JPH0871144A - Production of medical tube with surface treatment for hydrophilicity and medical tube - Google Patents

Abstract

PURPOSE: To obtain a medical tube showing small frictional resistance during insertion of the tube by irradiating the surface of a polyolefin medical tube with a specified dose of radiation in an inert gas atmosphere, effecting graft reaction under specified conditions to form base grafted chains, and then depositing a hydrophilic material on the surface. CONSTITUTION: The part of a polyolefin resin medical tube where treatment for hydrophilicity is to be applied is irradiated with radiation corresponding to 5 to 70 Mrad in an inert gas atmosphere. Then graft reaction is effected using graft monomers under conditions of <=70 deg.C/graft reaction temp., >5wt.% monomer density in the graft liquid, and <=100ppm oxygen density in the graft reaction system to form base grafted chains. Then a hydrophilic material is carried on the base grafted chains. Thus, a hydrophilic material is carried with the hydrophilic base graft chains on the surface of the polyolefin resin tube.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical tube and a method for manufacturing the same. More specifically, with respect to the mobility in a body lumen / tissue such as a blood vessel that is generally bent or highly constricted, a part or all of a catheter shaft and / or a balloon is subjected to a radiation graft reaction and a subsequent hydrophilization treatment, The present invention relates to a useful medical tube and a hydrophilic treatment method thereof.

[0002]

2. Description of the Related Art Medical devices such as blood vessels, ureters, digestive tracts, trachea, and other medical cavities inserted into body cavities or body tissues, such as guide wires and stylets, are used in cases of flexion, stenosis, and even more peripheral cases. In this regard, there is an increasing demand for lubricity that allows the target site to be reliably reached without damaging the tissue. That is, it goes without saying that it is desirable to impart excellent lubricity for the purpose of preventing damage to the mucous membrane and inflammation during indwelling in the tissue.

For the purpose of imparting this lubricity, it is practiced to use a low friction resistance material formed of a fluororesin or a polyethylene resin or to form a lubricating layer made of a fluororesin or a silicone resin on the surface of a base material. Has been done. Further, surface coating of silicone oil, olive oil, glycerin, xylocaine jelly and the like is already known.

Each of the above methods involves various problems that need further improvement. That is, a low friction resistance material obtained from a fluororesin, a polyethylene resin or the like is often insufficient in lubricity. On the other hand, it is self-evident that the surface coating method of oils is likely to cause deterioration of lubricity due to the outflow of the coating liquid and has a problem in terms of sustainability.

Further, in US Pat. No. 4,100,309, an interpolymer of polyvinylpyrrolidone and polyurethane is used as a coating layer to obtain a certain effect on lubricity and durability. However, it is necessary to use a base material capable of reacting with an isocyanate group such as polyurethane, and the base material is limited.

Further, Japanese Patent Laid-Open No. 59-81341 discloses a method in which an unreacted isocyanate group is formed on the surface of a medical device and then treated with a hydrophilic copolymer capable of reacting with it to perform a hydrophilic treatment. It is disclosed. Although lubricity and a certain degree of sustainability have been obtained by this treatment method, damage to the surface lubricating layer due to repeated friction cannot be ignored, and sufficient sustainability has not yet been obtained.

[0007]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a medical tube for use in a wet state of body fluids such as blood, digestive fluid, saliva, etc. and aqueous liquids such as physiological saline, water, etc. The present invention is to provide a medical tube and a method for producing the same, which has a low content, is excellent in its sustainability and storability, and has few restrictions on the types of applicable substrates.

As a typical example thereof, a PTCA dilatation catheter is used, by subjecting the catheter shaft / balloon to an appropriate portion of its surface to be hydrophilic, it is possible to bend the polyolefin catheter balloon which has been conventionally used while maintaining its flexibility. -It is intended to greatly improve the mobility in a highly stenotic blood vessel.

As a concrete method of such hydrophilic treatment, application of a plasma graft method in a liquid phase or a gas phase is considered. However, if it is made of a resin-based material combination that is flexible and thus causes shrinkage due to heating, such as a shaft / balloon of a dilatation catheter made of a polyolefin-based member, if the treatment temperature is increased, There is an urgent need to develop a more purposeful treatment method, because the thermal contraction and deformation of the constituent materials may be caused, and the safety of the dilatation catheter may be significantly impaired.

