JPH044906B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Field of Application> The present invention provides a method for treating the outer wall surface of at least a portion of the hollow fibers of an oxygenator with an acid solution, an albumin solution, polyhydroxyethyl methacrylate (hereinafter referred to as
This relates to a hollow fiber oxygenator that has been made hydrophilic and has improved blood wettability by chemical treatment such as PHEMA), discharge treatment such as corona or plasma, or ozone treatment. <Prior art and its problems> Various polymers have been used in medical equipment materials, but most of them are generally hydrophobic. However, depending on the application, there are many cases in which the surface requires hydrophilic treatment. For example, an artificial lung performs gas exchange by circulating blood in one direction and gas (oxygen) in the other through a gas exchange membrane in the housing, but the gas exchange membrane is usually made of polypropylene, polyethylene,
Hydrophobic membranes such as silicone are often used. By the way, before an artificial lung is used, a briming operation is normally performed to remove the air inside it, but since the membrane is hydrophobic, it is poorly compatible with water, making it difficult to completely remove air during the briming operation. In particular, in the case of hollow fiber oxygenators that use porous hollow fibers as glass exchange membranes and allow blood to flow outside the hollow fibers, there is a phenomenon in which air is trapped between the fibers of the hollow fibers. It can be seen strongly. As a result, the fibers become blocked by the air, resulting in so-called "stains", resulting in a disadvantage that the gas exchange performance deteriorates. <Problems to be Solved by the Invention> Therefore, an object of the present invention is to improve the wettability for blood and swimming fluid by hydrophilizing the outer wall surface of the hollow fiber, suppress the adhesion of air bubbles, An object of the present invention is to provide an artificial lung whose gas exchange performance does not deteriorate. <Means for Solving the Problems> The present invention provides a hollow fiber oxygenator in which the outside of the hollow fiber is a blood flow path and the inside of the hollow fiber is a gas flow path, in which the hollow fiber is formed of a polyolefin resin, and The present invention provides a hollow fiber oxygenator characterized in that only the outer wall surface of the hollow fiber is subjected to a hydrophilic treatment so that air bubbles are less likely to adhere to the outer wall surface of the hollow fiber. Here, it is preferable that the hydrophilized hollow fiber is such that when one of the hollow fibers is inserted into water in a direction perpendicular to the water surface, the liquid level rises upward along the outer wall of the hollow fiber. Hereinafter, the hollow fiber oxygenator of the present invention will be explained in more detail using a blood storage tank built into the oxygenator as a preferred embodiment. As schematically shown in FIG. 1, a hard-shell type blood storage tank 1 integrated with the oxygenator has a blood inlet 2, which communicates with the blood inlet, and which is connected to the blood inlet 2.
A blood inflow portion 5 having a bottom surface with almost no drop;
A blood storage section 6 that communicates with the blood inflow section and has a bottom surface that gradually descends from the blood inflow section 5;
The housing 7 is made of a hard member and has a blood outlet 3 provided at the bottom thereof. Here, the bottom surface of the blood inflow section 5, the bottom surface of the blood storage section 6, or the side surface of the housing 7 forms the blood flow path surface 4. A blood reservoir having such a configuration is installed in the extracorporeal circulation circuit of an oxygenator. For example, as shown in FIG. Suitably used. In the preferred embodiment shown in FIG.
The housing has a cylindrical housing main body 12 and mounting covers 13a and 13b that close both open ends of the housing, and inside the housing, a large number of hollow fiber membranes 14 are arranged parallel to each other along the longitudinal direction of the housing. They are spaced apart. Both ends of these hollow fiber membranes 14 are connected to partition walls 15a, 15 with their respective openings not closed.
b is held in a fluid-tight manner by the housing body 12. Further, a gas inflow port 17 is provided in a gas inflow space 16 that communicates with the internal space of the hollow fiber membrane formed by one mounting cover 13a, the housing body 12, and the partition wall 15a, and a gas inflow port 17 is provided in the gas inflow space 16 that communicates with the internal space of the hollow fiber membrane formed by one mounting cover 13a, the housing body 12, and the partition wall 15a. Gas outflow ports 19 are provided in communication with the gas inflow space 18 that communicates with the internal space of the hollow fiber membrane formed by the partition wall 15b. Furthermore, the inner wall of the housing body 12 and both partition walls 15
a, 15b and the outer wall of the hollow fiber membrane 14, the blood chamber 20 has a blood inlet 21 and a blood outlet 2.
