JPH11290458A - Catheter and manufacture thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a catheter of favorable operability and a manufacturing method thereof capable of inserting it into a body to reach a target regio without injuring luminal wall. SOLUTION: In a catheter having lubricity when the surface is wetted, lubricity of a catheter tip part is the highest, while lubricity at a base part is the lowest. Solution including hydrophilic high polymer is brought to get in contact with the surface of the catheter to couple hydrophilic high polymer with the surface of the catheter, time to get solution including hydrophilic high polymer in contact with the catheter surface is changed in a catheter length direction. In bringing hidrophilic high polymer and solution including compound to react with hydrophilic high polymer to get in contact with the catheter surface for crosslinking hydrophilic high polymer for forming a crosslinked coating of hydrophilic high polymer on the catheter surface, thickness of the crosslinked coating is formed thicker at the tip part than at the base part.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a catheter and a method for manufacturing the same. The present invention relates to a catheter for performing diagnosis and a method for manufacturing the same.

[0002]

2. Description of the Related Art Conventionally, catheters have been used for administration of high-calorie infusions, blood access for hemodialysis, and the like.
Diagnosis and treatment have often been performed by injecting a contrast agent or drug into a target site via a transcatheter. A catheter used for such a purpose must be inserted as close as possible to a target site. In the vicinity of the target site, the lumen of a living body, mainly a blood vessel, is generally small in diameter and is bent, so that the catheter follows the shape of the bent lumen and can pass without damaging the lumen wall. It must be flexible, but at the same time it must be rigid enough to allow the catheter tip to be inserted into the target site by manipulation from outside the body. To meet such performance requirements, two approaches have been taken.

[0003] One method is to impart lubricity to the catheter surface to reduce friction with the lumen wall. As such a method, Japanese Patent Application Laid-Open No. 54-29343 discloses a method of forming an interpolymer of polyvinylpyrrolidone and polyurethane on the surface, and Japanese Patent Application Laid-Open No. 59-81341 discloses a method of forming an A method of covalently bonding a hydrophilic polymer to the isocyanate of the reaction is disclosed in Japanese Patent Application Laid-Open No. 58-19 / 1983.
No. 3,766 discloses methods of forming a coating of polyethylene oxide on the surface via a compound having an isocyanate group. In Japanese Patent Publication No. 33181/1989, a method of covalently bonding a maleic anhydride polymer to the surface is disclosed. In Japanese Patent Application Laid-Open No. 6-7426, a polymer material is swollen with a polar solvent and the hydrophilicity in the solvent is increased. Japanese Patent Application Laid-Open No. 5-76590 discloses a method for imparting lubricity by impregnating a polymer material with a water-soluble polymer compound. A method is disclosed.

[0004] Another approach is to mold the distal portion with a flexible material and the proximal portion with a rigid material. JP-A-48-42589 discloses a plastic tube in which materials having different flexibility are joined. Also, JP-A-58-218966, JP-A-60-31765, and JP-A-7-308385.
Japanese Patent Application Laid-Open No. 7-148264 discloses a two-layer tube formed of a layer made of a highly flexible material and a layer made of a highly rigid material. A catheter is disclosed in which the flexibility of the distal portion is greater than the flexibility of the proximal portion by varying the ratio of both layers or by confining a layer of a rigid material to the proximal portion.

[0005]

By appropriately combining the above approaches and the two approaches, it is possible to prevent the catheter wall from being damaged when the catheter moves toward the target site in the body lumen. Fewer catheters are being manufactured. Such a catheter is usually housed in a cylindrical container called a sheath, and when used, the sheath is filled with saline or heparinized saline to wet the catheter surface and improve the slip of the catheter. Remove from sheath and insert into body. However, since the catheter having high flexibility and lubricity is slippery, it has a drawback that it is difficult to remove the catheter from the sheath and insert it into the body. In particular, in the catheter in which the ratio of the length of the body insertion portion to the entire catheter is large, and the length from the catheter distal portion to the proximal portion is relatively long,
In order to avoid slipperiness, it was difficult to remove the sheath from the sheath only at the proximal end, and insert it into the body or withdraw it from the body. An object of the present invention is to provide a catheter with good operability, which can be inserted into a target site without damaging a lumen wall when inserted into a body, and a method for manufacturing the same.

