JPS6264371A - Membrane type artificial lung - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION 10 Background of the Invention (Technical Field) The present invention relates to an artificial lung. To be more specific, the present invention provides an artificial lung that removes carbon dioxide from the blood and adds oxygen to the blood during extracorporeal blood circulation. This relates to a membrane oxygenator that is free from the risk of

(Prior Art) Membrane oxygenators, which perform gas exchange by bringing blood into contact with oxygen-containing gas through a gas exchange membrane with good gas permeability, have been used as an auxiliary means for open heart surgery. There is. There are two types of gas exchange membranes used in such membrane oxygenators: homogeneous membranes and porous membranes.

Currently, silicone membranes are mainly used as homogeneous membranes. However, since the homogeneous film uses a silicone film, it is not strong enough and IJ! Thickness: 100μm
Therefore, there is a limit to gas permeation, and the permeation of carbon dioxide gas is particularly poor. In addition, in order to achieve the desired gas exchange capacity, for example, when tens of thousands of hollow fiber membranes are bundled, the equipment becomes larger and the amount of priming increases.
[Zarani 2] It is also expensive in terms of strikes.

On the other hand, porous membranes made of various materials such as polyethylene, polypropylene, polytetrafluoroethylene, polysulfone, polyacrylonitrile, polyurethane, and polyamide are known.

This porous membrane has many fine pores that communicate in the membrane thickness direction, but since the membrane is hydrophobic, blood does not pass through the pores, and blood flow through the membrane is limited. without causing plasma leakage from the road side to the other gas flow path side.
It is possible to add oxygen in the gas to the blood and remove carbon dioxide from the blood into the gas. However, since the porous membrane G31 has high water vapor permeability, not only the performance deteriorates due to condensation water, but also plasma leakage may actually occur when blood is circulated for a long time. Such a phenomenon is also observed in artificial lungs that have been tested for water leakage during the manufacturing stage and confirmed to be free of water leakage, and is a phenomenon that occurs during use.

In order to eliminate these various drawbacks of porous membranes, the present inventors first developed an artificial lung (special @ No. 1972-92.325) in which the micropores of a porous membrane were plugged with silicone oil. of,
An artificial lung made by slightly improving the micropores of a porous membrane and closing them with silicone rubber (Patent Application No. 105.384/1984)
proposed.

Although this artificial lung, which is made by blocking the microscopic pores of a porous membrane with silicone rubber, has solved the problem of plasma leakage seen in conventional oxygenators using porous membranes, its ability to remove carbon dioxide has cannot be said to be sufficient, for example, E CC
O2R(EXtl'a corporeaI CO2R
It is difficult to remove the amount of carbon dioxide produced by a living body with a small extracorporeal circulation blood flow rate, such as em0Val (extracorporeal carbon dioxide removal).

II. OBJECTS OF THE INVENTION Accordingly, it is an object of the present invention to provide a novel membrane oxygenator. The present invention also provides an oxygenator that removes carbon dioxide from blood and adds oxygen to the blood during extracorporeal blood circulation, which has a high carbon dioxide removal ability and is free from the risk of plasma leakage even when used for a long period of time. The purpose is to provide a membrane oxygenator. The main purpose of the present invention is to provide a membrane oxygenator most suitable for ECCO2R.

The purpose of the above development is to use a gas exchange membrane with a wall thickness of 5 to 8 Oμm.
In an oxygenator using a porous hydrophobic membrane with a porosity of 20 to 80% and a pore diameter of 0.01 to 5 μm, the pores are occluded with fine particles smaller than the pore diameter, and the gas exchange membrane is at least connected to blood. This is achieved by a membrane oxygenator whose contact surfaces are hydrophobic.

The present invention provides a membrane oxygenator in which the gas exchange membrane is a hollow fiber membrane. In the present invention, the hollow fiber membrane has an inner diameter of 100 to
A 1000 μm membrane does not exhibit a membrane-type oxygenator. The present invention does not refer to a membrane oxygenator in which the pores are filled and occluded with the fine particles. The present invention
This figure shows a membrane oxygenator in which the fine particles are made of a hydrophobic substance. The present invention also provides a membrane oxygenator in which the fine particles are made of a hydrophilic substance, and at least the blood contact surface is coated with a hydrophobic substance. The present invention further provides a membrane oxygenator in which the gas exchange membrane is made of olefin resin. The present invention also provides a membrane oxygenator in which the gas exchange membrane is made of polypropylene. The present invention also provides a demolding oxygenator in which the microparticles have a particle size of about 0.003 to 1.0 μm.

