JP2932189B2 - Porous hollow fiber membrane and hollow fiber membrane oxygenator - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a porous hollow fiber membrane having a three-dimensionally complicated hole path and a wall thickness set within a certain range, and a hollow hollow fiber membrane. It relates to a fibrous membrane oxygenator.

[Prior art] In recent years, in cardiac surgery and the like, in order to guide a patient's blood outside the body, add oxygen thereto, and remove carbon dioxide,
Hollow fiber fall membrane oxygenator for extracorporeal circulation is used.

This hollow fiber membrane-type artificial lung is provided, for example, by bundling a plurality of porous hollow fiber membranes having a large number of communication holes communicating with the inner surface side of the membrane wall in a housing, and forming the porous hollow fiber. Blood flows and circulates on one of the inner surface side and outer surface side of the membrane, and blows oxygen-containing gas to the other side, thereby performing gas exchange through communication holes in the membrane wall of the porous hollow fiber membrane.

As a porous hollow fiber membrane used for such a hollow fiber membrane-type artificial lung, a porous hollow fiber membrane which has a crack formed in an axial direction by stretching and has a physically formed communication hole is conventionally known.

As another porous hollow fiber membrane, a porous hollow fiber membrane having a communication hole in which a three-dimensionally complicated passage is formed by, for example, a chemical method is known.

Further, it is also known to apply stretching to these porous hollow fiber membranes to increase the breaking strength by performing a heat treatment or to perform crimping. According to this, the breaking strength is increased due to a large breaking strength. In particular, since the decrease in the effective membrane area is suppressed, and the gap is positively formed between the porous hollow fiber membranes by crimping, and the dispersibility between the hollow fiber membranes is improved, particularly, the hydrophobic porous membrane is preferably used. When blood is flowed to the outer surface side and oxygen-containing gas is blown to the inner surface side of the hollow fiber membrane, the so-called air trap state in which oxygen-containing gas accumulates between the porous hollow fiber membranes is avoided. The effective membrane area is effectively secured, and the gas exchange capacity is improved.

[Problems to be Solved by the Invention] By the way, among the above-mentioned conventional porous hollow fiber membranes, those having communication holes formed physically have a film thickness of 40 μm or less. 20 ~
Since it is a 25 μm thin film, the formed communication holes are uneven, exhibiting a slit shape in the axial direction and a linear shape in the film thickness direction,
The porosity is high, and thus the permeability of water vapor is also high, so that the gas exchange capacity is reduced due to the dew condensation water, and blood cells and plasma leak from the hollow fiber membrane easily occur in a short time. Gas exchange becomes impossible, the effective membrane area is reduced, and the gas exchange ability is reduced, which is a problem.

On the other hand, in those having communication holes in which three-dimensionally complex holes are formed, those having a film thickness of 40 μm or more are also possible. Although the problem has been considerably improved, the control of blood cell and plasma leaks from the hollow fiber membrane is still insufficient, so that blood cells and plasma leak during normal operation time, such as in cardiac surgery. However, there is a possibility that the amount of leakage may gradually increase, and the effective membrane area may not be sufficiently secured, and the gas exchange capacity may not be satisfactory.

The present invention has been made in view of the above problems,
The purpose is to use a hollow fiber membrane having communication holes formed three-dimensionally intricately and by setting its thickness within a certain range, for example, in a hollow fiber membrane type oxygenator equipped with it,
Porous hollow fiber membrane and hollow fiber membrane type capable of obtaining sufficient fluid treatment capacity such as suppressing blood cell and plasma leak from the hollow fiber membrane, securing sufficient effective membrane area, and improving gas exchange capacity To provide an artificial lung.

[Means for Solving the Problems] In order to solve the above-mentioned conventional problems, in the present invention, a porous hollow fiber membrane made of a polyolefin having a substantially circular cross section and performing fluid treatment on a fluid flowing on an inner surface or an outer surface is used. The inner surface side of the porous hollow fiber membrane exhibits a dense layer in which the polyolefin fine particles are tightly bound, and the outer surface side has a porous layer in which polyolefin fine particles are bonded in a chain form, and the outer surface is more outward than the inner surface. A porous hollow fiber membrane in which fine communication holes are formed up to the side, with a wall thickness of 27 to 60 μm, a porosity of 30 to 50%, and a gas flux of 15000 to 35000 / h · m ²
0.5 atm, the average particle size of the polyolefin fine particles is 0.
1 to 2.0 μm, the average pore diameter of the porous hollow fiber membrane is 0.1 to
The present invention proposes a porous hollow fiber membrane having a thickness of 1.0 μm, which is obtained by stretching the porous hollow fiber membrane by 10 to 25%.

Further, in the above configuration, the present invention also proposes a porous hollow fiber membrane obtained by crimping the porous hollow fiber membrane.

In the present invention, the porous hollow fiber membrane has the above-described configuration in which blood flows on one of the inner surface and the outer surface of the porous hollow fiber membrane, and gas exchange is performed between the blood and the other oxygen-containing gas. The present invention proposes a hollow fiber membrane type artificial lung characterized by a configuration in which a plurality of hollow fiber membranes are bundled and housed in a housing.