[0006]

Means for Solving the Problems The present inventors have made intensive studies to solve such problems, and as a result, by increasing the lubricity of the distal end portion of the catheter and decreasing the lubricity of the proximal end portion, The present inventors have found that in a patient's body, particularly in a thin lumen near a target site, damage to the inner wall of the lumen can be suppressed due to the high lubricity of the catheter tip portion, and the catheter can be easily inserted. That is,
The present invention, a catheter having a lubricity when the surface is wet, the catheter having the highest lubricity at the distal end of the catheter and the lowest lubricity at the proximal end,
When the hydrophilic polymer is brought into contact with the surface of the catheter by bringing the solution containing the hydrophilic polymer into contact with the surface of the catheter, the time for bringing the solution containing the hydrophilic polymer into contact with the surface of the catheter is reduced by the length of the catheter. The method of manufacturing a catheter, characterized in that the catheter is changed in the vertical direction, and further, the surface of the catheter is brought into contact with a solution containing a hydrophilic polymer and a compound that reacts with the hydrophilic polymer to crosslink the hydrophilic polymer. The gist of the present invention is a method for producing a catheter, characterized in that when forming a crosslinked film of a hydrophilic polymer, the thickness of the crosslinked film is larger at the distal end portion than at the base end portion.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.

The catheter of the present invention has lubricity when the surface is wet, and has the highest lubricity at the distal end and the lowest lubricity at the proximal end. The height of the lubricity of the catheter surface may change continuously or stepwise as long as the distal portion is higher than the proximal portion. Further, it may be composed of a portion where the degree of lubricity changes continuously and a portion where the lubricity changes stepwise. Further, at least one of a portion where the lubricity is continuously changed or a portion where the lubricity is changed stepwise may be present at a plurality of locations.

The height of the lubricity at each of the distal end portion, the proximal end portion, and the intermediate portion between the distal end portion and the proximal end portion can be increased stepwise even if the lubricity continuously changes within each portion. Or may be constant. The lubricity may be continuously changed in at least a part of the part consisting of the distal end part and the intermediate part and the part consisting of the intermediate part and the base end part. The height of the lubricity on the tip side and the tip portion of the intermediate portion may be the same or different. Further, the lubricity at the base end side and the base end portion of the intermediate portion may be the same or different. In the case where the lubricity in the intermediate portion changes continuously or in a stepwise manner, a gap having a high lubricity does not occur from the distal end portion to the proximal end portion of the catheter. It is preferable because the insertion and withdrawal operations can be performed smoothly and damage to the inner wall of the lumen is less likely to occur as compared with those having the above.

Here, the lubricity in the present invention is evaluated based on the coefficient of friction measured by the following gradient method, and the smaller the coefficient of friction, the higher the lubricity. The friction coefficient is measured by first arranging two lubricated catheters on an inclined plate and placing a 100 g weight on the catheters. Next, the catheter was wetted with water, the inclined plate was inclined at a constant speed, the angle of the inclined plate when the weight began to slide was measured, and the tangent was used as the coefficient of friction.

