JPH0440026B2 - - Google Patents

Description

BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to membrane oxygenators. Specifically, the present invention provides for extracorporeal blood circulation,
In an artificial lung that removes carbon dioxide from the blood and adds oxygen to the blood, it has excellent gas exchange ability, especially carbon gas removal ability, has low plasma leakage even after long-term use, and is biocompatible. This relates to a membrane oxygenator that has a high rate of oxidation and low platelet loss. (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. In addition to having good gas permeability, this gas exchange membrane also has high mechanical strength, no leakage of plasma even when blood circulates for a long period of time, and no damage to the blood even if it comes into contact with blood. That is, performance such as not causing blood coagulation, microthrombus formation, platelet loss, plasma protein denaturation, hemolysis, etc. is required. There are currently two types of gas exchange membranes used in membrane oxygenators: homogeneous membranes and porous membranes.
Silicone membranes are mainly used, while various materials such as polyethylene, polypropylene, polytetrafluoroethylene, polysulfone, polyacrylonitrile, polyurethane, and polyamide are used for porous membranes. however,
Silicone homogeneous membranes do not have sufficient strength and cannot be made thicker than 100 μm, which limits their gas permeability, particularly for carbon dioxide gas, and they cannot achieve the desired gas exchange performance. Therefore, for example, when tens of thousands of hollow fiber membranes are bundled, the apparatus becomes large and the amount of priming increases, and the cost is also high. On the other hand, porous membranes have many fine pores that communicate in the membrane thickness direction, but because the membrane is hydrophobic, plasma does not pass through the pores, that is, the blood flow path side of the membrane Adding oxygen in the gas to the blood without causing plasma leakage from one side to the other gas flow path side,
It also makes it possible to remove carbon dioxide from the blood into gas. However, porous membranes are highly permeable to water vapor, so not only do they degrade in performance due to condensation, but when blood is circulated for long periods of time, large amounts of plasma may actually leak out. This phenomenon is also observed in artificial lungs that have been tested for water leakage at the manufacturing stage and found to be free of abnormalities, and is a phenomenon that occurs during use. In addition, few porous membranes can be said to have sufficient material from the viewpoint of biocompatibility such as platelet loss. In order to eliminate these various drawbacks of porous membranes, the present inventors first developed an artificial lung (patent application No. 1983-1983), which is made by plugging the micropores of a porous membrane with silicone oil.
He proposed an artificial lung (Japanese Patent Application No. 105384-1983), which was made by further improving the pores of a porous membrane and blocking them with silicone rubber. 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,
It has been difficult to remove the amount of carbon dioxide produced by a living body with a small amount of extracorporeal circulation blood flow, as in ECCO ₂ R (Extra Corporeal CO ₂ Removal). OBJECTS OF THE INVENTION Therefore, an object of the present invention is to provide a novel membrane oxygenator. The present invention also provides an artificial lung that removes carbon dioxide from the blood and adds oxygen to the blood during extracorporeal blood circulation.
It is an object of the present invention to provide a membrane oxygenator that has particularly excellent carbon dioxide removal ability, has low plasma leakage even after long-term use, has high biocompatibility, and has low platelet loss. A further object of the present invention is to provide a membrane oxygenator most suitable for ECCO ₂ R. What achieves the above object is a membrane oxygenator using a porous membrane with a wall thickness of 5 to 80 μm, a porosity of 20 to 80%, and a pore diameter of 0.01 to 5 μm as the gas exchange membrane. The pores are blocked by fine particles smaller than the pore diameter, and at least the surface of the gas exchange membrane that comes into contact with blood is coated with a biocompatible hydrophobic resin,
Furthermore, the air flux of the membrane oxygenator is 750
It is a membrane oxygenator with a pressure of ml/min・m ²・mmHg or less. Furthermore, the air flux of the membrane oxygenator of the present invention is
It is desirable that it is 500ml/min・m ²・mmHg or less. Further, it is desirable that the gas exchange membrane of the present invention is a hollow fiber membrane. Further, the hollow fiber membrane of the present invention preferably has an inner diameter of 100 to 1000 μm.