2 are provided in communication. The oxygenator 11 shown in this embodiment is of a type in which oxygen-containing gas such as air is blown into the interior space of the hollow fiber membrane 14 and blood is caused to flow outside the hollow fiber membrane 14 to perform gas exchange. The materials used for the hollow fiber membrane 14 include:
Any membrane may be used as long as it is made of a hydrophobic polyolefin resin that is commonly used in oxygenators; for example, polytetrafluoroethylene, polypropylene, etc. are preferable. The blood inlet 2 of the blood reservoir 1 configured as described above with reference to FIG. 1 is fluid-tightly connected to the blood outlet 22 of the artificial lung 11. On the other hand, a heat exchanger 23 is attached to the blood inlet 21 of the oxygenator. In the heat exchanger 23, a large number of heat exchange tubes 25 are arranged in a casing 24 in parallel and spaced apart from each other along the longitudinal direction of the casing 24, and both ends of the heat exchange tubes 25 are Each opening is held in a liquid-tight manner on the side wall of the casing 24 by a partition wall (not shown) in an unblocked state. A blood inflow port 27 and a blood inlet 21 of the oxygenator 11 communicate with a space 26 formed by this partition wall, the side wall of the casing 24, and the outer wall of the heat exchange tube 25. 26
A water inlet port 28 communicating with the outside of one of the partition walls of the casing 24 and a water inlet port 28 that communicates with the outside of one of the partition walls of the casing 24 are also provided in the internal space of the heat exchange tube 25 that is liquid-tightly separated from the casing 24.
Water outlet ports (not shown) communicating with the outside of the other partition wall of 4 are configured to communicate with each other. Therefore, the heat exchanger 23 shown in this embodiment
Blood flows into the heat exchanger 23 from the blood inlet port 27 and flows outside the heat exchange tube 25, and at this time, hot or cold water flows into the heat exchange tube 25 from the water inlet port 28. , heat exchange tube 15
warms or cools blood that comes into contact with it. However, it is also possible to similarly use a heat exchanger in which blood flows inside the heat exchange tube and a cooling or heating medium flows outside the heat exchange tube. In such an artificial lung, the entire blood flow path surface from the blood inlet 21 to the blood outlet 22 where blood may come into contact with the oxygenator member, in particular, only the outer wall of the hollow fiber membrane is subjected to hydrophilic treatment. This is its feature. In addition, in a hollow fiber bundle consisting of a plurality of hollow fibers, not all of the hollow fibers necessarily need to be subjected to hydrophilic treatment. for example,
If more than half of the hollow fiber bundles are hydrophilized and arranged evenly with those that are not treated, or if the central part of the hollow fiber bundle is restrained and constricted in the axial direction by the oxygenator housing, at least this restraint part is It can be treated to make it hydrophilic. Since the present invention is a hollow fiber oxygenator in which the outside of the hollow fiber is used as a blood flow path and the inside of the hollow fiber is used as a gas flow path, only the outer wall of the hollow fiber is subjected to hydrophilic treatment. If the pores of the hollow fiber become hydrophilic, plasma in the blood will leak into the gas flow path, causing problems. There are various methods for making the blood flow path surface hydrophilic.
