JP2000084369A - Hallow fiber membrane type gas-liquid gas exchanging device and gas exchange - Google Patents

Abstract

PROBLEM TO BE SOLVED: To make the subject device most suitable for an oxygenator capable of remarkably improving the gas exchanging efficiency, requiring excellent oxygen supply capacity and excellent carbon dioxide removing capacity from blood and requiring to be small sized, low in priming quantity and low in pressure loss of blood flow. SOLUTION: An external circulation type hollow fiber membrane type gas- liquid gas exchanging device, which is formed by using a hollow fiber membrane sheet formed by arranging hollow fiber membranes 5 having 150-390 μm outside diameter substantially in parallel at 120-280 μm interval, laminating so that the equivalent diameter (Dv) calculated by Dv=4×(the whole space volume occupied by the sheet laminated body)/(the whole effective outside surface area) is 165-325 μm and incorporating in a housing, and a gas exchanging method are provided.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention is used as an external perfusion type gas-liquid gas exchange device using a hollow fiber membrane. For example, as an industrial application, a building air conditioner for deoxidizing water for a boiler and preventing corrosion of piping. It is used for deaeration of service water, deaeration of ultrapure water used for manufacturing semiconductors, deaeration of ion exchange water, deaeration of reverse osmosis membrane supply water, deoxygenation and decarbonation gas of power generation water. It is also used in the food industry for producing beer and sake, degassing water for food production, and the like. further,
INDUSTRIAL APPLICABILITY The present invention is used as a medical application for deaeration of a filling solution of a dialysis module, deaeration of water for injection, and the like, and is particularly suitably applicable to an artificial lung for reviving a patient's blood in extracorporeal blood circulation such as during cardiac surgery.

[0002]

2. Description of the Related Art Various types of artificial lungs have been used as replacements or aids for living lungs during open heart surgery or long-term respiratory assistance. These artificial lungs substitute for the gas exchange function of supplying oxygen to blood and removing carbon dioxide among the functions of a living lung. At present, hollow fiber membrane-type artificial lungs have become the mainstream, and are roughly classified into two types. One is a so-called internal perfusion type artificial lung that performs gas exchange by flowing blood inside the hollow fiber, and the other is to perform gas exchange by bringing blood into contact with the outside of the hollow fiber and flowing oxygen mixed gas inside the hollow fiber. This is a so-called external perfusion type artificial lung. The external perfusion type oxygenator is capable of suppressing the pressure loss of the blood flow to a low level, has excellent gas exchange efficiency, and is becoming the mainstream of the hollow fiber membrane type oxygenator.

For example, in Japanese Patent Publication No. 5-201111, a gas-permeable hollow fiber arranged in a sheet shape is wound around a porous core,
Oxygen passes through the inside of the hollow fiber, blood flows outside the hollow fiber,
An oxygenator for performing gas exchange is disclosed.

In Japanese Patent Publication No. Hei 4-2066, adjacent hollow fibers are wound in a circular shape so as to intersect with each other to form a circular hollow fiber layer having a hollow portion at the center thereof. The filling rate of the hollow fibers in the fiber layer is 0.45
An oxygenator with a ０．８0.80 is disclosed.

[0005] Japanese Patent Publication No. 6-96098 discloses that the density of warp and the thickness of a sheet forming a hollow fiber sheet in an artificial lung in which hollow fiber sheets are laminated and incorporated in a housing are set to specific values, and the sheet thickness is reduced. An artificial lung in which channeling and stagnation of blood is suppressed by setting the product of the hollow fiber density and the lamination density of the sheet to a specific value range value calculated based on the outer diameter of the hollow fiber is disclosed.

Japanese Patent Publication No. Hei 7-98061 discloses that in an artificial lung in which a laminate of cord-like hollow fiber sheets is incorporated in a rectangular cylindrical housing, the blood flow rate per unit cross-sectional area perpendicular to the blood flow direction is 50 mL /. An artificial lung in which channeling and stagnation of blood flow are suppressed by maintaining a relationship of ΔP / T · I · n ≦ 1 when a pressure loss at min / cm 2 is ΔP is disclosed.

[0007] Usually, a required performance required for a gas-liquid gas exchange device is an excellent gas exchange capability. In particular, an artificial lung for medical use is required to have an excellent ability to supply oxygen to blood and an excellent ability to remove carbon dioxide from blood. In addition to this, the oxygenator is required to have a small burden on the living body to the patient, the membrane area in direct contact with the blood is small, the size is small, the priming amount of the blood is small, and the pressure loss of the blood flow is small. Is required not to cause blood damage.

It is widely known that the gas exchange performance of a membrane oxygenator is rate-limiting at the blood-side membrane, and various structures of the oxygenator are used to destroy the blood-side membrane as much as possible. It is being actively studied.

[0009] In recent years, research and development of a hollow fiber membrane external perfusion type artificial lung capable of suppressing pressure loss of blood flow and improving gas exchange capacity per unit membrane area have been actively conducted and commercialized. It is getting. However, in the conventional technology, the technical elements required for improving performance, particularly for efficiently destroying the blood-side membrane and improving its gas exchange efficiency, are unclear, and as a result, the gas exchange efficiency is reduced. A satisfactory oxygenator has not yet been developed.

