WO2022202805A1

WO2022202805A1 - Hydrophilic copolymer and medical instrument

Info

Publication number: WO2022202805A1
Application number: PCT/JP2022/013126
Authority: WO
Inventors: 政則倉本
Original assignee: テルモ株式会社
Priority date: 2021-03-22
Filing date: 2022-03-22
Publication date: 2022-09-29
Also published as: JP2024060627A

Abstract

The purpose of the present invention is to provide a novel hydrophilic copolymer capable of forming a surface lubrication layer that exhibits durability (lubricity-maintaining properties). The present invention pertains to a hydrophilic copolymer that contains a structural unit derived from polymerizable monomer (A) having a sulfobetaine structure, a structural unit derived from polymerizable monomer (B) having at least one group selected from the group consisting of sulfonic acid group (-SO3H), sulfuric acid group (-OSO3H), sulfurous acid group (-OSO2H) and salts thereof, and a structural unit derived from polymerizable monomer (C) having a -Si(R1)a(OR2)3-a group (wherein: R1s independently represent a linear or branched alkyl group having 1-20 carbon atoms, a linear or branched acyl group having 2-21 carbon atoms or a linear or branched ether group having 2-21 carbon atoms; R2s independently represent a hydrogen atom, a linear or branched alkyl group having 1-20 carbon atoms, a linear or branched acyl group having 2-21 carbon atoms or a linear or branched ether group having 2-21 carbon atoms; and a is an integer of 0-2).

Description

Hydrophilic copolymers and medical devices

The present invention relates to a medical device having a hydrophilic copolymer and a surface lubricating layer formed using the hydrophilic copolymer.

In recent years, catheters have become thinner in order to access more peripheral lesions. Therefore, the clearance between the catheter and the inner surface of the body lumen becomes extremely small, and high frictional resistance is generated on the surface of the catheter. Therefore, there is a demand for a coating that imparts lubricity and durability (lubricating properties) to the catheter surface.

In addition, when coating a base material such as a catheter, it is recommended to select a low-toxic solvent such as water, alcohol, or a water/alcohol mixed solvent from the viewpoint of application to biomaterials and worker safety. preferable. Therefore, the constituent components of the coating are required to dissolve or disperse in such solvents (solvent solubility).

For the above purpose, International Publication No. 2018/038063 (corresponding to US Patent Application Publication No. 2019/0185776) describes a polymerizable monomer (A)-derived structural unit having a sulfobetaine structure, a sulfone A polymerizable monomer having at least one group selected from the group consisting of an acid group (--SO ₃ H), a sulfate group (--OSO ₃ H), a sulfite group (--OSO ₂ H) and a salt group thereof A hydrophilic copolymer is disclosed which includes a structural unit derived from (B) and a structural unit derived from a polymerizable monomer (C) having a photoreactive group.

An object of the present invention is to provide a new hydrophilic copolymer capable of forming a surface lubricating layer exhibiting durability (lubricity maintaining property).

Another object of the present invention is to provide a new hydrophilic copolymer having solvent solubility.

An object of the present invention is to provide a medical device having a surface lubricating layer that exhibits durability (lubricity maintaining property) using the hydrophilic copolymer.

In view of the above problems, the inventors have conducted intensive research. As a result, a structural unit derived from the polymerizable monomer (A) having a sulfobetaine structure, a structural unit derived from the polymerizable monomer (B) having a sulfonic acid group/salt, etc., a silyl ether group (-SiOR ) and a structural unit derived from the polymerizable monomer (C) having ) can achieve the above objects.

In other words, the above objectives can be achieved by the following.

[1] A structural unit derived from a polymerizable monomer (A) having a sulfobetaine structure, a sulfonic acid group (--SO ₃ H), a sulfate group (--OSO ₃ H) and a sulfite group (--OSO ₂ H), and A structural unit derived from the polymerizable monomer (B) having at least one group selected from the group consisting of these salt groups, and a —Si(R ¹ ) _a (OR ² ) _3-a group (R ¹ are each independently a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched acyl group having 2 to 21 carbon atoms, or a linear or branched chain having 2 to 21 carbon atoms or a branched ether group; each R ² is independently a hydrogen atom, a straight or branched alkyl group having 1 to 20 carbon atoms, or a straight or branched acyl group having 2 to 21 carbon atoms or a linear or branched ether group having 2 to 21 carbon atoms; a is an integer of 0 to 2). Hydrophilic copolymer.

[2] The hydrophilic copolymer according to [1] above, wherein the polymerizable monomer (A) is represented by the following formula (1):

In the above formula (1),
R ¹¹ is a hydrogen atom or a methyl group,
Z ¹ is an oxygen atom or -NH-,
R ¹² and R ¹⁵ are each independently a linear or branched alkylene group having 1 to 20 carbon atoms,
R ¹³ and R ¹⁴ are each independently a straight or branched chain alkyl group having 1 to 20 carbon atoms.

[3] The hydrophilic copolymer according to [1] or [2] above, wherein the polymerizable monomer (B) is represented by the following formula (2), (3) or (4):

In the above formula (2),
R ²¹ is a hydrogen atom or a methyl group,
Z ² is an oxygen atom or -NH-,
R ²² is a linear or branched alkylene group having 1 to 20 carbon atoms,
X is a group selected from the group consisting of a sulfonic acid group (--SO ₃ H), a sulfate group (--OSO ₃ H) and a sulfite group (--OSO ₂ H) and salt groups thereof;

In the above formula (3),
R ³¹ is a hydrogen atom or a methyl group,
R ³² is a single bond or a linear or branched alkylene group having 1 to 20 carbon atoms,
X is a group selected from the group consisting of a sulfonic acid group (--SO ₃ H), a sulfate group (--OSO ₃ H) and a sulfite group (--OSO ₂ H) and salt groups thereof;

In the above formula (4),
R ⁴¹ is a hydrogen atom or a methyl group,
R ⁴² is a linear or branched alkylene group having 1 to 20 carbon atoms,
X is a group selected from the group consisting of sulfonic acid group (--SO ₃ H), sulfate group (--OSO ₃ H) and sulfite group (--OSO ₂ H) and salt groups thereof.

[4] The hydrophilic copolymer according to any one of [1] to [3] above, wherein the polymerizable monomer (C) is represented by the following formula (5):

In the above formula (5),
R ⁵¹ is a hydrogen atom or a methyl group,
Z ³ is an oxygen atom or -NH-,
R ⁵² is a linear or branched alkylene group having 1 to 12 carbon atoms,
R ⁵³ is —OR ² , R ⁵⁴ and R ⁵⁵ are each independently —R ¹ or —OR ² , wherein R ¹ and R ² each independently have 1 carbon atom ∼4 straight or branched chain alkyl groups, straight or branched chain acyl groups of 2 to 5 carbon atoms, or straight or branched chain ether groups of 2 to 5 carbon atoms.

[5] a substrate layer, a surface lubricating layer formed on at least a portion of the surface of the substrate layer and containing a crosslinked product of the hydrophilic copolymer according to any one of [1] to [4]; A medical device with

[6] The medical device according to [5] above, wherein the medical device is a catheter, a stent or a guidewire.

FIG. 2 is a partial cross-sectional view schematically showing the layered structure of the surface of a representative embodiment of the medical device according to the present invention. In FIG. 1, 1 indicates a substrate layer; 2 indicates a surface lubricating layer; and 10 indicates a medical device. FIG. 2 is a partial cross-sectional view schematically showing a configuration example with a different layered configuration on the surface as an application example of the embodiment of FIG. 1 ; In FIG. 2, 1 indicates a substrate layer; 1a indicates a core portion of the substrate layer; 1b indicates a substrate surface layer; 2 indicates a surface lubricating layer; and 10 indicates a medical device. 1 is a schematic diagram of a lubricity and durability testing device (friction measuring device) used in Example 1-2 and Comparative Example 1-2. FIG. 1 is a drawing showing lubricity and durability test results in Example 1-2 and Comparative Example 1-2.

Hereinafter, the embodiments for carrying out the present invention will be described in detail. The present invention is not limited to the following embodiments, and can be modified in various ways within the scope of the claims. Throughout this specification, expressions in the singular should also be understood to include their plural concepts unless specifically stated otherwise. Thus, articles in the singular (eg, "a," "an," "the," etc. in the English language) should be understood to include their plural concepts as well, unless specifically stated otherwise. Moreover, it should be understood that the terms used in this specification have the meanings commonly used in the relevant field unless otherwise specified. Thus, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification (including definitions) will control.

Also, in this specification, the range "X to Y" includes X and Y and means "X or more and Y or less". As used herein, "A and/or B" means at least one of A and B, and includes both A and B or either A or B. Unless otherwise specified, measurements of operations and physical properties are performed under the conditions of room temperature (20 to 25° C.)/relative humidity of 40 to 60%.

In this specification, the term "(meth)acryl" includes both acryl and methacryl. Thus, for example, the term "(meth)acrylic acid" includes both acrylic acid and methacrylic acid. Similarly, the term "(meth)acryloyl" includes both acryloyl and methacryloyl. Thus, for example, the term "(meth)acryloyl group" includes both acryloyl and methacryloyl groups.

In addition, unless otherwise defined herein, the term "substituted" means a C1-C30 alkyl group, a C2-C30 alkenyl group, a C2-C30 alkynyl group, a C1-C30 alkoxy group, an alkoxycarbonyl group (-COOR, R is C1-C30 alkyl group), halogen atom (F, Cl, Br or I atom), C6-C30 aryl group, C6-C30 aryloxy group, amino group, C1-C30 alkylamino group, cyano group, nitro group, thiol group, a C1-C30 alkylthio group or a hydroxyl group. It should be noted that when a group is substituted, that form of substitution is excluded as included in the definition before the substituted structure is further substituted. For example, when a substituent is an alkyl group, this alkyl group as a substituent is not further substituted with an alkyl group.

Further, in the present specification, when a structural unit is defined as "derived from" a certain monomer, the structural unit is one of the polymerizable unsaturated double bonds of the corresponding monomer. It means a divalent constitutional unit generated by bond cleavage.

<Hydrophilic copolymer>
According to the first aspect of the present invention, a structural unit derived from a polymerizable monomer (A) having a sulfobetaine structure, a sulfonic acid group (--SO ₃ H), a sulfate group (--OSO ₃ H) and a sulfite group (—OSO ₂ H) and a structural unit derived from a polymerizable monomer (B) having at least one group selected from the group consisting of salt groups thereof, and —Si(R ¹ ) _a (OR ² ) _3-a group (each R ¹ is independently a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched acyl group having 2 to 21 carbon atoms, or a a linear or branched ether group of 2 to 21; each R ² is independently a hydrogen atom, a linear or branched alkyl group of 1 to 20 carbon atoms, a linear or branched acyl group, or a linear or branched ether group having 2 to 21 carbon atoms; a is an integer of 0 to 2) derived from polymerizable monomer (C) A hydrophilic copolymer is provided comprising a structural unit of The hydrophilic copolymer according to the present invention can form a surface lubricating layer exhibiting excellent durability (lubricity maintaining property). Moreover, the hydrophilic copolymer according to the present invention has good solvent solubility. Therefore, the layer (surface lubricating layer) formed using the hydrophilic copolymer can exhibit excellent durability (lubricating property). In addition, a layer (surface lubricating layer) formed using the hydrophilic copolymer can exhibit excellent lubricity. Furthermore, the hydrophilic copolymer has good solvent solubility (in particular, solubility in water, alcohol, and water/alcohol mixed solvent).

