JP2010269307A - Hollow fiber microporous membrane and membrane oxygenator formed by incorporating the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide hollow fiber microporous membranes demonstrating sufficient plasma leakage resistance and stable and excellent gas exchangeability over a long and continuous use, and an oxygenator incorporated therewith. <P>SOLUTION: The hollow fiber microporous membrane is formed of hydrophobic elements with an oxygen gas flux of 10×10<SP>-5</SP>to 500×10<SP>-5</SP>[cm<SP>3</SP>(STP)/cm<SP>2</SP>/sec/cmHg], an ethanol flux of 2-80 [ml/min/m<SP>2</SP>], and communication holes of an average hole radius of 0.008-0.07 μm. The membrane oxygenator incorporated with the hollow fiber microporous membrane has excellent changeability of oxygen with carbon dioxide compared to conventional microporous membranes and membrane oxygenators incorporated therewith, and has plasma leakage resistance allowing a long term continuous use for more than one week. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a membrane oxygenator for adding oxygen to blood and removing carbon dioxide such as carbon monoxide or carbon dioxide in extracorporeal blood circulation.

  Currently, artificial lungs are widely used in open-heart surgery under direct vision, which requires a short time. In recent years, there has been a strong demand for the development of an artificial lung that can be used continuously for a long period of time for continuous cardiopulmonary assistance after surgery, respiratory assistance for premature infants, and cardiac assistance for patients with acute heart failure. In addition, in order to reduce the burden on the patient during the operation, there is a demand for the realization of a compact and compact artificial lung with excellent gas exchange efficiency with a small blood filling amount and a small membrane area in contact with blood. However, the above-mentioned prior art does not necessarily satisfy both the requirements of sufficient gas exchange performance necessary for realizing compactness and downsizing and so-called long-term durability that can be used for a long time without leakage of plasma. .

  For example, an oxygenator incorporating a homogenous membrane typified by a silicone membrane may be mentioned, but the homogenous membrane has poor gas exchange performance although there is no concern about plasma leakage, and thus requires a large membrane area, that is, a large oxygenator. Since a large amount of priming blood is required, the biological load is large and the application range is limited.

  In addition, an artificial lung incorporating a polypropylene microporous membrane has been developed. Although the microporous membrane exhibits excellent gas exchange performance in a short time of use, the microporous portion is gradually removed with the passage of blood perfusion time. The plasma component leaks and cannot be used.

  As an artificial lung incorporating a polypropylene microporous membrane, for example, Japanese Patent Publication No. 3-21188 discloses the application of a polypropylene porous membrane with a pore size and porosity produced by a melting method to an artificial lung. Has been.

JP-B-4-39371 discloses a hollow fiber membrane made of polyolefin produced by a temperature-induced phase separation method (TIPS method), and has a relatively dense layer on the inner surface side of the hollow fiber, A hollow having an aggregated layer of independent particles having an average particle size of 0.1 μm to 10 μm on the outer surface side, a fine communication hole diameter penetrating the membrane wall, and specifying the membrane porosity and the oxygen gas flux Application of a thread membrane to an artificial lung is disclosed.

Furthermore, JP-A-5-64663 discloses a porous polypropylene hollow fiber membrane produced by the TIPS method, wherein the hollow fiber inner surface has a porosity of less than 10%, a porosity of 1 to 35%, oxygen The gas flux is 10 to 1000 [ml / min / m 2 / mmHg] and the water permeability is 0.01 to 1.0 [ml / min / m 2 / mmHg]. Excellent gas exchange performance and plasma leakage over a long period of time A porous hollow fiber membrane that cannot be released and has excellent durability is disclosed.

  However, these have a larger average pore size than the present invention, and there is a point that oxygen gas exchange performance is excellent in short-time use, but plasma components leak from the microporous part with the passage of blood perfusion time, so long-term durability It was inferior to.

