JPH0763592B2 - Hollow fiber membrane and hollow fiber membrane type artificial lung using the same - Google Patents

Description

TECHNICAL FIELD 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 type artificial lung using the hollow fiber membrane. Is.

[Prior Art] In recent years, in heart surgery, etc., the blood of the patient is guided outside the body,
To add oxygen to this and remove carbon gas,
A hollow fiber membrane type artificial lung that constitutes an extracorporeal circulation circuit is used.

This hollow fiber membrane-type artificial lung is generally formed by bundling and storing a plurality of hollow fiber membranes in a housing, and circulating blood as a fluid to be processed either inside or outside the hollow fiber membranes. , Blowing an oxygen-containing gas as a processing fluid to the other,
A desired gas exchange is carried out by bringing gas and liquid into contact with each other through the membrane wall of the hollow fiber membrane. Of these hollow fiber membrane-type artificial lungs, the so-called external perfusion type, in which blood is circulated outside the hollow fiber membrane and oxygen-containing gas is blown into the inside, is a circulation type because there is little pressure loss in the blood flow. Since it is not necessary to provide a blood-sending pump in front of the artificial lung in the circuit, blood can be sent to the artificial lung only by removing blood from the human body, which is particularly preferable.

As a hollow fiber membrane used in such a hollow fiber membrane artificial lung, a hydrophobic porous hollow fiber membrane such as polypropylene is mainly used in terms of gas permeability, mechanical strength and the like.

[Problems to be Solved by the Invention] By the way, in the above-mentioned hydrophobic porous hollow fiber membrane, conventionally, in the housing, the gap between the hollow fiber membrane and the hollow fiber membrane is narrow, and along the axial direction. They were bundled and stored in a state where they did not change positively. In such a state, when blood is flown in the hollow fiber membrane internal space and oxygen-containing gas is flown outside in the axial direction of the hollow fiber membrane bundle, the flow of oxygen-containing gas becomes a laminar flow on the surface of the hollow fiber membrane. The exchange capacity cannot be expected to improve beyond a certain level. Further, by bundling the hollow fiber membranes, it is difficult for oxygen-containing gas to enter the gaps between the hollow fiber membrane bundles, and the hollow fiber membranes in the central portion have not been effectively used.

In addition, since the hollow fiber membrane is hydrophobic, bubbles that have not been removed during priming tend to accumulate in the gap, particularly in the case of the external perfusion type, and a so-called air trapped state occurs. As a result, blood circulation becomes poor,
In addition, the contact of blood and oxygen-containing gas through the membrane wall of the hollow fiber membrane is hindered by the mass of air-trapped air bubbles,
Therefore, the effective membrane area is reduced, and as a result, the gas exchange capacity of the artificial lung is reduced, which is a problem.

Therefore, various proposals have been made, for example, by crimping the hollow fiber membranes and subjecting the average crimping amplitude, crimping rate, and the like to certain conditions, the width between the hollow fiber membranes along the axial direction is increased. What has been devised is to form a gap that changes.

The present invention is also made in view of such problems,
The purpose is to crimp the hollow fiber membranes under a condition different from that of the above proposal, so that when the hollow fiber membranes are bundled, the gap between the hollow fiber membranes is narrow and does not change positively. Turbulence is caused in the flow of blood or oxygen-containing gas flowing outside the hollow fiber membrane, thereby enhancing the gas exchange capacity, and further, for example, through the membrane wall of the hollow fiber membrane, oxygen inside When the contained gas is blown and the blood flows outside, it suppresses the generation of air traps in the gap, improves the blood flow, and provides a sufficient effective membrane area for contacting the blood with the oxygen-containing gas. A hollow that secures and improves the gas exchange capacity, smooths the fluid flow in the gap, positively and sufficiently secures an effective membrane area where the fluid can contact through the membrane wall, and improves the fluid treatment capacity. Fiber membrane and its hollow fiber membrane type artificial To provide a.

