JPS61249478A - Antithrombotic obturator for stay catheter in blood vessel - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention can be easily inserted into a catheter,
The present invention also relates to an obturator for occluding the inside of a catheter in order to prevent blood coagulation within the catheter and to secure a flow path within the catheter, and relates to an obturator for an intravascular indwelling catheter that has excellent antithrombotic properties. .

(Prior Art) Conventionally, plastic catheters have been used when administering blood transfusions, infusions, etc. to patients. If such a catheter is used to perform intermittent blood transfusions or infusions, or if blood transfusions or infusions are interrupted and the catheter is left in the blood vessel, blood may enter the catheter and cause the blood to clot. However, there was a problem in that the inside of the catheter was occluded.

For this reason, anticoagulants such as heparin are injected into the catheter to prevent blood from coagulating inside the catheter, or a metal or plastic optulator is inserted into the catheter.

A method has been adopted to prevent blood from flowing toward the catheter (Japanese Unexamined Patent Publication No. 56-68459).

(Problems to be Solved by the Invention) However, the method of injecting an anticoagulant into a catheter is troublesome to operate, and there are cases where it is not preferable to inject the anticoagulant. for example.

The use of anticoagulants is not preferred in intermittent blood tests, etc., as it may lead to errors.

In addition, in both metal and plastic obtululators, a small amount of blood flows into the catheter through the gap between the catheter and the obtululator, causing blood to coagulate. This is unavoidable, and even if an obturator is used, it is not possible to push out all the blood inside the catheter, so the catheter must be plugged with some blood remaining inside. In either case, blood clots will occur within the catheter. and,
When blood coagulation occurs within such a catheter, there is a problem in that the obturator cannot be removed, or even if it is removed, the flow path of the catheter becomes narrow, resulting in a decrease in flow rate.

It is therefore an object of the present invention to provide an obturator that can prevent blood coagulation within a catheter.

(Means for Solving the Problems) As a result of intensive research to achieve the above objectives, the present inventors have found that a fibrinolytic active substance is immobilized on the surface of an obturator made of a polymeric substance. discovered scales that prevented blood coagulation within the catheter, and completed the present invention.

That is, the present invention provides an obtululator for an intravascular indwelling catheter that obstructs a flow path in an indwelling intravascular catheter. This is an antithrombotic obturator for intravascular indwelling catheters.

The optulator of the present invention uses a polymeric substance as a material. Preferred polymer materials include natural polymers such as natural rubber, cellulose, starch, collagen, agarose, dextran, proteinaceous materials, polystyrene, polyamide, polyester, polyamino acid, polyethylene, polyurethane, polypropylene, silicone resin, and polyvinyl chloride. , polymethacrylic acid ester, polyvinyl alcohol, ethylene/hinyl acetate copolymer, and other synthetic polymers.

The fibrinolytic active substance immobilized on the surface of the optulator of the present invention refers to a substance involved in the dissolution of fibrinolyte, such as plasmin.

Briclase. Examples include urokinase, streptokinase, and tissue plasminogen activator.

In order to immobilize these fibrinolytic active substances on polymeric substances, known enzyme immobilization methods can be used.
Methods described in JP-A No. 8390, JP-A-54-26394, etc. can be used.

In order to create the optulator of the present invention, the optulator may be formed from a polymeric substance by a known method, and a fibrinolytic active substance may be immobilized on the resulting optulator, or a fibrinolytic active substance may be immobilized on the resulting optulator. The obturator may be formed using a polymeric material on which a dissolved active substance is immobilized.

The optulator of the present invention has a diameter that is approximately the same as the inner diameter of an intravascular indwelling catheter, a cylindrical or rod-like shape with a rounded tip, and a length that is the same as the catheter or several centimeters longer. It is appropriate to have a shape. Furthermore, the obturator of the present invention may have a hub compatible with the catheter hub attached to the other end that is not inserted into the catheter.

(Example) The present invention will be described in further detail with reference to Examples below. The fibrinolytic activity was measured using a fibrin plate prepared by adding a thrombin saline solution to an aqueous fibrinogen solution, with reference to the revised 27th edition of "Clinical Test Methods Summary" (Metal Publishing) VI-110, edited by Kanai and Kanai. It was measured using

That is, after placing a sample piece on a fibrin plate and leaving it for 24 hours at 37°C, the degree of dissolution of fibrin around the sample piece was determined by (major axis) x (minor axis) Il1m! It was expressed as

Example 1 A rod-shaped polyvinyl chloride optulator with an outer diameter of 0.9w+ea and a length of 27c+m was prepared using 2 (wt/V)% of maleic anhydride-methyl vinyl ether copolymer and 1% of polyethylene glycol with a molecular weight of 400 ( wt/V)%
After immersing in the dissolved acetone solution for 1 minute at room temperature,
It was heated under reduced pressure at 0 to 100°C for 2 hours. This obturator was added to a physiological saline solution of urokinase (600 units/m
1) and left at 70°C for 24 hours, and then washed with physiological saline.