In the present specification, "polymerizable monomer (A) having a sulfobetaine structure" is also simply referred to as "polymerizable monomer (A)" or "monomer (A)". In addition, the “structural unit derived from the polymerizable monomer (A) having a sulfobetaine structure” is also simply referred to as “structural unit (A)”.

In the present specification, "at least one group selected from the group consisting of a sulfonic acid group (--SO ₃ H), a sulfate group (--OSO ₃ H) and a sulfite group (--OSO ₂ H), and groups of salts thereof ” is also simply referred to as “sulfonic acid group/salt, etc.”. In addition, "polymerization having at least one group selected from the group consisting of sulfonic acid group (--SO ₃ H), sulfate group (--OSO ₃ H), sulfite group (--OSO ₂ H) and salt groups thereof "Polymerizable monomer (B)" is also simply referred to as "polymerizable monomer (B)" or "monomer (B)". In addition, "polymerization having at least one group selected from the group consisting of sulfonic acid group (--SO ₃ H), sulfate group (--OSO ₃ H), sulfite group (--OSO ₂ H) and salt groups thereof A "structural unit derived from the functional monomer (B)" is also simply referred to as a "structural unit (B)".

As used herein, the term “—Si(R ¹ ) _a (OR ² ) _3-a group (R ¹ is each independently a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched acyl group of 2 to 21 carbon atoms, or a linear or branched ether group of 2 to 21 carbon atoms; each R ² is independently a hydrogen atom, 1 to 20 carbon atoms; a linear or branched alkyl group, a linear or branched acyl group having 2 to 21 carbon atoms, or a linear or branched ether group having 2 to 21 carbon atoms; is an integer of 2)” may be simply referred to as “-Si(R ¹ ) _a (OR ² ) _3-a group” or “-Si(R ¹ ) _a (OR ² ) _3- a group according to the present invention”. called. In addition, the “polymerizable monomer (C) having a —Si(R ¹ ) _a (OR ² ) _3-a group according to the present invention” is simply “polymerizable monomer (C)” or “monomer Also referred to as "body (C)". In addition, the “structural unit derived from the polymerizable monomer (C) having a —Si(R ¹ ) _a (OR ² ) _3-a group according to the present invention” is also simply referred to as “structural unit (C)”.

In the present specification, "the structural unit (A) derived from the polymerizable monomer (A), the structural unit (B) derived from the polymerizable monomer (B), and the polymerizable monomer (C) derived A hydrophilic copolymer containing a structural unit (C)" is also simply referred to as a "hydrophilic copolymer according to the present invention", a "hydrophilic copolymer", or a "copolymer".

Each polymerizable monomer constituting the hydrophilic copolymer according to the present invention will be described below.

[Polymerizable monomer]
(Monomer (A))
Monomer (A) is a polymerizable monomer having a sulfobetaine structure. Here, the term “sulfobetaine structure” means that a positive charge and a negative charge containing a sulfur element are present at positions that are not adjacent to each other, and a dissociable hydrogen atom is not bound to an atom having a positive charge, and a charge refers to a structure in which the sum of is zero.

The sulfobetaine structure contained in the structural unit (A) derived from the monomer (A) has an excellent effect of imparting lubricity. Therefore, when a medical device (for example, a guide wire) provided with a surface lubricating layer formed using a hydrophilic copolymer having a structural unit (A) derived from a monomer (A) absorbs water, the surface lubricating layer swells. When this medical device is inserted into a biological lumen such as a blood vessel and comes into contact with the biological lumen wall, hydrated water oozes out on the surface of the lubricating surface layer. is hindered. Therefore, the surface lubricating layer formed using the hydrophilic copolymer according to the present invention can exhibit excellent lubricity. This effect is particularly effective when the clearance between the catheter and the inner surface of the body lumen is extremely small.

Examples of the monomer (A) include, but are not particularly limited to, compounds represented by the following general formula.

In the above general formula, R ^a and R ^d are each independently an optionally substituted alkylene group having 1 to 30 carbon atoms or an optionally substituted arylene group having 6 to 30 carbon atoms. R ^b and R ^c may each independently be an optionally substituted alkyl group having 1 to 30 carbon atoms or an aryl group having 6 to 30 carbon atoms which may be substituted; may be an ethylenically unsaturated group such as an acryloyl group, a methacryloyl group or a vinyl group. However, in the above general formula, the sum of positive charges and negative charges is zero.

Examples of alkylene groups having 1 to 30 carbon atoms include methylene group, ethylene group, trimethylene group, propylene group, isopropylene group, butylene group, isobutylene group, sec-butylene group, tert-butylene group, pentamethylene group, A hexamethylene group and the like can be mentioned.

Examples of arylene groups having 6 to 30 carbon atoms include phenylene groups, naphthylene groups, anthracenylene groups, phenanthrenylene groups, pyrenylene groups, perylenylene groups, fluorenylene groups, and biphenylene groups.

Examples of alkyl groups having 1 to 30 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group and n-pentyl group. , iso-pentyl group, tert-pentyl group, neopentyl group, n-hexyl group, 2-ethylhexyl group, n-heptyl group, n-octyl group and the like.

Examples of aryl groups having 6 to 30 carbon atoms include phenyl, biphenyl, terphenyl, pentalenyl, indenyl, naphthyl, azulenyl, heptalenyl, and biphenylenyl groups.

Above all, the monomer (A) is preferably a compound represented by the following formula (1), from the viewpoint of further improving durability (lubricity maintenance) (and lubricity). That is, in a preferred embodiment of the present invention, the polymerizable monomer (A) is represented by the following formula (1).

In formula (1) above, R ¹¹ is a hydrogen atom or a methyl group. Z ¹ is an oxygen atom (--O--) or --NH--, preferably an oxygen atom (--O--).

Further, in the above formula (1), R ¹² and R ¹⁵ are each independently a linear chain having 1 to 20 carbon atoms from the viewpoint of further improving durability (lubrication maintenance property) (further lubricity). or a branched alkylene group, preferably a linear or branched alkylene group having 1 to 12 carbon atoms, more preferably a linear or branched alkylene group having 1 to 8 carbon atoms, and still more A linear or branched alkylene group having 1 to 6 carbon atoms is preferable, a linear alkylene group having 1 to 3 carbon atoms (methylene group, ethylene group or trimethylene group) is more preferable, and ethylene is particularly preferable. or trimethylene group. Here, R ¹² and R ¹⁵ may be the same or different, preferably R ¹² and R ¹⁵ are different. At this time, the combination of R ¹² and R ¹⁵ is particularly preferably a combination of R ¹² =ethylene group and R ¹⁵ =trimethylene group.

In the above formula (1), R ¹³ and R ¹⁴ are each independently a linear or branched chain having 1 to 20 carbon atoms, from the viewpoint of further improving durability (lubrication maintenance property) (further lubricity). A chain alkyl group, preferably a straight or branched chain alkyl group having 1 to 12 carbon atoms, more preferably a straight or branched chain alkyl group having 1 to 8 carbon atoms, still more preferably It is a straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms, more preferably a methyl group or an ethyl group, particularly preferably a methyl group. Here, R ¹³ and R ¹⁴ may be the same or different, but are preferably the same, more preferably both are methyl groups.

^In one embodiment of the present invention, in the polymerizable monomer (A), R ¹¹ is a hydrogen atom or a methyl group; Z ¹ is an oxygen atom (—O—) or —NH—; and R ¹⁵ are each independently a linear or branched alkylene group having 1 to 8 carbon atoms; R ¹³ and R ¹⁴ are each independently a linear or branched chain having 1 to 8 carbon atoms is represented by the above formula (1), which is an alkyl group of

^In one embodiment of the present invention, in the polymerizable monomer (A), R ¹¹ is a hydrogen atom or a methyl group; Z ¹ is an oxygen atom (—O—) or —NH—; and R ¹⁵ are each independently a linear or branched alkylene group having 1 to 6 carbon atoms; R ¹³ and R ¹⁴ are each independently a linear or branched chain having 1 to 4 carbon atoms is represented by the above formula (1), which is an alkyl group of

In one embodiment of the present invention, in the polymerizable monomer (A), R ¹¹ is a hydrogen atom or a methyl group; Z ¹ is an oxygen atom (-O-); R ¹² and R ¹⁵ are Each independently represents a methylene group, an ethylene group or a trimethylene group; R ¹³ and R ¹⁴ each independently represent a methyl group or an ethyl group, represented by the above formula (1).

In one embodiment of the present invention, in the polymerizable monomer (A), R ¹¹ is a hydrogen atom or a methyl group; Z ¹ is an oxygen atom (--O--); R ¹² is an ethylene group; R ¹⁵ is a trimethylene group; and R ¹³ and R ¹⁴ are methyl groups, represented by the above formula (1).

Examples of the compound represented by the above formula (1) include {2-[(meth)acryloyloxy]ethyl}dimethyl-(3-sulfopropyl)ammonium hydroxide, {2-[(meth)acryloyloxy]ethyl } dimethyl-(2-sulfoethyl) ammonium hydroxide, {2-[(meth)acryloyloxy]ethyl}diethyl-(2-sulfoethyl)ammonium hydroxide, {2-[(meth)acryloyloxy]ethyl}diethyl-( 3-sulfopropyl)ammonium hydroxide, {3-[(meth)acryloyloxy]propyl}dimethyl-(2-sulfoethyl)ammonium hydroxide, {3-[(meth)acryloyloxy]propyl}dimethyl-(3-sulfo Propyl) ammonium hydroxide, {3-[(meth)acryloyloxy]propyl}diethyl-(2-sulfoethyl)ammonium hydroxide, {3-[(meth)acryloyloxy]propyl}diethyl-(3-sulfopropyl)ammonium Hydroxides, among others, {2-[(meth)acryloyloxy]ethyl}dimethyl-(3-sulfopropyl)ammonium hydroxide, [3-(methacryloylamino)propyl]dimethyl(3-sulfopropyl)ammonium Hydroxides are preferred, {2-[(meth)acryloyloxy]ethyl}dimethyl-(3-sulfopropyl)ammonium hydroxide being more preferred. The above compounds may be used alone or in combination of two or more.

Either a synthetic product or a commercially available product may be used for the monomer (A). As a commercial product, it can be obtained from Sigma-Aldrich Japan LLC. Moreover, when synthesizing, A.I. Laschewsky, Polymers, 6, 1544-1601 (2014), etc. can be referred to.

In addition, the monomer (A) is not limited to the compound represented by the above general formula, and may be a compound having a positive charge at the end.

