JPH0549694A - Adsorber of contrast medium - Google Patents

Abstract

PURPOSE:To allow the selective adsorption away of a contrast medium without removing useful materials, such as albumin and immune globulin by constituting the contrast medium adsorber of a water-insoluble porous body having a carbide surface. CONSTITUTION:A cap 6 having a bodily fluid introducing port 5 is screwed via a packing 4 extended with a filter 3 on the inner side to the aperture at one end of a cylinder 2 of an adsorbing device 1. A gap 8 having a bodily fluid leading out port 7 is screwed via a packing 4' extended with a filter 3' on the inner side to an aperture at the other end of the cylinder 2 to form a container. The contrast medium adsorber consisting of the water-insoluble porous body having the carbide surface, such as spherical active carbon of a petroleum pitch system, is packed and held between the filters 3 and 3' to form an adsorber chamber 9. The blood taken out of the inside of the body is directly passed through the adsorbing device 1 and is thereby purified. The contrast medium in the bodily fluid is selectively adsorbed away at a high rate in this way.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a contrast agent adsorbent for selectively adsorbing a contrast agent used for blood vessel contrast enhancement. In recent years, a method of angiography using a contrast agent has been clinically used as a means for early detection of abnormalities in blood vessels and organs.
Although this angiography with a contrast agent is very useful clinically, it is also known that there are side effects due to the contrast agent. Examples include skin, cutaneous appendage disorders, cardiovascular disorders, respiratory disorders, or urinary disorders. In particular, when a contrast medium is used in a patient with organ dysfunction such as renal failure, the side effect is serious because it is not rapidly excreted from the body. Therefore, a technique for selectively removing the contrast agent from the blood to prevent side effects is desired.

[0002]

2. Description of the Related Art The existing technologies usable for the above purposes are:
There are (1) plasma exchange and (2) plasma filtration. Plasma exchange is a method in which plasma, which is a filtered component thereof, is separated from blood containing a contrast agent by a hollow fiber membrane, plasma containing the contrast agent is discarded, and frozen fresh plasma or albumin solution is replenished.

However, in this method, albumin, immunoglobulin, which is a useful component in blood together with a contrast agent,
Blood coagulation system proteins, complement components, hormone systems, etc. are discarded at the same time, and because the fresh replenisher, frozen fresh plasma or albumin solution, is of biological origin, infection with an infectious disease is likely to occur. It has various problems such as difficulty in acquisition and high price. Plasma filtration is a method of filtering and discarding all molecules smaller than the contrast agent from blood, and replenishing the electrolyte.

In this method, less material is discarded than plasma exchange. However, it has the disadvantage that useful components in the blood that are smaller than the contrast agent are discarded, and because the pore size distribution of the plasma filtration membrane is not constant, there is also a large loss of protein that is greater than the contrast agent, which results in low loss. There are some problems such as sometimes falling into protein plasma.

[0005]

As described above, the conventional techniques cannot avoid the removal of useful components in blood, and it has been impossible to selectively remove only the contrast agent in blood.
An object of the present invention is to provide a technique for selectively removing a contrast agent in blood, which is less likely to remove useful substances such as albumin and immunoglobulin, and is an adsorption capable of selectively adsorbing and removing the contrast agent. To provide the body.

[0006]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies in accordance with the above object, and as a result, by using a water-insoluble porous material having a carbonized surface such as activated carbon, a surprisingly high rate was achieved. Moreover, they have found that they can selectively adsorb a contrast agent, and have completed the present invention. That is, the gist of the invention resides in an adsorbent for a contrast agent (hereinafter simply referred to as the present adsorbent), which is characterized by comprising a water-insoluble porous material having a carbonized surface.

The contrast agent targeted by the present adsorbent will be described in more detail. The molecular weight used for intravascular administration is about 8 × 1.
It is an ionic or nonionic contrast agent of 0 ³ or less. Specific examples include iopamidol, amidotrizoic acid, iohexol, iotalamic acid, iodoamide, metrizoic acid, metrizamide, iohexol, and other monomers, and ioxaglic acid, adipiodone, iotroxic acid,
Examples thereof include dimers such as iodoxamic acid and iotrolan.