Some of the methods applicable in the present invention will be described below. (1) Acid treatment The acids used include KM _o O ₄ /H ₂ SO ₄ solution,
There are solutions such as K ₂ Cr ₂ O ₇ /H ₂ SO ₄ , but especially
A KM _o O ₄ /H ₂ SO ₄ solution is preferred. The concentration of each component in this solution is KM _o O ₄ 0.05-1wt%,
90 to 100 wt% of H ₂ SO ₄ is preferred for hydrophilization. Furthermore, the acid mixture is not limited to the above-mentioned mixed acids, and a single acid such as H ₂ SO ₄ alone may be used. (2) Albumin aqueous solution treatment It is suitable for hydrophilization to use an albumin aqueous solution of 0.5 to 8 w/v%. (3) PHEMA treatment Treatment is performed using PHEMA, that is, polyhydroxyethyl methacrylate, and its concentration is preferably 0.05 to 4 wt% for hydrophilization. (4) Corona discharge treatment Corona discharge treatment is a method of causing so-called corona discharge on a material and introducing hydrophilic groups to the surface, and the treatment time is determined depending on the degree of hydrophilization required. (5) Plasma treatment Plasma treatment is a method of treating the surface of a polymer using active species created by glow discharge, and the treatment time is determined depending on the degree of hydrophilization required. (6) Ozone treatment Ozone treatment is a method of introducing hydrophilic functional groups onto the surface by applying ozone to the surface. The treatment time is determined depending on the required degree of hydrophilization. As mentioned above, there are various methods for making the oxygenator hydrophilic, but the easiest way to evaluate the degree of hydrophilicity is to evaluate the wettability of the oxygenator to water. Whether the hollow fiber has hydrophilicity is determined by
When one of the fibers is inserted into water in a direction perpendicular to the water surface, if the liquid surface rises upward along the outer wall of the hollow fiber, it can be said that the fiber has hydrophilic properties. On the other hand, in the case of hollow fibers that have not been subjected to hydrophilic treatment, the liquid level will be depressed downward along the outer wall of the hollow fibers. <Operation of the invention> In an oxygenator device in which a blood storage tank 1 is integrated with an oxygenator 11 and a heat exchanger as shown in FIG. The blood that is heated or cooled while reaching the blood inlet 21 of the artificial lung 11 flows through the inner space of the hollow fiber membrane 14 via the hollow fiber membrane 14 while passing through the blood chamber 20. gas exchange with oxygen-containing gas, removing carbon dioxide from the blood and supplying the oxygen consumed by itself. Here, the blood flow path surface of the oxygenator member, particularly preferably the entire surface of the blood flow path surface outer wall 14a of the hollow fiber membrane 14, is made hydrophilic by the above-described hydrophilization method to improve its wettability with respect to blood. As a result, the fibers do not become blocked by the air and create "stains" as in the prior art described above, and the blood flowing into the blood chamber 20 can flow smoothly without being stagnant. gas exchange is carried out efficiently. The blood supplied with oxygen in this manner flows out from the blood outlet 22 of the artificial lung 11 and flows into the blood reservoir 1 from the blood inlet 2 of the blood reservoir 1 which is in communication with it. The blood introduced from the blood inlet 2 reaches the blood inflow part 5 which is communicated with the blood inlet 2, is smoothly sent through the blood flow path surface 4, flows quietly into the blood storage part 6, and is stored. Ru. <Examples> The present invention will be specifically described below based on Examples. Comparative Example An oxygenator with a membrane area of 3.1 m ² was fabricated using 34,000 microporous polypropylene hollow fibers with an outer diameter of 300 microns. Example 1 0.4% KM _o was added to an artificial lung prepared in the same manner as in the comparative example.
After filling the oxygenator with an O ₄ /concH ₂ SO ₄ solution and leaving it for 5 minutes while tapping the constriction part of the oxygenator, the internal fluid was drained, washed with water, and air-dried. Example 2 A 4% albumin solution 2 was applied to an oxygenator prepared in the same manner as in the comparative example while hitting the constriction part of the oxygenator.
/min for 5 minutes and then air-dried. Example 3 1w/V% was applied to an artificial lung prepared in the same manner as in the comparative example.
After filling the oxygenator with a methanol solution containing PHEMA and leaving it for 1 minute while tapping the constriction part of the oxygenator, the internal fluid was drained and air-dried. Example 4 The same microporous polypropylene hollow fiber used in the comparative example was wrapped with a Teflon sheet of 80 μm in thickness using a corona discharge device (HFS202, manufactured by Kasuga Electric Co., Ltd.) to a width of 10 mm and a length of 20 mm. A current of 120 V and 6.5 A was applied to the electrode to perform corona discharge treatment, and the fiber was wound onto a bobbin at a winding speed of 50 m/min, and then an oxygenator similar to the comparative example was assembled using this hollow fiber. Example 5 The same microporous polypropylene hollow fiber as used in the comparative example was cut to a length of 50 cm.
