JPH09234245A - Outside perfusion type artificial lung - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve the gas exchange efficiency of an artificial lung device and to reduce hemolysis as much as possible by setting the ratio of the longer diameter to the orthogonally crossing shorter diameter of the cross section of a hollow part of a cylindrical hollow fiber bundle at a prescribed value. SOLUTION: This artificial lung is constituted so that the blood introduced from a pipe connection opening 8 formed at one end of a hollow part 14 of the cylindrical hollow fiber bundle into the hollow part 14 can flow through gaps between hollow fibers 1, go out of the hollow fiber bundle, flow between the hollow fiber bundle and the housing 6 and flow out of a pipe connection opening 13 of the housing 6, and reversely, the blood introduced from the pipe connection hole 13 of the housing 6 can enter the hollow fiber bundle from the outer surface of the hollow fiber bundle, flow through gaps of the hollow fiber 1, enter the hollow part 14, and flow out of the pipe connection opening 8 connected to the hollow part. In this case, the ratio of the longer diameter to the orthogonally crossing shorter diameter of the cross section of the hollow part 14 of the cylindrical hollow fiber bundle is set at 1.5-50, and a core pipe 4 with many holes 3 formed on the wall is attached in the hollow part 14.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an artificial lung that removes carbon dioxide from blood by bringing oxygen-containing fluid into contact with blood that has been circulated extracorporeally through a gas-permeable membrane and supplying oxygen to the blood through the membrane. The present invention relates to an external perfusion type artificial lung that causes blood to flow outside a hollow fiber membrane and oxygen-containing fluid to flow inside a hollow fiber membrane.

[0002]

2. Description of the Related Art Artificial lungs using a hollow fiber membrane (hereinafter sometimes simply referred to as "hollow fiber") are divided into an internal perfusion type in which blood flows inside the hollow fiber and an external perfusion type in which blood flows outside the hollow fiber. To be Here, in any case, an oxygen-containing gas or an oxygen-dissolved liquid is caused to flow on the side of the hollow fiber membrane opposite to the blood. The external perfusion type has a high gas exchange efficiency, so the priming volume can be reduced by making the artificial lung compact, and the shear rate between the blood and the membrane can be reduced, so that hemolysis (destruction of red blood cells) can be suppressed. There is a feature of. There are methods such as countercurrent, cocurrent, and cross flow in the externally perfused oxygenator, but the cross flow method, which has the highest gas exchange efficiency in terms of chemical engineering, has many holes in the tube wall. A hollow fiber bundle is arranged around the cylindrical core tube in a concentric cylindrical shape, and the blood introduced into the artificial lung from the mouth of the core tube flows out from the hole in the core tube wall, and the hollow fiber gap is removed. It flows radially outward and out of the hollow fiber bundle and out of the oxygenator through the housing connection (or vice versa, blood introduced into the housing enters the hollow fiber bundle from outside the hollow fiber bundle). , Flows through the hollow fiber gap, enters the core tube through the hole in the core tube wall, and flows out of the artificial lung from the mouth of the core tube) (hereinafter referred to as concentric circle type)
(For example, Japanese Unexamined Patent Publication (Kokai) No. 58-155862) and a type in which blood flows in one direction in parallel through a gap between hollow fibers of a plate-shaped or block-shaped hollow fiber bundle (hereinafter referred to as a parallel flow type) have been known. (For example, JP-A-1-104271).

[0003]

The concentric type oxygenator is easy to manufacture and has a high gas exchange efficiency, but hemolysis is liable to occur, and the allowable operating condition range for not causing hemolysis is narrow.
Therefore, there is a problem that the amount of gas exchange per membrane area of the artificial lung is low. Further, there is a drawback that the pressure loss on the blood side is also large. As a result of studying these causes, the present inventors have found that in a concentric type cross-flow external perfusion type artificial lung, the flow velocity of blood in the vicinity of the core tube (hence, the shear rate with the hollow fiber membrane) is the outer peripheral portion. I found this to be the cause of the above problems, faster than near. For example,
Generally, the gas exchange efficiency through the membrane becomes higher as the shearing rate between blood and the hollow fiber membrane becomes higher. On the other hand, if the shear rate becomes too high, hemolysis will occur. In the concentric type oxygenator, when the blood shear rate of the oxygenator was increased in order to improve the gas exchange efficiency, the shear rate in the vicinity of the core tube was excessively increased, resulting in hemolysis. On the other hand, the parallel flow type does not have such a defect, but since a short path of blood is likely to occur at the contact portion between the hollow fiber bundle and the housing, a manufacturing process such as resin filling of the contact portion is required.
When the hollow fiber bundle is formed by stacking the hollow fiber sheets, it is difficult to pack it at a high density, which is a manufacturing problem.