[Means for Solving the Problems] In order to solve the above conventional problems, the present invention provides:
A hydrophobic porous hollow fiber having a membrane wall, through which the fluid to be treated is fluid-processed between the fluid to be treated on either the inside or the outside of the membrane and the fluid to be treated on the other side. A hollow fiber membrane is proposed, which is characterized in that the crimping rate of the hollow fiber membrane after sterilization is set in the range of 0.1 to 0.7%.

In the above structure, a structure having a crimp ratio of 0.3 to 0.5% is proposed.

Further, in the above configuration, the inner diameter of the hollow fiber membrane is 100
A structure having a thickness of ˜500 μm and a wall thickness of 27 to 80 μm is proposed.

Furthermore, in the present invention, the treated fluid is blood, the treated fluid is an oxygen-containing gas, gas exchange is performed through the membrane wall of the hollow fiber membrane, and the hollow fiber membrane is provided in a plurality of housings. The present invention proposes a hollow fiber membrane type artificial lung that is bundled and housed.

With the above-described structure, in the hollow fiber membrane according to the present invention and the hollow fiber membrane-type artificial lung using the same, the hydrophobic porous hollow fiber membrane is crimped, and the hollow fiber membrane is sterilized after sterilization. Reduction rate from 0.1 to
Since it is set in the range of 0.7%, a sufficiently large gap is formed between the hollow fiber membranes and the hollow fiber membranes are positively changed along the axial direction of the hollow fiber membranes. When an oxygen-containing gas is blown as the treatment fluid inside the fiber membrane and blood is circulated and circulated as the fluid to be treated outside, a proper gap is formed between the hollow fiber membranes, so that good blood circulation is achieved. And the 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, sufficient effective membrane area is secured, and turbulent flow is generated in the blood flow. As a result, a high gas exchange capacity can be 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 where the fluid can contact through the membrane wall of the hollow fiber membrane is positive and sufficient. Therefore, the fluid processing ability can be improved.

[Example] Hereinafter, the hollow fiber membrane of the present invention for an artificial lung will be described.

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

Crimping is applied to the porous hollow fiber membrane. When applying the crimp, the hollow fiber membrane is stretched.
This stretching is intended to improve the breaking strength of the hollow fiber membrane and to obtain an appropriate shrinkage ratio to impart crimp,
The heat shrinkage before crimping is 6 ± 2% (shrinkage after oven treatment at 75 ° C. for 30 minutes) is good.

In crimping, the crimping rate is set in the range of 0.1 to 0.7%. The crimp rate in the present application is a value after the sterilization process because an artificial organ such as an artificial lung in which the hollow fiber membrane is used is sterilized before use. When the crimping rate is less than 0.1%, when the hollow fiber membrane is incorporated into, for example, an artificial lung, the gap between the hollow fiber and the hollow fiber cannot be sufficiently secured, and turbulent flow is generated in the fluid flowing outside the hollow fiber membrane. It does not reach the point where it is generated. On the other hand, if the crimping rate exceeds 0.7%, for example, when an artificial lung is created using a hollow fiber membrane, the artificial lung may become unnecessarily large, and in particular, the bundle diameter of the hollow fiber membrane becomes large. If it passes, the membrane may be excessively contacted with the inner wall of the housing during the work of inserting the artificial membrane into the housing, and as a result, a so-called fiber pin hole may be formed in the membrane, which is not preferable. The range is more preferably 0.3 to 0.5%.

The hollow fiber membrane can be manufactured by the following method. For example, after being spun, the hollow fiber membrane which has been made porous by a stretching method or a phase separation method is wound around a suitable bobbin or the like in a cross winding to provide crimp, and then, under appropriate conditions, for example, It is obtained by heat-treating at 60 ° C for about 24 hours to fix the crimped state. At this time, heat setting during crimping is performed more than necessary, the film structure is changed, and, for example, if the porosity is reduced by 20% or more from the state before crimping, , The effect of the crimp is not exhibited, and conversely, the heat setting is insufficient, and the desired crimped state is maintained during the assembly of the artificial lung, but the hollow fiber is caused by the residual stress after that. Even if the film is tensioned and the crimp is lost, the effect cannot be obtained.