[0010]

The present inventors have made intensive studies on the optimal design of an external perfusion type hollow fiber membrane type gas-liquid gas exchange device in which hollow fiber membrane sheets are laminated and incorporated in a housing, and are surprising. In particular, using a hollow fiber having a specific range of outer diameter, using a hollow fiber sheet having a specific hollow fiber membrane interval in which hollow fiber membranes are arranged substantially in parallel, and specifying the hollow fiber membrane sheet The gas exchange efficiency can be significantly improved and the pressure loss of the liquid flow (blood flow) can be suppressed to an extremely low value as compared with the conventional one by laminating so as to have an equivalent diameter and incorporating it into the housing. An invention relating to a perfusion type hollow fiber membrane type gas-liquid gas exchange device is provided.

[0011]

The present invention provides (1) an outer perfusion type hollow fiber membrane type gas-liquid gas exchange device, wherein the outer diameter of the hollow fiber membrane is 150 μm to 390 μm and the interval between the hollow fiber membranes is Using a hollow fiber membrane sheet in which hollow fiber membranes of 120 μm to 280 μm are arranged substantially in parallel, (Equation 1) Dv = 4 × (total space volume occupied by the sheet laminate) / (total of hollow fiber membranes) An external perfusion type hollow fiber membrane type gas-liquid gas exchange device, which is incorporated in a housing in a state where the equivalent diameter calculated by the effective external surface area is 165 μm to 325 μm, 2) The outer diameter of the hollow fiber membrane is from 180 μm to 250 μm
m, and the hollow fiber interval of the hollow fiber sheet is 150 μm or more.
(1) The gas-liquid gas-exchange device of (1), wherein the hollow fiber membrane has an oxygen permeation rate of 260 μm and Dv of 215 μm to 320 μm. 5 × 10-5 [cm3 (STP) / cm2 /
s / cmHg] to 350 x 10-5 [cm3 (STP) /
cm2 / s / cmHg], which is a hollow fiber asymmetric membrane made of a poly (4-methylpentene-1) -based resin, wherein the gas-liquid gas exchange device according to (1) or (2) is used. (4) In the external perfusion type hollow fiber membrane type gas-liquid gas exchange device, the outer diameter of the hollow fiber membrane is 150 μm to 39 μm.
0 μm, and the interval between the hollow fiber membranes is 120 μm to 280 μm.
m, using a hollow fiber membrane sheet in which hollow fiber membranes are arranged substantially in parallel, (Equation 1) Dv = 4 × (total space volume occupied by the sheet laminate) / (total effective volume of the hollow fiber membrane) Using an external perfusion type hollow fiber membrane type gas-liquid gas exchange device characterized in that it is incorporated in a housing in a state where the equivalent diameter calculated by the following formula is 165 μm to 325 μm. A gas-liquid gas exchange method characterized in that gas exchange is performed by crossing and flowing substantially vertically through the laminated hollow fiber membrane sheets.

Here, the equivalent diameter (Dv) is defined by (Equation 1).
Dv = 4 × (total space volume occupied by the sheet laminate) / (total effective external surface area of the hollow fiber membrane), wherein the molecule of the formula is calculated from the volume occupied by the hollow fiber membrane sheet laminate This is the volume of the space obtained by subtracting the volume occupied by the thread membrane.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION The typical and best modes of the embodiment of the present invention will be specifically shown in the examples described later, and the outline thereof is as follows.

The outer diameter of the hollow fiber of the present invention is from 150 μm to 39 μm.
The outer diameter may be 0 μm, and an appropriate outer diameter can be selected depending on the application.

The thickness of the hollow fiber membrane is 15 μm to 80 μm.
m is preferred. The film thickness governs the strength and durability of the hollow fiber membrane, and the optimum film thickness can be selected for the material constituting the membrane, the structure of the membrane, and the application of the present invention. Generally, the smaller the outer diameter, the thinner the film thickness required for maintaining strength and durability.

Surprisingly, in the present invention, the gas exchange efficiency can be improved as the outer diameter of the hollow fiber is reduced within the range of the present invention, even if the filling rate of the hollow fiber in the membrane module is the same. Furthermore, although the durability and strength of the hollow fiber can be dramatically improved by reducing the diameter, it is preferable. However, when the outer diameter of the hollow fiber is 150 μm or less, handling at the time of manufacturing a membrane module becomes difficult.

When the oxygen-containing gas flows inside the hollow fiber and is preferably used as an artificial lung for gas exchange with blood flowing outside the hollow fiber, the gas exchange efficiency is increased and the gas exchange capacity is sufficient with a small membrane area. Although a small-diameter hollow fiber is preferable in order to realize a small-sized artificial lung module with a small amount of blood priming, an inner diameter is necessarily narrowed by reducing the outer diameter of the hollow fiber.

The gas pressure on the gas phase side must be kept sufficiently lower than the pressure on the blood side so as to prevent air bubbles from being generated on the blood side. Also, during clinical use, a considerable amount of water vapor permeates into the hollow fiber from the blood side, and depending on the use conditions, this water vapor condenses at the outlet of the artificial lung gas, the hollow fiber membrane is closed, and the gas exchange capacity with time increases. May cause a significant decline. To prevent these phenomena, the inside diameter of the hollow fiber needs to be a certain thickness.