Further, the particle size of the fine particles that block the pores of the porous membrane of the present invention is preferably about 0.003 to 1.0 μm. Furthermore, the fine particles that block the pores of the porous membrane of the present invention are preferably silica particles. Further, it is desirable that the biocompatible hydrophobic resin of the present invention is a fluorine-containing resin. Further, it is desirable that the biocompatible hydrophobic resin of the present invention is a vinyl copolymer containing a vinyl monomer having a perfluoroalkyl side chain as one component. Further, it is desirable that the biocompatible hydrophobic resin of the present invention is a vinyl block copolymer. Further, the vinyl block copolymer of the present invention is preferably a (meth)acrylate copolymer containing as one component a (meth)acrylate monomer having a perfluoroalkyl side chain. Further, in the vinyl block copolymer of the present invention, the weight ratio of the polymer component made of the vinyl monomer having a perfluoroalkyl side chain to the polymer component made of other monomers constituting the copolymer is 0.25 to 1.5. is desirable. Further, the perfluoroalkyl side chain of the present invention is -CH ₂ CH ₂
(CF ₂ ) ₇ CF ₃ is desirable. Further, the biocompatible hydrophobic resin of the present invention is preferably coated with a film thickness of 0.001 to 10 μm. Further, it is preferable that the gas exchange membrane of the present invention is made of olefin resin. Furthermore, it is desirable that the olefin resin of the present invention is polypropylene. Specific Structure of the Invention The present invention will be explained in more detail below based on the drawings. FIG. 1 is an enlarged sectional view showing the detailed 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 membrane oxygenator 1 is a porous membrane with a wall thickness of 5 to 80 μm.
m, preferably 10 to 60 μm, porosity 20 to 80%,
Preferably 30 to 60%, and the pore diameter is 0.01 to 5 μm.
Preferably it is about 0.01 to 1 μm. In this embodiment, the gas exchange membrane has an inner diameter of 100~
It has a hollow fiber shape of 1000 μm, preferably 100 to 300 μm. Each pore 3 of the gas exchange membrane 2 is blocked with fine particles 4 smaller than the pore diameter, and at least the surface of the gas exchange membrane that comes into contact with blood is covered with a biocompatible hydrophobic resin coating 5.
It is coated with. In this embodiment, each pore 3 is closed by filling the inside of the pore 3 with fine particles 4. In addition, as shown in FIG. 2, the inner surface of the gas exchange membrane 2 The fine particles 4 are attached to the surface of the pores 3 on the side or on the outer surface side of the gas exchange membrane 2 with an adhesive or the like as shown in FIG. Good too. As a result of each of the pores 3 being blocked by the fine particles 4, the gas exchange membrane 2 has ultra-fine pores that cannot be seen under an electron microscope, and these ultra-fine pores are formed on the inner and outer surfaces of the gas exchange membrane. penetrates through. As the material of the gas exchange membrane 2, hydrophobic polymers such as polypropylene, polyethylene, polytetrafluoroethylene, polysulfone, polyacrylonitrile, and cellulose acetate may be used, but olefin resins are preferred, and particularly preferred. , polypropylene, and preferably polypropylene in which micropores are formed by a stretching method or a solid-liquid phase separation method. 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. Inorganic substances such as carbon, or polymer latexes such as polystyrene latex, styrene rubber (SBR) latex, and nitrile rubber (NBR) latex may be used. Among these materials, silica is particularly desirable. Note that the surface characteristics of the fine particles 4 are important from the viewpoint of plasma leakage during use of an oxygenator, but as detailed below, in the present invention, the surface characteristics of the gas exchange membrane 2 that come into contact with blood ( (including the surface of the microparticles 4 that comes into contact with blood) is coated with a biocompatible hydrophobic resin, so even if the microparticles are made of a hydrophilic material such as silica, the microparticles are especially treated to be hydrophobic. There's no need. In addition, the average particle size of the fine particles is 0.003 to 1.0 μm,