  JP-A-60-150757 discloses a microporous hollow fiber membrane produced by a melting method having a porosity of 30 to 90 vol%, a water pressure of 4 kg / cm 2 or more, and a bubble point of 7 kg / cm 2. An application of a polyethylene hollow fiber membrane having a micropore diameter opened in a strip shape in a range of ˜15 kg / cm 2 to an artificial lung is disclosed. However, it has a strip shape and is different from the present invention.

  On the other hand, for the purpose of partially improving these problems, Japanese Patent Publication No. 2700170 has a non-porous thin film layer that does not substantially have so-called communication holes communicating with the membrane wall and therefore does not substantially transmit ethanol as a liquid. Artificial lungs incorporating hollow fiber microporous membranes have been proposed. The microporous membrane has a barrier layer having an oxygen transmission rate of 1 × 10 −6 [cm 3 (STP) / cm 2 / sec / cm Hg] or more and substantially impervious to ethanol, and has a porosity of 7 Although a membrane oxygenator using a hollow fiber membrane made of a polyolefin-based polymer of ˜50% is disclosed, this oxygenator significantly improves plasma leakage resistance and oxygen supply ability to blood. Although recognized, the performance of removing carbon dioxide from blood was not always satisfactory.

  As described above, the microporous membrane made of polypropylene resin, which is widely used at present, exhibits excellent oxygen gas exchange performance only for short-term use, but cannot be used continuously for a long time due to the occurrence of plasma leak. The reliability limit of usable time was about 6 hours at most. Intraoperative plasma leaks have had serious consequences for patients, and intraoperative oxygenator replacement has been associated with great effort and great risk.

  Furthermore, it is not only applicable to normal open heart surgery but also to open heart surgery over a long period of time, and also to the application of the auxiliary circulation field that requires long-term continuous use such as ECMO and PCPS for more than one week. However, a hollow fiber microporous membrane capable of exhibiting sufficient plasma leakage resistance and stable and excellent gas exchange performance, and an artificial lung incorporating the hollow fiber membrane have not been known to date.

  Regarding the mechanism of gas transfer between the blood phase and the gas phase performed through the membrane, it is applicable not only to normal open heart surgery but also to open heart surgery over a long period of time, and also to ECMO, PCPS, etc. To provide a hollow fiber microporous membrane capable of exhibiting sufficient plasma leakage resistance and stable and excellent gas exchange performance even in applications in the auxiliary circulation field where continuous use is required, and an artificial lung incorporating the same Is an issue.

  As a result of intensive research on a microporous membrane that is excellent in gas exchange performance between blood and gas and that can completely prevent plasma leakage even during long-term use, the inventors have been characterized by specific characteristic values. Compared to conventional microporous membrane, the membrane made of polyolefin polymer has excellent oxygen and carbon dioxide exchange performance and is hollow with plasma leakage resistance that can be used continuously for a long period of one week or longer. A thread microporous membrane was found and the present invention was discovered.

  That is, the present invention

(1) The oxygen gas flux of the microporous hollow fiber membrane made of a hydrophobic material is 10 × 10 5 [cm 3 (STP) / cm 2 / s / cm Hg] —500 × 10 5 [cm 3 (STP) / cm 2 / s / cmHg], the average pore radius of the communication holes is 0.008 μm to 0.07 μm, the open area ratio is 0.02 to 2%, and the ethanol flux of the membrane is 2 ml / min / m 2? A hollow fiber microporous membrane characterized by being 80 ml / min / m 2;

(2) The hollow fiber microporous membrane according to (1) above, wherein the hydrophobic material comprises a poly (4-methylpentene-1) polymer,

(3) The hollow fiber microporous membrane according to (1) or (2) above, wherein the hollow fiber microporous membrane is a membrane produced by a melt spinning method,

(4) To provide a membrane oxygenator in which the hollow fiber microporous membrane according to any one of (1) to (3) is incorporated.

  According to the present invention, it is possible to provide a hollow fiber microporous membrane that has excellent oxygen and carbon dioxide exchange performance and that does not leak plasma components even during long-term use, and an artificial lung incorporating the same.

