CA1324470C

CA1324470C - Porous hollow fiber membrane, method for production thereof, and oxygenator using the hollow fiber membrane

Info

Publication number: CA1324470C
Application number: CA000581450A
Authority: CA
Inventors: Kousuke Kido; Ken Tatebe
Original assignee: Terumo Corp
Current assignee: Terumo Corp
Priority date: 1987-10-29
Filing date: 1988-10-27
Publication date: 1993-11-23
Anticipated expiration: 2010-11-23
Also published as: JPH01115364A; JPH067859B2

Abstract

ABSTRACT OF THE DISCLOSURE
The present invention is directed to a hydrophobic porous hollow fiber membrane possessing an inside diameter in the range of 150 to 300 microns, a wall thickness in the range of 10 to 150 microns, and a substantially circular cross section, which porous hollow fiber membrane possesses an average crimp amplitude in the range of 35 to 120% of the outside diameter, a maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio in the range of 0.01 to 0.1, and a crimp ratio in the range of 1.0 to 3.0%, a method for the production thereof, and an oxygenator using the same.

Description

~ 324470 POROUS HOLLOW FIBER MEMBRANE, METHOD FOR PRODUCTION THEREOF, AND
OXYGENATOR USING THE HOLLOW FIBER MEMBRANE

sAc~GRouND OF THE INVENTION

5 Field of the Invention:
This invention relates to a porous hollow fiber membrane, a method for the production thereof, and an oxygena~or using the hollow fiber membrane. More particularly, this invention relat~s to a porous hollow 10 fiber membrane possessing a high gas-~xchange capacity and, at the same time, offering a large available membrane area for the exchange of gas, a method ~or the production thereof, and an oxygenator using the hollow fiber membrane. Still more particularly, this invention 15 relates to a porous hollo~ fiber membrane which, no matter whether the oxygenator to be u~ed may be adapted to pass blood inside or outside the hollow fiber membrane, re~rains from inflicting damage to the blood cell components or aggravat~ng pressure loss, exhibits 20 high efficiency in e~tablishing gas-liquid contact, suffers fro~ no blood plasma leakage over a protracted ~ervice, and manife~ts a high gas-exchange càpacity, a method for the production thereof, and an oxygenator u~ing the hollo~ fiber membrane.
25 De~cription of the Prior Art:
; Generally in the surgical operation of the bR~rt, for example, an oxygenator of hollow fiber mombrane i~ u~ed in the extracorporeal ~irculation ~y~tem for the purpo~ of leading a patient's blood out 30 of hiQ body and adding oxygen to and r~moving carbon ~ diox~de ga~ from~the blood. T~e hollow fiber membranes a~aila~bla for the oxygenator of this nature fall under t~o kinds; homogenous membranes and porous membranes.
The homogeneous membranes attain movement of a gas by 35 the molecules of the permeating gas being dissolved and - 1 - ~' '''", ,.' :.' ' dispersed in the membrane. These homogeneous membranes are represented by silicone rubber (commercialized by Senkouika Kogyo under trademark designation of "Mella-Siloz," for example). In the homo~eneous membranes, the silicone rubber membrane is the only product that has been heretofore accepted as practicable from the standpoint of gas permeability. The silicone rubber membrane is not allowed to have any smaller wall thickness than loo ~m on account of limited strength. Thus, it has a limited capacity for permeation of gas and it is particularly deficient in the permeation of carbon dioxide gas. Moreover, the silicone rubber has a disadvantage that it is expensive and difficult to fabricate.
By contrast, in the porous membranes, since the micropores possessed by the membrane are notably large as compared with the molecules of a gas to be permeated, the gas passes the micropores in the form of volume flow. Various oxygenators using such microporous membranes as microporous polypropylene membrane have been proposed, for example. It has been proposed, for example, to produce porous polypropylene hollow fibers by melt spinning polypropylene through hollow fiber pxoducing nozzles at a spinning temperature in the range of 210 to 270C at a draft ratio in the range of 180 to 600, then subjecting the resultant hollow threads of polypropylene to a first heat treatment at a temperature not exceeding 155C, stretching the heated hollow threads by a ratio in the range of 30 to 200~ at a temperature not exceeding 110C, and thereafter subjecting the stretched hollow threads to a second heat treatment at a temperature exceedinq that of the first heat treatment and not exceeding 155C. These porous hollow fibers obtained by the method just mentioned are physically caused to form micropores therein by the hollow threads of polypropylene being stretched. These micropores, therefore, are linear LC :*b - 2 -'~S ~ ` :
,, micropores e~tending substantially perpendicularly horizontally relative to the wall thic~ness proportionately to the degree of stretching while forming cracks in the axial direction of hollow fiber. Th~s, they have a cross section in the shape of a slit. Further, the micropores run substantially linearly and continuously through the wall thickness and occur in a high void ratio. The porous hollow fibers, therefore, have a disadvantage that they have high permeability to steam and, after a protracted use for extracorporeal circulation of blood, suffer from leakage of blood plasma.
As a porous membrane incapable of blood plasma leakage, for example, there has been proposed a porous polyolefin hollow fiber membrane which is produced by mixing a polyolefin, an organic filler uniformly dispersible in the polyolefin in the molten state thereof and easily soluble in a liquid extractant to be used, and a crystal seed forming agent, melting the resultant mixture, discharging the molten mixture through annular spinning nozzles and, at the same tim~, introducing an inert gas into the inner cavities of the spun tubes of the molten mixture, causing the resultant hollow threads to contact a cooling and solidifying liquid incapable of dissolving t~e polyolefin thereby cooling and solidifying the hollow threads, then bringing the cooled and `~
solidified hollow threads into contact with a liquid extractant incapable of dissolving the polyolefin, thereby axtracting the organic filler from the hollow threads. The polypropylene hollow fiber membrane which, as one species of the hollow fiber membranes, is produced by using as a cooling and solidifying liquid a specific cooling and solidifying liquid heretofore favourably utilized on account of the ability thereof to dissolve the organic filler dies not ~`
suffer from blood plasma leakage because the pores formed therein are small in diameter and complex in channel pattern. ~
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_ 3 -._ ';:'., :.' Since this membrane has a smal~2po~l Q nsity per unit area, it has a possibility of exhibiting a gas-exchange capacity insufficient for the membrane to be used effectively in an oxygenator. It also has another possibility that the low molecular component of the polyolefin will mingle into the cooling and solidifying liquid capable of dissolving the organic filler and eventually adhere to the inner wall of the cooling bath tube and cause deformation of the shape of the hollow fiber with elapse of time.
10To overcome the impact of such a drawback as mentioned above, there has been proposed a porous polyolefin hollow fiber membrane which is produced by mixing polypropylene, an organic filler uniformly dispersible in the polypropylene in the molten state thereof and readily soluble in a liquid extractant to be used, and a crystal seed forming agent, melting the resultant ~ixture and discharging the molten mixture through annular spinning nozzles into hollow threads, allowing the hollow threads to contact a liquid made `.
of tha organic filler or a similar compound thereby cooling and solidifying the hollow threads, then bringing the cooled and solidified hollow threads into contact with a liquid Qxtractant incapable of melting the propylene thereby extracting the organic filler from the hollow threads. The hollow fiber membrane produced by this method is free from the ~rawbacks described so far~ During the course of the cooling, however, the orqanic filler or the cooling and solidifying liquid remains locally on the outermost surface of hollow fibers before these hollow fibers are thoroughly cooled and solidified and the compositional proportion of polypropylene is lower in the outermost surface than elsQwhere in the entire wall thickness and, as a result, the pores in the outer surface of the hollow fiber are large . .

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and the propylene particles are interconnected in the parttern of a network and distributed in a heavily rising and falling state. The hollow fibers of this nature pose no problem whatever when they are used in an 5 oxygenator of the type adapted to effect addition of oxygen to blood and removal of carbon dioxide gas therefrom by flowing the blood inside the hollow fibers and blowing an oxygen-containing gas outside the hollow tubes. When the hollow fibers are used in an oxygenator 10 of the type adapted to effect the same functions by flowing blood outside the hollow fibers and blowing the oxygen-containing gas inside the hollow fibers, however, they have a disadvantage that the aforementioned behavior of the outer surface inflicts damage to the blood cell components and aggravateSthe pressure loss.
The hollow fiber membrane, without reference to the type of oxygenator, has a disad~antage that the ~ork of assembling the hollow fibers into the oxygenator neither proceeds efficiently nor produces a desirable potting 20 because the adjacent hollow fibers coalesce. In the case of -the oxygenator which is $ormed of the porous hollow fiber membranes obtained as described above and is operatea by circulating blood outside the hollow fiber membranes and blowing an oxygen-containing gas 25 inside the hollo~ fiber membranes, if the gaps between the ad~acent hollow fibers are narrow and substantially uniform in width throughout the entire length of hollow fibers, the air or the oxygen-containing gas is liable to stagnate easily in these gaps because of the 30 hydrophobicity of the hollow fiber membranes. If the stagnation of the air or the oxygen-containing gas or the so-called phenomenon of air trap arises in the gaps b~tween the adjacent hollow fibers, it impairs the flow of blood and entails a disadvantage that the clusters of 35 t~e entrapped air or oxygen-containing gas obstruct the blood from gaining access to the air or oxygen-containing gas through the hollow fiber `
_ 5~

