JP2007325639A - Catheter tube - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a catheter tube having excellent lubricity and blood compatibility (biological compatibility) within the body cavity which is strongly coated (covered) with a hydrophilic polymer presenting lubricity when being wet or a functional polymer having excellent blood compatibility (biological compatibility) that allows the catheter tube to maintain its function even when the tube comes into contact with the blood or the living tissue. <P>SOLUTION: The catheter tube 1 comprises an outer layer 3 and an inner layer 2. The outer surface of the outer layer is coated (covered) with a hydrophilic polymer or a functional polymer with excellent blood compatibility (biological compatibility). A material forming the outer layer has high adhesiveness to such polymers than a material forming the inner layer. In addition, one of the outer layer or the inner layer is made of a material containing a thermoplastic elastomer as a main component and the other is made of a material containing a non-resilient material having compatibility with the thermoplastic elastomer as a main component. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

The present invention relates to a catheter tube whose outer surface is coated with a hydrophilic polymer or a functional polymer excellent in blood compatibility or biocompatibility.
Furthermore, the present invention also provides a catheter tube body and a surface lubrication layer comprising a hydrophilic polymer that exhibits a lubricity when wet coated on the outer surface of the catheter tube body or blood or biological tissue. The present invention relates to a catheter tube having a surface blood (bio) compatible layer provided with a functional polymer excellent in blood compatibility or biocompatibility having an effect that does not impair the function as a catheter tube.
The present invention also relates to a catheter tube having a structure in which the outer surface of the inner tube is fixed (fused) to the inner surface and / or the outer surface of the outer tube, such as a rapid exchange type catheter tube.

In general, the catheter tube has rigidity suitable for each part of the catheter tube for the purpose of reducing tissue damage such as blood vessels and improving operability for accessing the target site. The physical properties of these are finely adjusted.
As a method for preparing the physical properties, a material obtained by blending a relatively soft material such as an elastomer and a material having relatively high rigidity is often used, and physical properties required for each part (for example, bending rigidity, Depending on the torsional rigidity or the like, the blend ratio of the blend is also changed in each part of the catheter tube.

On the other hand, in order to increase the passage of blood vessels and the like into body cavities, a method of coating the outer surface of the tube body of the catheter tube with a hydrophilic polymer that exhibits lubricity when wet is used.
In addition, adhesion and activation of platelets on the surface of the catheter tube leads to a decrease in the function of the catheter tube and the generation of a thrombus in the living body. Therefore, even if it comes into contact with blood or living tissue, the function as the catheter tube is impaired. The functional polymer excellent in blood compatibility or biocompatibility so as not to adversely affect the living body has been used.

  A catheter tube coated with a hydrophilic polymer or a functional polymer excellent in blood compatibility or biocompatibility may be subjected to high friction when it is advanced in a thin and winding blood vessel or a guiding catheter. It must be ensured that the coating does not easily peel off. The hydrophilic polymer from the catheter tube surface, or the functional polymer excellent in blood compatibility or biocompatibility is desorbed, peeled off, or eluted, which is problematic in terms of safety and sustainability of the effect. is there. Therefore, it is required that the hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility is stably fixed on the outer surface of the tube body without easily peeling off on the surface of the substrate. The

With respect to the above requirement, in Patent Document 1, a polymer solution containing a mixture of a hydrophilic polymer having a reactive functional group in the molecule and a polymer having a functional group capable of reacting with the reactive functional group is used as a substrate surface. A medical device is disclosed in which a surface lubricant layer is formed on the surface of a base material by impregnating the polymer with each other and then reacting polymers to form a crosslinked structure to insolubilize the polymer.
Even with a medical device such as Patent Document 1, the surface lubricating layer can be fixed to the equipment to some extent firmly, but a coating material and a coating method that can be more firmly fixed are desired.

JP-A-8-24327

  The present invention relates to a catheter tube prepared with appropriate physical properties (for example, bending rigidity, torsional rigidity, etc.), and a hydrophilic polymer that exhibits lubricity when wet on the catheter tube substrate surface, or blood A functional polymer with excellent blood compatibility or biocompatibility that has an effect that does not impair the function as a catheter tube even when it comes into contact with a living tissue, and is coated with a large amount of a strong functional polymer. Another object is to provide a catheter tube excellent in blood compatibility or biocompatibility.

The object is solved by the present inventions (1) to (29) below.
(1) A catheter tube comprising two layers of an outer layer and an inner layer,
The outer surface of the outer layer is coated with a hydrophilic polymer,
The outer layer forming material has higher adhesion to the hydrophilic polymer than the inner layer forming material, and
One of the materials for forming the outer layer and the inner layer is a material mainly composed of a thermoplastic elastomer, and the other is a material mainly composed of an inelastic material compatible with the thermoplastic elastomer.
(2) A catheter tube comprising two layers of an outer layer and an inner layer,
The outer surface of the outer layer is coated with a functional polymer excellent in blood compatibility or biocompatibility,
The outer layer forming material has higher adhesion to the functional polymer that is superior in blood compatibility or biocompatibility than the inner layer forming material, and
One of the materials for forming the outer layer and the inner layer is a material mainly composed of a thermoplastic elastomer, and the other is a material mainly composed of an inelastic material compatible with the thermoplastic elastomer.
(3) The material for forming the outer layer is more preferable than the material for forming the inner layer.
The catheter tube according to (1), wherein the hydrophilic polymer is highly swellable with respect to a solvent.
(4) The material for forming the outer layer is more preferable than the material for forming the inner layer.
The catheter tube according to (2) above, wherein the functional polymer excellent in blood compatibility or biocompatibility is highly swellable with respect to a solvent.
(5) The catheter tube according to (1) or (3) above, wherein the hydrophilic polymer has a functional group capable of hydrogen bonding with the material forming the outer layer.
(6) The catheter tube according to (2) or (4), wherein the functional polymer excellent in blood compatibility or biocompatibility has a functional group capable of hydrogen bonding with the material forming the outer layer.
(7) One of the materials forming the outer layer and the inner layer is nylon, and the other is nylon elastomer,
Any one of (1), (3) and (5) above, wherein the hydrophilic polymer has a higher order structure in the molecule and the higher order structure of the outer layer forming material in the molecule. Some catheter tubes.
(8) One of the materials forming the outer layer and the inner layer is polyester, and the other is a polyester elastomer,
Any one of (1), (3) and (5) above, wherein the hydrophilic polymer has a higher order structure in the molecule and the higher order structure of the outer layer forming material in the molecule. Some catheter tubes.
(9) One of the materials forming the outer layer and the inner layer is nylon, and the other is nylon elastomer,
(2), wherein the functional polymer having excellent blood compatibility or biocompatibility has the same higher order structure as the higher order structure in the molecule of the outer layer forming material. The catheter tube of either (4) or (6).
(10) One of the materials forming the outer layer and the inner layer is polyester, and the other is a polyester elastomer,
(2), wherein the functional polymer having excellent blood compatibility or biocompatibility has the same higher order structure as the higher order structure in the molecule of the outer layer forming material. The catheter tube of either (4) or (6).
(11) The catheter tube according to (5) or (6) above, wherein the functional group capable of hydrogen bonding is an ester bond or an amide bond.
(12) The catheter tube according to any one of (7) to (10) above, wherein the higher order structure is a linear alkyl group.
(13) The catheter tube according to (12), wherein the linear alkyl group has 4 or more carbon atoms.
(14) The catheter tube according to (12), wherein the linear alkyl group has 8 or more carbon atoms.
(15) The catheter tube including an outer tube and an inner tube that passes through at least a distal end portion of the outer tube, and the outer tube is the catheter tube of any one of (1) to (14). A catheter tube characterized by.
(16) The catheter tube according to (15), wherein at least one of at least a part of the inner surface of the inner tube and at least a part of the outer surface of the inner tube contains an adhesive polymer.
(17) The catheter tube according to (16), wherein at least a part of the outer surface of the outer layer of the outer tube contains an adhesive polymer.
(18) The catheter tube according to (15) or (16) above, wherein at least a part of the inner surface of the inner tube of the outer tube and at least a part of the outer surface of the inner tube are fused.
(19) The catheter tube according to (18), wherein at least a part of the outer surface of the outer tube of the outer tube and at least a part of the outer surface of the inner tube are fused.
(20) The catheter tube according to (15), wherein an intermediate adhesive layer is provided at least at a part between the inner surface of the inner tube and the outer surface of the inner tube.
(21) The catheter tube according to (20), further comprising an intermediate adhesive layer on at least a part between the outer surface of the outer tube and the outer surface of the inner tube.
(22) The catheter tube according to any one of (15) to (21), wherein an inner surface of the inner tube is formed of a low friction material.
(23) The catheter tube as described in (22) above, wherein the low friction material is polyethylene or polypropylene.
(24) The catheter tube according to (22) or (23), wherein an outer surface of the inner tube is formed of a material compatible with at least one of the low friction material and the inner layer of the outer tube. .
(25) The catheter tube according to (24), wherein the outer surface of the inner tube is formed of a material compatible with the outer layer of the outer tube.
(26) Any of the above (15) to (25), wherein the catheter tube includes an expansion body having a distal end portion fixed to the distal end portion of the inner tube and a proximal end portion fixed to the distal end portion of the outer tube. Some catheter tubes.
(27) The catheter tube according to (26), wherein the expansion body is made of a material mainly composed of nylon or nylon elastomer.
(28) The catheter tube according to (26) or (27), wherein at least one of a distal end portion and a proximal end portion of the expansion body is fused to the inner tube or the outer tube.
(29) The catheter tube according to any one of (26) to (28), further including a stent attached to an outer surface of the expansion body.