[0004]

Means for Solving the Problems As a result of intensive studies in view of the above consideration, the present inventor has found an artificial lung structure in which the defects of the concentric circle type are eliminated and the concentric circle type is easily manufactured. Arrived That is, the present invention provides: An external perfusion type artificial lung in which a hollow fiber membrane bundle bundled in a tubular shape is provided in a housing, the hollow fiber bundle having a minor axis perpendicular to the major axis in a cross section of a hollow portion of the tubular hollow fiber bundle. 1. Externally perfused oxygenator, characterized in that the ratio is 1.5 to 50. 2. The artificial lung according to 1 above, which has a core tube having a large number of holes in the tube wall in the hollow portion of the tubular hollow fiber bundle. 3. The artificial lung according to 1 or 2 above, which has a short diameter of 0.3 to 2 cm. The ratio of the minor axis orthogonal to the major axis to the major axis is 2 to
4. The artificial lung according to the above 1, 2, or 3, which is 20. The above-mentioned 1 in which the tubular hollow fiber bundle is a braided body of hollow fiber membranes.
5. The artificial lung according to any one of 4 to 6; 6. The artificial lung according to 5 above, wherein the braided body of hollow fiber membranes is a sheet-shaped material composed of hollow fiber membranes or hollow fiber membranes and other yarns wound in a tubular shape. The artificial lung according to the above 5, wherein the braided body of the hollow fiber membrane is a cylindrically wound cord-shaped sheet composed of the hollow fiber membrane and other yarns.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The artificial lung of the present invention comprises a hollow fiber membrane bundle (hereinafter referred to as a tubular hollow fiber bundle) bundled in a tubular shape provided in a housing. In the center, there is a portion not filled with the hollow fiber membrane, that is, a hollow portion. The feature of the artificial lung of the present invention is that the hollow section at the center of the tubular hollow fiber bundle has a cross section (hereinafter, the cross section is simply referred to as a cross section).
The shape is flat, and the ratio of the minor axis orthogonal to the major axis to the major axis in the cross section of the cavity is 1.5 to 50.
(Hereinafter, this ratio is referred to as the ratio of the short diameter to the long diameter). Here, the major axis represents the longest diameter in the cross section of the hollow portion, and the minor axis represents the longest diameter of the diameters orthogonal to the major axis. In the artificial lung of the present invention, the ratio of the short diameter to the long diameter is preferably 2 to 20, more preferably 3 to 10. If the ratio of the minor axis to the major axis of the cavity is too small, the same drawbacks as the concentric type occur, and if the ratio of the minor axis to the major axis is too large, the processing accuracy of the hollow fiber bundle cavity or core tube is required. Manufacturing difficulties such as an increase in the level and difficulty in uniformly filling the hollow fiber bundle occur.

The cross-sectional shape of the hollow portion of the tubular hollow fiber bundle is arbitrary as long as the ratio of the minor axis to the major axis is within the above range, for example, an ellipse, a rectangle, a rectangle with rounded corners, a gourd shape, a rhombus, a triangle. Other shapes such as ellipses, rectangles,
Alternatively, a rectangle with rounded corners is preferable in terms of performance, compactness, ease of manufacture, and the like. The rectangle with rounded corners is preferably rounded so that the short side is substantially a semicircle, because the effect of the present invention is exhibited, and coagulation due to blood retention is less likely to occur. Further, the size of the hollow portion can be selected as an arbitrary value depending on the size of the artificial lung to be designed (that is, processing capacity), but the short diameter of the hollow hollow fiber bundle cross section is 0.3 to
It is preferably 2 cm, more preferably 0.5 to 1 cm. If it is larger than this, the priming volume increases, and if it is smaller, the manufacturing becomes difficult. The thickness of the tubular hollow fiber bundle is also arbitrary, and an arbitrary value can be selected depending on the required characteristics of the artificial lung to be designed, but it is 1 to 10 cm.
Is preferable, and 2-5 cm is more preferable. Further, the uniformity of the thickness is also arbitrary, but it is preferable in terms of performance that the thickness is almost the same in any part of the tubular hollow fiber bundle.

