JPH04193178A - Hollow thread membrane type oxygenator module - Google Patents

Abstract

PURPOSE:To obtain an oxygenator module having a high gas exchange capability and generating no problem such as thrombus in use for a long period by using a straight tube-shaped blood passage provided in a fixed member and opened on both ends and a hollow thread membrane screen opened and fixed with an opening end on the outer wall face of the fixed member and provided in the blood passage. CONSTITUTION:A screen laminated with a screen made of hollow thread membranes 1a and a screen made of hollow thread membranes 1b in turn perpendicularly to each other is fixed nearly perpendicularly to a blood passage 6b. Both opening ends of the hollow thread membranes 1a are opened and fixed on the opposite outer wall faces 6a-1, 6a-2 of the fixed member 6 respectively, and both opening ends of the hollow thread membranes 1b are opened and fixed on the opposite outer wall faces 6a-3, 6a-4 respectively. The gas containing oxygen is introduced into the hollow sections of the hollow thread membranes 1a, 1b from adjoining outer wall faces 6a-1, 6a-3 side, and the gas gas-exchanged on hollow thread membrane walls is discharged from opposite outer wall faces 6a-2, 6a-4 side.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides a method in which the fixing member (botting member) for fixing the hollow fiber membrane has a structure that also serves as a blood passage wall, and has a high gas exchange ability. The present invention relates to an external perfusion type hollow fiber membrane oxygenator module that can be used for a long period of time and has a structure suitable for miniaturization.

[Conventional technology]

An oxygenator using a hollow fiber membrane is a microporous hollow fiber membrane made of a hydrophobic polymer such as polyolefin, or a gas permeable homogeneous hollow fiber membrane such as silicone. Blood is brought into contact with oxygen-containing gas, and gas exchange occurs between them. Blood flows through the hollow part of the hollow fiber membrane,
There are two methods: an internal perfusion method in which gas flows outside the hollow fiber membrane, and an external perfusion method in which gas flows through the hollow part of the hollow fiber membrane and blood flows outside.

In the internal perfusion method, if blood is evenly distributed and supplied to a large number of hollow membranes, there is no channeling (unbalanced flow) of the blood, but the blood flowing through the hollow part of the hollow fiber membrane is a laminar flow, and the blood is oxygenated ( In order to increase the oxygen transfer rate per unit layer area, it is necessary to reduce the inner diameter of the hollow fiber membrane. For this reason, hollow fiber membranes having an inner diameter of about 150 to 300 μm are being developed for use in oxygenators. However, even if the diameter is made smaller, oxygenation will not be dramatically improved as long as the blood flows laminarly, and as the diameter is further made smaller, crotch ink (a phenomenon in which the hollow space is blocked by blood clots) is more likely to occur. This point is a major obstacle to practical use.

In general, artificial lungs use tens of thousands of hollow fiber membranes in bundles, but in order to sufficiently and evenly distribute and supply gas to the outer walls of each of these many hollow fiber membranes, special care must be taken. consideration is necessary. In addition, when the distributed supply of gas is insufficient, the carbon dioxide gas discharge ability (carbon dioxide transfer rate per unit layer area) decreases.

On the other hand, the external perfusion system is superior to the internal perfusion system in that gas distribution is good, gas pressure loss is small, and a structure for creating turbulence in the flow of perfused blood can be easily designed.

In the external perfusion method, insufficient oxygenation due to blood channeling and the occurrence of blood clots in blood stagnation areas are closely related to the internal structure of the blood passageway, and the selection of the internal structure of the blood passageway is based on these factors. This is extremely important in preventing this.

As an external perfusion type hollow fiber membrane oxygenator module having a structure for preventing blood channeling, a module in which a baffle plate is disposed within a blood passage is known.

For example, as shown in FIGS. 8(A) and 8(B),
No. 0-193469 discloses a blood flow path 1 in which the width is narrowed by a baffle plate 14 in a contact chamber 12 having an elongated and rectangular cross section.
An external perfusion type hollow fiber membrane type oxygenator module is disclosed which has a structure in which a plurality of small chambers 13 are divided through 5.

