JP2002035557A - Hollow fiber microporous membrane and membrane type oxygenator having the same incorporated therein - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hollow fiber microporous membrane capable of developing sufficient blood plasma leak resistance and stable and excellent gas exchange capacity even in long-term continuous use, and an oxygenator having the same incorporated therein. SOLUTION: The hollow fiber microporous membrane, which comprises a hydrophobic material of which the oxygen gas flux is 10×10-3-500×10-5 [cm3 (STP)/cm2/sec/cmHg] and the ethanol flux is 2-80 [ml/min/m2] and which has open cells with a mean pore radius of 0.008-0.07 μm, and the oxygenator having the same incorporated therein have excellent oxygen and carbon dioxide exchange capacity and blood plasma leak resistance enabling continuous use over long period of time of one week or more as compared with a conventional microporous membrane and an oxygenater having the same incororated therein.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

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.

[0002]

2. Description of the Related Art At present, an artificial lung is widely used in open-heart surgery under direct vision, which requires a short time. In recent years, there has been an urgent need for the development of an artificial lung that can be used continuously for a long period of time for continuous cardiopulmonary support during and after surgery, respiratory support for premature infants, and cardiac support for patients with acute heart failure. Further, in order to reduce the burden on the patient during the operation, there is a demand for a small and compact oxygenator having a small blood filling amount, a small membrane area in contact with blood, and excellent gas exchange efficiency. However, the above prior arts do not necessarily satisfy both requirements of sufficient gas exchange performance necessary for realizing compactness and miniaturization and so-called long-term durability that can be used for a long time without plasma leakage. .

[0003] For example, there is an oxygenator incorporating a homogeneous membrane typified by a silicone membrane, but the homogeneous membrane is inferior in gas exchange performance although there is no concern about plasma leakage, and therefore has a large membrane area, that is, a large oxygenator. And a large amount of priming blood is required, so that the biological load is large and the application range is limited.

Although an artificial lung incorporating a microporous membrane made of polypropylene has been developed, the microporous membrane exhibits excellent gas exchange performance when used for a short period of time, but the microporous membrane becomes finer as blood perfusion time elapses. There is a disadvantage that the plasma component leaks out of the porous portion and becomes unusable.

[0005] As an artificial lung incorporating a microporous polypropylene membrane, for example, Japanese Patent Publication No. 3-21188 discloses an artificial lung using a polypropylene porous membrane having a defined pore size and porosity produced by a melting method. Application is disclosed.

Japanese Patent Publication No. 4-39371 discloses a hollow fiber membrane made of polyolefin produced by a temperature-induced phase separation method (TIPS method), wherein a relatively dense layer is formed on the inner surface side of the hollow fiber. With an average particle size of 0.1 μm on the outer surface
A hollow fiber membrane having an aggregated layer of independent particles of 10 μm to 10 μm and having a fine communication pore diameter penetrating the membrane wall, and specifying the porosity of the membrane and the flux of oxygen gas, can be applied to an artificial lung. It has been disclosed.

Furthermore, Japanese Patent Application Laid-Open No. 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%,
The porosity is 1 to 35%, and the oxygen gas flux is 10 to 10
00 [ml / min / m ² / mmHg], water permeability is 0.0
1 to 1.0 [ml / min / m ² / mmHg],
There is disclosed a porous hollow fiber membrane having excellent gas exchange performance, excellent plasma durability over a long period of time, and excellent durability.

[0008] However, these have a larger average pore diameter than the present invention, and although they have an advantage in oxygen gas exchange performance when used for a short time, plasma components leak from the microporous part with the passage of blood perfusion time. It had poor long-term durability.

Further, Japanese Patent Application Laid-Open Publication No. Sho 60-150575 discloses that the porosity of a microporous hollow fiber membrane produced by a melting method is 3%.
0 to 90 vol%, water permeation pressure is 4 kg / cm ² or more, and bubble point is 7 kg / cm ^{2 to} 15 kg / cm ^2.
The application of a hollow fiber membrane made of polyethylene having a small pore diameter formed in a strip shape in the range of (1) to an artificial lung is disclosed. However, it is opened in a strip shape, which is different from the present invention.

