JPH0984871A - Medical tube and manufacture thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve adhesion strength between a first resin layer and a second resin layer by a simple method. SOLUTION: This medical tube 1 is constituted of a laminate of a first resin layer 11 composing an inner layer (inner tube) and a second layer 12 composing an outer layer (outer tube). The first resin layer 11 is, for example, a base layer and the second resin layer 12 is, for example, a ground layer to form a lubricating and/or antithrombotic layer. In the medical tube 1 thus obtained, an interface 13 of the first and second resin layers 11, 12 is bonded by irradiating radiation.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a medical tube and a method for manufacturing the same. More specifically, the present invention relates to various medical catheters such as micro catheters, angiographic catheters, and balloon catheters, or medical tubes applied to a tube material for manufacturing them, and a manufacturing method thereof.

[0002]

2. Description of the Related Art As a tube material for manufacturing a shaft having excellent operability which can be used for a catheter and a balloon which can be expanded and contracted, a tube made of a single layer of resin and a plurality of resins are used. A tube formed by stacking layers is known.

In this case, the adjacent resin layers are adhered to each other with, for example, an adhesive, but the adhesive force at the interface between the resin layers may be weak in whole or in part. Therefore, when the catheter is inserted into a body cavity such as a blood vessel and curved along the body cavity, there is a problem that the interface between the resin layers may peel off. Furthermore, the method of adhering the resin layers to each other with an adhesive has a problem that the number of steps is large and the manufacturing is time-consuming.

Further, medical devices such as catheters to be inserted into the trachea, digestive tract, urethra, blood vessels and other body cavities and tissues,
The surface of the base material of medical devices such as guide wires and tylets inserted into these is coated with a hydrophilic resin for the purpose of preventing damage to the tissue during insertion operation and improving operability by imparting lubricity. Although a treatment is performed, a base intermediate layer may be provided on the base resin layer in order to obtain excellent adhesion with the hydrophilic resin. Also in this case, as described above, if the adhesion between the base resin layer and the base intermediate layer is weak, the interface may peel off.

Further, the hydrophilic resin has an adhesive force due to the binding or cross-linking of the reactive functional group present in the base resin layer or the underlayer intermediate layer to which it is bonded with the hydrophilic group in the hydrophilic resin. However, this adhesion is weak, the hydrophilic resin may be partially peeled off, and there is a problem of poor durability.

There is also a method of obtaining or improving the adhesion between the resin layers by heating, but such a method has the following restrictions. For example, in the case of a catheter having a small diameter such as an angiography catheter or a PTCA catheter or a balloon such as a balloon of a balloon catheter, which is required to have flexibility, as a constituent material thereof,
A polyolefin resin such as low density polyethylene is used, but since the material itself is flexible, it shrinks or deforms due to heating, so that the processing temperature in the manufacturing or assembling process cannot be increased. In particular, for low density polyethylene, it was difficult to avoid heat shrinkage and deformation even by the liquid phase or gas phase plasma grafting method.

[0007]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a medical tube capable of improving the adhesion between the first resin layer and the second resin layer by a simple method of irradiation, and a method of manufacturing the same. To provide a method.

Another object of the present invention is to provide a medical tube capable of improving the adhesion between a third layer such as a lubricating layer or an antithrombogenic layer and its underlying layer, and a method for producing the same. is there.

[0009]

This and other objects are achieved by the present invention which is defined below as (1) to (11).

(1) A medical tube having a first resin layer and a second resin layer, which has a laminated portion where the first resin layer and the second resin layer overlap each other, A medical tube characterized in that in the laminated portion, the first resin layer and the second resin layer are interface-bonded by irradiation of radiation.

(2) The medical tube according to (1) above, wherein the first resin layer is a base material layer and the second resin layer is a functional layer.

(3) The second resin layer is an underlayer, and the third layer is formed on the surface of the underlayer opposite to the base layer. Medical tube.

(4) The medical tube according to the above (3), wherein the third layer is a layer made of a hydrophilic substance and having lubricity when wet.

(5) The medical tube according to the above (3), wherein the third layer is composed of an antithrombotic substance.

(6) The underlayer comprises an acid anhydride, a carboxyl group or a salt thereof, a sulfone group or a salt thereof, an ester group, an epoxy group, an amino group, a phenol group, a hydroxyl group, an acid halide group, an iminocarbonic acid ester group, At least one selected from the group consisting of a halogen atom (group), a diazonium group, an azite group, an isocyanate group, and an aldehyde group.
(3) A layer comprising a resin which directly has a functional group of some kind or is secondarily derivable, or a layer containing monomers which can be converted to the resin by irradiation of radiation. The medical tube according to any one of (1) to (5).

(7) The medical tube according to any one of the above (3) to (6), wherein the adhesion between the second resin layer and the third layer is enhanced by irradiation with radiation.

(8) The medical tube according to any one of (1) to (7), wherein the second resin layer is made of a polyolefin material.

(9) The medical tube according to any one of (1) to (8) above, wherein the medical tube is an expandable / contractible balloon or a tube for producing the balloon.

(10) A tube formed by concentrically stacking the first resin layer and the second resin layer is irradiated with radiation to form the first resin layer and the second resin layer. A method for producing a medical tube, characterized by interfacially adhering the interface of 1., and then forming a third layer having hydrophilicity or antithrombogenicity on the outer peripheral surface and / or the inner peripheral surface of the tube.

