JPH0656676A - Suspension for blood vessel embolization - Google Patents

Abstract

PURPOSE:To provide a suspension to be injected through a catheter into the blood vessel for occluding specific parts. CONSTITUTION:This suspension for blood vessel embolization is prepared by suspending a high water-absorbing resin particles which are mainly made of a polymer from sodium acrylate or a copolymer from sodium acrylate and vinyl alcohol and have an average particle size of less than about 1.0mm diameter in an oily contrast medium.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a suspension for embolization of blood vessels, and more specifically, for embolizing a specific portion of a blood vessel,
TECHNICAL FIELD The present invention relates to a suspension for vascular embolization that is injected via a catheter.

[0002]

2. Description of the Related Art Conventionally, the problems to be solved by the invention
Cyanoacrylates (isobutyl-2-cyanoacrylate) used in arterial embolization, especially embolization of intracranial arteriovenous malformations
late, n-butyl cyanocrylat
e) is recognized as a useful embolic material, but ni
It takes experience to adjust the concentration in order to polymerize in dus (arteriovenous malformation), often causes catheter occlusion due to polymerization in the catheter, or adhesion between the catheter and the polymerized Cyanacrylates It has drawbacks such as danger. A small amount of Cyanoacrylate to solve the adhesion problem
Although a method of injecting s in several times has been proposed, it still requires careful attention. These c
EVA to make up for the shortcomings of yanoacrylates
L (Ethylene Vinyl Alcohol
Copolymer) is used in many facilities, but it requires an organic solvent and may have poor compatibility with catheters. Therefore, development of an embolic substance that is easy to handle and has no toxicity is desired. On the other hand, Polyvinyl Al was used as the embolization material.
There are many reports using cohol (PVA) and sutures,
Since the catheter is frequently occluded and the artery is blocked on the central side, the rate of recanalization of arteriovenous malformation is high.
A material that can be plugged near the idus is desirable. For this reason, Ethanol and Avitene (microfi
It is necessary to devise such as using a mixture of brilliant collagens. Thus, the conditions required for the embolic substance during intracranial embolization include passing through an extremely fine catheter, good contrast, not passing through nidus, having a permanent embolic effect, and not toxic.

[0003]

The present invention comprises a polymer of sodium acrylate or a polymer of acrylic soda and vinyl alcohol as a main component, and has an average particle size of about 1.0.
It is a suspension for vascular embolism, which is obtained by suspending super absorbent polymer particles having a size of not more than mm in an oily contrast medium. That is, in this invention, the superabsorbent resin particles are water, that is, blood (water in)
It is intended to cause blood vessels to act as an embolic substance by utilizing the fact that they instantly absorb water and swell when they meet with each other (for example, absorb and swell 1000 times the water content of their own weight). By suspending it in an oily contrast medium, the water absorption swelling is delayed so that the action as an embolic substance occurs only at a desired portion of a blood vessel, not inside the catheter or a portion adjacent to the catheter.

The superabsorbent resin particles used in the present invention are mainly composed of a polymer of sodium acrylate or a polymer of sodium acrylate and vinyl alcohol. In particular, as the main components thereof, vinyl acetate-saponified acrylic acid ester copolymer, saponified vinyl acetate-methyl maleate copolymer, isobutylene-maleic anhydride copolymer cross-linked product,
Starch-Acrylonitrile Graft Copolymer Saponification Product,
Specific examples include cross-linked sodium polyacrylate and cross-linked products of polyethylene oxide.

As the super absorbent polymer particles, those having an average particle size of about 1.0 mm or less, preferably 0.9 mm or less are used. Further, by appropriately selecting the average particle size of these, a desired portion of the blood vessel can be plugged.

In the present invention, these superabsorbent resin particles are suspended in an oily contrast medium to form a suspension. In this case, 10 to 2 superabsorbent resin particles are added to 1 ml of the oily contrast medium.
It is preferred to suspend 0 mg. As the oily contrast agent, a contrast agent [lipiodol (registered trademark)] composed of iodinated ken oil fatty acid ethyl ester, a contrast agent containing amidotrizoic acid (as an anhydride), sodium hydroxide and meglumine [urographin (registered trademark) )], Amidotrizoic acid (as an anhydride) and meglumine-containing contrast agents [angiographin (registered trademark)] and the like. When the obtained suspension is injected into a specific part of a blood vessel (for example, an artery) by a catheter, the superabsorbent resin particles are surrounded by an oil-based contrast agent and flow to the periphery of the blood vessel, where the oil content of the film is lost. When it separates and comes into contact with water in blood, it immediately absorbs water (for example, 2-3 seconds), increases in diameter (for example, 4.5 times), and acts as an embolic substance.

Examples of the use of the suspension for vascular embolization according to the present invention will be given below.

B) Embolization of malignant tumor Poor blood vessels N-100 (S) and Lipiodol suspension (10 mg / ml) Blood vessel rich N-100 (M) or N-10
0 (L) and suspension of lipiodol (10 mg / ml) N-100 and S-50 were mixed to make a suspension with lipiodol (10 to 15 mg / ml), where N-100: sodium acrylate Coalescence, S-50: acrylic acid / vinyl alcohol copolymer, (S) (M) (L) indicate the particle size, and the average particle size is 0.20 mmφ, 0.53 m in order.
mφ and 0.88 mmφ.