The filling form of the hollow fibers in the tubular hollow fiber bundle is arbitrary. The hollow fiber bundle may be a bundle of a large number of hollow fibers that are substantially parallel to each other. However, in order to keep the hollow fiber intervals uniform and prevent short paths in the blood flow path, hollow fibers or hollow fibers may be bundled together. More preferably, it is a braided body composed of and other yarns. The shape and style of the hollow fiber braid are arbitrary, for example, those formed by twill winding of hollow fibers, laminates of sheet-like products formed by plain weaving of hollow fibers or pearl weave, hollow fibers and others. Preferable examples include a laminated body of a cord-shaped sheet composed of the above yarn. Among these, a stack of sheet-like materials is preferable because it can be made compact by increasing the packing density of the hollow fibers and is easy to manufacture. Is more preferable. In particular, a structure in which a sheet-like material is rolled into a cylinder is preferable because it is easy to manufacture. The blind-shaped sheet can be manufactured by, for example, knitting, weaving, adhering, or the like using a hollow fiber as a weft and another yarn as a warp. In the artificial lung of the present invention, it is also preferable to fix the shape of the tubular hollow fiber bundle by covering the inner surface and / or the outer surface of the tubular hollow fiber bundle with a net or tying it with a thread. It is also preferable to fix the mutual positions of the hollow fibers by adhesion or fusion.

The blood-side shear rate and pressure loss of the artificial lung can be changed by the shape of the tubular hollow fiber bundle. For example,
When the circumferential length of the tubular hollow fiber bundle is increased, the shear rate and pressure loss decrease, and when the thickness of the tubular hollow fiber bundle is increased, the pressure loss increases.
Also, these values increase with increasing packing density of the hollow fibers. By trial, the optimum value of the balance between the gas exchange capacity and the shear rate or pressure loss can be obtained within the above size range.

The artificial lung of the present invention preferably has a core tube having a large number of holes in the tube wall in the hollow portion of the tubular hollow fiber bundle. Although the cross-sectional shape of the core tube is arbitrary, it is preferably a single or plural circle, a single or plural rectangle, or a rectangle with rounded corners. The rectangle with rounded corners is preferably rounded so that the short side is substantially a semicircle. The core tube is also
An aggregate of a plurality of tubes or an article having a reinforcing wall partially or entirely inside the core tube is also preferable in order to increase the stability of the cross section of the core tube.

There may be a partial or full gap between the core tube and the tubular hollow fiber bundle, and the inner boundary surface between the core tube and the tubular hollow fiber bundle may be wholly or partially. May be in contact with. It is also possible to install a non-woven fabric, a net or the like between the core tube and the tubular hollow fiber bundle. The core tube and the tubular hollow fiber bundle are
It is preferable that they are in direct contact with each other or directly across a non-woven fabric or a net. The shape and diameter of the hole made in the wall of the core tube,
Although the number is arbitrary, it can be determined in consideration of the shear rate and the pressure loss at the set blood flow rate of the artificial lung. The core tube may be a porous body such as a sintered body or a net-like one. A pipe connection port is provided in a part of the core tube. When the artificial lung does not have a core tube, the pipe connection port can be directly provided in the hollow portion of the tubular hollow fiber bundle.

The hollow fiber membrane used in the artificial lung of the present invention is
As long as the membrane is permeable to gas but impermeable to blood components, the material, membrane morphology, membrane shape and the like are arbitrary, and membranes conventionally used in hollow fiber membrane oxygenators can be used. Examples of the film material include polyolefin resins such as polypropylene and poly-4-methylpentene-1, silicone resins such as polydimethylsiloxane and copolymers thereof, and fluorine resins such as PTFE and vinylidene fluoride. Examples of the membrane form include a porous membrane, a heterogeneous membrane, a composite membrane, a homogeneous membrane and the like. As the membrane shape, the outer diameter of the hollow fiber is 0.05-5 m
It can be m. The filling rate of the hollow fibers in the hollow fiber bundle (the area ratio of the hollow fibers to the unit cross-sectional area) is 20 to 75.
%, The hollow fiber gap may be 0.05-3 mm. Other dimensions and shapes relating to the present artificial lung are arbitrary.

The artificial lung of the present invention comprises a hollow fiber membrane bundle as described above provided in a housing. As the housing, one generally used as an external perfusion type can be used. The cross-sectional shape of the housing does not necessarily have to be similar to the outer shape of the tubular hollow fiber bundle, but a structure with less dead volume is preferable. The external dimensions of the oxygenator may be 2-15 cm short side, 5-30 cm long side, 10-50 cm long.