(11) Each tube is irradiated with radiation to a tube formed by concentrically stacking the first resin layer, the second resin layer, and the third layer having hydrophilicity or antithrombogenicity, and irradiating each layer. At least the interface between the first resin layer and the second resin layer among the interfaces of 1. is adhered at the interface.

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, a medical tube and a method for producing the same according to the present invention will be described in detail with reference to the preferred embodiments shown in the accompanying drawings.

1 and 2 are partially cutaway perspective views showing examples of the construction of the medical tube of the present invention.
The medical tube 1 shown in FIG. 1 is composed of a laminated body in which a first resin layer 11 forming an inner layer (inner tube) and a second resin layer 12 forming an outer layer (outer tube) are laminated. .

In this medical tube 1, the case where both the first resin layer 11 and the second resin layer 12 form a base material layer, and the case where the first resin layer 11 and the second resin layer 12 are In some cases, either one constitutes the base material layer. In the latter case, the other layer is, for example, a functional layer having a predetermined function such as a protective layer, a lubricating layer, a water repellent layer, an antithrombogenic layer, a base layer, a rigidity imparting layer, a reinforcing layer, and an insulating layer. preferable. In such a medical tube 1, the interface 13 between the first resin layer 11 and the second resin layer 12 is interface-bonded by irradiation with radiation.

In the medical tube 5 shown in FIG. 2, a first resin layer 51 forming an inner layer and a second resin layer 52 forming an intermediate layer are laminated, and a third layer forming an outer layer on the outer side thereof. The layer 53 is covered with a laminated body. In this case, the first resin layer 51 constitutes a base material layer, and the second resin layer 52 constitutes a base layer for forming the third layer 53. The third layer 53 is made of a hydrophilic substance,
It is a layer having lubricity when wet (lubrication layer) or an antithrombotic layer made of an antithrombotic substance.

Although not shown, the medical tube of the present invention has a first resin layer (base layer), a second resin layer (base layer), a third resin layer, and a third resin layer from the outside to the inside. It may be laminated in the order of layers (lubricating layer or antithrombogenic layer), or from the outside to the inside, a third layer (lubricating layer or antithrombogenic layer), a second resin layer (underlayer), The first resin layer (base material layer), the second resin layer (base layer), and the third layer (lubrication layer or antithrombotic layer) may be laminated in this order. Further, any intermediate layer may be interposed between each layer.

In such a medical tube 5, at least the interface 54 between the first resin layer 51 and the second resin layer 52 is interface-bonded by irradiation of radiation. The interface 55 between the second resin layer 52 and the third layer 53 is
It is preferable that the adhesion is enhanced by irradiation with radiation.

Next, each layer 11, 12, 51, 52, 53
The constituent materials of will be described.

[1] First resin layers 11 and 51, second resin layer 12 Examples of the constituent material of the first resin layers 11 and 51 and the second resin layer 12 include polyethylene, polypropylene, ethylene- Polyolefin such as vinyl acetate copolymer, modified polyolefin, halogenated polyolefin, polyurethane, polyamide, polyethylene terephthalate, polyester such as polybutylene terephthalate, polycarbonate, polyacetal, polyarylate, liquid crystal polymer, polyphenylene sulfide, polyether, polyetherimide, Polyethersulfone, polyetheretherketone, polyimide, fluororesin, phenolic resin, epoxy resin, or various copolymers (block or graft copolymers), elastomers,
Examples thereof include polymer blends and polymer alloys.

Incidentally, such a resin material contains an acid anhydride group, a carboxylic acid group, a sulfonic acid group, an alkali metal alcoholate group, an amino group, an alkali metal amide group, a magnesium halide group, a fluorine-boron complex group and the like. (In this case, the third layer 53 can be directly formed) or may not contain these groups.

In the case of the medical tube 1, the first resin layer 1
As the first and second resin layers 12, any of these resin materials can be used in combination. Further, various additives such as a polymerization initiator, a polymerization accelerator, a polymerization retarder, a plasticizer, a contrast agent, a reinforcing material and a pigment may be added to the resin material.

Further, in order to induce the development of interfacial adhesion by irradiation with radiation and enhance the adhesive strength, a substance (for example, a monomer or oligomer having a functional group described later) which initiates or accelerates the reaction of interfacial adhesion by irradiation with radiation is used. It is preferable to mix it in the resin material or carry it near the interface.

[2] Second Resin Layer (Underlayer) 52 Examples of materials for the second resin layer (underlayer) 52 include acid anhydrides, carboxyl groups or salts thereof, sulfone groups or salts thereof, esters. Functional groups such as groups, epoxy groups, amino groups, phenol groups, hydroxyl groups, acid halide groups, iminocarbonate groups, halogen atoms (groups), diazonium groups, azido groups, isocyanate groups, aldehyde groups (reactive functional groups) Examples of the resin include a resin that directly has or is secondarily derivable.

For example, it has a functional group such as an acid anhydride group, a carboxylic acid group, a sulfonic acid group, an alkali metal alcoholate group, an amino group, an alkali metal amide group, a magnesium halide group, a cyano group, and a fluorine-boron complex group. Modified polyolefins are preferably used.

The constituent material of the underlayer may include monomers that can be converted into the resin as described above by irradiation of radiation, that is, those containing the above-mentioned monomer or oligomer having a functional group.