[0010]

In order to solve the above-mentioned technical problems, the present invention provides a medical tube made of a polyolefin-based resin with a constant dose of a radiation of an inert gas at least on the surface of the surface of the medical tube subjected to the hydrophilic treatment. By irradiating under an atmosphere, then using a graft monomer, a graft reaction is carried out under specific conditions to form a base graft chain, and a hydrophilic substance is supported on the base graft chain, so that the surface of the medical tube is hydrophilized. It is something to give.

[0011]

Basic Steps of the Invention The basic constitution of the present invention is roughly summarized in the following three steps: Radiation irradiation step 5Mrad to 70M at least on the surface of the surface of the medical tube made of a polyolefin resin to be subjected to hydrophilic treatment.
Radiation equivalent to rad is applied in an inert gas atmosphere.

Subsequent Grafting Reaction Step Then, a grafting monomer is used to carry out a grafting reaction under the following conditions to obtain a surface-hydrophilized medical tube: grafting reaction temperature ≦ 70 ° C. monomer concentration in grafting liquid ≧ 5 weight % Oxygen concentration in graft reaction system ≤ 100 ppm Supporting step of hydrophilic substance Natural polymer substance group (starch type, cellulose type,
Tannin / Nignin type, Polysaccharide type, Protein type, and Synthetic water-soluble polymer group (PVA type, Polyethylene oxide type, Acrylic acid type, Maleic anhydride type,
Phthalic acid type, water soluble polyester, ketone aldehyde resin, acrylamide type, polyvinylpyrrolidone type, polyamine type, polyelectrolyte, water soluble nylon type, acrylamide type, acrylate type, vinyl heterocyclic ring type, acrylic acid type glycidyl acrylate type A hydrophilic substance selected from the group consisting of an acrylamide type, an acrylate type, a vinyl heterocyclic ring type, and an acrylic acid type glycidyl acrylate type. .

[0013]

DETAILED DESCRIPTION OF THE INVENTION A medical tube to which the present invention is applicable is illustrated.

Outer surface or inner surface of catheters for intravascular insertion or indwelling such as angiography catheters, cerebrovascular treatment catheters, dilators, introducers, thermodilution catheters, IVH catheters, indwelling needles and the like. Alternatively, the outer surface of the dilator or introducer for these catheters. By subjecting the above-mentioned tube or the like to the hydrophilic treatment of the present invention, the insertion resistance of the catheter into the blood vessel is reduced, and thus the coronary insertion resistance of the guide wire is reduced.

Part or all of the outer or inner surface of various balloon catheters, catheters such as urethral / urethral catheters, and balloons. By subjecting the above-mentioned tube or the like to the hydrophilic treatment of the present invention, the frictional resistance can be reduced, so that the tube can be easily inserted, and it can reach the periphery and exceed the bent portion.

Outer or inner surface of catheters such as a gastric tube catheter, feeding catheter, tube feeding tube orally or nasally inserted or left in the digestive tract. By subjecting the above-mentioned tube or the like to the hydrophilic treatment of the present invention, the resistance of catheters to be inserted into the tube is reduced, and the swallowing of the patient himself / herself becomes easy.

Outer or inner surface of catheters to be placed upon oral or nasal insertion of endotracheal tube, oxygen catheter, tube / cuff of oxygen canula, endotracheal suction catheter, etc.

Outer or inner surface of catheters for placement in various body cavities or tissues such as suction catheters, drainage catheters, rectal catheters. The hydrophilicity of the present invention has the merit that the adherence of interstitial fluid and the like is reduced and the lumen flow path can be secured for a long time.

The outer surface of the endoscope tube for insertion into various body cavities.

In addition, the inner and outer surfaces or inner surfaces of medical devices which require low frictional resistance (lubricity) during indwelling or sliding in the body.