The artificial lung of the present invention will be described more specifically below with reference to the examples of the structures shown in FIGS. The hollow fibers (1) are installed in a cylindrical bundle in the housing (6), and the housing (6) is provided with a pipe connection port (13) for connecting the inside and outside of the housing. Also,
Similar to the known external perfusion type artificial lung, in order to separate the space communicating with the inside of the hollow fiber from the space communicating with the outside, the tubular hollow fiber bundle is hermetically filled with resin between the hollow fibers at the end thereof. Yes (7, 7 '). Furthermore, the core tube and the tubular hollow fiber bundle,
Also, the hollow fiber bundle and the housing (6) are hermetically sealed at the end of the hollow fiber bundle by an arbitrary method (7,
7 '). The sealing method can be implemented by, for example, resin filling, adhesion, O-ring or packing, and fitting. That is, in the present artificial lung, blood introduced into the hollow portion (14) of the tubular hollow fiber bundle from the pipe connection port (8) provided at one end of the hollow portion of the hollow fiber bundle has a hollow fiber (1). ) To the outside of the hollow fiber bundle, flows between the hollow fiber bundle and the housing (6) to flow out of the pipe connection port (13) of the housing (6), or vice versa. Blood introduced from the pipe connection port (13) of (6) enters the hollow fiber bundle from the outer surface of the hollow fiber bundle, flows through the gap of the hollow fiber (1), and enters the hollow portion (14) of the hollow fiber bundle. Pipe connection port (8) that enters and is connected to the cavity
It is configured to flow out from. When the artificial lung has a core tube (4), a large number of holes (3) provided in the core tube (4) for blood introduced from a pipe connection port (8) provided in the core tube (4) To enter the hollow part (14) of the tubular hollow fiber bundle from vice versa or vice versa.
To enter the core tube (4) through a large number of holes (3) provided in the tube wall of the core tube (4) and flow out to the outside from a pipe connection port (8) connected to the core tube (4). It is configured. The cavity (14) is flat, and the minor axis (16) orthogonal to the major axis (15) in the cross section of the cavity (14) is orthogonal to the major axis (15).
The ratio is 1.5 to 50.

On the other hand, inside the hollow fiber (1), a fluid containing oxygen, preferably a gas containing oxygen, is configured to flow from one end of the hollow fiber to the other end. That is, at both ends of the hollow fiber bundle, caps (9,
10) is attached, and the pipe connection ports (11, 12) are provided in the space communicating with the inside of the hollow fiber.

[0015]

EXAMPLES The present invention will be described in more detail below with reference to examples. [Example 1] (Production of artificial lung) Outer diameter 0.23 mm, oxygen permeation rate 1 x
A heterogeneous hollow fiber membrane (1) made of poly (4-methyl-1-pentene) having a non-porous layer on the outer surface of 10 ⁻⁴ [cm ³ / cm ² · s · cmHg] was used as a weft, and a polyester yarn ( 2)
By knitting as a warp yarn, as shown in FIG.
A blind sheet having a knitting density of 26 filaments / cm was produced. Next, the artificial lung shown in FIGS. 2 to 4 was produced. That is, the outer diameter of the cross section is a rectangle having a short side of 8 mm, a long side of 40 mm, and rounded corners so that the short side becomes a semicircle, and a polycarbonate wall having a large number of holes (3) having a diameter of 3 mm. Made of core tube (4)
About 25 m in thickness of the cord-shaped sheet of hollow fiber membrane (1) around
A polyethylene mesh (5) of about 12 mesh was wound around it for about m. The hollow fiber used is 240
It was 00. The cross section of this is a rectangle with rounded corners so that the short side is substantially a semicircle, and the inner diameter is 62 x 94 m.
It is loaded into a polycarbonate housing (6) having a length of m and a length of 100 mm, and urethane resin is filled to a thickness of 16 mm at each end of the housing. Airtight seals (7) were made between the tubes (4) and between the hollow fiber bundle and the housing (6).
A pipe connection port (8) was provided at one port of the core tube (4).
The other port of the core tube (4) was sealed with resin. Caps (9, 10) were attached to both ends of the hollow fiber bundle.
Each cap has a pipe connection port (11, 12), and the housing also has a pipe connection port (13). The effective membrane area (based on the outer surface of the hollow fiber) of this artificial lung was 1.2 m ² . The ratio of the major axis to the minor axis of the hollow portion of the hollow fiber bundle is 5.1.