It is a model figure which shows the structural example of the oxygenator of this invention. It is a model figure which shows the lamination | stacking state of the saddle-shaped hollow fiber sheet which shows the structural example of this invention.

The present invention will be described in more detail.
The membrane used in the present invention is a microporous membrane having fine pores (voids) inside the membrane and having communication holes in which the front and back of the membrane are substantially communicated by pores.

  The “hydrophobic material” used in the present invention means a material having a contact angle with water of 90 ° or more. Specifically, polyolefin resins such as polypropylene, polyethylene, polybutylene, poly-4-methyl-1-pentene, tetrafluoroethylene, tetrafluoroethylene perfluoroalkoxy vinyl ether copolymer, polyvinylidene fluoride, etc. A fluororesin, a polyacetal resin, etc. are mentioned.

  The higher the hydrophobicity of the membrane material, the better. From this point, a polyolefin-based resin that is highly hydrophobic and easy to process is preferable, and among them, a poly-4-methyl-1-pentene-based resin is particularly preferable.

  When the microporous membrane of the present invention is applied to an artificial lung, the risk of plasma leakage increases as the diameter of the communication hole increases and the hole area ratio increases. On the other hand, in order to impart sufficient oxygen, carbon monoxide and carbon dioxide (hereinafter referred to as “carbon dioxide”) gas exchange performance to the membrane, there are communication holes in the membrane and the membrane has an appropriate gas permeability. It is necessary to have.

  Therefore, the membrane used in the present invention has an average pore radius of communication holes of 0.008 to 0.07 μm, preferably 0.01 to 0.045 μm, more preferably 0.02 to 0.040 μm. The rate is 0.02 to 2%, preferably 0.05 to 1.5%, more preferably 0.3 to 1.2%.

  However, the average communication hole radius as referred to in the present invention can be determined by the method described in page 1805 of Journal of Applied Polymer Science VOL.18, PP.805-819, 1974. The average communication hole radius of the present invention is a value measured using nitrogen gas.

That is, the average communication hole diameter was determined from the pressure dependency of the gas flux.
The calculation was performed based on the following formula.

J = K × ΔP / L (1)
J: Gas flow rate, ΔP: Pressure difference, L: Film thickness

K = K0 + (B0 / η) × ΔP1 (2)
K0: Knudsen permeability coefficient, B0: Geometric factor η: Gas viscosity, ΔP1: Average pressure = (P1 + P2) / 2

r = (B0 / K0) (3/16) (2RT / π) 1 / 2M? 1/2 (3)
r: average communication hole diameter, M: gas molecular weight

The gas flux is measured while changing the pressure, and the slope (= B0 / η) and intercept (= K0) of the graph are obtained from (2). The average communication hole diameter r is obtained by substituting these values into (3).

  Moreover, the open area rate as used in the field of this invention is calculated | required with the following method. It calculates from the value of the average communicating hole diameter calculated | required by said method, and the ethanol flux.

ε = 8LVη / (r2ΔP)
L: Film thickness, V: Ethanol flux, η: Ethanol viscosity, r: Average communication hole diameter, ΔP: Pressure difference between inside and outside of membrane wall

Plasma leakage basically occurs from a microporous part that has been hydrophilized.
Further, the communication pore diameter of the microporous membrane exists with a certain distribution.

  A preferred hollow fiber microporous membrane in the present invention is a microporous membrane having a bubble point (using ethanol as a liquid) of 10 kgf / cm 2 or more as an index indicating the maximum value of the communication pore diameter of the membrane.

  In the microporous membrane of the present invention, the gas flow rate of oxygen permeating the membrane wall when measured in a gas-gas system, that is, the oxygen flux is 10 × 10 −5 to 500 × 10 −5 [cm 3 (STP) / cm 2 / sec / cm Hg], preferably 10 × 10 −5 to 250 × 10 −5 [cm 3 (STP) / cm 2 / sec / cm Hg] (calculated by a measuring method according to ASTM D1434).