[Operation] According to the porous hollow fiber membrane and the hollow fiber membrane-type oxygenator of the present invention having the above-described configurations, the thickness of the porous hollow fiber membrane is 27 to 60 μm.
m, and other conditions such as the porosity and the average pore diameter of the hollow fiber membrane are also set to the specific numerical ranges described above. Since it has a configuration in which stretching is performed, the breaking strength of the air-permeable fiber is improved.For example, in a hollow fiber membrane-type oxygenator equipped with the same, the leak of blood cells and plasma from the hollow fiber membrane is suppressed and effective. The membrane area is sufficiently secured and the gas exchange capacity is improved.
The liquid processing ability can be improved.

EXAMPLES Hereinafter, the porous hollow fiber membrane and the hollow fiber membrane-type oxygenator of the present invention will be described based on the first example of the hollow fiber membrane-type oxygenator shown in FIG.

In the drawing, reference numeral 1 denotes a polyolefin hydrophobic porous hollow fiber membrane having a substantially circular cross section. Blood, which is a fluid to be subjected to fluid treatment, flows on the inner surface side of the porous hollow fiber membrane 1, and oxygen-containing gas is blown on the outer surface side thereof.
Gas exchange between carbon dioxide in the blood and oxygen in the oxygen-containing gas is performed through a communication hole communicating the inner and outer surfaces of the membrane wall. Therefore, the hollow fiber membrane oxygenator 20 in the present embodiment is of the internal perfusion type.

The communicating hole exhibits a dense layer in which polyolefin fine particles are tightly bound on the inner surface side of the porous hollow fiber membrane, and a porous layer in which the polyolefin fine particles are bonded in a chain shape on the outer surface side. Since it is formed finely to the side, the pore diameter is small, and the pore path is complicated, so that the gas permeability is enhanced and the leak of blood cells and plasma is suppressed.

Here, it is preferable that the porosity of the communication hole is 30 to 50% and the gas flux is 15000 to 35000 / hour · m ² · 0.5 atm.

In other words, the gas flux is 15000 / hour · m ² · 0.5at
If it is smaller than m, sufficient oxygen will not be supplied to the blood. Conversely, if it is larger than 35000 / hr · m ² · 0.5 atm, there is a risk of blood cell and plasma leaks. A more preferred gas flux is 22000-27200 / hour · m ² · 0.5 atm.

The average particle size of the polyolefin fine particles is 0.1
And the average pore diameter of the porous hollow fiber membrane 1 is:
Those having a thickness of 0.1 to 1.0 μm are good.

Further, in the porous hollow fiber membrane 1, a stretching of 30% or less, preferably 5 to 30%, more preferably 10 to 25% is added thereto, and then a heat treatment is performed to improve the breaking strength. Have been.

If the stretching is less than 1%, the breaking strength of the porous hollow fiber membrane 1 cannot be substantially improved, while the stretching is 30%.
If it exceeds, the microstructure of the porous hollow fiber membrane 1 is affected, and the porosity, gas flux, etc. change,
This is because there is a possibility that the gas exchange capacity is reduced and plasma leakage is caused. The heat treatment is performed at a temperature of 70 to 130 ° C. for 5 seconds to 120 minutes. This heat treatment stabilizes the structure of the hollow fiber membrane and increases the dimensional stability.

The inner diameter of the porous hollow fiber membrane 1 is in the range of 100 to 500 μm, and its thickness is 27 to 80 μm, preferably 27 to 80 μm.
It is set within the range of 60 μm. If the thickness of the porous hollow fiber membrane 1 is less than 27 μm, the hollow fiber membrane becomes hydrophilic in a short time and plasma leakage occurs. On the other hand, if it exceeds 80 μm,
When the hollow fiber membrane is used for an artificial lung, if the effective membrane area is sufficiently ensured, the artificial lung module becomes large,
Conversely, if you try to reduce the size of that module,
The number of hollow fiber membranes required to obtain a given effective membrane area,
It is no longer housed in the module housing.

The porous hollow fiber membrane 1 can be manufactured, for example, through the following steps.

