizable monomer has the following general formula (h4)
• R 1 is (A) General formula (2) below -R 3 -NH-R 4 (2)
• R 3 is an alkylene group having 3 to 20 carbon atoms, which may be linear or branched, and may have a substituent.
• R 4 represents a (meth)acryloyl group or a vinyl group-containing alkyl group having 3 to 50 carbon atoms.
• (a) General formula (3) below -R 5 -NHCONH-R 6 (3) R 5 is an alkylene group having 3 to 20 carbon atoms, which may be linear or branched, and may have a substituent.
• R 6 represents a (meth)acryloyloxyalkyl group having 4 to 50 carbon atoms or a vinyl group-containing alkyl group having 3 to 50 carbon atoms. ) or (c) the following general formula (4) -R 5 -OCONH-R 6 (4) ( R5 and R6 are the same as above.) represents one of the following.
• R 2 represents a hydrogen atom, an acyl group having 2 to 50 carbon atoms, or an alkyl group having 1 to 30 carbon atoms.
• R H can include the above-mentioned host groups. Note that the host group here has a structure represented by general formula (5).
• -CONHR 8 is preferably a methyl carbamate group or an ethyl carbamate group.
• -CONHR 8 is an ethyl carbamate group from the viewpoint that the cyclodextrin derivative is easily dissolved in other polymerizable monomers used together, and the polymer made of the cyclodextrin derivative is easy to form host-guest interaction. It is preferable that
• R 1 and R H having the polymerizable unsaturated group are connected via a nitrogen atom derived from an amino group.
• R 1 is (a) The following general formula (h4-1) -R 3 -NH-R 4 (h4-1) (R 3 is an alkylene group having 3 to 20 carbon atoms, which may be linear or branched, and may have a substituent.
• R 4 represents a (meth)acryloyl group or a vinyl group-containing alkyl group having 3 to 50 carbon atoms.
• It is expressed as
• the cyclodextrin derivative (h4) having the structure represented by general formula (h4-1) has a structure derived from a diaminoalkyl compound, R 2 -NR 3 -NH-.
• the diaminoalkyl compound used for producing the cyclodextrin derivative is unfavorable in terms of toxicity if the number of carbon atoms in the alkyl group is too small. Furthermore, if the distance between the main chain of the cyclodextrin derivative of the present invention and the cyclodextrin during polymerization is too short, the degree of freedom of the molecule including steric hindrance will decrease, which is not preferable in terms of functional expression.
• the carbon number R 3 of the diaminoalkyl group is preferably 3 to 20. More preferably 3 to 10, still more preferably 3 to 5.
• R 1 represents (a) the following general formula (3) -R 5 -NHCONH-R 6 (3)
• R 5 is an alkylene group having 2 to 20 carbon atoms, which may be linear or branched, and may have a substituent.
• R 6 represents a (meth)acryloyloxyalkyl group having 4 to 50 carbon atoms or a vinyl group-containing alkyl group having 3 to 50 carbon atoms. ).
• the cyclodextrin derivative has a functional group that exhibits radical polymerizability via a urea bond, and has a (meth)acryloyloxyalkyl group or a vinyl group-containing alkyl group. It has a structure that has
• the number of carbon atoms in the alkyl group of the (meth)acryloyloxyalkyl group is preferably 1 to 10, and specific examples include structures derived from isocyanates such as 2-methacryloyloxyethyl isocyanate and 2-acryloyloxyethyl isocyanate.
• the number of carbon atoms R 5 in the diaminoalkyl group is preferably 3 to 20 for the same reason as R 3 above. More preferably, it is 3-10.
• R 1 is (c) the following general formula (4) -R 5 -OCONH-R 6 (4) (R 5 and R 6 are the same as above).
• the cyclodextrin derivative has a functional group exhibiting radical polymerizability via a urethane bond, and has a (meth)acryloyloxyalkyl group or a vinyl group-containing alkyl group. It has a structure that has
• a host monomer corresponding to (h4) it is preferable to use a host monomer corresponding to (h4) in that the resulting polymer has particularly excellent physical properties.
• the compounds represented by (h1) to (h4) mentioned above are, for example, the known compounds disclosed in Patent Documents 2 to 5 mentioned above. Therefore, it can be manufactured by referring to these documents.
• host group-containing polymerizable monomer represented by formula (h1) include the following (h1-1) to (h1-6).
• methylation of the cyclodextrin site and methylation of the amide site can be carried out in one step reaction, and compounds represented by formulas (h1-1), (h1-2) and (h1-3) can be easily prepared.
• the advantage is that you can get The same applies to formulas (h2-1), (h2-2) and (h2-3) below.
• R 1 is -CONH-, and are ⁇ -cyclodextrin derivatives and ⁇ -cyclodextrin derivatives, respectively.