Arrange them so that they do not overlap in the tank, 10 ^-1 torr, 30
Plasma treatment was performed at ~40°C, 100W, 2min. An artificial lung similar to that of the comparative example was produced using the obtained plasma-treated hollow fiber. Example 6 After sealing the gas port of an artificial lung prepared in the same manner as in the comparative example, ozone generated at 0.8/minO ₂ and 100V was applied from the blood inflow port for 3 minutes using an ozone generator (Japan Ozone Co., Ltd.). The inflow was allowed to pass. Thereafter, air was allowed to flow in and pass through to remove ozone, and the outer wall surface of the hollow fiber was treated to be hydrophilic. Test Example 1 The oxygen adding capacity of the artificial lungs produced in Comparative Example and Examples 1 to 6 was measured according to AAMI standards. The results are shown in Table 1. Regarding the performance of each oxygenator in Table 1, the indications have the following meanings. Before beating: After priming the oxygenator with bovine blood, blood oxygenation capacity was immediately measured. After hitting: After the above-mentioned priming, the middle constriction part of the artificial lung was hit strongly with a pin 150 times while blood was being circulated, and the oxygenation capacity of the blood was then measured.

[Table] Test Example 2 A test was conducted to measure the hydrophilicity of the hollow fibers used in the oxygenators produced in Comparative Examples and Examples 1 to 6. Water was placed in a beaker, and each of the above-mentioned hollow fibers was inserted one by one into the water from above in a direction perpendicular to the water surface. As a result, a meniscus was formed at the boundary between the hollow fiber outer wall and the liquid level, but in the case of the comparative example, the liquid level was depressed downward along the hollow fiber outer wall, and in the case of Examples 1 to 6, the liquid level was It was confirmed that the fibers rose upward along the outer wall of the hollow fibers, giving them hydrophilic properties. <Effects of the Invention> In the oxygenator of the present invention, the outer wall surface of the hollow fiber membrane is treated with acid, albumin, PHEMA, etc.
Since it has been made hydrophilic by corona discharge treatment, plasma treatment, ozone treatment, etc., it has extremely good wettability with priming liquid and blood. Therefore, since air bubbles are less likely to adhere to the outer wall surface of the hollow fiber membrane, blood can flow smoothly without being blocked by air bubbles between the fibers, and gas exchange can be performed efficiently.

[Brief explanation of drawings]

FIG. 1 is a longitudinal sectional view showing an embodiment of a blood storage tank applied to the present invention and a conventional example. FIG. 2 is a partially cutaway front view showing an artificial lung device having a hollow fiber membrane applied to the present invention. Explanation of symbols, 1...Blood storage tank, 2...Blood inlet, 3...Blood outlet, 4...Blood flow path surface (blood contact surface), 5...Blood inflow part, 6...Blood storage part, 1
1... Artificial lung, 14... Hollow fiber membrane, 14a... Hollow fiber membrane outer wall (blood contact surface), 16... Gas inflow space, 17... Gas inflow port, 18... Gas outflow space, 19... Gas outflow port, 20...Blood chamber, 21...Blood inlet, 22...Blood outlet,
23... Heat exchanger, 25... Heat exchange tube, 27
...Blood inflow port, 28...Water inlet port.

Claims (1)

[Scope of Claims] 1. In a hollow fiber oxygenator in which the outside of the hollow fiber is a blood flow path and the inside of the hollow fiber is a gas flow path, the hollow fiber is formed of a polyolefin resin, and the hollow fiber is made of a polyolefin resin. A hollow fiber oxygenator characterized in that only the wall surface is subjected to a hydrophilic treatment so that air bubbles are difficult to adhere to the outer wall surface of the hollow fiber. 2. Claim 1, wherein the hydrophilized hollow fiber is such that when one of the hollow fibers is inserted into water in a direction perpendicular to the water surface, the liquid level rises upward along the outer wall of the hollow fiber. Hollow fiber oxygenator described in Section 1.