(Measurement) Using fresh heparin-added bovine blood, a standard venous blood having a temperature of 36 ° C., a hemoglobin content of 120 g / l, an oxygen saturation of 65% and a carbon dioxide partial pressure of 6.0 kPa (45 mmHg) was prepared. , Is introduced into the pipe connection port (8) leading to the core tube of the present artificial lung, and is made to flow out from the pipe connection port (13) provided in the housing, while the pipe connection ports 11 to 12 provided in the cap are changed to 99 Oxygen gas of .99% was allowed to flow in the same amount as the blood flow rate (V / Q ratio of 1.0). When the blood flow rate and the oxygen flow rate were changed, the blood flow rate (maximum blood flow rate) at which the oxygen saturation of the blood flowing out from the pipe connection port (13) was 95% was 6200 ml / min. The pressure difference between the pipe connection port (8) and the pipe connection port (13) (that is, the pressure loss of the artificial lung) at a blood flow rate of 6000 ml / min was 8.8 kPa (66 mmHg).

[Embodiment 2] The core tube has a cross-sectional dimension (outer dimension) of a minor axis of 8 mm and a major axis of 20 mm, a housing dimension (inner dimension) of 62 × 74 mm, and two hollow fibers.
1100 and housing length 110
An artificial lung having an effective membrane area of 1.2 m ² was prepared in the same manner as in Example 1 except that the size was mm. With this artificial lung,
When the same test as in Example 1 was conducted, the maximum blood flow was 6
The pressure loss was 100 ml / min, and the pressure loss at a blood flow rate of 6000 ml / min was 16.9 kPa (127 mmHg).

[Comparative Example 1] A polycarbonate circular tube having an outer diameter of 8 mm was used as the core tube, the housing was a cylinder having an inner diameter of 62 mm, and the number of hollow fiber fillings was 148.
00 and the housing length is 143 mm
Similar to Example 1 except that the effective film area was 1.
A 2 m ² concentric oxygenator was prepared. When the same test as in Example 1 was performed using this artificial lung, the maximum blood flow was 6000 ml / min, and the pressure loss at a blood flow rate of 6000 ml / min was 29.1 kPa (218 mmHg).

[0019]

EFFECTS OF THE INVENTION Most of the hollow fiber membranes have substantially the same operating conditions as compared to an artificial lung in which the hollow section of the tubular hollow fiber bundle is circular, and the shear rate and pressure loss on the blood side are small. ,
There is a high degree of freedom in designing artificial lungs, such as less hemolysis and higher gas exchange efficiency. Further, it is easier to manufacture than a parallel-flow type oxygenator, and a highly accurate oxygenator can be manufactured with high productivity.

[Brief description of drawings]

FIG. 1 is a sketch of a hollow-fiber cord-shaped sheet used in Example 1.

FIG. 2 is a front view (lower right view), a plan view (upper right view) and a side view (lower left view) of an artificial lung produced in Example 1.

FIG. 3 is a sectional view of part A in FIG.

FIG. 4 is a sectional view of a B part in FIG.

[Explanation of symbols]

 1 Hollow Fiber Membrane 2 Polyester Thread 3 Hole 4 Core Tube 5 Net 6 Housing 7, 7'Sealing Section 8 Core Tube Pipe Connection Port 9 Cap 10 Cap 11 Cap Pipe Connection Port 12 Cap Pipe Connection Port 13 Housing Pipe Connection port 14 Cavity 15 Long diameter 16 Short diameter

Claims (7)

[Claims] 1. An externally-perfused oxygenator having a tubular bundle of hollow fiber membranes provided in a housing, wherein the major axis relative to the major axis in the cross section of the hollow portion of the tubular hollow fiber bundle. The external perfusion type artificial lung, wherein the ratio of orthogonal minor axes is 1.5 to 50. 2. The artificial lung according to claim 1, wherein the hollow portion of the tubular hollow fiber bundle has a core tube having a large number of holes in the tube wall. 3. The minor axis is 0.3 to 2 cm.
Or the artificial lung according to 2. 4. The artificial lung according to claim 1, 2 or 3, wherein the ratio of the short diameter orthogonal to the long diameter to the long diameter is 3 to 10. 5. The artificial lung according to any one of claims 1 to 4, wherein the tubular hollow fiber bundle is a braided body of hollow fiber membranes. 6. The artificial lung according to claim 5, wherein the braided body of hollow fiber membranes is a sheet-shaped material composed of hollow fiber membranes or hollow fiber membranes and other yarns wound in a tubular shape. . 7. The artificial lung according to claim 5, wherein the braided body of the hollow fiber membrane is a cylindrically wound cord-shaped sheet composed of the hollow fiber membrane and other yarns.