• -Cyclodextrin derivatives ⁇ -cyclodextrin derivatives having a host group from which one hydroxyl group has been removed.
• the hydrogen atoms of the N-1 hydroxyl groups are substituted with methyl groups.
• At least one X is a hydrogen atom, and at least one X is -CONHC 2 H 5 (ethyl carbamate group). n is 5, 6 or 7.
• the compound represented by formula (h1-10) has a host group in which R 1 in formula (h1) is -CONH- and one hydroxyl group is removed from a cyclodextrin derivative. Further, the hydrogen atoms of N-1 hydroxyl groups in the cyclodextrin derivative are substituted with the above-mentioned X.
• host group-containing polymerizable monomer represented by formula (h2) include the following (h2-1) to (h2-9).
• Compounds represented by formulas (h2-7), (h2-8) and (h2-9) have formulas (h2) in which R 1 is -COO-, and are ⁇ -cyclodextrin derivatives and ⁇ - Cyclodextrin derivatives and ⁇ -cyclodextrin derivatives have a host group with one hydroxyl group removed. Furthermore, in each of the cyclodextrin derivatives, the hydrogen atoms of the N-1 hydroxyl groups are substituted with methyl groups.
• host group-containing polymerizable monomer represented by formula (h3) include the following (h3-1) to (h3-6).
• functional groups exhibiting polymerizability include alkenyl groups, vinyl groups, etc., as well as -OH, -SH, -NH 2 , -COOH, -SO 3 H, -PO 4 H, isocyanate groups, and epoxy groups ( glycidyl group), etc.
• These polymerizable functional groups can be introduced into the cyclodextrin or cyclodextrin derivative by substituting the hydrogen atom of one or more hydroxyl groups of the cyclodextrin. As a result, a host group-containing polymerizable monomer having a functional group exhibiting polymerizability is formed.
• Examples of host group-containing polymerizable monomers include compounds in which a host group is bonded (for example, covalently bonded) to a vinyl compound having a radically polymerizable functional group.
• the host group-containing polymerizable monomer can be one of the compounds represented by formula (h1), formula (h2), formula (h3), and formula (h4), or two types of compounds can be used alone. It can contain more than one species.
• Ra in formula (h1), formula (h2), and formula (h3) may be the same or different from each other.
• R H in formula (h1), formula (h2), formula (h3), and formula (h4), and R 1 in formula (h1), formula (h2), and formula (h3) are each the same or different from each other. There are cases.
• the substituents defined in formulas (h1) to (h4) are not particularly limited.
• substituents include an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 2 to 20 carbon atoms, an alkynyl group having 2 to 20 carbon atoms, a halogen atom, a carboxyl group, a carbonyl group, a sulfonyl group, a sulfone group, and a cyano group. Examples include groups.
• R 1 is a divalent group formed by removing one hydrogen atom from an amino group which may have one substituent, then the amino group The nitrogen atom of can be bonded to the carbon atom of the C ⁇ C double bond.
• R 1 is a divalent group formed by removing one hydrogen atom from an amide group which may have one substituent, then the amide group carbon atoms can be bonded to the carbon atoms of the C ⁇ C double bond.
• R 1 is a divalent group formed by removing one hydrogen atom from an aldehyde group
• the host group-containing polymerizable monomers represented by (h1) to (h3) are, for example, (meth)acrylic acid ester derivatives (i.e., R 1 is -COO-), (meth)acrylamide derivatives (i.e., R It is preferable that 1 is -CONH- or -CONR-, and R has the same meaning as the above substituent. In this case, the polymerization reaction can proceed more easily, and the toughness and strength of the resulting polymer material can also be higher.
• (meth)acrylic in this specification refers to either acrylic or methacryl.
• the polymer compound having a host group includes a monomer unit based on the host group-containing polymerizable monomer and a monomer unit based on other radically polymerizable monomers described in detail below.
• the polymer and resin composition of the present invention essentially contain a structural unit derived from a monomer having a hydroxyalkyl (meth)acrylate and/or an alkoxyalkyl (meth)acrylate and a host group. Furthermore, in order to obtain the effect of improving physical properties by such a host group, it is preferable that the resin further has a guest group or has a structure in which the main chain of the resin penetrates the host group. .
• the polymer and resin composition of the present invention can have crosslinks in the molecule due to host-guest interaction. By introducing such crosslinks, the physical properties of the resin can be made similar to biological materials such as blood vessels.
• guest group The type of guest group is not limited as long as it is a group capable of host-guest interaction with the above-mentioned host group, and a wide range of known guest groups can be exemplified.
• Examples of the guest group include linear or branched hydrocarbon groups having 3 to 30 carbon atoms, cycloalkyl groups, aryl groups, heteroaryl groups, and organometallic complexes, which have one or more substituents. You can leave it there. More specific guest groups include chain or cyclic alkyl groups having 4 to 18 carbon atoms. The chain alkyl group having 4 to 18 carbon atoms may be either straight chain or branched. The cyclic alkyl group may have a cage structure.