Preferably, the outer diameter is 180 for use in artificial lungs.
It is in the range of μm to 250 μm, and the inner diameter is preferably 140 μm or more. Especially for applications that can be used continuously for several days to several weeks, such as ECMO and PCPS applications,
The outer diameter of the hollow fiber is preferably 200 μm to 250 μm, and the inner diameter is preferably 150 μm or more.

The present invention is also characterized in that hollow fiber membrane sheets in which the hollow fiber membranes are arranged in parallel at equal intervals on at least the same lamination surface are stacked and used in a housing. .

There is no limitation on the method of forming the hollow fiber membrane sheet. For example, a monofilament or multifilament yarn made of polyester, polyamide, polyurethane, polyacrylonitrile, or the like is used as a warp, and hollow fiber membranes serving as wefts are braided at equal intervals. By doing so, it can be formed preferably. As a method of industrially forming a hollow fiber membrane sheet, for example, Russell knitting and the like are known.

The thickness of the warp is preferably 5 to 30 denier. In particular, a 10 to 25 denier multifilament made of polyester is particularly preferable because it has excellent flexibility and strength, has little change with time, and does not damage the hollow fiber during sheet formation and with time.

In the present invention, the interval between the hollow fiber membranes of the hollow fiber membrane sheet is in the range of 120 μm to 280 μm, and (Equation 1)
The equivalent diameter Dv of the laminated hollow fiber sheet represented by
It is characterized by being in the range of 5 μm to 325 μm. As a result, it is possible to realize an external perfusion type gas-liquid gas exchange device that simultaneously satisfies high gas exchange efficiency and low liquid pressure loss.

The number of laminated hollow fiber membrane sheets is preferably 20 or more, more preferably 50 or more, and most preferably 70 or more. The gas exchange efficiency by the external perfusion method according to the present invention can be significantly improved by reducing the interval between the hollow fiber membranes of the hollow fiber membrane sheet and decreasing Dv.
When m or less and / or Dv is 165 μm or less, the pressure loss of the liquid flow becomes extremely large, and the range of development to various industrial practical uses is limited.

The hollow fiber membrane interval and Dv of the sheet can be appropriately selected within the scope of the present invention according to the required performance of the application of the gas-liquid gas exchange device.

For example, in the production of ultrapure water for semiconductor production used for degassing of dissolved gas from water, a sub flow that requires a relatively low processing flow rate and a high degree of deaeration with a dissolved oxygen concentration of 1 ppb or less is required. For the purpose of application in a system, the interval between the hollow fibers is preferably 120 μm to 260 μm,
Dv is preferably from 165 μm to 260 μm.

In addition, the concentration of dissolved oxygen in the production of power water is 5%.
For applications requiring a large amount of water with a relatively low degassing level of about 0 PPB, the interval between the hollow fiber membranes of the hollow fiber sheet is 200 μm.
280 μm is preferable, and Dv is 200 μm to 325 μm.
m is preferred.

When used for an artificial lung for medical use, the interval between hollow fibers of the hollow fiber membrane sheet is preferably 150 μm to 260 μm, and Dv is 215 μm to 325 μm because low blood flow pressure loss and high gas exchange efficiency are required. Preferably, there is.

In applications such as PCPS and ECMO which are premised on long-term continuous use for several days in artificial lung applications, the interval between hollow fibers is 180 μm to 260 m, and D
v is preferably 230 μm to 325 μm.

The hollow fiber membrane applied to the present invention is not particularly limited as long as it has appropriate durability, mechanical strength and gas permeability, and there are no particular restrictions on its material, manufacturing method, membrane structure, and the like. Polyolefin resins such as polypropylene, polybutylene and poly (4-methylpentene-1), silicone resins such as dimethylsiloxane, various fluororesins such as polytetrafluoroethylene and perfluoroalkoxy fluororesins, and various polyimide resins are preferable. Can be used for

As the membrane structure of the hollow fiber membrane, various membranes having a so-called sandwich structure in which a thin film such as a microporous membrane, a homogeneous membrane, a heterogeneous membrane, a composite membrane, or a urethane is sandwiched between microporous membranes can be applied.

The method for producing these films is not limited, and for example, films produced by a melting method, a wet method, a dry-wet method and the like can be applied.

In particular, a heterogeneous hollow fiber membrane having a dense layer on the membrane wall made of a poly (4-methylpentene-1) -based resin has excellent permeability for gases such as oxygen, nitrogen and carbon dioxide, and is hydrophobic. It has high water vapor barrier properties and is most suitable for industrial and medical gas-liquid gas exchange equipment. The formation position of the dense layer of the hollow fiber membrane is not particularly limited, and may be formed on the outer surface and / or the inner surface of the hollow fiber membrane. However, the dense layer is particularly formed on the outer surface of the hollow fiber membrane. A hollow fiber membrane made of a poly (4-methylpentene-1) resin has a low complement activity of blood, has excellent affinity with blood, has no long-term plasma leak, and has no deterioration in gas exchange performance. It is most suitably applied for external perfusion type artificial lung. The poly (4-methylpentene-1) -based resin has a gas permeability of about 10 times that of the material itself as compared with polypropylene generally used for artificial lungs, and has essentially communicated with the hollow fiber membrane wall. Compared with a microporous polypropylene membrane in which gas exchange is performed only in the microporous portion, gas exchange can be performed on the entire membrane surface, which is extremely preferable.