IIl. Specific configuration of the invention Hereinafter, the present invention will be explained in more detail based on the drawings.

FIG. 1 is an enlarged sectional view showing a detailed 4fS structure of a gas exchange membrane in an embodiment of the membrane oxygenator of the present invention.

As shown in FIG. 1, the gas exchange membrane 2 of the demolding oxygenator 1 is a hydrophobic porous membrane with a wall thickness of 5 to 80 μm, preferably 10 to 60 μm, and a porosity of 20 to 60 μm. 80%, preferably 30-60%, and the pore size is 0.01-5 μm1
Preferably it is about 0.01 to 1 μm. In this embodiment, the gas exchange membrane has an inner diameter of 100 to 10
00 μm, preferably 100 to 300 μm, in the form of hollow fibers. Therefore, each pore 3 of the gas exchange membrane 2
are clogged with microparticles 4 that are smaller in diameter than the pores and are hydrophobic at least on the surface that comes into contact with blood. Therefore, at least the surface of the gas exchange membrane 2 whose pores 3 are blocked by the fine particles 4 that come into contact with blood is kept -hydrophobic. In this embodiment, each pore 3 is closed by filling the inside of the pore 3 with fine particles 4.
As shown in FIG. 2, on the inner surface side of the gas exchange membrane 2, or on the outer surface side of the gas exchange membrane 2 as shown in FIG. It may be occluded with the fine particles 4 attached thereto. As a result of each of the pores 3 being blocked by the fine particles 4 in this manner, the gas exchange membrane 2 has ultra-fine pores that cannot be confirmed under an electron microscope.

As the material of the gas exchange 11ffi membrane 2, hydrophobic polymers such as polypropylene, polyethylene, polytetrafluoroethylene, polysulfone, polyacrylonitrile, and cellulose acetate can be used, but polyolefin resins are preferred, and particularly preferred. is polypropylene, and most preferably polypropylene in which micropores are formed by a stretching method or a solid-liquid phase separation method.

On the other hand, the materials of the fine particles 4 that block the pores 3 of the gas exchange membrane 2 include silica, alumina, zirconia, magnesia, barium sulfate, calcium carbonate, silicate, titanium oxide, silicon carbide, carbon black, and white. An inorganic substance such as carbon, or a polymer latex such as polystyrene latex, styrene rubber (SBR) latex, or nitrile rubber (NBR>latex) may be used.However, if the material of these fine particles 4 is hydrophobic. In this case, it can be used as it is to close the pores 3, but if the material of the particles is hydrophilic, at least one of the particles 4 comes into contact with blood before or after the pores 3 are blocked. It is necessary to coat the surface with a hydrophobic material such as silicone.The diameter of the fine particles 4 is 0.003 to 1.0 μm, preferably 0.003 to 0.0 μm.
．． It is 5 μm.

The pores 3 of the gas exchange membrane 2 can be blocked with fine particles 4, for example, as follows.

That is, fine particles 4 are placed in the pores 3 of the hollow fiber gas exchange membrane 2.
To fill and close the gas exchange membrane 2, the gas exchange membrane 2 is first made hydrophilic with alcohol or the like. Next, an aqueous dispersion of the fine particles as described above is poured into the hollow system of the gas exchange membrane 2 and filtered. Then, the fine particles 4 contained in the aqueous dispersion are caught in the pores 3 of the gas exchange membrane 2, and the pores 3 are filled with the fine particles 4, causing clogging, and the pores 3 are completely clogged.
is occluded. Next, the inside of the hollow fiber is washed with a suitable fluid such as air or water to remove the dispersion liquid remaining inside the hollow fiber.

In general, when the fine particles 4 are hydrophilic, for example, dimethylpolysiloxane, methylphenylpolysiloxane,
For example, 1,1,2- of silicone such as methylvinylpolysiloxane-methylphenylvinylbolysiloxane, aminoalkylsiloxane, dimethylsiloxane copolymer, etc.
A solution of a halogenated hydrocarbon such as trichloro-1,2,2-trifluoroethane, trichlorofluoromethane, 1,1,2.2-tetrachloro-1,2-difluoroethane, etc. is flowed inside the hollow fiber. A silicone solution is applied to the surface of the fine particles 4 filled inside, and then the silicone solution remaining inside the hollow fiber is removed and dried to coat the surface of the fine particles 4 with a hydrophobic thin film of silicone.