Preferably, the thickness is about 0.003 to 0.5 μm. On the other hand, the biocompatible hydrophobic resin that coats at least the surface of the gas exchange membrane that comes into contact with blood includes:
There are fluorine-containing resins and silicone rubbers, and these substances are suitable also because of their high gas permeability. As the silicone, a room temperature curable (RTV) silicone is used, and it may be either a one-part type or a two-part type. For example, as a two-component RTV silicone rubber, a polymer of vinylmethylsiloxane and methylhydrogensiloxane is preferred. Furthermore, from the viewpoint of biocompatibility, it is preferable to use a material that does not contain silica. In addition, polytetrafluoroethylene, polytrifluoroethylene, etc. are also used as fluorocarbon resins, but vinyl copolymers containing a vinyl monomer having perfluoroalkyl side chains as one component have excellent biocompatibility. It is particularly desirable because it has gas permeability. A vinyl copolymer containing a vinyl monomer having a perfluoroalkyl side chain as one component is a copolymer consisting of any vinyl monomer and a vinyl monomer having a perfluoroalkyl side chain, preferably any vinyl monomer. So-called A-B, in which a block made of a homopolymer of a vinyl monomer having a perfluoroalkyl side chain is bonded to a base block made of a base polymer (that is, it may be a homopolymer, a block copolymer, a random copolymer, etc.). It is a type block copolymer. Vinyl monomers having perfluoroalkyl side chains include -CH ₂ (CF ₂ ) ₂ H, -CH ₂
Perfluoroalkyl groups such _{as ( CF2} ) _4H , _-CH2CF3 , _-CH2CH2 ( _{CF2 ) 7CF3 ,} preferably _-CH2CH2
There are perfluoroacrylates and perfluoromethacrylates having (CF ₂ ) ₇ CF ₃ as a side chain. On the other hand, examples of the vinyl monomer constituting the base block include methyl methacrylate, ethyl methacrylate, butyl methacrylate, 2-
Examples include alkyl methacrylates such as ethylhexyl methacrylate, and alkyl acrylates such as methyl acrylate, ethyl acrylate, and butyl acrylate. In addition, in a vinyl block copolymer containing a vinyl monomer having a perfluoroalkyl side chain as one component, the polymer component consisting of the vinyl monomer having a perfluoroalkyl side chain and the other vinyl monomers constituting the copolymer are The weight ratio to the polymer content is 0.25~
1.5, preferably 0.3 to 1.2. In other words, if the weight ratio is 0.25 or more, the microphase separation structure necessary for suppressing platelet adhesion will be reliably expressed, while if the weight ratio is 1.5 or less, it will be easier to dissolve in a solvent and the processability will be reduced. Good and desirable. The block copolymer is obtained by obtaining a vinyl polymer as a base block having a peroxy bond in the main chain, and then polymerizing perfluoroacrylate by dispersion polymerization using this polymer as a polymerization initiator. Vinyl block copolymers containing vinyl monomers having perfluoroalkyl side chains as one component include ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone, methanol, ethanol, n-butanol,
Alcohols such as sec-butanol, ethyl acetate,
It is soluble in esters such as butyl acetate, ethers such as dimethylformamide, tetrahydrofuran, diethyl ether, methyl cellosolve, and ethyl cellosolve, and organic solvents such as chloroform. The membrane oxygenator of the present invention can be easily manufactured, for example, as follows. That is, first, the hollow fiber gas exchange membrane 2 is made hydrophilic using alcohol or the like. Next, an aqueous dispersion of the fine particles 3 as described above is poured into the hollow fibers 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 so as to cause clogging, and the pores 3 are closed. Obstructed.
Furthermore, it is preferable to fill the pores 3 by filtering the dispersion liquid through a gas exchange membrane. 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. After the pores 3 of the gas exchange membrane 2 are blocked with the fine particles 4 in this way, the solution or reaction solution of the biocompatible hydrophobic resin is introduced into the fine particles 4 into the pores 3.
The blood contacting surface of the gas exchange membrane 2 filled with the solvent is brought into contact with the blood contacting surface by dipping or flowing, and then the solvent is evaporated or reaction-cured to form a film. For example, as a biocompatible hydrophobic resin, one vinyl monomer having a perfluoroalkyl side chain is used as a biocompatible hydrophobic resin.