A PTCA dilatation catheter can be particularly mentioned as a catheter to which the hydrophilization treatment of the present invention can be particularly preferably applied. As is well known, the technique of percutaneously inserting / expanding a catheter into a blood vessel is generally performed to treat a lesion involving a blood vessel, and when performing such a vasodilation, a guiding catheter is used. -Expansion catheters and guide wires are commonly used. Typical examples of conventional balloon manufacturing methods used for this balloon catheter are US Pat. Nos. 4093484, 4154244, and 4254774. Balloons can be made from various known polymeric materials that are generally thermoplastic. Among the known polymeric materials described in the above patents, polyurethane; polyvinyl chloride; thermoplastic elastomers; silicon carbonate copolymers; ethylene vinyl acetate copolymers; ethylene-butylene-styrene block copolymers; polystyrene; acrylonitrile copolymers. Various polyolefins such as polyethylene and polypropylene; polyethylene terephthalate and polyester copolymers; thermoplastic rubber; polyamide; polytetrafluoroethylene.

Among these, the balloon portion of the catheter used for dilatation is required to have various characteristics depending on the state of the lesion, but a common requirement is to improve the safety of the balloon catheter. Therefore, it is required to have a high breakdown voltage. In addition, in a procedure applied to a blood vessel with more advanced stenosis, there is a demand for a balloon that is flexible, has excellent traveling properties, and has high safety. The term "blood vessel" used in the present invention is meant to include not only coronary blood vessels but also all blood vessels including coronary blood vessels, such as peripheral blood vessels.

The performance and function of the balloon portion of such a catheter are required to have various characteristics as described above depending on the state of the lesion. Polyethylene terephthalate type balloons are generally useful as balloons having high pressure resistance and no compliance or small size (eg, Japanese Examined Patent Publication No. 63-2665).
No. 5). However, this type of balloon is too stiff to be used for dilating a blood vessel with flexion and severe stenosis, and cannot exhibit sufficient trackability. In addition, a polyamide (nylon) -based balloon can provide a balloon that is semi-compliant and has a relatively high pressure resistance as compared with a polyolefin or the like (eg, JP-A-3-57462).
However, after all, blood vessels with extremely bending and severe stenosis,
It has been pointed out that it tends to be a little too stiff when applied to more peripheral blood vessels.

Therefore, in this percutaneous angioplasty,
In the case of application to a blood vessel thinner than a peripheral blood vessel, there is an increasing demand for a dilatation catheter having a flexible tip portion including a balloon portion, and in this sense, a polyolefin balloon is considered to be suitable. In a flexible and relatively high-pressure balloon-loaded dilatation catheter obtained by suitable resin selection and suitable balloon molding, part or all of the shaft / balloon may be subjected to a hydrophilic treatment by a radiation graft reaction. Conceivable.

Shaft under relatively mild graft conditions
By performing hydrophilic treatment on the balloon, heat shrinkage,
Deformation does not substantially occur, and by imparting hydrophilicity,
It is possible to provide a balloon catheter having excellent running property in blood vessels.

Base Material Resin The polymer material used as the base material of the medical tube of the present invention is a polyolefin resin. Typical examples of such resins include various polyethylene / polypropylene and their copolymers, olefinic elastomers, ethylene / vinyl acetate copolymers, ethylene / butylene / styrene / block copolymers, polystyrene, acrylonitrile copolymers, and various diene polymers. Is mentioned.

As a preferable resin, a copolymer of ethylene and α-olefin can be mentioned, and various kinds of α-olefins to be copolymerized are known, but the preferable α-olefin in the present invention has 3 or more carbon atoms. Those having 4 or more carbon atoms, and particularly preferably 6 carbon atoms.

One of the preferred embodiments of the present invention is a catheter equipped with a balloon as a medical tube.
The step of subjecting the balloon to the hydrophilic treatment according to the present invention will be described in detail later. First, an example of forming the original tube (crosslinked tube) of the balloon from the base resin will be illustrated.

Extrusion Molding of Base Resin → Original Tube First, an original tube (for blow molding) having a predesigned dimension is molded. The tube molding method can be manufactured by an extrusion molding method, a copper wire coating method including a step of coating a metal wire with a resin, and then removing a copper wire serving as an inner core. The hollow extrusion method can also be preferably applied.

In extruding the original tube, cooling of the extruded tube immediately after being discharged from the die is an important requirement for blow moldability, and suitable cooling temperature conditions are set in accordance with the characteristics of the polymer material. Generally, water is used as a cooling medium, but when a lower temperature is required, a cooling medium may be used instead of the cooling water, and cooling to 0 ° C. or lower may be performed as necessary. is there. In the original tube extrusion molding of the present invention, by performing a multilayer extrusion, or by performing a multilayer coating also in the copper wire coating method,
An original tube having a multi-layer structure can be manufactured.
The resin of each layer constituting the multilayer structure can be selected from the group consisting of the same or different polymer materials as the resin of the other layers. In selecting a resin, it is a requirement that the resin of the present invention and the original tube can be formed and blow-molded together. Such a multilayer structure can be utilized to further enhance the effects of the present invention such as improvement of surface characteristics, improvement of releasability during blow molding, and increase of strength.

