JPH0550300B2 - - Google Patents

Description

[Detailed description of the invention]

(Industrial Application Field) The present invention eliminates blood stagnation and air bubble retention at the blood port (blood inlet/outlet), and can evenly distribute blood to each hollow fiber, allowing for long-term use. The present invention relates to a hollow fiber type blood processing device. (Prior Art) Conventionally, blood processing devices using hollow fibers as separation membranes have been widely used as hemodialysis devices, artificial liver devices, plasma separation devices, and artificial lung devices. Generally, many of such blood processing apparatuses are cylindrical. Taking a cylindrical blood processing device as an example, its structure is shown in FIG. In FIG. 5, reference numeral 1 denotes an inlet side blood port with a circular cross section for guiding blood into the internal space of the hollow fiber 5 and isolating it from the outside, and blood 10 is introduced from a blood inlet 20 provided at the top of the port. be done. 1
Reference character a designates an exit port with a circular cross section for collecting the blood that has passed through the internal space of the hollow fibers, leading it out through the blood outlet 20a into a tube of a certain size, and isolating it from the outside. 2 is port 1 or port 1
port 1 or port 1a so that a does not separate from the outer cylinder 3, and in order to guide the blood introduced into the port into the internal space of the hollow fiber 5 without leaking to the outside.
This is a fixing cap for bringing the hollow fiber bundle into close contact with the partition wall 6 which fixes the hollow fiber bundle via the packing 12. The outer cylinder 3 is preferably cylindrical and made of transparent, hard synthetic fibers, and its internal space 9 is filled with several hundred to ten thousand hollow fibers 5. Further, this outer cylinder 3 is provided with an inlet 4 for the blood purification fluid 11 and an outlet 4a for the harmful substances in the blood. A large number of hollow fibers 5 are filled in the internal space 9 of the outer cylinder 3,
Both ends of the hollow fiber 5 are fluid-tightly fixed by partition walls 6 having excellent blood compatibility, and the internal space of the hollow fiber 5 communicates with the internal space 8 of the blood port. The partition wall 6 is generally made of polyurethane resin;
As a result, the internal space 8 of the blood port is isolated from the internal space 9 of the outer cylinder 3, and the internal space 8 of the port and the internal space 9 of the outer cylinder 3 are in contact only through the wall membrane of the hollow fiber 5. It's getting old. That is, the introduced blood 10 enters the internal space of the hollow fibers via the space 8 in the inlet port, and harmful substances in the blood are discharged into the internal space 9 of the outer cylinder 3 through the wall membrane of the hollow fibers. The purified blood is returned to the body via the space inside the outlet port 1a. On the other hand, harmful substances discharged into the internal space 9 of the outer cylinder 3 are taken out to the outside via the outlet 4a together with the blood purification fluid 11 introduced from the inlet 4 as necessary. As an improved example of such an axially symmetric blood port, Japanese Patent Application Laid-open No. 139274/1983 discloses that the angles φ and θ shown in FIG. 6 are 60 to 85 degrees and 7 to 23 degrees, respectively.
A blood port is disclosed that has a funnel-shaped space shaped to have a height h of 1.5 to 3.5 mm. Furthermore, in Japanese Patent Publication No. 60-5308, as an example of a non-axisymmetric port, as shown in Figures 7 and 8, blood is introduced and discharged horizontally and tangentially to the cut surface of the hollow fiber bundle. A recessed blood port is disclosed. (Problems to be Solved by the Invention) However, such conventional cylindrical blood processing devices have the following drawbacks. In particular, they do not use anticoagulants such as heparin at all, or
Alternatively, there is a practical problem in the case of hemodialysis therapy in which the amount used is reduced or in the case of long-term use over several days. In other words, in FIG. 5, the structure of the blood port 1 used is such that when blood is introduced into the port from the entrance point A of the port, it first collides with the center of the cut surface of the hollow fiber bundle, and then the blood enters the hollow fiber bundle. Blood is dispersed to the hollow fibers at the outer periphery due to the pressure (or resistance) in the inner space of the fibers and the partition wall that fixes the hollow fiber bundle. Therefore, the velocity of blood flowing through the space inside the port is high in the center area directly below the blood inlet/outlet, but as it flows in all directions of 360°, the velocity decreases rapidly, especially at the outer periphery. There is an area around the port where blood stagnates. As a result, the performance as a blood processing device deteriorates, and when blood is returned after blood processing, the blood return speed is different between the center and the outer periphery, so the internal space of the hollow fibers near the outer periphery and the blood stagnate. This causes residual blood and blood clots in the affected area. Particularly when blood processing is performed for a long period of time, blood may clot in the internal space of the hollow fiber where the blood velocity is slow or around the port where blood stagnates, resulting in areas where blood flow stops and blood processing becomes impossible. There is. In order to overcome these drawbacks of the conventional device, Japanese Patent