  The non-aggregating gas such as oxygen, nitrogen, carbon dioxide, etc. of the hollow fiber microporous membrane of the present invention has almost the same gas flux when measured by a gas-gas system through the membrane. As a result of examining the gas exchange performance with blood, it was found that carbon dioxide gas is significantly different from oxygen gas. Therefore, even if the above-mentioned oxygen flux is less than 10 × 10 −5 [cm 3 (STP) / cm 2 / sec / cm Hg], the oxygen exchange performance is not significantly reduced, but sufficient In order to exhibit a sufficient ability to remove carbon dioxide, the film must have an oxygen flux of at least 10 × 10 −5 [cm 3 (STP) / cm 2 / sec / cm Hg].

  The upper limit of the oxygen flux of the microporous membrane of the present invention is 500 × 10 −5 [cm 3 (STP) / cm 2 / sec / cm Hg]. If it is larger than this, it will be difficult to control the blood gas concentration during treatment and surgery.

  The ethanol flux exhibited by the microporous membrane of the present invention is an index that indicates the degree of presence of the communication holes, as is the oxygen gas flux of the membrane. In the present invention, the ethanol flux of the membrane was measured by measuring the amount of ethanol leaked as liquid from the opposite side of the membrane by applying a differential pressure of 0.5 kgf / cm2 from the inside or outside of the hollow fiber after the membrane was sufficiently wetted with ethanol. Can be obtained. The ethanol flux of the present invention is 2 to 80 [ml / min / m 2], preferably 7 to 60 [ml / min / m 2], more preferably 32 to 40 [ml / min / m2] based on the outer diameter of the hollow fiber. m2].

  If it is less than 2 [ml / min / m 2], the membrane cannot exhibit a sufficient gas exchange performance, particularly the ability to remove carbon dioxide from blood. If it is greater than 80 [ml / min / m 2], plasma leakage cannot be prevented in the blood circulation over a long period of time, and stable gas exchange performance cannot be obtained.

  According to the present invention, a hollow fiber microporous membrane having optimum characteristics can be selected even when characteristics required for an artificial lung differ depending on the type of treatment, the condition of a patient to be applied, and the like. For example, when long-term plasma leakage resistance and stable gas exchange performance are required such as ECMO for respiratory assistance for neonatal respiratory failure, the upper limit of the communication hole radius is 0.04 μm, and the upper limit of ethanol flux The hollow fiber microporous membrane of the present invention having a value of 45 ml / min / m 2 can be suitably applied.

  For example, when a large amount of blood perfusion is required during an operation such as severe thoracic aortic disease of an adult, the lower limit of the oxygen flux is 40 × 10 −5 [cm 3 (STP) / cm 2 / sec / cm Hg], A hollow fiber microporous membrane having a lower limit value of the communication hole average radius of 0.02 μm and a lower limit value of ethanol flux of 15 ml / min / m 2 can be suitably applied.

  The hollow fiber microporous membrane of the present invention may be subjected to various treatments generally performed for the purpose of improving the biocompatibility of an artificial lung, for example, a blood contact surface of the membrane with an antithrombotic treatment with a heparin compound, etc. The membrane surface may be hydrophilized by plasma treatment, corona discharge treatment or the like. The hollow fiber microporous membrane of the present invention does not impair excellent gas exchange performance and plasma leakage resistance even in such surface treatment.

  When incorporating the hollow fiber membrane of the present invention into an artificial lung module, the hollow fiber may be incorporated in a bundled state, and if necessary, the hollow fiber membranes may be arranged in a sheet form so that the intervals between the hollow fibers are uniform. May be used.

  The hollow fiber of the present invention may be a hollow fiber having a substantially circular or elliptical cross-sectional shape, and the dimensions are not particularly limited, but preferably the outer diameter is 150 μm to 400 μm, the inner diameter is 120 μm to 360 μm, and the film thickness Is 15 μm to 60 μm.

