JPH03146121A - Hollow fiber membrane and hollow fiber membrane-type breathing simulator using the membrane - Google Patents

Abstract

PURPOSE:To make the effective membrane surface area positive and sufficient and heighten fluid treatment ability by making curling ratio of a porous hollow fiber membrane with which a fluid to be treated is treated in the inside or outside of the membrane wall be 0.1-0.7%. CONSTITUTION:Hollow fiber membranes having curling ratio 0.1-0.7% are prepared and fluids to be treated are treated mutually through a membrane while one fluid to be treated is in the inside or outside and the other fluid to be treated is in the other side of a membrane. About 10000-60000 of said porous hollow fiber membranes 6 and hollow fiber membrane bundles 13 are put in housing 2 in the longitudinal direction to give a hollow fiber membrane-type breathing simulator. Contact of oxygen-containing gas of a fluid to be treated with blown to a gas chamber 9 with blood which is a fluid to be treated and flows in the inside of the hollow fiber membranes 6 from a blood storage space 27 through the membrane walls of the hollow fiber membranes 6 is carried out uniformly in the whole surface areas of the hollow fiber membranes 6 and effective membranes' surface area is attained sufficiently.

Description

Detailed Description of the Invention [Field of Industrial Application 1] The present invention relates to a hollow fiber membrane in which fluid treatment such as gas exchange is performed through a membrane wall, and a hollow fiber membrane oxygenator using the same. It is.

[Prior art] In recent years, in heart surgery, etc., the patient's blood is guided outside the body.
In order to add oxygen to this and remove carbon dioxide gas,
A hollow fiber membrane oxygenator is used to constitute the extracorporeal circulation circuit.

This hollow fiber membrane oxygenator consists of a plurality of hollow fiber membranes bundled and housed in a housing in an AQ, and blood is circulated as a fluid to be treated either inside or outside of the hollow fiber membranes. In this system, an oxygen-containing gas is blown to the other side as a processing fluid, and the gas and liquid are brought into contact with each other through the membrane wall of the hollow fiber membrane, thereby performing the desired gas exchange. Among these hollow fiber membrane oxygenators, the so-called external perfusion type oxygenator circulates blood outside the hollow fiber membrane and blows oxygen-containing gas inside the membrane.
Since the pressure loss in the bloodstream is small, there is no need to install a blood pump at the artificial lung in the circulation circuit, and therefore blood can be drawn into the artificial lung by removing blood only by the drop from the human body. Therefore, it is particularly preferable.

As the hollow fiber membrane used in such a hollow fiber membrane oxygenator, a hydrophobic porous hollow fiber membrane such as polypropylene is mainly used from the viewpoint of gas permeability, mechanical strength, etc.

[Problems to be Solved by the Invention] By the way, in the above-mentioned hydrophobic porous hollow fiber membrane, conventionally, the gap between the hollow fiber membranes is narrow in the housing, and the gap between the hollow fiber membranes is narrow along the axial direction. In a state of no active change, it was laid back and stored away. In this state, when blood flows into the inner space of the hollow fiber membrane and oxygen-containing gas flows outside in the axial direction of the hollow fiber membrane bundle, the flow of oxygen-containing gas becomes laminar on the surface of the hollow fiber membrane, so the gas Improvement in exchange capacity cannot be expected beyond a certain point. Furthermore, by bundling the hollow fiber membranes, it is difficult for oxygen-containing gas to enter the gaps between the bundles of hollow fiber membranes, so that the hollow fiber membranes in the center are not effectively utilized.

In addition, since the hollow fiber membrane is hydrophobic, it is especially
? In the case of n'' flow, air bubbles that were not removed during brimming tend to accumulate in the gap, resulting in a so-called air-trapped state. This allows trtt
= circulation becomes poor, and contact between blood and oxygen-containing gas through the membrane wall of the hollow fiber membrane is inhibited by the mass of air-trapped air bubbles, thus reducing the effective membrane area.
As a result, there were problems such as a decrease in the gas exchange ability of the oxygenator.