First, as shown in FIG. 2, a blend 51 of a polyolefin, an organic filler, and a plasma nucleating agent is supplied from a hopper 52 to a kneader, for example, a single screw extruder 53, and the blend 51 is melt-kneaded. After being extruded, it is sent to a spinning device 54 and discharged into a gaseous atmosphere, for example, air from an annular spinning hole (not shown) of a spinneret 55, and the hollow material 56 that has come out contains a cooled solidified liquid 57. It is introduced into the cooling tank 58 and is cooled and solidified by contact with the cooling solidified liquid 57. In this case, the contact between the hollow material 56 and the cooling solidification liquid 57 is performed, for example, by allowing the cooling solidification liquid 57 to pass through a cooling solidification liquid flowing pipe 59 provided downward through the bottom of the cooling tank 58. It is preferable that the hollow material 56 is caused to flow downward and to make the hollow material 56 contact in parallel with the flow. The cooled solidified liquid 57 that has flowed down is received and stored in the solidification tank 60, and the hollow material 56 is introduced thereinto, turned by the deflection rod 61, and solidified by sufficiently contacting the solidified cooling liquid 57. The accumulated cooling solidified liquid 57 is discharged from the circulation line 63 and circulated to the cooling tank 58 by the circulation pump 64. Next, the solidified hollow material 56 is guided by a drive roll 62a to a shower-conveyor-type extractor 67 that dissolves the organic filler and drops an extract 65 that does not dissolve the polypropylene in a shower shape. In this extractor 67, the hollow material 56 is
While being conveyed on the belt conveyor 66, the porous hollow fiber membrane 1 is sufficiently brought into contact with the extraction liquid 65 to extract and remove the remaining organic filler, thereby imparting porosity. Drive roll 62
porous hollow fiber membrane 1 derived from extractor 67 by b
After being subjected to further steps such as re-extraction and drying (not shown) as necessary, is guided to the heat treatment apparatus 70 by the drive roll 62c.

At this time, tension acts between the drive roll 62c and the first roller 69 of the heat treatment device 70, and the porous hollow fiber membrane 1
Is subjected to a predetermined proportion of stretching. Inside the heat treatment device 70,
The porous hollow fiber membrane 1 is maintained at a predetermined temperature condition by a heating means such as a heater 68, and is heat-treated while moving between the rollers in the heat treatment apparatus 70, thereby stabilizing the membrane structure. The porous hollow fiber membrane 1 derived from the heat treatment device 70 is wound up on a bobbin 72 by a winding device 71.

Further, the porous air-permeable membrane 1 wound on the bobbin 72 is
After the crimping step, the crimp is performed. That is, with respect to the porous hollow fiber membrane 1,
Wrap it in a cross wound and crimp it, then, for example, at 60 ° C
For 24 hours to fix the crimped state.

Next, the spinning method in the above manufacturing steps will be specifically described. Polyolefin used as a raw material of the porous hollow fiber membrane 1 includes propylene homopolymer,
There are ethylene homopolymers and block polymers with other monomers containing propylene as a main component, and those having a melt index (MI) of 5 to 70 are preferable, and those having an MI of 10 to 40 are particularly preferable. Further, among the above-mentioned polyolefins, a polypropylene homopolymer is particularly preferred, and among them, those having high crystallinity are most preferred.

The organic filler needs to be capable of being uniformly dispersed in the polyolefin while the polyolefin is being melted, and to be easily soluble in the extract as described later. Examples of such organic fillers include liquid paraffin (number average molecular weight of 100 to 2,000), α-olefin oligomers such as ethylene oligomer (average molecular weight of 100
2,000), propylene oligomer, (average molecular weight 100-
2,000), ethylene-propylene oligomer (average molecular weight 100 to 2,000), paraffin wax (number average molecular weight 200 to 2,500), various hydrocarbons and the like, and liquid paraffin is preferred.

The mixing ratio of the polypropylene and the organic filler is 35 to 150 parts by weight, preferably 50 to 100 parts by weight, based on 100 parts by weight of the polypropylene. That is, if the amount of the organic filler is less than 35 parts by weight, a porous hollow fiber membrane having a sufficient gas permeability cannot be obtained. Is reduced. For such raw material blending, for example, a raw material is prepared by a pre-kneading method in which a mixture having a predetermined composition is melt-kneaded using an extruder such as a twin-screw extruder, extruded, and then pelletized. As a crystal nucleating agent, the melting point is
It is an organic heat-resistant substance having a temperature of 150 ° C. or higher (preferably 200 to 250 ° C.) and a gelation point higher than the crystallization start temperature of the polyolefin used. The reason for incorporating such a crystal nucleating agent is to reduce the size of the polyolefin particles, thereby narrowing the voids between the particles, that is, the communication holes, and increasing the pore density. As an example, for example, benzylidene sorbitol, 1,3,2,4-benzylidene sorbitol, 1,3,2,4-bis (p-methylbenzylidene)
Sorbitol, 1,3,2,4-bis (p-ethylbenzylidene) sorbitol, sodium bis (4-t-butylphenyl) phosphate, sodium benzoate, adipic acid, talc, kaolin and the like are crystal nucleating agents. Benzylidene sorbitol, especially 1,3,2,4
-Bis (p-ethylbenzylitene) sorbitol, 1.
3,2,4-Bis (p-methylbenzylidene) sorbitol is preferable since it hardly elutes into blood.

The compounding ratio of the polypropylene and the crystal nucleating agent,
Crystal nucleating agent is 0.1 to 100 parts by weight of polypropylene
It is 5 parts by weight, preferably 0.3 to 1.0 part by weight.