A polyolefin-based resin material can be mentioned as a material that more remarkably exhibits the effects of the present invention. Typical examples of this resin include various polyethylenes, polypropylenes and their copolymers, olefinic elastomers, ethylene-vinyl acetate copolymers (EVA), ethylene-butylene-styrene block copolymers, polystyrene-acrylonitrile copolymers. Examples thereof include coalesce and various diene-based polymers.

As a more preferable resin, low density polyethylene, particularly a copolymer of ethylene and α-olefin can be mentioned. In this case, the type of the α-olefin to be copolymerized is not particularly limited, but one having 3 or more carbon atoms is preferable, one having 4 or more carbon atoms is more preferable, and one having 6 or 8 carbon atoms is further preferable.

Such a resin is particularly suitable for use in balloons described below, tubes for producing the balloon, or catheters required to have flexibility such as a catheter having a small diameter (microcatheter). There is.

The second resin layer (base layer) 52 is formed on the surface of the tube when the first resin layer (base material layer) 51 is made of a hydrophobic polymer. It prevents peeling of the third layer (lubrication layer, antithrombogenic layer, etc.) 53 and contributes to a dramatic improvement in durability (sustainability of effect).

[3] Third Layer (Lubrication Layer) 53 The third layer (lubrication layer) 53 is made of a hydrophilic substance. This hydrophilic substance includes natural polymer substances (eg, starch type, cellulose type, tannin / nignin type, polysaccharide type, protein) and synthetic polymer type substances (PVA type, polyethylene oxide type). , Acrylic acid type, maleic anhydride type, phthalic acid type, water-soluble polyester, ketone aldehyde resin, (meth) acrylamide type, vinyl heterocyclic ring type, polyamine type, polyelectrolyte, water-soluble nylon type, glycidyl acrylate type )
There is. More specifically, the following natural or synthetic polymeric substances or derivatives thereof can be mentioned.

<Natural Polymer> Starch-based Example: Carboxymethyl starch, dialdehyde starch

Cellulose system Example: CMC, MC, HEC, HPC

Tannin-Nignin Example: Tannin, Nignin

Polysaccharide system Example: sodium alginate, gum arabic, guar gum, tragacanth gum, tamarind

・ Protein example: gelatin, casein, glue, collagen

<Synthetic water-soluble polymer>

PVA type example: polyvinyl alcohol

Polyethylene oxide type: polyethylene oxide, polyethylene glycol

Acrylic acid and its salt type Examples: Sodium polyacrylate, acrylic acid, methacrylic acid

Maleic anhydride type Example: methyl vinyl ether maleic anhydride copolymer, methyl vinyl ether maleic anhydride ammonium salt

Vinyl ether type Example: vinyl ether

Phthalic acid type example: polyhydroxyethyl phthalic acid ester

Water-soluble polyester Example: Polydimethyl roll propionate

Ketone aldehyde resin Example: methyl isopropyl ketone formaldehyde resin

Acrylamide / methacrylamide system Example: Dialkylacrylamides (dimethylacrylamide, diethylacrylamide, methylethylacrylamide, diisopropylacrylamide, etc.), monoalkylacrylamides (methylacrylamide, ethylacrylamide, isopropylacrylamide, etc.), and other acrylamides (2-Methylpropanesulfonic acid acrylamide, dimethylaminopropyl acrylamide, etc.), acrylamide, and corresponding methacrylamides of chemical structure

Vinyl heterocyclic ring system Examples: vinyl pyridines (2-vinyl pyridine, 4-vinyl pyridine, etc.), vinyl pyrrolidone, N-1,2,4-
Triazolyl ethylene, etc.

Polyamine type: Polyethyleneimine

Polyelectrolyte Example: polystyrene sulfonate, polyacrylamide quaternized product, polyvinyl sulfonate sodium

Acrylate / methacrylate type Polyalkylene glycol acrylates (glyceryl acrylate, etc.), hydroxyalkylene acrylates (hydroxyethyl acrylate, hydroxypropyl acrylate, etc.), and methacrylates of the corresponding chemical structure, etc.

Others: Water-soluble nylon

Among these, in particular, a cellulosic polymer material (for example, hydroxypropyl cellulose),
Polyethylene oxide-based polymer (polyethylene glycol), maleic anhydride-based polymer (eg, maleic anhydride copolymer such as methyl vinyl ether maleic anhydride copolymer), acrylamide-based polymer (eg, polydimethyl) Acrylamide), water-soluble nylon (for example, AQ-Nylon P-70 manufactured by Toray Industries, Inc.)
Is preferable because a low coefficient of friction can be stably obtained.

As the derivative of the polymer substance,
It may be water-soluble or insolubilized. For example,
Condensation of the polymer substance, addition, substitution, oxidation, esterification product obtained by a reduction reaction, salt, amidation product, anhydride, halide, etherification product, hydrolyzate, acetalization product, formalization product, alkylolation product, Quaternary compound, diazo compound, hydrazide compound, sulfonate compound, nitrate compound, ion complex; diazonium group, azido group, isocyanate group, acid chloride group, acid anhydride group, iminocarbonic acid ester group, amino group, carboxyl group, epoxy group , A hydroxyl group, an aldehyde group and the like, a cross-linked product with a substance having two or more reactive functional groups; a vinyl compound, acrylic acid, methacrylic acid, a diene compound, a copolymer with maleic anhydride and the like.