Before rough drying, it is preferable to wash the inside of the hollow fiber with a fluid that does not dissolve the silicone.

Note that although the pores 3 of the gas exchange membrane 2 can be clogged with fine particles in this manner before the oxygenator is assembled, it is more preferable to perform the operation after the module is assembled.

FIG. 4 shows the assembled state of a hollow fiber membrane oxygenator, which is an embodiment of the membrane oxygenator of the present invention. That is,
The hollow fiber membrane oxygenator 1 is equipped with a housing 5, which is provided with annular male-threaded mounting covers 7, 8 at both ends of a cylindrical body 6, and inside the housing 5. , the whole is spread over a large number, for example 10,00
Fine particles 4 have 0 to 6 o, ooo pores 3 as described above.
Gas exchange membranes 2 in the form of hollow fibers are arranged in parallel and spaced from each other along the longitudinal direction of the housing 5. Both ends of the gas exchange membrane 2 are supported in a liquid-tight manner by partition walls 9 and 10 within the mounting cover 7.8 with their respective openings not being closed. Further, each corner u9.10, together with the outer periphery of the gas exchange membrane 2 and the inner surface of the housing 5, forms an oxygen chamber 11 which is a first mass transfer chamber.
, which is closed and isolates the oxygen chamber 11 from a blood circulation space (not shown), which is a second mass transfer fluid space formed inside the gas exchange membrane 2 .

One mounting cover 7 is provided with an inlet 12 for supplying oxygen, which is the first mass transfer fluid. The other mounting cover 8 is provided with an outlet 13 for discharging oxygen.

It is preferable that the inner surface of the cylindrical main body 6 of the housing 5 is provided with a restricting portion 14 for aperture that protrudes and is located at the center in the axial direction. That is, the restraint part 14 is formed integrally with the inner surface of the cylindrical body 6, and tightens the outer periphery of the hollow fiber bundle 15 made up of a large number of gas exchange membranes 2 inserted into the cylindrical body 6. It looks like this. In this way, the hollow fiber bundle 15 is constricted at the center in the axial direction to form a constricted portion 16, as shown in FIG. Therefore, the filling rate of the gas exchange membrane 2 differs in each part along the axial direction, and is highest in the central part. Note that, for reasons to be described later, the desirable filling rate of each part is as follows. First, the filling rate in the central constricted portion 16 is about 60 to 80%, and in the narrow cylindrical body 6, it is about 30 to 60%.
The filling rate at both ends of the hollow fiber bundle 15, that is, on the outer surface of the partition walls 9.10, is about 20 to 40%.

Next, the formation of the partition walls 9 and 10 will be described.

As mentioned above, the partition wall 9.10 fulfills the important function of isolating the inside and outside of the gas exchange membrane 2.

Usually, the partition walls 9 and 10 are made by pouring a highly polar polymeric potting material such as polyurethane, silicone, epoxy resin, etc. onto the inner wall surfaces at both ends of the housing 5 using a centrifugal injection method, and then hardening the material. More specifically, first, a large number of hollow fiber membranes 2 longer than the length of the housing 5 are prepared, both open ends of which are sealed with a highly viscous resin, and then lined up inside the cylindrical body 6 of the housing 5. position. After this, the installation is carried out by completely covering both ends of the gas exchange membrane 2 with a type cover having a diameter larger than that of the cover 7.8, and by rotating the housing 5 around the central axis of the housing 5. Inject the polymer potting material from the side. When the resin has hardened after pouring, the mold cover is removed and the outer surface of the resin is cut with a sharp knife to expose both open ends of the gas exchange membrane 2 to the surface.

The partition walls 9.10 are thus formed.

The outer surfaces of the partition walls 9 and 10 are respectively covered with channel forming members 17 and 18 having annular convex portions.