• the substituent is the same as the above-mentioned substituent, and includes, for example, a halogen atom (e.g., fluorine, chlorine, bromine, etc.), a hydroxyl group, a carboxyl group, an ester group, an amide group, an optionally protected hydroxyl group, etc. be able to.
• a halogen atom e.g., fluorine, chlorine, bromine, etc.
• guest groups include, for example, alcohol derivatives; aryl compounds; carboxylic acid derivatives; amino derivatives; azobenzene derivatives having a cyclic alkyl group or phenyl group; cinnamic acid derivatives; aromatic compounds and their alcohol derivatives; amine derivatives; ferrocene derivatives; azobenzene; naphthalene derivative; anthracene derivative; pyrene derivative; perylene derivative; clusters composed of carbon atoms such as fullerene; A monovalent group formed by removing an atom) can also be mentioned.
• guest group examples include t-butyl group, n-octyl group, n-dodecyl group, isobornyl group, adamantyl group, and groups to which the above substituents are bonded.
• a guest group-containing polymerizable monomer is a compound in which a polymerizable monomer is substituted with a guest group.
• the type of guest group is not limited as long as it is a group capable of host-guest interaction with the host group.
• guest groups include linear or branched hydrocarbon groups having 3 to 30 carbon atoms, linear or branched fluoroalkyl groups having 3 to 30 carbon atoms, cycloalkyl groups, aryl groups, heteroaryl groups, and organometallic groups. Examples include complexes, which may have one or more substituents. More specific guest groups include chain or cyclic alkyl groups having 4 to 18 carbon atoms. The chain alkyl group having 4 to 18 carbon atoms may be either straight chain or branched. The cyclic alkyl group may have a cage structure.
• the substituent is the same as the above-mentioned substituent, and includes, for example, a halogen atom (e.g., fluorine, chlorine, bromine, etc.), a hydroxyl group, a carboxyl group, an ester group, an amide group, an optionally protected hydroxyl group, etc. be able to.
• a halogen atom e.g., fluorine, chlorine, bromine, etc.
• guest groups include, for example, alcohol derivatives; aryl compounds; carboxylic acid derivatives; amino derivatives; azobenzene derivatives having a cyclic alkyl group or phenyl group; cinnamic acid derivatives; aromatic compounds and their alcohol derivatives; amine derivatives; ferrocene derivatives; azobenzene; naphthalene derivative; anthracene derivative; pyrene derivative; perylene derivative; clusters composed of carbon atoms such as fullerene; A monovalent group formed by removing an atom) can also be mentioned.
• guest groups include fluorinated alkyl groups such as -CH 2 CH 2 CF 2 CF 2 CF 2 CF 2 CF 3 groups, t-butyl group, n-octyl group, n-dodecyl group, isobornyl group.
• examples include adamantyl groups, adamantyl groups, and groups to which the above-mentioned substituents are bonded.
• guest group-containing polymerizable monomers include vinyl polymerizable monomers to which the guest groups are bonded (hereinafter sometimes referred to as "guest group-containing vinyl monomers"). be able to.
• the guest group-containing vinyl monomer has the following general formula (g1)
• Ra represents a hydrogen atom or a methyl group
• R G represents the guest group
• R 2 has the same meaning as R 1 in formula (h1).
• the guest group-containing vinyl monomer examples include the monomer shown as RF6 in Examples, n-hexyl (meth)acrylate, n-octyl (meth)acrylate, and n-(meth)acrylate.
• Examples include glycol acrylate, isostearyl
• the guest group-containing vinyl monomer can be produced by a known method. Moreover, a commercially available product can also be used as the guest group-containing polymerizable monomer.
• a polymer having the above-mentioned host group-containing polymerizable monomer as a constituent unit can be a flexible crosslinked polymer depending on the type of the host group-containing vinyl monomer and other polymerizable monomers described in detail below.
• the term "mobile crosslinked polymer” as used herein means that the crosslinking points in the polymer are formed to be movable.
• the main chain of another polymer has a structure in which the ring of the host group (cyclodextrin structure) bonded to the polymer side chain is penetrated, and the main chain can slide through the ring of the host group.
• a polymer formed in this way can be called a flexible crosslinked polymer. If the polymeric material is a flexible crosslinked polymer, it can have better toughness.
• the polymer of the polymerizable monomer mixture forms a flexible crosslinked polymer. It's easy to do. This is because polymerization proceeds while a monomer having such a size that can penetrate through the ring of the host group (cyclodextrin structure).