In the hydrophilic copolymer of the present invention, the content of the structural unit (A) derived from the monomer (A) is the structural unit derived from all the monomers constituting the hydrophilic copolymer (hereinafter referred to as "total unit When the total of 100 mol% of the structural units derived from the polymer) is 100 mol%, it is preferably 0.05 to 99 mol%, more preferably 1 to 98 mol%, and even more preferably 30 mol%. more than 95 mol%, more preferably 50 to 90 mol%, particularly preferably 60 to 80 mol%. Within such a range, the lubricity and solvent solubility are well balanced. The mol % is substantially equivalent to the ratio of the charged amount (mol) of the monomer (A) to the total charged amount (mol) of all the monomers when producing the polymer.

Each structural unit (A) constituting the hydrophilic copolymer may be the same (derived from a single monomer (A)) or different (derived from two or more monomers (A)). There may be.

(monomer (B))
The monomer (B) is at least one selected from the group consisting of a sulfonic acid group (--SO ₃ H), a sulfate group (--OSO ₃ H), a sulfite group (--OSO ₂ H) and salts of these groups. It is a polymerizable monomer having one group. These sulfonic acid groups, sulfate groups, sulfite groups, or salt groups thereof (sulfonic acid groups/salts, etc.) are easily anionized in an aqueous solvent. As a result, electrostatic repulsion occurs between the polymers, the interaction between the sulfobetaine structures is reduced, and the polymer becomes easier to dissolve or disperse in the aqueous solvent (improves the solvent solubility of the hydrophilic copolymer). ). Therefore, the hydrophilic copolymer according to the present invention can exhibit excellent solvent solubility (in particular, excellent solubility in water, alcohol, and water/alcohol mixed solvent) due to the presence of the structural unit (B).

Among them, from the viewpoint of further improving solvent solubility, the monomer (B) is preferably a compound represented by the following formula (2), (3) or (4), and the following formula (2) It is more preferably a compound represented by That is, in a preferred form of the present invention, the polymerizable monomer (B) is represented by the following formula (2), (3) or (4). In a more preferred form of the invention, the polymerizable monomer (B) is represented by the following formula (2).

In formula (2) above, R ²¹ is a hydrogen atom or a methyl group. Z ² is an oxygen atom (--O--) or --NH--, preferably --NH--.

In the above formula (2), R ²² is a straight or branched alkylene group having 1 to 20 carbon atoms, preferably a straight chain having 1 to 12 carbon atoms, from the viewpoint of further improving solvent solubility. or a branched alkylene group, more preferably a linear or branched alkylene group having 1 to 8 carbon atoms, still more preferably a linear or branched alkylene group having 1 to 6 carbon atoms and particularly preferably a branched alkylene group having 3 to 5 carbon atoms. A branched alkylene group having 3 to 5 carbon atoms is -CH(CH ₃ )-CH ₂ -, -C(CH ₃ ) ₂ -CH ₂ -, -CH(CH ₃ )-CH(CH ₃ )- , -C(CH ₃ ) ₂ -CH ₂ -CH ₂ -, -CH(CH ₃ )-CH(CH ₃ )-CH ₂ -, -CH(CH ₃ )-CH ₂ -CH(CH ₃ )-, A group represented by -CH ₂ -C(CH ₃ ) ₂ -CH ₂ -, -C(CH ₃ ) ₂ -CH(CH ₃ )-, etc. (provided that the above groups in formula (2) are linked The order is not particularly limited), and among them, a group represented by -C(CH ₃ ) ₂ -CH ₂ - is particularly preferred.

In the above formula (2), X is selected from the group consisting of a sulfonic acid group (--SO ₃ H), a sulfate group (--OSO ₃ H), a sulfite group (--OSO ₂ H) and a salt group thereof. is the base. Examples of the salt form of the above groups include sodium salts and potassium salts of the above groups, preferably sodium salts. A group selected from the group consisting of a sulfonic acid group, a sulfuric acid group, and a salt group thereof is preferable from the viewpoint of the dissociation degree of the acid (that is, the ease of anionization) and the solvent solubility of the hydrophilic copolymer. and more preferably a sulfonic acid group or a salt group thereof (especially a sodium sulfonate group (--SO ₃ Na)) in view of the availability of the monomer.

In one embodiment of the present invention, in the polymerizable monomer (B), R ²¹ is a hydrogen atom or a methyl group; Z ² is an oxygen atom ⁽ —O—) or —NH—; is a linear or branched alkylene group having 1 to 6 carbon atoms; X is a group selected from the group consisting of a sulfonic acid group, a sulfuric acid group and a salt group thereof, the above formula (2) is represented by

In one embodiment of the present invention, in the polymerizable monomer ⁽ B), R ²¹ is a hydrogen atom or a methyl group; Z ² is -NH-; is a branched alkylene group; X is a group selected from the group consisting of a sulfonic acid group, a sulfate group, and sodium salt groups and potassium salt groups thereof, represented by the above formula (2).

In one embodiment of the present invention, in the polymerizable monomer (B), R ²¹ is a hydrogen atom or a methyl group; Z ² is -NH-; R ²² is -C(CH ₃ ) ₂ —CH ₂ —; and X is a sulfonic acid group (—SO ₃ H) or a sodium sulfonate group (—SO ₃ Na), represented by the above formula (2).

Examples of the compound represented by the above formula (2) include 2-(meth)acrylamido-2-methyl-1-propanesulfonic acid, 1-[(meth)acryloyloxymethyl]-1-propanesulfonic acid, 2 -[(meth)acryloyloxy]-2-propanesulfonic acid, 3-[(meth)acryloyloxy]-1-methyl-1-propanesulfonic acid, 2-sulfoethyl (meth)acrylate, 3-sulfopropyl (meth) Examples include acrylates and salts thereof (especially sodium salts). Among these, 2-(meth)acrylamido-2-methyl-1-propanesulfonic acid and salts thereof are preferred, and 2-(meth)acrylamido-2-methyl-1-propanesulfonic acid and 2-(meth)acrylamide -2-Methyl-1-propanesulfonic acid sodium salt is more preferred. These compounds may be used alone or in combination of two or more.

The compound represented by the above formula (2) may be either a synthetic product or a commercial product, and commercial products can be obtained from Sigma-Aldrich Japan LLC, Tokyo Kasei Kogyo Co., Ltd., etc.

In formula (3) above, R ³¹ is a hydrogen atom or a methyl group.

In formula (3) above, R ³² is a single bond or a linear or branched alkylene group having 1 to 20 carbon atoms. Here, examples of the alkylene group include methylene group, ethylene group, trimethylene group, propylene group, isopropylene group, butylene group, isobutylene group, sec-butylene group, tert-butylene group, pentamethylene group, hexamethylene group and the like. is mentioned. R ³² is preferably a single bond or a linear or branched alkylene group having 1 to 12 carbon atoms, more preferably a single bond or a linear or branched alkylene group having 1 to 8 carbon atoms. , still more preferably a single bond or a linear or branched alkylene group having 1 to 4 carbon atoms, particularly preferably a single bond.

In the above formula (3), X is selected from the group consisting of a sulfonic acid group (--SO ₃ H), a sulfate group (--OSO ₃ H), a sulfite group (--OSO ₂ H) and a salt group thereof. is preferably selected from the group consisting of a sulfonic acid group, a sulfuric acid group, and a salt group thereof, from the viewpoint of the dissociation degree of the acid (that is, the ease of anionization) and the solvent solubility of the copolymer. A sulfonic acid group or a salt thereof group is more preferable in terms of the availability of the monomer.

Examples of the compound represented by the above formula (3) include vinylsulfonic acid, allylsulfonic acid, methallylsulfonic acid, salts thereof, and the like. These compounds may be used alone or in combination of two or more.

The compound represented by the above formula (3) may be either a synthetic product or a commercial product, and commercial products can be obtained from Asahi Kasei Finechem Co., Ltd., Tokyo Kasei Kogyo Co., Ltd., etc.

In formula (4) above, R ⁴¹ is a hydrogen atom or a methyl group.

In the above formula (4), R ⁴² is a linear or branched alkylene group having 1 to 20 carbon atoms, preferably a linear or branched alkylene group having 1 to 12 carbon atoms, and more A linear or branched alkylene group having 1 to 8 carbon atoms is preferable, and a linear or branched alkylene group having 1 to 6 carbon atoms is more preferable. Here, since specific examples of the alkylene group are the same as those of the above formula (3), description thereof is omitted here.

In the above formula (4), X is selected from the group consisting of a sulfonic acid group (--SO ₃ H), a sulfate group (--OSO ₃ H), a sulfite group (--OSO ₂ H) and a salt group thereof. is preferably selected from the group consisting of a sulfonic acid group, a sulfuric acid group, and a salt group thereof, from the viewpoint of the dissociation degree of the acid (that is, the ease of anionization) and the solvent solubility of the copolymer. A sulfonic acid group or a salt thereof group is more preferable in terms of the availability of the monomer.

Examples of compounds represented by the above formula (4) include 2-sulfoxyethyl vinyl ether, 3-sulfoxy-n-propyl vinyl ether, 2-propene-1-sulfonic acid, 2-methyl-2-propene-1- sulfonic acids, salts thereof, and the like. These compounds may be used alone or in combination of two or more.

Either a synthetic product or a commercially available product may be used as the compound represented by the above formula (4). As a commercially available product, 2-methyl-2-propene-1-sulfonic acid sodium salt manufactured by Tokyo Chemical Industry Co., Ltd. can be used.

In the hydrophilic copolymer of the present invention, the content of structural units derived from the monomer (B) is preferably 0.1 to 99 when the total of structural units derived from all monomers is 100 mol%. mol%, more preferably 0.2 to 90 mol%, still more preferably 0.5 to 80 mol%, particularly preferably 1 to 70 mol%, and most preferably 20 to 60 mol% %, more preferably more than 25 mol % and less than 50 mol %, most preferably more than 28 mol % and less than 40 mol %. Within such a range, the lubricity and solvent solubility are well balanced. The mol % is substantially equivalent to the ratio of the charged amount (mol) of the monomer (B) to the total charged amount (mol) of all the monomers when producing the polymer.

Each structural unit (B) constituting the hydrophilic copolymer may be the same (derived from a single monomer (B)) or different (derived from two or more monomers (B)). There may be.

(monomer (C))
Monomer (C) is a polymerizable monomer having a —Si(R ¹ ) _a (OR ² ) _3-a group. Here, a is an integer from 0 to 2, ie the monomer (C) has at least one silyl ether group (-Si-OR ² ). A silyl ether group produces a silanol group (--Si--OH) when hydrolyzed. The silanol group (R ² = hydrogen atom) of the hydrophilic copolymer or the alkoxy group (-OR ² group) of the hydrophilic copolymer is converted by hydrolysis (hereinafter collectively referred to as “hydrophilic copolymer The coalesced silanol groups and the like” or “silanol groups and the like”) undergo dehydration condensation with hydroxyl groups (—OH) present on the surface of the substrate layer to form chemical bonds. As a result, the hydrophilic copolymer according to the present invention can be firmly immobilized on the surface of a substrate (for example, a material having a hydroxyl group on its surface, such as a metal material or a resin, especially a metal material). In addition, the silanol group etc. of the hydrophilic copolymer undergoes dehydration condensation with a silanol group etc. present in another structural unit (C) to form a siloxane bond (--Si--O--Si-- bond between the structural units (C). ). As a result, the layer (surface lubricating layer) formed using the hydrophilic copolymer according to the present invention has high film strength (high strength of crosslinked structure). Therefore, the layer formed using the hydrophilic copolymer according to the present invention (the surface lubricating layer containing the crosslinked product of the hydrophilic copolymer according to the present invention) is excellent in durability (lubricity maintaining property). The above effects can be achieved particularly remarkably when the monomer (C) has two or more silyl ether groups (a is 0 or 1, especially 0).