On the other hand, for the purpose of partially improving these problems, Japanese Patent Publication No. 2700170 discloses a non-porous material which does not substantially have a so-called communication hole communicating with a membrane wall and therefore does not substantially transmit ethanol as a liquid. An artificial lung incorporating a microporous hollow fiber membrane having a thin film layer has been proposed. The microporous membrane has an oxygen transmission rate of 1 × 10 ⁻⁶ [cm ³ (STP) /
cm ² / sec / cmHg] or more, and has a barrier layer that is substantially impermeable to ethanol, and has a porosity of 7 to 50.
%, A membrane-type oxygenator using a hollow fiber membrane made of a polyolefin-based polymer is disclosed. However, this oxygenator has significant improvements in plasma leak resistance and ability to supply oxygen to blood. However, the performance of removing carbon dioxide from blood was not always satisfactory.

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

Further, the present invention is applied not only to normal open heart surgery but also to open heart surgery for a long time.
A hollow fiber microporous membrane capable of exhibiting sufficient plasma leak resistance and stable and excellent gas exchange performance even in applications to the assisted circulation field, which requires long-term continuous use such as CPS for one week or more, The implanted oxygenator has not been known to date.

[0013]

The present invention relates to a mechanism of gas transfer between a blood phase and a gas phase through a membrane, which is applied not only to normal open heart surgery but also to open heart surgery for a long time, and furthermore, to ECMO. And microporous hollow fiber membranes that can exhibit sufficient plasma leak resistance and stable and excellent gas exchange performance even in applications to the assisted circulation field, which requires long-term continuous use such as PCPS or PCPS for one week or more. An object of the present invention is to provide an artificial lung incorporating the same.

[0014]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies on a microporous membrane which is excellent in blood-gas gas exchange performance and which can completely prevent plasma leakage even after long use. A membrane made of a polyolefin polymer characterized by specific characteristics has superior oxygen and carbon dioxide gas exchange performance compared to a conventional microporous membrane, and can be used continuously for a long period of one week or more. The present inventors have found a hollow fiber microporous membrane having excellent plasma leak resistance, and have discovered the present invention.

That is, the present invention provides:

(1) Microporous hollow fiber made of hydrophobic material
The oxygen gas flux of the film is 10 × 10 ^{? Five}[Cm^Three(ST
P) / cm^Two/ S / cmHg]? 500 × 10^{? Five}[Cm
^Three(STP) / cm^Two/ S / cmHg] of the communication hole
The average pore radius is between 0.008 μm and 0.07 μm,
The porosity is 0.02 to 2%, and the ethanol
Box is 2ml / min / m^Two? 80ml / min / m^Two
A hollow fiber microporous membrane,

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

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

(4) An object of the present invention is to provide a membrane oxygenator incorporating the microporous hollow fiber membrane according to any one of the above (1) to (3).

[0020]

DETAILED DESCRIPTION OF THE 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 surfaces of the membrane are substantially communicated by the 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 and poly-4-methyl-1-pentene, tetrafluoroethylene, tetrafluoroethylene perfluoroalkoxyvinylate copolymers, polyvinylidene fluoride, etc. Fluororesin, polyacetal resin and the like can be mentioned.

The higher the hydrophobicity of the membrane material, the more preferable. From this point, a polyolefin resin, which has high hydrophobicity and is easy to process, is preferable.
1-pentene resins are particularly preferred.

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 communicating hole increases and the porosity increases. On the other hand, in order to impart sufficient gas exchange performance of oxygen, carbon monoxide, and carbon dioxide (hereinafter referred to as "carbon dioxide") to the membrane, the membrane has a communication hole and the membrane has an appropriate gas permeability. Need to have

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

However, the average communicating hole radius referred to in the present invention is 1
974, Journal of Applied Polymer Science VOL.18, PP.8
05-819) No. 18, page 805. The average communication hole radius of the present invention is a value measured using nitrogen gas.