Further, in the porous hollow fiber membrane of the present invention, the porosity is 30 ~
50%, preferably 37 to 43%, and the oxygen gas flux is 15000 to 35000 / min · m ² · 0.5 atm, preferably 22.
When it is 000 to 27200 / min · m ² · 0.5 atm, even more excellent effects can be expected when used for an artificial lung.

As the material of the hollow fiber membrane, for example, polyolefin such as polypropylene or polyethylene, or hydrophobic synthetic resin such as polytetrafluoroethylene can be used. Among them, various physical properties such as mechanical strength, heat resistance, and processability can be used. Polypropylene is particularly preferable because it is excellent and it is easy to impart porosity.

Next, a hollow fiber membrane type artificial lung using the hollow fiber membrane will be described with reference to the drawings.

FIG. 1 shows a first embodiment of the hollow fiber membrane type artificial lung, in which blood is circulated as a fluid to be treated inside the hollow fiber membrane 6,
This is a so-called internal perfusion type in which an oxygen-containing gas is circulated and blown with an oxygen-containing gas as a processing fluid to the outside of the hollow fiber membrane 6. The hollow fiber membrane-type artificial lung 1 comprises a housing 2, which is integrally formed with a tubular body 3 and expanded diameter portions 4 and 5 with annular projections formed at both ends thereof. Has been done. In the housing 2, a plurality of, for example, 10,000
About 60,000 porous hollow fiber membranes 6 are bundled and housed as a hollow fiber membrane bundle 13 along the longitudinal direction of the housing 2. Both ends of the hollow fiber membrane 6 are separated from each other by the partition walls 7, while the openings of the hollow fiber membranes 6 are not closed in the mounting covers 4 and 5.
Liquid-tightly supported by 8. The partition walls 7 and 8 form a gas chamber 9 between the outer peripheral surface of the porous hollow fiber membrane 6 and the inner surface of the housing 2. Above mounting cover 4,
Of the five, one mounting cover 4 is provided with an oxygen-containing gas inlet 10 for supplying an oxygen-containing gas, and the other mounting cover 5 is provided with an oxygen-containing gas outlet 11 for discharging the oxygen-containing gas. Has been.

Regarding the filling rate of the hollow fiber membranes 6, the filling rate A in the central portion of the hollow fiber membrane bundle 13 in the tubular body 3 is about 55 to 65%, and both ends of the hollow fiber bundle 13, that is, partition walls. It is good if the filling rate B on the outer surface of 7, 8 is about 40 to 50%, and the filling rate A
Is 57 to 63% and the filling rate B is 43 to 47%.

The partition walls 7 and 8 are polymer potting materials with high polarity,
For example, it can be obtained by pouring polyurethane, silicone, epoxy resin or the like into the inner wall surfaces of both ends of the housing 2 by using a centrifugal injection method and curing the resin.

The outer surface of one of the partition walls 7 has a substantially conical blood port cover.
Covered with 15. The blood port cover 15 is liquid-tightly attached to the mounting cover 4 by the mutual engagement of the annular projection 15a formed on the inner peripheral surface thereof and the annular projection 4a formed on the outer peripheral surface of the mounting cover 4. It is fitted and a blood port region 23 is formed therein.
A blood outlet port 26 is formed in the blood port cover 15.

A heat exchanger 12 is connected to the other partition wall 8. The heat exchanger 12 comprises a housing 13,
The reference numeral 13 includes a tubular body 13a and a fitting member 13b.
A plurality of stainless steel pipes 14 are arranged in the cylindrical main body 13a, and the partition wall 1 is formed in a state where the openings at both ends thereof are not closed.
Liquid-tightly supported via 7,18. Also, the cylindrical body 13
Cold and hot water flow ports 19 and 20 are provided on the peripheral side of a, and a flow path of cold water or hot water is formed in the tubular main body 13a, whereby blood circulating in the pipe 14 reaches a desired temperature. It is supposed to be adjusted. The outer surface of the partition 18 located on the opposite side of the partition 8 is covered with a blood port cover 16 similar to the blood port cover 15. In the figure, 24 is a blood port region, and 25 is a blood inlet. Mating member 13b
Is liquid-tightly fitted to the expanded diameter portion 5 similarly to the blood port cover 15, and a blood storage space 27 is formed between the partition walls 17 and 5.

