JPH10234857A - Obturator for intravascular indwelling catheter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve the insertion property into a catheter, and prevent blood in a gap between the catheter and an obturator from coagulating by forming the obturator in such a manner than the surface of the obturator may show a lubricating property when being wet. SOLUTION: This obturator for intravascular indwelling catheter (hereinafter, obturator) is normally formed of a high molecular material such as natural rubber or cellulose, but may be formed of a raw material other than high molecular materials such as a metal. The length is not specifically restricted, and preferably is the same as the length of an intravascular indwelling catheter to be used, or longer by several centimeters. The shape is preferably made in such a manner that the leading end located at an intracorporeal side is rounded. Then, e.g. a surface coating of a hydrophilic polymer, or a treatment such as bridging film forming of a hydrophilic polymer, is performed so that the surface of the obturator may show a lubricating property when being wet. By this constitution, by a contact with blood, etc., the lubricating property manifests, and the frictional resistance is reduced, and the insertion becomes smoother.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an obturator for an indwelling catheter in a blood vessel, and more particularly, to insert the catheter into a catheter to prevent blood coagulation in the catheter and secure a flow path in the catheter. The present invention relates to an obturator for an indwelling intravascular catheter, which has excellent insertion properties and antithrombotic properties, and is used for such a purpose.

[0002]

2. Description of the Related Art Conventionally, when performing blood transfusion, transfusion, or the like on a patient, a plastic catheter has been used. When intermittent blood transfusion or transfusion is performed using such a catheter, or when blood transfusion or transfusion is interrupted, if the catheter is left in the blood vessel, blood enters the catheter and coagulates. However, there is a problem that the inside of the catheter is blocked. Therefore, an anticoagulant such as heparin is injected into the catheter to prevent blood from coagulating in the catheter, or a metal or plastic obturator is inserted into the catheter to prevent blood from flowing into the catheter. A method for preventing this is taken (JP-A-55-68459).

[0003]

However, the method of injecting an anticoagulant into a catheter is complicated in operation,
In some cases, it is not preferable to inject an anticoagulant. For example, in an intermittent blood test or the like, the use of an anticoagulant is not preferable because it causes an error. In addition, although a small amount of a metal obturator or a plastic obturator is small from the gap formed between the catheter and the obturator, blood flows into the catheter and causes blood coagulation, In addition, even if an obturator is used, it is not possible to push out all the blood in the catheter, so that the blood is plugged with a small amount of blood remaining in the catheter. Solidification will occur. If blood coagulation occurs in the catheter in this manner, the obturator may not be able to come off, or even if it comes off, the clot may damage the inner wall of the catheter, which often makes it easier for blood clots to form on the inner wall of the catheter . Also,
There has been a problem that the clot formation narrows the flow path of the catheter and consequently reduces the flow rate. When the flow path of the catheter is narrowed and the flow rate is reduced, the burden on the patient is increased because the catheter must be removed and a new catheter must be inserted.

[0004] The above problems can be solved by preventing coagulation of blood flowing or remaining in the catheter and by reducing the amount of blood flowing or remaining in the catheter. As a method for preventing coagulation of blood flowing or remaining in the catheter, Japanese Patent Publication No. 4-61
No. 663 discloses a method for immobilizing a fibrinolytic active substance on the surface of an obturator. In this method, coagulation of blood cannot be prevented if the fibrinolytic active substance loses its activity. In particular, the diameter of the obturator is almost the same as the inner diameter of the catheter in order to reduce blood inflow and residual, so the fibrin immobilized on the surface due to friction between the obturator and the inner wall of the catheter during insertion. The lytic active may lose activity and is not a reliable method of preventing blood clotting in the gap between the catheter and the obturator. As a method of reducing the amount of blood flowing into or remaining in the catheter, reduce the difference between the inner diameter of the catheter and the diameter of the obturator,
It is conceivable to reduce the gap between the catheter and the obturator. However, the catheter passes through a curved blood vessel, and when the catheter is ligated with a suture to fix the catheter, the lumen of the catheter may be narrowed. When the difference between the inner diameter of the catheter and the inner diameter of the catheter is small, the resistance at the time of inserting the obturator into the catheter increases, and the operability may deteriorate or the catheter may be damaged.

