Note: Descriptions are shown in the official language in which they were submitted.
~ 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
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1 324470
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
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1 324470
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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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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1 324470
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
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1 324470
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
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1 324470
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
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1 324470
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
1 324470
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
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1 324470
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
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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
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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
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1 324470
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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1 324470
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
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1 324470
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
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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
- 17 -
- 1 324470
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
- 18 -
1 324470
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
- 20 -
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
- 21 -
. . ~ . .
1 32447D
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.
- 22 -
1 324470
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
. .
- 23 -
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
- 24 - -
-~'
1 324470
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
. . .
- 25 -
1 324470
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
": `
- 26 -
,
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
- 27 -
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,
- 28 -
I 324470
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.
- 29 -
1 324470
~ 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
- 30 -
, '.: "
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
- 33 -
~ 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
'
- 34 -
,~ :
1 324470
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
- 35 -
1 324470
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
- 36 -
~, .. .. .
1 324470
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
- 37 -
1 324470
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
- 38 -
1 324470
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
- '
- 39 -
.: ~
:
1 324470
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,
. . .
.
- 40 - `~.
1 324470
--~¦ '`~ o N O
J u ~!1 N ~ ~
~1 o '. .
u~ ~
~I w ~1 ... :
;~ il r ~
3 i ::
,`:,~
.
_41-
1 324470
C
`
o ~ ~ `
C ~ .
o
~. ~
~ ~: 5 ~ ` ~
.... ~ X
,
42- `"` `` ` ~`
` j ,
: ~`
~`: ~ :: ` ~ ` "
` ~ :: ,
1 32447~
~ C
, ~ o ,~
.~ ~ ~ , .
U ~ ,
=¦ u~ ~
O E
1!1¦ o r
~ `_ `
;~lo
- I ` ~ .. ` . . :`.;
a ~ ~a
c ~ ~ a
. ~..
43
~'',~",
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1 324470
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 _
1 324470
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
- 45 -
1 324470
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.
" o ~ 1 324470
E¦ o ~
'E~
ol N ~ ~, O
¦ = o ~ O O
~ Q
~q
.~ U~ ~
l ~ ~1 ~ a s
;~1 1 ~ o ~ ~71
~ .
N
IA N ~ '-- ~ O
`.
- 47 - ;
1 3 2 4 4 7 ~ ¦ b¦ ~
ul ~ ~ c
~c~
cl N ~ 5¦ ; S;
, 1 1 ~
~ 5 ` ~7
~I N ~ N N ~ ~
a ~
O ~ ~0 0 ~ O
a ~ ~ ~' Y
1 324470
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
- 49 -
1 324470
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
- 50 -
1 324470
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). ;~ ~
,'., .
- 51 ~
vl 1 324470
~ ol ~ ~ I
ol~ O O a~
~o~ ~ 5
2 ~
3 ~ ~ E ~ 8
` `~ " ~ B
v 3
-s2-
1 324470
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.
- 53 -
,~ ,,., '"
- 1 324470 c
8 N N
'~ .
D e
il o r I O ~ 3 ~ o o
x ~ ~o
~ ~ o o ~ ~
~3 N ~1
0 U~ U~ ~ o ~ N
~0 1'~ ~ O r~ O
~ ~ ou j 0~
1 . ~ ~ o~ `"
~ 7 ~ o
¦¦~ 2 ~ -'
`~ ~ i~ ` ``'
o O
j
ô 1 .~ ~1 8
t b t ~ ~ a 5
a ~ ~ ~o a ~0 - ~ x ~0 ~
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t324470 ~c~l ~ ~
N 1~ N ~ ~ il N N
~¦ o
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~i ~ ~ ¦ N N . -
N -- ~
s s ~ a 1 9 ~
--55-- `
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~ -
1 324470
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 _
1 324470
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
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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
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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
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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%.
.