Application Laid-Open No. 57-86359 discloses a blood port which has a specific funnel-shaped internal space whose bottom is the end face of the hollow fiber bundle, and which has a blood inlet at the top. A device using this method has been proposed. It is true that with this device, the blood supplied to the port is distributed easily within the funnel-shaped internal space, so blood flows into the hollow fibers at a nearly uniform speed both in the center and on the outer periphery of the hollow fiber bundle. Although this advantage exists, it is still unsatisfactory with regard to the rapid decrease in blood flow rate in the internal space of the port from the inflow/outlet toward the port periphery and the stagnation of blood in the port periphery. In Japanese Patent Publication No. 60-5308, as shown in Figures 7 and 8, blood flows in from the tangential direction of the circular section of the inlet port, and the cut surface of the hollow fiber membrane bundle A blood port of the type introduced above, on a cut surface of a fixed hollow fiber membrane while spiraling around, ie inside the hollow fiber membrane, is shown. In this case, blood is guided from the tangential direction to the outer periphery, which occupies a relatively large area on the cut surface of the hollow fiber membrane, and then the blood layer thickness gradually decreases toward the center, so that the outer periphery and the inner periphery are hollow. The velocity of blood flowing into the internal space of the fiber membrane group, the vertical component and the horizontal component of the blood velocity in the blood port relative to the cut plane of the hollow fiber membrane are kept more uniform than in the blood port shown in FIG. Because the flow path is long at the thick outer periphery, the attenuation of the horizontal component is large, and the structure of the blood port near the outer periphery is complex, which tends to cause stagnation, and if the distribution of hollow fibers is poor, the Overflow also occurs, resulting in thrombus formation,
In addition to easily causing air bubbles to accumulate, there were other problems such as the port becoming bulky and increasing the amount of blood filled. As mentioned above, these conventionally known blood ports are susceptible to air bubble retention, thrombus and blood clot formation,
Problems associated with this, such as performance deterioration of blood processing equipment and residual blood, have not been fully resolved, especially when blood processing is performed without using anticoagulants such as heparin, or with reduced usage. In particular, when performing long-term blood processing over several days, the hollow fibers become severely blocked due to the above reasons.
There was a problem that it was not practical. Therefore, the problem to be solved by the present invention is to provide a blood treatment method that has an improved blood port that reduces the accumulation of air bubbles, thrombus, and blood clots, and prevents blockage of hollow fibers even after long-term continuous use. The question is how to obtain the device. (Means for Solving the Problems) As mentioned above, conventionally known blood ports have sought to uniformly flow blood into the interior of each hollow fiber membrane in a hollow fiber bundle, but heparin When the amount of blood is reduced or when used for a long period of time over several days, thrombus formation occurs at the blood port, resulting in a decrease in the performance of the blood processing device, a decrease in platelets, etc., and this is not practically satisfactory. As a result of intensive research by the present inventors to improve this point, we found that the thickness of the internal space of the blood port, the direction of blood introduction/output, and the position of the introduction/exit are extremely important. The present inventors have discovered that measuring the uniform inflow of blood is more effective in solving the above problems, and have completed the present invention. That is, the present invention is a blood processing device in which a blood port is attached to at least one end of a cylindrical module in which a hollow fiber bundle with an open end is housed so as to form a disc-shaped internal space, When the thickness h (cm) of the disc-shaped space of the blood port is s0.9m ² with respect to the membrane area s (m ² ) of the module, h0.237×{(s−0.9)×
4.23+1}×1/√s, when s< ^0.9m2 , the relationship h0.237×√+0.025 is satisfied, and the blood is provided close to the outer periphery of the disc-shaped space of the port. This blood processing device is characterized in that an inlet or an outlet is provided so that the blood is introduced into or led out from a tangential direction of 60 degrees or less with respect to a disc-shaped space through an opening. In particular, the present invention is characterized by a sufficiently thin disc-shaped blood port internal space defined by the above formula and a blood inlet or outlet provided close to the outer periphery of the space. , Blood is introduced and extracted from the tangential direction of the disc-shaped space at an angle of 60 degrees or less. (Refer to Figures 1 to 4) In a blood port having such a structure, the internal space of the port is thin, so the spiral flow of blood within the port is further strengthened, and the blood flows on the open end surface of the hollow fiber bundle. Component of velocity parallel to the end surface (horizontal component)