[0005] It is an object of the present invention to provide an obturator having a good insertion property into a catheter and capable of preventing coagulation of blood in a gap between the catheter and the obturator.

[0006]

Means for Solving the Problems The present inventors have studied to achieve the above object, and as a result, by configuring the surface of the obturator so as to exhibit lubricity when wet, the obturator has an improved structure. Even if the difference between the diameter and the inner diameter of the catheter is reduced, good insertion properties can be maintained, and blood inflow into the gap between the obturator and the catheter and residual blood can be reduced to reduce blood coagulation. It is possible to prevent obstruction of the catheter lumen, and furthermore, by using an obturator with a wet lubricity on the surface, it is possible to insert the obturator into a catheter in which a fibrinolytic active substance is immobilized. As a result, the present inventors have found that as a result of preventing inactivation of the fibrinolytic active substance due to friction at the time of insertion, the effect of preventing blood coagulation can be enhanced, and arrived at the present invention.

That is, the present invention relates to an intravascular indwelling catheter obturator for closing an intravascular indwelling catheter flow path, characterized in that the surface of the obturator exhibits lubricity when wet. The gist is an obturator for use.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

[0009] The obturator for an indwelling intravascular catheter of the present invention (hereinafter simply referred to as an obturator) has lubricity when its surface is wet.

The indwelling catheter according to the present invention includes a catheter for performing blood transfusion, infusion, and infusion of a drug solution,
Examples include catheters for performing hemodialysis, catheters for angiography, and the like.

The obturator of the present invention is generally made of a polymer material, but may be made of a material other than the polymer material such as a metal. Preferred polymer materials include, for example, natural rubber, cellulose, starch, collagen, agarose, dextran, natural polymers such as proteins,
Examples include synthetic polymers such as polystyrene, polyamide, polyester, polyamino acid, polyethylene, polypropylene, polyurethane, silicone resin, polyvinyl chloride, polymethacrylate, polyvinyl alcohol, and ethylene-vinyl acetate copolymer.

The length of the obturator of the present invention is not particularly limited, but is preferably the same as the length of the indwelling intravascular catheter to be used or several centimeters longer than the indwelling intravascular catheter. .

The shape of the obturator of the present invention is not particularly limited, but is preferably a tubular shape whose inside end is rounded. Further, the obturator may have a lumen penetrating from one end to the other end.

The obturator of the present invention may be one in which a hub compatible with a catheter hub or an extension tube and a connector connected to an infusion infusion line are attached to an end of the obturator that is not inserted into the catheter.

The obturator of the present invention can be obtained by injection molding, extrusion, dipping, casting, or the like even if a commercially available obturator is treated so that the surface exhibits lubricity when wet. An obturator manufactured by a method or the like may be processed so that the surface shows lubricity when wet.

To make the surface of the obturator exhibit lubricity when wet, for example, a method of coating the surface with a hydrophilic polymer, a method of immobilizing the hydrophilic polymer on the surface, and a method of coating the surface with the hydrophilic polymer The surface of the obturator may be treated by a method of forming a crosslinked film of the above. Among the above methods, a method of immobilizing a hydrophilic polymer and a method of forming a crosslinked film of a hydrophilic polymer are preferable from the viewpoint of durability of lubrication.

Here, the hydrophilic polymer is a polymer containing one or more hydrophilic functional groups such as a hydroxyl group, an amino group, a carboxyl group and an acid anhydride group per monomer unit.
Alternatively, it is a polymer containing an ether bond, an amide bond, an ester bond, or the like, and may be water-soluble or water-insoluble. Specifically, polyvinyl alcohol, polyacrylic acid, ethylene-acrylic acid copolymer, styrene-acrylic acid copolymer, acrylic acid copolymer such as methyl vinyl ether-acrylic acid copolymer, polymethacrylic acid,
Polylactic acid, polyamide, alginic acid, cellulose, starch, chitin, chitosan, polyethylene glycol, polyethyleneimine, polyallylamine, ethylene-maleic anhydride copolymer, styrene-maleic anhydride copolymer, methyl vinyl ether-maleic anhydride copolymer Coalescing,
And derivatives of these compounds.