The water-insoluble porous material having a carbonized surface in the present invention means a substance which is solid in water and whose surface is carbonized like activated carbon.

As the shape of the water-insoluble porous material having a carbonized surface, any of spherical shape, granular shape, thread shape, hollow fiber shape, flat membrane shape and the like can be effectively used. From the viewpoint of circulation of body fluid during circulation of body fluid,
Spherical or granular is more preferably used. The spherical or granular average particle size of 10 to 2500 μm is easy to use, but the range of 25 μm to 1000 μm is preferable, and 50 μm to 600 μm is more preferable.

The water-insoluble porous material having a carbonized surface is required to be a porous material from the viewpoint that the adsorption surface area of the contrast agent can be made large and the practical adsorption ability can be obtained. The exclusion limit molecular weight (protein) of the porous body may be at least the molecular weight of the contrast agent to be adsorbed. If specifically shown, 2
The range of x10 ² to 2x10 ⁷ is preferable. More preferably, it is 2 × 10 ² to 2 × 10 ⁴ .

The pore size distribution of the porous body can be obtained from the mercury intrusion curve by the mercury intrusion method (for example, Catalyst Engineering Course-4, "Catalyst Measurement Method", Catalysis Society of Japan, published by Jishin Shokan, pages 69-73). The number of pores having a diameter of 0.1 nm or more is preferably large, and it is preferable that the pores are gathered in the range of 0.1 nm to 200 nm. More preferably 0.1n
m to 100 nm, and more preferably 0.
The range of 1 nm to 10 nm is the most desirable.

Activated carbon generally has a molecular weight of 10
It is a typical example of a water-insoluble porous body having a carbonized surface that is also used for adsorption of substances of ⁴ or less, but there are powdery, granular (crushed), spherical, and other shapes depending on the manufacturing method, There are various pore distributions, such as one distributed in the smaller pores, one distributed in the larger pores, and two distributions in the small areas and the large areas.
The activated carbon is preferably in the form of particles, particularly in the form of spheres, and the pore distribution is large in the preferred pore size range described above.

As a method for producing activated carbon, wood, brown coal,
Peat, etc. are treated with chemicals (zinc chloride, phosphoric acid, etc.) as an activator to dry-distill, charcoal, etc. are activated with steam, and petroleum pitch is used as a raw material for beading and activation. It is possible to use the method that has been used. Further, the granular activated carbon may be granulated into a spherical shape.

In the adsorbent of the present invention, the water-insoluble porous material having a carbonized surface may be surface-treated to control the adhesion of platelets in order to improve the affinity with blood. This can be achieved, for example, by providing a coating layer of a low-adhesive platelet material on the surface of the water-insoluble porous body having a carbonized surface that comes into contact with blood cells.

As the platelet low-adhesion material, a polymer material having a hydroxy group such as hydroxyethyl methacrylate and hydroxyethyl acrylate, vinylamine,
Copolymers of a monomer having a basic nitrogen-containing functional group such as dimethylaminoethyl (meth) acrylate and a polymerizable monomer having no basic nitrogen-containing functional group, a sulfonic acid group, a carboxylic acid group, etc. Polymeric materials having negatively charged functional groups, block copolymers such as segmented polyurethane and segmented polyester, and graft copolymers such as copolymers of monomers having polyethylene oxide chains and other polymerized monomers. Examples thereof include polymers.

The adsorbent of the present invention is generally used by being filled and held in a container having a body fluid outlet. An example of the adsorber 1 filled with the present adsorbent is shown in FIG.
A cap 6 having a bodily fluid introduction port 5 through a packing 4 having a filter 3 inside, at an opening of one end of the cylinder 2.
Is fitted with a screw, and the body fluid outlet 7 is inserted into the other end opening of the cylinder 2 through a packing 4 ′ having a filter 3 ′ stretched inside.
The cap 8 having the above is screw-fitted to form a container, and the adsorbent layer 9 is formed by filling and holding the adsorbent in the gap between the filters 3 and 3 ′.