The blood port of the present invention is much faster than the conventionally known blood ports, and therefore has a great effect of suppressing the accumulation of air bubbles in the blood port and the adhesion of platelets that cause thrombus formation. The thinner the thickness of the internal space of the blood port, which is an important factor in the present invention, the more effective it is, but in reality, the size of the blood processing device, the required blood flow rate during blood processing, the viscosity of blood, and the use of antithrombotic agents. It is necessary to set a value suitable for each blood processing device, taking into consideration factors such as the amount. According to the research results of the present inventors, when the thickness h (cm) of the disc-shaped space of the blood port is s0.9m ² with respect to the membrane area s (m ² ) of the module, h0.237×{(s −0.9)×4.23
+1}×1/√s When s<0.9m ² , h0.237×√+0.025 Preferably When s0.9m ² , h0.142×{(s−0.9)×4.23+
1}×1/√s When s<0.9m ^{2 ,} h0.142×√+0.015 It is important to satisfy the following relationship in order to prevent thrombus formation and bubble retention at the blood port portion. If h is thicker than this, a sufficient effect cannot be achieved, and a wide ring-shaped thrombus is formed on the outer periphery of the port. The above formula was determined experimentally using various modules with different membrane areas (modules with membrane areas of 0.1 to 10 ^m2 are usually used),
Although its meaning is not strictly clear, the horizontal component of the blood velocity on the open end surface of the hollow fiber bundle is
It suggests that something more than a certain amount is necessary. Additionally, the shape of the internal space of the blood port has a substantially uniform thickness.
The thin disk shape (h) is important as a requirement of the present invention, and those with unevenness or rough edges are undesirable because they tend to accumulate in those areas. Another feature of the present invention is that the blood inlet or outlet to the blood port is provided close to the outer periphery of the thin disc-shaped port, and
Through its mouth, the upper and lower angles are 60° to the disc-shaped space.
It is at the point where blood is introduced or extracted from the following tangential directions: In the present invention, if the center of the inlet or outlet is separated from the center of the opening end surface of the hollow fiber bundle and the outer periphery by 1/3 or more of the maximum distance on the outer periphery of the hollow fiber bundle, air bubbles will be retained and thrombus formation will be inhibited. decreases rapidly. If the vertical angle is larger than 60°, a sufficient spiral flow cannot be generated in the blood on the opening end surface of the hollow fiber bundle, and a thrombus is likely to form within the port.
The opening end of the blood introduction/outlet to the port is usually provided on the upper surface side of the disc-shaped space, that is, on the opposite side to the opening end surface of the hollow fiber bundle. When blood is introduced into the port at an angle close to horizontal, it may be provided on the side circumference of the disc-shaped space, but the opening end of the blood introduction outlet into the port should be as flat as possible, for example, rectangular. It is preferable to have a cross section of Note that polypropylene, polycarbonate, polymethacrylate, etc. which are commonly used as blood port members can also be used in the present invention.
The inner surface that comes into contact with blood is preferably coated with a polymer that does not easily coagulate blood, such as silicone or segmented polyurethane. In addition, in the present invention, openings other than the blood inlet and outlet, such as a blood collection port, an infusion port, a heparin injection port, a sensor insertion port, an air vent, etc., may be provided in the blood port portion, but as few as possible. It is preferable to limit the amount to 100% because thrombus formation is less likely to occur. (Example) Examples 1 to 2 and Comparative Examples 1 to 3 Inner diameter with a thin silicone rubber layer on the inner surface
Polysulfone hollow fiber membrane 4000 with 320μ and outer diameter 480μ
The book was assembled into a cylindrical module with a membrane area of 1.0 m ² by a known method, and both ends were cut to form a circular hollow fiber bundle opening end face with a diameter of 36 mm. Various blood ports (polycarbonate A blood processing device of the same type and size with different blood port structures was obtained by connecting and fixing the inner surface coated with segmented polyurethane. The structure of the blood port used in the experiment is shown in Figure 3, with h = 3 mm and 2 mm.
As a comparative example, one with h = 5 mm and the shape shown in Figure 6 with φ = 75°, θ = 15°, d = 1.5 mm, and h = 2.0 mm.
and the shape shown in Fig. 7, h = 5 mm,
In addition, there were five types in which the blood inlet and outlet were provided horizontally with respect to the opening end surface of the hollow fiber bundle. Using 5 piglets with an average weight of 3.5 kg, each was connected to the blood processing device and the activated clotting time of the blood was measured.
Extracorporeal circulation was performed for 3 days while controlling the blood flow rate to be 200 seconds, flowing blood at an average blood flow rate of 250 c.c./min on the inner surface of the hollow fiber membrane, and flowing oxygen on the outer surface of the hollow fiber membrane. Table 1 shows changes in the oxygen capacity of each blood processing device during extracorporeal circulation, the degree of thrombus formation in the blood port at the end of extracorporeal circulation, and the state of occlusion of hollow fibers. From these results, it is clear that the blood processing device of the present invention exhibits high antithrombotic properties over a long period of time and has stable blood processing performance.