In this embodiment, with the above configuration, a gap is formed between the hollow fiber membranes so that the gap is sufficiently large and positively changes along the axial direction of the hollow fiber membranes. Therefore, the oxygen-containing gas blown into the gas chamber 9 and forming the processing fluid satisfactorily flows through the gap. Further, the contact of the oxygen-containing gas with the blood that flows inside the hollow fiber membrane 6 from the blood storage space 27 and is the fluid to be treated through the membrane wall of the hollow fiber membrane is uniform over the entire surface of the hollow fiber membrane 6. Therefore, the effective film area is sufficiently secured. As a result, a high gas exchange capacity can be obtained, and the fluid processing capacity of the fluid to be processed can be improved.

Next, as a second embodiment of the hollow fiber membrane-type artificial lung of the present invention, blood is circulated as a fluid to be processed outside the hollow fiber membrane,
A so-called external perfusion type in which an oxygen-containing gas is blown as a treatment fluid inside the hollow fiber membrane will be described with reference to FIG. The hollow fiber membrane type artificial lung 31 according to the present embodiment is a housing
32, and oxygen-containing gas port covers 34 and 35 provided at both ends thereof. In the housing 32,
The hollow fiber membrane 6 is supported via the partition walls 7 and 8 as in the above-described embodiment. The partition walls 7 and 8 form a blood chamber 39 in the housing 32, and the oxygen-containing gas port cover 3 is formed.
Oxygen-containing gas port regions 34a, 35a are formed in 4,35. The housing 32 is provided with a blood inlet 45 for supplying blood and a blood outlet 46 for discharging blood. Oxygen-containing gas port cover 34,35
An oxygen-containing gas inlet 40 and an oxygen-containing outlet 41 are formed in each of them.

In the present embodiment, due to the above-described configuration, the gap between the hollow fiber membranes 6 is formed to be sufficiently large and positively change along the axial direction of the hollow fiber membranes 6, so that priming is performed. At times, the air bubbles that have not been removed are less likely to stay in the gap, and thus are less likely to be so-called air trapped. This improves the circulation of blood in the gap, and is caused by the air trapped air bubble mass.
Inhibition of contact between blood and oxygen-containing gas through the membrane wall of the hollow fiber membrane 6 is eliminated, and therefore an effective membrane area is sufficiently secured.

In addition, turbulence occurs in the blood flow, and the gas exchange capacity is improved.

Other functions and effects are similar to those of the above-described embodiment.

Although the present invention has been described above with reference to the embodiments, the present invention is not limited to the above embodiments, and various modifications can be made without departing from the spirit of the invention.

Next, the present inventor conducted the following experiment in order to confirm the effect of the above-mentioned embodiment.

(Experimental Example) A porous hollow fiber membrane according to this Experimental Example was produced by the following method.

180-220μ inner diameter with fine pores with an average pore radius of about 500Å formed by the micro phase separation method belonging to the phase separation method.
m, wall thickness about 50 μm polypropylene porous hollow fiber membrane wound around a bobbin with a diameter of 97 mm in a cross winding, at 60 ° C
Crimping was applied by heat treatment in an oven for 24 hours. Here, the crimp rate is as shown in Table 1.

Using the hollow fiber membrane 6 thus obtained, the first
The same artificial lung (CX-II, CX-II) 1A as the hollow fiber membrane oxygenator 1 according to Example 1 is used as Example 1 and the hollow fiber membrane oxygenator 31 according to the second embodiment is used. Similar artificial lungs (CX-E) 1B manufactured by Terumo Corp. were prepared as Example 2, and the oxygen gas addition ability and the carbon gas elimination ability were measured. The results are shown in Table 1.

(Comparative example) In order to be proportional to the above experimental example, a polypropylene porous hollow fiber having an inner diameter of 200 μm and a wall thickness of 21.5 μm, which has fine pores with an average pore radius of 684Å formed by axially stretching by a stretching method. Using the membrane as it is without crimping,
An artificial lung was created in the same manner as in the above-mentioned experimental example, one corresponding to the artificial lung 1A was designated as the artificial lung 2A, and one corresponding to the artificial lung 1B was designated as the comparative lung 2B, and the oxygen gas addition ability was used. And the carbon gas elimination capacity were measured. The results are shown in Table 1.