  In addition, when using the hollow fiber of the present invention as an artificial lung by internal perfusion, the total area inside the normal hollow fiber is 0.1 to 7 m2, and the number of hollow fibers is 1,000 to 100, A typical cylindrical type includes 000 hollow fibers and has a gas exchange portion with an outer diameter of 25 cm or less and a length of 30 cm or less.

  Furthermore, when used in external perfusion, the hollow fiber is included so that the total area of the outside of the hollow fiber is usually 0.1 to 3.5 cm2, and the number of hollow fibers is 1,000 to 60,000, The gas exchange part is typically a cylindrical type having an outer diameter of 20 cm or less and a length of 30 cm or less.

  There is no restriction | limiting in the manufacturing method of the hollow fiber microporous membrane of this invention, It can manufacture by a conventionally well-known manufacturing method.

For example, a crystalline thermoplastic polymer resin is melted by heat, and during the spinning process, a temperature gradient and shear force are effectively applied in the spinning direction to grow a laminated lamella structure, and heat treatment is performed as necessary. Then, a so-called melt spinning method in which a microporous film is formed by stretching and opening the interface of the laminated lamellar crystals,

A so-called wet film-forming method in which a dope solution obtained by dissolving a polymer in an appropriate solvent is introduced into a non-solvent to cause phase separation to form a microporous film,

Alternatively, a liquid that does not dissolve the polymer material as necessary, kneading the polymer material with an organic filler that is easily dispersed in the polymer under thermal melting or a crystal nucleation agent as necessary. Examples of the method include a so-called heat-induced phase separation method in which a microporous membrane is obtained by cooling and solidifying in a solid, and then extracting and removing the kneaded product with an appropriate liquid.

  The melt spinning method makes it easy to control the dimensions of the membrane, the pore diameter of the communication holes, the aperture ratio, etc., and can stably produce membranes with uniform characteristics, and it can be obtained without using additives or solvents. This is the most preferable production method because of the excellent safety of the obtained film.

  Membrane characteristics such as gas flux, communicating pore diameter and open area ratio of the hollow fiber microporous membrane obtained by the melt spinning method are greatly influenced by the crystallization characteristics of the crystalline polymer material used. For example, when a highly crystalline polymer material such as high-density polyethylene or polypropylene is used to produce the hollow fiber microporous membrane of the present invention, conditions for slightly suppressing crystal growth may be applied in a known melt spinning method.

  In addition, when using a thermoplastic polymer resin having poor crystallinity compared to polyethylene or polypropylene, for example, a resin such as poly-4-methyl-1-pentene, it is necessary to adjust the condition range to grow crystals by spinning. Accordingly, the hollow fiber microporous membrane of the present invention can be prepared by stretching the spun yarn after heat treatment.

Further, in detail, the melt spinning method in the present invention refers to a melt strand in a hollow shape at a melting point of the resin to a melting point + 100 ° C. using a double tube nozzle capable of forcingly supplying the hydrophobic material of the present invention into the hollow fiber. , Wind a breeze (less than 1m / sec) around the spinning cylinder (room temperature ± 30), cool and solidify at ℃, wind around a spool with a spinning draft of about 100-2,000,

  Next, heat treatment is performed for 1 minute to 24 hours in an atmosphere of (Tg + 50) ° C. (where Tg is the glass transition point) and below the melting point while being wound around the spool. Next, this is stretched between rollers at a draw ratio of 1.1 to 3.0 times, and continuously tensioning the shrinkage force of the hollow fiber in an atmosphere of (melting point−50) ° C. to (melting point−20) ° C. This means that heat fixation is carried out for several seconds while relaxing slightly (0.8 to 0.9 times), and the hollow fiber microporous membrane of the present invention can be produced by this method.

  The shape and form of the artificial lung to which the hollow fiber microporous membrane of the present invention is applied are not limited, and may be a so-called internal perfusion type artificial lung that allows blood to flow inside the hollow fiber as the form of the artificial lung. Alternatively, a so-called external perfusion oxygenator may be used, which exchanges gas by flowing blood. The external perfusion oxygenator is the most preferable form because it can suppress blood flow pressure loss to a low level and is excellent in gas exchange efficiency per unit membrane area.

