JPH1024103A - Membrane oxygenator - Google Patents

Abstract

(57) [Problem] To provide a membrane-type artificial oxygenator using a hollow fiber, which does not cause a decrease in gas exchange performance even when used for a long time, in an external perfusion type membrane-type oxygenator. SOLUTION: Both the gas contact surface and the blood contact surface of the hollow fiber are subjected to a hydrophilic treatment.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a membrane oxygenator. More specifically, the present invention relates to an external perfusion type membrane oxygenator using a hollow fiber, wherein both the gas contact surface and the blood contact surface of the hollow fiber are subjected to a hydrophilic treatment.

[0002]

2. Description of the Related Art Among the functions of a living lung, an artificial lung substitutes a gas exchange function for enriching oxygen in blood and removing carbon dioxide, and is researched and developed as an auxiliary means for open heart surgery. At present, the bubble-type oxygenator and the membrane-type oxygenator are in practical use.

[0003] A membrane oxygenator is a technique in which venous blood is brought into contact with gas through a membrane to increase the oxygen concentration of venous blood and simultaneously release carbon dioxide into the gas. It has advantages such as being closer to a living lung, having less blood damage, and having a smaller priming volume, and has been frequently used clinically.

[0004] Generally, most of the polymers used as materials for the membrane-type oxygenator are hydrophobic polymers such as polyolefins. The artificial lung usually performs a priming operation to remove the internal air prior to use.However, in the priming operation, the outside of the hollow fiber that is the contact surface with blood is made hydrophilic to improve the familiarity with water. Has been proposed in Japanese Patent Publication No. 4-4906.

[0005]

However, when only the contact surface with blood is hydrophilized, there is no particular problem in the operation in a short time, but if the device is used for a long time, the water in the blood is converted into water vapor as a film. , And condensed and stay inside the hollow fiber. If water stays inside the hollow fiber, the flow of gas flowing inside the hollow fiber is hindered, and the gas exchange performance is reduced. Further, as a secondary effect, it also causes leakage of active components in blood due to hydrophilicity of the membrane. Accordingly, an object of the present invention is to provide a membrane-type oxygenator in which gas does not deteriorate due to water remaining on the inner surface of a hollow fiber through which gas flows.

[0006]

Means for Solving the Problems The present inventors have intensively studied to achieve the above object, and the water vapor that has permeated the membrane is condensed due to the temperature difference between blood and gas, and the condensed water droplets are converted to a hydrophobic membrane. A water droplet with a small contact angle is formed on the surface, and it is determined that the water droplet aggregates and grows to block the flow of gas inside the hollow fiber, and both the gas contact surface and the blood contact surface of the hollow fiber undergo hydrophilic treatment. Then, it was found that a membrane-type oxygenator free of the above problems could be obtained, and the present invention was achieved.
That is, the present invention relates to an external perfusion type membrane oxygenator in which gas flows in the hollow portion of a hollow fiber and blood flows outside the hollow fiber, and both the gas contact surface and the blood contact surface of the hollow fiber are hydrophilized. It is a membrane oxygenator characterized by being processed.

The material of the hollow fiber membrane used in the present invention is not particularly limited as long as it is a hydrophobic polyolefin polymer, and examples thereof include poly-4-methylpentene-1, polypropylene and polyethylene. it can. The outer diameter of the hollow fiber is usually 50-2000 μm, and the film thickness is 3-50.
0 μm. If the outer diameter or the film thickness is too small, the pressure loss when flowing the fluid becomes large, and if it is too large,
Since it is difficult to realize compactness of the apparatus, the outer diameter of the hollow fiber is preferably 100 to 500 μm, and the film thickness is preferably 6 to 100 μm.

In the present invention, it is important that both the gas contact surface and the blood contact surface of the hollow fiber are subjected to a hydrophilic treatment. Known methods can be used for the hydrophilization treatment. For example, sulfuric acid, hydrochloric acid, phosphoric acid, chloric acid, p-toluenesulfonic acid, potassium permanganate / sulfuric acid, sulfuric acid / chromic acid can be used. Examples thereof include oxidizing acid compound treatment such as a mixed system, alkali treatment, corona discharge treatment, plasma treatment, and ozone treatment. Also,
Heparinization, albumin coat, PHEMA coat, M
Anticoagulation treatment such as PC coating, graft polymerization, multilayer polymerization and the like are also effective.

Whether or not the surface is hydrophilic can be determined by measuring the contact angle between the film and bubbles in water by a modified Hamilton method. Hamilton's modified method is described in Journal of Colloid and Interface Science, Vol. 40, No. 2 (Journal of Co.).
lloid and Interface Science
ce, Vol. 40, no. 2, August 197
2, A Technique for the Cha
rectification of Hydrophi
like Solid Solid Surfaces, W.C. C. HA
MILTON) is a method for measuring the contact angle between a film and bubbles in water. That is, the contact angle of the sample before and after the hydrophilic treatment is measured according to Hamilton's modified method, and if the contact angle with water is smaller,
It can be determined that a hydrophilic treatment has been performed.

In the oxygenator of the present invention, both the inner and outer surfaces of the hollow fiber are subjected to hydrophilic treatment. However, when the outer surface, which is the blood contact surface, is further treated with an antithrombotic material, the blood contact surface is provided with antithrombotic properties. Therefore, it is preferable. To impart antithrombotic properties,
The outer surface subjected to the hydrophilic treatment may be subjected to an imine treatment and a silane treatment as necessary, and then coated with an antithrombotic material. As an antithrombotic material, it is preferable to use heparin from the viewpoint of availability and price.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION In order to obtain an artificial lung of the present invention, first, a hollow fiber using a polyolefin-based polymer such as poly-4-methylpentene-1 as a membrane material is produced by a known method. Perform hydrophilic treatment. The hydrophilic treatment may be performed according to the above-mentioned known method.