(B) Example of embolization of arteriovenous varices (AVM) Low Flow Type: N-100 (S) and Piodol suspension (10 mg / ml) High Flow Type: N-100 and S-50
To make a suspension with Lipiodol (10-15m
g / ml)

C) Example of embolization of arterial hemorrhage S-50 having a diameter slightly larger than the diameter of a blood vessel that is bleeding is counted by several pieces and suspended with a contrast medium, and the suspension is injected until bleeding stops.

[0011]

【Example】

Example 1 In order to confirm that the suspension for vascular embolization according to the present invention actually has an embolization effect, an embolization blood vessel model (1) as shown in FIG. 1 assuming an arteriovenous aneurysm was prepared. The embolized blood vessel model (1) has a cylindrical shape (height: 2 mm, diameter: 18 m) in a plastic chamber (2) having a volume of about 2.0 ml.
m) urethane foam sponge (open cell) (3)
Is filled. Blood passes through this chamber (2) without resistance. This embolized blood vessel model (1) 500 m
1 to 1,000 ml of physiological saline bottle (4) is connected to this bottle using the automatic pressurizing device (5).
Apply a steady pressure of 0 mmHg to create a steady flow in the chamber (2).
Shed to. Note that (6) is a pressure gauge, and (7) is a microcatheter. The following 2 as urethane foam sponge
Filled with kinds of things. That is, low flow type: average size of eyes of urethane foam 0.5 mm high flow type: average size of eyes of urethane foam 0.9 mm The flow rate of physiological saline was measured to determine the embolization effect.

A) low flow type AVM
Embolization of model (see FIGS. 1, 2 and 4) N-100 (S) 40m using a suspension of N-100 (S) 76% urographine and lipiodol
Stop the water flow. On the other hand, when N-100 (M) is used, the same suspension suspends the water flow at 5 mg or less. N-
The larger the amount of 100, and the larger the particle size,
Easy to get clogged.

B) high flow type AV
Embolization of M model (see FIGS. 1, 2, and 5) No embolization effect is observed in a suspension of N-100 (M) 76% urographine and lipiodol. S-
By adding 50 (M), an embolizing effect appears. N
With -100 (L) + S-50 (L), an embolic effect appears even with a small amount of 10 mg. N-100 (S) + S-50
In (S), there is no embolic effect. N-100 (S) + S-
Even with 50 (S), if suspended with angiographin, it becomes S
-50 particles become large and have an embolic effect. As a result, S-5 is used for embolization of AVM with fast blood flow.
It is extremely important to mix 0.

Clinical example a) 26-year-old female uterine bleeding after abortion Pelvic arteriography: An expansion of the right uterine artery and an abnormal blood vessel that spirally expands in line with the uterus are observed. Further, leakage of the contrast medium was observed outside the blood vessel, and bleeding was confirmed. Selective right uterine artery: A catheter is selectively inserted into the right uterine artery for imaging. Selective right uterine arteriography (post-embolization): S-50 (M) 5
After taking up mg of water with adjusted saline, suspending it in Lipiodol and injecting it through the catheter, photography was performed. The abnormal blood vessels disappeared, and leakage of the contrast agent outside the blood vessels was no longer observed,
Only normal uterine artery muscles have been removed. Postoperatively, bleeding from the uterus stopped. The features of the embolic substance when the suspension for vascular embolization according to the present invention is used are listed below. B) No toxicity / irritation: There is already data on this point. As far as one can imagine from the study of the tissue reaction of the conventional embolic material, there is no particular problem. In clinical experience with 10 cases, there is no pain during injection. B) Low viscosity: A suspension of a concentration slightly higher than that of Lipiodol and a very high concentration can be passed through the microcatheter with a 1.0 ml syringe. C) Good contrast property: Since Lipiodol is used as a suspension, it looks very clear under fluoroscopy. In addition, the effect of embolism can be confirmed by the accumulation of Lipiodol in the embolization site. D) Do not block the catheter: Do not clog the catheter because the particles do not have the property of aggregating. The lack of adhesion eliminates the risk of catheter and blood vessel adhesion. E) The embolization site can be adjusted: the size of particles can be adjusted. The method is controlled by (S) (M) (L) or the size of the particles is controlled by the contrast agent to be suspended. By this, the diameter of the blood vessel that can be embolized can be determined in advance.

[0015]

EFFECT OF THE INVENTION By using the suspension for vascular embolization according to the present invention, there is no toxicity / irritation, low viscosity, good contrast, no catheter occlusion, and the embolization site can be adjusted. The effect is obtained.

[Brief description of drawings]

FIG. 1 is an explanatory diagram showing the amount of liquid that N-100 (10 mg) can absorb.

FIG. 2 is an explanatory diagram showing changes in the diameter of S-50 in the presence of various liquids.

FIG. 3 is a schematic configuration explanatory diagram of an embolized blood vessel model.

FIG. 4 is a graph showing the embolic effect of the LOW FLOW model.

FIG. 5 is a graph showing the embolic effect of the HIGH FLOW model.

Claims (1)

[Claims] 1. Superabsorbent resin particles having a polymer of sodium acrylate or a polymer of acrylic soda and vinyl alcohol as a main component and having an average particle diameter of about 1.0 mm or less are suspended in an oil-based contrast agent. A suspension for embolization of blood vessels.