Therefore, various proposals have been made, for example, by crimping the hollow fiber membrane and applying certain conditions to the average crimp amplitude, crimp rate, etc., the width can be increased along the axial direction at each hollow fiber crotch. Provisions have been made to create a variable gap.

The present invention was also made in view of such problems,
The purpose is to crimp the hollow fiber membranes under conditions different from those proposed above, so that when the hollow fiber membranes are bundled, the gaps between each hollow fiber membrane are narrow and do not change actively. This method eliminates the turbulence in the flow of blood or oxygen-containing gas flowing outside the hollow fiber membrane, thereby increasing the gas exchange capacity, and further, for example, through the membrane wall of the hollow fiber membrane,
When oxygen-containing gas is blown inside and blood flows outside, an effective membrane that suppresses the generation of air traps in the gap, improves blood flow, and makes contact between blood and oxygen-containing gas. Smooth fluid flow in the gap by ensuring sufficient area and improving gas exchange ability,
It is an object of the present invention to provide a hollow fiber membrane and a hollow fiber membrane type oxygenator using the hollow fiber membrane, which actively and sufficiently secures an effective membrane area that can be contacted with fluid through the membrane wall, and improves fluid handling capacity.

[Means for Solving the Problems] In order to solve the above-mentioned conventional problems, the present invention has the following features:
A hydrophobic porous hollow fiber having a membrane wall, through which the fluid to be treated is fluid-treated between either one of the fluid to be treated and the other fluid to be treated on the inside or outside of the membrane wall. The present invention proposes a hollow fiber membrane characterized by a structure in which the crimp rate is set in the range of 0.1 to 0.7%.

In the above structure, a structure in which the crimp rate is 0.3 to 0.5% is proposed.

Further, in the above configuration, the inner diameter of the hollow fiber membrane is 10
A structure having a thickness of 0 to 500 μm and a wall thickness of 27 to 80 μm is proposed.

Further, in the present invention, the fluid to be treated is blood, the fluid to be treated is an oxygen-containing gas, gas exchange is performed through the membrane wall of the hollow fiber membrane, and the hollow fiber membrane is located within the housing; We propose a hollow fiber membrane oxygenator that is bundled and housed.

With the above configuration, in the hollow fiber membrane according to the present invention and the hollow fiber membrane oxygenator using the same, the hydrophobic porous hollow fiber membrane is crimped, and the crimp rate is 0.1 to 0. Since the gap is set in the range of 7%, the gap between the hollow fiber membranes is sufficiently large and actively changes along the axial direction of the hollow fiber membrane. When oxygen-containing gas is blown into the inside of the thread membrane as a treatment fluid, and blood is circulated and distributed as a fluid to be treated on the outside, appropriate gaps are created between the respective middle school thread membranes, so that good blood flow can be achieved. The blood and oxygen-containing gas are brought into contact with each other through the membrane wall of the hollow fiber membrane, and the contact between the blood and the oxygen-containing gas is made uniform over the entire surface of the hollow fiber membrane. As a result, a high gas exchange capacity is obtained, and the flow of the fluid to be treated or the fluid to be treated in the gap becomes smooth, and the effective membrane area that can be contacted by the fluid through the membrane wall of the hollow fiber membrane is increased. target+“
This makes it possible to improve fluid handling capacity.

Examples] Hereinafter, a hollow fiber membrane of the present invention for use in an artificial lung will be described.

The hollow fiber membrane according to this example has an inner diameter of 100 to 500.
um, preferably 150-300 μm, wall thickness 27-300 μm
It is a hydrophobic porous hollow fiber membrane having a diameter of 80 μm, preferably 40 to 60 μm.

This porous hollow fiber membrane is crimped. In imparting this crimp, the hollow fiber membrane is stretched.

This stretching is done to improve the breaking strength of the hollow fiber membrane and to obtain an appropriate shrinkage rate for imparting crimps. Shrinkage/V,) after oven treatment is good.