[Problems to be solved by the invention] However, in hollow fiber membrane oxygenator modules that use baffles, blood flow is not always sufficient, and when used for a long period of time, blood clots may form in the baffles and the function may deteriorate. There is a problem with this.

The present invention was made in order to solve the problems with the conventional external perfusion type hollow fiber membrane oxygenator module described above, and has a high gas exchange ability and does not cause problems such as blood clots even during long-term use. Another object of the present invention is to provide an external perfusion type hollow fiber membrane oxygenator module having a structure suitable for miniaturization.

[Means for Solving the Problems] A hollow fiber membrane oxygenator module of the present invention capable of achieving the above object includes a straight blood passageway opened at both ends provided in a fixing member, and a large number of hollow fiber membranes. A hollow fiber membrane screen is provided in the blood passage by opening and fixing each open end to the outer wall surface of the fixing member, and a gas inlet and gas conductor for flowing oxygen into these hollow fiber membranes. It is characterized by having an outlet, and a blood inlet and a blood outlet for flowing blood into the blood passage.

In the present invention, a screen made of a large number of hollow fiber membrane sheets is provided in a straight blood passage, and the fixing member of the hollow fiber membrane sheet also serves as a wall of the blood passage. Appropriate turbulence is generated to prevent channeling, gas exchange is efficient, and there are no structures in the blood passageway that can cause thrombus formation, resulting in good long-term usability. It is possible to reduce the size without sacrificing these characteristics.

The material for the fixing member in the hollow fiber membrane oxygenator module of the present invention may be any material that can stably fix the hollow fiber membrane, form a blood passage with good fluid permeability, and is safe. Can be used without restrictions. Examples include unsaturated polyester resins, epoxy resins, polyurethane resins, etc. Among these, polyurethane resins that have a proven track record for medical use are preferred.

Various types of hollow fiber membranes can be used as the hollow fiber membranes constituting the hollow fiber membrane screen. Examples include hollow fiber membranes.

In addition, the type of hollow fiber membrane can be selected depending on the purpose of the oxygenator. For example, microporous polypropylene hollow fiber membranes and microporous polyethylene hollow fiber membranes are suitable for short-term surgical procedures. In addition, for long-term use such as ECMO, it is preferable to use a non-porous membrane to prevent plasma leakage, for example, a three-layer composite hollow membrane with a porous layer arranged on both sides of a non-porous layer. Thread membranes can be mentioned.

Hereinafter, the present invention will be explained in more detail with reference to the drawings.

1 and 2 show an example of fixing the hollow fiber membrane screen in the hollow fiber membrane oxygenator module of the present invention in a cross section perpendicular to the straight blood passage 6b formed in the fixing member 6. It is a diagram.

The screen shown in FIG. 1 is a parallel type screen formed by fixing a large number of hollow fiber membranes 1 in a row substantially parallel to each other, and each hollow fiber membrane crosses the blood passage 6b in a substantially perpendicular direction. There is.

Both open ends of each hollow fiber membrane are connected to the outer wall surface 6a facing the fixing member 6.
-1 and 6a-2 and are fixed with openings, respectively.

The flow of the oxygen-containing gas in this parallel screen involves introducing the oxygen-containing gas into the hollow portion of each hollow fiber membrane from one outer wall surface 6a-1 (or 6a-2) side, and the other outer wall surface. This is performed by deriving the gas from the 6a-2 (or 6a-1) side after gas exchange at the hollow fiber membrane wall.

FIG. 2 shows a screen in which a screen made of hollow fiber membranes 1a and a screen made of hollow fiber membranes 1b are alternately laminated so as to be substantially perpendicular to each other, and are fixed substantially perpendicularly to a blood passage 6b.

Both open ends of the hollow fiber membrane 1a are opened and fixed to opposing outer wall surfaces 6a-1 and 6a-2 of the fixing member 6, and both open ends of the hollow fiber membrane 1b are fixed to opposing outer wall surfaces 6a-1 and 6a-2. External wall surface 6
They are opened and fixed to a-3 and 6a-4, respectively.

In this type of screen, the adjacent outer wall surface 6a
-1 and 6a-3 (or 6a-4) side, oxygen-containing gas is introduced into the hollow part of each hollow fiber membrane, and the outer wall surfaces 6a-2 and 6a-4 (or 6a-3) facing these are introduced into the hollow part of each hollow fiber membrane. )
Gas for sludge exchange on the hollow fiber membrane wall is led out from the side.