These channel forming members 17 and 18 are respectively liquid distribution members 19 and 19.
．． 20 and threaded rings 21.22, and a projection 23.20 as an annular convex portion provided near the peripheral edge of this liquid distribution member 19.20. ,． 24 are brought into contact with the partition walls 9 and 10, respectively, and the threaded rings 21.22 are fixed by being screwed onto the covers 7.8, respectively, thereby forming the inflow chamber 25 for blood, which is the second mass transfer fluid. and an outflow port 26 are formed, respectively. A second mass transfer fluid, a blood mass 27, and an outlet 28 are formed in the channel-forming members 17, 18, respectively.

The gaps at the peripheral edges of the partitions 9, 10 formed by the partitions 9, 10 and the channel forming members 17, 18 are filled with one of at least two holes 31, 32 communicating with the gaps. The partition walls 9, 1 are filled with the agent 33, 34.
sealed in contact with 0. Alternatively, it is sealed via an O-ring (not shown).

In the Yuji hollow fiber membrane oxygenator, the first mass transfer fluid is an oxygen-containing gas such as air or blood;
The second mass transfer fluid is blood or an oxygen-containing gas. Thus, if the first mass transfer fluid is a gas, the second mass transfer fluid is blood, while if the first mass transfer fluid is blood, the second mass transfer fluid is a gas.

The above explained the case of a hollow fiber membrane oxygenator.
In the case of lower membrane oxygenators, such as stacked membranes, membranes wound into a coil, or folded in a zigzag pattern, the pores of the gas exchange membrane used are smaller than the pore diameter, and at least blood If the surface that comes into contact with the liquid is similarly blocked by hydrophobic fine particles, the gas exchange ability, especially the C○2 removal ability, will be high and there will be virtually no leakage of certain blood even when used for a long time. A membrane oxygenator is obtained.

EXAMPLES Hereinafter, the present invention will be explained in detail with reference to examples.

Example 1 and Comparative Example 1 Using a polypropylene hollow fiber membrane with an inner diameter of 200 μm, a wall thickness of 25 μm, a porosity of 45%, and an average pore diameter of 700, a hollow fiber membrane as shown in FIG. 4 with a membrane area of 1.6 doors was prepared. A type oxygenator lung 1 was assembled. Ethanol is introduced from the blood mass 25 of the hollow fiber membrane oxygenator 1 to make the hollow fiber gas exchange membrane 2 hydrophilic, and then a silica (colloidal silica, average diameter 1008)/aqueous dispersion is added from the blood mass 25. The gas was filtered through the gas exchange membrane 3, and the pores of the gas exchange membrane were filled with silica. Next, distilled water was introduced to thoroughly remove the silica/water dispersion remaining inside the hollow fiber gas exchange membrane, and then drying was performed. After drying, an additional 2% by weight methylhydrodiene polysiloxane/Freon solution is flowed inside the hollow fiber gas exchange membrane. After drying, the silica particles filled in the pores of the gas exchange membrane were coated with silicone.

When the gas exchange membrane of the obtained membrane oxygenator was observed with an electron microscope (magnification: 100x), the pores had almost disappeared. However, as will be explained later, this artificial lung allows air to pass through it, so it can be inferred that the pores of the gas exchange membrane are not completely blocked, but rather have an ultra-microporous membrane. Ta.

The air permeation flow rate of the obtained membrane oxygenator (Example 1) was measured to be 1000 ml/min -rd -mmH
g, and the air permeation flow rate of the membrane oxygenator (comparative example 1) before filling with silica particles is 1900 m/min・, -g.
It was lower than that of i-mmHg.

To roughly evaluate the gas exchange capacity of these artificial lungs,
In vitro and animal studies were performed.

1) In vitro evaluation using fresh heparinized blood, oxygen gas partial pressure 35 mmHg
Venous blood having a partial pressure of carbon dioxide gas of 451111118 g was prepared, and the performance was evaluated by circulating it through the blood flow path of an artificial lung. The hemoglobin content of the fresh blood used was 1
2 g/old and the temperature was 37°C.

The relationship between blood flow rate, oxygen gas addition ability, and carbon dioxide removal ability when the ratio of oxygen flow ml to blood flow rate is 1 is as shown in Table 1 and FIG. 5.

Furthermore, the relationship between the oxygen flow rate and the carbon dioxide removal ability when the blood flow rate was 1500 rnIl/min was as shown in Table 2 and FIG. 6.

2) Animal test A 30-hour venous-arterial partial extracorporeal circulation test was conducted using a mongrel dog. The relationship between the circulation test and plasma leakage was as shown in Table 3 and Figure 7.