The obturator with immobilized urokinase obtained in this way was cut into a length of 2I11 m and the 9 wA fibrinolytic activity was measured. Fibrin was dissolved.

Example 2 Outer diameter 0.9sua, inner diameter 0.3+++m, length 27c+
A cylindrical polyurethane obturator with a closed tip was placed in an acetone solution containing 2 (wt/V)% maleic anhydride-methyl vinyl ether copolymer and 1 (wt/V)% polyethylene glycol having a molecular weight of 400. The sample was immersed in water for 30 seconds at room temperature, and then heated under reduced pressure at 90 to 100°C for 2 hours. This obturator was immersed in a physiological saline solution of urokinase (600 units/all), left at 7° C. for 24 hours, and then washed with physiological saline.

The thus obtained obturator with immobilized urokinase was cut into lengths of 2,111,111 mm and fibrinolytic activity was measured. Fibrin was dissolved.

Example 3 A rod-shaped obturator made of aminoacecooled polyvinyl alcohol (degree of aminoacetalization 1 mol %) with a diameter of 0.9 mm and a length of 27 cm was placed in a 5 wt % acetone solution of an ethylene-maleic anhydride copolymer. It was soaked and left at room temperature for 5 hours. After being left standing, the obturator was washed with acetone and then dried.

After drying, the obturator was immersed in a physiological saline solution of streptokinase (600 units/mj) and heated at 4°C and 24°C.
After leaving it for a while, it was washed with physiological saline.

The thus obtained obturator with immobilized streptokinase was cut into pieces of 2 mm in length and fibrinolytic activity was measured. .

Example 4 human melanoa+ instead of urokinase
An obturator in which tissue plasminogen activator was immobilized and immobilized was obtained in the same manner as in Example 1 except that tissue plasminogen activator separated and purified from a cellline was used.

Cut this obturator to length 21II11.

When fibrinolytic activity was measured, the obturator piece had 21X19+as (399fI1m”) around it.
fibrin was dissolved.

Example 5 The obturator on which the fibrinolytic active substance obtained in Examples 1 to 4 was immobilized was placed in the rabbit vena cava (a polyurethane vascular indwelling catheter (outer diameter 1.52 m)).
After inserting the catheter into a tube (inner diameter: 0.97 mm+, length: 25 cm) and leaving it for 10 days, the catheter was removed and the state of thrombus adhesion inside the catheter was observed. No thrombus was observed at all.

As a comparative example, when the optulator used in Examples 1 to 4 on which the fibrinolytic active substance was not immobilized was inserted into a catheter similarly placed in the rabbit vena cava, 2
A thrombus formed within the catheter after 0 days of indwelling.

(Effects of the Invention) The optulator for an intravascular catheter of the present invention has a fibrinolytic active substance immobilized on its surface and has antithrombotic properties, so blood that flows into the catheter or remains Do not solidify.

Therefore, when the optulator of the present invention is used, the intravascular indwelling catheter can be used for blood transfusion, infusion, etc. immediately after the optulator is removed.

Patent Applicant: Yu-qPt% Co., Ltd. Procedural Dispute Book 1) May 31, 1985 1, Indication of Case Patent Application No. 1988-91613 2, Title of Invention Antithrombotic Optics for Intravascular Catheter Tutor 3, Relationship with the case of the person making the amendment Patent applicant Address: 1-50 Higashihonmachi, Amagasaki City, Hyogo Prefecture 541 Address: 4-68 Kitakyutabe-cho, Higashi-ku, Osaka Name: U=
Tei Riki Co., Ltd. Patent Department Tel: 06-281-5258 (dial-in) 4, Subject of amendment (1) Column 5 of “Detailed Description of the Invention” of the specification, Contents of amendment (1) Specification, page 10 Correct "Comparative example" in line 4 to "Comparison".

(2) "20" in line 7 of the same page of the same book is corrected to "2".

Claims (2)

[Claims] (1) In an obtululator for an intravascular indwelling catheter that occludes a flow path in an indwelling intravascular catheter, the material of the obtululator is made of a polymeric substance, and a fibrinolytic active substance is immobilized on the surface. An antithrombotic obturator for intravascular indwelling catheters. (2) The obturator for an intravascular indwelling catheter according to claim 1, wherein the fibrinolytic active substance is urokinase.