~.:, ., membranes, lend themselves to descreasing the available membrane area, cmd degrade the oxygenator's gas-exchange capacity.
An object of this invention, therefore, is to 5 provide an improved porous hollow fiber membrane, a method for the production thereof, and an oxygenator using the hollow fiber membrane. Another object of this invention is to provide a porous hollow fiber membrane possessing a high gas-exchange capacity and, at the same 10 time, offering a large available membrane area for exchange of gas, a method for the production thereof, and an oxygenator using the hollow fiber membrane. A
further object of this invention is to provide a porous hollow fiber membrane of polypropylene which, without 15 refersnce to the type of oxygenator, refrains from ~ .~ ~ damage to the blood cell components and - aggravating the pressure loss, entails no blood plasma lea~age over a protracted service, experiences no decline of the gas-exchange capacity due to the air ~0 trap, exhibits a high gas-exchange capacity, and warrants favorable u~e in an oxygenator using the hollow fiber membrane~ Yet another object of this invention is to provide a porou~ hollow fiber membrane possessing a smooth outer surface and defying coalescence of the 25 ad~acent hollow fibers during the assembly of an oxyganator, a method }or the production thereof, and an oxygenator using the hollow fiber membrane.
SUNNARY OF THE INVENTION
~ The ob~ects mentioned above are accomplished 30 by a hydrophobic porous hollow fiber memlbrane possessing an in~ida diameter in the range of 150 to 300 microns, a wall thickness in ~he range of 10 to 150 microns, and a substantially circular cross section, which porous hollo~ fiber membrane possesses an average crimp 35 amplitude in the range of 35 to 120~ of the outside diameter, a maximum crimp amplitude~crimp half cycle period at maximum crimp amplitude ratio in the range of O . 01 to o.l, and a crimp ratio in the range of 1.0 to 3 .0% .
This invention also discloses a porous hollow S fiber membrane wherein the void ratio is in the range of 5 to 60~. This invention further discloses a porous hollow fiber membrane wherein the oxygen gas flux is in the range of 0.1 to 2,000 1/min.m2.atm~ This invention discloses a porous hollow fiber membrane wherein the 10 inside diameter is in the range of 180 to 250~m and the wall thic~ness is inJthe range of 20 to 100 ~m. This invention also discloses a porous hollow fiber membrane which is made o~ polypropylene. This invention further discloses a porous hollow fiber membrane wherein the 15 average cr~mp ampli~ude is in the range of 50 ~o 100~ of the outside diameter, the maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio is in the range of 0.02 to 0.05, and the crimp ratio is in the range of 2.Q to 3.0%. This invention discloses a 20 hydrophobic porous hollow fiber membrane which is a porous hollow fiber membrane of a polyolefin. This invention also disclsoes a porou~ hollow fiber membrane ~herein minute polyolefin particles intimately are bound and allowed to form a tightly packed layer on the inner 25 surface side of the hollow fiber m~mbrane, minute polyolefin particles are bount after the pattern of chains and allo~ed to ~orm a porous layer on the outer ~urfacn side of the hollow fiber membrane, and very small through holes are formed in tbe hollow fiber 30 membrane as extended from the inner surface side to the outer surface ~ide. This invention further discloses a porous hollo~ fiber membrane wherein the average crimp amplitude is in the range of 50 to 100~ of the outside diameter, the maximum crimp amplitude/crimp half cycle 35 period at maximum crimp amplitude ratio is in the range of 0.02 to 0.05, and the crimp ratio is in the range of 2.0 to 3.0%. This invention discloses a porous hollow fiber membrane wherein the solid phase in the innersurface of the hollow fiber membrane has polypropylene particles partly exposed through the surface and preponderantly fused and bound intimately to give rise 5 to a continuous phase, the solid layer in the interior through the outer surface of the membrane has polypropylene particles ~rranged in the axial direction of fiber ~o give rise to a multiplicity of polypropylene clusters, and the gaps between the solid phases are 10 interconnected in the ~orm o a three-dimensional network to give rise to through holes. This invention also discloses a porous holow fiber membrane wherein the polypropylene particles have an average particle diameter in the range of 0.1 to 2.0 microns and an 15 average pore diameter in the inner surface in the range of 0.1 to 1.0 micron. This invention further discloses a porous hollow fiber membrane which, when used in an oxygenator, is substanti~lly free from leakage of blood plasma and decline of gas-exchange capacity within 30 20 hours of service. This invention discloses a porous hollow fiber membrane which, when used in an oxygenator, inflicts damage sparingly on blood cell components.
This invention di~clo~es a porou~ hollow fiber membrane wherein the average crimp amplitude is in the range ~of 25 50 to 100~ of the outsid~ diameter, the maximum crimp amplitude/crimp half cycle period at `maximum crimp amplitude is in the range of 0.02 to 0.05, and the crimp ra~io is in the range of 2.0 to 3.0~.
The ob~ects mentioned above are also 30 accompli~hed by a method for the production of a porous hollow fiber membrane, which is characterized by mixing a polyolefin, an organic filler uniformly dispersible in the polyolefin in the molten state thereof and easily ~oluble in a liguid extractant to be used, and a crystal 35 seed forming agent, melting the resultant mixture and di~charging the molten mixture through annular spinning nozzles into hollow threads, allowing the hollow threads to contact a cooling and solidifying liquid incapable of dissolving th~e polyolefin thereby cooling and solidifying the hollow threads, then bringing the resultant cooled and solidified hollow threads into 5 contact with the liquid extractant incapable of dissolving the polyolefin thereby extracting the organic filler from ~he hollow threads, and thermally crimping the hollow threads thereby forming porous hollow fiber membranes possessing an average crimp amplitude in the 10 range of 35 to 120~ of the outside diameter, a maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio in the range of 0.01 to 0.1, and a crimp ratio in the range of 1.0 to 3.0%.
This invention discloses a method for the 15 production of a porous hollow fiber membrane wherein the crimp is formed by causing the produced hollow fiber membrane to be cross wound on a bobbin and then heat set. This invention also discloses a method for the production of a porous hollow fiber membrane wherein the ~0 heat setting is carried out at a temperature in the range of 50 to 100C for a period in the range of 2 to 48 hours. This invention further discloses a method for the production of a porous hollow fiber membrane wherein the polyolefin is polypropylene. This invention 25 disclo~es a mthod for the production of a porous hollow ~iber membrane ~herein the organic filler is a hydrocarbon having a boiling point exceeding the melting point of the polyolefin. This invention also discloses a method for the production of a porous hollow fiber 30 membrane wherein the ~ydrocarbon is liquid paraffin or an ~ -olefin oligomer. This invention further discloses a method fcr the production of a porous hollow fiber membrane wherein the amount of the organic filler to be incorporated therein is in the range of 35 to 170 35 parts by weight, based on 100 parts by weight of the polyolefin. Thi-~ invention discloses a method for the production of a porous hollow fiber membrane wherein the t 324470 crystal seed forming agent is an organic heat-resistant substance possessing a melting point exceeding 150C and a gelling point exceeding the crystallization initiating point of th polyolefin to be used. This invention also 5 discloses a method for the production of a porous hollow fiber me~rane wherein the amount of the crystal seed forming agent to be incorporated therein is in the range of 0.1 to 5 parts by weight, based on 100 parts by weight of the polyolefin. This invention further 10 discloses a method for the production of a porous hollow fiber membrane wherein tne cooling and solidifying liquid possesses a specific heat capacity in the range of 0.3 to 0.7 cal~g. ~is invention discloses a method for the production of a porous hollow fiber membrane 15 wherein the cooling and solidifyinq liquid is silicone oil or polyethylene glycol. This invention also discloses a method for the production of a porous hollow fiber membrane wherein the polydimethyl siloxane possesses a viscosity ~n the range of 2 to 50 cSt at 20 20C. This invention $urther discloses a method for the production of a porous hollow fiber membrane wherein the polyethylene glycol possesses an average molecular `
weight in the range of 100 to 400. This invention discloses a method for the production of a porous hollow 25 fib*r membrane ~herein the organic filler is liquid paraffin. This invention also discloses a method for the production of a porous hollow fiber membrane wherein the amount of the organic filler to be incorporated therein is in the range of 35 to 170 parts by weight, 30 based on 100 parts by weight of polypropylene. This invention further discloses a method for the production of a porous hollow fiber membrane wherein the crystal seed forming agent is an organic heat-resistant substance possessing ~ melting point exceeding 150 and 35 a gelling point exceeding the crystallization initiating point of the polypropylene to be used. This invention disclo~es a method for the production of a porous hollow - 10 - . ,:

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fiber membrane wherein the amount of the crystal seed forming agent to be incorporated therein is in the range of 0.1 to 5 parts by weight, based on 100 parts by weight of the polypropylene to be used.
The objects mentioned above are further accomplished by an oxygenator provided with hollow fiber membranes as gas-exchange membranes, which oxygenator is characterized by using hydrophobic porous hollow fiber membranes as gas-exchange membrane.
BRIEF DESCRIPTION OF THE DRAl~INGS
I Fig. 1 is a schematic cross section of an apparatus to be used in the method for the production of poro~s hollow fiber membrane contemplated by the present invention, Fig. 2 is a half cross section illustrating a typical hollow-fiber membrane type oxygenator as one embodiment of the present invention, Fig. 3 is a cross section illustrating dif ferent portions of the embodiment of Fig. 2 relative - `
20 to the packing ratio of hollow fiber membranes, - Fig. 4 is a half cross section illustrating another typical hollow-fiber membrane type oxygenator as another e~bodiment of this invention, and ~ig~ 5 is a diagram illustrating the position 25 at ~hich the maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio (A~B) is mea~ured~
~XPLANATION OF PR~FERRED ~NBODIMENT
The porous hollow fiber membrane of the 30 present invention is a hydrophobic porous hollow fiber membrane possessing an inside diameter in the range of 150 to 300 microns, preferably 180 to 250 microns, a ~all thickness in the range o~ 10 to 150 microns, prefera~ly 20 to 100 microns, and a substantially 35 circular cross section, which porous hollow fiber membrane is characterized by possessing an average crimp amplitude in the range of 35 to 120~, preferably 50 to -- 11 -- ' `

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I 32447~
100%, of the outside diameter, a maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio in the range of 0.01 to 0.1, preferably 0.02 to 0.05, and a crimp ratio in the range of 1.0 to S 3.0%, preferably 2.0 to 3.0%. In the porous hollow fiber membrane of this invention, the average crimp amplitude is defined by the range of 35 to 120% of the outside diameter for the following reason. If the average crimp amplitude is less than 35~ of the outside 10 aiameter, there arises the possibility that when porous hollow fiber membranes are incarporated in an oxygenator, the gaps allowed to intervene between the adjacent hollow fibers are not amply large and are liable to entail ready stagnation of air or an 15 oxygen-containing gas therein. Conversely, if the average crimp amplitude exceeds 120~ of the outside diameter, the disadvantage ensues that the gaps allowed to intervene between the individual hollow fibers during the incorporation of the porous hollow fiber membrane 20 into the oxygenator cannot be easily retained in a size falling within a prescribed range. The maximum crimp a~plitude/crimp half cycle period at maximum crimp amplitude ratio is defined by the range of 0.01 to 0.1 for the following reason. If the maximum crimp 25 amplitude/crimp half cycle period at maximum crimp a~plitude ratio is less than 0.01, there similarly ~ri~es the poQ~ibility that when porous hollow fiber membr~nes are incorporated in an oxygenator, the gaps allowed to intervene between the adjacent hollow fibers 30 are not amply large and are liable to entail ready stagnation of air or an oxygen-containing gas therein.
Conversely, if the maxi~um crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio exceeds 0.1, the disadvantage ensues that the gaps allowed to 35 intervene between the individual hollow fibers during the incorporation of the porous hollow fiber membranes into the oxygenator are susceptible to larger variation .. ~. . ; ~ . . ~ , . . , , . :. , .. -- 1 324~7`~
in size than is tolerable and the flow of blood passed through the gaps suffers from heavy pressure loss. The crimp ratio is also defined by the range of 1.0 to 3.0%
for the following reason. If the crimp ratio is less 5 than 1.O%, the gaps allowed to intervene between the individual hollow fibers during the incorporation of the porous hollow fiber membranes into the oxygenator are not fully effectively augmented by crimping.
Conversely, if the crimp ra~io exceeds 3.0~, the lo possibili~y ens~es that the oxygenator produced as a mo~ule by the use of the porous hollow fiber membranes assumes a larger size than is tolerable.
So long as the porous hollow fiber membrane of this invention possesses the attributes described above, 15 the methods for manufacture, specifically for crimping and for impartation of porosity are irrelevant. Such a porous hollow fiber membrane as satisfying the requirement may be obtained, for example, by preparing a hollow fiber membrane spun out and vested with a porous 20 texture by the stretching method or the extraction method, cross ~inding it on a suitable bobbin, and heat treating the resultant roll of hollow fiber membrane approximately under the conditions of 60C and 18 hours thereby setting the hollow fiber membrane in the crimped 2~ state. If the thermal setting aimed ~t the impartation of crimp is performed more than is necessary and the texture of membrane i5 consequently altered and specifically the void ratio existing before the crimping is lowered in a ratio of more than 60t under the impact 30 of the heat treatment, then the thermal setting fails to manifest the effect thereo$ sufficiently~ If the th~rmal setting is insufficient and the hollow fiber membrane which retains the crimped state desirably during the course of module assembly is consequently 35 suffered to lose crimp under the tension subsequently .: ,. ~ ' exerted thereon by the residual stress, then the thermal setting does not manifest the effect thereof as expected.
The porous hollow fiber membrane of the 5 present invention can be expected, when it is used in an oxygenator, to manifest the effect thereof more advantageously when it possesses a void ratio in the range of 5 to 60~ and an oxygen gas flux in the range of 0.1 to 2,000 1/min.m2.atm., preferably 100 to 1,500 10 l/min.m .atm. If the void ratio is less than 10%, there arises th~ possibility that the porous hollow fiber membrane is deficient in gas-exchange capacity.
Conversely, if the void ratio exceeds 60~, the porous hollow fiber membrane has the possibility of entailing 15 leakage of blood plasma. If the opening ratio is less than 10~, there is the possibility that the formation of through holes in the void parts of the hollow fiber membrane does not take place suficiently and the porous hollow fiber membrane betray deficiency in gas-exchange 20 capacity. Conversely, if the opening ratio exceeds 30~, the through holes are deprived of necessary complexity of pattern and the porous hollow fiber membrane is susceptible of blood plasma leakage. If the oxygen gas flux deviates from the range of 100 to l,S00 25 lit/min.m2.atm, there arises the possibility that the por~us hollo~ fiber membrane fails to fulfil the function as a ga~-exchange membrane. The polypropylene par~icleæ and the through holes or the gaps between the par~icles ~ith ~ointly constitute the porous hollow 30 fiber membrane o th~ present invention can be regulated in ~ize and degree of distribution under desirable conditions. The average particle diameter of the polypropylene particles is desired to be in t~e range of 0.1 to 2.0 ~m, pre~erably 0.2 to 1.5 ~m, and the average 35 diameter of the pores in the inner surface i-q desired to be in the range of 0.1 to 1.0 ~m, preferably 0.3 to 0.6 ~m.