Examples of the hydrophilic substance preferably used in the present invention include block polymers having an epoxy group and macromonomers. The former block polymer is preferably a block copolymer composed of a site exhibiting lubricity and a site having an epoxy group. The site that exhibits lubricity may be any as long as it exhibits lubricity in body fluids or aqueous solvents, but considering the ease of synthesis and operability,
Acrylamide, polymer composed of acrylamide derivative, N, N-dimethylaminoethyl acrylate, sugar,
Examples thereof include polymers having a structural unit of a monomer having a phospholipid in the side chain, maleic anhydride-based polymers, and the like. The maleic anhydride-based polymer may be water-soluble or insolubilized as long as it contains a maleic anhydride-based polymer as a main component and exhibits lubricity when wet. Further, for example, considering that the polymer is dissolved in a solvent for swelling the underlayer resin for coating, a polymer soluble in an organic solvent, that is, an amphipathic polymer is preferable.

On the other hand, in the macromonomer, it is preferable that the branch portion is a portion that exhibits lubricity and the trunk portion is a portion that has a domain that is crosslinked or polymerized by heat treatment. Specifically, for example, a macromonomer of glycidyl methacrylate and dimethylacrylamide, glycidyl methacrylate and maleic anhydride-
Macromonomer with hydroxyethyl methacrylate copolymer, glycidyl methacrylate and maleic anhydride-
Examples include macromonomers with acrylamide copolymers.

[4] Third layer (antithrombotic layer) 53 The third layer (antithrombotic layer) 53 is composed of an antithrombotic substance. Examples of the antithrombotic substance include heparin and A
Examples include thrombolytic agents such as CD, CPD, TPA and urokinase, and natural antithrombotic substances such as elastin.

Of the antithrombotic substances, heparin will be representatively described. As a method of fixing heparin to the surface of the second resin layer (underlayer), a method of ionically bonding heparin to the underlayer resin (Japanese Patent Publication No. 54-18317), a method of covalently bonding (Japanese Patent Publication No. 55-46741, Tokufair 6
No. 38851).

For devices such as catheters used in contact with blood such as blood vessel catheters, artificial organs such as artificial blood vessels, artificial lungs, artificial hearts, blood transfer tubes used in blood extracorporeal circulation circuits, blood bags, etc. It is useful to form such an antithrombotic layer.

Next, a preferred example of the method for producing a medical tube according to the present invention will be described.

[First Method] First, for example, a hollow extrusion molding method by one-step or multi-step co-extrusion or sequential extrusion, a core wire coating method (a metal core wire is coated with a plurality of resins simultaneously or sequentially, and then, A tube comprising a laminate of the first resin layer / the second resin layer (any of which may be inside) is manufactured by a method of removing the core wire) or by applying and drying a solution. Next, irradiating the tube with radiation,
The interface between the first resin layer and the second resin layer is interface-bonded.

[Second Method] After the tube is manufactured by the first method, the surface of the second resin layer is subjected to a hydrophilic treatment, that is, a third layer is formed.

[Third Method] First, for example, a hollow extrusion molding method by one-step or multi-step coextrusion or sequential extrusion, a core wire coating method (a plurality of resins are simultaneously or sequentially coated on a metal core wire, and then A tube comprising a laminate of the first resin layer / the second resin layer / the third layer is manufactured by a method of removing the core wire), applying a solution, drying, or a combination of these methods.

Next, the tube is irradiated with radiation,
The interface between the first resin layer and the second resin layer is interface-bonded. In addition, the irradiation of the radiation causes the second resin layer and the third resin layer
Depending on the composition of the layer and the condition of the interface between them, the adhesion between the second resin layer and the third layer is also strengthened.

Radiation irradiation in the first to third methods will be described in detail below. The principle of improving the adhesive force at the interface of each layer by irradiation with radiation is mainly by covalent bonds by cross-linking, but in addition, ionic bonds, physicochemical bonds (bonds by van der Waals force), and adhesion In some cases. In the present invention, these are collectively referred to as interfacial adhesion by irradiation with radiation.

In the present invention, it is preferable to use a medical tube having a layer made of polyethylene or polypropylene as a base material layer after radiation cross-linking with an electron beam or the like.
It may be preferable to an uncrosslinked tube. In such a case, it is possible to simultaneously improve the performance of the resin layer by cross-linking and the adhesive strength of the interface by irradiating radiation, which is preferable.

Further, the radiation sterilization applied to the medical instrument and the irradiation of radiation for the interfacial adhesion can be combined. As the type of radiation, a preferable radiation is appropriately selected and used from among various conventionally known radiations according to its characteristics. Typical radiations are ultraviolet rays, electron beams, α
-, Β-, γ-ray, neutron ray and the like can be mentioned, and electron beam and γ-ray are preferable.

The atmosphere at the time of irradiation with radiation depends on the purpose.
Air, oxygen or an inert gas atmosphere can be mentioned. Typical examples of the inert gas include nitrogen, argon, neon and mixed gas thereof. The radiation irradiation temperature is appropriately determined according to the composition of the resin to be adhered, etc., but in the case of the tube having the above-mentioned polyolefin-based material, a temperature at which the polyolefin-based material does not undergo thermal deformation, particularly 70 ° C. or less. Is preferred.