The —Si(R ¹ ) _a (OR ² ) _3-a groups present in each structural unit (C) of the hydrophilic copolymer may be the same or different.

In the —Si(R ¹ ) _a (OR ² ) _3-a group, each R ¹ is independently a linear or branched alkyl group having 1 to 20 carbon atoms, It is a linear or branched acyl group, or a linear or branched ether group having 2 to 21 carbon atoms. When a is 2, each R ¹ may be the same or different.

Examples of linear or branched alkyl groups having 1 to 20 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, iso-pentyl group, tert-pentyl group, neopentyl group, n-hexyl group, n-heptyl group, n-octyl group, 2-ethylhexyl group and the like. A linear or branched acyl group of 2 to 21 carbon atoms is represented by -C(=O)-R ³ , where R ³ is a linear or branched acyl group of 1 to 20 carbon atoms. is an alkyl group. A linear or branched ether group having 2 to 21 carbon atoms is represented by —R ⁵ —OR ⁴ , where R ⁴ is a linear or branched chain having 1 to 11 carbon atoms. and R ⁵ is a linear or branched alkylene group having 1 to 10 carbon atoms. Here, the alkyl groups for R3 and ^R4 ^are the same as described above. Alkylene groups for ^R5 include methylene, ethylene, trimethylene, triethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, pentylene groups, and the like. is mentioned. Among these, R ¹ is a linear or branched alkyl group having 1 to 4 carbon atoms, a linear or branched acyl group having 2 to 5 carbon atoms (e.g., an acetyl group (-C(=O )CH ₃ ), propionyl group (-C(=O)C ₂ H ₅ ), butyryl group (-C(=O)C ₃ H ₇ ), isobutyryl group (-C(=O)CH(CH ₃ ) ₂ ), valeryl group (-C(=O)C ₄ H ₉ ), isovaleryl group (-C(=O)CH ₂ CH(CH ₃ ) ₂ ), pivaloyl group (-C(=O)C(CH ₃ ) ₃ )), or straight or branched chain ether groups of 2 to 5 carbon atoms (e.g., —CH ₂ OCH ₃ , —C ₂ H ₄ OCH ₃ , —C ₃ H ₆ OCH ₃ , —CH ₂ OC ₂ H ₅ , —C ₂ H ₄ OC ₂ H ₅ , —C ₃ H ₆ OC ₂ H ₅ ), methyl group, ethyl group, propyl group, isopropyl group, —C ₂ H ₄ OCH ₃ is more preferred, a methyl group or an ethyl group is even more preferred, and a methyl group is particularly preferred.

In the —Si(R ¹ ) _a (OR ² ) _3-a group, each R ² is independently a hydrogen atom, a linear or branched alkyl group having 1 to 20 carbon atoms, or 2 carbon atoms. ∼21 linear or branched acyl groups, or linear or branched ether groups of 2 to 21 carbon atoms. When a is 0 or 1, each R ² may be the same or different. A linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched acyl group having 2 to 21 carbon atoms, or a linear or branched ether group having 2 to 21 carbon atoms, Since it is the same definition as R ¹ above, the explanation is omitted here. Among these, R ² is a linear or branched alkyl group having 1 to 4 carbon atoms (methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group). group), linear or branched acyl groups having 2 to 5 carbon atoms (e.g., acetyl group (-C(=O)CH ₃ ), propionyl group (-C(=O)C ₂ H ₅ ), butyryl group (-C(=O)C ₃ H ₇ ), isobutyryl group (-C(=O)CH(CH ₃ ) ₂ ), valeryl group (-C(=O)C ₄ H ₉ ), isovaleryl group (- C(=O)CH ₂ CH(CH ₃ ) ₂ ), a pivaloyl group (—C(=O)C(CH ₃ ) ₃ )), or a linear or branched ether group having 2 to 5 carbon atoms ( _For _example _, _-CH2OCH3 _, _-C2H4OCH3 _, _-C3H6OCH3 _, _-CH2OC2H5 _, _-C2H4OC2H5 _, _-C3H6OC2H _{_} _{_} _{_} _{_} ₅ ), more preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, or -C ₂ H ₄ OCH ₃ , still more preferably a methyl group or an ethyl group, and a methyl group is particularly preferred.

In the -Si(R ¹ ) _a (OR ² ) _3-a group, a is an integer of 0 to 2, preferably 0 or 1, more preferably 0.

In one embodiment of the present invention, the monomer (C) is a compound represented by the following formula (5) or (6).

In formulas (5) and (6) above, R ⁵¹ is a hydrogen atom or a methyl group.

In formula (5) above, Z ³ is an oxygen atom or —NH—, preferably an oxygen atom (—O—).

In the above formulas (5) and (6), R ⁵² is a single bond or a linear or branched alkylene group having 1 to 12 carbon atoms, preferably a linear or branched chain having 1 to 12 carbon atoms. is an alkylene group of, more preferably a linear or branched alkylene group having 1 to 8 carbon atoms, even more preferably a linear or branched alkylene group having 1 to 6 carbon atoms, still more preferably It is a straight-chain alkylene group having 1 to 3 carbon atoms (methylene group, ethylene group or trimethylene group), and trimethylene group is particularly preferred.

In formulas (5) and (6) above, —Si—(R ⁵³ )(R ⁵⁴ )(R ⁵⁵ ) is —Si(R ¹ ) _a (OR ² ) _3-a . Here, from the viewpoint of further improving durability (lubricity maintaining property) (and lubricity), a in the —Si(R ¹ ) _a (OR ² ) _3-a group is preferably 0 or 1. Preferably, it is 0. That is, R ⁵³ is —OR ² , and R ⁵⁴ and R ⁵⁵ are each independently preferably —R ¹ or —OR ² , more preferably —OR ² . At this time, R ¹ and R ² are the same as defined for R ¹ and R ² in the —Si(R ¹ ) _a (OR ² ) _3-a group, respectively. From the viewpoint of further improving durability (lubricity maintaining property) (further lubricity), R ¹ and R ² each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms (e.g., methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group), linear or branched acyl group having 2 to 5 carbon atoms (e.g., acetyl group ( —C(=O)CH ₃ ), propionyl group (—C(=O)C ₂ H ₅ ), butyryl group (—C(=O)C ₃ H ₇ ), isobutyryl group (—C(=O)CH (CH ₃ ) ₂ ), valeryl group (-C(=O)C ₄ H ₉ ), isovaleryl group (-C(=O)CH ₂ CH(CH ₃ ) ₂ ), pivaloyl group (-C(=O) C(CH ₃ ) ₃ )), or straight or branched chain ether groups containing 2 to 5 carbon atoms (e.g., —CH ₂ OCH ₃ , —C ₂ H ₄ OCH ₃ , —C ₃ H ₆ OCH ₃ , —CH ₂ OC ₂ H ₅ , —C ₂ H ₄ OC ₂ H ₅ , —C ₃ H ₆ OC ₂ H ₅ ), methyl group, ethyl group, propyl group, isopropyl group, —C ₂ H ₄ OCH ₃ is more preferable, a methyl group or an ethyl group is more preferable, and a methyl group is particularly preferable.

Above all, the monomer (C) is preferably a compound represented by the following formula (5), from the viewpoint of further improving durability (lubricity maintaining property) (further lubricity). That is, in a preferred embodiment of the present invention, the polymerizable monomer (C) is represented by the following formula (5).

In the above formula (5), R ⁵¹ is a hydrogen atom or a methyl group; Z ³ is an oxygen atom (—O—) or —NH—; R ⁵² is a linear chain having 1 to 12 carbon atoms or a branched alkylene group; R ⁵³ is —OR ² , and R ⁵⁴ and R ⁵⁵ are each independently —R ¹ or —OR ² , where R ¹ and R ² are Each independently, a linear or branched alkyl group having 1 to 4 carbon atoms, a linear or branched acyl group having 2 to 5 carbon atoms, or a linear or branched chain having 2 to 5 carbon atoms is an ether group of

In one embodiment of the present invention, in the polymerizable monomer (C), R ⁵¹ is a hydrogen atom or a methyl group; Z ³ is an oxygen atom (—O—) or —NH—; R ⁵² is a linear or branched alkylene group having 1 to 6 carbon atoms; R ⁵³ and R ⁵⁴ are each independently —OR ² , wherein R ² is each independently methyl R ⁵⁵ is —R ₁ or —OR ₂ , ^{wherein R 1} _and R ² ^are ^each independently , methyl group, ethyl group, propyl group, isopropyl group, or —C ₂ H ₄ OCH ₃ , represented by the above formula (5).

In one embodiment of the present invention, in the polymerizable monomer (C), R ⁵¹ is a hydrogen atom or a methyl group; Z ³ is an oxygen atom (-O-); R ⁵² is a methylene group , an ethylene group or a trimethylene group; R ⁵³ and R ⁵⁴ are each independently —OR ² , wherein R ² is each independently a methyl group or an ethyl group; R ⁵⁵ is , —R ¹ or —OR ² , wherein R ¹ and R ² are each independently a methyl group or an ethyl group, represented by the above formula (5).

In one embodiment of the present invention, in the polymerizable monomer (C), R ⁵¹ is a hydrogen atom or a methyl group; Z ³ is an oxygen atom (—O—); R ⁵² is a trimethylene group and R ⁵³ , R ⁵⁴ and R ⁵⁵ are each independently a methoxy group (-OR ² , R ² =methyl group), represented by the above formula (5).

