JP4744129B2 - Catheter tube - Google Patents

Description

  The present invention relates to a medical catheter tube that is inserted into a blood vessel or other body cavity and used for diagnosis or treatment.

  In recent years, in order to reduce the physical and time burden of patients, examples of using catheters for diagnosis and treatment methods are increasing. Generally, a catheter is inserted into a living body through a blood vessel, ureter, trachea, esophagus, etc., and has high operability as a medical instrument for accurately reaching a predetermined living body site without damaging a blood vessel wall or a living organ. In addition to structural requirements for safety, injecting drugs, etc. from the outside to a predetermined site in the patient's body through the tube lumen formed by the inner layer resin, discharging body fluid, etc. in the body, Maintaining and expanding the lumen diameter to allow other therapeutic devices to pass through and lubrication of the lumen surface (the inner surface of the tube of the inner resin layer) and the drug passing through it or other therapeutic devices or guide wires It is said that.

  In response to the structural requirements as described above, the conventional catheter is, for example, a flexible and flexible tip for insertion without damaging blood vessels and living organs, and a continuous tip. A torque transmission portion (main body portion) that retains torque transmission properties for reliably reaching the predetermined portion. In addition, the torque transmission part (main body part) is provided with a reinforcing layer using a metal wire on the inner layer tube or is made of a hard material in order to improve torque transmission. In addition, the tip is made of a soft material so that it is easy to bend and rich in elasticity, or it is made by connecting a tube without a reinforcing layer containing a metal wire as a tip to the main body (torque transmission part). It is.

  As a conventional catheter manufacturing method, first, an inner resin layer is provided on a metal wire (core wire), and if necessary, corrosion resistance is provided on the outer periphery of the inner resin layer tube formed on the resulting metal wire (core wire). There is known a manufacturing method in which a metal wire (reinforcing material) is used to reinforce, an outer layer resin layer is provided so as to cover the inner layer resin layer tube or the reinforcement, and a metal wire (core wire) is drawn from the obtained multilayer tube body Yes. For example, see Patent Document 1.

  Furthermore, in order to meet the above-mentioned required performance with respect to the inner resin layer of the catheter, particularly the lumen surface, a variety of catheter tubes have been developed. As a constituent material of the inner resin layer, high density polyethylene is used. (Hereinafter abbreviated as HDPE) There are many examples of using a resin or a fluororesin, particularly a PTFE resin. Catheter tubes using HDPE resin or PTFE resin for the inner resin layer have low inner surface friction and excellent lubricity. Effective in terms of ease. In this case, polyamide, polyurethane resin, or the like is used as a constituent material of the outer resin layer in order to mix an X-ray contrast agent or maintain strength and workability at the tip, and also reduce the outer diameter of the catheter. In order to increase the inner diameter of the inner resin layer, it is required to form an inner resin layer made of HDPE resin or PTFE resin very thin. In the case of HDPE resin and PTEF resin, PTFE resin is preferred for clinical use from the viewpoints of heat resistance and durability and the purpose of reducing frictional resistance with the guide wire. In general, it is well known that PTFE resin is the lowest among various materials in comparison of dynamic friction resistance values of materials themselves, and it is known that PTFE is superior in heat resistance and chemical resistance.

JP 2000-316977 A

  Medical devices such as catheters need to be sterilized before use due to the fact that they are used on living bodies. There are various types of sterilization methods such as gas and steam, but these have problems such as the toxicity of gas and the long processing time required for sterilization. In recent years, sterilization by radiation such as electron beams has attracted attention. It's getting on.

  However, PTFE has a very low resistance to radiation, and has a problem that it deteriorates remarkably. PTFE resin is deteriorated by irradiation with ionizing radiation of 1 kGy or more (collapse type), and mechanical properties are extremely deteriorated at an absorbed dose of around 25 kGy, which is a sterilization dose generally used for γ-ray and electron beam sterilization. In particular, it is known that the breaking elongation is greatly reduced. Therefore, it is said that radiation sterilization cannot be applied to a catheter tube using PTFE resin as an inner layer. Even if it is adapted, the PTFE resin after radiation sterilization has a significantly reduced elongation at break. Therefore, when the catheter tube is bent, the inner layer is liable to be peeled off or cracked, resulting in a decrease in strength and quality deterioration of the catheter tube itself. It is not preferable.