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The mi~terials available for the construction of the porous hollow fiber membrane of the present inventioin include hydrophobic synthetic resins represented by such polyolefins as polypropylene and 5 polyethylene and polytetrafluoroethylene, for example.
Among other hydkophobic synthetic resins mentioned above, polypropylene is particularly advantageous in excellin~ in various properties such as mechanical s~rength, thermal stability, and fabricability and 10 permitting easy impartation of porosity.
The cross-sectional configuration of ~he hollow fiber membrane is variable in some measure with the production conditions used for the hollow fiber membrane. Generally, very small polyolefin particles 15 are closely bound to form a tightly packed layer on the inner surface side and similarly small polyolefin particles are bound after the=pattern of chains to form a porous layer on the outer surface side and very thin thr~ugh holes are formed as extended from the inner 20 surface side to the outer surface side. ~hough the microstructure of the hollow fiber membrane made of polypropylene is variable ~ith th~ production conditions used for the hollow fiber membrane, it generally assumes the follo~ing pattern where, as the cooling and 25 solidifying liquid, there is used a solution which shows no compatibility with an organic filler and po~se~ses a ~pecific heat capacity in the range of 0.3 to 0.7 cal/g.
Specifically on the inner surface side, the Qolid phase has polypropylene particles partly exposed fsom the 30 surface and preponderantly fused and bound intimately, n~mely fused and then eooled and solidified to give rise to a continuous phase. In the interior of the membrane, the solid pha~e is formed of numerous polypropylene particles, which are randomly dispersed without any 35 directionally in the circumferential direction and are mutually bound to form clusters in the axial direction of fiber. These polypropylene clusters are : "

interconnected through the medium of polypropylene fibrils. In the interior of the membrane, therefore, the solid phase is thought to be formed of a host of polypropylene clusters which are each composed of 5 polypropylene particles linked in the axial direction of fiber. In the outer surface similarly to the interior of the membrane, the solid phase is formed by the aggregation of a multiplicity of polypropylene clusters each similarly composed of polypropylene particles 10 linked in the axial direction of fiber. ~he gaps intervening betwe?en such solid phases, in the wall thickness of the hollow fiber inclusively of the inner surface and the outer surface, form long paths extending from the inner surface? to the outer surface. These 15 pores are not extended linearly but continued reticularly in a complicated pattern to give rise to a three-dimensional network o~ through holes. This complexity of the through holes in distribution is evinced by the fact that the porous hollow fiber 20 membrane of this invention posse-~ses an extremely low birefringence ratio in the range of 0.001 to 0.01 in the axial direction of fiber and a small orientation of polypropylene crystals.
In the porous hollow fiber membrane of the 25 pre~ent invention, the inner surface assumes desirable &~ ~ including smoo~hness because it comprises A `~ polypropylene particles which are partially exposed from th~ surface and proponderantly fused and bound closely to form a continuous phase and void portions which 30 occupy the remaining matrix as described above. When this porous hollow fiber membrane is used in an oxygenstor ~? such a manner a-~ to pass blood through the inner cavity thereof, it neither inflicts any damage to the blood cell componentq nor aggravates pressure loss.
35 The oute~ surface thereof similarly assumes desirable surface ~u ~ ~ ~ inclusive of smoothness ~ecause it comprises a solid phase of a multiplicity of 1 32447~
polypropylene clusters each composed of polypropylene particles orderly arranged in the axial direction of fiber and void portion soccupying the remaining matrix.
When the porous hollow fiber membrane is used in an 5 oxygenator in such a manner as to pass blood outside the hollow fiber, it neither inflicts any damage to the blood cell components nor aggravates pressure loss.
Further, the pores of the porous hollow fiber membrane which serve as routes for passage of gas while the 10 membrane is used in the oxygenator are formed of a three-dimensional networ~ of through holes connected reticularly in a complicated pattern. No matter whether the blood for extracorporeal circulation is passed inside or outside the hollow fiber membrane, the blood 15 plasma component is not allowed to pass through the long complicated rough routes offered by the pores. For instance, in the case of the extracorporeal circulation for 30 hours, it is observed neither occurence of blood plasma leakage nor substantially decreasing the 20 gas-exc~ange capacity.
- Further, the porous hollow fiber membrane of , this invention is, as q~cribed below, effected to Y~ A ~ ermal crimping~ a~ter ~ it porosity by means of extracting, to obtain a crimped porous hollow fiber 25 membrane treated with crimping without changing any f~atures as de~cribed above, which membrance possesses a~ ~verag~ crimp amplitude in the ragne of 35 to 120~, preferably 50 to 100%, of the outisde diameter, a mRximum cri~p amplitude/crimp half crycle period at 30 maximum crimp amplitude ratio in the range of 0.01 to 0.1, preferably 0.02 to 0.05, and a crimp ra~io in the range of 1.0 to 3.0~, preferably 2.0 to 3.0~.
~ 6~ The treatment with crimping as described above has ~ following advantage. For example, when an 35 oxygenator which is formed of such po~ous hollow fiber as treated above is operated by ~riCo~a ~ blood out~ide the hollow fiber membrance, while blowing an oxygen-containing gas inside the hollow fiber in the oxygenator, since gaps be~ween the hollow fibers are relatively large and varied within a prescribed range over front and rear sides thereof in spite of the hollow r S fiber being hydr~ hob~ 7 the air or oxygen-containing A gas ~4 hardly ~u~Sc~aK~t~-sC~gn~e in the gaps. Thus, the hollow fiber membrane ensures satisfactory flow of blood and uniform contact of the blood with the oxygen-containing gas throughout the entire surface of 10 the hollow fiber membrane. The hollow fiber membrane, therefore, manifests the gas-exchange capacity very efficiently.
The method for the production of a porous hollow fiber membrane contemplated by this invention is 15 characteri2ed by mixing a polyolefin, an organic filler uniformly dispersible in the polyolefin in the molten state thereof and easily soluble in a liquid extractant to be used, and a crystal seed forming agent, melting the resultant mixture and discharging the molten mixture 20 through an annular ~pinning nozsle, allowing the d~scharged hollow thread to contact a cooling and solidifying liquid thereby cooling and solidifying the hollow thread, bringing the cooled and solidified hollow thread into contact ~ith the liquid extractant incapable 25 of dissol~ing the polyolefin thereby extracting the organic filler from the hollow thread, and thermally crimping the resultant hollow fiber membrane thereby forming a porous hollow fiber membrane possessing an averàge crimp amplitude in the range of 35 to 120% of 30 the outside diameter, a maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio in ~he range of 0.01 to 0.1, and a crimp ratio in the range of 1.0 to 3.0~. $he porous hollow fiber membrane of polyolefin ~hich is obtained by causing the organic 35 filler incorporated in the molted dope as the raw material to be cool~ed and ~olidified and subsequently extracted therefrom with the liquid extractant as described above acquires a texture such that, the inner surface side thereof has very small polyolefin particles closely bound to form a tightly packed layer and the outer surface side thereof has very small polyolefin particles connected after the pattern of chains to form a porous layer, with very thin through holes formed as extended from the inner surface side to the outer surface side. Since the pores are so minute and so complicated in distribution the porous hollow fiber membrane acquires high permeability to gas and, at the same time, refrains from inducing the problem of blood plasma leakage. When the porous hollow fiber membrane of this texture is vested with crimps of a prescribed ratio as described above and the oxygenator produced by incorporating therein the porous hollow fiber membrane is operating by circulating blood outside the hollow fiber membrane and blowing an oxygen-containing gas inside the hollow fiber membraner the oxygen-containing gas such as air hardly stagnates in the gaps and the blood is passed very smoothly, and the blood and the oxygen-containing gas are brought into uniform contact throughout the entire surface of the hollow fiber membrane becaus~ the crimps of the description qiven above serve the purpose of in~erposing relatively large gaps between the adjacent hollow fibers and imparting alterations within a stated range to the hollow fibers throughout the whole length thereof. Thus, the porous hollow fiber membrane enjoys a very satisfactory gas-exchange capacity.
Now, the present invention will be described more specifically below with reference to embodiments thereof.
~ig. 1 is a schematic diagram illustrating a process of production embodying the method for the production of a porous hollow fiber membrane of the present invention. In the embodiment illustrated in LGY~ 19 --1 32447~
Fig. 1, a mixture 11 comprising a polyolefin, an organic filler, and a crystal seed forming agent is fed through a hopper 12 to a kneader such as, for example, a single-screw extruder 13, there to be melted and kneaded S and extruded. The extruded mixture is forwarded to a spinning device 14 and discharged through an annular spinning nozzle (not shown) of a spinneret 15 into a , gaseous atmosphere such as, for example, air. A hollow A ~ 16 emanating ~rom the annular spinning nozzle is 10 introduced into a cooling tank 18 containing a cooling and solidifying liquid 17 andJ cooled and solidified by being brought into contact with the cooling and solidifying liquid 17. In thi~ case, the contact between the hollow thread 16 and the cooling and 15 solidi~ying liquid 17 is desired to be established by causing the cooling and solidifying liquid 17 to flow down the interior of a cooling and solidifying liquid passing tube 19 disposed as thrust downwardly through the bottom of the cooling ta~nk 18 and allowing the 20 hollow thread 16 to come into ~e contact with the flow of ~he cooling and solidifying liquid, for example, as illustrated in Fig. 1. The descending cooling and solidifying liquid 17 is received and stored in a solidifying tank 20. Inside the solidifying tank 20, 25 the hollow thread 16 introduced therein is caused to change the direction of its travel by a directionchanging bar 21 so as to be amply exposed to the cooling and solidifying liquid 17 and consequently solidified. The cooling and solidifying liguid 16 which 30 accumulates in the solidifying tank 20 is discharged through a circulating line 23 and returned by a circulating pump 24 to the cooling tank 18. Then, the solidified hollow thread 16 is guided by drive rolls 22a to a shower-conveyor type extruding machine 27 adapted 35 to let a liquid extractant capable of dissolving the organic solvent and incapable of dissolving polypropylene fall in the form of shower. While the 1 32447~