When using a vinyl copolymer as a component, after bringing at least the blood contacting surface of the gas exchange membrane 2 into contact with a solution containing 1 to 10% by weight, preferably 3 to 5% by weight, of the copolymer, a solvent is added. A coating 5 is formed by evaporating the . Any of the above solvents can be used as the solvent, but
Preferred are single or mixed solvents of ketones and mixed solvents of these ketones and alcohols. However, it is necessary to control the evaporation of the solvent during film formation, for example, 4/6 (volume ratio) methyl ethyl ketone/methyl isobutyl ketone, (4/6)/10 (volume ratio) (methyl ethyl ketone/methyl isobutyl ketone). A mixed solvent such as /ethanol is suitable. In addition, when silicone rubber, such as a polymer of vinyl methyl siloxane and methylhydrogen siloxane, is used as the biocompatible hydrophobic resin, at least the blood contacting surface of the gas exchange membrane 2 is covered with 5 to 80% by weight of the silicone rubber, preferably 20% by weight of the silicone rubber. Coating 5 was formed by contacting with ~70% by weight solution and then reaction-curing at 20-30°C.
is formed. Solvents used include benzene, toluene, xylene, hexane, dichloromethane, methyl ethyl ketone, difluoroethane,
Examples include ethyl acetate, trifluorotrichloroethane, and mixtures thereof, and the solution also contains a platinum group metal element, oxide, compound, etc., such as chloroplatinic acid, as a curing crosslinking agent. Furthermore, if silicone rubber alone has a high viscosity and, for example, it is difficult for the solution to flow into the hollow fiber, which is the blood contact surface, dimethyl silicone oil, methyl phenyl silicone oil, methyl chlorophenyl silicone oil, branched It is also possible to blend silicone oil such as dimethyl silicone oil in a silicone rubber (solid content):silicone oil (liquid content) weight ratio of about 2:8 to 8:2. Further, the thickness of the coating 5 of this biocompatible hydrophobic resin is 0.001 to 10 μm, more preferably 0.1 to 5 μm.
It is. That is, if it is 10 μm or less, there is no risk of reducing the gas exchange ability of the gas exchange membrane 2,
Furthermore, when the gas exchange membrane is hollow fiber-like,
This is preferable because the blood flow path is not reduced. It should be noted that although the pores 3 of the gas exchange membrane 2 can be closed and the blood contact surface coated as described above, it is possible to carry out the process before assembling the membrane oxygenator, but it is more preferable to carry out the process after assembling the module. Furthermore, the air flux of the membrane oxygenator of the present invention obtained as described above is 750ml/min・m ²・
mmHg or less, so there is little plasma leakage.
Preferably it is 500 ml/min·m ² ·mmHg or less, more preferably 100 ml/min·m ² ·mmHg or less. That is, 500ml/min・m ²・mm
If it is below Hg, plasma leakage can be reliably suppressed even during long-term circulation use. FIG. 4 shows an 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 6, and the housing 6 is provided with annular male-threaded mounting covers 8 and 9 at both ends of a cylindrical main body 7. for,
The entire membrane is expanded, and a large number of pores 3, for example, 10,000 to 60,000 as mentioned above, are blocked by fine particles 4, and at least the blood contacting surface of the membrane is made of vinyl-based material containing perfluoroalkyl side chains as one component. Hollow fiber gas exchange membrane 2 coated with polymer
are arranged in parallel and spaced apart from each other along the longitudinal direction of the housing 6. To be more specific,
A vinyl copolymer is coated on the inner wall surface of the hollow fiber in a type of oxygenator in which blood flows into the interior of the hollow fiber, and on the outer wall surface of the hollow fiber in a type of oxygenator in which blood flows outside the hollow fiber. Then, both ends of the gas exchange membrane 2 are connected to the partition wall 1 in a state where the respective openings are not closed in the mounting covers 8 and 9.
0 and 11 in a liquid-tight manner. Further, each of the compartments 10 and 11, together with the outer peripheral surface of the gas exchange membrane 2 and the inner surface of the housing 6, constitutes an oxygen chamber 12, which is a first mass transfer chamber, and closes the oxygen chamber 12. The oxygen chamber 12 is isolated from a blood circulation space (not shown), which is a second mass transfer fluid space formed inside the oxygen chamber 12 . One mounting cover 8 is provided with an inlet 13 for supplying oxygen, which is the first mass transfer fluid. The other mounting cover 9 is provided with an outlet 14 for discharging oxygen. On the inner surface of the cylindrical main body 7 of the housing 6, there is a restricting portion 15 for aperture that protrudes from the center in the axial direction.
It is preferable to provide That is, the restraint part 15
is formed integrally with the inner surface of the cylindrical body 7, and is adapted to tighten the outer periphery of a hollow fiber bundle 16 consisting of a large number of gas exchange membranes 2 inserted into the cylindrical body 7. . In this way, the hollow fiber bundle 16 is narrowed at the center in the axial direction to form a narrowed portion 17, 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 17 is approximately 60 to 80%, and in the other cylindrical body 7 is approximately 30 to 60%, and the filling rate in the hollow fiber bundle 1 is approximately 60 to 80%.