According to the present invention, a large amount of a hydrophilic polymer or a functional polymer excellent in blood compatibility or biocompatibility can be firmly fixed to the catheter tube surface, and adhesion (peeling resistance) can be improved. It is possible to provide a catheter tube having excellent lubricity in a body cavity, blood compatibility or biocompatibility, and excellent durability.
Furthermore, coupled with the improvement in lubricity and the like, it is possible to provide a catheter tube excellent in insertability into a body cavity, pushability, torque transmission property, and the like.

  The catheter tube of the present invention is a catheter tube comprising two layers of an outer layer and an inner layer, and the outer surface of the outer layer is coated with a hydrophilic polymer or a functional polymer excellent in blood compatibility or biocompatibility. The outer layer forming material has higher adhesion to the hydrophilic polymer or functional polymer excellent in blood compatibility or biocompatibility than the inner layer forming material, and the outer layer and inner layer are formed. One of the materials is a material having a thermoplastic elastomer as a main component, and the other is a material having an inelastic material compatible with the thermoplastic elastomer as a main component.

The catheter tube of the present invention will be described based on a preferred embodiment shown in the accompanying drawings, but the catheter tube of the present invention is not limited to this.
FIG. 1 is a sectional view showing an example in which the catheter tube of the present invention is applied to a balloon catheter. In the balloon catheter 1 shown in FIG. 1, the catheter tube of the present invention is a tube used for the outer tube 3 and has a two-layer structure of an outer layer 3a and an inner layer 3b. A hydrophilic polymer is formed on the outer surface of the outer layer 3a. Or a coating layer 4 coated with a functional polymer excellent in blood compatibility or biocompatibility.
FIG. 2 is a cross-sectional view of the balloon catheter shown in FIG.
As shown in FIG. 1, the balloon catheter 1 includes a catheter tube composed of an inner tube 2, an outer tube 3, and a coating layer 4 and an expansion body (balloon) 5.
In addition, let the upper side of a figure be a front-end | tip part, and let the lower side be a base end part.
The inner tube 2 has a first lumen 21 whose tip is open. The first lumen 21 is a lumen for inserting a guide wire (not shown). The outer tube 3 is provided at a position where the inner tube 2 is inserted into the outer tube 3 and the tip is slightly retracted from the tip of the inner tube 2.
A second lumen 31 is formed by the inner surface of the outer tube 3 and the outer surface of the inner tube 2. The distal end of the second lumen 31 communicates with a base end portion 5b of an expansion body (balloon) 5 described later, and a liquid for containing the expansion body (balloon) 5 (for example, containing an angiographic contrast medium) flows in. Is done. The distal end portion of the outer tube 3 is fixed to the inner tube 2 without closing the second lumen 31.
Specifically, as shown in FIG. 2, the second lumen 31 is fixed by a part of the outer tube 3 and a part of the outer surface of the inner pipe 2 (adhering part 6), and the part 6a not fixed. The inside of the expansion body (balloon) 5 communicates.

  As a method for fixing the inner surface of the outer tube 3 and the outer surface of the inner tube 2, there are a method of fixing by adhesion and a method of fixing by thermal fusion, but it is easy to reduce the diameter by thermal processing after thermal fusion. In addition, heat fusion is preferable because flexibility is easily obtained.

  The expansion body (balloon) 5 has a base end portion 5 b fixed to the distal end portion of the outer tube 3, and a distal end portion 5 a fixed to the distal end portion of the inner tube 2, and the inner surface of the expansion body (balloon) 5 and the inner tube 2. An expansion space 51 is formed between the second lumen 31 and a base end portion 5b of the expansion space 51 via a portion 6a that is not fixed.

The materials for forming the outer layer 3a and the inner layer 3b of the outer tube 3 used in the present invention will be described below.
The material for forming the outer layer 3a of the outer tube 3 has higher adhesion to the hydrophilic polymer or functional polymer having superior blood compatibility or biocompatibility than the material for forming the inner layer 3b. It consists of a combination of a material mainly composed of a thermoplastic elastomer and the other material composed mainly of an inelastic material having compatibility with the thermoplastic elastomer.
If the forming material is used, the adhesion between the outer layer 3a of the outer tube 3 and the hydrophilic polymer, or the functional polymer excellent in blood compatibility or biocompatibility can be enhanced, and they are firmly fixed to each other. be able to.
The main component refers to at least 55 wt% or more of the entire material forming each of the outer layer 3 a and the inner layer 3 b of the outer tube 3, preferably 80 wt% or more, more preferably 90 wt% or more of the entire material. And that the thermoplastic elastomer occupies.

In addition, the combination of the materials for forming the outer layer 3a and the inner layer 3b of the outer tube 3 is formed of a material mainly composed of an inelastic material as one material and the material composed mainly of a thermoplastic elastomer as the other material. Therefore, the physical properties (rigidity) of the entire catheter tube can be made appropriate.
Further, in order to form the outer layer 3a and the inner layer 3b of the outer tube 3 using at least two different materials, these two materials are selected in consideration of physical properties such as hardness and bending elastic modulus of each material, By appropriately adjusting the thickness and thickness ratio of the outer layer 3a and the inner layer 3b of the outer tube 3, a catheter tube having desired physical properties can be produced. Therefore, it is possible to provide a catheter tube excellent in insertability into a body cavity, pushability, torque transmission property, and the like.

  Specific examples of the combination of the non-elastic material and the thermoplastic elastomer include nylon and nylon elastomer, polyester and polyester elastomer, and the like.

In addition, the material for forming the outer layer 3a of the outer tube 3 is a material having a higher swellability with respect to the solvent of the hydrophilic polymer or the functional polymer having superior blood compatibility or biocompatibility than the material forming the inner layer 3b. The more preferable. This is because the higher the solvent swellability is, the higher the adhesion becomes, and the hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility is easily impregnated and fixed more strongly by the outer layer 3b.
Specific examples of the hydrophilic polymer or the functional polymer solvent excellent in blood compatibility or biocompatibility are described later.
Among the forming materials, when the combination of the forming material of the outer layer 3a and the inner layer 3b of the outer tube 3 is a polyester and a polyester elastomer, the polyester elastomer generally has a higher solvent swellability than the polyester. In this case, it is preferable to use a polyester elastomer as the outer layer.

Examples of the nylon include aliphatic nylons such as nylon 6, nylon 66, nylon 610, nylon 612, nylon 11, nylon 12, and nylon 46, and copolymers of these aliphatic nylons.
As the nylon elastomer, for example, a nylon block such as nylon 6, nylon 11, or nylon 12 is used as a hard segment, and a polyether such as polytetramethylene glycol (PTMG) or a polymer such as polyester is used as a block copolymer. In addition, polymer alloys (polymer blend, graft polymerization, random polymerization, etc.) of the above-mentioned nylon and a flexible resin, those obtained by softening the above-mentioned nylon with a plasticizer, It is a concept including these mixtures.

Examples of the polyester include polyethylene terephthalate (PET) and polybutylene terephthalate (PBT).
As the polyester elastomer, there is a block copolymer in which a saturated polyester such as polyethylene terephthalate and polybutylene terephthalate is used as a hard segment, and a polyether such as polytetramethylene glycol (PTMG) or a polymer such as polyester is used as a soft segment. Typically, it is a concept that includes these polymer alloys and those obtained by softening the saturated polyester with a plasticizer or the like, and also a mixture thereof.

  The hydrophilic polymer forming the coating layer 4 or the functional polymer excellent in blood compatibility or biocompatibility is contained in the molecule, and the material forming the outer layer 3a of the outer tube 3 is contained in the molecule. The thing containing the same higher order structure as the higher order structure which has is preferable.

The higher order structure is not particularly limited as long as the outer layer 3a of the outer tube 3 and the hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility interact with each other. The group is preferably exemplified.
The linear alkyl group corresponding to the higher order structure may be bonded to another chemical structure such as a branched alkyl group adjacent to the linear part.
When the higher layer structure of the outer layer 3a of the outer tube 3 and the hydrophilic polymer, or the functional polymer excellent in blood compatibility or biocompatibility is a linear alkyl group, a zigzag structure formed by the linear alkyl group Due to the interaction between the higher-order structures such that they are mutually stuck, the polymer of the material for forming the outer layer 3a and the hydrophilic polymer, or the functional polymer excellent in blood compatibility or biocompatibility are attracted to each other, and the hydrophilicity A polymer or a functional polymer excellent in blood compatibility or biocompatibility can be firmly fixed to the outer surface of the outer layer 3a.
Therefore, a hydrophilic polymer or a functional polymer excellent in blood compatibility or biocompatibility can be firmly fixed to the outer surface of the outer layer 3a of the outer tube 3.
Even if the material for forming the outer layer 3a of the outer tube 3 is a material slightly inferior in swelling property, the outer layer 3a of the outer tube 3 and the hydrophilic polymer, or blood compatibility or biocompatibility are excellent due to the interaction. It is possible to firmly fix the functional polymer.