As a method of immobilizing the hydrophilic polymer on the surface of the obturator, when the obturator is formed of a polymer material, a functional group of the hydrophilic polymer is added to a functional group on the surface of the obturator. What is necessary is just to make it react. When the obturator surface does not have a reactive functional group, a functional group may be introduced into the surface by a known method such as plasma treatment. When the obturator is formed of a material other than a polymer material such as a metal, the surface may be coated with a polymer compound, and then a hydrophilic polymer may be bonded to the coated polymer compound. For example,
In the case of a polyamide obturator, an amino group is generated by hydrolyzing the surface with hydrochloric acid or the like, and polyacrylic acid is bonded to the amino group formed on the obturator surface using a condensing agent. Can be.

As a method of forming a crosslinked film of a hydrophilic polymer on the surface of the obturator, a method of heating, irradiating light, adding a catalyst or a crosslinker on the surface of the obturator with the hydrophilic polymer forming the crosslinked film is used. May be bonded to the reactive functional group of the hydrophilic polymer.

In forming the crosslinked film, the hydrophilic polymer may be brought into contact with the surface of the obturator and the reactive functional group of the hydrophilic polymer may be bound by the above method. Examples of the contacting method include a method of immersing the obturator in a solution in which the hydrophilic polymer is dissolved, a method of spraying the solution on the surface of the obturator, and a method of applying the solution to the surface of the obturator.

As the hydrophilic polymer forming the crosslinked film, a hydrophilic polymer having two or more reactive functional groups may be used alone or in combination of two or more. The crosslinked film is
As long as at least one kind of these hydrophilic polymers is contained, a polymer other than the hydrophilic polymer may be contained at the same time.

When a crosslinked film is formed from a hydrophilic polymer having a plurality of carboxyl groups or acid anhydride groups and a compound having a plurality of hydroxyl groups or amino groups, the crosslinked film can be formed without using a catalyst. Therefore, it is particularly preferable. For example, by immersing a polyethylene obturator in a methyl vinyl ether-maleic anhydride copolymer and polyethylene glycol in a methyl ethyl ketone solution, and then performing a heat treatment,
A crosslinked film can be formed on the obturator surface.

The obturator of the present invention may be treated so that the surface exhibits lubricity when wet, and then an antithrombotic drug may be immobilized thereon. Antithrombotic agents include heparin, urokinase, streptokinase, tissue plasminogen activator, and the like. These antithrombotic drugs
It can be immobilized on the obturator surface by directly or indirectly binding to the material forming the obturator. Further, the hydrophilic polymer may be bonded to a hydrophilic polymer immobilized on the obturator surface or a functional group of the hydrophilic polymer forming the crosslinked film when the crosslinked film is formed. In the present invention, when a large amount of the antithrombotic agent is immobilized, the antithrombotic agent acts as a cross-linking agent, and the lubricity of the obturator surface may be lost. Is particularly preferred.

As a method for immobilizing these antithrombotic agents to the obturator of the present invention, a known enzyme immobilizing method may be used. For example, "immobilized enzyme" (Ichiro Chibatake, Kodansha), JP-A-53-88390, JP-A-5-88390
The method described in JP-A-4-26394 can be used.

[0025]

The obturator for an indwelling intravascular catheter according to the present invention acts as a lubricant when the hydrophilic polymer on the surface comes into contact with an aqueous medium such as blood or saline, so that the obturator can be inserted into the catheter. To reduce frictional resistance.