The raw material mixture prepared in this way is a single screw extruder
Using 53, for example, 160 to 250 ° C, preferably 180 to 220 ° C
Is melted and kneaded at a temperature of, and if necessary, discharged from the annular spinning hole of the spinneret device 55 of the spinning device 54 into a gas atmosphere using a gear pump having a high degree of quantitativeness, thereby forming a hollow material 56. Note that an inert gas such as nitrogen, carbon dioxide, helium, argon, or air may be self-primed at the center of the inside of the circular spinning hole, or if necessary, these inert gases may be forcibly introduced. May be. Subsequently, the hollow object 56 discharged from the circular spinning hole is dropped, and is then brought into contact with the cooling solidified liquid 57 in the cooling tank 58. The falling distance of hollow objects is 5 to 1,000 mm
Is preferred, and particularly preferably 10 to 500 mm. That is, when the falling distance is less than 5 mm, pulsation occurs and the cooling solidified liquid 57
This is because the hollow object 56 may be crushed when it enters. In the cooling tank 58, the hollow object 56 is not sufficiently solidified yet, and since the center is gaseous, it is easily deformed by an external force. The cooling solidified liquid 57 is caused to flow down into the cooling solidified liquid flowing pipe 59 provided, and the hollow object 56 is forcibly moved by bringing the hollow object 56 into parallel contact along the flow, In addition, hollow deformation due to external force or fluid pressure can be prevented. At this time, the flow rate of the cooling solidified liquid 57 is sufficient under natural flow. The cooling temperature at this time is
The temperature is 10 to 60 ° C, preferably 20 to 50 ° C. That is, 10 ° C
If the temperature is less than 60 ° C., the solidification rate of cooling is too high, and most of the thick part becomes a dense tank, so that the gas exchange capacity becomes low. Not only does the particle size of the fine particles on the side become too large and the fine communication holes become too large, but the dense tank becomes extremely thin or disappears at a higher temperature. This may cause clogging or leakage of blood cells and plasma.

As the cooling solidified liquid 57, the polyolefin is not dissolved,
Any substance having a relatively high boiling point can be used.
Examples include alcohols such as methanol, ethanol, propanols, butanols, hexanols, octanols, and lauryl alcohol, liquid fatty acids such as oleic acid, palmitic acid, myristic acid, and stearic acid, and alkyl esters thereof. (E.g., esters such as methyl, ethyl, isopropyl, and butyl), octane, nonane, decane, kerosene, via, liquid hydrocarbons such as toluene, xylene, and methylnaphthalene, and 1,1,2-trichloro-1,2. , 2-trifluoroethane,
Trichlorofluoromethane, dichlorofluoromethane,
Examples thereof include halogenated hydrocarbons such as 1,1,2,2-tetrachloro-1,2-difluoroethane and the like, but are not limited thereto.

As a method for dissolving and extracting the organic filler, an extraction solution 65 is added to a hollow material 56 on a belt conveyor as shown in FIG.
The method is not limited to the shower method in which the shower is lowered, and the extraction tank method, when rewinding the hollow material 56 once wound up to another case, a rewinding method in which the case is immersed in the extraction solution 65, and the like is used. Any method may be used as long as the substance 56 can come into contact with the extract 65, and two or more of these methods may be combined.

As the extraction liquid 65, any one can be used as long as it does not dissolve the polypropylene constituting the porous hollow fiber membrane 1 and can dissolve and extract the organic filler. For example,
For example, methanol, ethanol, propanols, butanols, pentanols, hexanols, octanols, alcohols such as lauryl alcohol, 1,1,
2-trichloro-1,2,2-trifluoroethane, trichlorofluoromethane, dichlorofluoromethane, 1,1,2,2
-There are housing-containing hydrocarbons such as tetrachloro-1,2-difluoroethane and the like, and among these, halogenated hydrocarbons are preferable in terms of their ability to extract organic fillers, and in particular, in view of safety to the human body, fluorine chloride is preferred. Hydrocarbons are preferred.

The porous hollow fiber membrane 1 manufactured by the above method is a first hollow fiber membrane.
As shown in the figure, a large number of, for example, 10,000 to 100, are spread throughout a housing 2 formed of a cylindrical main body 3 and annular mounting covers 4, 5 with male threads located at both ends thereof.
The 60,000 pieces are arranged in parallel and separated from each other along the longitudinal direction of the housing 2 in a bundled state. Both ends of the porous hollow fiber membrane 1 are liquid-tightly supported by partitions 6 and 7 in the mounting covers 4 and 5 with their respective openings not closed. Each of the partition walls 6 and 7 forms a gas chamber 8 between the outer peripheral surface of the porous hollow fiber membrane 1 and the inner surface of the housing 2. Further, one mounting cover 5 is provided with an oxygen-containing gas inlet 9 for supplying an oxygen-containing gas, and the other mounting cover 4 is provided with an oxygen-containing gas outlet 10 for discharging the oxygen-containing gas. I have.