Poly (4-methylpentene) obtained by a melting method
1) Regarding a heterogeneous film using a base resin as a film material, for example, Japanese Patent Application No. 5-6656 and Japanese Patent Publication No. 7-12134
No. 0 discloses this.

A heterogeneous film made of poly (4-methylpentene-1) -based resin, which forms a film by using a solvent such as a wet method or a dry-wet method and utilizing the phase separation of a resin solution, is used. For example, “Journal of Membrane Science 118 (19
96) 49-61 ”and“ POLYMER, 1989, Vol 30, December base
2279-2282 "etc., and can be easily produced by a known spinning method. In the present invention, the oxygen transmission rate of the hollow fiber membrane which is an index of gas permeability of the membrane is 5 × 10 5 −
5 [cm3 (STP) / cm2 / s / cmHg] to 350
× 10-5 [cm3 (STP) / cm2 / s / cmHg]
It is characterized by applying a heterogeneous film made of poly (4-methylpentene-1) -based resin as a film material, and selects a film having an optimum gas permeation characteristic within the scope of the present invention according to an application field. it can.

When applied to an artificial lung, the oxygen transmission rate of the membrane is preferably 10 × 10 −5 [cm 3 (STP) / cm 2
/ S / cmHg] to 350 x 10-5 [cm3 (STP)
/ Cm2 / s / cmHg], and more preferably 2
5 × 10 −5 [cm3 (STP) / cm2 / s / cmH
g] to 350 × 10 −5 [cm 3 (STP) / cm 2 / s
/ CmHg]. Oxygen transmission rate is ASTM D14
This is a value measured according to No. 34.

The oxygen transmission rate of the membrane is 5 × 10 −5 [cm 3
(STP) / cm2 / s / cmHg] or less, particularly, the ability to remove carbon dioxide from blood is inferior, and the required membrane area is increased, making it difficult to realize a compact oxygenator.

Oxygen permeation through a heterogeneous membrane made of a poly (4-methylpentene-1) resin having a large effective membrane area for gas exchange and applied to the hollow fiber membrane type gas-liquid gas exchange apparatus of the present invention. The upper limit of the speed is 350 × 10-5 [cm3
(STP) / cm2 / s / cmHg].

Although there is no particular inconvenience due to the high oxygen permeation rate of the membrane itself, a further increase in the oxygen permeation rate of the membrane is caused by the occurrence of a so-called pinhole, which is a large pore diameter penetrating the membrane wall that allows plasma to leak during membrane formation. Results in a greater likelihood of When applied to an artificial lung, the denseness of the dense layer of the membrane is preferably not more than 0.04 μm at the maximum, and the area aperture ratio is preferably not more than 3%. The present invention also provides a method for performing gas exchange between a gas and a liquid with high efficiency while keeping the liquid flow pressure loss extremely low. That is, in the external perfusion type hollow fiber membrane type gas-liquid gas exchange device, the outer diameter of the hollow fiber membrane is 150 μm to 390 μm, and the interval between adjacent hollow fiber membranes is 120 μm to 280 μm.
m, wherein the hollow fiber membrane sheets in which the hollow fiber membranes are arranged substantially parallel to each other so as to have a Dv of 165 μm to 325 μm are incorporated in the artificial lung housing in a state of being laminated. It is characterized in that gas is exchanged by using a membrane-type gas-liquid gas exchange device and flowing liquid substantially perpendicularly across the surface of the laminated hollow fiber membrane sheet.

By making the liquid into a cross flow with the hollow fiber membrane sheet, the efficiency of stirring the liquid flow is increased, and thus the liquid-side boundary film for the gas movement, which is the rate-limiting gas-liquid system gas exchange efficiency. Can be efficiently reduced. Thereby, extremely high gas exchange efficiency can be realized.

Surprisingly, according to the present invention, the degree of improvement in the efficiency of gas transfer between the gas and the liquid through the membrane as the flow rate of the liquid increases can be specifically increased. As a result, the gas exchange ability is greatly improved. It is presumed that this is because the present invention can greatly increase the liquid flow velocity dependence of thinning the liquid-side gas transfer film layer. Of course, this does not limit the invention in any way.

By laminating the hollow fiber membrane sheets as described in the present invention, the liquid flow pressure loss in the cross flow is compared with the liquid flow pressure loss when the liquid flows in parallel to the direction of the hollow fibers in the hollow fiber membrane sheet. And extremely low. Thereby, a cross-fouro type gas-liquid gas exchange device can be easily configured.

In practicing the present invention, models of some preferred embodiments of the external perfusion type hollow fiber membrane type gas-liquid gas exchange apparatus according to the present invention are shown in FIGS. 1, 2 and 3.