As for the lubricity of the tip portion, the friction coefficient of the portion having the highest lubricity is preferably 0.3 or less, more preferably 0.2 or less. As for the lubricity of the base end portion, the coefficient of friction of the portion having the lowest lubricity is preferably 0.6 or more, more preferably 0.7 or more. Both the tip and the base have the highest lubricity on the tip, the base has lower lubricity than the tip, and the lubricity continuously changes in each part. preferable. Also, if there is a portion where the lubricity changes suddenly, the resistance suddenly increases at the portion where the lubricity changes when inserted into the body, and it may be very difficult to operate, so the proximal side of the distal end portion It is preferable that the difference in lubricity between the base portion and the distal end side is small. As such a catheter, for example, the friction coefficient on the distal side of the distal portion is 0.2 or less, and the friction coefficient on the proximal side is 0.3.
0.6, the coefficient of friction on the distal end side of the base end portion is 0.3-0.
6. Catheter having a coefficient of friction of 0.8 or more on the proximal side of the proximal portion.

If the lubricity of the distal portion and the proximal portion does not change continuously in any portion, a gap having a high lubricity may occur between the distal portion and the proximal portion. Therefore, it is preferable to provide an intermediate portion, which is lower than the distal end portion and has higher lubricity than the proximal end portion, between the distal end portion and the proximal end portion. In this case, the lubricating property of the tip portion has a friction coefficient of 0.3 or less, preferably 0.2 or less, and the friction coefficient of the middle portion is 0.3 to 0.6, preferably 0.4 to 0.4. 5, and the coefficient of friction of the base end portion is 0.6 or more, preferably 0.7 or more. In this case, it is preferable that the lubricity in the intermediate portion changes continuously or stepwise.

[0013] The length of the tip portion having high lubricity needs to be longer than the portion inserted into the small blood vessel near the target site when the catheter tip reaches the target site in the body. In the case where the catheter is inserted using, for example, a parent catheter, it is preferable that the catheter be longer than a portion protruding from the distal end of the parent catheter when the catheter is placed. Therefore, the length of the tip portion is preferably 5 cm or more, and more preferably 10 cm or more. Further, it is preferable that the flexibility of the distal end portion is higher than that of the proximal end portion, and that the rigidity of the proximal end portion is higher than that of the distal end portion. Further, it is also preferable that the flexibility of only the distal side of the distal portion having high lubricity is higher than that of the proximal portion, and that the rigidity of the proximal portion is higher than that of the distal portion. The catheter having the above characteristics has a characteristic that the lubricating property of the distal end portion is particularly good, so that the inner wall of the lumen is hardly damaged and the operation from the outside of the body is easy.

In the present invention, any method may be used for imparting lubricity. Examples of the method include a method in which a hydrophilic polymer such as a maleic anhydride polymer is covalently bonded to the catheter surface, The method of forming a crosslinked coating of a hydrophilic polymer on the catheter surface is preferable from the viewpoint of easy control of the lubricity. Examples of the crosslinked film of a hydrophilic polymer include a crosslinked film of a polymer having an acid anhydride group and a compound having a plurality of functional groups capable of reacting with the acid anhydride group, such as polyol and polyamine.

When the catheter of the present invention imparts lubricity by, for example, covalently bonding a maleic anhydride polymer, the contact time (reaction time) between the catheter surface and the maleic anhydride polymer solution is increased. By adjusting (time), the degree of lubricity in the catheter length direction can be easily changed. Specifically, the catheter is gradually immersed in a solution of a maleic anhydride-based polymer from the distal end, and then immersed to a target portion. The reaction time can be varied in the length direction of the rubber to change the degree of lubricity.

When lubricity is imparted by a method of forming a crosslinked film of a polymer having an acid anhydride group and a compound having a plurality of functional groups capable of reacting with an acid anhydride group, such as a polyol and a polyamine, on a catheter surface. After forming a crosslinked film from the distal end portion to the proximal end portion, a crosslinked film is formed again only on the distal end portion, so that the degree of lubricity can be changed. Alternatively, the degree of lubricity of the catheter surface can be changed by immersing the catheter in a solution in which the mixing ratio of the polymer having an acid anhydride group and the compound capable of reacting with the acid anhydride group is changed. .