  Patent Document 1 is a catheter tube having an inner resin layer and an outer resin layer on the inner resin layer for the purpose of improving the wear resistance of the catheter tube, and the inner resin layer contains a crosslinked PTFE resin. A catheter tube characterized by being made of PTFE resin is disclosed. Since the cross-linked PTFE resin is a cross-linked polymer, its processability is worse than that of the non-cross-linked PTFE resin, so that it cannot be processed into a tube as it is and is molded as a blend with the non-cross-linked PTFE resin. However, in that case, since uncrosslinked PTFE resin must be the main component in the matrix, the radiation sterilization resistance is equal to or less than that of the uncrosslinked PTFE resin, so that the radiation sterilization resistance as a catheter tube cannot be obtained.

  The present invention has been devised to solve such problems. An object of the present invention is to provide a catheter tube having an inner resin layer imparted with radiation sterilization resistance while maintaining the lubricity characteristics of PTFE resin that has been suitably used for an inner layer of a conventional catheter tube.

  Such an object is achieved by the present inventions (1) to (5) below.

  (1) A catheter tube having a lumen and having a resin layer which is made of only a crosslinked PTFE resin and defines the inner surface of the lumen.

  (2) The catheter tube according to (1), further including an outer resin layer that covers an outer surface of the inner resin layer.

  (3) The catheter tube according to (2), wherein a reinforcing layer is further provided at a boundary portion between the inner resin layer and the outer resin layer.

  (4) The catheter tube according to (3), wherein the reinforcing layer is made of a metal wire.

  (5) The catheter tube as described in (1) above, wherein the inner resin layer is composed of only PTFE resin crosslinked by radiation.

  The catheter tube according to the present invention uses cross-linked PTFE resin for the inner resin layer, and can be adapted for radiation sterilization. Cross-linked PTFE resin is equivalent to uncross-linked PTFE resin in terms of slidability, durability, and chemical resistance, and is superior to HDPE resin. It can contribute to medical economic efficiency and environmental load reduction.

  Hereinafter, the catheter tube of the present invention will be described in detail based on a preferred configuration example shown in the accompanying drawings.

  FIG. 1 is an overall view showing an embodiment of a catheter tube of the present invention. FIG. 2 is a longitudinal sectional view of the catheter tube shown in FIG.

  The catheter tube 1 includes a main body 100 having a distal end 101 and a proximal end 102, and a hub 103 connected to the proximal end 102 of the main body 100. Further, a lumen 104 penetrating from the hub 103 to the tip 101 is formed.

  As shown in FIG. 2, the main body 100 of the catheter tube 1 of the present invention is constituted by an inner resin layer 2 and an outer resin layer 3 made of a crosslinked PTFE resin. The thickness of the cross-linked PTFE resin layer of the inner layer 2 is preferably 0.1 to 1000 μm, more preferably 1 to 100 μm. The cross-linked PTFE resin layer of the inner layer 2 is intended to provide a function of lubrication and chemical resistance, and is preferably thinner. The thickness and configuration of the outer resin layer 3 are determined according to desired catheter tube characteristics. That is, the resin material and the hardness may be different on the proximal side, the intermediate portion, and the distal end portion, and it is preferable in terms of catheter operability such as the ability to follow the blood vessel to bend, and the proximal side is harder and softer toward the distal end 101. Moreover, you may provide the reinforcement layer 4 which consists of a single or several metal wire or a non-metal wire between the said inner resin layer 2 and the said outer resin layer 3 as needed. The reinforcing layer 4 preferably has a form in which a linear body is braided or spirally wound.

  As a manufacturing method of the catheter tube in this embodiment, after creating the inner resin layer 2 made of a crosslinked PTFE resin, the reinforcing layer 4 is provided around the inner resin layer 2, and the outer resin layer 3 is further formed therearound.

  The inner layer resin layer 2 made of a crosslinked PTFE resin can be produced by a method of irradiating an electron beam after creating a PTFE tube by a known method, or by irradiating an electron beam to the PTFE membrane to produce a crosslinked PTFE membrane. There is a method of processing, but the former is easier to manufacture.