The filling rate at both ends of the partition wall 6, that is, on the outer surfaces of the partition walls 10 and 11, is about 20 to 40%. Next, the formation of the partition walls 10 and 11 will be described. As described above, the partition walls 10 and 11 perform the important function of isolating the inside and outside of the gas exchange membrane 2. Usually, these partition walls 10, 11
is 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 6 using a centrifugal injection method and hardening the material. More specifically, first, a large number of hollow fiber membranes 2 longer than the length of the housing 6 are prepared, and after sealing both open ends with a resin with high viscosity, the inside of the cylindrical body 7 of the housing 6 is Place them side by side. After that, completely cover both ends of the gas exchange membrane 2 with a mold cover having a diameter larger than that of the mounting covers 8 and 9.
The housing 6 is centered around the central axis of the housing 6.
While rotating, the polymer potting material is introduced from both ends. Once 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 10 and 11 are thus formed. The outer surfaces of the partition walls 10 and 11 are respectively covered with flow path forming members 18 and 19 having annular convex portions. The flow path forming members 18 and 19 are respectively composed of liquid distribution members 20 and 21 and screw rings 22 and 23, and the end surfaces of protrusions 24 and 25 are formed as annular convex portions provided near the peripheral edges of the liquid distribution members 20 and 21. are brought into contact with the partition walls 10, 11, respectively, and fixed by screwing the screw rings 22, 23 onto the mounting covers 8, 9, respectively.
An inflow chamber 26 and an outflow chamber 27 for blood, which is a mass transfer fluid, are respectively formed. A blood inlet 28 and an outlet 29, which are a second mass transfer fluid, are formed in the flow path forming members 18 and 19, respectively. These partition walls 10, 11 and flow path forming members 18, 1
The gaps at the peripheral edges of the partition walls 10, 11 formed by the partition walls 10, 9 are filled with fillers 34, 35 from one of at least two holes 32, 33 communicating with the gaps. 11. Alternatively, it is sealed via an O-ring (not shown). In the hollow fiber membrane oxygenator, the first mass transfer fluid is an oxygen-containing gas such as air or blood, and 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, whereas if the first mass transfer fluid is blood, the second mass transfer fluid is a gas. be. The above explanation has been about hollow fiber membrane oxygenators, but flat membrane oxygenators such as stacked membranes, single membranes wound into a coil, and folded in a zigzag pattern can also be used. If the pores of the gas exchange membrane are blocked by fine particles smaller than the pore diameter, and at least the blood contact surface is coated with a biocompatible hydrophobic resin, the blood platelets etc. that come in contact with the gas exchange membrane are highly biocompatible. It is possible to obtain a membrane oxygenator with extremely little damage to the membrane, excellent gas exchange ability, and no risk of plasma leakage even after long-term use. Hereinafter, the present invention will be explained in more 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 Å,
A hollow fiber membrane oxygenator 1 as shown in FIG. 4 with a membrane area of 1.6 m ² was assembled. Ethanol is introduced into the hollow fiber membrane oxygenator through the blood inlet to make the hollow fiber gas exchange membrane hydrophilic, and then silica (colloidal silica, average diameter 100 Å)/aqueous dispersion is introduced into the blood inlet for gas exchange. It was filtered through a membrane and silica was filled into the pores of the gas exchange membrane. Next, distilled water was introduced to thoroughly remove the silica/water dispersion remaining inside the hollow fiber gas exchange membrane, followed by drying. A mixed solvent solution of methyl ethyl ketone/methyl isobutyl ketone (volume ratio 4:6) of various concentrations of methyl methacrylate/butyl methacrylate)-perfluoropropyl acrylate copolymer (weight ratio (25:25):50) was added to the hollow fiber shape. After filling the inside of the gas exchange membrane for 3 minutes, the liquid was discharged and air was blown through to remove the solvent and form a film. When the gas exchange membrane of the obtained membrane oxygenator was observed using an electron microscope (magnification: 10,000 times), the pores had almost disappeared. However, the air flux of the obtained membrane oxygenator was measured as shown in Table 1, and from this it was inferred that it was an ultra-microporous membrane. For comparison, Comparative Example 1 was prepared without filling with fine particles and without resin coating.