Examples of the polymerizable monomer (C) having a —Si(R ¹ ) _a (OR ² ) _3-a group include vinyltrimethoxysilane, dimethylethoxyvinylsilane, dimethoxymethylvinylsilane, diethoxymethylvinylsilane, triethoxy vinylsilane, triisopropoxyvinylsilane, vinyltris(2-methoxyethoxy)silane, trimethoxy(7-octen-1-yl)silane, allyltrimethoxysilane, allyltriethoxysilane, 3-(methoxydimethylsilyl)propyl acrylate, 3- (Methoxydimethylsilyl)propyl methacrylate, 3-(trimethoxysilyl)propyl acrylate (3-(acryloxy)propyltrimethoxysilane), 3-[dimethoxy(methyl)silyl]propyl methacrylate, 3-[dimethoxy(methyl)silyl ] Propyl acrylate, 3-[trimethoxysilyl]propyl methacrylate, 3-[diethoxy(methyl)silyl]propyl methacrylate, 3-[diethoxy(methyl)silyl]propyl acrylate, 3-(triethoxysilyl)propyl methacrylate, 3- (Triethoxysilyl) propyl acrylate, 3-[dimethoxy(methyl)silyl]propyl acrylate, 3-[dimethoxy(methyl)silyl]propyl methacrylate, [dimethoxy(methyl)silyl]methyl methacrylate, [dimethoxy(methyl)silyl]methyl acrylates, 3-(ethoxydimethylsilyl)propyl methacrylate, 3-(ethoxydimethylsilyl)propyl acrylate, (triethoxysilyl)methyl methacrylate, (triethoxysilyl)methyl acrylate and the like. The polymerizable monomer (C) having a —Si(R ¹ ) _a (OR ² ) _3-a group is 3-(methoxydimethylsilyl)propyl acrylate, 3-(methoxydimethylsilyl)propyl methacrylate, 3-( Trimethoxysilyl)propyl acrylate (3-(acryloxy)propyltrimethoxysilane), 3-[dimethoxy(methyl)silyl]propyl methacrylate, 3-[dimethoxy(methyl)silyl]propyl acrylate, 3-[trimethoxysilyl] Propyl methacrylate, 3-[diethoxy(methyl)silyl]propyl methacrylate, 3-[diethoxy(methyl)silyl]propyl acrylate, 3-(triethoxysilyl)propyl methacrylate, 3-(triethoxysilyl)propyl acrylate, 3-[ Dimethoxy(methyl)silyl]propyl acrylate, 3-[dimethoxy(methyl)silyl]propyl methacrylate, [dimethoxy(methyl)silyl]methyl methacrylate, [dimethoxy(methyl)silyl]methyl acrylate, 3-(ethoxydimethylsilyl)propyl methacrylate , 3-(ethoxydimethylsilyl)propyl acrylate, (triethoxysilyl)methyl methacrylate, (triethoxysilyl)methyl acrylate, and 3-(trimethoxysilyl)propyl acrylate (3-(acryloxy)propyltri methoxysilane), 3-[dimethoxy(methyl)silyl]propyl methacrylate, 3-[dimethoxy(methyl)silyl]propyl acrylate, 3-[trimethoxysilyl]propyl methacrylate, 3-[diethoxy(methyl)silyl]propyl methacrylate, 3-[diethoxy(methyl)silyl]propyl acrylate, 3-(triethoxysilyl)propyl methacrylate, 3-(triethoxysilyl)propyl acrylate, 3-[dimethoxy(methyl)silyl]propyl acrylate, 3-[dimethoxy(methyl ) silyl]propyl methacrylate, [dimethoxy(methyl)silyl]methyl methacrylate, [dimethoxy(methyl)silyl]methyl acrylate, (triethoxysilyl)methyl methacrylate, (triethoxysilyl)methyl acrylate, and 3- (trimethoxysilyl) propyl acrylate (3-(acryloxy) propyltrimethoxysilane), 3-[tri Particular preference is given to methoxysilyl]propyl methacrylate, 3-(triethoxysilyl)propyl methacrylate, (triethoxysilyl)methyl methacrylate. The above compounds may be used alone or in combination of two or more.

Either a synthetic product or a commercially available product may be used for the monomer (C). As a commercial product, it can be obtained from Tokyo Chemical Industry Co., Ltd., Sigma-Aldrich Japan LLC, and the like.

In the hydrophilic copolymer of the present invention, the content of structural units derived from the monomer (C) is preferably 0.1 to 40 when the total of structural units derived from all monomers is 100 mol%. mol %, more preferably 0.5 to 30 mol %, still more preferably 1 to 25 mol %, particularly preferably 1.2 to 20 mol %, and most preferably 1.5 to It is 15 mol %, particularly preferably more than 1.5 mol % and less than 10 mol %, and most preferably 2 mol % or more and less than 5 mol %. Within such a range, the hydrophilic copolymer can sufficiently bond with the substrate layer, so the layer formed using the hydrophilic copolymer (surface lubricating layer; hereinafter the same) is A layer (for example, a material having a hydroxyl group on its surface, such as a metal material or a resin, especially a metal material) can be more firmly immobilized on the surface. Further, within such a range, a sufficient amount of the structural units (C) of the surface lubricating layer formed using the hydrophilic copolymer form a siloxane bond (--Si--O--Si-- bond). . Therefore, the surface lubricating layer formed using the hydrophilic copolymer has higher film strength (high strength of crosslinked structure). Therefore, the durability of the surface lubricating layer formed using the hydrophilic copolymer can be further improved. In addition, within such a range, other monomers (monomers (A) and (B)) can be present in sufficient amounts, so that the hydrophilic copolymer can have a sufficient amount of monomers (A). Lubricity and durability, as well as solvent solubility by the monomer (B) can be more effectively improved. The mol% is substantially equivalent to the ratio of the charged amount (mol) of the monomer (C) to the total charged amount (mol) of all the monomers when producing the polymer.

Each structural unit (C) constituting the hydrophilic copolymer may be the same (derived from a single monomer (C)) or different (derived from two or more monomers (C)). There may be.

The hydrophilic copolymer of the present invention contains polymerizable monomers other than the above monomer (A), monomer (B) and monomer (C) ( hereinafter also referred to as “other monomers”). When the hydrophilic copolymer has constitutional units derived from other monomers, examples of other monomers include methyl vinyl ether, ethyl vinyl ether, propyl vinyl ether, acrylic acid, methacrylic acid, and N-methylacrylamide. , N,N-dimethylacrylamide, acrylamide, acryloylmorpholine, N,N-dimethylaminoethyl acrylate, vinylpyrrolidone, 2-methacryloyloxyethylphosphorylcholine, 2-methacryloyloxyethyl-D-glycoside, 2-methacryloyloxyethyl- Examples include D-mannoside and hydroxyethyl methacrylate. In the hydrophilic copolymer of the present invention, the content of structural units derived from other monomers is preferably less than 10 mol% with respect to 100 mol% of the total amount of structural units derived from all monomers, More preferably less than 5 mol%, still more preferably less than 1 mol% (lower limit: more than 0 mol%). Preferably, the hydrophilic copolymer of the present invention contains a structural unit (A) derived from the monomer (A), a structural unit (B) derived from the monomer (B), and a monomer (C) composed of structural units (C) derived from (content of structural units derived from other monomers=0 mol %). The mol% is substantially equivalent to the ratio of the charged amount (mol) of the other monomers to the total charged amount (mol) of all the monomers when producing the polymer.

In one embodiment of the present invention, the hydrophilic copolymer is composed of polymerizable monomer (A), polymerizable monomer (B), polymerizable monomer (C) and other polymerizable monomers. total content of structural units derived from the polymerizable monomer (A), structural units derived from the polymerizable monomer (B) and structural units derived from the polymerizable monomer (C) The amount exceeds 95 mol % with respect to 100 mol % of the total amount of structural units derived from all monomers.

In one embodiment of the present invention, the hydrophilic copolymer is composed of polymerizable monomer (A), polymerizable monomer (B), polymerizable monomer (C) and other polymerizable monomers. total content of structural units derived from the polymerizable monomer (A), structural units derived from the polymerizable monomer (B) and structural units derived from the polymerizable monomer (C) The amount exceeds 99 mol % with respect to 100 mol % of the total amount of structural units derived from all monomers.

In one embodiment of the present invention, the hydrophilic copolymer is composed of a polymerizable monomer (A), a polymerizable monomer (B), and a polymerizable monomer (C).

The terminal of the hydrophilic copolymer according to the present invention is not particularly limited, and is appropriately defined depending on the type of raw material used, but is usually a hydrogen atom. The structure of the copolymer is also not particularly limited, and may be any of random copolymer, alternating copolymer, periodic copolymer and block copolymer.

[Physical properties of hydrophilic copolymer]
The hydrophilic copolymer according to the present invention has excellent solvent solubility, particularly excellent solubility in water, a lower alcohol, or a mixed solvent of water and a lower alcohol. Here, "lower alcohol" refers to alcohols having 1 to 3 carbon atoms, ie methanol, ethanol, n-propanol or isopropanol. As a result, the solvent having low toxicity can be applied to the coating liquid, so that the safety of the operator can be ensured. Furthermore, solvents containing lower alcohols are rapidly removed from the coating film due to their high evaporation rate. Therefore, the drying process can be simplified in the coating of medical devices, and the coating work can be performed quickly. The term "excellent in solvent solubility" means that it dissolves or disperses in the solvent preferably at 1% by weight or more (more preferably 5% by weight or more, particularly preferably 10% by weight or more). At this time, the time required for dissolution or dispersion is preferably within 2 hours.

The weight average molecular weight of the copolymer is preferably several thousand to several million. In the present invention, the "weight average molecular weight" is a value measured by gel permeation chromatography (GPC) using polyethylene glycol as a standard substance.

[Method for producing hydrophilic copolymer]
The method for producing the hydrophilic copolymer according to the present invention is not particularly limited, and known polymerization methods such as radical polymerization, anionic polymerization, and cationic polymerization can be employed, and radical polymerization, which is easy to produce, is preferably used.

In the polymerization method, the above monomer (A), monomer (B), monomer (C), and optionally other monomers are usually stirred together with a polymerization initiator in a polymerization solvent. and a method of copolymerizing by heating.

Although the polymerization temperature is not particularly limited, it is preferably 25 to 100°C, more preferably 30 to 80°C. The polymerization time is also not particularly limited, but preferably 30 minutes to 24 hours, more preferably 1 to 5 hours.

Examples of the polymerization solvent include water; alcohols such as methanol, ethanol, propanol, n-butanol and 2,2,2-trifluoroethanol; polyhydric alcohols such as ethylene glycol, diethylene glycol, propylene glycol and dipropylene glycol; is preferably an aqueous solvent of From the viewpoint of dissolving raw materials used for polymerization, these may be used alone or in combination of two or more.

The concentration of the polymerizable monomer is not particularly limited, but the total solid content (g) of each polymerizable monomer with respect to the polymerization solvent (mL) is preferably 0.05 to 1 g / mL, more preferably 0.1 to 0.5 g/mL. Moreover, the ratio of the preferred charged amount (mol) of each monomer to the total charged amount (mol) of all monomers is as described above.

The reaction solution containing the polymerizable monomer may be degassed before adding the polymerization initiator. The degassing treatment may be performed, for example, by bubbling the reaction solution with an inert gas such as nitrogen gas or argon gas for about 0.5 to 5 hours. During the deaeration treatment, the reaction solution may be heated to about 30 to 100.degree.

Conventionally known polymerization initiators can be used for the production of the copolymer, and are not particularly limited. -Methoxy-2,4-dimethylvaleronitrile), 4,4'-azobis (4-cyanovaleric acid), 2,2'-azobis (2,4-dimethylvaleronitrile) and other azo polymerization initiators; Potassium sulfate (KPS), sodium persulfate, persulfates such as ammonium persulfate, hydrogen peroxide, t-butyl peroxide, oxidizing agents such as methyl ethyl ketone peroxide, sodium sulfite, sodium hydrogen sulfite, ascorbine A redox polymerization initiator or the like in combination with a reducing agent such as an acid can be used.

The blending amount of the polymerization initiator is preferably 0.01 to 10 mol%, more preferably 0.1 to 5 mol%, relative to the total amount (mol) of the polymerizable monomers.

Furthermore, if necessary, chain transfer agents, polymerization rate modifiers, surfactants, and other additives may be used as appropriate during polymerization.