  The PTFE tube in the former is generally formed by extruding raw materials such as PTFE fine powder and PTFE coating dispersion on a metal core wire. There may or may not be a core wire during electron beam irradiation.

  The core wire may be any of copper, aluminum, iron, silver, platinum, gold and the like, or an alloy thereof, or an alloy obtained by adding tin, zinc or the like to these alloys. Further, the core wire is preferably a single wire from the viewpoint of the smoothness of the inner surface of the tube, but may be a stranded wire if necessary, or may be a single wire or a material plated in a lump. The most preferable examples from the viewpoint of workability and cost include a single-line tin-plated annealed copper wire and silver-plated annealed copper wire.

  The cross-linked PTFE resin used in the present invention has a melting point of 270 ° C. to 320 ° C. and a peak calorific value (ΔH) of −30 to −30 in the endothermic curve observation of the crystalline melting point of the resin using a differential scanning calorimeter (hereinafter abbreviated as DSC). What shows 40 [J / g] is preferable. In uncrosslinked PTFE, the melting point is 330 to 350 ° C., and ΔH is −20 to −30 [J / g]. It is known that the crystallinity is lowered as the crosslinking proceeds. However, if the crystallinity is lowered so much, the strength and elongation of the material itself are lost, which is not preferable. Specifically, cross-linked PTFE having a melting point of 280 ° C. or lower and −20 [J / g] or lower is not preferable because the mechanical properties are weak when the catheter tube is used and the requirement is not satisfied. In addition, those having a melting point of 350 ° C. to 320 ° C. and ΔH of −50 to −60 [J / g] cause the main chain of the polymer to be cut by electron beam irradiation, and the ultra low molecular weight PTFE resin alone or super It is a mixture of a low molecular weight PTFE resin and an ultra-low molecular weight crosslinked PTFE resin, and the strength and elongation at break are remarkably low. When this is also used as a catheter tube, the mechanical properties do not satisfy the requirements, which is not preferable. In some cases, a mixed peak (multi-peak) or a shoulder peak may be recognized as a cross-linked / un-cross-linked transition state. In this case, confirmation of mechanical strength before and after radiation sterilization is necessary, and it cannot always be used. On the other hand, there are some that can be used if you are careful, but you need to be aware that they are unstable. Therefore, it is more preferable to show a single peak, a melting point of 280 ° C. to 320 ° C., and a peak heat value (ΔH) of −30 to −40 [J / g].

  In the present invention, the method of crosslinking the PTFE resin is not particularly limited, but a method of irradiating ionizing radiation is effective. Preferably, it is carried out by irradiating an electron beam with an acceleration voltage of 100 keV or higher in a state where the coated PTFE resin is heated to near 330 ° C. to 350 ° C. in a deoxygenated atmosphere or under inert gas substitution. An electron beam having an acceleration voltage of 100 keV or more is preferable in that a high time dose rate can be easily obtained. More specifically, since it varies depending on the diameter of the PTFE resin layer and the thickness of the coating, it is necessary to appropriately select the production conditions. However, the acceleration voltage is preferably 300 KeV to 10 MeV, and the irradiation dose is preferably in the range of 1 kGy to 10 MGy, and 200 kGy. A range of ˜1 MGy is more preferred.

  The produced cross-linked PTFE resin can be subjected to the DSC analysis to determine whether it can be used. Inappropriate irradiation conditions may cause problems such as cracks, blisters, pinholes, shrinkage deformation, etc. in the crosslinked PTFE resin tube. Even the DSC data range is excluded. It is preferable to perform a surface treatment on the outer surface of the inner resin layer of the formed crosslinked PTFE resin because it can improve the adhesion with the outer resin layer. For example, corona treatment, plasma treatment, UV treatment, tetraetch treatment and Graft polymerization, anchor coating agent application, and adhesive application performed together with these various surface treatments may be appropriately performed.