• Whether or not the copolymer or resin composition forms a mobile crosslinked polymer can be determined, for example, from the results of a swelling test of the copolymer or resin composition. For example, when polymer A1-1 is prepared without using a chemical crosslinking agent and the obtained polymer A1-1 is added to a solvent, if a swelling phenomenon is observed without dissolving, the mobility It can be determined that a crosslinked polymer is formed, and when it is dissolved, it can be determined that a mobile crosslinked polymer is not formed.
• Mobile crosslinked polymers are formed in such a way that in addition to the polymer forming a crosslinked structure, the crosslinking points are movable, allowing the polymer chain to slide within the host group ring. ing. Thereby, even if stress is applied to the mobile crosslinked polymer, an effect of relieving the stress is exerted. As a result, mobile crosslinked polymers can have superior toughness and strength and can be materials with excellent fracture energy. From this point of view, it is preferable that the polymeric material contains as a structural unit a monomer containing a polymerizable monomer having a size that can penetrate the host group of the host group-containing vinyl monomer.
• radically polymerizable monomers do not fall under the above-mentioned alkoxy (meth)acrylates, host group-containing monomers, and guest group-containing monomers, and are the above-mentioned host group-containing polymerizable monomers and guest groups described below.
• Various compounds that can be copolymerized with the contained polymerizable monomer can be mentioned.
• Examples of the other radically polymerizable monomers include various known vinyl polymerizable monomers.
• Ra is a hydrogen atom or a methyl group
• R3 is a halogen atom, a hydroxyl group, a thiol group, an amino group that may have one substituent or a salt thereof, one substituent carboxyl group or a salt thereof which may have one or more substituents, an amide group or a salt thereof which may have one or more substituents, a phenyl group which may have one or more substituents
• R 3 when R 3 is a carboxyl group having one substituent, the hydrogen atom of the carboxyl group is a hydrocarbon group, methoxypolyethylene glycol (the number of units of ethylene glycol is 1 to 20, preferably 1 to 10, particularly preferably 2 to 5), ethoxypolyethylene glycol (the number of ethylene glycol units is 1 to 20, preferably 1 to 10, particularly preferably 2 to 5), etc. ).
• R 3 when R 3 is an amide group having one or more substituents, that is, a secondary amide or a tertiary amide, one hydrogen atom or two hydrogen atoms of the primary amide Examples include amide groups in which atoms are independently substituted with hydrocarbon groups or hydroxyalkyl groups (eg, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl).
• R 3 is a carboxyl group in which a hydrogen atom is substituted with an alkyl group having 1 to 10 carbon atoms, or an amide in which one or more hydrogen atoms are substituted with an alkyl group having 1 to 10 carbon atoms. It is preferable that it is a group. In this case, the other radically polymerizable monomers have relatively high hydrophobicity, and copolymerization with the host group polymerizable monomer easily proceeds. More preferably, the alkyl group as a substituent has 2 to 8 carbon atoms, particularly preferably 2 to 6 carbon atoms, and in this case, the toughness and strength of the resulting polymer material are likely to be improved. This alkyl group may be either straight chain or branched.
• monomer represented by formula (a1) examples include (meth)acrylic acid, allylamine, maleic anhydride, methyl (meth)acrylate, ethyl (meth)acrylate, and n-(meth)acrylate.
• the content of the hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate (A) is 80 to 80% by mass based on 100% by mass of the total monomer components. It is preferably 99.5% by mass.
• the monomer composition of the present invention has biocompatibility. , a polymer having physical properties similar to biological materials.
• the content of the hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate (A) is less than 80% by mass, biocompatibility may decrease.
• the content of the hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate is preferably 85% by mass or more, more preferably 90% by mass or more, based on 100% by mass of the total monomer components.
• the content of the hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate is preferably 99% by mass or less, more preferably 98% by mass or less, based on 100% by mass of the total monomer components.
• the content of the host group-containing polymerizable monomer unit is not particularly limited.
• the host group-containing polymerizable monomer unit can be contained in an amount of 0.01 to 10 mol % based on the total number of moles of monomer units constituting the copolymer or resin composition.
• host-guest interactions and mobile crosslinkable polymers are likely to occur in the polymeric material, and mechanical strength is likely to be improved.
• the host group-containing polymerizable monomer unit preferably contains 0.05 mol % or more, and 0.1 mol % or more of the host group-containing polymerizable monomer unit based on the total number of moles of the monomer units constituting the copolymer or resin composition of the present invention. It is more preferable to contain mol% or more, further preferably to contain 0.5 mol% or more, and especially preferably to contain 1 mol% or more. Further, the host group-containing polymerizable monomer unit preferably contains 8 mol% or less, and 6 mol% or less, based on the total number of moles of monomer units constituting the copolymer or resin composition of the present invention. It is more preferable to contain less than or equal to 5 mol %, even more preferably to contain 5 mol % or less, and particularly preferably to contain 4 mol % or less.