  If the number of carbon atoms in the linear alkyl group forming the higher order structure of the hydrophilic polymer or functional polymer excellent in blood compatibility or biocompatibility is 4 or more, more preferably 8 or more, It is considered that the interaction (anchoring effect) with the outer layer 3a of the tube 3 can be sufficiently expected.

For example, if the material forming the outer layer 3a of the outer tube 3 is nylon 12, it has a straight chain alkyl group having 11 carbon atoms in its molecule, so that it is a hydrophilic polymer, blood compatible or biocompatible The functional polymer having excellent properties only needs to have a higher order structure including a linear alkyl group having 11 carbon atoms in the same number as the outer layer 3a. The linear alkyl group that forms a higher order structure of a functional polymer that is superior in blood compatibility or biocompatibility may not necessarily have the same number of carbon atoms in the linear alkyl group that forms the higher order structure of the outer layer 3a. Specifically, the number of carbons contained in the linear alkyl group forming the higher order structure of the hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility is higher in the outer layer 3a of the outer tube 3. It may be the same as or less than the number of carbon atoms contained in the structure.
Therefore, when the outer layer 3a of the outer tube 3 is nylon 12, the higher order structure of the hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility is a linear alkyl group having 11 or less carbon atoms. I just need it.
Similarly, when the outer layer 3a of the outer tube 3 is nylon 11, it has a higher order structure containing a straight-chain alkyl group having 10 carbon atoms in the molecule, so that it is a hydrophilic polymer or blood compatible. Or the carbon number of the linear alkyl group contained in the high order structure of the functional polymer excellent in biocompatibility should just be 10 or less.
Similarly, when the outer layer 3a of the outer tube 3 is nylon 610, since it has a higher order structure containing a linear alkyl group having 9 carbon atoms in the molecule, it is a hydrophilic polymer, or blood compatible or The linear alkyl group contained in the higher order structure of the functional polymer having excellent biocompatibility may have 9 or less carbon atoms.
In addition, when the outer layer of the outer tube 3 is nylon 6, since a linear alkyl group having 5 carbon atoms is present in the higher order structure in the molecule, it can be made hydrophilic polymer, blood compatible or biocompatible. If an excellent functional polymer is an acrylate ester or acrylamide polymer having a linear alkyl group having 5 or 4 carbon atoms, these 5 or 4 linear alkyl groups interact with each other. , Adhesion is good.
When the outer layer 3a of the outer tube 3 is a polyester elastomer having polyethylene terephthalate and polybutylene terephthalate as hard segments and polytetramethylene glycol (PTMG) as a soft segment, the number of carbon atoms in the molecule is four. Since a straight-chain alkyl group is present, adhesion is good if the polymer is a hydrophilic polymer containing a straight-chain alkyl group having 4 carbon atoms, or a functional polymer excellent in blood compatibility or biocompatibility.

The hydrophilic polymer means a polymer compound having a water absorption of 1 wt% or more when immersed in physiological saline.
Lubricity that develops on the surface of the catheter tube when wet occurs when the hydrophilic polymer absorbs an aqueous solvent such as physiological saline, buffer solution, and blood. That is, it is considered that water existing on the surface of the catheter tube is caused by expressing a lubricating function by fluid lubrication at the interface in contact with the blood vessel wall. Therefore, the hydrophilic polymer in the present invention preferably has a water absorption rate of 100 wt% or more in the temperature (usually 30 to 40 ° C.) region where the catheter tube is used in order to develop surface lubricity.

Specific examples of the hydrophilic polymer include water-soluble monomers (monomers that absorb the aqueous solvent) such as acrylamide and derivatives thereof, vinylpyrrolidone, acrylic acid, methacrylic acid, and derivatives thereof. It is a polymer compound having a polymer contained as a constituent component.
Specific examples of the water-soluble monomer include, for example, N-methylacrylamide, N, N-dimethylacrylamide, acrylamide, acryloylmorpholine, N, N-dimethylaminoethyl acrylate, vinylpyrrolidone, and 2-chlorooxyethyl. Examples include phosphorylcholine, 2-methacryloyloxyethyl-D-glycoside, 2-methacryloyloxyethyl-D-mannoside, and vinyl methyl ether.
In the polymer containing the above water-soluble monomer as a constituent component, the portion derived from the water-soluble monomer exhibits surface lubricity when wet.

  The ratio of the number of higher-order structures in the molecule and the number of sites that exhibit lubricity when wet may be 1: 1 to 1:50 in the hydrophilic polymer. This is because the hydrophilic polymer and the outer layer 3a of the outer tube 3 can be firmly fixed, and the lubricity of the catheter tube surface can be exhibited well when wet. Among the above ratios, 1:10 to 1:40 is more preferable, and 1:20 to 1:30 is more preferable.

As a method for producing a hydrophilic polymer having a higher order structure, a monomer having a higher order structure and a water-soluble monomer may be copolymerized.
Specifically, for example, in the molecule, a polyoxide having a linear alkyl group and a peroxide group bonded to both ends of the linear alkyl group, and the water-soluble monomer are combined. The method of polymerizing is mentioned.

  The functional polymer excellent in blood compatibility or biocompatibility means a polymer compound that does not impair the function as a catheter tube even when it comes into contact with blood or biological tissue.

Specific examples of the functional polymer excellent in blood compatibility or biocompatibility include, for example, alkoxyalkyl (meth) acrylate, aminoalkyl (meth) acrylate, aminoalkyl (meth) acrylamide, and quaternary thereof. It is a polymer compound having a polymer containing a monomer such as a derivative such as an ammonium salt as a constituent component.
In the polymer containing a monomer such as the above alkoxyalkyl (meth) acrylate as a constituent component, a site derived from the alkoxyalkyl (meth) acrylate or the like exhibits blood compatibility or biocompatibility.

  Examples of the alkoxyalkyl (meth) acrylate include methoxymethyl (meth) acrylate, methoxyethyl (meth) acrylate, methoxypropyl (meth) acrylate, methoxybutyl (meth) acrylate, ethoxymethyl (meth) acrylate, ethoxyethyl (meth) ) Acrylate, ethoxypropyl (meth) acrylate, ethoxybutyl (meth) acrylate, propoxymethyl (meth) acrylate, propoxyethyl (meth) acrylate, propoxypropyl (meth) acrylate, and propoxybutyl (meth) acrylate. Among these, methoxyalkyl (meth) acrylate is preferable from the viewpoint of economy and operability, and 2-methoxyethyl (meth) acrylate is particularly preferable.

  Specific examples of the aminoalkyl (meth) acrylate include aminomethyl (meth) acrylate, aminoethyl (meth) acrylate, aminoisopropyl (meth) acrylate, amino normal butyl (meth) acrylate, and N-methylaminoethyl. (Meth) acrylate, N-ethylaminoisobutyl (meth) acrylate, N-isopropylaminomethyl (meth) acrylate, N-isopropylaminoethyl (meth) acrylate, N-normalbutylaminoethyl (meth) acrylate, N-tertiary Butylaminoethyl (meth) acrylate, N, N-dimethylaminomethyl (meth) acrylate, N, N-dimethylaminoethyl (meth) acrylate, N, N-dimethylaminopropyl (meth) acrylate, N, N-di Tylaminobutyl (meth) acrylate, N-methyl-N-ethylaminoethyl (meth) acrylate, N-methyl-N-butylaminoethyl (meth) acrylate, N, N-diethylaminoethyl (meth) acrylate, N, N -Diethylaminopropyl (meth) acrylate, N, N-dipropylaminoethyl (meth) acrylate, N, N-dipropylaminopropyl (meth) acrylate, N, N-diaminobutylpropyl (meth) acrylate.

  Specific examples of the aminoalkyl (meth) acrylamide include aminomethyl (meth) acrylamide, aminoethyl (meth) acrylamide, aminoisopropyl (meth) acrylamide, amino normal butyl (meth) acrylamide, and N-methylaminoethyl. (Meth) acrylamide, N-ethylaminoisobutyl (meth) acrylamide, N-isopropylaminomethyl (meth) acrylamide, N-isopropylaminoethyl (meth) acrylamide, N-normalbutylaminoethyl (meth) acrylamide, N-tertiary Butylaminoethyl (meth) acrylamide, N, N-dimethylaminomethyl (meth) acrylamide, N, N-dimethylaminoethyl (meth) acrylamide, N, N-dimethylaminopropyl ( T) acrylamide, N, N-dimethylaminobutyl (meth) acrylamide, N-methyl-N-ethylaminoethyl (meth) acrylamide, N-methyl-N-butylaminoethyl (meth) acrylamide, N, N-diethylaminoethyl (Meth) acrylamide, N, N-diethylaminopropyl (meth) acrylamide, N, N-dipropylaminoethyl (meth) acrylamide, N, N-dipropylaminopropyl (meth) acrylamide, N, N-diaminobutylpropyl ( And (meth) acrylamide.