The irradiation dose of radiation is appropriately determined depending on the purpose of irradiation, the composition of the resin to be adhered, and the like. When irradiation is performed simply for the purpose of improving the adhesive force at the interface between the first resin layer and the second resin layer, the object can be achieved with a relatively small radiation dose.

The resins are roughly classified into cross-linking type polymers and decomposing type polymers in terms of the chemical change of the resin by irradiation of radiation, but their usefulness depends on the type of radiation and the dose. Can be set to maximize performance. For example, at least one of the first resin layer and the second resin is easily decomposed by irradiation with radiation (decomposition type)
In this case, it is preferable that the irradiation amount of radiation is set to the minimum amount necessary for interfacial adhesion. Further, even if it is basically a decomposing type such as polyester, as long as it has resistance (resistance) to irradiation, the irradiation amount of radiation is increased to some extent, and the adhesive force at the resin layer interface is extremely high. Can be one.

When the adhesion of the third layer made of a hydrophilic substance to the second resin layer is enhanced by irradiation with radiation, for example, the interface between the first resin layer and the second resin layer is used. After securing the irradiation dose of radiation necessary for adhesion, a device such as adding a radiation dose for improving the adhesive strength at the interface between the second resin layer and the third layer is implemented as necessary.

The dose of radiation can be appropriately changed according to the site of the medical tube. For example, the radiation dose can be made different between the balloon portion and the portion other than the balloon in the balloon catheter.

In a balloon catheter or a catheter shaft made of a polyolefin resin material, for example, a crosslinked tube obtained by irradiating a radiation in a specific range of dose exhibits excellent blow moldability. Taking an electron beam as an example, in the generation of a crosslinked structure by irradiation,
Besides the dose, the irradiation atmosphere is also relevant. It is also affected by the molecular structure (particularly the degree of branching) of the resin to be irradiated, the shape and size of the member.

From the above, for example, in the tube manufactured by blow molding such as a balloon or the tube for manufacturing a balloon subjected to blow molding, a suitable range of the degree of crosslinking was found. That is, in terms of gel fraction as an index of the degree of crosslinking, in the present invention, the gel fraction of the radiation (electron beam) crosslinked resin is 0.
It is preferably 75 to 0.95. The gel fraction is 0.
When it is less than 75, the improvement of the stretching property and the burst pressure due to the irradiation are insufficient, and when the gel fraction exceeds 0.95, the crosslinked structure becomes too strong and the flexibility is often impaired. . The range of the gel fraction is more preferably 0.80 to 0.92, particularly preferably 0.8.
It is 2 to 0.90. For the radiation irradiation suitable for the catheter shaft, a preferable dose is selected according to the purpose for which the catheter shaft is used.

Next, the third method in the second and third methods
The method for forming this layer will be described in detail. Applying (or dipping) a substance (for example, a hydrophilic substance) forming the third layer in a molten or solution form on the surface of the second resin layer (underlayer), and then applying heating or radiation irradiation. This makes it possible to firmly adhere to the second resin layer.

When the constituent substance of the third layer is temporarily supported by dipping the solution, the immersion time is set to the first and second times.
The tube made of the resin layer is not deformed (dimension does not significantly change) and is appropriately adjusted within a range in which the required physical properties are maintained, but from the viewpoint of operability, 1 second to 1 is preferable.
The time is about 0 minutes, more preferably about 10 seconds to 5 minutes, further preferably about 30 seconds to 3 minutes.

After the solution (or dispersion liquid) of the constituent material of the third layer is applied to the surface of the second resin layer (base layer), it is dried if necessary. The drying conditions such as a drying method, a drying temperature, and a drying time are such that the third layer can firmly adhere to the second resin layer. The drying method may be natural drying, heat drying, or the like, but heat drying is preferable. In this case, the drying temperature is set to a temperature at which the tube does not deform.

As a preferred example of the medical tube of the present invention,
A balloon that can be expanded / contracted or a balloon catheter equipped with the balloon (eg, PTCA expansion catheter, I
ABP catheter, endotracheal tube).
By forming a third layer (lubrication layer) on all or part of the balloon (for example, on the catheter tip side in the longitudinal direction of the balloon), that is, by hydrophilizing the balloon, a balloon such as a polyolefin-based material can be formed. In addition to the flexibility of the constituent materials, it is possible to obtain lubricity when wet, and by these synergistic effects, running and pushing in the body cavity (blood vessel, trachea, digestive tract, etc.) that is bent, branched, or narrowed It is possible to greatly improve the durability, the followability, the kink resistance, and the safety. Furthermore, since the adhesion of the third layer (lubrication layer) is also high,
Peeling is less likely to occur, and durability, that is, the durability of the above effects, is excellent.

Further, the medical tube of the present invention can be applied to a catheter shaft in a balloon catheter or other catheters, and in this case as well, the whole or a part of the catheter shaft is subjected to a hydrophilic treatment (the third method). (Formation of a layer) can be performed, and thereby the above effect is exhibited. Further, regarding the formation of the third layer (antithrombotic layer), that is, the antithrombotic treatment,
Similar to the above, excellent antithrombotic property and its durability are exhibited.