  The basic performance of an oxygenator, such as gas exchange efficiency, low blood damage (low blood pressure pressure loss), etc., also depend greatly on the structure of the oxygenator. Examples of preferred forms / shapes of the artificial lung incorporating the hollow fiber membrane of the present invention are described in detail in, for example, Japanese Patent Laid-Open No. 10-256425.

  The hollow fiber microporous membrane of the present invention is excellent in blood gas exchange, that is, oxygen supply to blood and removal of carbon dioxide from blood, and an artificial lung using the membrane is not limited to general open heart surgery. It can be suitably used as an oxygenator for respiratory assistance and percutaneous cardiopulmonary assistance for patients with acute lung failure and heart failure who require long-term use.

Example 1
4-methyl-1-pentene polymer (trade name: TPX, manufactured by Mitsui Chemicals) is a hollow tube nozzle having a structure capable of forcibly supplying gas into the hollow fiber, and at a molten resin temperature of 280 ° C., it is hollow. The melted strand was extruded onto the spool, and wound around a spool with a spinning draft of about 750 while cooling and solidifying by blowing fine wind from around the spinning cylinder.

Next, the unstretched spun yarn is wound on a spool and heat-treated in an atmosphere of about 190 ° C. for about 2 hours, and then stretched between rollers at a draw ratio of 2 times, and continuously hollowed in an atmosphere of 195 ° C. A hollow fiber composed of a microporous membrane having an outer diameter of 240 μm and a wall thickness of 32 μm was prepared by performing heat setting for about 1 second while slightly relaxing while applying a tension that antagonized the contraction force of the yarn.
(Example 2)
A hollow fiber made of a microporous membrane having an outer diameter of 236 μm and a wall thickness of 33 μm was prepared in the same manner as in Example 1 except that the temperature of heat setting was 215 ° C. and the relaxation rate during heat setting was slightly increased.
(Comparative Example 1)
Using a double tube spinning nozzle, a polypropylene resin melted at 235 ° C. and extruded with a melt flow rate of 6 g / min in the form of a hollow strand while flowing nitrogen inside the nozzle is cooled by blowing a breeze around the spinning tower. The spool was wound up with a spinning draft 770 while solidifying. Next, the hollow strand wound on the spool was heat-treated in an atmosphere at about 130 ° C. for about 2 hours. Next, the strand is stretched between rollers at a stretch ratio of 2 times, and is heat-fixed for about 1 second while being slightly relaxed in an atmosphere of about 130 ° C. to form a microporous film having an outer diameter of 236 μm and a wall thickness of 30 μm. Hollow fibers were prepared.
(Comparative Example 2)
Poly-4-methyl-1-pentene polymer is extruded into a hollow strand shape at a spinning temperature of 285 ° C. using a double tube spinning nozzle, and a gentle breeze is flowed directly from the periphery of the spinning tower directly below the nozzle to solidify the molten strand. The film was taken up with a spinning draft 780 and continuously heat treated in an air atmosphere at about 230 ° C. for about 3 seconds, followed by continuous stretching between rollers of about 1.8, continuously at 195 ° C. Heat-fixed for about 1 second while applying a tension that antagonizes the contraction force in the atmosphere of the above to prepare a hollow fiber composed of a microporous membrane having an outer diameter of 230 μm and a wall thickness of 32 μm and a slightly dense thin film layer on the outer surface did.
(Comparative Example 3)
Poly 4-methyl-1-pentene polymer was dissolved at about 16 [wt%] in cyclohexane heated to about 60 ° C. Next, about 3 [wt%] ethanol was added to the solution, filtered through a stainless steel filter having a pore size of 5 μm, and degassed to obtain a dope for preparing a hollow fiber microporous membrane. Ethanol was used as the dope hollow fiber inner tube liquid heated to about 50 ° C., passed through about 30 cm of air from a hollow nozzle, led to a coagulation bath filled with ethanol, solidified, and wound on a spool. After being immersed in methanol for about 24 hours, drying and heat treatment were performed for about 24 hours in a hot air drying furnace adjusted to 80 ° C. The obtained hollow fiber membrane had a slightly dense layer on the outer surface, and a hollow fiber made of a microporous membrane having an outer diameter of 320 μm and a wall thickness of 55 μm was prepared.