Irradiation of original tube with electron beam → crosslinked tube In some cases, it is preferable to use a medical tube made of polyethylene, which has been subjected to radiation crosslinking with an electron beam or the like, than a tube that has not been crosslinked. The purpose of the present invention is to carry out hydrophilic treatment by utilizing radiation crosslinking, but radiation irradiation may be performed independently or in common with such radiation crosslinking for another purpose, and it can be classified as follows: Aspect 1 Irradiation / grafting reaction (simultaneous generation of cross-linking structure) for the purpose of forming the underlying graft chain
→ Supporting hydrophilic substance Embodiment 2 Radiation irradiation for cross-linking purpose → Radiation irradiation / grafting reaction for the purpose of forming the underlying graft chain → Supporting hydrophilic substance As described above, in one of the preferred embodiments of the present invention, as a medical tube, There is a catheter equipped with a balloon, and by applying a surface hydrophilization treatment to the shaft tube including a part or all of the balloon portion of such a catheter, in addition to the flexibility inherent to polyolefin described above, the hydrophilic treatment of the shaft / balloon is also performed. Due to the synergistic effect of the two actions, it is expected that the running property in a blood vessel that is bent and highly constricted can be greatly improved, and the medical tube for balloon molding will be described in detail below.

It is known that a crosslinked tube obtained by irradiation with an electron beam having a specific dose exhibits suitable blow moldability. In general, in the formation of a crosslinked structure by electron beam irradiation, the irradiation atmosphere is also related to the dose. It is also affected by the molecular structure of the resin to be irradiated (particularly the degree of branching) and the shape and size of the member. In view of the above, in the present invention, a suitable range of cross-linking shall be explained by the gel fraction used as one of the indicators of the degree of cross-linking among experts in the art.

In the present invention, the gel fraction of the electron beam crosslinked tube evaluated by a known measuring method is preferably 0.75 to 0.95. If it is less than 0.75, the improvement of the stretching characteristics and the burst pressure by electron beam irradiation are insufficient. On the other hand, when it exceeds 0.95, the crosslinked structure becomes too strong,
Flexibility is often compromised. The range of the gel fraction is more preferably 0.80 to 0.92, and particularly preferably 0.82 to 0.90. Although it is possible in principle to generate a crosslinked structure by γ-ray irradiation instead of electron beam irradiation, the irradiation time is generally extremely long. As the monomer (including oligomer) used for forming the underlying graft chain of the medical tube of the present invention, those capable of introducing a reactive functional group into the substrate or on the surface of the substrate are particularly preferable. In addition to this covalent bond, the mechanism (bond form) for supporting the hydrophilic substance may be an ionic bond, physicochemical adhesion or adhesion, or a concerted effect of these.

In the radiation graft technique, a simultaneous irradiation method in the presence of a monomer and a pre-irradiation method in which the generation of reaction active points (radicals) and the graft reaction are separately performed are known.

In the simultaneous irradiation method, in addition to homopolymerization (formation of homopolymer) of coexisting monomers simultaneously,
In the case of a liquid phase reaction, the properties of the reaction system may change with time such that the liquid viscosity of the reaction system increases, and a uniform graft layer may not be obtained, which is not preferable. On the other hand, in the pre-irradiation method adopted in the present invention, process factors such as temperature, time, pressure and capacity can be set independently of the subsequent graft reaction step, and the irradiation method has a high degree of freedom.

In the present invention, the first step is to irradiate at least a portion of the surface of the medical treatment tube made of polyolefin resin, which is subjected to the hydrophilic treatment, with a radiation equivalent to 5 Mrad to 70 Mrad in an inert gas atmosphere. As necessary. Taking an electron beam as an example of radiation, when the dose of radiation is less than 5 Mrad, the effect of the graft reaction is small and sufficient lubricity cannot be obtained. on the other hand,
If it exceeds 70 Mrad, the cross-linking density may be high, so that the workability and assemblability as a catheter may be poor, and in extreme cases, defects such as deformation during the sterilization process may occur.