The definitions and measuring methods of each term in this specification are as follows.

Inner diameter, wall thickness 10 hollow fiber membranes can be extracted arbitrarily and sharpened with a razor
Cut into 3mm length. The cross section is projected with a universal projector (Nikon profile projector-V-12), and its outer diameter d ₁ and inner diameter d ₂ are measured with a measuring instrument (Nikon digital counter CM-6S), and the wall thickness t is t = d ₁ It was calculated by -d _{2 and} was taken as the average value of 10 lines.

Porosity (%) Approximately 2 g of hollow fiber membrane is taken and cut into 5 mm or less slices with a sharp razor. The porosity of the obtained sample is obtained by applying a pressure up to 1000 kg / cm ² with a mercury porosimeter (Model 65A, manufactured by Carlo Erba Co.) and the total amount of pores (pore volume of hollow fiber per unit weight).

Crimping rate Since the artificial lung is usually sterilized before use, the hollow fiber membrane taken out from the artificial lung was measured after the sterilization.

Sterilization was carried out by ethylene oxide gas sterilization, and the conditions are as follows. That is, EOG / CO ₂ : 20/80
(%), Temperature: 55 ~ 65 ℃, humidity: 50 ~ 80% RH, pressure: 0.8 ~
1.2 kg / cm ² , ethylene oxide concentration: 550-750 mg /,
Action time: 150-210 minutes.

As the sample length of the extracted hollow fiber membrane, the artificial lung 1
It was 70 mm for A and 2A, and 100 mm for artificial lungs 1B and 2B.

As the measurement method, the crimp rate measurement method of JIS L 1074 6.11.2 was referred to.

Specifically, a tensile tester manufactured by Shimadzu Corporation, Autograph, AGS-100A was used as a tester, and the pulling speed thereby was set to 1 mm / min.

First, a load of 1 g was applied to the hollow fiber membrane of the above sample length by this tester, the load at that time was set to a, and then 10
Let b be the length when a load of g is applied, and use the cycle test mode of the strograph to load the load between 1g and 10g three times.
A cycle test was conducted at the above-mentioned tensile speed, and the average value of three times was used as each value of a and b. From the measured values of a and b, the crimp ratio was obtained by the following calculation formula.

Crimping rate (%) = (ba) / a × 100 Oxygen gas flux A porous hollow fiber membrane having an effective length of 23 cm and an effective membrane area of 0.1 m ² was prepared, and after closing one end, A pressure of 0.5 atm was applied to the inside of the hollow fiber membrane with oxygen, and the flow rate of oxygen gas when in a steady state was read by a flow meter (Kusano Rikagaku Kikai Seisakusho, float meter).

Oxygen gas addition ability, carbon gas elimination ability (artificial lungs 1A and 2A) The hollow fiber membrane 6 has an effective length of 80 mm and a membrane area of 3.0 m _2, and bovine blood (standard venous blood) is placed inside the hollow fiber membrane 6. A single path is used to flow at a flow rate of 5 / min, pure oxygen is flowed to the outside of the hollow fiber membrane 6 at a flow rate of 5 / min, and the pH of the bovine blood at the inlet and outlet of the artificial lung and the partial pressure of carbon dioxide (PCO) ₂ ) Oxygen gas partial pressure (PO ₂ ) was measured by a blood gas measuring device (Radioometer BGA3 type), and the partial pressure difference between the artificial lung inlet and the artificial lung outlet was calculated. Details of the specifications of the artificial lung module are shown in Table 2.

(Oxygenator 1B and 2B) The effective length of the hollow fiber membrane 6 is 140 mm, the membrane area is 5.0 m ^2, and bovine blood (standard venous blood) is placed on the outside of the hollow fiber membrane 6 in a single path (5/5). At a flow rate of min, pure oxygen is flown inside the hollow fiber membrane 6 at a flow rate of 5 / min, pH of bovine blood at the inlet and outlet of the artificial lung, carbon gas partial pressure (PCO ₂ ), oxygen gas partial pressure (PO ₂ ) was measured by a blood gas measuring device (BGA3 type, manufactured by Radiometer), and the partial pressure difference between the artificial lung inlet and the artificial lung outlet was calculated. Details of the specifications of the artificial lung module are shown in Table 2.