(Test Example 1)
The oxygen flux, average communication hole radius, ethanol flux, and open area ratio of the membrane were examined. The results are shown in Table 1.

(Test Example 2)
Using hollow fibers made of microporous membranes prepared in Examples 1 and 2 and Comparative Examples 1 to 3, hollow fiber sheets having a number of driven hollow fibers of 24 / cm were formed by chain knitting using polyester as warp. A laminate of the present hollow fiber sheet is formed as shown in FIG. 1 as a model diagram, and this laminate is then incorporated into a square module as shown in the model diagram of FIG. An external perfusion oxygenator with an effective membrane area of approximately 0.4 m 2 was prototyped.

  The performance evaluation was performed with bovine blood according to the method of AAMI (ASSOCIATION FOR THE ADVANCEMENT OF MEDICAL INSTRUMENTATION). Fresh cow blood that was anticoagulated with ACD was adjusted to oxygen saturation 65%, hemoglobin (Hb) 12 g / dl, excess base (BE) 0 mEq / l, dissolved carbon dioxide partial pressure 45 mmHg, temperature 37 ° C, At the same time as bovine blood was poured from 1 in 2, the gas exchange performance was measured by setting oxygen gas to V / Q = 1 (oxygen flow rate / blood flow rate) from 3 in FIG. The results are shown in Table 2.

  However, the maximum blood flow rate shown in Table 2 means that the oxygen content of bovine blood containing 12 g / dl of Hb, blood temperature of 37 ° C., oxygen saturation of 65%, and BE of 0 is 45 ml / l (blood The standard blood flow rate is the maximum blood that can reduce the carbon dioxide content by 38 ml / l (blood flow rate). Indicates the flow rate. The maximum blood flow shown in this example is a value after blood is perfused for about 6 hours.

  The evaluation of plasma leakage resistance was performed using ACD bovine blood preserved with sodium azide and, if necessary, antibiotics such as pentocillin. Model of artificial lung used in the experiment Bovine blood prepared at about 37 ° C. while flowing pure oxygen at 2 l / min from 3 in FIG. 2 was perfused in a loop at a flow rate of 2 l / min, and the portion 4 in FIG. The amount of protein in the trapped aggregate water was measured periodically. The protein component was detected using a commercially available protein test paper using color change caused by tetrabromophenol. The bovine blood was replaced with a fresh one approximately every 24 hours. The results are shown in Table 3.

* 1; Fire at the gas outlet

1: Blood inflow / outlet 2: Blood inflow / outlet 3: Gas inflow / outlet 4: Gas inflow / outlet 5: Hollow fiber membrane sheet laminate 6: Hollow fiber membrane sheet 7: Hollow fiber membrane sheet warp

Claims (4)

The oxygen gas flux is 10 × 10 −5 to 500 × 10 −5 [cm 3 (STP) / cm 2 / sec / cm Hg], the ethanol flux is 2 to 80 [ml / min / m 2], and the average pore radius is 0 A hollow fiber microporous membrane made of a hydrophobic material having communication holes of .008 to 0.07 μm. The hollow fiber microporous membrane according to claim 1, wherein the hydrophobic material is a poly (4-methylpentene-1) polymer. The hollow fiber microporous membrane according to claim 1 or 2, wherein the hollow fiber microporous membrane is a membrane produced by a melt spinning method. A membrane oxygenator comprising the hollow fiber microporous membrane according to any one of claims 1 to 3.

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