On the inner surface of the cylindrical main body 3 of the housing 2, there may be provided a throttle restricting portion 11 which is located at the center in the axial direction and protrudes. As described above, the gas exchange capacity can be improved by providing the restricting restricting portion 11 at the center portion. However, since the porous hollow fiber membrane 1 is crimped as described above, such a restricting operation is performed. A high gas exchange capability can be obtained without providing the restraint portion 11 for use. The constraining portion 11 is formed integrally with the tubular body 3 on the inner surface of the tubular body 3, and is a hollow fiber bundle made up of a number of porous hollow fiber membranes 1 inserted into the tubular body 3.
The outer circumference of 12 is to be tightened. In this way, the hollow fiber bundle 12 is narrowed down at the center in the axial direction, and forms the narrowed portion 13. Therefore, the filling rate of the porous hollow fiber membrane 1 differs in each part along the axial direction, and is highest in the central part.

The outer surfaces of the bulkheads 6 and 7 have a conical blood port cover 1.
Covered with 4,15 respectively. This blood port cover 1
Reference numerals 4 and 15 are screwed and fixed to the mounting covers 4 and 5, respectively, and a blood inflow chamber 16 and a blood inflow chamber 17 are formed therein. The blood port covers 14 and 15 are provided with a blood inlet 18 and a blood outlet 19, respectively.

In the present embodiment, with the above-described configuration, the leakage of blood cells and plasma from the porous hollow fiber membrane is suppressed, the effective membrane area is sufficiently secured, and the gas exchange ability is improved. It becomes possible.

In addition, a sufficiently large gap is obtained between each of the porous hollow fiber membranes 1 by crimping. Therefore, the oxygen-containing gas blown into the gas chamber 8 satisfactorily flows through the gap. The breaking strength of the hollow fiber membrane is improved, and therefore, when the hollow fiber membrane is disposed in the housing 2, breakage is less likely to occur. As a result, the effective membrane area is sufficiently ensured, and the gas exchange capacity is high. Thus, the priming volume can be reduced, and the burden on the patient can be reduced during cardiac surgery and the like.

Next, as another embodiment of the hollow fiber membrane type artificial lung of the present invention, a so-called external perfusion type in which blood flows on the outer surface side of the porous hollow fiber membrane 1 and oxygen-containing gas is blown on the inner surface side. Will be described with reference to FIG. The hollow fiber membrane-type artificial lung 21 according to the present embodiment includes a housing 22 and oxygen-containing gas port covers 23 and 24 provided at both ends thereof. Inside the housing 22, as in the previous embodiment, the partition 6,
7 and the same porous hollow fiber membrane 1 as in the first embodiment.
Is supported. The partition walls 6 and 7 allow the housing 22
Inside, a blood chamber 25 is formed, and inside the oxygen-containing gas port covers 23 and 24, the inflow chamber and the outflow chamber 23a and 24a of the oxygen-containing gas are provided.
Is formed. The housing 22 has a blood inlet 26 for supplying blood and a blood outlet for discharging blood.
27 are provided respectively. An oxygen-containing gas inlet 27 and an oxygen-containing gas outlet 28 are formed in the oxygen-containing gas port covers 23 and 24, respectively.

Other configurations are the same as those of the hollow fiber membrane-type artificial lung 20 according to the above-described first embodiment, and a description thereof will be omitted.

In this embodiment, with the above configuration, the oxygen-containing gas blown into the inside of the porous hollow fiber membrane 1 from the oxygen-containing gas inflow chamber 23a through the communication hole of the porous hollow fiber membrane 1 When contacting the blood flowing through the gap between the porous hollow fiber membranes 1,
It is difficult for the air to be trapped in the gap, and therefore, for the so-called air trap. This improves the flow of blood in the gap and eliminates the inhibition of blood and oxygen-containing gas coming into contact with the oxygen-containing gas through the porous hollow fiber membrane 1 due to the lump of oxygen-containing gas trapped in the air. And
Therefore, a sufficient effective area is ensured.

Other operations and effects are the same as those of the first embodiment.

Next, as a third embodiment of a hollow fiber membrane oxygenator, an oxygenator with a heat exchanger capable of adjusting the temperature of blood circulated extracorporeally will be described with reference to FIG.

The heat exchanger 31 has a cylindrical housing 32, and a heat exchange tube 33 through which blood flows is housed in the cylindrical housing 32. The heat exchange tube 33 is formed of a number of heat exchange thin tubes, and as a material of the heat exchange tube 33, a metal tube having high heat conductivity, for example, a stainless tube, aluminum, or a copper tube is often used. , Having an inner diameter of 0.5 to 10 mm, preferably 2 to 5 mm, are housed in the housing in an amount of about 10 to 2,000, preferably about 50 to 1,000. In FIG. 4, a straight tube is used as the heat exchange tube 33, but is not limited thereto, and may be a spiral tube.