Comparative Example 2 Inner diameter 200μ, wall thickness 25μ, porosity 45%, average pore diameter 7
Using a polypropylene-silicone composite membrane made of polypropylene hollow fibers coated with silicone rubber,
An artificial lung module with an effective membrane area of 1.6 mm was fabricated. Similar to Example 1 and Comparative Example 1, in vitro tests and animal tests were conducted on this oxygenator module. The results are shown in Tables 1 to 3 and Figures 5 to 7, respectively.

(Left below) Regret ==tBay JV, Specific Effects of the Invention As stated since the Song Dynasty, the present invention [is
v5~80μ771%2 In an oxygenator using a porous hydrophobic membrane with a porosity of 20~80% and a pore size of 0.01~5 μm, the pores are smaller than the pore size and at least the surface that comes into contact with blood. It is a membrane-type oxygenator characterized by being blocked by hydrophobic fine particles, and its gas exchange membrane is presumed to have ultra-fine pore channels, and has a high gas exchange ability, especially carbon dioxide removal ability. Although it is very high,
There is no risk of plasma leakage even after long-term use. For this reason,
Like ECC02R, it is possible to remove the amount of carbon dioxide produced by the living body with a small amount of extracorporeal circulation.

In addition, the gas exchange membrane is a hollow fiber membrane, preferably an inner diameter of 100~
If the hollow fiber membrane is 1000 μm and is made of polyolefin, preferably polypropylene, the gas exchange performance will be better. ~0.5μm
The risk of blood or leakage is smaller if the device is filled with fine particles.

[Brief explanation of drawings]

FIG. 1 is an enlarged sectional view of a gas exchange membrane in one embodiment of the membrane oxygenator of the present invention, FIGS. 2 and 3 are enlarged sectional views of a gas exchange membrane in another embodiment, and FIG. 5 is a partial cross-sectional view of a hollow fiber membrane oxygenator, which is an embodiment of the membrane oxygenator of the present invention, and FIG. 5 shows the relationship between oxygen gas addition ability and carbon dioxide removal ability with respect to blood flow rate of the oxygenator. The graph, FIG. 6, is a graph showing the relationship between the oxygen meteor and the carbon dioxide removal ability of the oxygenator, and FIG. 7 is a graph showing the relationship between the extracorporeal circulation time and the amount of plasma leakage. DESCRIPTION OF SYMBOLS 1... Membrane oxygenator, 2... Gas exchange membrane, 3... Pore, 4... Fine particles, 5... Housing, 6... Cylindrical main body, 9.10... Partition wall, 11... First mass transfer chamber, 12.13... First mass transfer fluid introduction outlet, 15... Hollow fiber bundle, 27.28... Second mass transfer fluid introduction outlet. . Figure 1 Figure 2 Figure 3 Figure 5? Figure 6 oaA amount (ffl/m+n) Figure 7

Claims (9)

[Claims] (1) As a gas exchange membrane, the wall thickness is 5 to 80 μm, the porosity is 2
In an oxygenator using a porous hydrophobic membrane with a pore size of 0 to 80% and a pore size of 0.01 to 5 μm, the pores are clogged with microparticles that are smaller than the pore size and at least the surface that contacts blood is hydrophobic. A membrane oxygenator characterized by: (2) Claim 1 in which the gas exchange membrane is a hollow fiber membrane
Membrane oxygenator described in section. (3) The membrane oxygenator according to claim 2, wherein the hollow fiber membrane has an inner diameter of 100 to 1000 μm. (4) The membrane oxygenator according to any one of claims 1 to 3, wherein the pores are filled with the fine particles and are occluded. (5) The membrane oxygenator according to any one of claims 1 to 4, wherein the fine particles are made of a hydrophobic substance. (6) The fine particles are fine particles made of a hydrophilic substance, and further,
The membrane oxygenator according to any one of claims 1 to 4, wherein at least the blood contacting surface is coated with a hydrophobic substance. (7) The membrane oxygenator according to any one of claims 1 to 6, wherein the gas exchange membrane is made of olefin resin. (8) The membrane oxygenator according to claim 7, wherein the gas exchange membrane is made of polypropylene. (9) The membrane oxygenator according to any one of claims 1 to 8, wherein the fine particles have a particle size of about 0.003 to 1.0 μm.