• the content of the guest group-containing polymerizable monomer unit is not particularly limited.
• the guest group-containing polymerizable monomer unit can be contained in an amount of 0.01 to 10 mol % based on the total number of moles of monomer units constituting the copolymer or resin composition of the present invention.
• host-guest interaction is likely to occur in the polymeric material, and mechanical strength is likely to be improved.
• the guest group-containing polymerizable monomer unit preferably contains 0.05 mol% or more, and 0.1 mol% or more, based on the total number of moles of the monomer units constituting the polymer compound having a guest group.
• the guest group-containing polymerizable monomer unit preferably contains 8 mol% or less, and 6 mol% or less, based on the total number of moles of monomer units constituting the copolymer or resin composition of the present invention. It is more preferable to contain less than or equal to 5 mol %, even more preferably to contain 5 mol % or less, and particularly preferably to contain 4 mol % or less.
• the polymerization method of the polymer constituting the copolymer or resin composition of the present invention is not particularly limited, and can be carried out by a general method. Specifically, radical polymerization by heat, radical polymerization by light, anionic polymerization, cationic polymerization, etc. can be mentioned. Among these, radical polymerization is particularly preferred.
• the photopolymerization initiator is not particularly limited and includes, for example, 1-hydroxycyclohexylphenylketone (trade name: IRGACURE184), 2-hydroxy-2-methylpropiophenone (trade name: IRGACURE1173), 2-methyl-1- Acetophenones such as [4-(methylthio)phenyl]-2-morpholinopropan-1-one, 1-[4-(2-hydroxyethoxy)phenyl]-2-hydroxy-2-methyl-1-propan-1-one, etc.
• benzoin system initiator such as benzoin, 2,2-dimethoxy-1,2-diphenylethan-1-one
• benzophenone [4-(methylphenylthio)phenyl]phenylmethanone, 4-hydroxybenzophenone
• Benzophenone initiators such as 4-phenylbenzophenone and 3,3',4,4'-tetra(t-butylperoxycarbonyl)benzophenone
• Thioxanthone initiators such as 2-chlorothioxanthone and 2,4-diethylthioxanthone
• Acylphosphine oxide initiators such as 2,4,6-trimethylbenzoyl-diphenylphosphine oxide, bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide
• 1,2-octanedione 1-[4-(phenylthio) ) phenyl], 2-(0-benzoyloxime), ethanone, 1-[9-ethyl
• Conditions for photopolymerization are not particularly limited, and examples of light sources include high-pressure mercury lamps, LED lamps, metal halide lamps, and the like.
• the radical polymerization initiator is not particularly limited, and includes azobisisobutyronitrile (AIBN), 4,4'-azobis(4-cyanovaleric acid), 2,2'-azobis(2-methylbutyronitrile), Dimethyl 2,2'-azobis(2-methylpropionate), 2,2'-azobis(2,4-dimethylvaleronitrile), benzoyl peroxide, dicumyl peroxide, di-tert-butyl peroxide, cumene hydroperoxide, etc. can be used.
• the amount of the thermal polymerization initiator used is preferably 0.1 to 2% by weight based on the total amount of monomers constituting the copolymer or resin composition of the present invention.
• the copolymer or resin composition of the present invention contains structural units derived from a host group-containing vinyl monomer and a guest group-containing vinyl monomer, in its production, the host group-containing vinyl monomer and the guest group-containing vinyl monomer are It is also possible to form a clathrate compound 1 of the vinyl monomers contained therein and perform polymerization using this.
• the host group-containing vinyl monomer and the guest group-containing vinyl monomer meric clathrate 1 may be formed.
• the step for forming the clathrate compound 1 may be referred to as the "clathrate compound forming step.”
• This clathrate compound 1 is formed by host-guest interaction between a host group and a guest group.
• the monomer A1 can become a more uniform solution, so that the polymerization reaction A1 can easily proceed, and the resulting polymer is free from the formation of host-guest interactions.
• the toughness and strength of the resulting polymer material tend to improve.
• the ultrasonic treatment in the clathrate compound formation step is not particularly limited, and can be performed, for example, by a known method.
• the conditions for the heat treatment in the clathrate compound formation step are also not particularly limited.
• the heating temperature is 20 to 100°C, preferably 50 to 80°C.
• the heating time is 1 minute to 12 hours, preferably 15 minutes to 1 hour.
• the heating means is not particularly limited either, and examples thereof include a method using a hot stirrer, a method using a constant temperature bath, and the like.
• the ultrasonic treatment can also be performed together with or in place of heating.
• a clathrate compound formation step whether or not a clathrate compound has been formed can be determined, for example, by visually observing the state of monomer A. Specifically, if no clathrate is formed, monomer A is in a suspended state or in a phase-separated state when left to stand, but when a clathrate is formed, monomer A becomes gel-like or cream-like. It can become a state with viscosity such as. Additionally, monomer A1 can become transparent once the clathrate is formed.