FIG. 1 is a model diagram of an external perfusion type gas-liquid gas exchange device in which a hollow fiber membrane sheet is wound around a porous pipe and incorporated in a cylindrical housing. Arrows shown by solid lines in the figure schematically show the flow of the liquid. In the figure, reference numeral 6 denotes a resin sealing portion, which uses a urethane resin and / or an epoxy resin and / or a silicone resin to support and fix the hollow fibers to the housing in a liquid-tight manner. The hollow fiber membrane has an opening inside the outside of both sealing resins. When used as an artificial lung, blood is poured into a perforated pipe around which a hollow fiber is wound from 1 in the figure. The blood mainly flows uniformly from the porous portion in the radial direction of the hollow fiber wrapper, flows through the space between the sheet wrapper and the housing, and is discharged from 2 in the figure. In the meantime, from FIG. 3, for example, an oxygen mixed gas is flowed into the inside of the hollow fiber at an appropriate flow rate to supply oxygen to the blood via the hollow fiber membrane and remove carbon dioxide from the blood. If necessary, for example, a heat exchange mechanism such as a fin type or a tube type II can be provided inside and / or outside the perforated pipe. The model diagram of the external perfusion type gas-liquid gas exchange device shown in FIG. 3 is characterized in that the central perforated pipe is divided into two parts by a central partition. In the figure, the liquid poured from 1 flows radially in a cross flow from the porous portion of the porous pipe through the hollow fiber interval of the hollow fiber membrane sheet winding, crosses the hollow fiber membrane sheet again, and flows into the porous pipe. It flows out from the middle 2.

When used as an artificial lung, it is possible to exchange oxygen by injecting an oxygen mixed gas into the inside of the hollow fiber from 3 in FIG. When producing degassed water or the like for industrial use, the inside of the hollow fiber can be depressurized by a vacuum pump or the like from 3 and / or 4 in FIG. 3 to degas the liquid.

The gas-liquid gas exchange device having the basic structure shown in the model in FIG. 3 can increase the substantial sheet thickness in which liquid flows crossing the sheet, and can increase the liquid flow velocity.
As a result, the stirring effect on the liquid side can be improved, the liquid-side boundary film can be further thinned, and a significant improvement in gas exchange efficiency can be expected.

FIG. 4 is a model diagram of a gas-liquid gas exchange device having a shape in which hollow fiber membrane sheets are laminated and incorporated in a rectangular cylindrical housing. When used as an artificial lung, gas can be exchanged by pouring blood from FIG. 1 and flowing blood perpendicularly to the lamination surface of the hollow fiber sheet. If necessary, a heat exchange mechanism can be provided on the blood entry side.

[0048]

Example 1 Hollow fiber outer diameter 260 μm, inner diameter 205 μm, oxygen transmission rate of the membrane 40 × 10 −5 [cm 3 (STP) / cm 2 / s / c]
mHg], using a hollow fiber heterogeneous membrane made of a poly (4-methylpentene-1) -based resin as a material, and using a 20-denier polyester multifilament as a warp yarn and setting the number of hollow fibers to 21 / cm. 227 μm spacing
Was formed by Russell knitting. This hollow fiber membrane sheet was folded and laminated as shown in the model diagram in FIG. 5 so that the equivalent diameter Dv became 320 μm. Next, this hollow fiber sheet laminate is assembled into a rectangular tube type module as shown in the model diagram in FIG. 4, and both ends of the hollow fiber are sealed with a polyurethane resin by a known centrifugal sealing method. The end face was cut so as to open. Further, both sides of the sheet laminate and the side of the housing are bonded using urethane resin so that liquid (blood) does not leak from the side of the folded sheet, and the effective cross-sectional area through which blood passes is about 50 cm2 and the effective membrane area ( A rectangular tube type module having a hollow fiber outer diameter of about 1.2 m2 was prepared. AAMI (ASSOCIATION FOR THE ADOVANCEMENT OF
MEDICAL INSTRUMENTATION), oxygen saturation: 65
%, Hemoglobin: 12 g / dL, excess base: 0 mEq /
L, using a bovine blood adjusted to a partial pressure of dissolved carbon dioxide of 45 mmHg and a temperature of 37 ° C., pouring the bovine blood from 1 in FIG. 4 and simultaneously converting the oxygen gas from V / Q = 1 (gas flow rate /
(Gas flow rate), the gas exchange performance of the module poured into the hollow fiber was measured. Standard O ₂ (oxygen) blood flow of 6.5
L / min, and the standard CO ₂ (carbon dioxide) blood flow rate was 5.8 L / min. The blood flow pressure loss when the blood flow through the module is 6 L / min is 48 mm.
Hg.

Here, the standard O ₂ blood flow rate means that the blood containing 12 g / dL of Hb at 37 ° C., 65% O ₂ saturation, and 0 excess base (BE) is passed through an artificial lung. It indicates the maximum blood flow at which the O ₂ content can be increased by 45 mL / L (standard condition), which means that the standard CO ₂ blood flow contains 12 g / dL of Hb at 37 ° C. and an O ₂ saturation of 6
5% excess base (BE) 0 blood shows the maximum blood flow rate at which its CO ₂ content can be reduced by 38 mL / L (standard condition) by passing through an artificial lung.