  In the functional polymer excellent in blood compatibility or biocompatibility, the ratio between the number of higher-order structures in the molecule and the number of sites expressing blood compatibility or biocompatibility is 1: 1 to 1. It may be 1:50. With the ratio, the functional polymer excellent in blood compatibility or biocompatibility and the outer layer of the outer tube 3 can be firmly fixed, and blood compatibility or biocompatibility can be improved. Because. In addition, it is more preferable if it is 1: 10-1: 40 among the said ratio, and if it is 1: 20-1: 30, it is still more preferable.

As a method for producing a functional polymer having a higher-order structure and excellent blood compatibility or biocompatibility, a monomer containing a higher-order structure and a monomer excellent in blood compatibility or biocompatibility are copolymerized. Just do it.
Specifically, for example, in the molecule, a linear alkyl group, a polyoxide having a peroxide group bonded to both ends of the linear alkyl group, and a monomer excellent in blood compatibility or biocompatibility , And a method of copolymerizing.

When the hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility has a functional group and structure capable of hydrogen bonding with the material for forming the outer layer 3a of the outer tube 3 in the molecule, By forming a hydrogen bond between the molecule or the functional polymer excellent in blood compatibility or biocompatibility and the outer layer 3a of the outer tube 3, the hydrophilic polymer or blood compatibility or biocompatibility is excellent. The functional polymer and the outer layer 3a of the outer tube 3 can be more firmly fixed.
The functional group and structure capable of hydrogen bonding are not particularly limited, but are preferably an amide bond or an ester bond.
The hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility has a functional group and a structure capable of hydrogen bonding with the material for forming the outer layer 3a of the outer tube 3 in the molecule at the end of the higher-order structure. If so, it is more preferable.
Specifically, when the outer layer 3a of the outer tube 3 is nylon or nylon elastomer having an amide group, a hydrophilic polymer having an ester bond, or a functional polymer excellent in blood compatibility or biocompatibility is used. In the case of a polyester or polyester elastomer having an ester group, a hydrophilic polymer having an amide bond, or a functional polymer excellent in blood compatibility or biocompatibility is preferable.

The hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility is a structure other than a site that expresses a higher order structure and a specific function (surface lubricity, blood compatibility or biocompatibility). May be included.
Specific examples of the structure include the hydrophilic polymer or a functional polymer excellent in blood compatibility or biocompatibility and a physiologically active substance such as an antithrombotic agent, an anticancer agent, an immunosuppressive agent, an antibiotic or insulin. Reactive functional group that functions as an acceptor of the physiologically active substance is mentioned when coating (coating) on (a hydrophilic polymer having a reactive functional group that functions as an acceptor of the physiologically active substance, or blood compatibility) Or a functional polymer with excellent biocompatibility). Specific examples of the reactive functional group that functions as an acceptor for the physiologically active substance include an epoxy group, an acid chloride group, and an aldehyde group.

The hydrophilic polymer having a reactive functional group that functions as an acceptor of the physiologically active substance, or the functional polymer excellent in blood compatibility or biocompatibility is a reactivity that functions as an acceptor of the physiologically active substance. It is a polymer compound having a polymer containing a monomer containing a functional group as a constituent component.
Examples of the monomer containing a reactive functional group that functions as an acceptor for the physiologically active substance include monomers having a reactive heterocyclic ring such as glycidyl acrylate and glycidyl methacrylate, acrylic acid chloride, methacrylic acid chloride, and the like. Examples thereof include a monomer having an acid chloride in the molecule and a monomer having an isocyanate group in the molecule such as acryloyloxyethyl isocyanate.
As a preferable monomer containing a reactive functional group that functions as an acceptor of the physiologically active substance, the functional group is an epoxy group, the reaction is accelerated by heat, and the handling is relatively easy, or glycidyl methacrylate. Is mentioned.

  When the hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility has the higher-order structure and a functional group that functions as an acceptor of the physiologically active substance, The number of functional groups that function as acceptors is preferably 50% or less, and preferably 30% or less, based on the sum of the higher order structure and the number of hydrophilic functional groups or blood compatible functional groups. More preferably, it is more preferably 10% or less.

As a method for producing a hydrophilic polymer having a reactive functional group that functions as an acceptor for the higher-order structure and the physiologically active substance, a monomer containing a higher-order structure and a reactivity that functions as an acceptor for the physiologically active substance are used. A monomer having a functional group may be copolymerized with a water-soluble monomer.
Specifically, for example, in a molecule, a polyalkyl oxide having a linear alkyl group, a peroxide group bonded to both ends of the linear alkyl group, and glycidyl (meth) acrylate, and the water-soluble And a method of copolymerizing with a monomer.

  As a solvent used when coating the hydrophilic polymer or the functional polymer excellent in blood compatibility or biocompatibility on the outer layer 3a of the outer tube 3, the coating (coating) should be performed without any problem. It is not particularly limited as long as it does not impair the function of each functional group, but examples include methyl ethyl ketone, acetone, tetrahydrofuran, dioxane, dimethylformamide, alcohols, dimethyl sulfoxide, etc. Can do.

  In the material for forming the inner tube 2 used in the present invention, the inner surface is made of polyethylene such as low-density polyethylene, high-density polyethylene, or linear low-density polyethylene in order to increase the lubricity of the guide wire. It is preferable to use a low friction material such as polypropylene, fluorine resin, or the like. Among these, polyethylene is more preferable, and high-density polyethylene is more preferable.

However, when nylon, nylon elastomer, polyester, or polyester elastomer is used as the material for the inner layer 3b of the outer tube 3, these materials and the material for forming the inner tube 2 are not compatible and cannot be fused.
Therefore, it is necessary to form the outer surface of the inner tube 2 and the inner surface of the inner layer 3b of the outer tube 3 with mutually compatible materials. Specifically, a so-called adhesive polymer is contained in at least one forming material of at least a part of the outer surface of the inner tube 2 and at least a part of the inner surface of the inner layer 3b of the outer tube 3. Alternatively, instead of containing the adhesive polymer in the outer tube 3 and the inner tube 2, an intermediate adhesive layer (not shown) having the adhesive polymer may be provided between the inner tube 2 and the outer tube 3. Furthermore, the inner tube 2 may have a three-layer structure of an outer layer made of a material compatible with an inner layer made of a low friction material, an intermediate adhesive layer, and an inner layer of the outer tube.

As the adhesive polymer, for example, a polyolefin such as polyethylene, polypropylene, and ethylene-vinyl acetate copolymer has a functional group such as unsaturated carboxylic acid such as maleic acid, fumaric acid, cinnamic acid, crotonic acid, and linoleic acid. A modified polyolefin obtained by copolymerizing monomers is preferred. Examples of other adhesive polymers include acid functionalized ethyl vinyl acetate resin, acid functionalized ethylene acrylate polymer, anhydrous functionalized ethyl vinyl acetate copolymer, acid and acrylate functionalized ethyl vinyl acetate resin, anhydrous functionalized ethyl vinyl acetate copolymer, And anhydrous functionalized ethyl vinyl acetate resin.
Further, as the outer surface of the inner tube 2, at least a part of the forming material of the inner layer 3b of the outer tube 3, or a copolymer having the forming material as one component [for example, the inner layer 3b of the outer tube 3 is formed of nylon. In this case, as the material for forming the outer layer of the inner tube 2, a material obtained by blending nylon or a copolymer (block copolymer) containing nylon as one component (for example, a hard segment) with the adhesive polymer may be used. By such blending, the compatibility of the materials forming the layers to be fused together is improved.

  The material for forming the expansion body (balloon) 5 used in the present invention is not particularly limited, but is preferably formed of a material mainly composed of a material compatible with the material for forming the outer tube 3. This is because a compatible material can be easily heat-sealed. If the material of the expansion body (balloon) 5 is incompatible, it is preferable to contain the adhesive polymer in the material.

A stent (not shown) can be attached to the expansion body (balloon) 5. When a stent (not shown) is attached, the expansion body (balloon) 5 is folded and attached to a body portion having substantially the same diameter, and the stent is expanded by the expansion force of the expansion body (balloon) 5. The In addition, the catheter tube equipped with such a stent is also protected by the present invention.
Examples of the stent include a coiled stent, a net-like stent, a tubular stent (for example, a hollow tubular body provided with a large number of pores on its side surface), and the like.
In the case of a self-expanding stent, the material of the stent is, for example, a pseudoelastic metal such as stainless steel, Ni—Ti alloy, Cu—Zn alloy, Ni—Al alloy, tungsten, tungsten alloy, titanium, Various metals such as titanium alloy and tantalum are listed, and it is necessary that the shape can be restored. On the condition that this is satisfied, a relatively high-rigidity polymer material such as polyamide, polyimide, ultra-high molecular weight or high-molecular weight polyolefin (polyethylene, polypropylene, etc.), fluorine-based resin, or the like may be appropriately combined.