[0026]

Next, the present invention will be described specifically with reference to examples. Example 1 Polyurethane [manufactured by Thermedics,
Tecoflex] by an extruder.
Extrusion molding at 0 ° C, outer diameter 3.83mm, inner diameter 3.15mm
Tube and diameter 2.60mm, 2.80mm, 3.00mm
Obturator was obtained. The following processing was performed on the obtained obturator. Each of the above obturators was used as a methyl vinyl ether-maleic anhydride copolymer [Gantrez, manufactured by ISP (ISP)].
4% and polyethylene glycol (made by Ishizu Pharmaceutical) 0.5
% For 1 minute in a methyl ethyl ketone solution containing
It was dried in a dryer at 50 ° C. for about 12 hours. Next, the obturator was washed with acetone, dried in a drier at 40 ° C., and immersed in distilled water at room temperature for 48 hours. The surfaces of these obturators were very slippery when wet with water.

The coefficient of friction of the obtained obturator was measured by the following method. Two obturators were fixed in a flat plate so as to be parallel, and wetted with physiological saline.
On top of that, a collagen film was stuck on the lower surface.
g was placed, one end was raised at a constant speed, and the inclination angle when the weight started to slide was measured. The tangent of the inclination angle was defined as the friction coefficient. For comparison, the coefficient of friction of an untreated obturator after being molded by an extruder was measured by the same method as described above. Table 1 shows the measurement results of an obturator having a diameter of 2.60 mm. In addition, diameter 2.
Even with an 80 mm and 3.00 mm obturator, the same results were obtained as with a 2.60 mm diameter obturator.

[0028]

[Table 1]

Next, each obturator obtained by the above treatment was immersed in distilled water and passed through a tube in water to check the resistance. For comparison, an untreated obturator formed by an extruder was passed through a tube in the same manner to check the resistance. Table 2 shows the results.

[0030]

[Table 2]

From the above results, the obturator that has been lubricated has a small surface frictional resistance when wet, and has good insertability into a catheter. It is also clear that a lubricated obturator can use a thicker obturator than an untreated obturator for a catheter of the same inner diameter.

Example 2 The polyurethane tube prepared in Example 1 was immersed in a 2% solution of a methyl vinyl ether-maleic anhydride copolymer in methyl ethyl ketone for 2 hours at room temperature, and washed with acetone. After drying this tube in a dryer at 50 ° C., 5
A physiological saline solution of urokinase (manufactured by Midori Cross) of 00 international units / ml was sucked into the tube, and allowed to stand at 5 ° C. for 72 hours. After washing with distilled water, it was dried with a vacuum dryer. The urokinase activity of the urokinase-immobilized tube obtained by this method was determined by the synthetic substrate method (Morita et al, J. B.
iochem., 82, 1495 (1977)) and found to be 12.5 ± 3.2 international units per cm ^{2 of} tube lumen surface area. Next, the tube was immersed in distilled water, and a 2.8 mm diameter obturator, which had been lubricated in Example 1, was repeatedly inserted through water 100 times, and then the activity of urokinase was measured in the same manner. . For comparison, a 2.8 mm-diameter obturator that had not been lubricated in Example 1 was repeatedly inserted into the tube in the same manner, and the activity of urokinase was measured. As a result, the activity per cm ^{2 of the} tube lumen surface area was 1.6 ± 1.1 international units when the untreated obturator was used, but the lubricated obturator was used. In that case, it was 11.3 ± 4.1 international units. From the above, it is clear that when the lubricated obturator was used, the friction with the tube was reduced, and the inactivation of urokinase was suppressed.

Example 3 A polyamide-based elastomer (Grillamide, manufactured by EMS) was extruded at 200 ° C. and had an outer diameter of 3.83.
mm, 3.15 mm inside diameter tube and 2.60, 2.8 diameter
A 0, 3.00 mm obturator was obtained. The following processing was performed on the obtained obturator. These obturators were immersed in an acetone solution containing 4% of methyl vinyl ether-maleic anhydride copolymer and 0.2% of glycerin (manufactured by Ishizu Pharmaceutical Co., Ltd.) for 1 minute, and then dried in an oven at 80 ° C. for about 6 hours. Dried. Next, the obturator was washed with acetone, dried in a drier at 40 ° C., and immersed in a 0.1 M acetate buffer at room temperature for 48 hours. The surface of the obturator subjected to the above treatment was extremely slippery when wet with water.