Example 2 O.D. 225 μm, I.D. 170 μm, oxygen permeation rate of membrane 5
20 denier polyester multifilament using a hollow fiber membrane heterogeneous membrane made of 4 × 10-5 [cm3 (STP) / cm2 / s / cmHg] poly (4-methylpentene-1) -based resin The number of hollow fibers driven into the warp is 2
A hollow fiber membrane sheet having 4 fibers / cm and a hollow fiber interval of 200 μm was formed by Russell knitting. This sheet was laminated so as to have an equivalent diameter of 280 μm, and a rectangular tube-shaped module having an effective area of about 50 m 2 for passing blood and an effective winding area of 1.2 m 2 was prepared as in Example 1. The gas exchange performance of the module was measured using bovine blood in the same manner as in Example 1. As a result, the standard O ₂ blood flow was 15.
3 L / min and standard CO ₂ blood flow of 13 L / m
was in. The blood flow through the module is 6L
The blood flow pressure loss at / min was 52 mmHg.

Example 3 The outer diameter was 205 μm, the inner diameter was 150 μm, and the oxygen permeation rate of the membrane was 67 × 10 −5 [cm 3 (STP) / cm 2 / s / cmHg].
Using a hollow fiber membrane heterogeneous membrane made of poly (4-methylpentene-1) -based resin described above, using 20 denier polyester multifilaments as warp yarns and setting the number of hollow fibers to be about 28 / cm, Approximately 158μm
The hollow fiber membrane sheet was prepared by Russell knitting.
This sheet is laminated so that the equivalent diameter is 215 μm, and the effective area through which blood passes is about 50 as in Example 1.
A square tube type module having an effective winding area of 1.2 m 2 in cm 2 was prepared. As in Example 1, the gas exchange capacity of the module was measured using bovine blood. Blood flow is 16L /
At the time of min, the oxygen transfer rate was 48 mL / min, and the standard O ₂ blood flow rate could not be measured. The standard CO ₂ blood flow was 15.2 mL / min. When the blood flow through the module is 6 L / min, the blood pressure loss is 120
mmHg.

Example 4 Hollow made of poly (4-methylpente-1) resin having an outer diameter of 330 μm, an inner diameter of 220 μm, and an oxygen permeation rate of the membrane of 72 × 10 −5 [cm 3 (STP) / cm 2 / cmHg]. A hollow fiber sheet was formed by Russell knitting using a non-homogeneous fiber membrane, a multifilament made of 20 denier polyester as a warp, the number of hollow fibers being driven at 21 fibers / cm, and the interval between hollow fibers of about 154 μm. This hollow fiber sheet is formed into a cylindrical pipe having a diameter of about 2 cm and having a large number of holes as shown in the model diagram in FIG. 1 and the clearance at the beginning of winding of the pipe and the hollow fiber sheet is about 0.2 cm. It was wound spirally so that the equivalent diameter of the occupied portion was 290 μm. Next, this hollow fiber sheet roll is incorporated into a cylindrical housing having an inner diameter of about 7.5 cm, both ends of the module are sealed by a known centrifugal sealing method using a polyurethane resin, and then both ends of the module are cut to form a hollow. The inside of the thread membrane was opened. The effective length of the hollow fiber sheet winding is about 6 cm, and the clearance between the outer periphery of the hollow fiber sheet winding and the cylindrical housing is about 0.5 cm.
cm and a cylindrical module having a hollow fiber effective membrane area of 1.2 m2.

Bovine blood was prepared in the same manner as in Example 1, and 1 in FIG.
At the same time, the cow gas is poured and oxygen gas
At / Q = 1, the gas exchange performance was measured by pouring inside the hollow fiber. As a result, the standard O ₂ blood flow rate was 7.8 L / min, and the standard CO ₂ blood flow rate was 6.3 L / min.

In the model experiment, the blood flowing out of the central perforated tube flows through the hollow fiber wound body in the radial direction almost vertically and reaches the gap between the hollow fiber sheet wound body and the outer housing of the module and flows out from 2 in FIG. I confirmed the thing.

Example 5 Using the hollow fiber membrane sheet used in Example 2, 9 in FIG.
As shown in the model diagram, in a cylindrical pipe having a large number of holes on the outer periphery provided with a partition at the center, the clearance at the beginning of winding of the pipe and the hollow fiber sheet is about 0.2 cm, and the hollow fiber sheet occupies The equivalent diameter of the part is 265μm
And wound it in a spiral. Next, this hollow fiber sheet winding body is assembled into a cylindrical housing having an inner diameter of about 7 cm, both ends of the module are sealed by a known centrifugal sealing method using a polyurethane resin, and then both ends of the module are cut to form a hollow fiber. The inside was opened.
A cylindrical module having an effective length of a hollow fiber sheet roll of about 6 cm and an effective area of a hollow fiber membrane of 1.2 m2 was prepared.

Bovine blood was adjusted in the same manner as in Example 1, and 1 in FIG.
At the same time, the cow gas is poured and oxygen gas
At / Q = 1, the gas exchange performance was measured by pouring inside the hollow fiber. At a blood flow rate of 16 mL / min, the oxygen transfer rate to the blood is about 50 mL / min, and the CO ₂ removal rate is about 4
It was 2 mL / min, and both oxygen and carbon dioxide were so large that the standard blood flow could not be measured. In addition, blood flow 6
The blood flow pressure loss at L / min was 77 mmHg.