According to the above-mentioned method, a catheter whose lubricity varies in the longitudinal direction of the catheter can be obtained. However, the lubrication treatment may be performed on the entire catheter, or may be performed on a part of the catheter. It may be. Usually, a catheter has a hub for connecting a syringe or the like when injecting a drug, a contrast agent, or the like. However, it is preferable that there is no lubricity in the vicinity of the hub for better operability because of good operability. Therefore, it is preferable that the lubricity treatment in which the lubricity is changed in the length direction is performed on a portion excluding the vicinity of the hub.

[0018]

Next, the present invention will be described in detail with reference to examples. In addition, all% in an Example means a weight%.

Reference Example (Test of Surface Lubricity) The surface lubricity of a sample was tested by measuring the coefficient of friction by a tilt method. That is, about 22
2 samples cut to the length of 2 cm on a flat plate (inclined plate)
The books were fixed in parallel and wetted with saline.
On top of that, a collagen film was stuck on the lower surface.
g, put one end of the inclined plate at a constant speed,
The inclination angle when the weight began to slide was measured, and the tangent of the inclination angle was expressed as a friction coefficient.

Example 1 A catheter made of polyurethane (Tecoflex manufactured by Thermedics) (0.65 m inner diameter)
m, outer diameter 1.00 mm, length 1 m) 5% maleic anhydride-methyl vinyl ether copolymer having a molecular weight of about 69,000 (manufactured by ISP Co., Ltd.) and polyethylene glycol having a molecular weight of 400 (Maruzen) Manufactured by Yakuhin Kogyo Co., Ltd.)
% For 1 minute at room temperature in acetone solution containing
For 24 hours. Then 50cm from the tip of this catheter
Was again immersed in the above acetone solution, and dried again at 60 ° C. for 24 hours. After immersing this catheter in distilled water for 72 hours,
Further, it was washed 10 times with distilled water. The distal end portion, the proximal end portion, and the untreated catheter of this catheter (sample 1) were subjected to measurement of a coefficient of friction by a tilt method. The coefficients of friction were 0.02, 0.6 and 0.9, respectively.

COMPARATIVE EXAMPLE 1 The same polyurethane catheter used in Example 1 was treated with a maleic anhydride-methyl vinyl ether copolymer having a molecular weight of 69,000 [ISP Co., Ltd.
Manufactured by Toshiba Corporation) was immersed in an acetone solution containing 5% and 0.1% of polyethylene glycol having a molecular weight of 400 (manufactured by Maruzen Pharmaceutical Co., Ltd.) at room temperature for 1 minute and then dried at 60 ° C. for 24 hours. Next, this catheter is immersed again in the acetone solution, and then
Dry at 60 ° C. for 24 hours. This catheter was immersed in distilled water for 72 hours, and then further washed 10 times with distilled water. By this treatment, a catheter was obtained in which the entire surface of the catheter had the same coefficient of friction as the tip portion of the catheter described in Example 1 (Sample 2).

A polyethylene tube (inner diameter 2 mm, length 2 mm) was formed by spirally winding the lubricating catheters (sample 1 and sample 2) prepared in Example 1 and Comparative Example 1 on a cylinder having a diameter of 2 cm in water at 37 ° C. 1 m), and the insertion distance was measured. At the time of insertion, the catheter was operated while wearing surgical rubber gloves. At this time, ease of operation was also evaluated. Table 1 shows the results.

[0023]

[Table 1]

From Table 1, it is clear that the catheter of the present invention is excellent in insertion distance and operability.