hollow thread 16 is being conveyed on the belt conveyor - 26 in the extruding machine 27, it is brought into ample contact with the liquid extractant 25 and deprived of the residual organic filler through extraction and S consequently transformed into a hollow fiber membrane 16. The hollow fiber membrane 16' led out of the extruding machine 27 by drive rolls 22b is optionally passed through the steps of re-extraction and drying (not shown) and then guided by drive rolls 22c to a 10 winding device 28 and, in this winding device 28, cross wound on a bobbin 2~. Further, the hollow fiber membrane 16' taken up on the bobbin 29 is subjected to a heat treatment under suitable conditions to be set in a crimped state.
The species of polypropylene available as the raw material in the present invention include propylene homopolymer, ethylene homopolymer, and block polymers using propylene as a main componnt and incorporating other monomers therein, for example. The polyolefin to 20 be used is desired to possess a melt index ~M.I.) in the range of 5 to 70, pre$erably 10 to 40. Among other polyolefins mentioned above, propylene homopolymer is usable particularly advantageously. The propylene hom~polymer is desired to possess as high crystallinity 25 a~ po~sible.
The organic filler is required to be uniformly dispersible in the polyolefin while the polyolefin is in the molten state thereof and easily soluble in the liquid extractant as specifically described later on.
30 The organic fillers answering the description include liquid paraffins tnumber average molecular weight 100 to 2,000), ~ -olefin oligomers ~such as, for example, ethylene oligomers (n ~ er average molecular weigh~ 100 ~A~ to 2,000), propylene ~ (number average molecular 35 weight 100 to 2,000), and ethylene-propylene oligomers (number average moleculr weight 100 to 2,000)], paraffin . . ~ . .

waxes (number average mo ecular weight 200 to 2,500), and various hydrocarbons. Among other organic fillers mentioned above, liquid paraffins prove advantages.
The mixing ratio of the polypropylene to the 5 organic filler is desired to be such that the amount of the organic filler is in the range of 35 to 170 parts by weight, preferably 80 to 150 parts by weight, based on 100 parts by weight of the polypropylene. If the amount of the organic filler is less than 35 parts by weight, 10 the produced porous hollow fiber membrane possesses no 2mp~le permeability to gas. Conversely, if the amount exceeds 170 parts by weight, the produced mixture possesses too low viscoisty to be efficiently molded into a h~llow thread.
The raw materials is prepared (designed) by the premix method which comprises melting and kneading the mixture of the prescribed percentage composition by the use of an extruder such as, for example, a twin-screw extruding machine, extruding the resultant 20 molten blend, and then pelletizing the extruded blend.
- The crystal seed forming agent to be in the ra~ material for this invention is an organic heat-resistant substance possessing a melting point exceeding 150C tpreferably falling in the range of 200 25 to 250C) and a gelling point exceeding the crystallization initiating point ~f the polyole~in to be used. The crystal seed forming agent is incorporated for the sa~e of diminishing the polyolefin particles in size, reducing the gaps between the adjacent particles 30 namely the through holes in thickness, and heightening the pore density. The crystal seed forming agents available herein include 1,3,2,4--dibenzylidene sorbitol, 1,3,2,4-bis(p-methylbenzylidine~ sorbitol, 1,3,2,~,-bis~p-ethylbe~zylidene)-sorbitol, 35 bi-~(4-t-butylpheny~ sodium benzoate, adipic acid, talc, and kaolin, for example.

Among other crystal seed forming agents mentioned above, benzylidene sorbitol and particularly 1, 3, 2, 4-bis ( p-ethylbenzylidene)sorbitol and 1,3,2,4-bis(p-methylbenziliden)sorbitol are advantageous 5 in being dissolved out sparingly into blood.
The mixing raito of the polypropylene to the crystal seed forming agent is desired to be such that the amount of the crystal seed forming agent is in the range of 0.1 to 5 parts by weight, perleferably 0.2 to 10 1.0 parts by weight, based on 100 parts by weight of the polypropylene.
The mixture prepared as the raw material as described above is further melted and kneaded by the use of an extruder such as, for example, a singlescrew 15 extruder, at a temperature in the range of 160 to 250, preferably 180 to 220C and discharged, optionally by use of a gear pump of high metering accuracy, into the gaseous atmosphere through the annular nozzle of the spinning device to give rise to a hollow thread. The 20 central part inside the annular nozzle may be caused to inhale spontaneously such a gas as nitrogen, carbon dioxide gas, helium, ar~on, or air or to introduce the gas forcibly~ Then, the hollow thread discharged through the annular nozzle is let fall and subsequently 25 brought into contact with the cooling and solidifying liquid in the coolinq ~ank. The di-~tance of this de~cent of the hollow thread is desired to be in the range of 5 to 1,000 mm, preferably 10 to 500 mm. ThiQ
range i~ critical. If the di~tance of fall i~ les~ than 30 5 mm, the falling hollow thread is pulsated and posibly cru~hed at the moment of the entry thereof in the cooling and solidifyig liquid. Inside the cooling tank, the hollow thread has not yet been thoroughly solidified and iQ suscep~ible of deformation under the external 35 force because it contains a gas in the cavity thereof.
The hollow thread 16 can be forcibly moved and, at the 9ame time, prevented from being deformed under the . .

1 324~7~

external force (such as the pressure of fluid) by allowing the cooling and solidifyig liquid 17 to flow down the interior of the cooling and solidifying liquid passing tube 19 disposed as thrust downwardly through 5 the bottom of the cooling tank 18 and allowing the hollow thread 16 to come into paxallel contact with the downward flow of the cooling and solidifying liquid, for example, as illustrated in Fig. 1. As regard the flow rate of the cooling and solidifying liquid in this case, 10 that which is attained by spontaneous flow is sufficient. At this time, the cooling temperature is desired to be in the range of 1~ to 90C, preferably 20 to 75~C. If this cooling temperature is lower than 10C, the cooling and solidifying proceeds so fast that 15 the greater part of the wall of hollow fiber forms a tightly packed layer and the porous hollow fiber suffers `
from deficiency in gas-ex~hange capacity. Coversely, if this temperature exceeds ~0C, the speed of ~ ``
crystallization of the polyolefin is so slow that the 20 very thin through holes gro~ in diameter and the tightly packed layer grow very thin. This tightly packed layer is not fo D d at all when the temperature is higher. If th~ porou~ hollow fiber membrane of this quality i~ used i~ the oxygenator, it has the possibility of entailing 25 ~ither clogging or blood plasma leakage.
For the cooling and solidifying liquid to fulfil its purpose, it has only to refrain from dissolving the polyolefin and possess a relatively high boiling point. The substances which meet the 30 description include alcohols such as methanol, ethanol, propanols, butanols, hexanols, octanols, and lauryl alcoholS liquid fatty acids such as oleic acid, palmitic acid, myri~tic acidl, and ~tearic acid and alkyl ester thereof (~uch as ester of methyl, ethyl, isopropyl, or 35 butyl) liquid hydrocarbons such a~ octane, nonane, decane, ketosene, gas oil, toluene, xylene, and methyl n~phthalene; and halogenated hydrocarbons such as -~' 1,1,2-trichloro-1,2,2,-trifluoroethane, - trichlorofluoromethane, dichlorofluoromethane, and 1,1,2,2-tetrachloro-1,2,-difluoroethane, for example.
Of course, these are not the only substances available 5 for the purpose.
The cooling and solidifying liquid to be used in this invention brings about particularly desirable results when it exhibits no compatibility with the organic filler to be used and possesses a specific heat 10 capacity in the range of 0.3 ~o 0.7 cal/g, preferably O.3 to 0.6 cal/g. Typical examples of the cooling and solidifying liquid answering the description include silicone oils such as dimethyl silicone oil and methylphenyl silicone oil which have a dynamic viscosity 15 in the range of 2 to 50 cSt, preferably 8 to 40 cSt, at 20C and polyethylene glycols which have an average molecular weight in the rangè~of 100 to 400, preferably 180 to 330. The coolinq and solidifying liquid is re~uired to be incompatible with the organic filler to 20 be used and to possess a specific heat capacity in the r~nge of 0.3 to 0.7 cal~g for the following reason.
If the cooling and solidifying liquid happens to be a liquid capable of dissolving the organic filler, such as when a halogenated hydrocarbon is used 25 as the cooling and solidifying liquid where liquid paraffin i~ ~elected a~ the organic filler, the organic filler i~ di~solved and extracted while the phase separation bet~een the polypropylene and the organic filler ii3 proceeding within the cooling and solidifying 30 liquid, with the re~ult that the organic filler is ~ormed to pa~9 from the in~ide to the outQide of the hollow thread. When the hollow thread in thi~ state is completely cooled and solidified, the content of the org~nic filler in the hollow thread i-~ low near the ~5 inner surface. After the organic filler is completely dl~-~olved and extracted, the opening ratio is unduly low on the inner ~urface. Thus, the finally produced porous . . .

hollow fiber membrane is suspected to suffer from deficiency in gas-exchange capacity. In this particular case, the disadvantage may possibly ensue that even the low molecular component of the polypropylene is 5 extracted from the hollow thread and accumulated on the inner wall of the cooling and solidifying liquid passing tube 19 to such an extent that the cooling and solidifying liquid passing tube 19 will have no sufficiently large inside diameter and the hollow thread 10 will be disfigurea~ If the cooling and solidifying liquid happens to be a compound identical or similar to the organic filler, such as when a liquid paraffin is used as the cooling and solidifying liquid where a liquid paraffin having a number average molecular 15 weight similar to that of the liguid paraffin used as the cooling and solidi*ying liquid is used as the organic filler, since the~ organic filler (liquid paraffin) is not appreciably migrated in the hollow thr~ad, the hollow thre!ad acquires a pore density as 20 prescribed and not unduly large specific hea~ and, therefore, accelerates the crystallization of polypropylene at a proper cooling 3peed and assume~ a ~t~ble ~hape. During the course of the cooling, ho~ver, the organic filler or the cooling and 25 ~olidifying liquid is locally distributed in the outenmost surface of the hollow thraad before the hollow thread i~ thoroughly cooled and solidified, with the result that the polypropylene content of the hollow thread i~ low in the outermost surface and the pore~ in 30 the outer surface of t~e hollow thread are large and the ~olid pha~e ha~ polypropylene particles di~persed in the form of a network so as to give rise to a surface abundant with ~harp rieses and falls. If the cooling ~nd solidifying liquid happens to be a liquid 35 incompatible with and inactive to the organic filler and yet ample in specific heat capacity, such as when water, a ~ub~tance having such a large specific heat capacity ": `