As shown by the solid arrows in FIG. 3 in the model experiment, the blood flowing out of the central perforated tube flows almost vertically through the hollow fiber sheet winding in the radial direction, and the blood flows out of the hollow fiber sheet winding. It was confirmed that the space reached the gap with the outer housing of the module, and then the wound hollow fiber membrane sheet flowed almost vertically to the perforated pipe side and flowed out from 2 in FIG.

Example 6 A hollow fiber made of a poly (4-methylpente-1) resin having a hollow fiber outer diameter of 180 μm, an inner diameter of 120 μm, and an oxygen permeation rate of 25 × 10 −5 [cm 3 / Cm 2 / cmHg] was used. Using a heterogeneous yarn membrane, a hollow fiber membrane sheet was prepared in which multifilaments made of 20 denier polyester were used as warp yarns and the number of hollow fibers was 31 / cm and the interval between hollow fibers was about 147 μm. This sheet is wound around a pipe having a nominal diameter of about 3 cm having a large number of holes opened on the outer periphery so that the equivalent diameter of the sheet winding becomes 190 μm, and a sheet winding having a membrane area based on the outer diameter of the hollow fiber membrane of 90 m2 is wound. Created. This sheet wound body is loaded into a module case of about 50 cm in length made of a hard vinyl chloride pipe having a nominal diameter of 25 cm, and a urethane resin and an epoxy resin are used as a sealing resin, as shown in FIG. 1 by a known centrifugal sealing method. An industrial external perfusion module was created as shown in the model diagram. 3 in FIG.
And 4 were connected to an oil rotary vacuum pump having a pumping speed of about 48 m3 / hr, and the vacuum pressure inside the hollow fiber membrane was set to about 23 mmH.
g, water saturated with air at 25 ° C. from 1 in FIG. 1 was poured. The dissolved oxygen concentration of the degassed water flowing out from 2 in FIG. 1 was measured by a polarographic oximeter. The water degassed to a dissolved oxygen concentration of about 1 ppb
L / min could be obtained.

Comparative Example 1 Outer diameter 260 μm, inner diameter 205 μm, oxygen permeation rate 3 of membrane
0 × 10-5 [cm3 (STP) / cm2 / s / cmH
g], using a hollow fiber heterogeneous membrane made of poly (4-methylpentene-1) -based resin as a raw material, and using 30 denier polyester multifilaments as warp yarns and forming hollow fibers into 22 / cm hollow fibers. A hollow fiber sheet having an interval of 204 μm was formed by Russell knitting. This sheet was laminated so that the equivalent diameter Dv became 360 μm, and the effective cross-sectional area through which blood passed was 50 cm 2 as in Example 1.
Thus, a prismatic module having an effective membrane area of 1.2 m 2 (based on the outer diameter of the hollow fiber) was prepared.

Gas exchange performance was measured using bovine blood in the same manner as in Example 1. As a result, the standard O ₂ blood flow was 4.2 L /
min, and the standard CO ₂ blood flow rate is 3.8 L / min.
Met. The blood flow through the module is 6L / mi
The blood pressure loss at the time of n was 46 mmHg.

Comparative Example 2 The outer diameter is about 260 μm, the inner diameter is about 200 μm, and the oxygen transmission rate of the membrane is about 400 × 10 −5 [cm 3 / cm 2 / s / cmHg].
Using a hollow fiber microporous membrane made of polypropylene resin as a material, the number of hollow fibers driven is 18 / multifilament made of 30 denier polyester.
cm, and a hollow fiber sheet having a hollow fiber interval of 313 μm was formed. This sheet was laminated so that the equivalent diameter Dv was 275 μm, and a rectangular tube type module having an effective sectional area of about 50 cm 2 through which blood passed and an effective membrane area of 1.2 m 2 was prepared as in Example 1. The gas exchange performance of the module was measured using bovine blood in the same manner as in Example 1. As a result, the standard O ₂ blood flow rate was 2.9 L / min, and the standard CO ₂ blood flow rate was 2.5 L / min. The blood flow pressure loss when the blood flow through the module was 6 L / min was 46 mmHg.

Comparative Example 3 The outer diameter is about 380 μm, the inner diameter is about 330 μm, and the oxygen transmission rate of the membrane is about 700 × 10 −5 [cm 3 / cm 2 / s / cm Hg].
The hollow fiber microporous membrane made of polypropylene polymer is used, and the number of hollow fibers to be driven is 17 using multifilaments made of 30 denier polyester as warp yarns.
The hollow fiber sheet was formed with the number of fibers / cm and the interval between the hollow fibers being about 220 μm. This hollow fiber sheet was laminated so that the equivalent diameter Dv was about 470 μm, and a rectangular tube type module having an effective area for blood passage of about 50 cm 2 and an effective winding area of 1.2 m 2 was prepared as in Example 1. . The gas exchange performance of the module was measured using bovine blood in the same manner as in Example 1. As a result, the standard O ₂ blood flow was 2.3 L / mi.
n, and the standard CO ₂ blood flow was 2.2 L / min. The blood flow rate through the module is 6 L / min.
At that time, the blood flow pressure loss was 42 mmHg.