In addition, the material for forming the catheter tube of the present invention may contain other additives as long as the function of the present invention is not impaired.
Examples of the additive include pigments, dyes, X-ray contrast agents (barium sulfate, tungsten, bismuth oxide, etc.), heat stabilizers, physiologically active substances, reinforcing agents (glass fiber, carbon fiber, etc. that do not harm the living body) , Talc, mica, viscosity favorite, potassium titanate fiber, etc.), filler (carbon black, silica, alumina, titanium oxide, metal powder, wood powder, rice husk, etc.), heat stabilizer, oxidative degradation inhibitor, UV absorber , Lubricants, mold release agents, crystal nucleating agents, plasticizers, flame retardants, antistatic agents, foaming agents and the like.

  As described above, the balloon catheter 1 to which the catheter tube according to the present invention is applied has been described with reference to the accompanying drawings. However, these are merely examples in which the catheter tube of the present invention is applied. The length, the thickness of the tube wall, the shape and the like are not particularly limited, and can be appropriately selected depending on the purpose of use.

For example, a rapid exchange type catheter as described in JP-A-2005-278684 may be used. In this case, at least a part of the outer surface of the inner tube 2 and at least a part of the inner surface of the outer layer 3a of the outer tube 3 are fixed (fused), and at least a part of the outer surface of the outer tube 3 is fixed (fused). Fusion).
Further, if the materials for forming the outer layer 3a of the outer tube 3 and the inner tube 2 are compatible, at least a part of the inner surface of the inner layer 3b of the outer tube 3 and at least a part of the outer surface of the inner tube can be heat-sealed. In addition, at least a part of the outer surface of the outer layer 3a of the outer tube 3 and at least a part of the outer surface of the inner tube 2 can be heat-sealed. However, if there is no compatibility, the adhesive polymer is contained in at least one forming material of at least a part of the inner surface of the inner layer 3b of the outer tube 3 and at least a part of the outer surface of the inner tube 2, and the outer tube 3, the adhesive polymer is contained in at least a part of the outer surface of the outer layer 3a. Alternatively, instead of containing the adhesive polymer in the outer tube 3 and the inner tube 2, an intermediate adhesive layer (not shown) having the adhesive polymer may be provided between the inner tube 2 and the outer tube 3.

The catheter tube (outer tube 3 in FIG. 1) of the present invention may be a single tube catheter.
The single tube catheter is not particularly limited. For example, a guiding catheter, a contrast catheter, PTCA, PTA, and IABP balloon catheters, ultrasonic catheters, atherectomy catheters, endoscope catheters, The present invention can be applied to various catheters such as indwelling catheters, drug solution administration catheters, and microcatheters, introducer sheaths, and the like.
The guiding catheter has an outer diameter of 1.0 to 3.5 mm, preferably 1.5 to 3.0 mm, and a length of 50 to 130 cm, preferably 80 to 100 cm.
The microcatheter has an outer diameter of 0.3 to 1.5 mm, preferably 0.7 to 1.0 mm, and a length of 50 to 200 cm, preferably 80 to 150 cm.
The introducer sheath has an outer diameter of 1.0 to 4.0 mm, preferably 2.0 to 3.0 mm, and a length of 50 to 300 mm, preferably 100 to 150 mm.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

<Preparation of hydrophilic polymer having a higher order structure having a linear alkyl group having 8 carbon atoms>
After 29.7 g of triethylene glycol was added dropwise to 72.3 g of sebacic acid dichloride at 50 ° C., hydrochloric acid was removed under reduced pressure at 50 ° C. for 3 hours, and 22.5 g of the oligoester was added to methyl ethyl ketone 4. 5 g was added, and the mixture was added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of a surfactant dioctyl phosphate, and 120 g of water, and reacted at −5 ° C. for 20 minutes.
The reaction product is washed with water and washed with methanol, and then dried to obtain a polyperoxide having a linear alkyl group having 8 carbon atoms and a peroxide group bonded to both ends of the alkyl group in the molecule. Obtained. 0.5 g of this polyperoxide was used as an initiator, 9.5 g of glycidyl methacrylate (GMA), and 30 g of benzene as a solvent, and polymerization was carried out with stirring at 80 ° C. for 2 hours under reduced pressure.
The reaction product was purified by using diethyl ether as a poor solvent and tetrahydrofuran as a good solvent to obtain polyglycidyl methacrylate (PPO-GMA) having a plurality of peroxide groups in the molecule. Subsequently, 9.0 g of PPO-GMA was charged with 9.0 g of dimethylacrylamide and 90 g of dimethyl sulfoxide as a solvent. After sealing under reduced pressure, the mixture was heated to 80 ° C. and subjected to a polymerization reaction for 18 hours.
After the reaction, the poor solvent is purified with diethyl ether and the good solvent is tetrahydrofuran, and a hydrophilic polymer having a higher-order structure having a linear alkyl group having 8 carbon atoms [block of dimethylacrylamide (DMAA) -glycidyl methacrylate (GMA) Copolymer P (DMAA-b-GMA)] was obtained. The structure of this polymer was identified by NMR and IR measurements.

化１に示す構造において、ＤＭＡＡが湿潤時に潤滑性を発現する部位であり、炭素数８の直鎖のアルキル基が高次構造であり、前記アルキル基の両末端に形成されたエステル結合がチューブ基材（外層）の形成材料（例えば、アミド結合）と水素結合可能な官能基である。ＧＭＡのエポキシ基は、生理活性物質のアクセプターとして機能する反応性官能基である。

In the structure shown in Chemical Formula 1, DMAA is a site that exhibits lubricity when wet, linear alkyl groups having 8 carbon atoms have a higher order structure, and ester bonds formed at both ends of the alkyl groups are tubes. It is a functional group capable of hydrogen bonding with a material for forming a base material (outer layer) (for example, amide bond). The epoxy group of GMA is a reactive functional group that functions as an acceptor for a physiologically active substance.

<Evaluation of slidability and peel resistance of a single-layer tube coated with a hydrophilic polymer having a higher order structure having a linear alkyl group having 8 carbon atoms>
[Example 1]
Nylon 12 (manufactured by EMS Japan Co., Ltd., grill amide L16 grade) was extruded by a conventional method to produce a single-layer tube having an outer diameter of 1.0 mm and an inner diameter of 0.7 mm.
The single-layer tube is dissolved in 2.5 parts by weight of a hydrophilic polymer [P (DMAA-b-GMA)] having a higher-order structure having a linear alkyl group having 8 carbon atoms and 97.5 parts by weight of tetrahydrofuran. Dipped in the coating solution for 5 seconds, pulled up from the solution at a rate of 3000 mm / min from one end of the single-layer tube, dried at 80 ° C. for 60 minutes, and the linear alkyl group having 8 carbon atoms on the outer surface. A single-layer tube coated with a hydrophilic polymer [P (DMAA-b-GMA)] having a higher-order structure having the following structure was obtained.
A single-layer tube coated with a hydrophilic polymer [P (DMAA-b-GMA)] having a higher-order structure having a straight-chain alkyl group having 8 carbon atoms, and the carbon number 8 being a comparison thereof. Using a single-layer tube 10 that is not coated (coated) with a hydrophilic polymer having a higher-order structure having an alkyl group, a slidability test, evaluation of peel resistance, and measurement of a swelling rate were performed.

(Slidability test method)
As shown in FIG. 3, water 9 is put on the upper side of the valve body 8 of the sliding resistance measuring jig 7, a single-layer tube 10 is inserted into the valve body 8, and an autograph is used under the following conditions. The sliding resistance value when sliding 50 times repeatedly was measured.
・ Stroke: 20mm
・ Speed: 500mm / min
-Holding core: Stylet φ0.38
・ Valve: A silicon plate (Dow Corning Q7-4735 Thickness 1.3mm) with a 24G needle. As an indicator of slidability (surface lubricity), sliding resistance value after 50 tests In addition, a change in sliding resistance value (Δ sliding resistance value) was calculated using the following formula as a continuous index of lubricity.
ΔSliding resistance value = (Final sliding resistance value) − (Initial sliding resistance value)

(Evaluation method for peel resistance)
The layer coated with the hydrophilic polymer [P (DMAA-b-GMA)] having a higher-order structure having a linear alkyl group having 8 carbon atoms was evaluated in a peeled state by tactile sensation.

(Measurement method of swelling rate)
The single-layer tube 10 was cut into a sheet of 20 mm × 30 mm × 0.2 mm (the weight at this time is Wo) as a base material and immersed in 25 ml of a solvent (tetrahydrofuran). Immediately after the immersion, the solvent present on the surface was wiped off, the weight change (ΔW) was calculated, and the swelling ratio was calculated based on Equation 1.

[Example 2]
A single-layer tube 10 was made of nylon 11 (manufactured by Atchem Co., Ltd., BESV OA FDA grade) in the same manner as in Example 1, and the same tests and evaluations were performed.

[Example 3]
A single-layer tube 10 was made of nylon elastomer (manufactured by MMS Japan Co., Ltd., Grillamide ELY2694 grade) in the same manner as in Example 1, and the same tests and evaluations were performed. The nylon elastomer has a structure in which the soft segment is PTMG having a linear alkyl group having 4 carbon atoms and the hard segment is nylon 12.

[Comparative Example 1]
A single-layer tube 10 was made of polypropylene (manufactured by Mitsui Oil Industries, Ltd., Hipole F401 grade) in the same manner as in Example 1, and the same tests and evaluations were performed.