The adsorbent layer 9 may be filled with the present adsorbent alone, or may be mixed or laminated with another adsorbent. The capacity of the adsorbent layer 9 is 10 to 10 when used for extracorporeal circulation.
About 500 ml is suitable. When the adsorber of the present invention is used for extracorporeal circulation, there are roughly the following two methods.
One is to separate the blood taken out from the body into a blood plasma component and a blood cell component by using a centrifugal separator or a membrane plasma separator, and after passing the plasma component through the adsorber for purification,
It is a method of returning it to the body together with the blood cell component, and the other one is a method of directly passing blood taken out of the body to the adsorber for purification. Regarding the passage rate of blood or plasma, since the adsorption capacity of this adsorbent is very high, it is possible to make the particle size of this adsorbent coarse and to reduce the packing degree, so that the shape of the adsorbent layer A high passing speed can be given regardless of how. Therefore, a large amount of body fluid can be treated.

The body fluid may be passed through continuously or intermittently depending on the clinical need or the condition of the equipment.

Example 1. Petroleum pitch-based spherical activated carbon (MZ
-AZ, manufactured by Kureha Chemical Industry Co., Ltd.) was used as the "water-insoluble porous body having a carbonized surface". Using this "activated carbon" as an adsorbent, the following adsorption experiment was conducted. Contrast agent (Eiken Chemical Co., Hexabrix 320, 100 ml of this contrast agent
6 ml of a solution in which 53.330 g of ioxaglic acid was contained) was prepared so that the concentration of ioxagric acid would be 1.7%.
Then, 1 ml of "activated carbon" was added, and the mixture was allowed to infiltrate at 37 ° C for 2 hours. After that, "activated carbon" was allowed to settle, and the concentration of the contrast agent only in the supernatant was measured by absorbance at a wavelength of 244 nm, and the ioxagluic acid concentration in the supernatant was determined from the separately measured standard solution. As a result of the adsorption experiment, the original solution concentration was 1.7%, but the concentration after adsorption was 0.04
%Met. That is, 97.6 of ioxaglic acid in the test solution
% Could be adsorbed.

Example 2. The same experiment as in Example 1 was carried out by using the activated carbon used in Example 1 coated with polyhydroxyethylmethacrylate. Poly-hydroxy-ethyl-meth-acrylate is
60 g of ethyl meta acrylate and 387 of ethanol
After adding g to a flask and adjusting the temperature to 57 ° C., 0.24 g of azobisisobutyronitrile was added, and polymerization was carried out while stirring for 7.5 hours. The coating of the polymer on the activated carbon was carried out by immersing the activated carbon in a 1 wt% ethanol solution of the polymer for 15 minutes, collecting the activated carbon, and drying with hot air.

As a result of the adsorption experiment, the original liquid concentration was 1.7%, and the concentration after adsorption was 0.06%. That is, 96.5% of ioxaglic acid in the test solution could be adsorbed. 1 ml
The column (diameter 8 mm, length 20 mm) was packed with the adsorbent of the present example, and fresh human blood supplemented with heparin was flowed through this column for 30 minutes at a flow rate of 0.5 ml / min, but blood coagulation was observed. There wasn't. Also, 75% of the platelets passed.

[0022]

The contrast agent adsorbent of the present invention adsorbs and removes the contrast agent in the body fluid with high efficiency and selectively, and the adsorber using the adsorbent is very compact and simple and safe. Is. INDUSTRIAL APPLICABILITY The present invention can be applied to general usage of purifying and regenerating body fluids such as blood and plasma, and is effective for reliable treatment in suppressing side effects associated with administration of a contrast agent in blood.
Further, the adsorbent of the present invention can be used not only as a therapeutic device filled in a container but also as an affinity adsorbent for separating and purifying a contrast agent.

[Brief description of drawings]

FIG. 1 is a schematic cross-sectional view showing one example of the form of an adsorber using a contrast medium adsorbent of the present invention.

[Explanation of symbols]

 1 Adsorber 2 Cylinder 3,3 'Filter 4,4' Packing 5 Body fluid inlet 6 Cap 7 Body fluid outlet 8 Cap 9 Adsorbent layer

Claims (1)

[Claims] 1. A contrast agent adsorbent comprising a water-insoluble porous material having a carbonized surface.