The balloon in the balloon catheter is
It can be manufactured from various thermoplastic resins. Examples of the resin of the first resin layer or the second resin layer forming the balloon include polyurethane, polyvinyl chloride, thermoplastic elastomer, silicon-carbonate copolymer, ethylene-butylene-styrene block copolymer,
Various polyolefins such as polystyrene, acrylonitrile copolymer, polyethylene, polypropylene, ethylene-vinyl acetate copolymer, polyethylene terephthalate,
Examples thereof include polyester copolymers, thermoplastic rubbers, polyamides, and polytetrafluoroethylene.

When classified according to the resin constituting the balloon,
It is as follows.

Polyethylene terephthalate type and various engineering plastic type balloons: This balloon is useful as a balloon having high pressure resistance and no compliance or small (Japanese Patent Publication No. 63-26655).

Polyamide type balloon: A semi-compliant balloon having a relatively high pressure resistance as compared with polyolefin and the like (Japanese Patent Laid-Open No. 3-57462).

Polyolefin balloon: It is highly flexible and has excellent crossability.

According to the manufacturing method of the present invention, the hydrophilic treatment or antithrombotic treatment can be performed on the balloon or the catheter shaft under relatively low treatment temperature conditions, so that the surface is hydrophilic and lubricated without heat shrinkage or deformation. It is possible to provide a balloon catheter having excellent anti-thrombotic properties and a balloon catheter having excellent running properties in a body cavity such as a blood vessel.

In the present invention, the balloon having a layer composed of a copolymer of ethylene and α-olefin starts from a polymer material having a high flexibility and is manufactured under various manufacturing conditions from the molding of the balloon to the post-treatment. By maintaining the flexibility peculiar to polyolefin by subtly controlling it, excellent lubricity or antithrombogenicity can be imparted by the surface hydrophilization treatment or antithrombotic treatment, which is an extremely useful balloon (medical tube ) Can be provided.

The hydrophilic treatment of this balloon catheter is
It can be carried out at any stage of the tube immediately after extrusion, after assembling into a catheter, or an intermediate stage therebetween. As an example, FIG. 3 shows the timing when hydrophilic treatment is applied to both the shaft and the balloon in the manufacturing process of the PTCA dilatation catheter. The hydrophilic treatment can be performed at any stage indicated by an arrow in FIG.

Next, a medical tube (medical device) to which the present invention can be applied will be illustrated. A. Angiography catheter, cerebrovascular treatment catheter,
Catheter for intravascular insertion or indwelling such as thermodilution catheter, IVH catheter, indwelling needle, etc.
Or dilators, stylets, introducers and guide wires for these catheters.

B. Various balloons or balloon catheters.

C. Catheter such as gastric tube catheter, feeding catheter, tube for feeding tube and the like, which are inserted or placed in the digestive organ orally or nasally.

D. Oxygen catheters, oxygen canulas, endotracheal tube tubes and cuffs, tracheostomy tube tubes and cuffs, endotracheal suction catheters and other catheters that are inserted or placed orally or nasally.

E. Catheters that are inserted or left in various body cavities or tissues such as suction catheters, drainage catheters, abdominal cavity catheters, rectal catheters, urethral catheters, and trocar tubes.

F. An endoscopic tube that is inserted into various body cavities.

G. Stents, artificial blood vessels, artificial trachea,
Artificial bronchus, colostomy etc.

H. Various medical devices such as artificial lungs, artificial hearts, artificial kidneys, reservoirs, bubble traps and drip chambers, and members that constitute an extracorporeal circulation circuit such as a circuit tube forming a blood flow path.

I. Blood bags, blood component bags, infusion bags, infusion bags, drainage bags, and other bags, or members connected to these, such as tubes and connectors.

J. Testing instruments and treatment instruments that require low frictional resistance (lubricity) during indwelling and sliding in the body, and testing instruments and treatment instruments that require antithrombogenicity.

K. Various air supply tubes and liquid supply tubes.

L. contact lens.

[0107]

EXAMPLES Specific examples of the present invention will be described below. (Example 1) A shaft tube was manufactured by executing the following steps.

[1] Production of base material tube Low-density polyethylene (C6 LLDPE resin: manufactured by Tosoh Corporation, trade name: Nipolon-Z, melt flow rate = 2.
Pellets having a weight of 0 g / 10 min and a specific gravity of 0.935) were melted by an extruder and extruded to coat the outer peripheral surface of a copper wire having a diameter of 0.35 mm. The diameter of this resin-coated copper wire is 0.76mm
Met. Therefore, the thickness of the tube which is the covering layer is 2
05 μm.

[2] Formation of Underlayer The resin-coated copper wire was treated with modified polyethylene (a product for Sumitomo Chemical Co., Ltd., product: Bondyne AX-83, which is a resin for the underlayer).
It was dipped in the toluene solution of 90) and dried to form a base layer. Then, the inner copper wire was removed from the resin-coated copper wire to obtain a two-layer laminated tube. When forming the underlayer, the resin concentration in the solution was variously changed, and the thickness of the underlayer was set in multiple steps within the range of 0.8 to 2.0 μm.

[3] Preparation of cross-linked tube An electron beam was applied to the laminated tube in air at an irradiation dose of 3
Irradiate with 5 Mrads. As a result, the resin of each layer of the laminated tube was further crosslinked, and the interface between both layers was interfacially bonded.

Then, maleic anhydride was used as a monomer for forming a graft chain on the laminated tube, and toluene (oxygen concentration in toluene was 5 ppm) was used as a solvent. The graft reaction was carried out in 3 hours.