• Host group-containing vinyl monomers have a high affinity with guest group vinyl monomers because the host group has a hydrocarbon group, etc., so compared to conventional host group-containing vinyl monomers. , clathrate compound 1 is more likely to be formed. As a result, when monomer A1 forms clathrate compound 1, monomer A1 tends to form a more uniform solution, and the toughness and strength of the polymeric material tend to improve significantly.
• monomer A1 from which clathrate compound 1 has been formed in the clathrate compound formation step is used as a raw material for polymerization reaction A1, and when monomer A1 further contains a third polymerizable monomer, The third polymerizable monomer may be added to monomer A1 after clathrate 1 is formed, or may be added to monomer A1 before clathrate 1 is formed. .
• the polymerization initiator, solvent, etc. may be added either before or after the formation of the clathrate compound 1.
• polymerization reaction A1 a polymerization initiator can be used in addition to monomer A1.
• the type of polymerization initiator is not particularly limited, and the above-mentioned known polymerization initiators can be used.
• a solvent may be used in the polymerization reaction A1, and when a solvent is used, the type of solvent is not particularly limited. The amount of solvent used is also not particularly limited.
• polymerization reaction A1 can also be carried out in the absence of a solvent.
• Monomer A1 contains a host group-containing vinyl monomer, and in particular, since the host group has a hydrocarbon group, etc., monomer A1 is suitable for both hydrophilic and hydrophobic polymerizable monomers. It also shows high affinity for Therefore, in the polymerization reaction A, a uniform solution of monomer A1 can be obtained without using a solvent.
• the present invention may further include a polymer (B) obtained by carrying out a polymerization reaction in a resin component (A) having a host component as described above and, if necessary, a guest component.
• the amount of resin component (A) in the polymerization of polymer (B) is preferably 10 to 50% by weight based on the total amount of resin component (A) and solvent.
• the polymer (B) is preferably obtained by polymerization of unsaturated bonds.
• the monomers constituting such a polymer are not particularly limited, and may include various acrylic monomers, vinyl monomers, and the like.
• the obtained polymer will have a polymer present in the resin chain having a three-dimensional structure of the resin component (A), so that the effects of the present invention can be favorably obtained. can.
• Such monomers include the above-mentioned hydroxyalkyl (meth)acrylate and/or alkoxyalkyl (meth)acrylate (A), and specific examples include, for example, 2-methoxy Examples include ethyl (meth)acrylate, 2-ethoxyethyl (meth)acrylate, 4-methoxybutyl (meth)acrylate, and 4-ethoxybutyl (meth)acrylate.
• the monomers are not limited to these monomers as long as they are polar monomers that dissolve with the resin component (A) and have moderate compatibility so as not to cause partial separation or crystallization even after polymerization. Two or more of these may be used in combination.
• the polymerization method for the polymer (B) is not particularly limited, and can be carried out by a general method. Specifically, radical polymerization by heat, radical polymerization by light, anionic polymerization, cationic polymerization, etc. can be mentioned. Among these, radical polymerization is particularly preferred.
• the photopolymerization initiator is not particularly limited, and examples include 1-hydroxycyclohexylphenyl ketone (trade name: IRGACURE184), 2-hydroxy-2-methylpropiophenone (trade name: IRGACURE1173), 2-methyl-1- Acetophenones such as [4-(methylthio)phenyl]-2-morpholinopropan-1-one, 1-[4-(2-hydroxyethoxy)phenyl]-2-hydroxy-2-methyl-1-propan-1-one, etc.
• benzoin system initiator such as benzoin, 2,2-dimethoxy-1,2-diphenylethan-1-one
• benzophenone [4-(methylphenylthio)phenyl]phenylmethanone, 4-hydroxybenzophenone
• Benzophenone initiators such as 4-phenylbenzophenone and 3,3',4,4'-tetra(t-butylperoxycarbonyl)benzophenone
• Thioxanthone initiators such as 2-chlorothioxanthone and 2,4-diethylthioxanthone
• Acyl phosphine oxide initiators such as 2,4,6-trimethylbenzoyl-diphenylphosphine oxide, bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide
• 1,2-octanedione 1-[4-(phenylthio) ) phenyl], 2-(0-benzoyloxime), ethanone, 1-[9-ethy
• Conditions for photopolymerization are not particularly limited, and examples of light sources include high-pressure mercury lamps, LED lamps, metal halide lamps, and the like.
• the radical polymerization initiator is not particularly limited, and includes azobisisobutyronitrile (AIBN), 4,4'-azobis(4-cyanovaleric acid), 2,2'-azobis(2-methylbutyronitrile), Dimethyl 2,2'-azobis(2-methylpropionate), 2,2'-azobis(2,4-dimethylvaleronitrile), benzoyl peroxide, dicumyl peroxide, di-tert-butyl peroxide, cumene hydroperoxide, etc. can be used.