A preferred radiation dose is 10 Mrad-60.
Mrad, particularly preferably 15 Mrad to 50 M
It is rad.

In the present invention, the intensity of the radiation source can be adjusted for the purpose of controlling the properties of the graft layer. That is, when it is desired to limit the graft layer to the vicinity of the surface, the intensity of the radiation source is slightly lowered. On the other hand, for example, when it is desired to express the grafting effect to a considerably deep portion by the electron beam irradiation method, the acceleration voltage is set high and the deep portion is also deepened. It is possible to take measures such as generating sufficient radical active points as necessary.

In the present invention, the atmosphere during the irradiation of radiation is an inert gas atmosphere. Typical examples of the inert gas are nitrogen, argon, neon, helium, and mixed expectation thereof. When irradiation is performed in an atmosphere such as air, it is often necessary to carry out the graft reaction immediately immediately after irradiation. On the other hand, in an inert gas atmosphere, active points such as radicals generated by irradiation of radiation work effectively, and the graft reaction in the next step proceeds smoothly. When a long time elapses before the graft reaction after irradiation with radiation, low-temperature storage is generally performed in order to preserve active sites such as radicals. The radiation irradiation temperature is preferably 70 ° C. or lower at which the polyolefin-based tube of the present invention does not cause undesired deformation. In the above-described embodiment of the present invention, irradiation under an inert atmosphere is not always necessary for radiation crosslinking for the purpose of crosslinking only, and it can be performed under a normal air atmosphere.

Grafting reaction step In the present invention, the functional group that contributes to the carried expression is
There is no particular limitation as long as it can preferably exhibit reaction, bonding, crosslinking, adhesion and adhesion with a hydrophilic substance, but a covalent bond can be at least partially involved from the viewpoint of maintaining a lubricating surface continuously. Needless to say, is preferable.

Representative functional groups are exemplified below: In addition to acid anhydride, carboxyl group, epoxy group, amino group, phenol group, hydroxyl group, acid halide group, iminocarbonate group, halogen atom (group) A diazonium group, an azite group, an isocyanate group, and an aldehyde group that can be secondarily derived through these functional groups can be mentioned.
Particularly, a carboxyl group, an epoxy group, an amino group, an isocyanate group and an aldehyde group are preferable.

Specific monomers (including oligomers) for introducing these functional groups are described in conventionally known patent specifications (for example, Japanese Patent Publication No. 1-331).
No. 81), but specifically, the following monomers can be used.

Acid anhydride system example: Maleic anhydride, Monomer having carboxyl group Example: Acrylic acid, methacrylic acid, Monomer having epoxy group Example: Glycidyl methacrylate, Monomer having amino group Example: Various aminoalkyl meta Acrylate-Monomers having phenolic groups-Monomers having hydroxyl groups Example: Hydroxyethyl methacrylate-Monomers having acid halide groups Example: Acrylic chloride, methacrylic acid chloride-Monomers having iminocarbonate ester groups Example: Iminoethylcarbonate methacrylate Monomer having halogen atom (group) Example: vinyl chloride, vinylidene chloride Also, a monomer having a diazonium group, an azite group, an isocyanate group, or an aldehyde group that can be secondarily induced through these functional groups. The following are exemplified by.

Among these monomers (maleic acid), the following are particularly useful maleic anhydride, acrylic acid and methacrylic acid.

The above graft monomer is used to carry out a graft reaction under the following reaction conditions: Graft reaction temperature ≤ 70 ° C Monomer concentration in graft liquid ≥ 5% by weight Oxygen concentration in graft reaction system ≤ 100 ppm Graft reaction temperature is When the temperature exceeds 70 ° C, the polyolefin-based tube of the present invention often causes unfavorable deformation. Since the graft reaction rate is affected by temperature, it is preferably 10 ° C or higher, more preferably 20 ° C or higher.

In the present invention, the concentration of the monomer in the graft liquid is 5% by weight or more. If it is less than 5% by weight, the lubricity is often poorly expressed by the graft reaction. The preferable monomer concentration is 10% by weight or more, and particularly preferably 15% by weight or more. In the present invention, the graft reaction step can be carried out both in the liquid phase and the gas phase. In the case of liquid phase graft, various solvents other than water and alcohol can be used as the diluting solvent. In particular, the thickness of the graft layer and the anchoring distance from the base material interface can be controlled by appropriately selecting the base material-solvent swelling property.