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

J = K × ΔP / L (1) J: gas flow rate, ΔP: pressure difference, L: film thickness

K = K ₀ + (B ₀ / η) × ΔP ₁ (2) K ₀ : Knudsen permeability coefficient, B ₀ : geometric factor η: gas viscosity, ΔP ₁ : average pressure = (P1 + P2) / 2

R = (B ₀ / K ₀ ) (3/16) (2RT / π) ^1/2 M ^{? 1/2} (3) r: average communicating hole diameter, M: gas molecular weight

The gas flux is measured by changing the pressure,
From (2), the slope of the graph (= B ₀ / η) and the intercept (= K ₀ )
Ask for. The average communication hole diameter r is obtained by substituting these values into (3).

The porosity referred to in the present invention is determined by the following method. It is calculated from the average communicating hole diameter and the value of ethanol flux obtained by the above method.

Ε = 8LVη / (r ² ΔP) L: film thickness, V: ethanol flux, η: ethanol viscosity, r: average communicating hole diameter, ΔP: pressure difference between membrane wall and outside

The plasma leak basically occurs from the microporous portion that has been hydrophilized. In addition, the communication pore diameter of the microporous membrane exists with a certain distribution.

In the preferred microporous hollow fiber membrane of the present invention, a bubble pump (using ethanol as a liquid) which is an index indicating the maximum value of the communicating pore diameter of the membrane is 10 kgf / cm.
It is a microporous membrane showing ^two or more.

Gas-gas system in the microporous membrane of the present invention
The gas flow rate of oxygen passing through the membrane wall when measured at
And the oxygen flux is 10 × 10^-Five~ 500 × 10
^-Five[cm^Three(STP) / cm^Two/ Sec / cmHg], preferred
Or 10 × 10^-Five~ 250 × 10 ^-Five[cm^Three(STP)
/ Cm^Two/ Sec / cmHg] (ASTM D14
34).

The non-aggregating gas such as oxygen, nitrogen and carbon dioxide in the microporous hollow fiber membrane of the present invention has substantially the same gas flux when measured by a gas-gas system through the membrane. When examining the gas exchange performance with blood through the membrane,
It became clear that the case of carbon dioxide was significantly different from the case of oxygen. Therefore, the above-mentioned oxygen flux is 10
× 10 ^-5 [cm ³ (STP) / cm ² / sec / cmHg]
Even if it is less than 10, the oxygen exchange performance does not significantly decrease, but on the other hand, the oxygen flux of the film is at least 10 × 10 ⁻⁵ [ cm ³ (STP) / cm ² / sec / c
mHg] or more.

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

The ethanol flux of the microporous membrane of the present invention is an index indicating the degree of the existence of the communication holes, similarly to the oxygen gas flux of the membrane. In the present invention, the ethanol flux of the membrane is obtained by, after sufficiently wetting the membrane with ethanol, applying a differential pressure of 0.5 kgf / cm ² from the inside or outside of the hollow fiber to the amount of ethanol leaked out as a liquid from the opposite side of the membrane. It can be determined by measuring. Ethanol flux of the present invention, based on the outer diameter of the hollow fiber, 2 to
80 [ml / min / m ² ], preferably 7 to 60 [m
1 / min / m ² ], more preferably 32 to 40 [m
1 / min / m ² ].

If it is less than 2 [ml / min / m ² ], the membrane cannot exhibit sufficient gas exchange performance, in particular, performance of removing carbon dioxide from blood. 80 [ml / min /
m ² ], it is not possible to prevent plasma leak and obtain stable gas exchange performance in blood circulation over a long period of time.

According to the present invention, a microporous hollow fiber membrane having optimum characteristics can be selected even when the characteristics required for an artificial lung differ depending on the type of treatment, the condition of the patient to be applied, and the like. For example, when long-term plasma leak resistance and stable gas exchange performance are required such as ECMO for the purpose of assisting respiratory failure of newborn infants, the upper limit of the communication hole radius is 0.04 μm, and the upper limit of ethanol flux is Value is 4
The microporous hollow fiber membrane of the present invention having a flow rate of 5 ml / min / m ² can be suitably applied.

When a large amount of blood perfusion is required during an operation such as severe thoracic aortic disease in an adult, the lower limit of the oxygen flux is 40 × 10 ⁻⁵ [cm ³ (STP) / c].
m ² / sec / cmHg], the lower limit of the average radius of the communication holes is 0.02 μm, and the lower limit of the ethanol flux is 15 ml / min / m ² .