The degree of hydrophilicity is determined by processing a hollow fiber into an appropriate shape, and measuring the contact angle between a film and bubbles in water by the above-mentioned modified Hamilton method. Confirmation of the effect of the present invention,
In accordance with the artificial lung performance evaluation standard (Japan Society for Artificial Organs), bovine blood whose hemoglobin, gas composition, etc. has been adjusted is allowed to flow into the artificial lung, blood at the entrance and exit of the artificial lung is collected, and the amount of oxygen and carbon dioxide transferred is measured. Done by

[0013]

【Example】

Example 1 and Comparative Example 1 Using a polypropylene hollow fiber having an inner diameter of 250 μm and an outer diameter of 300 μm, an artificial lung having a membrane area of 1.8 m ² was produced.
0.8% potassium permanganate / 2 on the blood contact surface (hollow fiber outer surface) and gas flow part (hollow fiber inner surface) of this oxygenator
A 0% aqueous sulfuric acid solution was perfused for 15 minutes to perform a hydrophilic treatment. The hydrophilization treatment may be performed separately on the outer surface of the hollow fiber and the inner surface of the hollow fiber. However, a 0.8% potassium permanganate / 20% sulfuric acid aqueous solution is passed through the outer surface of the hollow fiber, and continuously passed through the inner surface of the hollow fiber. Then, the hydrophilic treatment can be performed at once.

The hydrophilicity can be measured by using a goniometer-type contact angle measuring device (model G-1) manufactured by Elma Optical Co., Ltd.
Was used to measure the contact angle between the film and the bubbles by a modified Hamilton method, and it was confirmed that the contact angle was smaller than before the treatment. For comparison, an artificial lung in which only the blood contact surface was hydrophilized was prepared.

[0015] Bovine blood, hemoglobin 12g / dl,
Oxygen saturation (SvO ₂ ) = 55
%, Carbon dioxide partial pressure (PCO ₂ ) = 45 mmHg, and base excess (BE) = 0 meq / l. The bovine blood flows at a rate of 6 l / min to the outside of the hollow fiber of the oxygenator, the inner and outer surfaces of which are made of a hollow fiber whose surface is made hydrophilic.
0% oxygen gas was supplied at 6 l / min [gas flow rate (V) / blood flow rate (Q) = 1.0].

Blood was taken from the inlet and outlet of the oxygenator, and the amount of oxygen and carbon dioxide transferred was measured. The same test was performed for an artificial lung in which only the blood contact surface was hydrophilized.
The transfer amount of oxygen and the transfer amount of carbon dioxide were calculated by the following equations (1) and (2), and the effects were confirmed. FIG. 1 shows the change over time in the gas transfer amount at 360 minutes.

[0017]

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[0018]

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[0019]

[Table 1]

[0020]

[Table 2]

Example 2 and Comparative Example 2 Using a hollow fiber made of poly-4-methylpentene-1 having an inner diameter of 205 μm and an outer diameter of 255 μm, an artificial lung having a membrane area of 2.2 m ² was prepared. A 0.8% potassium permanganate / 20% sulfuric acid aqueous solution was perfused through the gas flow portion (the inner surface of the hollow fiber) of the oxygenator for 15 minutes to perform a hydrophilic treatment. Confirmation of hydrophilicity was performed in the same manner as in Example 1.

The blood contact surface (the outer surface of the hollow fiber) was similarly subjected to a hydrophilic treatment, and then perfused with a 1% glycidoxypropyltrimethoxysilane aqueous solution for 15 minutes and dried at 50 ° C. Further, a 0.09% polyethyleneimine aqueous solution was perfused for 2 hours, and a heparin solution into which an aldehyde group was introduced was perfused three times for 1.5 hours, and then washed with water and dried. For comparison,
An artificial lung was prepared in which only the blood contact surface was treated with heparin and the inner surface of the hollow fiber was not hydrophilized.

In the same manner as in Example 1, the effect was confirmed using the adjusted bovine blood. FIG. 2 shows the change over time in the gas transfer amount at 360 minutes.

[0024]

[Table 3]

[0025]

[Table 4]

[0026]

According to the present invention, it is possible to provide a membrane-type oxygenator in which the inner and outer surfaces of the hollow fiber are made hydrophilic. The membrane oxygenator of the present invention does not aggregate and stay inside the hollow fiber even when the water in the blood passes through the membrane as water vapor. Therefore, the membrane oxygenator of the present invention does not cause a decrease in gas exchange performance even when used for a long time, and is extremely useful.

[Brief description of the drawings]

FIG. 1 is a graph showing a change over time in a gas transfer amount in Example 1 and Comparative Example 1.

FIG. 2 is a graph showing a change with time of a gas transfer amount in Example 2 and Comparative Example 2.

Claims (3)

[Claims] 1. An external perfusion type membrane oxygenator in which a gas flows through a hollow portion of a hollow fiber and a blood flows outside the hollow fiber, wherein both a gas contact surface and a blood contact surface of the hollow fiber are hydrophilized. A membrane oxygenator, which is characterized in that: 2. The membrane oxygenator according to claim 1, wherein the blood contact surface is further treated with an antithrombotic material. 3. The membrane-type oxygenator according to claim 2, wherein said antithrombotic material is heparin.