• the amount of the thermal polymerization initiator used is preferably 0.1 to 2% by weight based on the total amount of monomers constituting the polymer (B).
• micronized cellulose fiber (C) When the polymer or resin composition of the present invention is used as a medical material, micronized cellulose fiber (C) may also be used in combination.
• Micronized cellulose fibers are wood fibers (pulp) that have been refined down to the nano-order, and have received particular attention in recent years as a naturally-derived material. The use of micronized cellulose fiber as a filler is being considered, and it is known that strength is improved when blended into a resin, and many studies have been made from this perspective.
• the particle size of the micronized cellulose fibers is not particularly limited, but preferably has an average particle size of 1 to 30 ⁇ m as measured by X-ray CT, for example.
• Such micronized cellulose fibers may be so-called cellulose nanofibers, which are micronized to the nano-order.
• suitable toughness can be obtained by using such finely divided cellulose fibers (C).
• the micronized cellulose fiber is not particularly limited, but it is particularly preferred that at least a portion of the hydroxyl groups on its surface be esterified with polycarboxylic acid. Such surface treatment is particularly preferred in that it increases the affinity with the copolymer or resin composition of the present invention or the polymer (B) and allows for uniform mixing.
• the micronized cellulose fiber (C) may be made of at least one of cellulose and a cellulose derivative.
• the cellulose material is preferably a cellulose derivative from the viewpoint of easy hydrogen bonding with the copolymer or resin composition of the present invention.
• the above-mentioned cellulose derivative is, for example, a compound in which cellulose is modified with another functional group, and can also be referred to as a so-called modified cellulose.
• the cellulose derivative has a structure in which a hydroxyl group in a structural unit constituting cellulose or a hydrogen atom of the hydroxyl group is substituted with another functional group.
• the cellulose has a structure in which a hydroxyl group in a structural unit constituting the cellulose is substituted with another functional group.
• the cellulose derivative is preferably cellulose modified with a compound having at least one functional group F selected from the group consisting of a carboxy group, a hydroxyl group, an amino group, and an amide group.
• the hydroxyl group in the structural unit (glucose unit) constituting cellulose is substituted with at least one functional group F selected from the group consisting of a carboxy group, a hydroxyl group, an amino group, and an amide group. It is preferable to have a structure. In this case, since hydrogen bonding with the polymer A is likely to occur in the cellulose material, the polymer composite material can have excellent flexibility, toughness, and hardness.
• the functional group F is preferably one selected from the group consisting of a carboxy group and a hydroxyl group.
• the cellulose derivative can be obtained, for example, by modifying cellulose with a compound having the above functional group (for example, functional group F).
• a compound having the above functional group for example, functional group F
• the compound having the above functional group is referred to as "compound F.”
• Compound F includes, for example, a compound having a carboxyl group, a compound having a hydroxyl group, a compound having an amino group, and a compound having an amide group.
• a compound having a carboxyl group for example, a compound having a hydroxyl group, a compound having an amino group, and a compound having an amide group.
• these compounds for example, a wide variety of known compounds can be employed.
• compound F examples include citric acid, succinic acid, malic acid, phthalic acid, isophthalic acid, terephthalic acid, trimesic acid, oxalic acid, adipic acid, azelaic acid, sebacic acid, maleic acid, malonic acid, etc. be able to.
• compound F is preferably citric acid, from the viewpoints of easy production of the cellulose derivative and easy hydrogen bonding with polymer A.
• the cellulose derivative is preferably citric acid-modified cellulose.
• the amount of the functional group derived from the compound F introduced is, for example, 0.1 to 5 mmol/g, preferably 0.5 to 3 mmol/g, and more preferably 1 to 2 mmol/g.
• a specific method for producing the cellulose derivative includes, for example, a method in which cellulose and the above compound F are reacted.
• the reaction method between cellulose and the above-mentioned compound F is not particularly limited, and for example, a wide variety of known condensation reactions, addition reactions, etc. can be employed.
• the reaction between cellulose and the above compound F can be carried out, for example, in the presence of a catalyst.
• the type of catalyst is not particularly limited, and examples include acids, alkalis, and the like.
• the catalyst is preferably an alkali, and specific examples include alkali metal hydroxides such as sodium hydroxide, ammonia, and organic amines.
• the reaction temperature between cellulose and the above-mentioned compound F is also not particularly limited, and can be appropriately selected depending on the reactivity and the like.
• the reaction between cellulose and the above compound F can be carried out at a temperature of 20 to 200°C, preferably 50 to 150°C.
• the reaction time is also not particularly limited, and can be set to an appropriate time depending on the reaction temperature, for example, from 30 minutes to 20 hours.