The microporous hollow fiber 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, an antithrombotic treatment of the blood contact surface of the membrane with a heparin compound or the like. Alternatively, the surface of the film may be made hydrophilic by plasma treatment, corona discharge treatment, or the like. The microporous hollow fiber membrane of the present invention does not impair the excellent gas exchange performance and plasma leak resistance even in such a surface treatment.

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

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

When the hollow fiber of the present invention is used as an artificial lung by internal perfusion, the total area of ordinary hollow fiber fibers is 0.1 to 7 m ² , and the number of hollow fibers is 1, 0
A typical example is a cylindrical type in which the hollow fibers are included so that the number becomes 100 to 100,000, and the size of the gas exchange portion is 25 cm or less in outer diameter and 30 cm or less in length.

Further, when used in external perfusion, the hollow fibers are usually arranged so that the total area outside the hollow fibers is 0.1 to 3.5 cm ² and the number of hollow fibers is 1,000 to 60,000. And the size of the gas exchange part is
A cylindrical type having an outer diameter of 20 cm or less and a length of 30 cm or less is typical.

The method for producing the microporous hollow fiber membrane of the present invention is not limited, and can be produced by a conventionally known production method.

For example, a crystalline thermoplastic polymer resin is thermally melted, and a temperature gradient and a shearing force are effectively applied to the material in the spinning process in the spinning direction to grow a laminated lamellar structure.
Furthermore, after performing a heat treatment as needed, stretching is performed, and a so-called melt spinning method for forming a microporous film by 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, the polymer material is kneaded with an organic filler which easily disperses in the polymer under heat melting and, if necessary, a crystal nucleating agent, and the melt-kneaded material is optionally mixed with the polymer material. Solidification by cooling in a liquid that does not dissolve, and then extracting and kneading the kneaded material with an appropriate liquid to obtain a microporous membrane,
A so-called heat-induced phase separation method may be used.

In the melt spinning method, it is easy to control the dimensions of the membrane, the diameter of the communicating holes, the opening ratio, and the like, and it is possible to stably produce a membrane having uniform characteristics. This is the most preferable production method because the obtained film is excellent in safety.

The membrane properties of the microporous hollow fiber membrane obtained by the melt spinning method, such as the gas flux, the diameter of the communicating pores and the porosity thereof, are greatly affected by the crystallization properties of the crystalline polymer material used. For example, when the hollow fiber microporous membrane of the present invention is manufactured using a highly crystalline polymer material such as high density polyethylene or polypropylene, conditions for slightly suppressing crystal growth in a known melt spinning method may be applied.

Further, a thermoplastic polymer resin having lower crystallinity than polyethylene or polypropylene, for example, poly 4-
When a resin such as methyl-1 pentene is used, the hollow fiber of the present invention is adjusted by adjusting the range of conditions for growing crystals during spinning and, if necessary, stretching the spun yarn after heat treatment. A microporous membrane can be prepared.

Further, in detail, the melt spinning method in the present invention refers to a method of using a double circular nozzle capable of forcibly supplying the hydrophobic material of the present invention to the inside of a hollow fiber using a melting point of resin to melting point + 100.
At ℃, the molten strand is extruded in a hollow shape, and a breeze (1 m / sec or less) is blown around the spinning cylinder (about ± 3 at room temperature).
0) While cooling and solidifying at ° C, wind it around a spool with a spinning draft of about 100 to 2,000,

Then, while being wound on the spool (Tg
+50) ° C. (however, Tg is a glass transition point) or higher and lower than the melting point, for 1 minute to 24 hours. Next, this is stretched between rollers at a stretching ratio of 1.1 to 3.0 times, and continuously tensioned against the contraction force of the hollow fiber in an atmosphere of (melting point −50) ° C. to (melting point −20) ° C. Means that heat setting is performed for a few seconds while relaxing slightly (0.8 to 0.9 times) while adding the microporous membrane of the present invention.