The atmosphere in which the polymerization reaction is carried out is not particularly limited, and it can be carried out in an air atmosphere, an inert gas atmosphere such as nitrogen gas or argon gas. Further, the reaction solution may be stirred during the polymerization reaction.

The copolymer may precipitate during the polymerization reaction. The copolymer after polymerization can be purified by general purification methods such as reprecipitation, dialysis, ultrafiltration and extraction.

The copolymer after purification can be dried by any method such as freeze drying, vacuum drying, spray drying, or heat drying. Drying is preferred.

The ratio of structural units derived from each polymerizable monomer in the obtained copolymer is confirmed by analyzing the peak intensity of the group contained in each structural unit using known means such as NMR and IR. can be done.

The unreacted monomer contained in the resulting copolymer is preferably 0.01% by weight or less with respect to the entire copolymer. The smaller the amount of unreacted monomers, the better (lower limit: 0% by weight). The content of residual monomers can be measured by known means such as high performance liquid chromatography.

<Medical equipment>
The present invention also provides a medical device having a substrate layer and a surface lubricating layer formed on at least a portion of the surface of the substrate layer and containing the above crosslinked hydrophilic copolymer. A hydrophilic copolymer according to the present invention has a structural unit (A) derived from a polymerizable monomer (A) having a sulfobetaine structure. Therefore, the medical device (surface lubricating layer) according to the present invention can exhibit excellent lubricity. Further, the hydrophilic copolymer according to the present invention has structural units (C) derived from polymerizable monomers (C) having a —Si(R ¹ ) _a (OR ² ) _3-a group. Therefore, the surface lubricating layer can be firmly fixed to the surface of the substrate (for example, a material having hydroxyl groups on its surface, such as a metal material or a resin, especially a metal material). In addition, the surface lubricating layer has high film strength (high strength of crosslinked structure). Therefore, the medical device (surface lubricating layer) according to the present invention is excellent in lubricity and durability (lubricity maintaining property). Moreover, the hydrophilic copolymer according to the present invention has a structural unit (B) derived from a polymerizable monomer (B) having a sulfonic acid group/salt or the like. Therefore, the hydrophilic copolymer exhibits good solubility in solvents (particularly water, alcohol, and water/alcohol mixed solvents). Therefore, a layer (surface lubricating layer) can be easily formed on the substrate layer by applying a coating liquid containing a hydrophilic copolymer to the substrate layer.

As used herein, a “crosslinked product of a hydrophilic copolymer” means that the silanol group (R ² =hydrogen atom) of the hydrophilic copolymer or the alkoxy group (—OR ² group) of the hydrophilic copolymer is hydrolyzed. A silanol group (silanol group of a hydrophilic copolymer, etc.) converted by a covalent bond (siloxane bond) with a silanol group of another hydrophilic copolymer, etc. to form a crosslinked structure, and a substrate layer (e.g., It is intended to have a structure that satisfies at least one of (1) and (2) covalent bonding with reactive groups (for example, hydroxyl groups) of inorganic materials such as metals). In particular, when a is 0 or 1, the silanol groups etc. of the hydrophilic copolymer can simultaneously bond with the silanol groups etc. of other hydrophilic copolymers and the reactive groups of the substrate layer. Therefore, a surface lubricating layer containing such a hydrophilic copolymer can increase the film strength and can be firmly fixed on the substrate layer, thereby further improving the durability (lubricity maintaining property).

Hereinafter, preferred embodiments of the medical device according to the present invention will be described with reference to the attached drawings.

FIG. 1 is a partial cross-sectional view schematically showing the layered structure of the surface of a representative embodiment of the medical device (hereinafter also simply referred to as "medical device") according to the present invention. FIG. 2 is a partial cross-sectional view schematically showing a configuration example with a different layered structure on the surface as an application example of the present embodiment. 1 and 2, 1 represents a substrate layer, 1a a core portion of the substrate layer, 1b a surface layer of the substrate, 2 a lubricating layer on the surface, and 10 a medical device.

As shown in FIGS. 1 and 2, in the medical device 10 of the present embodiment, the base layer 1 and at least a part of the base layer 1 are immobilized (in the drawings, the base layer in the drawing 1 and a surface lubricating layer 2 containing a hydrophilic copolymer immobilized on the entire surface (entire surface). The surface lubricating layer 2 is bonded to the substrate layer 1 via the silanol groups of the hydrophilic copolymer or the like.

Each configuration of the medical device of this embodiment will be described below.

(Base material layer (base material))
The substrate layer used in the present embodiment may be composed of any material as long as it can react (for example, dehydration condensation) with a silanol group of a hydrophilic copolymer to form a chemical bond. good. Specifically, the material that constitutes (forms) the base material layer 1 includes metal materials, polymer materials, ceramics, and the like. Here, as shown in FIG. 1, the base layer 1 may be entirely (whole) composed (formed) of any of the above materials, or as shown in FIG. The surface of the base layer core portion 1a composed (formed) of any of the above materials is covered (coated) with any other material by an appropriate method to constitute (form) the base material surface layer 1b. It may have a structure with As an example of the latter case, the surface of the base material layer core portion 1a made of a resin material or the like is coated with a metal material by an appropriate method (plating, metal vapor deposition, sputtering, or other conventionally known method). , a base material surface layer 1b formed; a high-strength material, which is flexible compared to a reinforcing material such as a metal material, is formed on the surface of the base material layer core part 1a formed of a hard reinforcing material such as a metal material or a ceramic material; The molecular material is coated by an appropriate method (a conventionally known method such as immersion (dipping), spraying (spraying), application/printing, etc.), or the reinforcing material of the base material layer core part 1a and the base material surface layer 1b are coated. For example, a base material surface layer 1b is formed by combining with a molecular material (appropriate reaction treatment). Therefore, the base material layer core portion 1a is a multilayer structure formed by laminating different materials in multiple layers, or a structure (composite) in which members formed of different materials for each part of the medical device are joined together. good too. Further, another middle layer (not shown) may be formed between the substrate layer core portion 1a and the substrate surface layer 1b. Furthermore, the substrate surface layer 1b may be a multilayer structure formed by laminating different materials in multiple layers, or a structure (composite) in which members formed of different materials for each part of the medical device are joined together. good.

Among the materials that constitute (form) the base material layer 1, the metal material is not particularly limited, and metal materials that are commonly used for medical devices such as catheters, stents, and guidewires are used. be. Specifically, various stainless steels (SUS) such as SUS304, SUS316, SUS316L, SUS420J2, SUS630, gold, platinum, silver, copper, nickel, cobalt, titanium, iron, aluminum, tin or nickel-titanium (Ni-Ti ) alloy, nickel-cobalt (Ni-Co) alloy, cobalt-chromium (Co-Cr) alloy, zinc-tungsten (Zn-W) alloy, and various other alloys. These may be used individually by 1 type, and may use 2 or more types together. As the metal material, a metal material suitable for use as a base layer for a catheter, stent, guide wire, or the like may be appropriately selected.

In addition, among the materials constituting (forming) the base material layer 1, the polymer material is not particularly limited, and is a polymer commonly used for medical devices such as catheters, stents, and guide wires. material is used. Specifically, polyethylene such as polyamide resin, linear low density polyethylene (LLDPE), low density polyethylene (LDPE), high density polyethylene (HDPE), polyolefin resin such as polypropylene, polyester resin such as polyethylene terephthalate, polystyrene, etc. styrene resin, cyclic polyolefin resin, modified polyolefin resin, epoxy resin, urethane resin, diallyl phthalate resin (allyl resin), polycarbonate resin, fluorine resin, amino resin (urea resin, melamine resin, benzoguanamine resin), acrylic resin, polyacetal resin , vinyl acetate resin, phenol resin, vinyl chloride resin, silicone resin (silicon resin), polyether resin, polyimide resin, and the like. These may be used individually by 1 type, and may use 2 or more types together. As the polymer material, a polymer material suitable for use as a base layer for catheters, stents, guide wires, and the like may be appropriately selected.

Further, the shape of the base material layer is not particularly limited, and may be appropriately selected from a sheet shape, a linear (wire) shape, a tubular shape, or the like, depending on the mode of use.

(Lubricating layer (surface lubricating layer))
The lubricating layer (surface lubricating layer) is carried on at least a part of the substrate layer (substrate) 1 . Here, the reason why the lubricating layer 2 is carried on at least a part of the surface of the base material layer 1 is that medical devices such as catheters, guide wires, and indwelling needles, which are intended for use, are not necessarily used for these medical devices. A lubricating layer not necessarily on all surfaces (entire surface) when wet, but only on parts (some or all) of the surface where the surface is required to be lubricious when wet is carried. Therefore, as described above, the lubricating layer is formed so as to cover both sides of the substrate layer as shown in FIGS. 1 and 2; forms formed; forms formed so as to partially cover both sides of the substrate layer in the same or different forms; forms formed so as to partially cover one side of the substrate layer.

The lubricating layer (surface lubricating layer) essentially contains a hydrophilic copolymer. The lubricating layer may contain other components in addition to the hydrophilic copolymer. Here, other components are not particularly limited. For example, when the medical device is intended to be inserted into a body cavity or lumen such as a catheter, anticancer agents, immunosuppressive agents, antibiotics, antirheumatic agents, antithrombotic agents, HMG-CoA reductase inhibitors, ACE inhibitors, calcium antagonists, antihyperlipidemic agents, integrin inhibitors, antiallergic agents, antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid improving agents, DNA synthesis inhibitors, tyrosine kinase inhibitors, Drugs (physiologically active substances) such as antiplatelet drugs, vascular smooth muscle proliferation inhibitors, anti-inflammatory drugs, bio-derived materials, interferons, and substances promoting NO production, and the like. Here, the amount of other components to be added is not particularly limited, and the amounts normally used are applied in the same manner. Ultimately, the amount of other ingredients to be added is appropriately selected in consideration of the severity of the disease to be applied, the weight of the patient, and the like. Preferably, the lubricating layer does not contain other components (consisting only of the hydrophilic copolymer). That is, in a preferred embodiment of the present invention, the lubricating layer is composed of the hydrophilic copolymer.

[Method for manufacturing medical device]
The method for producing a medical device according to the present invention (method for forming a surface lubricating layer on a substrate layer) is not particularly limited except for using the hydrophilic copolymer described above, and a known method is used in the same manner. Alternatively, it can be appropriately modified and applied. For example, a method of dissolving the hydrophilic copolymer according to the present invention in a solvent to prepare a coating liquid and coating the base layer of the medical device with this coating liquid is preferable. By such a method, it is possible to impart lubricity and durability (lubricating property) to the surface of the medical device.

(Coating process)
In the above method, the solvent used to dissolve the hydrophilic copolymer is the one described in the above [Physical properties of the hydrophilic copolymer] from the viewpoint of work safety (low toxicity). is preferred.