The oxygen concentration in the graft reaction system is 100 p
It is pm or less. Needless to say, the permissible oxygen concentration that exhibits sufficient lubricity varies depending on the type of the graft monomer, but it is preferably 50 ppm or less, particularly preferably 20 ppm or less.

Supporting Step for Hydrophilizing Substance As the hydrophilic substance, the following natural or synthetic polymer substances or derivatives thereof can be mentioned.

<Natural polymer> Starch-based example: Carboxymethyl starch, dialdehyde starch-Cellulose-based example: CMC, MC, HEC, HPC-Tannin, nignin-based Example: Tannin, nignin-Polysaccharide-based Example: Alginic acid Sodium, gum arabic, guar gum, tragacanth, tamarind ・ Protein example: Gelatin, casein, glue, collagen <Synthetic water-soluble polymer> ・ PVA type example: Polyvinyl alcohol ・ Polyethylene oxide type Example: Polyethylene oxide, polyethylene glycol ・ Acrylic acid ・And its salt system Example: Sodium polyacrylate, acrylic acid, methacrylic acid, and their metal salts ・ Vinyl ether system Example: Methyl vinyl ether maleic anhydride ammonium salt, vinyl ether ・ Phthalic acid Example: Polyhydroxyethyl phthalate ester · Water-soluble polyester Example: Polydimethyl roll propionate ester · Ketone aldehyde resin Example: Methyl isopropyl ketone formaldehyde resin · Acrylamide / methacrylamide type Example: Dialkyl acrylamides (dimethyl acrylamide, diethyl acrylamide, methyl) Ethyl acrylamide, diisopropyl acrylamide, etc.), monoalkyl acrylamides (methyl acrylamide, ethyl acrylamide, isopropyl acrylamide, etc.), other acrylamides (2-methylpropanesulfonic acid acrylamide, dimethylaminopropyl acrylamide, etc.), acrylamide, and corresponding chemistry Structures of each methacrylamide, ・ Vinyl heterocyclic ring system Example: Vinyl Rupyridines (2-vinylpyridine, 4-vinylpyridine, etc.), vinylpyrrolidone, N-1,2,4-
Triazolyl ethylene, etc. ・ Polyamine type Example: Polyethyleneimine ・ Polyelectrolyte Example: Polystyrene sulfonate, polyacrylamide quaternized product, sodium polyvinyl sulfonate ・ Acrylate / methacrylate type Polyalkylene glycol acrylates (glyceryl acrylate, etc.), hydroxyalkylene Acrylates (hydroxyethyl acrylate, hydroxypropyl acrylate, etc.) and corresponding methacrylates of the corresponding chemical structure-Others Examples: Water-soluble nylon Among these, especially cellulosic polymer substances (eg hydroxypropyl cellulose), Polyethylene oxide polymer (polyethylene glycol),
Maleic anhydride-based polymer (eg, maleic anhydride copolymer such as methyl vinyl ether maleic anhydride copolymer), acrylamide-based polymer (eg, polydimethylacrylamide), water-soluble nylon (eg, Toray) AQ-Nylon P-70) having a good property is preferable because a low coefficient of friction can be stably obtained.

As the derivative of the above-mentioned polymer substance,
It is not limited to a water-soluble substance, and if the water-soluble polymer substance is used as a basic constituent, there is no particular limitation, and even if it is insolubilized, it has a degree of freedom in the branched chain and it contains water. I wish I had it.

For example, an esterified product obtained by condensation, addition, replacement, oxidation, reduction reaction or the like of the above-mentioned polymer substance,
Salt, amidated product, anhydride, halide, etherified product, hydrolyzed product, acetalized product, formalized product, alkylolated product, quaternized product, diazotized product, hydrazide compound, sulfonated product, nitrated product, ion complex: diazonium group, A substance having two or more reactive functional groups, such as an azide group, an isocyanate group, an acid chloride group, an acid anhydride group, an iminocarbonic acid ester group, an amino group, a carboxyl group, an epoxy group, a hydroxyl group, and an alkyl group, and a crosslinked product;
Examples thereof include vinyl compounds, acrylic acid, methacrylic acid, diene compounds, and copolymers with maleic anhydride.