In crimp, the crimp rate is set in the range of 0.1 to 0.7%. When the crimp rate is less than 0.1%,
When a hollow fiber membrane is incorporated into an oxygenator, for example, the gaps between the hollow fibers are insufficient to create turbulence in the fluid flowing outside the hollow fiber membrane. On the other hand, if the crimp rate exceeds 0.7%, for example, when an oxygenator is created using a hollow fiber membrane, there is a risk that the oxygenator will be larger than necessary, which is not preferable. More preferably 0.3-0
．． It is in the range of 5%.

The hollow fiber membrane described above can be manufactured by the method shown below. For example, after being spun, a hollow fiber membrane made porous by a drawing method or a phase separation method is wound cross-wound around a suitable bobbin or the like to impart crimps, and then crimped under suitable conditions, e.g. It is obtained by heat treatment at 60° C. for about 24 hours to fix the crimp state. At this time, the heat setting during the application of crimp is performed more than necessary, and the membrane structure changes, for example, the porosity becomes 2
If the crimp decreases by more than 0%, the effect of crimp will not be exhibited, and conversely, heat fixation will be insufficient, making it difficult to maintain the desired crimp state when assembling the oxygenator. Even if the crimp is lost due to tension applied to the hollow fiber membrane due to the subsequent residual stress, the effect cannot be obtained.

Furthermore, in the porous hollow fiber membrane of the present invention, the porosity is 30
-50%, preferably 37-43%, and the oxygen gas flux is l5000-35000E/mi
n・m”0, 5 atm, preferably 22000
~b When used for an artificial lung, even more excellent effects can be expected.

As the material for the hollow fiber membrane, for example, polyolefins such as polypropylene and polyethylene, and hydrophobic synthetic resins such as polytetrafluoroethylene can be used. Polypropylene is particularly suitable because it has excellent properties and is easy to impart porosity.

Next, a hollow fiber membrane oxygenator using the above hollow fiber membrane will be explained based on the drawings.

FIG. 1 shows a first embodiment of the hollow fiber membrane type oxygenator, in which blood is circulated and distributed as the fluid to be treated inside the hollow fiber membrane 6, and oxygen is circulated as the fluid to be treated outside the membrane 6. It is a so-called internal perfusion type that blows the gas contained therein. This hollow fiber membrane oxygenator l includes a housing 2,
The housing 2 is integrally formed with a cylindrical main body 3 and enlarged diameter portions 4 and 5 with annular projections formed at both ends thereof. Inside the housing 2, a plurality of, for example 1000
0 to 60,000 porous hollow fiber membranes 6 are bundled together as a hollow fiber membrane bundle 13 along the longitudinal direction of the housing 2 and housed. Both ends of the hollow fiber membranes 6 are mounted within the cover 4.5 and supported in a liquid-tight manner by partition walls 7.8 with the openings 1 of each hollow fiber membrane 6 not being closed. This partition wall 7°8 allows the porous hollow fiber I! ! A gas chamber 9 is formed between the outer peripheral surface of the housing 26 and the inner surface of the housing 2. In the above installation, one of the covers 4 and 5 is installed, and the cover 4 has an oxygen-containing gas introduced to supply the oxygen-containing gas.
)O is provided, and the other attachment is provided in the cover 5 with an oxygen-containing gas outlet 1) for discharging oxygen-containing gas.

In addition, regarding the filling rate of the hollow fiber membrane 6, the filling rate at the center of the hollow fiber membrane bundle 13 in the cylindrical body 3 is about 55 to 6.
5%, and the partition wall 7.8 from both ends of the hollow system bundle 13, -)
It is good if the filling rate B on the outer surface of is about 40 to 50%, the filling rate A is 57 to 63%, and the filling rate B is 43 to 4.
Particularly preferred is 7%.

Note that the partition wall 7.8 is obtained by pouring a highly polar polymer bodding material such as polyurethane, silicone, epoxy resin, etc. onto the inner wall surfaces of both ends of the housing 2 using a centrifugal injection method and hardening the material.