Also, the concentration of the hydrophilic copolymer in the coating liquid is not particularly limited, but is preferably 0.01 to 50% by weight, more preferably 0.05 to 40% by weight, and even more preferably 0. .1 to 30% by weight. Within such a range, the coatability of the coating liquid is good, and the obtained surface lubricating layer has excellent lubricity and durability (lubricity maintaining property). In addition, a uniform surface lubricating layer having a desired thickness can be easily obtained with a single coating, which is preferable in terms of production efficiency. If the concentration of the hydrophilic copolymer is less than 0.01% by weight, it may not be possible to fix a sufficient amount of the hydrophilic copolymer on the surface of the substrate layer. On the other hand, when the concentration of the hydrophilic copolymer exceeds 50% by weight, the viscosity of the coating liquid becomes too high, and it may not be possible to obtain a surface lubricating layer having a uniform thickness. However, even if it deviates from the above range, it can be used sufficiently as long as it does not affect the effects of the present invention.

Before applying the coating liquid, the surface of the substrate layer may be pretreated by ultraviolet irradiation treatment, plasma treatment, corona discharge treatment, flame treatment, oxidation treatment, silane coupling treatment, phosphoric acid coupling treatment, or the like. When the solvent of the coating liquid is only water, it is difficult to apply it to the surface of the hydrophobic base material layer, but the surface of the base material layer is hydrophilized by plasma-treating the surface of the base material layer. As a result, the wettability of the coating liquid to the surface of the substrate layer is improved, and a uniform surface lubricating layer can be formed.

The method of applying the coating liquid to the surface of the substrate layer is not particularly limited, and may be a coating/printing method, an immersion method (dipping method, dip coating method), an atomization method (spray method), a spin coating method, or a mixing method. A conventionally known method such as a solution impregnation sponge coating method can be applied. Among these, the immersion method (dipping method, dip coating method) is preferable.

In addition, when forming a surface lubricating layer on the thin and narrow inner surface of a catheter, stent, guidewire, etc., the base layer may be immersed in a coating liquid to depressurize the inside of the system to degas. By depressurizing and defoaming, the solution can be quickly permeated into the thin and narrow inner surface, and the formation of the surface lubricating layer can be promoted.

Further, when the surface lubricating layer is formed only on a part of the substrate layer, only a part of the substrate layer is immersed in the coating liquid, and the coating liquid is coated on a part of the substrate layer. , a surface lubricating layer can be formed on a desired surface portion of the substrate layer.

If it is difficult to immerse only a part of the base material layer in the coating solution, a suitable member that can attach and detach the surface part of the base material layer that does not need to be formed with a surface lubricating layer in advance. After protecting (coating, etc.) with a material, the base material layer is immersed in the coating liquid, and after coating the base material layer with the coating liquid, the surface part of the base material layer that does not need to form a surface lubricating layer. A surface lubricating layer can be formed on a desired surface portion of the substrate layer by removing the protective member (material) and then reacting it by a heating operation or the like. However, in the present invention, the surface lubricating layer can be formed by appropriately utilizing conventionally known methods without being limited to these forming methods. For example, if it is difficult to immerse only a part of the base material layer in the mixed solution, instead of the immersion method, another coating method (for example, a predetermined surface portion of the medical device, the coating liquid, A coating method using a coating device such as a spray device, bar coater, die coater, reverse coater, comma coater, gravure coater, spray coater, doctor knife, etc.) may be applied. If both the outer surface and the inner surface of the cylindrical device need to have surface lubricating layers due to the structure of the medical device, it is possible to coat both the outer surface and the inner surface at once. An immersion method (dipping method) is preferably used because it can be used.

Through this process, a film of the coating liquid is formed on the base material layer.

(Immobilization step)
The film formed above is subjected to the immobilization step. As a result, the silanol groups and the like of the hydrophilic copolymer undergo dehydration condensation with the hydroxyl groups (--OH) present on the surface of the base material layer to form chemical bonds. Therefore, the hydrophilic copolymer according to the present invention can be firmly immobilized on the surface of a substrate layer (for example, a material having hydroxyl groups on its surface, such as a metal material or a resin, especially a metal material). In addition, the silanol group or the like present in the structural unit (C) of the hydrophilic copolymer undergoes dehydration condensation with the silanol group or the like present in another structural unit (C) to form a siloxane bond ( -Si-O-Si- bond). As a result, the surface lubricating layer formed using the hydrophilic copolymer according to the present invention has high film strength (high strength of crosslinked structure). Therefore, by using the hydrophilic copolymer according to the present invention, it is possible to form a surface lubricating layer having excellent durability (lubricity maintaining property). Also, the surface lubricating layer formed using the hydrophilic copolymer of the present invention (the surface lubricating layer containing the crosslinked product of the hydrophilic copolymer of the present invention) exhibits excellent lubricity.

Before the main immobilization step, the coating may be dried if necessary. Drying conditions are not particularly limited as long as the solvent can be removed from the film, and hot air treatment may be performed using a dryer or the like, or natural drying may be performed. Moreover, the pressure conditions during drying are not particularly limited, and drying can be performed under normal pressure (atmospheric pressure), or under increased pressure or reduced pressure. As a drying means (apparatus), for example, an oven, a vacuum dryer, or the like can be used, but in the case of natural drying, no particular drying means (apparatus) is necessary.

The method for immobilizing the hydrophilic copolymer on the surface of the substrate layer is not particularly limited, but for example, a method such as heat treatment can be used. Any heat treatment may be used as long as it can promote the dehydration condensation reaction of the hydrophilic copolymer (formation of chemical bonds with the base material layer and/or siloxane bonds between the structural units (C)). may be appropriately determined according to the material constituting the and the hydrophilic copolymer.

The conditions (reaction conditions) for such heat treatment may be those that allow the desired dehydration condensation reaction to proceed (accelerate). For example, the heat treatment temperature (set temperature of a heating device such as an oven) is preferably 25° C. or higher and 200° C. or lower, more preferably 50° C. or higher and 150° C. or lower. The heat treatment time is, for example, 1 hour or more and 48 hours or less, preferably 3 hours or more and 24 hours or less. Under such conditions, the dehydration-condensation reaction proceeds sufficiently, the surface lubricating layer is more firmly fixed to the substrate layer, and the film strength of the surface lubricating layer can be further improved. The pressure conditions during the heat treatment are not particularly limited, and the heat treatment can be performed under normal pressure (atmospheric pressure) or under increased pressure or reduced pressure. As a heating means (apparatus), for example, an oven, a dryer, a microwave heating apparatus, or the like can be used.

In addition to the above heat treatment, light, electron beams, and radiation can be exemplified, but are not limited to these.

After the heat treatment, the surface of the substrate layer may be washed with a solvent (for example, the solvent used for preparing the coating liquid) to remove unreacted hydrophilic copolymer.

The immobilization of the coating (surface lubricating layer) on the substrate layer and the siloxane bond in the coating (surface lubricating layer) can be confirmed using known analytical means such as FT-IR, XPS, and Raman spectroscopy. For example, it can be confirmed by performing FT-IR measurement after heat treatment and confirming the presence of -Si-O- bonds and siloxane structures (-Si-O-Si-).

According to the above method, in the medical device of the present invention, a surface lubricating layer is formed on the surface of the substrate layer using the hydrophilic copolymer of the present invention. As a result, the medical device according to the present invention can exhibit excellent durability (lubrication maintainability). Moreover, the medical device according to the present invention can exhibit excellent lubricity.

[Use of medical equipment]
The medical device according to the present invention is used in contact with body fluids, blood, etc., and has lubricity on the surface in body fluids and water-based liquids such as physiological saline, improving operability and reducing damage to tissue mucosa. can do Specific examples include catheters, stents, and guidewires used in blood vessels. That is, the medical device according to one embodiment of the invention is a catheter, stent or guidewire. A medical device according to one embodiment of the present invention is a stent or a guidewire. Also shown are the following medical devices:

(a) Catheters inserted or left in the gastrointestinal tract orally or nasally, such as gastric catheters, feeding catheters, tube feeding tubes, etc. (b) Oxygen catheters, oxygen cannulas, endotracheal tubes and cuffs Catheters inserted or left in the respiratory tract or trachea orally or nasally, such as tubes and cuffs of tracheostomy tubes, endotracheal suction catheters, etc. (c) Urethral catheters, urinary catheters, urethral balloon catheters and balloons (d) Catheters inserted or left in various body cavities, organs, tissues such as aspiration catheters, drainage catheters, rectal catheters (e) Indwelling needles, IVH Catheters, thermodilution catheters, angiographic catheters, vasodilation catheters, dilators, introducers, and other catheters inserted or left in blood vessels, or guide wires and stylets for these catheters ( f) Artificial trachea, artificial bronchi, etc. (g) Medical devices for extracorporeal circulation therapy (artificial lungs, artificial hearts, artificial kidneys, etc.) and their circuits.

Although the present invention will be specifically described below with reference to examples, the present invention is not limited by these examples. All parts and percentages in each example are based on weight. Unless otherwise specified, the room temperature storage conditions are all 23° C./55% RH.

<Production of copolymer>
[Production Example 1]
[2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MSPB) 1.82 g (6.5 mmol) manufactured by Sigma-Aldrich Japan G.K., 2-acrylamide-2- manufactured by Sigma-Aldrich Japan G.K. Methyl-1-propanesulfonic acid sodium salt (AMPS (Na)) 50 wt% aqueous solution 1.46 g (3.2 mmol) and Tokyo Chemical Industry Co., Ltd. 3-(acryloxy) propyltrimethoxysilane (in formula (5), R ⁵¹ = hydrogen atom, Z ³ = oxygen atom, R ⁵² = trimethylene group, R ⁵³ to R ⁵⁵ = methoxy group) (APTMSi) 0.070 g (0.3 mmol) in 2,2,2-trifluoroethanol/water (9/1 v/v) was dissolved in 10 mL of a mixed solvent to prepare a reaction solution. Next, this reaction solution was placed in a 30 mL eggplant-shaped flask, oxygen was removed by sufficient nitrogen bubbling, and 3.1 mg ( 0.010 mmol) was added, the vessel was quickly closed, and polymerization was carried out in a water bath at 40°C for 1 hour. Next, by precipitating the polymer in acetone and removing the supernatant by decantation, a copolymer having a composition (constituent unit ratio) (molar ratio) of MSPB:AMPS(Na):APTMSi=65:32:3 was obtained. Polymer A was obtained.

[Production Example 2]
[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MSPB) 2.71 g (9.7 mmol) manufactured by Sigma-Aldrich Japan LLC and 3-(acryloxy) manufactured by Tokyo Chemical Industry Co., Ltd. 0.070 g (0.3 mmol) of propyltrimethoxysilane (in formula (5), R ⁵¹ = hydrogen atom, Z ³ = oxygen atom, R ⁵² = trimethylene group, R ⁵³ to R ⁵⁵ = methoxy group) (APTMSi) A reaction solution was prepared by dissolving in 10 mL of a mixed solvent of 2,2,2-trifluoroethanol/water (9/1 v/v). Next, this reaction solution was placed in a 30 mL eggplant-shaped flask, oxygen was removed by sufficient nitrogen bubbling, and 3.1 mg ( 0.010 mmol) was added, the vessel was quickly closed, and polymerization was carried out in a water bath at 40°C for 1 hour. Next, the polymer was precipitated in acetone, and the supernatant was removed by decantation to obtain a copolymer B having a composition (constituent unit ratio) (molar ratio) of MSPB:APTMSi=97:3.

