JPH07289632A - In-blood toxic substance removing device - Google Patents

Abstract

PURPOSE:To separate and remove an organic compound which is adsorbed on a plasma protein through a hydrophobic bond. especially bilirubin by means of a batch hemodialysis, by setting a mean pore size of a semi-permeable membrane at a certain value in an artificial hemodialysis which is provided with an adsorbing means composed of a blood purification adsorbing material in a circulation system. CONSTITUTION:A perfusion solution 4 containing albumin is made contact with blood flow via a tubular semi-permeable membrane 2 and the mean pore size of the semi-permeable membrane 2 is set at 50-100Angstrom in a hemodialysis provided with an adsorbing means composed of a blood purification adsorbing material 7 in a circulation pathway 6 of the perfusion solution 4. A metabolized product bound to albumin in blood, especially bilirubin is made to pass through from the semi-permeable membrane 2 and is made to bind to albumin rapidly in the perfusion solution 4 by means of the adsorbing power of albumin.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a toxic substance removing apparatus for removing metabolites in blood by hemodialysis.
The device of the present invention is a system in which unnecessary components in blood transferred to the perfusion solution are removed and a dialyzing solution that is as clean as possible is constantly perfused.

[0002]

2. Description of the Related Art Among toxic substances dissolved in blood, there are a large number of organic compounds existing in a state of being adsorbed to proteins in blood such as neurotoxic substances which induce hepatic coma. . These adsorption states are considered to be a phenomenon in which molecules that do not easily form a bond with a water molecule in an aqueous solution or atomic groups in the molecule gather with affinity. This is sometimes called a hydrophobic bond.

Organic compounds adsorbed to proteins in blood in such a bound state are difficult to be separated and removed by general hemodialysis.

On the other hand, the apparatus for removing metabolites in blood by hemodialysis is roughly classified into a single-pass method in which a concentrated stock solution of perfusate is continuously diluted with water and used. There is a batch system in which a perfusate prepared in advance is circulated and used. The one-pass method requires a large amount of perfusate of about 300 liters and must be directly connected to the tap, and the apparatus applied to this method is expensive. There 7
A batch method that can be performed with about 0 liter of perfusate is widely used.

[0005]

DISCLOSURE OF THE INVENTION An object of the present invention is to separate and remove an organic compound, especially bilirubin, which is adsorbed on a plasma protein by a hydrophobic bond, by a batch type hemodialysis.

From the viewpoint of its existence in blood, bilirubin is classified into conjugated bilirubin that weakly binds albumin and unconjugated bilirubin that strongly binds albumin. In the present invention, bilirubin means both of them.

[0007]

According to the present invention, a blood flow is contacted with a perfusate containing albumin through a semipermeable membrane, and an adsorbent comprising a blood purification adsorbent in the circulation system of the perfusate. In the artificial dialysis provided with, the gist of the toxic substance removing device in blood is characterized in that the average pore diameter of the semipermeable membrane is 50 to 100 Å.

The structure of the present invention will be described in detail below. The semipermeable membrane used in the present invention is used for medical artificial dialysis, and the material thereof may be polyamide, boriacrylonitrile, cellulose triacetate, polysulfone or the like. Although slightly inefficient, polymethylmethacrylate can also be used. The semipermeable membrane used for medical artificial dialysis has an average pore diameter of 20 to 30 Å, but the feature of the present invention is that it is a high performance type having an average pore diameter of 30 to 100 Å.

The semipermeable membrane used in the present invention has a thickness of 15 to 60 μm.

In the present invention, the blood purification adsorbent is selected to remove the organic compound adsorbed on the plasma protein. For example, as disclosed in Japanese Examined Patent Publication No. 56-7437, a monomer mixture consisting of a crosslinkable polymerizable monomer and a monovinyl monomer is copolymerized to give an average pore diameter of 300Å to 9000.
Use a porous material that is Å.

Activated carbon which is commonly used as an adsorbent is creatine / vitamin B which is not strongly adsorbed to proteins in blood.
It adsorbs metabolites having a molecular weight of 2000 or less such as 12 but does not adsorb large molecules such as proteins, so that metabolites such as bilirubin bound to albumin are not adsorbed. Therefore, activated carbon is not suitable as the adsorbent for blood purification of the present invention.

However, the adsorbent for other purposes can be used in series / parallel or in a state where both are mixed with the adsorbent for blood purification of the present invention in the channel. Examples of adsorbents for other purposes include activated carbon / fibrous activated carbon for adsorbing creatine / uric acid and the like, and activated carbon / alumina combination for adsorbing inorganic phosphorus compounds in addition to creatine / uric acid and the like.

In the present invention, the concentration of albumin added to the perfusate may be higher than the concentration of albumin in blood, and is preferably 25 to 50 g / liter. This concentration
When the amount is 25 g / liter or less, the amount of the metabolite adsorbed is small, and when the amount is 50 g / liter or more, there is an economical problem that a large amount of expensive albumin is used.

[0014]

The principle of allowing albumin to be present in the perfusate in order to transfer the unwanted components in the blood to the perfusate is as disclosed and known in JP-A-49-42189.