The outer surface of one of the partition walls 7 is covered with a blood boat cover 15 having a substantially conical shape. The blood boat cover 5 is attached to the cover by an annular protrusion 15 formed on the inner circumferential surface thereof and an annular protrusion 4a formed on the outer circumferential surface of the cover 4, which engage with each other. 4 is fluid-tightly fitted,
A blood boat region 23 is formed inside the blood vessel. The blood boat cover 15 has a blood outlet 2.
6 is formed.

A heat exchanger I2 is connected to the other partition wall 8. The heat exchanger 1312 includes a housing 13, and the housing 13 includes a cylindrical main body 13a and a fitting member 13b. A plurality of stainless steel vibrators 14 are disposed within the cylindrical main body 13a, and are supported in a liquid-tight manner via partition walls 17 and 18 with openings at both ends thereof not being closed. In addition, cold and hot water flow ports 19 and 20 are provided on the circumferential side of the cylindrical body 13a, and a cold water or hot water flow path is formed in the cylindrical body 13a. The temperature is adjusted to the desired temperature. A partition wall 1 located on the opposite side to the partition wall 8
The outer surface of 8 is covered with a blood boat cover 16 similar to the blood boat cover 15 described above. In the figure, 24 is a blood boat area, and 25 is a blood introduction port. Fitting member 13b
is liquid-tightly fitted to the enlarged diameter portion 5 in the same way as the blood boat cover 15, and a blood storage space 27 is formed between the partition wall 17°5.
is formed.

In this example, with the above configuration, the gap is formed between the hollow fiber membranes to be sufficiently large (and to change actively along the axial direction of the hollow fiber membranes. Therefore, The oxygen-containing gas that is blown into the gas chamber 9 and forms the processing fluid flows well through the gap.

In addition, this oxygen-containing gas and the hollow fiber t! from the blood storage space 27! Contact with the blood flowing inside the A 6 and forming the fluid to be processed through the membrane wall of the hollow fiber membrane is made uniform over the entire surface of the hollow fiber membrane 6, and a sufficient effective membrane area is ensured. As a result, high gas exchange performance can be obtained, and the fluid processing performance of the fluid to be treated can be improved.

Next, as a second embodiment of the hollow fiber membrane type oxygenator of the present invention, blood is circulated as a fluid to be treated outside the hollow fiber membrane, and oxygen-containing gas is blown as a fluid to be treated inside the hollow fiber membrane. The so-called external perfusion type will be explained based on FIG. The hollow fiber membrane type oxygenator 31 according to this embodiment is composed of a housing 32 and oxygen-containing gas boat covers 34 and 35 provided at both ends of the housing 32. Housing 32
A hollow fiber membrane 6 is supported therein via partition walls 7 and 8, as in the previous embodiment. Due to the partition 7.8, a blood chamber 39 is formed in the housing 32, and oxygen-containing gas boat regions 34a, 35a are formed in the oxygen-containing gas boat cover 34.35.

The housing 32 is provided with a blood inlet 45 for supplying blood and a blood outlet 046 for discharging blood. An oxygen-containing gas inlet [ ] 40 and an oxygen-containing outlet 41 are formed in the oxygen-containing gas port covers 34 and 35, respectively.

In this embodiment, with the above configuration, the gaps between the hollow fiber membranes 6 are formed to be sufficiently large and actively change along the axial direction of the hollow fiber membranes 6, so that briming is prevented. At times, it becomes difficult for air bubbles that are not removed to remain in the gap, and thus become difficult to become so-called air traps. This improves the blood circulation in the gap and eliminates the obstruction of contact between the blood and oxygen-containing gas through the membrane wall of the hollow fiber membrane 6 caused by the air-trapped mass of air bubbles. Sufficient membrane area is ensured.

Further, turbulence occurs in the flow of blood, and gas exchange performance is improved.

Other functions and effects are the same as those of the above-mentioned embodiments. Although the present invention has been described above with reference to embodiments, the present invention is not limited to the above-mentioned embodiments, and the gist of the invention is not changed. Various changes are possible.

Next, the inventor conducted the following experiment in order to confirm the effects of the above embodiment.

(Experimental Example) A porous hollow fiber membrane according to this experimental example was manufactured by the method shown below.