, 1 32447~
of about l.o cal/g, is used where a liquid paraffin is used as the organic filler, there arises the possibility that, owing to the high cooling effect to be brought about consequently, the polypropylene is quickly cooled S and the outer s~rface is suffered to assume a state of partic~larly low cryst~linity. The possibility ensues, therefore, that the propylene fails to form very small particles and the hollow thread gives rise to a hollow fiber membrane containing unduly small pores in the 10 outer surface and consejquently exhibiting a low gas-exchange capacity. ~onversely, if the cooling and solidifying liquid happens to have a small specific heat capaci~y, the cooling effect is not enough for the hollow thread to be completed as a hollow yarn.
When a solution showing no compatibility with the oraganic filler and possessing a specific heat capacity in the range of 0.3 to 0.7 cal/g is used as the cooling and solidifying liquid, the otherwise possible ~ ~ localization of t~e distribution of ~he ~ filler i~ Ao in the outer surface of the hollow thread is precluded, the cooling of the polypropylene is allowed to proceed at a proper speed, and the cry~tallization of the pol~propylene is accelerated without adversely affecting the proper polypropylene ~istribution ratio in the outer 25 surface. As ~ result, the outer surface of the produced hollo~ fiber membrane, similarly to the interior ~hereof, is formed of an aggregate of a multiplicity of polypropylene clusters produced by very small polypropylene particles being bound in the axial 30 direction of fiber and is allowed to assume a smooth surface.
The hollow thread which has been cooled and ~olidified in the cooling and solidifying tank is forwarded via direction-changing bars to the extracting 35 m w hine, for example, there to be deprived of the organic filler by dissolution and extraction. For the purpose of the dissolution and extraction of the organic 1 32~470 filler, the sbowering method which comprises causing a liquid extractant to fall in~shower onto the hollow - ~thread on a belt conveyor as illustrated in Fig. 1 is not the only means avilable. The dissolution and 5 extraction may be otherwise attained by a method which resorts to an extracting tank or a rewinding method which resorts to immersion in the liquid extractant of a skein onto which the hollow thread already taken up on a winding roll is rewound or some other me~hod which is 10 capable of establishing contact of the hollow thread with the liquid extractant. Optionally, two or more such methods m~y be used as suitabley combined to ensure thoroughness of the contact.
For the li~uid extractant to fulfil the 15 purpose thereof, it has only to be incapable of dissolving the polypropylene forming the hollow fiber membrane and capable of di~solving and extracting the organic filler. Examples of the liquid extractant answering the description include alcohols such as 20 methanol, ethanol, propanols, butanols~ pentanols, hexanol~, octanols, and lauryl alcohol and halogenated hydrocarbons such as 1,1,2-trichloro-1,2,2,-trifluoroethane, trichlorofluoromethane, dichlorofluoromethane, and 1,1,2,2-tetrachloro-1,2,-25 difluoroethane. Among other liquid extractantsmentioned above, hydrogenated hydrocarbons are particularly advantageous in term~ o$ ability to effect ~he extraction of the organic filler and chlorofluorohydrocarbons are especially advantageous in 30 terms of safety for the human body. `
The porous hollow fiber membrane which is obtained as deQcribed above iQ ~ub~ected to a thermal crimping treatment. The thermal crimping treatment is almed solely at imparting crimps to the porous hollow 3~ fiber membrane in ~he prescribed ratio previously mentioned. The method which comprises cross winding the porous hollow fiber mem~rane on a bobbin, for example, and thermally setting it as wound on the bobbin as illustrated in Fig. 1 is not the only means available for the thermal crimping txeatment. Alternatively, this treatment may be effectively accomplished by a method 5 which comprises heating the porous hollow fiber membrane and passing the hot membrane between a pair of grooved rollers which are mutually meshed after the pattern of cogwheels or a method which comprises heating the porous hollow fiber membrane, forcing the hot membrane as 10 folded in a 2ig2ag pattern into a funnel-shaped hole, and pushing it out of the hole, for example.
In the method for the production of the porous hollow fiber membrane, since the porous hollow fiber membrane is made of a thermoplastic resin, the crimps in 15 the prescribed ratio can be imparted thereto by preparatorily heating the porous hollow fiber membrane ,. in a crimped state and allowing it cool thereby setting it in the crimped state. If the thermal treatment)~
performed for the impartation of such crimps to an undue 20 extent, the ex~ess heat goes to disfiguring the membrnae texture. If this disfigurement lowers the void ratio of the porous ~ollow fiber ~e~ rane even by more than 50~
fro~ the original value ~ before the impartation of crimps, the porous hollow fiber membrane i~ no longer 25 cap~ble of manife~ting the effect thereo~ fully. If the thermal treatment is insuf~icient, the porous hollow fiber membrane which retains a desired crimped state during the module assembly is eventaully deprived of crimp~ under the tQnsion exer~ed by the residual stress.
30 Again in this case, the porou~ hollow fiber member fails to manifest the ef~ect fully. In the method which compri~es cross winding the porous hollow fiber membrane on a bobbin and heat setting it as wound on the bobbin as illustrated in Fig. 1, therefore, the heat setting is 35 desired to be carried out at a temperature in the ~
of 50 to 100C, prefer~bly 60 to 80C, for a period in the range of 2 to 48 hours, preferably 6 to 36 hours.

~ he porous hollow fiber membrane obtained as described above is used optimally in the hollow fiber type oxygenator.
The hollow fiber membrane obtained by the 5 conventional stretching method possess too high permeability to as;to ~e~efficiently in the oxygenator.
~- ~hen the blood is ~rrcl~te~ inside the hollow fiber the 'àbility to add oxygen to the blood is affec~ed by the fact that the resistance offered by the membrane on the 10 side bordering on the blood is unduly large and the r~sistance offered by the hollow fiber membrane lacks constancy and the ability to remove carbon dioxide gas from ~he blood depends on the magnitude of the resistance offered by the hollow fiber membrane which 15 possesses unduly high permeability to gas. When t~
blood is circulated outside the hollow fiber, the ability to effect exchange of gases depends on the magnitude of the resistance offered by the hollow fiber membrane which again maniests unduly high permeability 20 to g~s.
The hollo~ fiber membrane of this invention itself possessses lower permeability to gas than the counter~ype obtained by the conventional stretching method. It fulfils the performance ~ully when it is ~25 used as incorporated in the oxygenator. Since it is produced by the extraction method, it cannot form pinholes susceptible of leakage of blood and, ~herefore, can be prevented from degradation of gas-exchange capacity.
Furth~r, the hollow fiber membrane which i_ obtained by using, as the cooling and solidifying liquid, a liquid identical or similar to the organic filler ha_ very small polypropylene particles connected after the pattern of a network so as to give rise to a 35 _urface abundant wi~h very sharp riQes and falls as previously mentioned~ When this hollow fiber membrane iQ incorporated in the oxygenator, therefore, there , '.: "

1 32447~
arises the pos~;ibility that the adjacent hollow fibers coalesce fast to such an extent that the work of assembly is complicated and the adhesive agent is obstructed from amply enveloping the individual hollow S fibers and giving rise to a desirable potting.
In the case of the hollow ~iber membrane obtained by the method of the present invention, such draw~acks as involved in ~he assembly of the oxygenator cannot occur because the outer surface thereof, 10 similarly to the interior thereof, is formed of an aggreagate of a multiplicity of polypropylene clusters composed of polypropylene particles connected in the axial direction of fiber and, therefore, is allowed to acquire satisfactory sur~ace quality inclusive of 15 smoothness. No matter whether the blood may be passed on the outer surface or the inner surface of the hollow fiber membrane, this hollow`fiber membrane inflicts no damage on t~e blood cell components and suffers from apparing pressure loss.
Further, since the hollow ~iber membrane obtained by the method of this invention contains crimps at a prescribed ratio as previously mentioned, the gaps betwecn the adjacent hollow fibers are relatively large and are variad ~ithin a limited range throughout the 25 entire length of fiber~ ~ven when the blood i9 circulated ou~de the hollow fibor membrane and the oxygon-containing gas is blown inside the hollow fiber m~mbrane, the stagnation of the oxygen-containing gas such ~ air can hardly occur in ~hese gaps. The hollow 30 fiber membr~ne, therefore, ensures smooth ~low of the blood and permits uniform contact between the blood and the oxygen-containing gas throughout the entire surface of the hollow fiber membrane and manifests a Qatisfactory ga~-exchange capacity fully.
Fig. 2 illustrates a typical hollow fiber mombrane type oxygenator as one embodiment ~first ombodiment) of th~s invention, spe~ifically assembled - 31 - ` `~

1 32`4~7~
for circulating blood inside the hollow fiber membrane and blowing the oxygen-containing gas outside the hollow fiber membrane. The hollow fiber membrane type oxygenator 51 is furnished with a housing 52. This 5 housing 52 is provided at the opposite ends of a tubular main body 53 respectively with annular male-thread fitting covers 54, 55. Inside the housing 52, a multiplicity in the range of 10,000 to 60,000, for example, of porous hollow fiber membranes 16' crimped at 10 a prescri~ed ratio previously mentioned are parallelly disposed in the longitudinal direction of the housing 52 as mutually separated. The opposite end parts of the porous hollow fiber membranes 16' are watertightly supported inside the fitting covers 54 ? 55 by diaphragms 15 57, 58 in such a manner that the openings thereof are not closed. The diaphragms 57, 58 define and enclose a gas compartment 59 jointly with the outer surfaces of the porous hollow fiber membranes 16' and the inner surface of the housing 52 and, at the same time, isolate 20 the gas compartment ~9 from the blood passing cavities tnoe shown) formed inside the porous hollow fiber membranes 16'. $he fitting cover 54 is provided with an oxygen-containing gas inlet 60 for supply of an `
oxygen-containing gas and the other fitting cover 55 25 ~it~ an oxygen-containing gas outlet 16 for d~scharge of the oxygen-containing gas.
The tubular main body 53 of tha housing 52 may be proviaed on the inner surface thereof at the center in the a~ial direction with an inwardly projected 30 constringent part 62. The constringent part 62 disposed in the central part can be expected to improve the `
gas-exchanqe efficiency. This high gas-exchange effici~ncy can be obtained without requiring the provi~ion of thi~ constringent part 62, however, because 35 the porous hollow fiber membrane~ 16' used in the oxygenator of the present invention are crimped at the pre~cribed ratio AS ~lready mentioned. The constringent - 32 - ~
` ' `