• reaction between cellulose and the above compound F can be carried out in various solvents or without solvent.
• the molecular weight of the cellulose or cellulose derivative contained in the cellulose material is also not particularly limited.
• the weight average molecular weight of cellulose or a cellulose derivative is 5,000 to 1,000,000, preferably 10,000 to 900,000, more preferably 100,000 to 800,000.
• the finely divided cellulose fibers are preferably blended in an amount of 1 to 10% by weight based on the weight of the copolymer or resin composition of the present invention. Blending in the above-mentioned ratio is preferable because physical properties can be suitably improved.
• the lower limit is more preferably 2% by weight, and even more preferably 4% by weight.
• the upper limit is more preferably 8% by weight, and even more preferably 6% by weight.
• the copolymer or resin composition of the present invention can be formed into a predetermined shape by molding a composition containing a solvent by a method such as a casting method.
• the copolymer or resin composition of the present invention can be particularly suitably used as a medical material.
• Specific examples of medical materials to which the above copolymer or resin composition can be applied include the following. Catheters inserted or placed in the gastrointestinal tract orally or nasally, such as gastric catheters, feeding catheters, and enteral feeding (ED) tubes; oxygen catheters, oxygen cannulas, endotracheal tube tubes and cuffs, and trachea.
• Catheters that are orally or nasally inserted or indwelled into the airway or trachea such as incision tubes and cuffs, and intratracheal suction catheters; urethral or urinary catheters, such as urinary catheters, urinary drainage catheters, and balloon catheters; Catheters inserted or indwelled in tubes; Catheters inserted or indwelled in various body cavities, organs, tissues, such as suction catheters, drainage catheters, rectal catheters; indwelling needles, thermodilution catheters, IVH catheters, blood vessels Catheters inserted or placed in blood vessels such as contrast catheters, vasodilator catheters, dilators or introducers; or guide wires, stylets, etc.
• catheters testing instruments for inserting various organs; Treatment equipment, etc.; stents, artificial blood vessels, artificial tracheas, artificial bronchi, etc.; medical devices for extracorporeal circulation treatment (artificial hearts, artificial lungs, artificial kidneys, artificial valves, etc.) and their circuits; artificial joints, artificial femoral heads, sutures. Threads, dental materials, various adsorbents, plasma exchange membranes, CAPD, IABP, pacemakers, blood bags, urine collection bags, blood transfusion sets; etc.
• the medical material of the present invention is an artificial blood vessel.
• the copolymer and resin composition of the present invention have physical properties similar to those of blood vessels and are also excellent in biocompatibility. Therefore, it can be particularly suitably used as a material for artificial blood vessels.
• the copolymer or resin composition of the present invention may be molded into a tube shape by a known method, or a known medical material may be molded into a tube shape, and the inner surface can be coated with the copolymer or resin composition of the present invention.
• TAc ⁇ CD monomer (TAc ⁇ CDAAmMe), RF6 monomer, and photoinitiator IRGACURE 184 were dissolved in liquid monomer 2-methoxyethyl acrylate (MEA). After that, it was irradiated with ultrasonic waves for 1 hour, poured into a Teflon (registered trademark) mold of 10 cm (length) x 10 cm (width) x 1 mm (depth), and then irradiated with ultraviolet light using a high-pressure mercury lamp for 1 hour. , a film was produced.
• Teflon registered trademark
• the results of the platelet adhesion test are shown in Figures 1 and 2.
• the measurement results of the contact angle are shown in FIG. 2.
• the resin using MEA has better platelet adhesion and inhibition of platelet activation than PET.
• platelet adhesion and platelet activation inhibiting effects almost equivalent to those of a homopolymer of MEA can be obtained. It is presumed that such low platelet adhesion and activation suppressing effects are achieved by hydrophilicity in water.
• HUVEC adhesion test method The polymer substrate was sterilized by UV irradiation for 30 minutes, washed with PBS, and then left in 500 ⁇ L of HUVEC medium (EGM-2, Lonza) for 1 hour at 37°C. Thereafter, HUVECs were seeded (1.0 ⁇ 10 4 cells/cm 2 ) and incubated for 1, 24, and 72 hours. After immobilizing HUVECs on the substrate with 4% paraformaldehyde solution, they were immobilized using Phalloidin, 4',6-diamidino-2-phenylindole, and anti-vinculin antibody (Alexa Fluor 488-conjugated anti-mouse IgG (H+L)). After immunostaining, it was observed using a confocal laser microscope.
• Example 2 had improved HUVEC adhesion compared to Comparative Example 1.
• Example 5 to 7 The monomers used in Examples 5 to 7 are as follows. Note that SH-02 was synthesized by the method described in the Examples of International Publication No. 2022/024908.
• the copolymer of the present invention can be suitably used as a medical material such as an artificial blood vessel.

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• 2023
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