Note that instead of the alternately laminated type shown in FIG. 2, a hollow fiber membrane screen woven perpendicularly to the phase U can also be used.

The type of hollow fiber membrane and its arrangement density in these types of screens are selected depending on the desired module function, but the arrangement density (filling rate) of the hollow fiber membrane is usually about 10 to 55%. It is said that

Next, examples of a gas exchange section in which a hollow fiber membrane screen is provided in a blood passage are shown in Figs.

The gas exchange section shown in FIG. 3 has a configuration in which four stages of alternately orthogonally laminated hollow fiber membrane screens shown in FIG. 2 are arranged in the direction of blood flow in the blood passage 6b.

The gas exchange section shown in FIG. 4 has a configuration in which the parallel screens shown in FIG. 1 are arranged in four stages in the direction of blood flow, and the direction of the hollow fibers M1 of each screen Each screen is fixed so that it is almost orthogonal to the even-numbered screens.

The gas exchange section shown in FIG. 5 has a configuration in which four stages of parallel screens shown in FIG. 1 are provided, as in FIG.
Each screen is fixed so that the hollow fiber membranes 1 of each screen are oriented in the same direction.

The structure of the screen placed in the gas exchange section is selected as appropriate depending on the desired function of the module, and screens with the same structure or screens with different structures may be used.
The direction in which the hollow fiber membranes are fixed in each screen can be changed as necessary.

In addition, the number of screens and the interval between them in the blood passage 6b are appropriately selected depending on the desired function of the module. For example, the density of the hollow fibers in the hollow fiber membrane sheet used as the screen, the membrane area, the blood passage It can be determined in relation to the inner diameter, length, etc.

In the illustrated example, the fixing member 6 has a rectangular parallelepiped shape, and there is a blood passage 6b in the shape of a straight tube with both ends open, that is, a hollow portion having a circular cross section and extending linearly without changing the inner diameter. It is provided. In this way, the blood passage 6b
By forming the tube into a straight tube and fixing the hollow fiber membrane screen by intersecting the tube, blood stagnation is less likely to occur, and the formation of blood clots can be effectively prevented during long-term use.

The shape (outer shape) of the fixing member 6 is usually a cube or a rectangular parallelepiped, but it may also be a cylinder, a polygonal column, or the like.

The inner diameter of the blood passage 6b is approximately 2c in terms of pressure loss.
From a practical point of view, it is preferably about 30 m or more.
It is preferable that it be about cm or less.

The angle of each screen with respect to the blood passageway 6b is approximately 6
The angle is preferably about 0 to 120 degrees, and particularly preferably 90 degrees (vertical).

That is, by making the blood flow substantially perpendicular to each other as shown in the figure, it is possible to cause appropriate turbulence in the blood and more effectively prevent the occurrence of channeling.

Further, the number of screens and the interval between them in the blood passage 6b are appropriately selected depending on the desired function of the module. For example, the density of the hollow fibers in the hollow fiber membrane sheet used as the screen, the membrane area, the blood flow It can be determined in relation to the inner diameter, length, etc. of the passage.

A gas inlet port is provided on the outer wall of the gas exchange section with the above configuration.
The external perfusion type hollow fiber membrane oxygenator module of the present invention can be manufactured by providing a gas outlet, a blood inlet, and a blood outlet.

An example is shown in FIG. FIG. 6(A) is a front view of an example of the external perfusion type hollow fiber membrane oxygenator module of the present invention, with the blood inlet 4 side facing the front, FIG. 6(B) is a plan view thereof,
FIG. 6(C) is a sectional view taken along line AA in FIG. 6(A). In addition, in FIG. 6(C), the horizontal hollow fiber membrane 1b is omitted.

This module has a gas exchange section in which 11 stages of alternately orthogonally laminated hollow fiber membrane screens shown in FIG. 7a, 7b, 8a, 8
b, 9.10, and gas inlet ports 2a, 3b, gas outlet ports 2b, 3b, blood inlet port 4, and blood outlet port 5 connected to the respective caps.