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 the form of the artificial lung may be a so-called internal perfusion type artificial lung in which blood flows inside the hollow fiber. A so-called external perfusion type artificial lung for performing gas exchange by flowing blood outside the thread may be used. The externally perfused oxygenator is the most preferable form because it can suppress the blood flow pressure loss to a low level and has excellent gas exchange efficiency per unit membrane area.

Gas exchange efficiency, low blood damage (low blood pressure loss), and the like, which are the basic performances of an artificial lung, greatly depend on the structure of the artificial lung. As a preferred form / shape example of an artificial lung into which the hollow fiber membrane of the present invention is incorporated, for example, Japanese Patent Application Laid-Open No. H10-25642.
5 publication.

The microporous hollow fiber membrane of the present invention is excellent in gas exchange of blood, ie, supply of oxygen to blood and removal of carbon dioxide from blood, and an artificial lung using the membrane is suitable for general open heart surgery. In addition, it can be suitably used as an artificial lung for respiratory support and percutaneous cardiopulmonary support for patients with acute lung failure and heart failure that require long-term use.

[0059]

EXAMPLES Example 1 A double-circle tube nozzle having a structure capable of forcibly supplying gas inside a hollow fiber with a 4-methyl-1-pentene polymer (trade name: TPX, manufactured by Mitsui Chemicals) was used.
The molten strand was extruded in a hollow shape at a molten resin temperature of 280 ° C., and was wound around a spool by a spinning draft of about 750 while blowing and blowing a breeze from around the spinning cylinder to solidify.

Next, the undrawn spun yarn is wound on a spool, heat-treated for about 2 hours in an atmosphere of about 190 ° C., and then drawn between rollers at a draw ratio of 2 times.
A hollow fiber consisting of a microporous membrane having an outer diameter of 240 μm and a wall thickness of 32 μm was prepared by performing heat fixing for about 1 second while slightly relaxing while applying a tension opposing the contraction force of the hollow fiber in an atmosphere at 95 ° C. . (Example 2) A hollow fiber made of a microporous membrane having an outer diameter of 236 µm and a wall thickness of 33 µm in the same manner as in Example 1, except that the atmosphere temperature for heat setting was 215 ° C and the relaxation ratio during heat setting was slightly increased. Was prepared. (Comparative Example 1) A double circular tube spinning nozzle was used to extrude a polypropylene resin melted at 235 ° C into a hollow strand shape while flowing nitrogen at a melt flow rate of 6 g / min. The spool was wound up by a spinning draft 770 while blowing a breeze to cool and solidify.
Then, the hollow strand wound on a spool is
The heat treatment was performed in an atmosphere at 0 ° C. for about 2 hours. Next, the strand is stretched between rollers at a stretching ratio of 2 times, and continuously relaxed slightly in an atmosphere of about 130 ° C. for about 1 hour.
Heat fixing was performed for 2 seconds to prepare a hollow fiber made of a microporous membrane having an outer diameter of 236 μm and a wall thickness of 30 μm. (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 circular tube spinning nozzle, and a gentle breeze is flowed from the periphery of the spinning tower immediately below the nozzle to solidify the molten strand and take it off with a spinning draft 780, and continuously. After about 3 seconds of heat treatment in an air atmosphere of about 230 ° C., continuous stretching between rollers of about 1.8 is performed continuously, and continuous stretching of 19 times is performed.
In a 5 ° C. atmosphere, heat fix for about 1 second while applying a tension that opposes the shrinkage force, outer diameter 230 μm, wall thickness 32 μm
A hollow fiber comprising a microporous membrane having a slightly dense thin film layer on the outer surface was prepared. Comparative Example 3 Poly 4-methyl-1-pentene polymer was dissolved in cyclohexane heated to about 60 ° C. at about 16 wt%. Next, about 3 [wt%] of ethanol was added to the solution, and the solution was filtered through a stainless steel filter having a pore size of 5 μm and subjected to a demolding method to obtain a dope for preparing a hollow fiber microporous membrane. Ethanol was used as the inner tube liquid of the dope hollow fiber heated to about 50 ° C., passed through air about 30 cm from the hollow nozzle, led to a coagulation bath filled with ethanol, solidified, and wound on a spool. After immersion in methanol for about 24 hours, 8
Drying and heat treatment were performed in a hot air drying oven adjusted to 0 ° C. for about 24 hours. The obtained hollow fiber membrane had a slightly dense layer on the outer surface, and a hollow fiber consisting of a microporous membrane having an outer diameter of 320 μm and a wall thickness of 55 μm was prepared.