Table 3 shows the properties of standard arterial blood in the artificial lungs 1A, 1B, 2A and 2B.

As a result, it has been clarified that the artificial lungs 1A and 1B according to the examples of the present invention, in particular, the external perfusion type artificial lung 1B has excellent gas exchange ability.

Further, for comparison with the present invention, Comparative Examples 3 to 6 in which the crimping ratio exceeds the upper and lower ranges of the set range of 0.1 to 0.7% of the present invention.
Is shown in Table 4.

Comparative Examples 3 and 4 show a case where the crimping rate is 1.0% which exceeds the upper limit of the set range of the present invention, and Comparative Examples 5 and 6 show a case where the crimping rate is 0.05% which is below the lower limit.

In Comparative Examples 3 and 4, the occurrence of fiber pinholes was often observed in the course of the experiment, and the data is after repairing them, but it takes labor to repair the pinholes and the workability is extremely poor. there were. Further, Comparative Examples 5 and 6 were inferior in gas exchange ability to the case of the present invention.

[Effects of the Invention] As described above, in the hollow fiber membrane according to the present invention and the hollow fiber membrane-type artificial lung using the hollow fiber membrane, the hydrophobic porous hollow fiber membrane is crimped to form the hollow fiber. The crimp rate after sterilization of the membrane is 0.
Since it is set in the range of 1 to 0.7%, a sufficiently large gap is formed between the hollow fiber membranes and the hollow fiber membranes, and the hollow fiber membranes are formed by actively changing along the axial direction of the hollow fiber membranes. When an oxygen-containing gas is blown into the hollow fiber membrane as a treatment fluid and blood is circulated and circulated as a fluid to be treated outside, a proper gap is formed between the hollow fiber membranes, so that good blood is obtained. And the blood and oxygen-containing gas are evenly contacted through the membrane wall of the hollow fiber membrane over the entire surface of the hollow fiber membrane, the effective membrane area is sufficiently secured, and the turbulent flow in the blood flow is further ensured. As a result, a high gas exchange capacity can be obtained, the flow of the fluid to be treated or the fluid to be treated in the gap becomes smooth, and the effective membrane area where the fluid can contact through the membrane wall of the hollow fiber membrane is positive and Sufficiently secured, it is possible to improve fluid processing capacity and Do not increase the bundle diameter of the empty fiber membrane excessively and eliminate the possibility of causing so-called fiber pinholes due to excessive contact when inserting this into the housing of the artificial lung, for example, and improve workability. And various effects such as easy miniaturization and design.

[Brief description of drawings]

FIG. 1 is a semi-longitudinal front view showing a first embodiment of the hollow fiber membrane-type artificial lung according to the present invention, and FIG. 2 is a half view showing a second embodiment of the hollow fiber membrane-type artificial lung according to the present invention. FIG. 1,31 …… Hollow fiber membrane oxygenator 2,32 …… Housing 6 …… Hollow fiber membrane

Claims (4)

[Claims] 1. A hydrophobic material having a membrane wall, wherein the fluid to be treated is fluid-processed between the fluid to be treated on either the inner side or the outer side thereof and the treatment fluid on the other side through the membrane wall. In the porous hollow fiber membrane of, the crimp ratio after sterilization treatment of the hollow fiber membrane is
A hollow fiber membrane characterized by being set in the range of 0.1 to 0.7%. 2. The hollow fiber membrane according to claim 1, wherein the crimping rate is 0.3 to 0.5%. 3. The hollow fiber membrane has an inner diameter of 100 to 500 μm and a wall thickness of
The hollow fiber membrane according to claim 1, which has a thickness of 27 to 80 µm. 4. The fluid to be treated is blood, and the treatment fluid is an 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 type artificial lung in which a plurality of the hollow fiber membranes are bundled and housed in a housing.