The caps joined to each outer wall surface of the fixing member 6 surround the fixing member 6 and are joined to each other, and have gas inlets 2a, 2b, gas outlets 3a, 3b, blood inlet 4 and blood outlet 5 The areas that communicate with each other are partitioned off from each other in a liquid-tight and air-tight manner. Each cap can be made of e.g. polymethyl methacrylate, polycarbonate, polyethylene,
Alternatively, it can be formed from polypropylene, etc., and the locations and number of stiffness inlets and outlets, the structure of the area communicating with these ports, etc. are not limited to the illustrated example,
It is selected depending on the structure of the hollow fiber membrane screen used.

Gas exchange in this module consists of gases containing oxygen (
Oxygen gas itself or a mixture of oxygen gas diluted with a gas such as nitrogen to an appropriate concentration) is introduced into the gas inlet 2a.
, 2b at a predetermined flow rate and pressure, and the surface liquid to be treated is introduced from the blood inlet 4 at a predetermined flow rate and pressure.

The gas introduced from the gas inlet ports 2a and 2b flows into the hollow portions of the hollow fiber membranes 1a and 1b through the openings of the hollow fiber membranes 1a and 1b on the outer wall of the fixing member 6 on the side of the inlet ports, and flows into the hollow portions of the hollow fiber membranes. Gas exchange occurs with the blood introduced into the blood passage 6b from the blood inlet 4 through the membrane wall, and is discharged from the other opening of each hollow fiber membrane to the outside of the module via the gas outlet 2a, 3b. be done. Further, blood flowing through the blood passage 6b and having an increased oxygen concentration due to gas exchange on the membrane walls of each hollow fiber membrane is taken out of the module from the blood outlet 5.

The module of the present invention having the above configuration can be manufactured, for example, as follows.

A stack of hollow fiber membrane screens is set in a mold and rotated at high speed around the center of the blood passage 6b. In this state, the fixing member is poured into the mold and kept rotating at high speed until it hardens, and then the module is taken out from the mold.

[Example] Hereinafter, the present invention will be explained in more detail with reference to Examples.

Example 1 A porous polyethylene layer with a thickness of 5 μm (
It has a three-layer structure: a 1 μm thick non-porous segmented polyurethane layer (intermediate layer), and a 19 μm thick porous polyethylene layer (inner layer), and a composite hollow fiber membrane with an inner diameter of 200 μm is attached to a fixing member made of polyurethane. A gas exchange section having the structure shown in FIG. 4 was manufactured by fixing the tube and forming a blood passage. A total of 60 hollow fiber membrane screens are arranged so that the odd-numbered stages and even-numbered stages are perpendicular to each other, and x = 1.
0.0 cm, y = 10.0 cm, z = 7.0 cm, screen opening 11 near 504 m, hollow fiber membrane spacing within the screen: 10 μm, blood passage inner diameter near Ocm, and assembled membrane area within the blood passage 0.5 m2.

Next, each cap made of polycarbonate having the structure shown in FIGS. 6(A) to 6(cl) was adhered to this waste exchange portion to obtain a hollow fiber membrane type oxygenator module of the present invention.

Blood supply amount per unit membrane area of the hollow fiber membrane of the obtained module (Q/S: fl, /min・m2
) to oxygen addition capacity (To2: ml/min・m2
) was measured under the following conditions, and the results shown in FIG. 7 were obtained.

Oxygenation measurement conditions: Blood used: Fresh heparinized blood (37°C, hematocrit 35%)
, pH 7,32, oxygen partial pressure 65 mmHg, hemocrobin concentration t2.5 g/dJ2) - Pure oxygen gas introduced into the hollow fiber membrane (37°C, flow rate 2J1/m'in) Temperature inside the module 37°C Oxygen addition calculation formula: % Formula %] α: Oxygen gas solubility (37°C, 0.03ml/It・mmHg) PvO
2: Oxygen partial pressure on the gas inlet side Pad2: Oxygen partial pressure on the gas outlet side Q: Blood flow rate (J2/m1n) S: Assembled membrane area in blood passage (m2) Comparative example 1 Hollow fiber membrane similar to Example 1 is fixed in a predetermined position in a polycarbonate housing with polyurethane as a fixing member with both ends open, thereby creating an external perfusion type hollow fiber membrane oxygenator module ( x-〇.6cm, y=1.8cm, z=20.
0cm, number of chambers = 5, filling rate of hollow fiber membrane in each chamber = 30
%, membrane area assembled in the contact chamber = 0.5 m').