In the surface-hydrophilized medical tube of the present invention, the hydrophilization can be carried out at any stage of the member tube immediately after extrusion, after assembling into a catheter, or an intermediate stage therebetween. As an example, PT
The timing of performing the hydrophilic treatment on both the shaft and the balloon of the CA dilatation catheter is exemplified below: Process Hollow extrusion of a polyolefin resin and molding of the original tube by an electric wire coating method.

The process tube is irradiated with radiation to form a crosslinked tube.

Blow molding is applied to the crosslinked tube,
Create an original balloon (heat treatment balloon). Prepare the shaft tube.

Assemble the PTCA dilatation catheter using the raw process balloon and shaft tube.

Process A hydrophilic PTCA dilatation catheter carrying a hydrophilic substance is prepared.

As described above, the PTCA dilatation catheter is roughly made in five stages. The timing for applying the underlayer graft chain, which is the pre-stage of the hydrophilization treatment, can be performed between the steps a to b, the steps b to c, and the steps c to. At timing a, only the balloon is hydrophilized, and the shaft tube must be hydrophilized at a later timing, but at timings b and c, both the balloon and the shaft tube can be hydrophilized. However, at timing b, the balloon and the shaft tube need to be hydrophilized respectively, but at timing c, the hydrophilic treatment of the balloon and the shaft tube can be performed at one time, so c is the most preferable timing. I can say. In this way,
The hydrophilic substance can be supported only where the underlying graft chain is formed by irradiation with radiation.

Further, even if the underlying graft chain is formed on the entire surface, only the portion on which the hydrophilic substance is carried is hydrophilized, so that the portion to be hydrophilized can be set at a desired position. For example, if you want to support only the tip of a medical tube, you only need to immerse only the tip in the reaction liquid of the hydrophilic substance, and if you want to partially hydrophilize it, apply masking etc. You may make it react by immersing in the reaction liquid of.

Specific examples of the present invention will be described below.

[0060]

Examples 1 to 6 Low density polyethylene (C6 LLDPE
Resin: Tosoh Co., Ltd. Nipolon-Z, melt flow rate = 1.0 g / 10 min, specific gravity 0.92) pellets were melted by an extruder and coated on a copper wire having a diameter of 0.5 mm.
The diameter of the coated electric wire was 0.940 mm. Therefore,
The thickness of the (coated) original tube corresponds to 220 μm. From the above alloy-coated copper wire, the inner core copper wire was removed to prepare an original tube.

An electron beam was applied to the above original tube at an irradiation dose of 30 Mr.
Irradiated under a nitrogen atmosphere with ad. Here, the purpose is to crosslink the original tube and at the same time to develop the starting point of radicals.

The above-mentioned original tube was prepared by using maleic anhydride as a monomer for forming a base graft chain, and using toluene as a solvent (oxygen concentration in toluene was 5 ppm) at 50 ° C.
The graft reaction was carried out by changing the monomer concentration and the grafting time.

On the tube on which the base graft was formed,
Table 1 shows the lubricity of a hydrophilization source tube obtained by reacting a chloroform solution of a dimethylacrylamide-glycidyl methacrylate copolymer as a hydrophilic substance under a pyridine catalyst.

[0064]

[Table 1]

[0065]

Example 7 The same method as in Example 1 except that the electron beam irradiation amount was 25 Mrad, the monomer concentration of maleic anhydride was 30% by weight, the grafting time was 2 hours, and the hydrophilic substance was changed to polyvinylpyrrolidone. The tube was hydrophilized with. The resulting tube showed good lubricity.

[0066]

[Example 8] Application to PTCA dilatation catheter Using the tube with electron beam irradiation and maleic anhydride as a base graft used in Example 5, a balloon-like shape can be obtained by blow pressurization in a constant temperature range. . Blow molding using an extruded original tube is described in, for example, JP-B-63-26655.
Also in this embodiment, the above tube is inserted into a balloon molding die having a cavity having a desired outer diameter dimension and set in a balloon molding machine. Next, the temperature is raised to an appropriate temperature and then stretched in the machine direction. In order to expand and shape the once stretched tube in a blow molding machine, any gas,
For example, a gas such as nitrogen can be used. Also,
Blow molding using heated gas or the like is also applicable. The above-mentioned longitudinal stretching step and blowing step can be carried out continuously in the same mold, and the temperatures of both steps can be set to the same level. By performing the above-described longitudinal stretching step to blowing step in multiple stages, a high pressure resistant balloon with less uneven thickness can be manufactured. A balloon was prepared by applying a blow molding machine for balloon molding and longitudinally stretching and blow molding at 105 ° C. In the test of the balloon alone,
In addition, the pressure resistance was relatively high (14 to 16 atm).