The results of measuring the air flux are also shown in Table 1.

[Table] In order to further evaluate the performance of these artificial lungs, in vitro tests and animal tests were conducted. 1 In vitro evaluation Using fresh heparinized bovine blood, oxygen gas partial pressure 35mm
Venous blood with a partial pressure of Hg and carbon dioxide gas of 45 mmHg was prepared and was passed through the blood flow path of the oxygenator to evaluate its performance. The hemoglobin content of the bovine blood used was 12 g/dl, and the temperature was 37°C. The relationship between the blood flow rate and the oxygen gas addition ability and carbon dioxide removal ability when the ratio of the oxygen flow rate to the blood flow rate is 1 is as shown in Table 2 and FIG. 5. Furthermore, the relationship between the oxygen flow rate and carbon dioxide removal ability when the blood flow rate was 1500 ml/min was as shown in Table 3 and FIG. 6. 2 Animal Test A 30-hour venous-arterial partial extracorporeal circulation test was conducted using mongrel dogs. The relationship between the circulation test and the amount of plasma leakage was as shown in Table 4 and Figure 7.
Furthermore, the degree of thrombocytopenia after 30 hours was as shown in Table 4. Example 6 The pores of the gas exchange membrane of a hollow fiber membrane oxygenator prepared in the same manner as in Examples 1 to 5 were blocked with silica particles in the same manner as in Examples 1 to 5, and then vinyl methylsiloxane and methylhydrogen were added to the gas exchange membrane. 2 with siloxane
A trifluorotrichloroethane solution (5% by weight) of RTV silicone rubber (silica-free) containing a liquid type chloroplatinic acid catalyst was filled inside the hollow fiber gas exchange membrane for 1 minute, and then the liquid was drained and air was introduced. The solvent was removed by blowing through the resin, and the film was cured at about 60°C to form a film. The air flux of the obtained membrane oxygenator was 35ml/
It was min・m ²・mmHg. Furthermore, in vitro tests and animal tests were conducted in the same manner as in Examples 1 to 5 to evaluate the performance of these artificial lungs. The results are shown in Tables 2 to 4 and Figures 5 to 7, respectively.

[Table] Example 1
O ₂ 0 32 58 76
84

[Table] 0
Example 1 0 163 178 186

【table】

【table】

[Table] Specific Effects of the Invention The membrane oxygenator of the present invention has a wall thickness of 5 to 80 μm, a porosity of 20 to 80%, and a pore diameter of 0.01 as a gas exchange membrane.
In a membrane oxygenator using a ~5 μm porous membrane,
The pores of the gas exchange membrane are occluded with fine particles smaller than the pore diameter, and further, at least the surface of the gas exchange membrane that comes into contact with blood is coated with a biocompatible hydrophobic resin, and the membrane is further coated with a biocompatible hydrophobic resin. The air flux of the artificial lung is 750ml/
min・m ²・mmHg or less, the gas exchange membrane is presumed to have an ultra-microporous structure, and although its gas exchange ability, especially carbon dioxide removal ability, is extremely high, it There is little leakage. Therefore, it is possible to remove the amount of carbon dioxide gas produced by the living body with a small amount of extracorporeal circulation like ECCO ₂ R. Furthermore, since the blood contacting surface of the inner surface of the gas exchange membrane is coated with a biocompatible hydrophobic membrane, when blood is circulated, contact with the membrane oxygenator causes blood coagulation, microthrombus formation, and platelet loss. Damage such as denaturation of plasma proteins and hemolysis is extremely small. Furthermore, when the membrane oxygenator of the present invention is adjusted to an air flux of 500 ml/min・m ²・mmHg or less, the effect of suppressing plasma leakage is even higher even during long-term circulation, and fine particles are reduced. In the case of silica, it has better gas exchange ability, especially carbon dioxide removal ability, and is also better in terms of manufacturing and cost. On the other hand, the biocompatible hydrophobic resin is a fluorine-containing resin, preferably a vinyl copolymer containing a vinyl monomer having a perfluoroalkyl side chain as one component, more preferably a vinyl copolymer having a perfluoroalkyl side chain ( In the case of (meth)acrylate block copolymers containing meth)acrylate monomers as one component, their biocompatibility is even better, and platelet loss in contact with blood in particular is kept extremely low; Since the resin has extremely good gas permeability, a decrease in the gas exchange ability of the gas exchange membrane due to coating is almost suppressed. Furthermore, these points are applicable when the weight ratio of the polymer component consisting of a vinyl monomer having a perfluoroalkyl side chain in the block copolymer to the polymer component consisting of other monomers constituting the copolymer is 0.25 to 1.5. , the perfluoroalkyl side chain is −CH ₂ CH ₂
(CF ₂ ) ₇ It becomes more noticeable when CF ₃ .