1 32447~
~art 62 is formed on the inner surface of the tubular main body 53 integrally with the tubular main body 53 and adapted to constrict the overall circumference of a hollow fiber bundle 63 composed of the multiplicity of S porous hollow fiber mem~ranes 16' inserted inside the tubular main body 53. ~hus, the hollow fiber bundle 63 is constricted at the center in the axial direction thereof to give rise ~o a constricted part 64. The packing ratio of hollow fiber membranes, therefore, 10 varies along the axial direction of t~ constricted part ~ 64 and reaches the maximum at the ~ e~cr. The packing `~``~ ratios at different parts æe desired to be selected as follo~s. The packing ratio A in the constricted part 64 at the center is approximately in the range of 60 to 15 80~, the packing ratio B in the interior of the tubular main body 53 approximately in the range of 30 to 60%, and the pacXing ratio C at the opposite ends of the ~hollow fiber bundle 63, namely on the outer surfaces of ~ diaphragms 57, 58, approximately in tha range of 20 20 to 40%.
Now, the formation of ~he diaphragm~ 57, 58 ~ill be des~ribed below~ ~s described above, the diaphragms 5~, 58 fulfil an important function of isolating the inner cavities of the porous hollow fiber 25 membranes 16' from the o~tside. Generally, ~he diaphragms 57 are produced by casting a macromolecular potting material of high polarity such as, for example, polyurethane, silicone, or epoxy resin on the opposite inner walls of the housing 52 by the centrifugal casting 30 method and ~lowing the deposited layers of the potting material to se~ To be more specific, a multiplicity of porous holow fiber membranes 16' of a length greater th~n the length of the housing 52 are prepared and, with the opposite open ends thereof filled with a highly 35 viscous resin, are arranged in place inside the tubular main body 53 of the housing 52. Then, with the opposite ends of the porous hollow fiber membranes 16' completely ~ 32447~
covered each with a pattern cover larger than the diameter of the fitting covers 54, 55, the housing 52 is rotated around the central axis of the housing 52 and, at the same time, the macromolecular potting material is 5 cast from the opposite end sides. When the cast resin is set, the pattern covers are removed and the outer lateral parts of the set layers of resin are cut off with a sharp blade and the opposite open ends of the porous hollow fiber membranes 16' are exposed. As a 10 result, the diaphragms 57, 58 are formed. -~
The outer surface of the diaphragms 57, 58 are respectively covered with flow path forming members 65, 66 each pro~ided ~ith an annular projection. These flow path forming members 65~ 66 respectively comprise liquid 15 distributing members 67, 68 and thread rings 69, 70.
Near the circumferential edges of the liqiud distributing members 67, -68 are respectively formed annular ridges 71, 72. By bringing the ends surfaces of the annular ridges 71, 72 into contact respectively with 20 the diaphragms 57, 58 and helically fixing the screw rings 69, 70 respectively on the fitting covers 54, 55, blood inlet compartment~ 73, 74 are formèd. These flow path forming members 65, 66 are provided respectively with a blo`od inlet 75 and a blood outlet 76. Two holes 25 77, 78 and ~9, 80 are formed so as to communicate respectively with the empty spaces formed around the peripheral cdges of the diaphragms 57, 58 by the diaphragms 57, 58 and the flow path forming members 65, 66. The flow path forming members 65, 66 are adapted to 30 seal the housing in such a manner that acess to the ~ `
diaphragms 57, 58 is attained respectively through either of the two holes. The sealing may be otherwise attained through the medium of an O-ring (not shown).
Fig. 4 illustrates another typical hollow 35 fiber membrane type oxygenator as another embodiment (second embodiment) of thi-~ invention, specifically assembled so as to circulate blood outside the hollow ' ,~ :

fiber membrane and blow an oxygen-cont~ining gas inside the hollow fiber. The hollow fiber membrane type oxygenator 81 is furnished with a housing 82. This housing 82 is provided at the opposite end parts of a 5 tubular main body 83 thereo~ respectively with annular fitting covers 84, 85. Inside the housing 82, a multiplicity in the range of 10,000 to 70,000, for example, of porous hollow fiber membranes 16' possessing the properties mentioned previously are parallelly 10 arranged in the longitudinal direction of the housing as mu~ually separated. The opposite end parts of the porous hollow fiber membranes 16' are watertightly suppor~ed in place respectively inside the fitting covers 84, 8S by diaphragms 87, 88 in such a manner that 15 the openings thereof are not closed. The diaphragms 87, 88 $orm and enclose a blood compartment 89 jointly with the peripheral surface of ~the porous hollo~ fiber membranes 16' and the inner surace of the housing 82 and isolate oxygen-containing gas flowing cavities (not 20 shown) formed inside the porous hollow fiber membranes 16' from the blood compartment 89 . The housing 82 is pro~ided in one part thereof with a blood inlet 95 or supply of blood and~in the other part thereof with a blood outlet 96 for discharge of blood.
The tubular main body 83 of the housing 82 may be provided on the inner surface thereof at the center in the axial direction with a pro~ecting constringent part 92. The constringent part 92 integrally with the tubular main body 83 and adapted to constrict the 30 overall periphery of a hollow fiber bundle 93 composed of a multiplicity of porous hollow fiber membranes 16' inserted in the interior of the tubular main body 83.
Thus, the hollow fiber bundle 93 is constricted at the center in the axial direction thereof to form a 35 constricted part 94. ~he packing ratio of hollow fiber membranes, therefore, varies in the axial direction of fiber snd reaches the maximum at the center. In the fitting covers 84, 85, an oxygen-containng gas inlet 90 and an oxygen-containinq gas outlet 91 are respectively formed. The other components and the method for the formation thereof are equivalent, with due 5 modifications, to those of the hollow fiber membrane type oxygenator of the first embodiment. Thus, the description thereof will be omitted.
Now, the present invention will be described more specifically below with reference to working 10 examples.
~kxamples 1 to 3 A porous hollow fiber membrane of polypropyleQe formed by being stretched in the axial direction by the stretching method, having an inside 15 diameter of 200 ~m and a wall thickness of 24 ~m and containing very small pores having an average radius of 700 A was cross wound on a bobbin 95 mm in diameter and then crimped by heat-treated at 60C for 18 hours. The porous hollow fiber membrane obtained consequently had 20 an average crimp amplitude of 70% of the outside diameter of the hollow fiber membrane, a maximum crimp `apmplitude/crimp half cycle period at maximum crimp amplitude ratio of 0.03, and a crimp ratio of 2.5%.
From this crimped porous hollow fiber membrane, an 25 oxygenator of the first embodimen~, an oxygenator of the s~con6 embodi ~ t, and an oxygenator conforming Bto~he ; A` ` first ~ , exc~pt that the hollow fiber ~m~h~
not constricted at the center in ~he axial direciton, (third embodiment) were produced as 30 respective module in the manner described below. They were tested for oxygen gas flux, ability to add oxygen ga~, and ability to remove carbon dioxide gas. The r sults are shown in Table 3.
Controls 1 and 2 For comparison, the ~ame oxygenator modules as those of ~xample 1 were produced by uising without any modification a porou~ hollow fiber membrane of ~, .. .. .

polypropylene formed by being stretched in the axial direction by the stretching method, having an inside diameter of 200 ~m and a wall thickness of 24~m, and containing very small pores having an average radius of 5 700A; the module of the first embodiment for Control 1 and that of the second embodiment for Control 2 respectively. These oxygenator modules wer~ tested for oxygen gas flux, ability to add oxygen gas, and ability to remove carbon dioxide gas. The results are shown in 10 Table 3.
~ he definitions of ~arious terms used in the specification and the methods for determination thereof are shown below.
Inside diameter and wall thickness .
1~ The proper~ie~s were determined by randomly ,~ drawing 10 of the ~ fiber membranes of a given oxygenator cutting them into tubes about 0.5 in length ~ith a sharp razor blade, projecting the sections of the tubes on a screen with a universal pro~ector ~Nikon~
20 Profile Projector V-12~, measuring the outside dimeters dl and inside diameters d2 of the pro~ected sections with a counter (Nikon Digital counter CM-6S), and calculating the ~all thickness t by the formula t - dl -d2. The respective averages each of 10 measured values 25 ~re reported.
Void ratio ~) This property was determined by taking about 2 g of the hollow fiber membrane~ of a given oxygenator, cutting them into tubes not more than 5 mm in length 30 with a sharp razor, pressing the resultant test specimen to a pressure of 1,000 k~/cm2 with a mercury porosimeter (Carlo ~rba Corp; Motem 65A), finding the total volume of pores (volume of pores in the hollow fiber per unit weight), and calculating the void raito.
35 Ave~ e crin~ mplitude and maximum crimp amplitude~crimp hali' cycle period at maximum crimp amplitud~ ratio A given hollow fiber membrane was tested for crimped condition by the measurement of rises and f alls on the membrane surface over a length of 35 mm with a universal surface shape tester (produced by Kosaka 5 Xenkyusho K.K. and marketed under product code of SE-3Sn) to determined the largest (A) o~ amplitudes found in round of measurement and the ratio ~A/B) of this maximum ~mplitude (A) to the distance (B) between the maximum point and the minimum point in the 10 amplitude. Ten rounds of the measurement were made per lot and the average of the ten found values was reported as the maximum crimp amplitude/crimp half cycle period Lat ma~ mum crimp amplitude ratio. The average of ten A ~ 1~ of the amplitudes found in one round of 15 measurement was reporeted as the average crimp amplitude.
Crimp ratio .
This property was determined by subjecting a given hollow fiber membrane in an initial length of 25 20 mm to a tensile test with a tensile tester tproduced by T~yo Seiki R.R. and marketed under trademark designation `of ~Strograph T~) thereby finding the lengths of the Qample acquired under two loads, 1 mg and 50 mg per denier, and dividing the difference of t~e, two distances 25 by the initial length. The ~ ~ quotient in p~rcentage was reported as the magnitude of this property.
n gas ~lux This property was determined by preparing a 30 miniature module 14 cm in available length and 0.025 m2 in available membrane ar~a with a given porous hollow fiber membrane, closing one end of the miniature module, exerting one at~osphere of pr~ssure on the interior of the hollow membrane with oxygen until a steady state was 35 obtain~d, and measuring the flow volume of oxygen gas with a flow meter ~produced by Kusano Rikagakukiki Seisakusho and marketed under trademark designation of "Flotomer"). The scale reading was reported as the magnitude of this property.
Ability to add oxygen gas and ability to removal carbon s dioxide gas -(First embodiment) These properties were determined by preparing an oxygena~or module 130 mm in available length and 5.4 m in available membrane area using a given hollow ~iber 10 membrane, passing bovine blood (standard venous blood) in a single path inside the hollow fiber membrane at a flow volume of 6~0 lit/min., passi~g purified oxygen outside the hollow fiber membrane at a flow volume of 6.0 lit/min~ measuring the pH, partial pressure of 15 carbon dioxide gas (PCO2), and partial pressure of oxygen gas (P02) of the bovine blood samples taken at the inlet and outlet of the oxygenator with a blood gas measuring device tproduced by R3diometer Corp. and marketed under product code of ~BGA 3~, and calculating 20 the differences of partial pressure at the inlet and outlet of the oxygenator. The detailed specification of `the oxygenator, module is shown in Table 1. The quality of the standard venous blood is shown in Table 2.
(Second embodiment~
2~ The properties were determined by preparimg an oxygenator module 90 mm in available length and 2.1 m2 in available membrane area using a given hollow fiber me~brane, passing bovine bload (standard venous blood) in ~ single path outside the hollow fiber membrane` at a 30 flow volume of 6.0 lit/min., passing purified oxygen inside the hollow fiber membrane at a flow rate of 6.0 lit/~in, measuring the pH value, partial pressure of o~ygen inside the hollow fiber membrane at a flow rate of 6.0 min, measuring the pH value, partial pressure 35 of carbon dioxide gas (PCO2), and partial pressure of `~
oxygen gas (PO2) of the bovine blood samples taken at the inlet and outlet of the oxygenator with a blood gas - ' .: ~
:

measuring device (produced by Radiometer Corp. and marketed under product code of "BGA3 n ) ~ and calculating the diference of partial pressures at the inlet and outlet of the oxygenator. The detailed specification of S the oxygenator module is shown in Table 1.
(Third embodiment) The properties were determined by preparing an oxygenator identical to the oxygenator of the first embodiment, except that the hollow fiber bundle was not 10 constricted at the center in the axial direction, and carrying out the same measurements as in the first embodiment, . . .