[4] Hydrophilization Treatment (Formation of Lubrication Layer) [0112] A chloroform solution (2.5% by weight) of a dimethylacrylamide-glycidyl methacrylate block copolymer was added as a hydrophilic substance to the tube on which the undercoat was formed by using pyridine. The reaction was carried out under a catalyst to form a lubricating layer.

When the surface of the shaft tube (n = 3) manufactured as described above was wetted with water and moistened, and its lubricity was examined, all showed good lubricity and slidability.

Example 2 Low density polyethylene was used as the constituent resin of the first resin layer (outer layer side), and high density polyethylene was used as the constituent resin of the second resin layer (inner layer side) by hollow coextrusion. A layer laminated tube was produced. The dimensions of the obtained tube are: outer diameter = 0.70 mm, outer layer thickness = 0.15.
mm, inner layer thickness = 0.025 mm, inner diameter 0.35 mm. This laminated tube was irradiated with an electron beam of 5 Mrads in air to bond the interface between the inner layer and the outer layer.

The two-layer laminated tube manufactured as described above and the same two-layer laminated tube (comparative example) except that the electron beam was not irradiated were cut into films with a cutter, and a friction tester (Kato Tech) was used. (Manufactured by Mfg. Co., Ltd.), and frictional force was repeatedly applied until peeling occurred. The friction tester used was a silicone rubber friction element to which a weight with a constant load was added.

The two-layer laminated tube of this example withstood repeated rubbing 20 times or more. On the other hand, in the tube not irradiated with the electron beam, peeling occurred less than 10 times. The inner surface frictional resistance of the two-layer laminated tube of this example was lower than the inner surface frictional resistance of the one-layer tube made of low density polyethylene irradiated with 5 Mrads of electron beam.

(Example 3) A two-layer laminated tube of the same size was manufactured in the same manner as in Example 2 except that the constituent resin of the first resin layer (outer layer side) was replaced with a polyester elastomer, and the same test was conducted. I went. The adhesiveness at the interface of the two-layer laminated tube of the present example was extremely higher than that of a similar tube that was not irradiated with an electron beam, and the sliding property of the inner surface was also excellent.

Example 4 High density polyethylene was used as the constituent resin of the first resin layer (outer layer side / base material layer), and maleic anhydride was modified as the constituent resin of the second resin layer (inner layer side / base layer). As polyethylene, a two-layer laminated tube was produced by hollow coextrusion. The size of the obtained tube is the outer diameter =
0.50 mm, outer layer thickness = 0.10 mm, inner layer thickness = 5 μm
The inner diameter was 0.30 mm.

On the surface of the second resin layer of this layer-stacked tube, a chloroform solution (2.5% by weight) of a dimethylacrylamide-glycidyl methacrylate block copolymer was reacted as a hydrophilic substance under a pyridine catalyst,
A third layer (lubrication layer) was formed.

The laminated tube (surface-hydrophilized microtube) thus obtained was irradiated with an electron beam of 10 Mrads in air to bond the interface between the first resin layer and the second resin layer and The adhesive force at the interface between the second resin layer and the third layer was enhanced. The laminated tube of this example was repeatedly curved and deformed, but no peeling occurred at the interface between the layers.

(Example 5) PTCA was performed as follows.
A dilatation catheter was manufactured. The electron-beam-irradiated maleic anhydride-underlaid graft tube used in Example 1 was inserted into a balloon molding die having a cavity having a desired outer diameter, and set in a balloon molding blow molding machine.

Next, in the blow molding machine, a temperature of 1
At 05 ° C., stretching in the longitudinal direction and blow molding by pressure were alternately performed a plurality of times to manufacture a balloon. When the physical properties of the balloon itself were examined, it was highly flexible and exhibited a relatively high pressure resistance (14 to 16 atm).

After thinning the joint portion (both ends) of the balloon with the shaft tube, the joint portion on the distal end side of the balloon is joined to the inner pipe shaft (made of polyolefin) of the double pipe, and the joint portion on the balloon base side is joined to each other. The outer tube shaft (made of polyolefin) of the heavy tube was joined, and further, the hub was joined to the proximal end of the double tube to assemble a PTCA dilatation catheter having a flexible tip.

For the outer tube shaft and the inner tube shaft, the same tube as that used in Example 1 was used, which was irradiated with an electron beam of 10 Mrads in a nitrogen atmosphere and was grafted with maleic anhydride.

On the outer surface of the PTCA dilatation catheter consisting of the tube graft-formed, a chloroform solution (2.5% by weight) of dimethylacrylamide-glycidyl methacrylate block copolymer as a hydrophilic substance was reacted under a pyridine catalyst. Then, the third layer (lubrication layer) was formed.

Regarding the PTCA dilatation catheter manufactured as described above, slidability in a blood vessel model, running property,
When the followability and kink resistance were examined, the evaluation results were as follows:
All were extremely good.

Further, with respect to the PTCA dilatation catheter of this example, the balloon was expanded and contracted many times and the shaft was repeatedly curved and deformed, but no peeling occurred at the interface of each layer at any part. .

Example 6 The same base layer resin (low density polyethylene) as that used in Example 1 was used as an inner layer, and a block copolymer of polyamide and polyether was used as an under layer resin. Combined (ATOCHEM, trade name:
A two-layer laminated tube was manufactured by coating an outer layer of PEBAX6333SA00) having a thickness of 30 μm.