[Comparative Example 2]
A single-layer tube 10 was made of polyethylene (manufactured by Nippon Polychem Co., Ltd., Mitsubishi Polyethylene-HD HY540 grade) in the same manner as in Example 1, and the same tests and evaluations were performed.

[Comparative Example 3]
A single-layer tube 10 was produced from a modified polyethylene (Mitchi Chemical Co., Ltd., Modic M512VF grade) in the same manner as in Example 1, and the same tests and evaluations were performed.

Table 1 shows characteristics of various materials of the single-layer tube 10. In addition, “existence” of the higher order structure shown in Table 1 has an alkyl group having 8 or more carbon atoms (the number of carbon atoms of the linear alkyl group contained in the higher order structure of the hydrophilic polymer). "Is not having an alkyl group having 8 or more carbon atoms."

  A hydrophilic polymer [P (DMAA] having a higher-order structure having a straight-chain alkyl group having 8 carbon atoms due to slidability and tactile sensation of the single-layer tube 10 produced in Examples 1-3 and Comparative Examples 1-3. -B-GMA)] is shown in Table 2 below, and the results of the swelling ratio when immersed in a tetrahydrofuran (THF) solution are shown in Table 2 below.

As is apparent from the results in Table 2, the material for forming the single-layer tube includes an amide bond capable of an ester bond and a hydrogen bond in the hydrophilic polymer, and a higher-order structure in the molecule of the hydrophilic polymer. In the case of nylon 12 and nylon 11 having the same higher order structure in the forming material, slidability and peel resistance were good.
On the other hand, the material forming the single-layer tube forms an amide bond capable of ester bonding and hydrogen bonding in the hydrophilic polymer, and a higher-order structure that is the same as the higher-order structure in the molecule in the hydrophilic polymer. In the case of polypropylene, polyethylene, and modified PE that are not included in the material, the slidability and peel resistance are poor.

  Nylon elastomer has the same higher order structure as nylon 12, but due to the presence of soft segments, the proportion of higher order structure to be incorporated in the molecule is smaller than that of nylon alone (nylon 12 homopolymer). For this reason, since the ratio of the higher order structure made into the polymer material which comprises a base material layer is small compared with nylon 12 and nylon 11, it is inferior to surface lubricity and peeling resistance compared with nylon 12 and nylon 11. However, it can be said that the surface lubricity and the peel resistance are excellent as compared with polypropylene or the like having no higher order structure.

The strong peel resistance of the nylon 12 is such that the hydrophilic polymer [P (DMAA-b-GMA)] having a higher order structure having a linear alkyl group having 8 carbon atoms has 8 carbon atoms. Each of the alkyl groups has a specific affinity for a higher-order structure constructed by the alkyl group having 11 carbon atoms in nylon 12, and the single-layer tube 10 formed of nylon 12 has a straight line having the carbon number of 8 above. The hydrophilic polymer having a higher-order structure having a chain alkyl group is strongly attracted, and as a result, the hydrophilic polymer having a higher-order structure having a larger amount of the linear alkyl group having 8 carbon atoms per unit area. It is thought that it adheres and is fixed to the surface of the single-layer tube 10 and has high coverage (adhesion, peel resistance).
Further, the ester group contained in the molecule of the hydrophilic polymer [P (DMAA-b-GMA)] having a higher-order structure having a linear alkyl group having 8 carbon atoms is made of nylon 12 from polyolefins such as polyethylene and polypropylene. Further, it is considered that hydrogen bonds with amide groups of polyamide-based resins such as nylon 11 are strongly attracted.

<Preparation of a hydrophilic polymer having a higher order structure having a linear alkyl group having 4 carbon atoms>
After 29.7 g of triethylene glycol was added dropwise to 72.3 g of adipic acid at 50 ° C., hydrochloric acid was removed under reduced pressure at 50 ° C. for 3 hours, and 2 g of oligoester was added to 4.5 g of methyl ethyl ketone. The solution was added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of a surfactant dioctyl phosphate and 120 g of water, and reacted at −5 ° C. for 20 minutes.
The reaction product is washed with water and washed with methanol, and then dried to obtain a polyperoxide having a linear alkyl group having 4 carbon atoms and a peroxide group bonded to both ends of the alkyl group in the molecule. Obtained. 0.5 g of this polyperoxide was used as an initiator, 9.5 g of glycidyl methacrylate (GMA), and 30 g of benzene as a solvent, and polymerization was carried out with stirring at 80 ° C. for 2 hours under reduced pressure.
The reaction product was purified by using diethyl ether as a poor solvent and tetrahydrofuran as a good solvent to obtain polyglycidyl methacrylate (PPO-GMA) having a plurality of peroxide groups in the molecule. Subsequently, 9.0 g of PPO-GMA was charged with 9.0 g of dimethylacrylamide and 90 g of dimethyl sulfoxide as a solvent. After sealing under reduced pressure, the mixture was heated to 80 ° C. and subjected to a polymerization reaction for 18 hours.
After the reaction, the poor solvent was purified with diethyl ether and the good solvent as tetrahydrofuran, and a hydrophilic polymer having a higher-order structure having a linear alkyl group having 4 carbon atoms [block of dimethylacrylamide (DMAA) -glycidyl methacrylate (GMA) Copolymer P (DMAA-b-GMA)] was obtained. The structure of this polymer was identified by NMR and IR measurements.

化２に示す構造において、ＤＭＡＡが湿潤時に潤滑性を発現する部位であり、炭素数４の直鎖のアルキル基が高次構造であり、前記アルキル基の両末端に形成されたエステル結合がチューブ基材（外層）の形成材料（例えば、アミド結合）と水素結合可能な官能基である。ＧＭＡのエポキシ基は、生理活性物質のアクセプターとして機能する官能基である。

In the structure shown in Chemical Formula 2, DMAA is a site that exhibits lubricity when wet, linear alkyl groups having 4 carbon atoms have a higher order structure, and ester bonds formed at both ends of the alkyl groups are tubes. It is a functional group capable of hydrogen bonding with a material for forming a base material (outer layer) (for example, amide bond). The epoxy group of GMA is a functional group that functions as an acceptor of a physiologically active substance.

<Evaluation of slidability and peel resistance of a single-layer tube coated with a hydrophilic polymer having a higher order structure having a linear alkyl group having 4 carbon atoms>

[Example 4]
Nylon 12 (manufactured by EMS Japan Co., Ltd., grill amide L16 grade) was extruded by a conventional method to produce a single-layer tube having an outer diameter of 1.0 mm and an inner diameter of 0.7 mm.
This single-layer tube was dissolved in 2.5 parts by weight of a hydrophilic polymer [P (DMAA-b-GMA)] having a higher order structure having a linear alkyl group having 4 carbon atoms and 97.5 parts by weight of tetrahydrofuran. Dipped in the coating solution for 5 seconds, pulled up from the solution at a rate of 3000 mm / min from one end of the single-layer tube, dried at 80 ° C. for 60 minutes, and the linear alkyl group having 4 carbon atoms on the outer surface. A single-layer tube coated with a hydrophilic polymer [P (DMAA-b-GMA)] having a higher-order structure having the following structure was obtained.
The single-layer tube 10 coated with the hydrophilic polymer [P (DMAA-b-GMA)] having a higher-order structure having a linear alkyl group having 4 carbon atoms, and the carbon number as a comparison thereof. Using the single-layer tube 10 that is not coated with a hydrophilic polymer having a higher-order structure having 4 linear alkyl groups, the above-described slidability test, evaluation of peel resistance, and measurement of swelling rate Was done in the same way.

[Example 5]
A single-layer tube 10 was made of nylon elastomer (manufactured by MMS Japan Co., Ltd., Grillamide ELY2694 grade) in the same manner as in Example 4, and the same tests and evaluations were performed. The nylon elastomer has a structure in which the soft segment is PTMG having an alkyl group having 4 carbon atoms and the hard segment is nylon 12.
[Example 6]
A single-layer tube 10 was made of polyester (PET) (manufactured by Nippon Unipet Co., Ltd., Unipet RT553CN grade) in the same manner as in Example 4, and the same tests and evaluations were performed.

[Example 7]
A single-layer tube 10 was produced from a polyester elastomer (Toyobo Co., Ltd., Perprene P80B grade) in the same manner as in Example 4, and the same tests and evaluations were performed. In addition, the structure of the said polyester elastomer is PTMG in which the soft segment as shown in Chemical Formula 3 has an alkyl group having 4 carbon atoms, and the hard segment is polyethylene terephthalate.

[Comparative Example 4]
A single-layer tube 10 was made of polypropylene (manufactured by Mitsui Oil Industries, Ltd., Hipole F401 grade) in the same manner as in Example 4, and the same tests and evaluations were performed.

[Comparative Example 5]
A single-layer tube 10 was produced from polyethylene (manufactured by Nippon Polychem Co., Ltd., Mitsubishi Polyethylene-HD HY540 grade) in the same manner as in Example 4, and the same tests and evaluations were performed.