(The average pore radius formed by the micro phase separation method, which belongs to the eye separation method, is approximately 500 micropores, with an inner diameter of 180 ~
A porous hollow fiber membrane made of polypropylene having a diameter of 220 μm and a wall thickness of 50 μm was wound crosswise around a bobbin having a diameter of 97 mm, and crimped by heat treatment in an oven at 60° C. for 24 hours. Here, the crimp ratio is as shown in Table 1.

Using the hollow fiber membrane 6 obtained in this way, the first
An oxygenator (manufactured by Terumo Corporation, CX-II) I8 similar to the hollow fiber membrane oxygenator 1 according to Example 1 is used as Example 1, and a hollow fiber membrane according to the second example is used as oxygenator 31. An artificial lung (Terumo Corporation'1, CX-E) IB similar to the above was prepared as Example 2, and the oxygen gas addition ability and carbon dioxide removal ability were measured. The results are shown in Table 1.

(Comparative example) In order to compare with the above experimental example, a polypropylene porous material with an inner diameter of 200 μm and a wall thickness of 21.5 μm, having an average pore radius of 684 micropores formed by stretching in the axial direction by a stretching method. The hollow fiber membrane was used without crimping (using it as it was) to create an oxygenator in the same manner as in the above experimental example, and the one corresponding to oxygenator IA was used as comparative example 1, and the one corresponding to oxygenator 2A and oxygenator IB was used. The artificial lung 2B was used as Comparative Example 2, and the oxygen gas addition ability and carbon dioxide removal ability were measured.The results are shown in Table 1.

Note that the definitions and measurement methods of each term in this specification are as follows.

Color position - Sato N Pull out 10 hollow fiber membranes arbitrarily and use a sharp razor to remove 10 hollow fiber membranes.
Slice into rounds about ~3mm long. Versatile: Project the cross section on the λ dead machine with a ConProfile projector-V-12), and use a ConDigital counter CM-6S as a measuring instrument.
), measure its outer diameter d1 and inner diameter d2, and calculate the wall thickness t as t=d
+ - d 2 was calculated, and the average value of 10 pieces was taken as the average value.

Porosity (%) Take about 2 g of hollow fiber membrane and cut into rounds of 5 mm or less using a sharp razor. The obtained sample was measured at 1000 kg/cm using a mercury porosimeter (Carlo Erba Model 65A).
” to obtain the porosity from the total pore volume (pore volume of the hollow fiber per unit weight).

Since the A-Kei oxygenator is usually sterilized before use, measurements were performed on the hollow fiber membrane taken out from the oxygenator after sterilization.

Sterilization was performed by ethylene oxide gas sterilization under the following conditions. That is, E OG/CO□:2
0/80 (%), temperature: 55-65℃, humidity: 50-8
0%RH 1 pressure crab 0.8-1, 2 kg/cm2,
Ethylene oxide concentration: 550-150 mg/E, action time = 150-210 minutes.

As the sample length of the hollow fiber membrane taken out, the artificial lung I
For A, 2A, 70mm, artificial lung IB, 2
For B, the length was 100 mm.

For measuring force C, JIS L 10746.1). 2
The method for measuring the crimp rate was used as a reference.

Specifically, the test machine was manufactured by Shimadzu Corporation.

An Autograph AGS-100A tensile tester was used, and the tensile speed was 1 mm/min.

First, a load of 1 g is applied to the hollow fiber membrane of the above sample length using this tester, and the load at that time is set as a, and then,
The length when a load of 10 g is applied is b, and a cycle test is performed between the Ig and 10 g loads three times at the above tension speed using the strograph cycle test mode, and the average value of the three times is a, b. From the measured values of a and b, the crimp ratio was obtained using the following formula.

Crimping rate (%) = (ba-a) /aX 100 oxygen gas flux porous hollow fiber membrane, effective length 23 cm, effective membrane area 0.1
After making one m2 and closing one end, apply a pressure of 0.5 atm inside the hollow fiber membrane with oxygen, and measure the flow rate of oxygen gas when it reaches a steady state using a flow meter (Kusano Rikagaku). The value was taken as the value read by a float meter (equipment manufacturer, float meter).