Next, the laminated tube was irradiated with an electron beam of 5 Mrads in the air to bond the interface between the inner layer and the outer layer. For the obtained electron beam irradiation laminated tube, according to the prescription described in Japanese Patent Publication No. 6-38851, first,
Ozone treatment, then 45 ° C. in 0.5% polyethyleneimine solution (manufactured by BASF, adjusted to pH = 10)
It was soaked for 24 hours. Subsequently, the tube was placed in a 0.5% (partial) desulfated heparin acetate buffer solution (pH = 4.
It was immersed in 5) at 45 ° C. for 24 hours, and further immersed in a 2.5% glutaraldecht acetate buffer solution (pH = 4.5) at room temperature for 24 hours. Then, the antithrombotic treatment (formation of an antithrombotic layer made of heparin) was completed by immersing in 1% NaBH ₄ carbonate buffer (pH = 10) at room temperature for 24 hours and drying.

The antithrombogenic tube produced as described above and the same tube except that the antithrombotic treatment was not performed were brought into contact with fresh blood (not anticoagulated) until blood coagulation occurred. When I measured the time,
It was confirmed that the antithrombotic tube of the present example exhibited an excellent antithrombotic property, as compared to the antithrombotic untreated tube, which took an extremely long time until blood coagulation. Further, the antithrombotic tube of this example was repeatedly curved and deformed, but no peeling occurred at the interface of each layer.

[0131]

As described above, according to the medical tube and the method for producing the same of the present invention, the adhesive force at the interface between the respective layers is high, and the interface peels even when the tube is curved or deformed. Is prevented.

Further, the surface of the medical tube can be provided with, for example, a third layer having excellent lubricity when wet or a third layer having antithrombotic property, which can be applied for the purpose of high function. In addition, the adhesion of the third layer is strong and
The peeling of the layer is prevented and the durability is excellent.

In particular, in a microcateter such as a PTCA dilatation catheter, the balloon or shaft made of a flexible material having a relatively high pressure resistance is subjected to a hydrophilic treatment so that the running property in the body cavity is improved. Excellent in pushability,
The followability, kink resistance, safety and durability of their effects are improved.

Further, according to the method for producing a medical tube of the present invention, the adhesion force at the interface between the layers can be increased by a simple method of irradiation, and the medical tube can be easily produced. Because it is possible, it has high productivity.

[Brief description of drawings]

FIG. 1 is a partially cutaway perspective view showing an embodiment of a medical tube of the present invention.

FIG. 2 is a partially cutaway perspective view showing another embodiment of the medical tube of the present invention.

FIG. 3 is a process drawing showing an example of the manufacturing process of the medical tube of the present invention.

[Explanation of symbols]

 1 Medical Tube 11 1st Resin Layer 12 2nd Resin Layer 13 Interface 5 Medical Tube 51 1st Resin Layer 52 2nd Resin Layer 53 3rd Layer 54, 55 Interface

Claims (11)

[Claims] 1. A medical tube having a first resin layer and a second resin layer, wherein the medical tube has a laminated portion where the first resin layer and the second resin layer overlap each other. In the portion, the medical tube, wherein the first resin layer and the second resin layer are interface-bonded by irradiation of radiation. 2. The medical tube according to claim 1, wherein the first resin layer is a base material layer, and the second resin layer is a functional layer. 3. The medical device according to claim 2, wherein the second resin layer is an underlayer, and a third layer is formed on a surface of the underlayer opposite to the base material layer. tube. 4. The third layer is made of a hydrophilic substance,
The medical tube according to claim 3, which is a layer having lubricity when wet. 5. The medical tube according to claim 3, wherein the third layer is composed of an antithrombotic substance. 6. The underlayer comprises an acid anhydride, a carboxyl group or a salt thereof, a sulfone group or a salt thereof, an ester group, an epoxy group, an amino group, a phenol group, a hydroxyl group, an acid halide group, an iminocarbonic acid ester group, a halogen. At least one selected from the group consisting of atom (group), diazonium group, azite group, isocyanate group, and aldehyde group.
4. A layer comprising a resin which directly has a functional group of some kind or is secondarily derivable, or a layer containing monomers which can be converted into the resin by irradiation of radiation. 5. The medical tube according to any one of 5. 7. The medical tube according to claim 3, wherein the adhesive force between the second resin layer and the third layer is enhanced by irradiation with radiation. 8. The medical tube according to claim 1, wherein the second resin layer is made of a polyolefin material. 9. The medical tube according to claim 1, wherein the medical tube is an expandable / contractible balloon or a tube for producing the balloon. 10. A tube formed by concentrically stacking the first resin layer and the second resin layer is irradiated with radiation to form the first resin layer and the second resin layer. A method for producing a medical tube, comprising interfacially adhering an interface, and then forming a third layer having hydrophilicity or antithrombogenicity on an outer peripheral surface and / or an inner peripheral surface of the tube. 11. A tube formed by concentrically stacking the first resin layer, the second resin layer, and a third layer having hydrophilicity or antithrombogenicity is irradiated with radiation to remove each layer. A method of manufacturing a medical tube, characterized in that at least an interface between the first resin layer and the second resin layer among the interfaces is interface-bonded.