[Comparative Example 6]
A single-layer tube 10 was made of modified polyethylene (Mitchi Chemical Co., Ltd., Modic M512VF grade) in the same manner as in Example 4, and the same tests and evaluations were performed.

Table 3 shows the characteristics of the structures of Examples 4 to 7 and Comparative Examples 4 to 6. In addition, “present” of the higher order structure shown in Table 3 has an alkyl group having 4 or more carbon atoms (the number of carbon atoms of the linear alkyl group contained in the higher order structure of the hydrophilic polymer), and “none” “Has no alkyl group having 4 or more carbon atoms”.

  Hydrophilic polymer [P (DMAA) having a higher-order structure having a linear alkyl group having 4 carbon atoms due to slidability and tactile sensation of the single-layer tube 10 produced in Examples 4 to 7 and Comparative Examples 4 to 6. -B-GMA)] in the peeled state and the results of the swelling rate during immersion in the tetrahydrofuran (THF) solution are shown in Table 4 below.

As a result of Table 4, the single-layer tube made of nylon 12 and polyester elastomer is covered with a hydrophilic polymer having a higher-order structure having a linear alkyl group having 4 carbon atoms (adhesion, peel resistance). I understand that is good.
On the other hand, the material forming the single-layer tube forms an amide bond capable of ester bonding and hydrogen bonding in the hydrophilic polymer, and a higher-order structure that is the same as the higher-order structure in the molecule in the hydrophilic polymer. In the case of polypropylene, polyethylene, and modified PE that are not included in the material, the slidability and peel resistance are poor.
Nylon elastomer has the same higher order structure as nylon 12, but due to the presence of soft segments, the proportion of higher order structure to be incorporated in the molecule is smaller than that of nylon alone (nylon 12 homopolymer). For this reason, since the ratio of the higher order structure made into the polymeric material which comprises a base material layer is small compared with nylon 12, it is inferior to surface lubricity and peeling resistance compared with nylon 12. However, it can be said that the surface lubricity and the peel resistance are excellent as compared with polypropylene or the like having no higher order structure.

In addition, since the polyester elastomer has high swellability with respect to a solvent (tetrahydrafuran) as compared with other materials, the hydrophilic property of the polyester elastomer is easy to enter the substrate. Therefore, it is considered that the hydrophilic polymer is firmly fixed on the tube base material, and the covering property (adhesion property, peel resistance) is enhanced.
In addition, since the polyester elastomer has the same higher order structure as the hydrophilic polymer, the interaction between these higher order structures and the solvent swellability are combined, and the peel resistance is higher than that of the polyester. Conceivable.
From the above, as the combination of the material of the outer layer and the inner layer of the catheter tube, when the nylon and the nylon elastomer are used, the former is preferably the outer layer, and when the polyester is the polyester elastomer, the latter is preferably the outer layer. .

<Preparation of functional polymer having a higher-order structure having a linear alkyl group having 8 carbon atoms and excellent in blood compatibility or biocompatibility>
After 29.7 g of triethylene glycol was added dropwise to 72.3 g of sebacic acid dichloride at 50 ° C., hydrochloric acid was removed under reduced pressure at 50 ° C. for 3 hours, and 22.5 g of the oligoester was added to methyl ethyl ketone 4. 5 g was added, and the mixture was added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of a surfactant dioctyl phosphate, and 120 g of water, and reacted at −5 ° C. for 20 minutes.
The reaction product is washed with water and washed with methanol, and then dried to obtain a polyperoxide having a linear alkyl group having 8 carbon atoms and a peroxide group bonded to both ends of the alkyl group in the molecule. Obtained. 0.5 g of this polyperoxide was used as an initiator, 9.5 g of glycidyl methacrylate (GMA), and 30 g of benzene as a solvent, and polymerization was carried out with stirring at 80 ° C. for 2 hours under reduced pressure.
The reaction product was purified by using diethyl ether as a poor solvent and tetrahydrofuran as a good solvent to obtain polyglycidyl methacrylate (PPO-GMA) having a plurality of peroxide groups in the molecule. Subsequently, 9.0 g of PPO-GMA was charged with 9.0 g of 2-methoxyethyl acrylate and 90 g of dimethyl sulfoxide as a solvent. After sealing under reduced pressure, the mixture was heated to 80 ° C. and subjected to a polymerization reaction for 18 hours.
After the reaction, the poor solvent is purified by diethyl ether and the good solvent is tetrahydrofuran, and a functional polymer (2-methoxyethyl) having a higher-order structure having a linear alkyl group having 8 carbon atoms and excellent in blood compatibility or biocompatibility. An acrylate (MEA) -glycidyl methacrylate (GMA) block copolymer [P (MEA-b-GMA)]) was obtained. This polymer was confirmed to be a polymer having a block structure shown in Chemical Formula 4 by NMR and IR measurements.

化４に示す構造において、ＭＥＡが血液適合性または生体適合性を発現する部位であり、炭素数８の直鎖のアルキル基が高次構造であり、前記アルキル基の両末端に形成されたエステル結合がチューブ基材（外層）の形成材料と水素結合可能な官能基である。ＧＭＡのエポキシ基は、生理活性物質のアクセプターとして機能する反応性官能基である。

In the structure shown in Chemical Formula 4, MEA is a site that expresses blood compatibility or biocompatibility, a linear alkyl group having 8 carbon atoms has a higher order structure, and esters formed at both ends of the alkyl group The bond is a functional group capable of hydrogen bonding with the forming material of the tube substrate (outer layer). The epoxy group of GMA is a reactive functional group that functions as an acceptor for a physiologically active substance.

<Release resistance of a single-layer tube made of various materials coated with a functional polymer having a higher order structure having a linear alkyl group having 8 carbon atoms and excellent in blood compatibility or biocompatibility; Evaluation of platelet adhesion suppression ability>
[Example 8]
Nylon 12 (manufactured by EMS Japan Co., Ltd., grill amide L16 grade) was extruded by a conventional method to produce a single-layer tube having an outer diameter of 1.0 mm and an inner diameter of 0.7 mm.
The monolayer tube 10 is composed of 2.5 parts by weight of a functional polymer [P (MEA-b-GMA)] having a higher-order structure having a linear alkyl group having 8 carbon atoms and excellent in blood compatibility or biocompatibility. And immersed in a coating solution dissolved in 97.5 parts by weight of tetrahydrofuran for 5 seconds, pulled up from the solution at a rate of 3000 mm / min from one end of the single-layer tube 10, and then dried at 80 ° C. for 60 minutes. Single-layer tube 10 coated with a functional polymer [P (MEA-b-GMA)] having a higher-order structure having a linear alkyl group having 8 carbon atoms and excellent in blood compatibility or biocompatibility Got.

  Single-layer tube 10 coated with a functional polymer [P (DMAA-b-GMA)] having a higher-order structure having a linear alkyl group having 8 carbon atoms and excellent in blood compatibility or biocompatibility. In addition, as a comparison, a homostructure 2-methoxyethyl acrylate polymer (Homo-PMEA) having no higher-order structure having a straight-chain alkyl group having 8 carbon atoms and a functional group capable of hydrogen bonding with a tube base material. The above-mentioned slidability test was performed in the same manner using the above-mentioned single-layer tube coated with and a single-layer tube uncoated (positive control), and then a platelet adhesion test was performed.

(Platelet adhesion test method)
After the slidability test (after sliding 50 times under the same conditions using the same jig as in FIG. 1), positive control (PC), [P (MEA-b-GMA)] and (Homo- The surface of each single-layer tube 10 coated with (PMEA) was contacted with human fresh platelet-rich plasma anticoagulated with sodium citrate for 30 minutes, rinsed with physiological saline, fixed with glutaraldehyde, and 0.5 mm ² The number of platelets adhering to was observed with an electron microscope.

[Example 9]
A single layer tube 10 of nylon 11 (manufactured by Atocum Co., Ltd., BESV OA FDA grade) was produced in the same manner as in Example 8, and the slidability test and the platelet adhesion test were conducted in the same manner.

[Example 10]
A single-layer tube 10 of nylon 610 (manufactured by Toray Industries, Inc., Amilan CM2001 grade) was produced in the same manner as in Example 8, and a slidability test and a platelet adhesion test were conducted in the same manner.

[Example 11]
A single-layer tube 10 was made of nylon 6 (Amilan CM1021FS, manufactured by Toray Industries, Inc.) in the same manner as in Example 8, and the slidability test and the platelet adhesion test were performed in the same manner.

[Example 12]
A single-layer tube 10 was made of nylon elastomer (manufactured by MMS Japan Co., Ltd., Grillamide ELY2694 grade) in the same manner as in Example 8, and the slidability test and the platelet adhesion test were similarly conducted. The nylon elastomer has a structure in which the soft segment is PTMG having a linear alkyl group having 4 carbon atoms and the hard segment is nylon 12.

[Comparative Example 7]
A single-layer tube 10 was made of polypropylene (manufactured by Mitsui Oil Industries, Ltd., Hipole F401 grade) in the same manner as in Example 8, and the slidability test and the platelet adhesion test were performed in the same manner.

[Comparative Example 8]
A single-layer tube 10 was made of polyethylene (manufactured by Nippon Polychem Co., Ltd., Mitsubishi Polyethylene-HD HY540 grade) in the same manner as in Example 8, and the slidability test and the platelet adhesion test were similarly conducted.