According to the present invention, a blood flow is contacted with a perfusate containing albumin through a semipermeable membrane, and metabolites bound to albumin in blood, particularly bilirubin, are passed through the semipermeable membrane, whereby It rapidly binds to albumin in the perfusate by adsorption force. The reason for this is unknown, but it is considered to be an agglutination reaction. For example, albumin serves as an agglutinogen and bilirubin serves as an agglutinin, and bilirubin acts as a bridge between albumin in blood and albumin in the perfusate, making aggregates for the time being, and the affinity between bilirubin and albumin in the perfusate. Is expected to overcome the affinity between bilirubin and albumin in blood. Based on such consideration, it was found that the object of the present invention can be achieved by setting the average pore size of the semipermeable membrane to 30 to 100Å.

It has been found that the object of the present invention can be achieved when the thickness of the semipermeable membrane is 15 to 50 μm.

According to the present invention, since the adsorbing means consisting of the adsorbent for blood purification is provided in the circulation system of the perfusate, only the unnecessary component in the blood adhered to the albumin in the perfusate, that is, the toxic substance is provided. Are adsorbed and removed. as a result,
A liquid containing albumin that is not bound to a toxic substance can always be reperfused to remove the toxic substance.

[0018]

EFFECTS OF THE INVENTION According to the present invention, toxic substances in blood can be efficiently removed through a semipermeable membrane, and artificial liver, artificial kidney,
It can be applied to toxic poisoning treatment.

[0019]

DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1 is an illustration of a specific example showing an embodiment of the present invention. In FIG. 1, blood enters at the inlet 1, passes through the inside of the tubular semipermeable membrane 2 and exits at the outlet 3 (eg, connecting the patient's artery to the inlet 1 and the vein to the outlet 3). The perfusate 4 is circulated in the circulation path 6 by the pump 5 as shown by the arrow. The unnecessary components in the perfusion solution are adsorbed by the blood purification adsorbent 7.

The blood discharged from the outlet 3 is not shown in the figure, but continuous hemofiltration (CHF) continuous hemodialysis (CHD).
Often connected to the circuit.

In the circulation path 6 for the perfusate 4, there is generally a stock tank for the perfusate (not shown). The liquid level in this stock tank rises due to the accumulation of some of the water in the blood. For this reason, some measures may be taken to keep the liquid level constant.

In the apparatus for removing toxic substances from blood shown in FIG. 1, hollow cellulose triacetate fiber (outer diameter about 250 μ, inner diameter about 200 μ, molecular weight cutoff about 10,000, length 20 cm) as tubular semipermeable membrane 2 1 15,000 pieces were bundled and used. The total effective dialysis area of this hollow fiber bundle was 1.5 square meters.

The pore diameter of the semipermeable membrane was 75Å.

Adsorbent 7 for liquid purification in the circulation system of perfusate
Was used 350 g of BR-350 manufactured by Asahi Medical Co., Ltd., which is a styrene / divinylbenzene copolymer resin. The adsorbent for blood purification is generally 350 g or less.

The following processing was carried out using the above apparatus. Plasma having a bilirubin concentration of 37 mg / deciliter (however, collected from the plasma exchange waste liquid) was maintained at 37 ° C. from the inlet 1 of the device, and continuously at a flow rate of 60 ml / min.
35 liters were supplied, taken out from the outlet 3 and circulated.

On the other hand, the perfusate was Kinderley AF-2 solution manufactured by Fuso Chemical Industry Co., Ltd. in which sodium chloride, potassium chloride, sodium bicarbonate, glucose, etc. were dissolved, and the osmotic pressure was adjusted to 298 mOsmol, and the temperature of the solution was adjusted. While maintaining the temperature at 37 ° C, 70 liters were continuously circulated at a flow rate of 30 ml / min. This perfusate contained 42 g / liter of albumin.

As a result of measuring the concentration of bilirubin in the perfusate by the diazo method, it was 0.6 mg / deciliter after 10 minutes, 0.7 mg / deciliter after 40 minutes, and 0.8 mg / deciliter after 60 minutes. Yes, 90
After minutes, it was 0.9 mg / deciliter, and after 120 minutes it was 0.9 mg / deciliter. This can be considered to indicate that bilirubin was transferred from the blood to the perfusate and adsorbed by the adsorbent.

The concentration of bilirubin in plasma after 120 minutes was 22 mg / deciliter, so about 5 g
Bilirubin of the above has passed from the plasma to the perfusate through the semipermeable membrane.

For comparison, the hole diameter of the tubular semipermeable membrane 2 is 30Å
The same measurement as in Example was carried out, but the concentration of bilirubin in plasma and perfusate hardly changed.

[Brief description of drawings]

FIG. 1 is a schematic view of an embodiment of the present invention.

[Explanation of symbols]

 1 Inlet 2 Tubular semipermeable membrane 3 Outlet 4 Perfusate 5 Pump 6 Circulation path 7 Blood purification adsorbent

Claims (2)

[Claims] 1. An artificial dialysis in which an albumin-containing perfusate is brought into contact with a blood stream through a semipermeable membrane, and an adsorbent comprising a blood purification adsorbent is provided in the circulation system of the perfusate. A device for removing toxic substances in blood, characterized in that the semipermeable membrane has an average pore size of 50 to 100 liters. 2. The device for removing toxic substances from blood according to claim 1, wherein the semipermeable membrane has a thickness of 15 to 50 μm.