[Table] ◎...Extremely less ○...Less △...Slightly more ×...More Examples 3 ^to 5 and Comparative Examples 4 to 6 This figure shows the degree of thrombus formation at the blood port after 2 days of extracorporeal circulation using a goat for an oxygenator module of 5.0 m ² and 5.0 m ² .

[Table] Examples 6 to 7 and Comparative Example 7 1 m ² hollow fiber membrane oxygenator 3 having a blood port shown in FIG. 1 with h=2 mm and vertical angles θ of 70°, 50°, and 30° Regarding the seeds, extracorporeal blood circulation was performed in the same manner as in Example 1 using three piglets. Table 3 shows the degree of thrombus formation at the blood port at the end of extracorporeal circulation. From this result, the vertical angle θ is 70°
It is clear that thrombus formation at the blood port is difficult to suppress.

[Table] ○...Less △...Slightly more ×...More (Effects of the invention) As described above, the blood processing device of the present invention has the internal space of the blood port formed into a sufficiently thin disc shape, and the outer periphery of the hollow fiber bundle. By providing a blood inlet or outlet in close proximity to the hollow fiber bundle opening end surface so that blood flows in and out at an angle of 60° or less to the opening end surface, the blood flow velocity is horizontal to the opening end surface. This device is significantly larger than conventional devices. Surprisingly, this structure has a small effect on the blood inflow speed into the hollow fiber, and a nearly uniform inflow speed is obtained, which has a strong effect of suppressing the accumulation of air bubbles and the formation of blood clots and blood clots inside the blood port. death,
As a result, it is possible to obtain a blood processing device that can be used continuously for a long period of time, which was not possible with conventional devices, and that can be used in practice even when the amount of antithrombotic agents such as heparin is reduced or is not used. That is, the present invention is effective for various artificial organs intended for long-term continuous use, blood processing devices, and blood processing devices for patients in situations where it is difficult to use antithrombotic agents such as heparin.

[Brief explanation of the drawing]

FIG. 1 is a sectional view showing an example of a blood port in the blood processing apparatus of the present invention, and FIG. 2 is a top view thereof. FIG. 3 is a sectional view showing another example of the blood port in the blood processing apparatus of the present invention, and FIG. 4 is a top view thereof. FIG. 5 is a partial sectional view showing the blood port portion of a conventional blood processing device, FIG. 6 is a model diagram showing another example of the blood port portion of the conventional blood processing device, and FIG. FIG. 8 is a partial sectional view showing another example of a conventional blood processing apparatus, and FIG. 8 is a sectional view taken from the negative side thereof. In the figure, h... Height of blood port, 1,1
a... Inlet side and outlet side blood ports, 2... Cap, 3... Outer cylinder, 4, 4a... Blood purification fluid inlet and outlet, 5... Hollow fiber, 6...
...Partition wall, 7...Cut surface of hollow fiber group, 8...Inner space of blood port, 9...Inner space of outer cylinder, 10
...Blood, 11...Blood purification fluid, 12...Packing, 20, 20a...Blood inlet and blood outlet, 21...O ring.

Claims (1)

[Scope of Claims] 1. A blood processing device in which a blood port is attached to at least one end of a cylindrical module in which a hollow fiber bundle with an open end is housed so as to form a disc-shaped internal space. , the thickness h (cm) of the disc-shaped space of the blood port is the membrane area s of the module
When s0.9m ² for (m ² ), h0.237×{(s−0.9)×
4.23+1}×1/√, when s< ^0.9m2 , the relationship h0.237×√+0.025 is satisfied, and the blood is provided close to the outer periphery of the disc-shaped space of the port. A blood processing device characterized in that an inlet or an outlet is provided so that the blood is introduced into or led out from a tangential direction at an angle of 60 degrees or less with respect to a disc-shaped space through an opening.