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Example 4 By use of a twin-screw extruder ~rod~ ed by Ikegai Iron Works, Ltd. and marketed under ~rcdk=J-code of ~nPCM-30-25n), 100 parts by weight of a propylene 5 homopolymer having a melt index (M.I.) of 23, 130 parts by weight of a liquid paraffin (number average molecular weight 324), and 0.5 part by weight of 1,3,2,4-bis(ethylbenzene)sorbitol as a crystal seed forming agent were melted and kneaded and extruded and 10 then pelletized. By use of a device illustrated in Fig.
2, namely a single-screw extruder (produced by Kasamatsu Seisakusho and marketed under product code of ~W0-30~), the pellets were melted at 180C and discharged in~o the ambient air at a rate of 3.6 to 5.0 g/min through an 15 annular spinning nozzle 4 mm in core diameter, 6 mm in inside diameter, 7 mm in outside diameter, and 15 mm in land length to let fall a hollow thread 16. The distance of this fall was 20 to 30 mm. Then, the hollow thread 16 was brought into contact with Freon~ 113 20 tl,l,2-trichloro-l~2~2~-trifluoroethylene) held as a cooling and solidifying liquid 17 in a cooling tank 18, and then cooled by being brought into parallel contact ~i~h a cooling and solidifying liquid 17 spontaneously falling down the interior of a cooling and solidifying 25 liquid passing tube 19. In this case, the temperàture of the cooling and solidifying liquid 17 was 20C.
Then, the hollo~ thread 16 waq introduced into the cooling and solidifying liquid 17 held in a solidifying tank 20, caused to change the direction of its travel by 30 a direction changing bar 21, led to a drive roll 22a operated at a winding speed of 80 m~min and, immediately in a shower con~eyor type extruder~ 7, showered with a liquid extractant 25 using Freon~113 for thorough extraction of the aforementioned liquid paraffin. The 35 hollow fiber membrane 16' which had been ves~ed with porosity as described above was taken out of the extruder 27 by means of drive rolls 22b, forwarded via - 44 _ drive rolls ~2c to a winder 28, and taken up by cross winding on a bobbin 29 having a diameter of 95 mm by means of the winder 28. The hollow fiber membrane 16' thus taken up in cross winding on the bobbin 29 was 5 crimped by being heat treated in an oven at 60C for 18 hours.
The porous hollow fiber membrane consequently obtained was found to possess an average crimp amplitude of 72~ of the outside diameter, a maximum crimp 10 amplitude~crimp half cycle period at maximum crimp amplitude ratio of 0.03, and a crimp ratio of 1.7~.
From the crimped porous hollow fiber membrane, an oxygenator of the first embodiment, an oxygenator of the second embodiment, and an oxygenator module (third 15 embod~ment) identical to that of the first embodiment, except that ~he hollow fiber bundle was not constricted t the ~R in the axial direction, were prepared~ The `oxygenator modules were tested for oxygen gas flux, ability to add oxygen gas, ability to remove carbon 20 dioxiae gas, and blood plasma leakage. The results are shown in Table 5. Table 4 show the conditions for the e~bodiments men~ioned above.
Control 3 A porous holl~w fiber membrane was prepared by 25 following the procedure of Example 4, except that the c~imping treatment was omitted. From this porous hollow fiber membrane, modul~s of an oxygenator of the first embodiment and an oxygenator o~ the second embodiment ~ere prepared. These modules were tested for oxygen gas 30 flux, ability to add oxygen ga~, ability ~o remove carbon dioxide gas, and blood plasma leakage. ~he results are ~hown in Table 5.
Control 4 A porou~ hollow fiber membrane of 35 polypropylene formed by being stretched in the axial direct~on by the stretching method, having an inside diameter of 200 ~m and a wall thickness of 25 ~m and containing very small pores 700 A in average radius was taken up in c:ross winding on a bobbin 95 mm in diameter and crimped by being heat treated in an oven at 60C for 18 hours. The porous hollow fiber membrane thus 5 obtained was found to have an average crimp amplitude of 70% of the outside diameter of hollow fiber membrane, a maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio of 0.03 , and a crimp ratio of 2.5~. From this porous hollow fiber membrane, 10 an oxygenator of the first embodiment, an oxygenator of the second embodiment, and an oxygenator of the third embodiment were produced. These oxygena~or modules were tested for oxygen gas flux, ability to add oxygen gas, ability to remove carbon dioxide gas, and blood plasma 15 leakage. The results are shown in Table 5.

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Example 5 A plorous hollow fiber membrane was obtained by following the procedure of Example 4, except that polyethylene glycol ~Mn = 200) was used in place of 5 Freon 113 (1,1,2-trichloro-1,2,2-trifluoroethylene) as the cooling and solidifying liquid.
This porous hollow fiber membrane was found to have an average crimp a~mplitude of 72~ of the outside diameter of the hollow fiber membrane, a maximum crimp 10 amplitude~crimp half cycle period at maximum crimp amplitude raito of 0.03, and a crimp ratio of 1.7~. The crimped porous hollow fiber membrane was tested for shape (inside diameter~wall thickness), void ratio, gas flux, and birefringence ratio as an index of crystal 15 orientation. The results are shown in Table 6. From this crimped porous hollow fiber membrane, an oxygenator of the first embodiment, an oxygenator of the second ~ -embodiment, and an oxygenator module ~third embodiment) identical to the oxygenator of the first embodiment, 20 e~cept that the hollow fiber bundle was not constricted at the center in the axial direction. These oxygenator `~ndules ~ere tested for ability to add oxygen gas, ~bility to remove carbon dioxide gas, and blood plasma leakage. The results are shown in Tablè 6.
25The data of ~ontrols 3 and 4 are also shown in the table. `
Throughout the whole text of this ` `
~p ification, the numerical values of the blood plasma "
leakage and the birefringence ratio are those determined 30 by the following method. `
~lood Plasma Leakage ThiR property was determined by preparing tbe ~ame oxyg~nator module as used in the test for the ability to add oxygen gas and the ability to remove 35 carbon dioxide gas, incorporating this oxygenator module in a partial V-A bypass circuit for the jugular vein-carotid artery cannulation using a mongrel (about 20 kg in weight), continuing extracorporeal circulation for 30 ho~rs, and measuring ~he amount of blood plasma ~ ~ ~ eaking from the interior of ~ hollow fiber. Where no `' visible leakage was detected, the condensed drop of S steam outside the hollow fiber was assayed for proteinaceous reaction in an effort to detect even a trace of blood plasma leakage.
Birefringence ratio ( ~n~ (retardation method) From a batch of hollow fiber membranes, 10 10 membranes were randomly taken. From the central parts of these samples, portions 3 cm in length were cut off.
By inserting oblique cuts at one end of these portions, test pieces were obtained.
These test pieces were placed on a slide 15 glass, impregna~ed with a soaking liquid ~liquid paraffin), and mounted on a rotary stage of a polarizing microscope. With the aid of a monochromic light source or a filter and with the compensator removed, the test pieces were rotated on the stage under cross Nicol prism 20 and then fixed at the position at which the vision was brightest (the position reached by 45 rotation from the darkest position)~ Then, the compensator was replaced and the ansly~er was rotated to find the angle (~ ) of rotation required in reaching the darkest position. The 25 retardation ~R) was calculated from the following formula and the birefrlngence ratio of the hollow fiber membrane was calculated from the following formula~ The average of the value o$ 10 mea~urements was reported a~
the magnitude of bire$ringencè factor.

Retardation, R = 11 80 ~ A

wherein is the wavelength used in the test.
Birefringence ratio, ~ n = dR

wherein d is the thickness of test piece (corrected with respect to the void ratio).
5 Conditions for measurement:
~olarizing microscope Nikon OPTIPHOTO-POL
Wavelength of light source 546 nm Compensator Compensator of Senarmont type : -Incidentally, a perfectly oriented polypropylene exhibits a birefringence ratio, ~ n, of 0.035 (reported in literature). ;~ ~

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v 3 -s2-Examples 6 to 8 Similar tests as in Example 4 were conducted by use of hollow fiber membranes obtained by repeating the procedure of Example 4 except that maximum crimp 5 amplitude/crimp half cycle ratios and crimp amplitudes of the outside diameter were varied as shown in Table 7.
The results are shown in Table 7.
Examples 9 to 11 :.
Similar tests as in Example 5 were conducted 10 by use of hollow fiber membranes obtained by repeating the procedure of Example 5 except that maximum crimp amplitude/crimp half cycle ratios and crimp amplitudes of the outside diameter were varied as shown in Table 8.
The results are shown in Table 8.

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1 3244~0 As described above, this invention is directed to a porous hollow fiber membrane of polyolefin having an inside diameter in the range of 150 to 300 ~m and a wall thickness in the range of 10 to 150 ~m and a wall 5 thickness in the range of 10 to 150 ~m and a substantially circular cross section, which porous hollow fiber membrane is characterized by the fact that the inner surface side thereof has very small particles of the polyolefin closely bound to form a tightly packed 10 layer~ ~he inner surface side thereof h~s very small particles of the polyolefin bound after the pattern of chains to form a porous layer, very thin through holes are formed as extended from the inner surface side to the outer surface side, and the hollow fiber membrane 15 has an average crimp amplitude in the range of 35 to 120% of the outside diameter, a maximum crimp amplitude/crip half cycle period at maximum crimp amplitude ratio in the range o$ 0.01 to 0~1, and a crimp ratio in the range of 1.0 to 3.0~. When an oxygenator 20 is produced by using the porous hollow fiber membrane and this oxygenator is operated for extracorporeal circulation by circulating blood outside the hollow fiber membrane and blowing an oxygen-gas containing gas in~ide the hollow fiber membrane, since the crimps`give 25 ri~e to relatively large gaps between the ad~acent hollow fi~ers and the gapQ ar~ varied within a prescribd range througho~t the entire length of hollow fiber, the oxygen-containinq gas ~uch as air i~ hardly ~uffered to stangnate in the gaps~ As a result, the oxygenator 30 en~oys a high ga-~-exchange capacity becau~e the blood is passed smoothly and the blood and the oxygen-containing ga-~ are brought into uniform mutual contact throughout ~he entire surface of the hollow fiber membrane. The oxygenator cannot entail the problem of blood plasma 35 le~kage, for example, on account of the texture of membrane. The effects of the porous hollow fiber membrane of this invention described above are - 5~ -manifested more advantageously when the porous hollow fiber membrane has a void ratio in the range of 5 to 60%
and a gas flux in the range of 100 to 1,500 liters/min.m2. atm, the polyolefin is polypropylene, and 5 the porous hollow fiber membrane has an average crimp amplitude in the range of 50 to 100% of the outside diameter, a maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio in the range of 0.02 to 0.05, and a crimp ratio in the range of 2.0 to 0 3 . 0~. ` Thus, this poro,us hollow fiber membrane is used more advantageous~for the oxygenator.
~-~ During the course of assembly of an oxygenator using the porous hollow fiber membrane, since this porous hollow fiber membrane has satisfactory surface 15 quality inclusive of smoothness, sucb drawbacks as coalescence of adjacent hollow fiber membranes and defective potting due ~to adhesive agent are not entailed. When the oxygenator using the porous hollow fiber membrane of such highly desirable quality is used 20 for extr~corporeal blood circulation by circulting the ~lood outside the hollow fiber membrane in the oxygenator and blowing the oxygen-containing gas inside the hollow fiber membrane, since the crimps gi~e rise to relatively large gaps between the ad~acent hollow fibers 25 and the gaps are varied within a prescribed range throughout the entire length of hollow fiber as described above, the oxygen-containing gas such as air i~ hardly suffered to stagnate in the gaps. As a ~ the oxygenator en~oys a high gas-exchange 30 capacity because the blood is passed smoothly and the blood and the oxygen-containing gas are brought into uniform mutual contact throughout the entire surface of the hollow fiber membrane. These features are manifested more ad~antageousy when the birefringence 35 r~tio of the porous hollow fiber membrane in the axial direction of fiber is in the range of 0.001 to 0.01.