Oxygen gas addition ability, carbon dioxide gas removal (oxygenator IA and 2A) Effective length of hollow fiber membrane 6 is 80 mm, membrane area is 3.0 m2
Then, 527 ml of bovine blood (standard venous blood) was poured inside the hollow fiber membrane 6 in a single path.
Pure oxygen is supplied to the outside of the hollow fiber membrane 6 at a flow rate of 5127
The pH of bovine blood at the inlet and outlet of the oxygenator was 5 carbon dioxide partial pressure (PCO2), oxygen gas partial pressure (P
O2) was measured using a blood gas measuring device (manufactured by Radiometer, BGA type 3), and the partial pressure difference between the oxygenator inlet and the oxygenator outlet was calculated. The details of the oxygenator module specifications are shown in Table 2.

(Artificial lungs IB and 2B) The effective length of the hollow fiber membrane 6 is 140 mm, and the membrane area is 5.0 m.
2, and a single pass of bovine blood (standard venous blood) to the outside of the hollow fiber membrane 6 to
/min to supply pure oxygen to the inside of the hollow fiber membrane 6.
The pH of bovine blood at the inlet and outlet of the oxygenator was measured at a flow rate of β/min.
The partial pressure difference between the oxygenator inlet and the oxygenator outlet was calculated. The details of the oxygenator module specifications are shown in Table 2.

In addition, the properties of standard arterial blood for artificial lungs IA, IB, 2A, and 2B are shown in Table 3.

The above results revealed that among the artificial lungs IA and IB according to the examples of the present invention, especially the external perfusion type artificial lung IB had excellent gas exchange ability.

Table 1 Table 2 Table 3 [Effects of the Invention] As explained above, in the hollow fiber membrane according to the present invention and the hollow fiber membrane oxygenator using the same, the hydrophobic porous hollow fiber Since the membranes are crimped and the crimp rate is set in the range of 0.1 to 0.7%, there is a sufficiently large gap between the hollow fiber membranes and the axis of the hollow fiber membranes. For example, when oxygen-containing gas is blown into the inside of a hollow fiber membrane as a processing fluid and blood is circulated and distributed outside as a fluid to be processed, Appropriate gaps between hollow fiber membranes result in good blood circulation, and contact between blood and oxygen-containing gas through the membrane wall of the hollow fiber membrane is made uniform over the entire surface of the hollow fiber membrane, making it effective. Sufficient membrane area is ensured, and turbulence is created in the flow of blood, resulting in high gas exchange performance.The flow of the fluid to be treated or the fluid to be treated in the gap is smooth, and the membrane wall of the hollow fiber membrane is The effective membrane area that can be contacted by the fluid is positively and sufficiently secured, and various effects such as improvement in fluid processing performance are achieved.

[Brief explanation of the drawing]

FIG. 1 is a semi-longitudinal front view showing a first embodiment of a hollow fiber membrane oxygenator according to the present invention, and FIG. 2 is a semi-longitudinal front view showing a second embodiment of a hollow fiber membrane oxygenator according to the present invention. FIG. ■, 31...Hollow fiber membrane oxygenator 2.32...Housing 6...Hollow fiber membrane

Claims (4)

[Claims] (1) Hydrophobic porous pores having a membrane wall, through which the fluid to be treated is treated between either the inside or outside of the fluid to be treated and the other fluid to be treated. A hollow fiber membrane characterized in that the crimp rate is set in the range of 0.1 to 0.7%. (2) The hollow fiber membrane according to claim 1, wherein the crimp ratio is 0.3 to 0.5%. (3) The hollow fiber membrane according to claim 1, wherein the hollow fiber membrane has an inner diameter of 100 to 500 μm and a wall thickness of 27 to 80 μm. (4) The fluid to be treated is blood, the fluid to be treated is oxygen-containing gas, and gas exchange is performed through the membrane wall of the hollow fiber membrane according to any one of claims 1 to 3,
A hollow fiber membrane oxygenator comprising a plurality of the hollow fiber membranes bundled and housed in a housing.