Both ends of the heat exchange tube 33 are attached to the housing 32 by partition walls 34, 3
5 is liquid-tight. As a material of the partition walls 34 and 35, a polymer potting agent such as polyurethane and silicone rubber is used. And. Around the heat exchange tube 33, partition walls 34 and 35 form a cylindrical housing 32.
A heat exchange fluid chamber is provided therein. The tubular housing 32 is provided with a heat exchange fluid inlet 36 and an outlet 37 communicating with the heat exchange fluid chamber.

The shape of the housing 32 is formed in a cylindrical shape, a polygonal cylindrical shape, or the like. Preferably, it is cylindrical. Further, as a material used for molding the housing 32, various materials such as polycarbonate, acrylic / styrene copolymer, acrylic / butylene copolymer can be used.

Further, a blood introduction port 39 having a blood inflow port 38 and communicating with the internal space of the heat exchange tube 33 is attached to the outside of the partition wall 34 in a liquid-tight manner. Further, the blood introduction port 39 is provided with a drug solution injection port 40 and a blood sampling port 41.
have. The blood introduction port 39 is mechanically fitted to the end of the housing 32, and the O-ring provided on the inner surface of the port 39 is in close contact with the outer peripheral edge of the partition wall 34, so that the two are liquid. Tightly sealed.

On the other hand, a heat exchange tube 33 is open at the end of the partition wall 35. The end of the enlarged diameter portion 32a of the housing 32 is mechanically fitted to the inflow end of the housing 2 of the hollow fiber membrane type artificial 44 similar to that of the first embodiment, The partition wall 35 of the heat exchanger 31 and the partition wall 6 of the hollow fiber membrane oxygenator 44 face each other, and both are sealed in a liquid-tight manner by an O-ring 42 provided therebetween. .

On the other hand, a blood outlet port 42 similar to the blood inlet port 39 is attached to an end of the hollow fiber membrane type artificial lung 44 on the outflow side of the housing 2.

 In the figure, reference numeral 43 denotes a blood outlet.

Further, the hollow fiber membrane type artificial lung 44 in this embodiment is not provided with the restricting restricting portion 11 as shown in FIG. 1, but the porous hollow fiber membrane 1 is crimped as described above. Therefore, a sufficient effective film area is secured.

As described above, the present invention has been described with reference to the embodiments. However, the present invention is not limited to the above embodiments, and can be variously modified without changing the gist of the present invention. The following experiment was performed on the oxygenator according to the above-described example in order to secure the effect.

(Experimental example) The porous hollow fiber membrane according to this experimental example was manufactured by the following method.

For 100 parts by weight of a propylene homopolymer having a melt index (MI) of 23, 130 parts by weight of liquid paraffin (number average molecular weight 324) and 1,3,2 as a crystal nucleating agent
• Charged with 0.5 parts by weight of 4-bis (ethylbenzene) sorbitol, a twin-screw extruder (PCM-30-, manufactured by Ikegai Iron Works Co., Ltd.)
The mixture was melt-kneaded according to 25), extruded, and pelletized. The pellets were melted at 180 ° C. using an apparatus as shown in FIG. 1, ie, a single screw extruder (Kasamatsu Seisakusho, WO-30) 53, and the core diameter was 4 mm, the inner diameter was 6 mm, the outer diameter was 7 mm, and the land length was 15 mm. Was discharged into the air at a discharge rate of 3.6 to 5.0 g / min from the circular spinning hole, and the hollow material 56 was dropped. The fall distance is 20-30mm
Met. Subsequently, the hollow material 56 is cooled and solidified in a cooling tank 58.
Freon 113 as 17 (1,1,2-trichloro-1,2,2-
After contact with trifluoroethylene), it was cooled by being brought into parallel contact with the cooling solidified liquid 57 flowing down naturally in the cooling solidified liquid flowing pipe 19. At this time, the temperature of the cooled solidified liquid 57 is 20 ° C.
Met. Then, after introducing the hollow material 56 into the cooling and solidifying liquid 57 in the solidification tank 60, it was turned by the turning rod 61 to 80 m /
The liquid paraffin was completely extracted with the extraction liquid 65 composed of Freon 113 in a shower-conveyor-type extractor 67, which was guided to the drive roll 21a with a winding speed of min. While the porous hollow fiber membrane 1 thus provided with porosity is taken out of the extractor 67 by the drive roll 62b and sent to the heat treatment device 70, the drive roll 62b
And the first roll 69 of the heat treatment apparatus 70 is stretched at the ratio shown in Table 1, and while passing through the heat treatment apparatus 70,
Heat treatment was performed at 0 ° C. for 20 seconds. The porous hollow fiber membrane 1 having passed through the heat treatment apparatus 30 was wound up by a winder 71 into a bohin 72. Further, it was wound up from the bobbin 72 to another bobbin (not shown) in a cross winding, and then heat-treated at 60 ° C. for 24 hours and crimped.

The porous hollow fiber membrane thus obtained, whose thickness is set in the range of 27 to 80 μm, has a shape (inner diameter / thickness), an elongation ratio, a porosity, a gas flux, and a polyolefin. The average particle diameter of the fine particles, the average pore diameter, the crimp ratio indicating the crimpability, the breaking strength, the oxygen gas adding ability, the carbon dioxide gas removing ability, and the leak of blood cells and plasma from the hollow fiber membrane were measured. The results obtained are shown in Tables 1 and 2 for plasma leaks and in Table 3 for others.