Example 2 A catheter made of polyurethane (Tecoflex manufactured by Thermedics) having an inner diameter of 0.65 mm and an outer diameter of 1.00 having a distal end portion 30 cm more flexible than a proximal end portion.
mm, length 1 m) 70% from the tip 1% of maleic anhydride-methyl vinyl ether copolymer having the same molecular weight as used in Example 1 and 0.05% of polyethylene glycol amine having a molecular weight of 4,000 (manufactured by Sanyo Chemical Industries, Ltd.) Was immersed in a methyl ethyl ketone solution containing for 15 seconds. Thereafter, it was dried at room temperature for 1 hour. Next, 40c from the tip of this catheter
m was immersed in a methyl ethyl ketone solution containing 4% of a maleic anhydride-methyl vinyl ether copolymer having the same molecular weight for 15 seconds. Then, it was dried at 60 ° C. for 2 hours, immersed in distilled water at room temperature for 1 hour, and then dried at 60 ° C. for 24 hours. The coefficient of friction at the distal, intermediate, and proximal ends of the catheter was 0.06, 0.5, and 0.9, respectively.

Example 3 80 cm from the tip of the same polyurethane catheter used in Example 2 was immersed in the same methyl ethyl ketone solution containing maleic anhydride-methyl vinyl ether copolymer and polyethylene glycol as in Example 2, After 15 seconds, it was pulled up from the immersion liquid to a length of 60 cm from the tip. Next, 0.5cm / min from the tip to the 40cm length
, And the remaining portion was pulled up at once. Thereafter, the catheter was dried at 60 ° C. for 18 hours, washed with water, and the coefficient of friction of the distal end portion, the intermediate portion, and the proximal end portion of the catheter was measured to be 0.06, 0.5, and 0.8, respectively.

Example 4 Ethylene-acrylate-maleic anhydride terpolymer (Bondane TX80 manufactured by Sumika CFD Chemical Co., Ltd.)
30) was formed into a catheter tube having an inner diameter of 1 mm and an outer diameter of 2 mm. The tube 2m was immersed in an acetone solution of 0.5% ethylenediamine (manufactured by Maruzen Pharmaceutical Co., Ltd.) for 30 minutes, washed and dried with acetone, and mixed with maleic anhydride-methyl vinyl ether having the same molecular weight as used in Example 1. 2cm in methyl ethyl ketone solution containing 1% of polymer
The tube is gradually immersed from one end at a speed of / min, and immediately after the whole is immersed in the solution, the tube is gradually taken out from the other end, and the immersion time at one end is about 3 hours.
The time was 20 minutes, and the immersion time at the other end was 20 to 30 seconds. After removing the whole, wash the tube with methyl ethyl ketone,
Further, it was washed with water. Samples of 30 cm each were taken from both ends and near the center of this tube, and the friction coefficient was measured by the tilt method. The friction coefficient of the end with the longer immersion time, the center, and the end with the shorter immersion time were measured. Are 0.04, 0.4 and 0 respectively.
8

[0028]

According to the catheter of the present invention, the inner wall of the lumen is hardly damaged when inserted into the body, and the insertion operation is easy. Further, the method for producing a catheter of the present invention can easily obtain the above-mentioned catheter.

Claims (5)

[Claims] Claims: 1. A catheter having a lubricating surface when wetted, wherein the catheter tip has the highest lubricity,
A catheter having the lowest lubricity at the proximal end. 2. The catheter according to claim 1, wherein the degree of lubricity of the surface of the catheter changes continuously from the distal end portion to the proximal end portion. 3. The catheter of claim 1, wherein the distal portion is more flexible than the proximal portion. 4. When a hydrophilic polymer-containing solution is brought into contact with the surface of the catheter to bind the hydrophilic polymer to the catheter surface, the time required for bringing the solution containing the hydrophilic polymer into contact with the catheter surface is reduced. 2. The method of manufacturing a catheter according to claim 1, wherein the length of the catheter is changed in the longitudinal direction. 5. When a hydrophilic polymer and a solution containing a compound which reacts with the hydrophilic polymer and crosslinks the hydrophilic polymer are brought into contact with the surface of the catheter to form a crosslinked film of the hydrophilic polymer on the surface of the catheter. 2. The method for manufacturing a catheter according to claim 1, wherein the thickness of the crosslinked film at the tip portion is larger than at the end portion.