Test Example 1 The membrane was examined for oxygen flux, average communicating hole radius, ethanol flux, and porosity. Table 1 shows the results.

[0062]

[Table 1]

(Test Example 2) Examples 1 and 2, Comparative Examples 1 to 3
Using hollow fibers consisting of a microporous membrane prepared in step 2, and knitting the number of hollow fibers by chain knitting using polyester as warp yarns.
Four / cm hollow fiber sheets were formed. This was formed into a laminate of the present hollow fiber sheet as shown in FIG. 1 as a model diagram, and then this laminate was assembled into a square module as shown in FIG. An external perfusion oxygenator having an effective membrane area of about 0.4 m ² was experimentally manufactured.

The performance evaluation was performed by AAMI (ASSOCIATION FOR TH
E ADVANCEMENT OF MEDICAL INSTRUMENTATION) using bovine blood. Fresh cochlear blood which has been subjected to anticoagulation treatment by ACD is subjected to hemoglobin (Hb) with an oxygen saturation of 65%.
Adjusted to 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 the middle 1, the oxygen exchange gas was set to V / Q = 1 (oxygen flow rate / blood flow rate) and the gas exchange performance was measured from 3 in FIG. The results are shown in Table 2.

However, the maximum blood flow rate shown in Table 2 is 12
g / dl of Hb, a blood temperature of 37 ° C., an oxygen saturation of 65%, a BE of 0, and an oxygen content of 45 ml of bovine blood.
/ L (blood flow), and the standard carbon dioxide blood flow uses bovine blood under the same conditions as oxygen,
Shows the maximum blood flow that can reduce its carbon dioxide content by 38 ml / l (blood flow). Note that the maximum blood flow shown in this embodiment is a value after blood is perfused for about 6 hours.

[0066]

[Table 2]

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

[0068]

[Table 3]

* 1; Fire at gas outlet

[0070]

According to the present invention, there is provided a hollow fiber microporous membrane having excellent oxygen and carbon dioxide gas exchange performance and free from leakage of plasma components even during long-term use, and an artificial lung incorporating the same. Can be.

[Brief description of the drawings]

FIG. 1 is a model diagram showing a configuration example of an artificial lung according to the present invention.

FIG. 2 is a model diagram showing a laminated state of a cord-like hollow fiber sheet showing a configuration example of the present invention.

[Explanation of symbols]

 1: blood inflow / outflow 2: blood inflow / outflow 3: gas inflow / outflow 4: gas inflow / outflow 5: hollow fiber membrane sheet laminate 6: hollow fiber membrane sheet 7: hollow fiber membrane sheet warp

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) // D01F 6/04 D01F 6/04 C F term (Reference) 4C077 AA03 BB06 KK11 LL05 LL17 LL22 LL23 NN10 PP08 4D006 MA01 MA22 MB03 MB06 MB10 MC22X NA21 NA62 NA66 PB62 PB64 PB67 PC48 4L035 AA09 BB31 BB40 BB55 BB89 BB91 CC02 CC07 CC13 DD03 DD07 DD14 FF01 FF10 MA06

Claims (4)

[Claims] 1. An oxygen gas flux of 10 × 10^-Five~ 5
00 × 10^-Five[Cm ^Three(STP) / cm^Two/ Sec / cm
Hg] and the ethanol flux is 2 to 80 [ml
/ Min / m^Two] And an average pore radius of 0.008 to 0.
Hollow fiber made of a hydrophobic material having a communication hole of 07 μm
Microporous membrane. 2. The hollow fiber microporous membrane according to claim 1, wherein the hydrophobic material is a poly (4-methylpentene-1) -based polymer. 3. The hollow fiber microporous membrane according to claim 1, wherein the hollow fiber microporous membrane is a membrane produced by a melt spinning method. 4. A membrane oxygenator incorporating the hollow fiber microporous membrane according to claim 1.