(Comparative Example) For comparison with the above experimental example, a porous hollow fiber membrane having a thickness outside the range of 27 to 80 μm and having a crack formed by stretching to form a physically communicating hole is the same as above. Was measured. The obtained results are shown in Tables 1 to 3 in the same manner as described above.

The definition of each term and the measurement method in these experimental examples and comparative examples are as follows.

Shape (inner diameter / thickness) Ten pieces of the obtained porous hollow fiber membranes are arbitrarily extracted, and a material prepared by cutting each porous hollow membrane into a length of about 0.5 mm with a sharp razor is prepared. Project the cross section with a universal projector (Nikon Profile Projector, V-12) and measure it (Nikon Digital Counter, CM-6S).
As shown in FIG. 5, the thickness t ₁ and t ₂ along one direction of the cut surface of the material and the inner diameter d ₁ are measured, and the thickness t ₃ and t along the direction perpendicular to the one direction. ₄ and measuring the inner diameter d _2. Then, the article of the porous hollow fiber membrane, obtains the respective mean value of the thickness _{t 1, t 2, t 3} , t 4 and an inner diameter d _1, d _2, averaged for further ten it, its The values are defined as the inner diameter and thickness of the porous hollow fiber membrane.

Porosity (%) Approximately 2 g of the obtained porous hollow fiber membrane is cut into a length of 5 mm or less using a sharp razor. The obtained material was measured using a mercury porosimeter (Carlo Elba, 65A type) at 1,000 kg /
Pressure is applied to cm ² , and the porosity is obtained from the total amount of pores (pore volume of the porous hollow fiber membrane per unit weight).

Gas flux The obtained porous hollow fiber membrane, effective length 23 cm, membrane area 0.1 m
^After making one mini-module and closing one end, a pressure of 0.5 atm was applied to the inside of the hollow fiber with oxygen, and the flow rate of oxygen gas when it was in a steady state was measured with a flow meter (Kusano Rikagaku Seisakusho, Ltd. (Float meter).

Oxygen gas addition ability, carbon dioxide gas removal ability (First embodiment) The obtained porous hollow fiber membrane is used, and the other points are the same as in the first embodiment shown in FIG. ²⁾ Create an artificial lung module, flow bovine blood (standard venous blood) inside the hollow fiber at a flow rate of 5.0 / min using a single path, and flow pure oxygen outside the hollow fiber at a flow rate of 5.0 / min. The pH of the bovine blood at the inlet and outlet of the artificial lung, the partial pressure of carbon dioxide (PCO ₂ ), and the partial pressure of oxygen gas (PO ₂ ) were measured with a blood gas measurement device (Radometer, BGA3 type). The partial pressure difference with the outlet was calculated.

(Second Embodiment) Using the obtained porous hollow fiber membrane, an artificial module having an effective length of 90 mm and a membrane area of 3.0 m ² was prepared in the same manner as the second embodiment shown in FIG. The bovine blood (standard venous blood) flows outside the thread at a flow rate of 5.0 / min in a single pass (Single Path), and pure oxygen flows at a flow rate of 5.0 / min inside the hollow fiber. The pH, the partial pressure of carbon dioxide (PCO ₂ ), and the partial pressure of oxygen gas (PO ₂ ) were measured with a blood gas measuring device (BGA3, manufactured by Radiometer), and the partial pressure difference between the inlet and outlet of the artificial lung was calculated.

Plasma leak An artificial lung module similar to that used for oxygen gas addition and carbon dioxide elimination was created, and partial VA bypass was performed by cervical stasis and carotid artery cannulation using a small dog (about 20 kg in body). The artificial lung module was charged in the circuit, extracorporeal circulation was performed for 30 hours, and it was observed whether plasma leaking from the inside of the porous hollow fiber membrane was observed.

Breaking strength (g / to) Ten pieces of a porous air-permeable membrane cut to a length of about 10 cm were prepared and measured one by one with a Toyo Seiki strograph T under the following conditions. Was calculated.

Chuck used: Wide box chuck Initial length: 20 mm Tensile speed: 20 mm / min Temperature: 23 ° C Crimp rate The measurement method used was the crimp rate measurement method of JIS L 1074 6.11.2.

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

First, a load of 1 g was applied to a porous hollow fiber membrane having a length of 70 mm by the present testing machine, and the weight at that time was defined as a.
The length when a weight of 10 g is applied is defined as b, and between the weights of 1 g and 10 g is 3 according to the cycle test mode of the strograph.
A cycle test was performed at the above-mentioned tensile speed, and the average value of the three times was defined as each value of a and b. From the measurement of a and b,
The crimp rate was obtained by the following formula.