[Comparative Example 9]
A single-layer tube 10 was made of modified polyethylene (Mitchi Chemical Co., Ltd., Modic M512VF grade) in the same manner as in Example 8, and the slidability test and the platelet adhesion test were performed in the same manner.

  Table 5 shows the features of the higher-order structures of Examples 8-12 and Comparative Examples 7-9. The “existence” of the higher order structure shown in Table 1 is not less than 8 carbon atoms (the carbon number of the linear alkyl group contained in the higher order structure of the functional polymer having excellent blood compatibility or biocompatibility) It shall have an alkyl group, and “none” shall not have an alkyl group having 8 or more carbon atoms.

  Table 6 shows the evaluation of the platelet adhesion suppression ability of the single-layer tubes 10 produced in Examples 8-12 and Comparative Examples 7-9.

For the single-layer tube 10 coated with Homo-PMEA that does not have an ester bond and a linear alkyl group and a higher-order structure not included in the forming material, the ester bond is formed on the forming material of the single-layer tube 10. Even when nylon 12, nylon 11, nylon 610, nylon 6 or nylon elastomer having a linear alkyl group is used, the coating layer is peeled off from the tube base material by the slidability test. Therefore, the platelet adhesion number became a value not much different from the positive control.
For the single-layer tube 10 coated with a functional polymer [P (MEA-b-GMA)] having a higher-order structure having a linear alkyl group having 8 carbon atoms and excellent in blood compatibility or biocompatibility, Also exhibited platelet adhesion suppression performance (blood compatibility), and among them, when platelets of nylon 12, nylon 11, nylon 610, and nylon elastomer were used as substrates, remarkable platelet adhesion suppression performance was exhibited.
Regarding the results of Nylon 12, Nylon 11, and Nylon 610, the carbon number of the linear alkyl group in the higher-order structure of the tube base material (single layer material) is a function that is excellent in blood compatibility or biocompatibility of the coating layer. It is estimated that the higher-order linear alkyl group contained in the polymer has more than 8 carbon atoms, so that the coating layer is not peeled off, the platelet adhesion number is low, and good blood compatibility can be exhibited. Is done.
In addition, an ester group contained in the molecule of the functional polymer [P (DMAA-b-GMA)] having a higher-order structure having a linear alkyl group having 8 carbon atoms and excellent in blood compatibility or biocompatibility. It is considered that hydrogen bonds with amide groups of polyamide resins such as nylon 12 and nylon 11 are strongly attracted from polyolefins such as polyethylene and polypropylene.

  Nylon elastomer has the same higher order structure as nylon 12, but due to the presence of soft segments, the proportion of higher order structure in the molecule is smaller than that of nylon alone (nylon 12 homopolymer). For this reason, since the proportion of the higher-order structure in the polymer material constituting the base material layer is smaller than that of nylon 12, the surface lubricity and peel resistance are inferior to those of nylon 12. However, it can be said that the surface lubricity and the peel resistance are excellent as compared with polypropylene or the like having no higher order structure.

  From these results, when nylon and nylon elastomer are used as a combination of materials for the outer layer and inner layer of the catheter tube, it is preferable to use nylon as the outer layer.

FIG. 1 is a sectional view showing an example in which the catheter tube of the present invention is applied to a balloon catheter. FIG. 2 is a cross-sectional view of the balloon catheter shown in FIG. FIG. 3 is a cross-sectional view of the sliding resistance measuring jig.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Balloon catheter 2 Inner tube 21 First lumen 3 Outer tube 31 Second lumen 3a Outer tube outer layer 3b Outer tube inner layer 4 Coating layer 5 Expansion body (balloon)
51 Extended space 5a Expanded body (balloon) distal end 5b Expanded body (balloon) proximal end 6 Adhered part 6a Non-adhered part 7 Sliding resistance measuring jig 8 Valve element 9 Water 10 Tube

Claims (29)

A catheter tube consisting of two layers, an outer layer and an inner layer,
The outer surface of the outer layer is coated with a hydrophilic polymer,
The outer layer forming material has higher adhesion to the hydrophilic polymer than the inner layer forming material, and
One of the materials for forming the outer layer and the inner layer is a material mainly composed of a thermoplastic elastomer, and the other is a material mainly composed of an inelastic material compatible with the thermoplastic elastomer. A catheter tube consisting of two layers, an outer layer and an inner layer,
The outer surface of the outer layer is coated with a functional polymer excellent in blood compatibility or biocompatibility,
The outer layer forming material has higher adhesion to the functional polymer that is superior in blood compatibility or biocompatibility than the inner layer forming material, and
One of the materials for forming the outer layer and the inner layer is a material mainly composed of a thermoplastic elastomer, and the other is a material mainly composed of an inelastic material compatible with the thermoplastic elastomer. The material forming the outer layer is more preferable than the material forming the inner layer.
The catheter tube according to claim 1, wherein the hydrophilic polymer is highly swellable with respect to a solvent. The material forming the outer layer is more preferable than the material forming the inner layer.
The catheter tube according to claim 2, wherein the functional polymer excellent in blood compatibility or biocompatibility is highly swellable with respect to a solvent.   The catheter tube according to claim 1 or 3, wherein the hydrophilic polymer has a functional group capable of hydrogen bonding with a material forming the outer layer.   The catheter tube according to claim 2 or 4, wherein the functional polymer excellent in blood compatibility or biocompatibility has a functional group capable of hydrogen bonding with a material forming the outer layer. One of the materials forming the outer layer and the inner layer is nylon, the other is nylon elastomer,
6. The catheter according to claim 1, wherein the hydrophilic polymer has a higher order structure in the molecule and a higher order structure that the material for forming the outer layer has in the molecule. tube. One of the materials forming the outer layer and the inner layer is polyester, the other is a polyester elastomer,
6. The catheter according to claim 1, wherein the hydrophilic polymer has a higher order structure in the molecule and a higher order structure that the material for forming the outer layer has in the molecule. tube. One of the materials forming the outer layer and the inner layer is nylon, the other is nylon elastomer,
5. The functional polymer excellent in blood compatibility or biocompatibility has a higher order structure in the molecule, which is the same as the higher order structure that the material for forming the outer layer has in the molecule. Or the catheter tube in any one of 6. One of the materials forming the outer layer and the inner layer is polyester, the other is a polyester elastomer,
5. The functional polymer excellent in blood compatibility or biocompatibility has a higher order structure in the molecule, which is the same as the higher order structure that the material for forming the outer layer has in the molecule. Or the catheter tube in any one of 6.   The catheter tube according to claim 5 or 6, wherein the functional group capable of hydrogen bonding is an ester bond or an amide bond.   The catheter tube according to any one of claims 7 to 10, wherein the higher order structure is a linear alkyl group.   The catheter tube according to claim 12, wherein the linear alkyl group has 4 or more carbon atoms.   The catheter tube according to claim 12, wherein the linear alkyl group has 8 or more carbon atoms.   It is the said catheter tube provided with the outer tube and the inner tube which penetrates at least the front-end | tip part of the said outer tube, Comprising: The said outer tube is the catheter tube in any one of Claims 1-14 characterized by the above-mentioned. Catheter tube.   The catheter tube according to claim 15, wherein at least one of at least a part of the inner surface of the inner tube and at least a part of the outer surface of the inner tube contains an adhesive polymer.   The catheter tube according to claim 16, wherein at least a part of the outer surface of the outer layer of the outer tube contains an adhesive polymer.   The catheter tube according to claim 15 or 16, wherein at least a part of the inner surface of the inner tube and at least a part of the outer surface of the inner tube are fused.   The catheter tube according to claim 18, wherein at least part of the outer surface of the outer layer of the outer tube and at least part of the outer surface of the inner tube are fused.   The catheter tube according to claim 15, further comprising an intermediate adhesive layer on at least a part between the inner surface of the inner tube and the outer surface of the inner tube.   21. The catheter tube according to claim 20, further comprising an intermediate adhesive layer on at least a portion between the outer surface of the outer tube and the outer surface of the inner tube.   The catheter tube according to any one of claims 15 to 21, wherein an inner surface of the inner tube is formed of a low friction material.   The catheter tube of claim 22, wherein the low friction material is polyethylene or polypropylene.   The catheter tube according to claim 22 or 23, wherein an outer surface of the inner tube is formed of a material compatible with at least one of the low friction material and the inner layer of the outer tube.   The catheter tube according to claim 24, wherein the outer surface of the inner tube is formed of a material compatible with the outer layer of the outer tube.   The catheter tube according to any one of claims 15 to 25, further comprising an expansion body having a distal end portion fixed to a distal end portion of the inner tube and a proximal end portion fixed to a distal end portion of the outer tube. .   27. The catheter tube according to claim 26, wherein the expansion body is made of a material mainly composed of nylon or nylon elastomer.   The catheter tube according to claim 26 or 27, wherein at least one of a distal end portion and a proximal end portion of the expansion body is fused to the inner tube or the outer tube.   The catheter tube according to any one of claims 26 to 28, further comprising a stent attached to an outer surface of the expansion body.

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