Further, when the gas exchange membrane is made of olefin resin, preferably polypropylene, it has excellent mechanical strength and can provide a more compact membrane oxygenator.

[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 sectional view of a hollow fiber membrane oxygenator, which is an embodiment of the membrane oxygenator of the present invention.
The figure is a graph showing the relationship between the oxygen gas addition capacity and the carbon dioxide removal capacity with respect to the blood flow rate of the artificial lung.
The figure is a graph showing the relationship between the oxygen flow rate 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. 1... Membrane oxygenator, 2... Gas exchange membrane, 3...
Pore, 4... Fine particle, 5... Coating, 6... Housing, 7... Cylindrical body, 10, 11... Partition wall, 1
2...First mass transfer chamber, 13, 14...First mass transfer fluid introduction outlet, 16...Hollow fiber bundle, 2
8, 29...Second mass transfer fluid introduction outlet.

Claims (1)

[Claims] 1. As a gas exchange membrane, the wall thickness is 5 to 80 μm, the porosity is
In a membrane oxygenator using a porous membrane with a pore size of 20 to 80% and a pore size of 0.01 to 5 μm, the pores of the gas exchange membrane are blocked by fine particles smaller than the pore size, and at least A membrane oxygenator, characterized in that the surface that comes into contact with blood is coated with a biocompatible hydrophobic resin, and the air flux of the membrane oxygenator is 750 ml/min·m ² ·mmHg or less. . 2. The membrane oxygenator according to claim 1, wherein the air flux of the membrane oxygenator is 500 ml/min·m ² ·mmHg or less. 3. The membrane oxygenator according to claim 1 or 2, wherein the gas exchange membrane is a hollow fiber membrane. 4. The membrane oxygenator according to claim 3, wherein the hollow fiber membrane has an inner diameter of 100 to 1000 μm. 5. The membrane oxygenator according to any one of claims 1 to 4, wherein the pores are filled with the fine particles and are occluded. 6. The membrane oxygenator according to any one of claims 1 to 5, wherein the fine particles are silica. 7. The membrane oxygenator according to any one of claims 1 to 6, wherein the fine particles have a particle size of 0.003 to 1.0 μm. 8. The membrane oxygenator according to any one of claims 1 to 7, wherein the biocompatible hydrophobic resin is a fluorine-containing resin. 9. Claim 8, wherein the biocompatible hydrophobic resin is a vinyl copolymer containing a vinyl monomer having a perfluoroalkyl side chain as one component.
Membrane oxygenator described in section. 10. The membrane oxygenator according to claim 9, wherein the biocompatible hydrophobic resin is a vinyl block copolymer. 11. The membrane-type artificial material according to claim 10, wherein the vinyl block copolymer is a (meth)acrylate copolymer containing as one component a (meth)acrylate monomer having a perfluoroalkyl side chain. lung. 12. Claim No. 1, wherein the weight ratio of the polymer component consisting of a vinyl monomer having a perfluoroalkyl side chain to the polymer component consisting of other monomers constituting the copolymer in the block copolymer is 0.25 to 1.5. The membrane oxygenator according to item 11. 13 The perfluoroalkyl side chain is -CH ₂
The membrane oxygenator according to any one of claims 9 to 12, which is CH ₂ (CF ₂ ) ₇ CF ₃ . 14 The biocompatible hydrophobic resin has a thickness of 0.0001 to 10μ
The membrane oxygenator according to any one of claims 1 to 13, which is coated with a film thickness of m. 15. The membrane oxygenator according to any one of claims 1 to 14, wherein the gas exchange membrane is made of polyolefin resin. 16. The membrane oxygenator according to claim 15, wherein the gas exchange membrane is made of polypropylene.