[0063]

According to the present invention, in an external perfusion type gas-liquid gas exchange device in which hollow fiber membrane sheets are stacked and assembled into a module, the outer diameter of the hollow fiber membrane and the hollow fiber membrane of a sheet in which hollow fibers are arranged substantially in parallel are provided. The distance and the equivalent diameter expressed by (Expression 1) Dv = 4 × (total space volume occupied by the sheet laminate) / (total effective outer surface area of the hollow fiber membrane) are defined, and the liquid is crossed over the sheet laminate surface. The gas exchange efficiency of the external perfusion type gas-liquid gas exchange device can be greatly improved by flowing the gas. Particularly, it is most suitable for an artificial lung that requires excellent oxygen supply capacity to blood and excellent ability to remove carbon dioxide from blood, and is required to be small, low in priming amount, and low in blood pressure drop. Applicable to

[0064]

[Brief description of the drawings]

FIG. 1 is a model diagram showing a structure of a cylindrical external perfusion type gas-liquid gas exchange device used in an embodiment of the present invention, and arrows in the figure show a model of a liquid flow.

FIG. 2 is a model diagram showing a laminated state of hollow fiber membrane sheets incorporated in a cylindrical external perfusion type gas-liquid gas exchange device whose model diagrams are shown in FIGS. 1 and 3.

FIG. 3 is a structural model diagram of a cylindrical external perfusion gas exchange device having a partition at the center of a perforated pipe used in an embodiment of the present invention. The arrow in the figure indicates a model of the flow of the liquid.

FIG. 4 is a structural model diagram of an external perfusion type gas-liquid gas exchange device of a rectangular tube type used in the present invention, wherein arrows in the figure indicate models of liquid flow.

FIG. 5 is a model diagram showing a laminated state of hollow fiber membrane sheets incorporated in the rectangular external perfusion type gas-liquid gas exchange device of FIG.

[Explanation of symbols]

 1, 2 Liquid inflow / outflow port 3, 4 Gas inflow / outflow port, deaeration port 5 Hollow fiber membrane 6 Sealing resin part 7 Perforated pipe 8 Hollow fiber membrane sheet warp 9 Perforated pipe

 ──────────────────────────────────────────────────続 き Continued on the front page F-term (reference) 4C077 AA03 AA05 AA25 BB06 CC06 GG02 KK15 KK19 KK23 LL05 LL12 LL13 PP08 PP13 PP16 4D006 GA32 HA02 HA05 HA08 HA19 JA02B JA02Z JA25A JA25B JA25Z MA01 MA06 MA22 MA23 MC22 MC28 MC30 MC58 MC65 NA04 NA05 NA21 PA10 PB02 PB09 PB62 PB64 PC02 PC12 PC31 PC44 PC45 PC48 4D011 AA17 AC10

Claims (4)

[Claims] In an external perfusion type hollow fiber membrane type gas-liquid gas exchange apparatus, the hollow fiber membrane having an outer diameter of 150 μm to 390 μm and an interval between the hollow fiber membranes of 120 μm to 280 μm is substantially used. Using hollow fiber membrane sheets arranged in parallel, the equivalent diameter (Dv) calculated by (Equation 1) Dv = 4 × (total space volume occupied by the sheet laminate) / (total effective external surface area of the hollow fiber membrane) ) Is 165 μm to 325 μm
m. An external perfusion type hollow fiber membrane type gas-liquid gas exchange device characterized in that it is incorporated in a housing in a state of being stacked so as to be m. 2. The hollow fiber membrane has an outer diameter of 180 μm to 250 μm.
And the hollow fiber membrane interval of the hollow fiber membrane sheet is 150 μm.
m to 260 μm, and Dv is 215 μm to 325
The external perfusion type hollow fiber membrane type gas-liquid gas exchange device according to claim 1, characterized in that it is μm. 3. The hollow fiber membrane has an oxygen permeation rate of 5
× 10-5 [cm3 (STP) / cm2 / s / cmHg]
~ 350 × 10-5 [cm3 (STP) / cm2 / s / c
3. The external perfusion type gas-liquid gas exchange device according to claim 1, wherein the device is a hollow fiber heterogeneous membrane made of a poly (4-methylpentene-1) -based resin having a mHg of 3 μm. 4. The external perfusion type hollow fiber membrane-type gas-liquid gas exchange device, wherein the hollow fiber membrane has an outer diameter of 120 μm to 390 μm, and the interval between the hollow fiber membranes is substantially 120 μm to 280 μm. Using hollow fiber membrane sheets arranged in parallel, the equivalent diameter (Dv) calculated by (Equation 1) Dv = 4 × (total space volume occupied by the sheet laminate) / (total effective external surface area of the hollow fiber membrane) ) Is 165 μm to 325 μm
The liquid is crossed substantially perpendicularly to the laminated hollow fiber membrane sheet by using an external perfusion type hollow fiber membrane type gas-liquid gas exchange device incorporated in the housing in a state where the liquid is laminated so as to be m. A gas-liquid gas exchange method characterized by performing gas exchange by flowing air.