When the oxygen capacity of this module was measured under the same conditions as in Example 1, the results shown in FIG. 7 were obtained. Compared to Example 1, the oxygen addition capacity was reduced by /J%.

Example 2 Example 1 except that the membrane area in the blood passage was 1.1 m2
A hollow fiber membrane type oxygenator module with a similar configuration was obtained.

Next, this oxygenator module was connected to a right ventricular assist device, which was placed between the goat's right atrium and pulmonary artery.

Anticoagulant therapy with heparin (10-40
U/kg/hr), the blood flow rate was increased to 1.54 with the right ventricular assist device! /min, and pure oxygen at a temperature of 38 to 40°C was flowed into the suspended part of the hollow fiber membrane in the oxygenator module at a flow rate of 2j2/min, and this state was maintained to monitor changes in gas exchange performance during long-term blood contact. Follow-up was performed using a blood gas analyzer (Corning Model 158), and the presence or absence of thrombus formation within the oxygenator module was examined.

As a result, no thrombus was observed even 72 hours after the start of the measurement, and the gas exchange performance was stable.

Comparative Example 2 Comparative Example 1 except that the membrane area in the blood passage was 1.1 m2
Using an oxygenator module prepared in the same manner as in Example 2, changes in gas exchange performance during long-term blood contact and the presence or absence of thrombus formation within the oxygenator module were investigated in the same manner as in Example 2.

As a result, 40 hours after the start of the measurement, it was confirmed that blood clots were attached within the module, and the gas exchange performance also deteriorated.

[Effects of the Invention] Since the hollow fiber membrane oxygenator module of the present invention has a straight blood flow path, blood stagnation is less likely to occur, and the occurrence of blood clots is prevented. In addition, it has a structure in which a hollow fiber membrane screen is fixed across the blood flow path, which can create appropriate turbulence in the blood flow, making it possible to obtain an efficient flow of blood without channeling. , the dregs exchange ability can be improved.

Moreover, by having the above structure, the hollow fiber membrane type oxygenator module of the present invention can be downsized without impairing these characteristics.

[Brief explanation of the drawing]

1 and 2 are cross-sectional views showing an example of the configuration of a hollow fiber membrane screen in a hollow fiber membrane oxygenator module of the present invention,
3 to 5 are perspective views of the gas exchange section showing an example of fixing the hollow fiber membrane screen, FIG. 6(A) is a front view of an example of the hollow fiber membrane type oxygenator module of the present invention, and FIG. B) is a plan view thereof, FIG. 6(C) is a cross-sectional view taken along line AA in FIG. 6(A), and FIG. Graph showing changes in performance, Figure 8 (
B) is a partial vertical cross-sectional view of a conventional hollow fiber prototype oxygenator module, and FIG. 8 (A') is a cross-sectional view taken along line BB in FIG. 1.1a, 1b: Hollow fiber membranes 2a, 2b, 16: Gas inlets 3a, 3b, 17: Gas outlet 4: Blood inlet 5: Blood outlet 6: Fixing members 6a-1 to 6a-4: Outside Wall surface 6b: Blood passages 7a, 7b, 8a, 8b, 9.10: Cap 11: Housing 12: Contact chamber 13: Small chamber 14: Baffle plate 15: Blood flow path Patent applicant Mitsubishi Rayon Co., Ltd.

Claims (1)

[Scope of Claims] 1) By fixing a straight tube-shaped blood passage provided in a fixing member with both ends open and a large number of hollow fiber membranes with their respective open ends opening on the outer wall surface of the fixing member. A hollow fiber membrane screen provided in the blood passage, a gas inlet and a gas outlet for flowing oxygen into these hollow fiber membranes, and a blood inlet and a blood outlet for flowing blood into the blood passage. A hollow fiber membrane oxygenator module comprising: 2) The hollow fiber membrane oxygenator module according to claim 1, wherein the hollow fiber membrane screen is arranged substantially perpendicular to the straight blood flow path.