Crimp rate (%) = (ba) / a x 100 Average particle size of polyolefin fine particles A porous hollow fiber membrane is hardened with an epoxy adhesive, put in liquid nitrogen, and folded in liquid nitrogen. The cross section was photographed with a scanning electron microscope at a magnification of 10,000 times, and the particle diameter was measured from the photographed photograph.

Average pore diameter Measured with a mercury porosimeter manufactured by Carlo Elba. That is, mercury is put around the porous hollow fiber membrane, and the measurement is performed in a state where the mercury is pressurized. At this time, the relationship between the pressure and the pore radius is obtained by knowing the surface tension of the porous hollow fiber membrane in advance, and the pore radius is obtained from the amount of mercury entering the pores at a constant pressure. Can be

Blood Cell Leak (Test for Blood Cell Leak by Temperature Change) Using the obtained porous hollow fiber membrane, an artificial lung module with an effective length of 140 mm and a membrane area of 5.0 m ² similar to the first embodiment shown in FIG. The blood was circulated alternately four rounds at a blood temperature of 37 ° C. for 10 minutes and then at a temperature of 25 ° C. for 10 minutes to perform a leak test. Table 1 shows the results. Here, the blowing rate of the oxygen-containing gas was 10 / min when the blood was at 37 ° C. and 4 / min when the blood was at 25 ° C., and the hematocrit value (Ht) was 35.0%.

(Circulation of blood, insufflation of oxygen-containing gas, blood cell leak test by stopping these circulations and insufflation) Create an artificial lung module similar to the fiber test by temperature change, and perform blood circulation and air insufflation for 30 minutes. , Their circulation,
The operation of stopping the blowing for 30 minutes was repeated five rounds, and a leak test was performed. Table 2 shows the results. Here, the blood flow rate is 2.0 / min, the air blowing rate is 2.5 / min, the hematocrit value (Ht) is 35.0%, and the blood temperature is
37 ° C.

As is clear from Tables 1 to 3, in the porous hollow fiber membrane and the hollow fiber membrane oxygenator in which the thickness of the porous hollow fiber membrane is set in the range of 27 to 80 μm, the thickness is 27 mm. Compared to those outside the range of ~ 80 μm, the leak of blood cells and plasma from the hollow fiber membrane, the ability to add oxygen gas, the ability to eliminate carbon dioxide,
Good results were obtained.

[Effect of the Invention] As described above, according to the porous hollow fiber membrane and the hollow fiber membrane type oxygenator according to the present invention, the thickness of the porous hollow fiber membrane is reduced.
It is set in the range of 27 to 60 μm, and other conditions such as the porosity of the hollow fiber membrane and the average pore diameter are also set in the specific numerical ranges defined in the present invention. Up to 25% stretched structure improves the breaking strength of the hollow fiber. For example, in a hollow fiber membrane-type artificial lung using the same, the leak of blood cells and plasma from the hollow fiber membrane is suppressed. As a result, various effects are exhibited, such as ensuring a sufficient effective membrane area, improving gas exchange performance, and improving fluid treatment performance.

[Brief description of the drawings]

FIG. 1 is a longitudinal sectional view of a first embodiment of a hollow fiber membrane-type oxygenator of the present invention, FIG. 2 is a schematic view showing a manufacturing process of a porous hollow fiber membrane of the present invention, and FIG. Of hollow fiber membrane type oxygenator
FIG. 4 is a semi-longitudinal sectional view showing an oxygenator with a heat exchanger as a third embodiment of the hollow fiber membrane-type artificial lung, and FIG. 5 is a porous hollow fiber membrane. FIG. 4 is an explanatory diagram of measurement of an inner diameter and a wall thickness of the sample. 1 ... porous hollow fiber membrane 2,22 ... housing 20,21,44 ... hollow fiber membrane oxygenator

Claims (3)

(57) [Claims] 1. A porous hollow fiber membrane made of a polyolefin having a substantially circular cross section for fluid treatment of a fluid flowing on an inner surface or an outer surface, wherein the polyolefin fine particles are densely packed on the inner surface of the porous hollow fiber membrane. The outer surface side is a porous hollow fiber membrane in which a fine layer of polyolefin is present as a porous layer bonded in a chain form and fine communication holes are formed from the inner surface side to the outer surface side while presenting a dense layer, Wall thickness 27-60μ
m, porosity 30-50%, gas flux 15000-35000
/ H · m ² · 0.5 atm, the average particle diameter of the polyolefin fine particles is 0.1 to 2.0 μm, and the average pore diameter of the porous hollow fiber membrane is 0.1 to 1.0 μm. twenty five%
A porous hollow fiber membrane characterized by being drawn. 2. The porous hollow fiber membrane according to claim 1, wherein the porous hollow fiber membrane is crimped. 3. The porous membrane according to claim 1, wherein blood flows through one of an inner surface and an outer surface of the porous hollow fiber membrane, and gas exchange is performed between the blood and the other oxygen-containing gas. A hollow fiber membrane-type oxygenator, comprising a plurality of hollow fiber membranes bundled together and housed in a housing.