- 57 _ This invention is also directed to a method for the production of a porous hollow fiber membrane, which is characterized by mixing a polyolefin, an organic filler uniformly dispersible in the polyolefin 5 in the molten state thereof and easily soluble in a liquid extractant to be used, and a crystal seed forming agent, melting the resultant mixture and discharging the molten mixture through annular spinning nozzles into hollow threads, allowing the hollow threads to contact a 10 cooliLng and soli~ifying liquid incapable of dissolving the polyolefin thereby cooling and solidifying the hollow threads, then bringing the resultant cooled and solidified hollow threads into contact with the liquid extractant incapable of dissolivng the polyolefin 15 thereby extractng the organic filler from the hollow threads, and thermally crimping the hollow threads thereby forming porous foliow fiber membranes posses-Ring an average crimp amplitude in the range of ~5 to 120~ of the outside diameter, a maximum crimp amplitude/crimp 20 ~alf eycle period at ~aximum crimp amplitude ratio in the range of 0.01 to 0~1, and a crimp ratio in the range of 1.0 to 3.0~. By this method can be produced a porous ~ollow fiber membrane which possesses such outQtanding properties as mentioned above, including an enhànced 25 guQ-liguia contact efficiency in the gas exchange and s~crificing none of the de_irable microporous texture and gas-exchange efficiency of the porous hollow fiber mombrane produced by the extraction method. In the method of the present invention for the production of a 30 porous hollow fiber membrane, the produced porous hollow fiber poQseQsing a shape abundant with gas-liquid contact efficiency, a texture notably excellent in other ,' properties, and a ~ behavior when the impartation of crimp~ ef~ecte~d by cross winding the hollow fiber 35 membrane on a bobbin and heat setting it as wound on the bobbin and this heat setting is carried out at a temperature in ~he range of 50 to 100C for a period in .

, .

the range ot- 2 to 48 hours. Further, the produced hollow fiber memt?rane enjoys a still better quality when the polyolefin is polypropylene, the organic filler is a .-; hydrocarbon having a boiling point exceeding the melting 5 point of the polyolefin, the hydrocarbon is a liquid paraffin or an ~ -olefin oligomer, the amount of the organic filler to be incorporated is in the range of 35 to 170 parts by weight, based on 100 parts by weight of the polyolefin, the crystal seed forming agent is an 10, organic heat-resistant substance having a metling point .
exceeding 150C and a gelling point exceeding the crystallization initiating point of the polyolefin to be used, and the amount of the crystal seed forming substance to be incorpora~ed is in the range of 0.1 to 5 15 parts by weight, based on 100 parts by weight of ~he polyole~in. .`.
This invention is further directed to an oxygenator provided with a hollow fiber membrane as a gas-exch~nge membrane, which oxygenator i5 characterized 20 by the fact that the gas-exchange me~brane is a porous ~hollow fiber memb?rane of a polyolefin having an inside diameter in the range of 150 to 300 and a wall thickness in the range of 10 to 150 ~m and a substantially .
circular cross section, the inner surface side thèreof 25 h~ very small particl~?~ of the polyolefin closely bound to form a tightly packed layer, the outer surface side hereof has ve?ry ~a~ particles of the polyolefin ~`~nterconnected after the pattern of chains to form a porous layer, very thin through holes are ~ormed as 30 extended from the inner surface side to the outer surface Qide, and the porous hollow fiber membrane has an ave?rage crimp? amplitude in the range of 35 to 120~ of the outs~de diame~e;r, a maximum crimp amplitude/crimp half cyc?le period at maximum crimp amplitude ratio in 35 the range of 1.0% to 3.0~. This oxygenator, therefore, does not suffer from such drawbacks as blood plasma leakage. When this oxygenator is used for ~ 59 ~

'' ' - ': ' ,': ~' , ' ; ; . : , - l 324470 extracorporeal circulation of blood by circulating the blood outside the hollow fiber membrane and an oxygen-containing gas inside the hollow fiber membrane, the possibilitv of ~he oxygen-containing gas stagnating 5 in the gaps intervening between the adjacent hollow fibers is nil and the gas-exchange is carried out efficiently. When the oxygenator is used for extarco~poreal blood circulatiogn by circulating the blood inside the hollow fiber membrane and blowing the 10 oxygen-containng gas outside the ho,llow fiber membnrane, it is capable of carrying out the gas exchange with high efficiency. In this case, the highly efficient gas exchange can be obtained without requiring the hollow fiber bundle to be constricted at the cen~er in the lS axial direction. In the oxygenato~ o~ the lung intended for passing the blood inside the ~lcw fiber membrane, since the steam contained in the oxygen-containng gas inside the oxygenator is condensed to form dew on the inner surface of the housing of the oxygenator, there 20 arises the possibility of water drops wetting the surface of the hollow fiber and the wetted hollow fiber adhering fast to the inner surface of the housing.
Thus, gaps of prescribed dimensional properties interposed between the hollow fiber bundle and the inner 25 surface of the housing so as to keep the hollow fiber bun a e from adher~ng fast to the inner surace of the housing. If a con~inuous gap is formed throughout the entire length of the hollow fiber bundle, the passage of gas occur~ exclusively in the continuous gap. Thus the 30 oxygenator is provided at the center in the axial direction with a constricted part which is intended to render the phenomenon o channeling difficult to occur.
Nhen the crimped hollow fiber membrane contemplated by the present invention is used, since the hollow fiber 35 membane itself is ~ , the dew possibly ormed on the inner surface of the housing cannot cause tight adhesion of the hollow fiber membrane to the inner surace of the ' -housing even if no large space is interposed between the hollow fiber membrane and the inner surface of the housing. Thus, the oxygenator is allowed to retain the gas-exchange efficiency intact even in the absence of 5 the constricted part. The oxygenator of this invention is enabled to manifest the quality more advantageously and even permit a reduction in size when the hollow fiber membrane has a void ratio in the range of 5 to 60~, a gas flux in the range of 100 to l,S00 10 li~ers/min.m2. atm, the polyolefin is polypropylene, and the hollow fiber membrane has an average crimp amplitude in the range of S0 to 100% of the outside diameter, a maximum crimp ampli~ude/crimp half cycle period at maximum crimp ampli~ude ratio in ~the range of 0.02 to 15 0.05, and a crimp ratio in the range of 2.0 to 3.0%.

.

Claims

1. A hydrophobic porous hollow fiber membrane possessing an inside diameter in the range of 150 to 300 microns, a wall thickness in the range of 10 to 150 microns, and a substantially circular cross section, which porous hollow fiber membrane possesses an average crimp amplitude in the range of 35 to 120% of the outside diameter, a maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio in the range of 0.01 to 0.1, and a crimp ratio in the range of 1.0 to 3.0%.

2. A porous hollow fiber membrane according to Claim 1, wherein the void ratio is in the range of 5 to 60%.

3. A porous hollow fiber membrane according to Claim 1, wherein the oxygen gas flux is in the range of 0.1 to 2,000 1/min.m2.atm.

4. A porous hollow fiber membrane according to Claim 1, wherein said inside diameter is in the range of 180 to 250µm and the wall thickness is in the range of 20 to 100 µm.

5. A porous hollow fiber membrane according to Claim 1, which is made of polypropylene.

6. A porous hollow fiber membrane according to Claim 2, wherein said average crimp amplitude is in the range of 50 to 1008 of the outside diameter, said maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio is in the range of 0.02 to 0.05, and said crimp ratio is in the range of 2.0 to 3.08.

7. A porous hollow fiber membrane according to Claim 1, which is a porous hollow fiber membrane of a polyolefin.

8. A porous hollow fiber membrane according to Claim 1, wherein minute polyolefin particles intimately are bound and allowed to form a tightly packed layer on the inner surface side of the hollow fiber membrane, minute polyolefin particles are bound after the pattern of chains and allowed to form a porous layer on the outer surface side of the hollow fiber membrane, and very small through holes are formed in the hollow fiber membrane as extended from the inner surface side to the outer surface side.

9. A porous hollow fiber membrane according to Claim 8, wherein said average crimp amplitude is in the range of 50 to 100% of the outside diameter, the maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio is in the range of 0.02 to 0.05, and the crimp ratio is in the range of 2.0 to 3.0%.

10. A porous hollow fiber membrane according to Claim 1, wherein the solid phase in the inner surface of said hollow fiber membrane has polypropylene particles partly exposed through the surface and preponderantly fused and bound intimately to give rise to a continuous phase, the solid layer in the interior through the outer surface of the membrane has polypropylene particles arranged in the axial direction of fiber to give rise to a multiplicity of polypropylene clusters, and the gaps between the solid phases are interconnected in the form of a three-dimensional network to give rise to through holes.

11. A porous hollow fiber membrane according to Claim 10, wherein the birefringence ratio in the axial direction of fiber of said porous hollow fiber membrane is in the range of 0.001 to 0.01.

12. A porous hollow fiber membrane according to Claim 10, wherein the average crimp amplitude is in the range of 50 to 100% of the outside diameter, the maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude is in the range of 0.02 to 0.05, and the crimp ratio is in the range of 2.0 to 3.0%.

13. A method for the production of a porous hollow fiber membrane, which is characterized by mixing a polyolefin, an organic filler uniformly dispersible in the polyolefin in the molten state thereof and easily soluble in a liquid extractant to be used, and a crystal seed forming agent, melting the resultant mixture and discharging the molten mixture through annular spinning nozzles into hollow threads, allowing the hollow threads to contact a cooling and solidifying liquid incapable of dissolving the polyolefin thereby cooling and solidifying the hollow threads, then bringing the resultant cooled and solidified hollow threads into contact with the liquid extractant incapable of dissolving the polyolefin thereby extracting the organic filler from the hollow threads, and thermally crimping the hollow threads thereby forming porous hollow fiber membranes possessing an average crimp amplitude in the range of 35 to 120% of the outside diameter, a maximum crimp amplitude/crimp half cycle period at maximum crimp amplitude ratio in the range of 0.01 to 0.1, and a crimp ratio in the range of 1.0 to 3.0%.

14. A method according to Claim 13, wherein the crimp is formed by causing the produced hollow fiber membrane to be cross wound on a bobbin and then heat set.

15. A method according to Claim 18, wherein said heat setting is carried out at a temperature in the range of 50° to 100°C for a period in the range of 2 to 48 hour.

16. A method according to Claim 13, wherein said cooling and solidifying liquid possesses a specific heat capacity in the range of 0.3 to 0.7 cal/g.

17. A method according to claim 16, wherein said cooling and solidifying liquid is silicone oil or polyethylene glycol.

18. An oxygenator provided with hollow fiber membranes as gas-exchange membranes, which oxygenator is characterized by the fact that said gas-exchange membranes are hydrophobic porous hollow fiber membranes set forth in any one of Claims 1 to 12.