[Production Example 3]
[2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MSPB) 1.87 g (6.7 mmol) manufactured by Sigma-Aldrich Japan G.K., 2-acrylamide-2- manufactured by Sigma-Aldrich Japan G.K. Methyl-1-propanesulfonic acid sodium salt (AMPS (Na)) 1.51 g (3.3 mmol) of 50 wt% aqueous solution was added to 10 mL of a mixed solvent of 2,2,2-trifluoroethanol/water (9/1 v/v). It was dissolved to prepare a reaction solution. Next, this reaction solution was placed in a 30 mL eggplant-shaped flask, oxygen was removed by sufficient nitrogen bubbling, and 3.1 mg ( 0.010 mmol) was added, the vessel was quickly sealed, and polymerization was carried out in a water bath at 40°C for 1 hour. Next, the polymer is precipitated in acetone, and the supernatant is removed by decantation to obtain a copolymer C having a composition (constituent unit ratio) (molar ratio) of MSPB:AMPS(Na)=67:33. Obtained.

<Solvent solubility test of hydrophilic copolymer>
[Example 1-1, Comparative Example 1-1]
The copolymers A and B obtained in Production Examples 1 and 2 above were evaluated for their solubility in water, methanol, and water/methanol mixed solvents having different mixing ratios. Specifically, each copolymer was added to a concentration of 1% by weight in a solvent (water or a mixed solvent of water and methanol (mixed volume ratio of water:methanol = 7: 3, 5:5, 3:7)) at 25° C., stirred for 2 hours, and visually tested for solubility according to the following criteria. Table 1 shows the results. In Table 1 below, "A/B" indicates the solubility of each copolymer in a mixed solvent of water and methanol (mixing volume ratio of water:methanol=A:B). For example, "10/0" indicates the solubility of each copolymer in water alone, and "7/3" indicates a mixed solvent of water and methanol (mixed volume ratio of water: methanol = 7:3). The solubility of each copolymer is shown.

[Solvent Solubility Judgment Criteria]
○: Dissolves or disperses ×: Neither dissolves nor disperses

<Sliding and durability test>
[Example 1-2]
The copolymer A (corresponding to the hydrophilic copolymer according to the present invention) obtained in Production Example 1 was dissolved in methanol/water (5/5 v/v) to a concentration of 10% by weight, and a coating liquid was prepared. was prepared. Copolymer A was uniformly dissolved and dispersed in the coating liquid.

Next, a plate (15 mm x 150 mm) made of stainless steel (SUS304) was dipped in the coating liquid and pulled up at a speed of 0.1 mm/sec. Next, this SUS plate was placed in a vacuum oven and heated at 130° C. under reduced pressure for 16 hours to obtain a SUS plate (sample A) on which a film of a crosslinked product of copolymer A was formed.

Next, the lubricity and durability (lubrication retention) of the obtained sample A were measured using a friction measuring machine (Handy Tribomaster TL201 manufactured by Trinity Lab Co., Ltd.) 20 shown in FIG. 3 according to the following method. evaluated.

That is, the sample 16 was fixed in a petri dish 12 and immersed in water 17 to a height where the entire sample 16 was immersed. This petri dish 12 was placed on the moving table 15 of the friction measuring machine 20 shown in FIG. A silicon terminal (φ10 mm) 13 was brought into contact with the sample 16, and a load 14 of 200 g was applied to the terminal. A sliding resistance value (gf) was measured when the moving table 15 was horizontally reciprocated 10 times with a sliding distance of 20 mm and a sliding speed of 16.7 mm/sec. By averaging the sliding resistance values during the outward travel from the 1st reciprocation to the 10th reciprocation for each reciprocation and plotting it on a graph as a test force, the change in the sliding resistance value for 10 repeated slidings was evaluated. .

[Comparative Example 1-2]
A coated sample (Sample B) was prepared and A sliding resistance value was measured.

The results of Example 1-2 and Comparative Example 1-2 are shown in FIG. In sample A of Example 1-2, the sliding resistance value hardly changed from 0 to 10 times of sliding, while sample B of Comparative Example 1-2 was slid during the initial sliding. The resistance value increased, suggesting the possibility that the surface of the surface lubricating layer was worn in the initial stage.

From the above results, the surface lubricating layer (including the crosslinked product of the hydrophilic copolymer) formed using the hydrophilic copolymer according to the present invention exhibits excellent lubricity and durability (lubricity maintaining property). It is considered that it can be demonstrated. The above effect is presumed to be due to the fact that the hydrophilic copolymer according to the present invention is firmly immobilized on the surface of the substrate layer, and that the film strength is enhanced by the formation of siloxane bonds between the structural units (C). be.

This application is based on Japanese Patent Application No. 2021-047162 filed on March 22, 2021, the disclosure of which is incorporated herein by reference.

1 base layer,
1a base layer core portion,
1b substrate surface layer,
2 surface lubricating layer,
10 medical devices,
12 Petri dishes,
13 silicon terminals,
14 load,
15 moving table,
16 samples,
17 water,
20 Friction measuring machine.

Claims

a substrate layer;
a surface lubricating layer formed on at least a portion of the surface of the base material layer and containing a crosslinked hydrophilic copolymer;
The hydrophilic copolymer contains a structural unit derived from a polymerizable monomer (A) having a sulfobetaine structure, a sulfonic acid group (--SO 3 H), a sulfate group (--OSO 3 H) and a sulfite group (-- OSO 2 H) and a structural unit derived from a polymerizable monomer (B) having at least one group selected from the group consisting of salt groups thereof, and -Si(R 1 ) a (OR 2 ) 3- a group (R 1 is each independently a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched acyl group having 2 to 21 carbon atoms, or 2 to 21 linear or branched ether groups; each R 2 is independently a hydrogen atom, a linear or branched alkyl group having 1 to 20 carbon atoms, a linear chain having 2 to 21 or a branched acyl group, or a linear or branched ether group having 2 to 21 carbon atoms; a is an integer of 0 to 2). medical devices, including units;
The medical device according to claim 1, wherein the polymerizable monomer (A) is represented by the following formula (1):

In the above formula (1),
R 11 is a hydrogen atom or a methyl group,
Z 1 is an oxygen atom or -NH-,
R 12 and R 15 are each independently a linear or branched alkylene group having 1 to 20 carbon atoms,
R 13 and R 14 are each independently a straight or branched chain alkyl group having 1 to 20 carbon atoms.
The medical device according to claim 1 or 2, wherein the polymerizable monomer (B) is represented by the following formula (2), (3) or (4):

In the above formula (2),
R 21 is a hydrogen atom or a methyl group,
Z 2 is an oxygen atom or -NH-,
R 22 is a linear or branched alkylene group having 1 to 20 carbon atoms,
X is a group selected from the group consisting of a sulfonic acid group (--SO 3 H), a sulfate group (--OSO 3 H) and a sulfite group (--OSO 2 H) and salt groups thereof;

In the above formula (3),
R 31 is a hydrogen atom or a methyl group,
R 32 is a single bond or a linear or branched alkylene group having 1 to 20 carbon atoms,
X is a group selected from the group consisting of a sulfonic acid group (--SO 3 H), a sulfate group (--OSO 3 H) and a sulfite group (--OSO 2 H) and salt groups thereof;

In the above formula (4),
R 41 is a hydrogen atom or a methyl group,
R 42 is a linear or branched alkylene group having 1 to 20 carbon atoms,
X is a group selected from the group consisting of sulfonic acid group (--SO 3 H), sulfate group (--OSO 3 H) and sulfite group (--OSO 2 H) and salt groups thereof.
The medical device according to any one of claims 1 to 3, wherein the polymerizable monomer (C) is represented by the following formula (5):

In the above formula (5),
R 51 is a hydrogen atom or a methyl group,
Z 3 is an oxygen atom or -NH-,
R 52 is a linear or branched alkylene group having 1 to 12 carbon atoms,
R 53 is —OR 2 , R 54 and R 55 are each independently —R 1 or —OR 2 , wherein R 1 and R 2 each independently have 1 carbon atom ∼4 straight or branched chain alkyl groups, straight or branched chain acyl groups of 2 to 5 carbon atoms, or straight or branched chain ether groups of 2 to 5 carbon atoms.
The medical device according to any one of claims 1 to 4, wherein the medical device is a catheter, stent or guidewire.
A structural unit derived from a polymerizable monomer (A) having a sulfobetaine structure, a sulfonic acid group (--SO 3 H), a sulfate group (--OSO 3 H) and a sulfite group (--OSO 2 H), and salts thereof and a —Si(R 1 ) a (OR 2 ) 3-a group (R 1 is each independently a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched acyl group having 2 to 21 carbon atoms, or a linear or branched chain having 2 to 21 carbon atoms; an ether group; each R 2 is independently a hydrogen atom, a linear or branched alkyl group having 1 to 20 carbon atoms, a linear or branched acyl group having 2 to 21 carbon atoms, or a linear or branched ether group having 2 to 21 carbon atoms; a is an integer of 0 to 2). polymer.
The hydrophilic copolymer according to claim 6, wherein the polymerizable monomer (A) is represented by the following formula (1):

In the above formula (1),
R 11 is a hydrogen atom or a methyl group,
Z 1 is an oxygen atom or -NH-,
R 12 and R 15 are each independently a linear or branched alkylene group having 1 to 20 carbon atoms,
R 13 and R 14 are each independently a straight or branched chain alkyl group having 1 to 20 carbon atoms.
The hydrophilic copolymer according to claim 6 or 7, wherein the polymerizable monomer (B) is represented by the following formula (2), (3) or (4):

In the above formula (2),
R 21 is a hydrogen atom or a methyl group,
Z 2 is an oxygen atom or -NH-,
R 22 is a linear or branched alkylene group having 1 to 20 carbon atoms,
X is a group selected from the group consisting of a sulfonic acid group (--SO 3 H), a sulfate group (--OSO 3 H) and a sulfite group (--OSO 2 H) and salt groups thereof;

In the above formula (3),
R 31 is a hydrogen atom or a methyl group,
R 32 is a single bond or a linear or branched alkylene group having 1 to 20 carbon atoms,
X is a group selected from the group consisting of a sulfonic acid group (--SO 3 H), a sulfate group (--OSO 3 H) and a sulfite group (--OSO 2 H) and salt groups thereof;

In the above formula (4),
R 41 is a hydrogen atom or a methyl group,
R 42 is a linear or branched alkylene group having 1 to 20 carbon atoms,
X is a group selected from the group consisting of sulfonic acid group (--SO 3 H), sulfate group (--OSO 3 H) and sulfite group (--OSO 2 H) and salt groups thereof.
The hydrophilic copolymer according to any one of claims 6 to 8, wherein the polymerizable monomer (C) is represented by the following formula (5):

In the above formula (5),
R 51 is a hydrogen atom or a methyl group,
Z 3 is an oxygen atom or -NH-,
R 52 is a linear or branched alkylene group having 1 to 12 carbon atoms,
R 53 is —OR 2 , R 54 and R 55 are each independently —R 1 or —OR 2 , wherein R 1 and R 2 each independently have 1 carbon atom ∼4 straight or branched chain alkyl groups, straight or branched chain acyl groups of 2 to 5 carbon atoms, or straight or branched chain ether groups of 2 to 5 carbon atoms.