After thinning the joint portion of the balloon with the shaft, the balloon tip joint portion is joined with the polyolefin inner pipe shaft, the base joint portion is joined with the polyolefin outer pipe shaft, and the hub is joined to the base portion. Assembled a good PTCA dilatation catheter with a flexible tip. Both the outer tube shaft and the inner tube shaft used for catheter assembly were irradiated with an electron beam in a nitrogen atmosphere at 10 Mrad,
Similarly, a tube on which maleic anhydride was grafted was used.

A tracker in a blood vessel model of a catheter obtained by reacting a chloroform solution of a dimethylacrylamide-glycidyl methacrylate copolymer as a hydrophilic substance with a dilatation catheter composed of a tube on which this underlayer was grafted under a pyridine catalyst. The evaluation result of the virility was superior to the comparative catheter which was not subjected to the hydrophilization treatment.

[0069]

Example 9 Methacrylic acid was used as a graft monomer instead of maleic anhydride, and the hydrophilic substance was
A PTCA dilatation catheter was prepared in the same manner as in Example 8 except that dimethylacrylamide was used.

[0070]

INDUSTRIAL APPLICABILITY According to the present invention, at least a portion of the surface of a medical treatment tube made of a polyolefin resin, which is subjected to a hydrophilization treatment, is irradiated with a predetermined amount of radiation in an inert gas atmosphere, and then a predetermined amount of graft monomer is used. Under this condition, a graft graft chain is formed to form a ground graft chain, and a hydrophilic substance is supported on the generated ground graft chain to perform hydrophilic treatment on the surface of a medical tube. It is possible to provide a useful medical tube because hydrophilicity can be easily imparted without impairing the above.

Further, since the portion imparting hydrophilicity can be limited to only the portion supporting the hydrophilic substance, there is an effect that the portion to be hydrophilized can be easily changed according to the purpose.

Claims (4)

[Claims] 1. At least a portion of the surface of a medical treatment tube made of a polyolefin resin to which hydrophilic treatment is applied, 5Mr.
Radiation equivalent to ad to 70 Mrad is irradiated in an inert gas atmosphere, and then a graft monomer is used to form a base graft chain by a graft reaction under the following conditions: graft reaction temperature ≦ 70 ° C. monomer concentration in graft liquid ≧ 5% by weight Oxygen concentration in graft reaction system ≤ 100 ppm Further, a method for producing a medical tube having a surface hydrophilized treatment, characterized in that a hydrophilic substance is supported on the formed underlayer graft chain. 2. It is manufactured by the manufacturing method according to claim 1.
A surface-hydrophilized medical tube characterized in that a hydrophilic substance is carried on the surface of a tube made of a polyolefin resin through a hydrophilic underlayer graft chain. 3. The base graft chain comprises an acid anhydride, a carboxyl group, an epoxy group, an amino group, a phenol group, a hydroxyl group, an acid halide group, an iminocarbonate group, a halogen atom (group), a diazonium group, an azite group, The medical tube according to claim 2, which is a monomer capable of directly or secondarily inducing a functional group selected from the group consisting of an isocyanate group and an aldehyde group. 4. The hydrophilic substance comprises a group of natural polymer substances (starch, cellulose, tannin / nignin, polysaccharides, proteins) and a group of synthetic water-soluble polymer substances (PVA). , Polyethylene oxide type,
Acrylic acid type, maleic anhydride type, phthalic acid type, water soluble polyester, ketone aldehyde resin, acrylamide type, polyvinylpyrrolidone type, polyamine type, polyelectrolyte, water soluble nylon type, acrylamide type, acrylate type, vinyl heterocyclic ring type The acrylic acid-based sidyl acrylate-based material is selected from the group consisting of:
Or the medical tube according to any one of 3).