  Examples of the material for the outer resin layer in the present invention include polyolefins such as polyethylene, polypropylene, and polybutadiene, soft / hard polyvinyl chloride, polyurethane, epoxy resin, cycloolefin, ethylene-vinyl acetate copolymer, polyethylene terephthalate, poly, and the like. Polyester such as butylene terephthalate, polyamide such as nylon 12, nylon 11, nylon 610, nylon 612, nylon 66, nylon 6, etc., polyether polyamide, polyether block amide, polyester polyamide, ABS resin, AS resin, fluorine resin, shape Various resin materials such as memory resin, styrene, polyolefin, polyurethane, polyester, polyamide, polybutadiene, trans polyisoprene, fluoro rubber, chlorination Examples include thermoplastic elastomer resins such as polyethylene, thermosetting elastomer resins such as silicone and vulcanized rubber, and combinations of two or more of these (polymer alloys, polymer blends, laminates, etc.) It is done. These are appropriately used according to the type of catheter to be applied and the type of blood vessel to be used.

  In addition, the catheter tube of this embodiment can further connect a flexible tip tube to the front-end | tip. The tip tube is usually formed of a single layer and does not have an inner layer with high lubricity. This is because the axial length of the tip tube is sufficiently shorter than that of the tube main body 100, so that a highly lubricious inner surface is not necessarily required. As the material of the tip tube, a material having very high flexibility and radiation resistance such as polyurethane elastomer is preferable.

(Formation of crosslinked PTFE resin layer)
A continuous wire was prepared by extrusion-coating PTFE resin at a thickness of 40 μm on a silver-plated annealed copper wire of φ0.65 mm. The conductor outer diameter of the core wire was 0.65 ± 0.015 mm, and the thickness of the PTFE resin layer was 0.04 ± 0.020 mm. Using this electron beam irradiation apparatus having an acceleration voltage of 800 keV on this PTFE-coated copper wire, electron beam irradiation was continuously performed at an irradiation dose of 370 kGy in a nitrogen gas atmosphere (oxygen concentration of 300 ppm or less) on both sides of the PTFE-coated copper wire. went.

(Evaluation of cross-linked PTFE resin tube)
The DSC analysis results of the tube obtained by removing the copper wire after irradiation and the intensity and elongation changes before and after electron beam sterilization (acceleration voltage 10 MeV, irradiation dose 33 kGy-air irradiation) were examined. The results are shown in Table 1.

From the tensile test results shown in Table 1, the strength maintenance rate of the uncrosslinked PTFE resin tube was 54% and the elongation maintenance rate was 5%. By sterilization, the strength was reduced by half and the elongation was reduced to 1/10 or less. On the other hand, in cross-linked PTFE, the strength maintenance ratio before and after sterilization is 104% (same elongation 84%), and almost no deterioration due to sterilization is observed. The material strength in terms of cross-sectional area is 44 MPa in the case of cross-linked PTFE resin, and the strength in practical use is generally 30 to 40 MPa because the material strength of HDPE resin and nylon resin generally used for catheter tubes is generally 30 to 40 MPa. It can be said that it is enough. That is, it can be seen that the cross-linked PTFE resin tube has almost no deterioration in physical properties before and after electron beam sterilization, and it is clear from comparison with unirradiated PTFE that it has radiation sterilization resistance.

  As a production condition of crosslinked PTFE, it is preferable to control the temperature range to around PTFE resin melting point 340 ± 10 ° C. However, since the control range is very narrow, the resulting tube is evaluated by DSC analysis each time, and the crosslinked PTFE resin tube It is preferable to confirm that it has been generated.

(Manufacture of catheter tubes and guidewire slidability evaluation)
On the continuous core wire having the crosslinked PTFE resin layer prepared as described above, a polyamide elastomer (PAE) (Pebax manufactured by Atochem) having a thickness of 120 μm is extrusion coated, and the core wire is drawn from the obtained multilayer coating. A two-layer catheter tube having an outer diameter of 0.97 mm (2.9 Fr.) was prepared as an example. As a comparative example, a catheter tube having the same configuration using uncrosslinked PTFE resin and HDPE resin was prepared. Comparative Example 1 had an inner diameter of 0.65 mm and an outer diameter of 0.97 mm, and the inner layer was an uncrosslinked PTFE resin (thickness 40 μm) and an outer layer polyamide elastomer resin (thickness 120 μm). In Comparative Example 2, the inner diameter was 0.65 mm, the outer diameter was 0.97 mm, and the inner layer was uncrosslinked HDPE resin (thickness 40 μm) and outer layer polyamide elastomer resin (thickness 120 μm).