Example 4 An obturator having a diameter of 2.80 mm extruded in Example 3 was immersed in 3N hydrochloric acid at 30 ° C. for 1 hour, and then washed with water.
It was dried, immersed in a 4% acetone solution of a styrene-maleic anhydride copolymer (SMA, manufactured by ISP (ISP)) for 2 hours, washed with acetone, dried, and dried at 5%
Was immersed in an aqueous solution of aminoacetalized polyvinyl alcohol (manufactured by Unitika Chemical Co., Ltd.) for 2 hours and then washed with water. Example 1 shows the lubricity of this obturator when wet.
Was measured in the same manner as described above. For comparison, the same measurement was performed on an obturator that had not been subjected to the above treatment. As a result, the friction coefficient of the lubricated obturator was 0.22, whereas that of the untreated obturator was 0.82.

Example 5 The obturator molded in Example 3 was immersed in an aqueous solution containing 10% polyacrylic acid (manufactured by Polyscience) and 1% polyvinyl alcohol (manufactured by Unitika Chemical Co.), and then heated at 100 ° C. Dried in the oven. The wet lubricity of this obturator was measured by the method used in Example 1. For comparison, the same measurement was performed on an obturator that had not been subjected to the above treatment. as a result,
The friction coefficient of the lubricated obturator is 0.2
It was 0, but the coefficient of friction of the untreated obturator was 0.82.

[0036]

The obturator for an indwelling catheter in a blood vessel according to the present invention reduces the frictional resistance between the catheter and the obturator when the obturator is inserted into the catheter indwelled in the blood vessel. Compared to the obturator, has better insertion into the catheter,
In addition, even when the lumen of the catheter is narrowed by ligating the catheter to fix the catheter, the catheter can be easily inserted. Further, the obturator for an indwelling catheter of the present invention can insert a thicker obturator than a conventional obturator for a catheter having the same inner diameter, so that the gap between the catheter and the obturator is reduced, As a result, the formation of thrombus in the catheter is suppressed. Furthermore, even when a drug such as a thrombolytic agent or a physiologically active substance is immobilized on the catheter lumen or the surface of the obturator, there is little inactivation.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yumiko Ogura 23 Uji Kozakura, Uji-city, Kyoto Pref.

Claims (8)

[Claims] 1. An intravascular indwelling catheter obturator used for closing an intravascular indwelling catheter flow path, wherein the surface of the obturator exhibits lubricity when wet. Obturator. 2. An obturator for an intravascular indwelling catheter used for closing a flow path in an intravascular indwelling catheter, wherein a hydrophilic polymer is immobilized on a surface of the obturator. 2. The obturator for an indwelling catheter according to 1 above. 3. An obturator for an indwelling intravascular catheter used for closing an intravascular indwelling catheter flow path, wherein a crosslinked film containing at least one kind of hydrophilic polymer is formed on the obturator surface. The obturator for an indwelling catheter in a blood vessel according to claim 1, characterized in that: 4. The blood vessel according to claim 3, wherein the crosslinked film is formed from a compound having two or more carboxyl groups or acid anhydride groups and a compound having two or more hydroxyl groups or amino groups. Obturator for indwelling catheter. 5. An intravascular indwelling catheter obturator used for closing an intravascular indwelling catheter flow path, wherein an antithrombotic agent is fixed on the surface of the obturator. 2. An obturator for an indwelling intravascular catheter according to any one of claims 3 and 4. 6. An obturator for an intravascular indwelling catheter used for closing a flow path in an intravascular indwelling catheter, wherein a crosslinked film containing at least one kind of hydrophilic polymer is formed on the obturator surface. ,
An intravascular indwelling catheter obturator, wherein an antithrombotic agent is bonded to the crosslinked film. 7. The indwelling intravascular catheter according to claim 6, wherein the cross-linked coating comprises a compound having two or more carboxyl groups or acid anhydride groups and a compound having two or more hydroxyl groups or amino groups. Obturator. 8. The obturator for an indwelling intravascular catheter according to claim 5, wherein the antithrombotic agent is urokinase.