(Internal lubricity evaluation test and results)
A lubricity evaluation test was conducted on the guide wire on the inner surface (lumen surface) of the catheter tube (non-sterile product) obtained in Examples and Comparative Examples 1 and 2. FIG. 3 is a schematic explanatory view of a lubricity evaluation test. A test body (catheter tube) having a total length of 100 mm was formed into a U shape having a semicircular portion with a diameter of 10 mm, and was fixed to a plastic mount with a transparent adhesive tape, and the slidability of the guide wire was evaluated. At this time, physiological saline is replenished to the lumen of the catheter tube 1 using a syringe. The stroke of the load cell 5 for tensile test is set to 50 mm, and the tip of the catheter tube 1 and the tip of the guide wire 5 are set to coincide with each other at the center of the stroke. The distance between the catheter tube insertion end and the guide wire gripping portion was 50 mm, and the stroke speed was 500 mm / min. The guide wire 6 used is a stainless steel spring guide wire (Cat. No. SSFU80-018) manufactured by Lake Reuge Co. (Lake Region, USA) and having an outer diameter of 0.018 inches. It was. The guide wire 6 was put in and out 250 times, and the force required at this time (the width obtained by adding the indentation load and the retraction load) was measured and used as an index for evaluating the inner surface lubricity. FIG. 4 is a schematic diagram of a chart showing the relationship between the indentation load and the number of withdrawals of the guide wire. As schematically shown in FIG. 4, the amplitude of the saw-shaped waveform in the measurement of the force required to move the guide wire 6 in and out is used as the measurement value. That is, (1) as an initial lubricity value, an average value from the third reciprocation to the fifth reciprocation (hereinafter referred to as an initial sliding resistance value), and (2) as a lubricity value for viewing durability, The values for the 100th and 250th round trips were used. In addition, after the test was completed, red ink was injected to observe the occurrence of scratches, wrinkles, and kinks on the inner surface of the catheter tube at the end of the test. The results are shown in Table 2.

From Table 2, the catheter tube having the uncrosslinked PTFE resin inner layer of Comparative Example 1 and the HDPE resin inner layer of Comparative Example 2 and the catheter tube of the crosslinked PTFE resin inner layer of Example 1 all have a sliding resistance value of about 100 times. It was found to have good guide wire slidability of 40 to 50 g. Comparative Example 1 also had the same value, but the catheter tube having the HDPE resin inner layer of Comparative Example 2 had a slightly high initial sliding resistance value, and the durability lubrication value tended to rise again from around 200 times. It was seen. There was no difference in initial sliding resistance value and durability lubricity between uncrosslinked and crosslinked PTFE. From the results of the inner surface observation, innumerable scratches were observed on the inner surface of the HDPE resin inner layer of Comparative Example 2, and it was assumed that this had an influence on the initial sliding resistance value and the lubrication durability. No scratches or the like were observed in uncrosslinked and crosslinked PTFE.

  In addition, the same experiment was performed on the catheter tubes of Examples and Comparative Examples 1 and 2 which were sterilized by electron beam. As a result, Comparative Example 1 could not be tested because the uncrosslinked PTFE resin inner layer was severely deteriorated and cracked when it was bent into a U shape and eventually broke. About Example and the comparative example 2, the result substantially equivalent to the non-sterile goods was obtained.

It is a whole side view which shows the Example of the catheter tube of this invention. It is a longitudinal cross-sectional view of the catheter tube shown in FIG. It is a model explanatory drawing of a lubricity evaluation test. It is a schematic diagram of the chart which shows the relationship between indentation load and the number of times of guide wire pulling out.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Catheter tube 2 ... Inner layer resin layer (crosslinked PTFE resin layer)
3 ... Outer resin layer 4 ... Reinforcing layer

Claims (5)

   A catheter tube having a lumen and having a resin layer which is composed only of a crosslinked PTFE resin and defines an inner surface of the lumen.   The catheter tube according to claim 1, further comprising an outer resin layer that covers an outer surface of the inner resin layer.   The catheter tube according to claim 2, wherein a reinforcing layer is further provided at a boundary portion between the inner resin layer and the outer resin layer.   The catheter tube according to claim 3, wherein the reinforcing layer is made of a metal wire. The catheter tube according to claim 1, wherein the inner resin layer is made of only PTFE resin crosslinked by radiation.

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