Device for transfer of medical substance

A medical device for the transfer of substances, includes a cylindrical housing and, a hollow fiber bundle of a plurality of hollow fiber membranes for transfer of the substances which bundle is inserted within the housing. A first substance transfer chamber is defined by the outer surfaces of the hollow fiber membranes and the inner wall surfaces of the housing, and a first substance transferring inlet and an outlet both communicate with the first substance transfer chamber. Partitions are arranged to support fixedly the opposite ends of the hollow fiber membranes in position, and separate the ends from the substance transfer chamber. A second substance transferring fluid inlet and an outlet communicate with the interior spaces of the hollow fiber membranes, which inlet and outlet are formed together with flow path forming members attached to the opposite ends of the housing, wherein each flow path forming member is provided with an annular protuberance. The flow path forming members and the partitions are fastened to each other by sealing interfacial gaps between them with a packing paterial applied to the outer edges of the protuberances of the flow path forming members, so as to contact the packing material with the partitions.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to a medical device for the transfer of substances 
(or device for transfer of medical substance). More particularly, the 
present invention relates to improvements in and concerning a medical 
device for the transfer of substances such as in an artificial lung or 
artificial kidney. 
2. Description of the Prior Art 
Various medical devices have been made available to date for the transfer 
of substances. As one version of an artificial lung, there has been known 
a hollow fiber type artificial lung which comprises a cylindrical housing, 
a hollow fiber bundle of a plurality of gas-exchange hollow fiber 
membranes and inserted within the housing, an oxygen chamber defined by 
the outer surfaces of the hollow fiber membranes and the inner wall 
surfaces of the housing, an oxygen inlet and an oxygen outlet both 
communicating with the oxygen chamber, partitions supporting opposite ends 
of the hollow fiber membranes fixed in position and isolating them from 
the oxygen chamber, and a blood inlet and a blood outlet communicating 
with the interior spaces of the hollow fiber membranes (Japanese Utility 
Model Disclosure (Jikkai) No. 138,947/1980. As one version of the 
artificial kidney, there has been known a hollow fiber type artificial 
kidney which comprises a cylindrical housing, a hollow fiber bundle of a 
plurality of hollow fiber membranes for dialysis and inserted within the 
housing, a dialytic chamber defined by the outer surfaces of the hollow 
fiber membranes and the inner wall surfaces of the housing, a dialytic 
liquid inlet and a dialytic liquid outlet communicating with the dialytic 
chamber, partitions supporting opposite ends of the hollow fiber membranes 
and separating them from the dialytic chamber, and a blood inlet and a 
blood outlet communicating with the interior spaces of the hollow fiber 
membranes (Compendium of Chemistry, Vol. 21 "Chemistry of Medical 
Materials," pages 144-146, published on Nov. 25, 1978 by Gakkai Shuppan 
Center Ltd.). 
In any of these conventional medical devices for the transfer of 
substances, however, the blood inlet and the blood outlet are formed with 
headers (blood distribution members) fastened to the opposite ends of the 
cylindrical housing. Generally for the purpose of preventing leakage of 
blood, these headers are sealed by being attached as tightly pressed to 
the partitions through the medium of O-rings of soft rubber fitted in 
grooves formed in the inner surfaces of the headers along the peripheries 
thereof. In a device of the kind sealed by this method, however, there is 
a possibility that, after a prolonged service, the partition materials 
(potting materials) at the opposite end faces of the device will cave in 
under the pressure of the O-rings and induce the phenomenon of blood 
leakage. If the O-rings are not neatly fitted in the aforementioned 
grooves, no blood leakage will occur immediately after the device has been 
assembled. When the device is heated as during sterilization with ethylene 
oxide gas, for example, leakage of blood starts to occur through the 
O-rings. It is, therefore, difficult for the O-rings to be safely checked 
for blood leakage before the device is sterilized. 
Further, Schnell U.S. Pat. No. 4,283,284 discloses a hollow fiber dialyzer 
end seal system having an inner sleeve and an outer sleeve at both ends 
formed coaxially each other, holding each end of a bundle of hollow fibers 
in the inner sleeve by potting agents, contacting a seal ring of an end 
closure member with each end of the inner sleeve to fix with an enlarged 
manifold end by screw means and sealing by injecting a sealant partially 
into a space formed between the inner and outer sleeves and the end 
closure member through holes. However, in such end seal system, not only a 
large amount of the sealant is required because of large space, but also 
it is feared that a dialytic solution may leak through a gap between the 
enlarged manifold ends and the outer sleeves to invade into the space 
because the space lacks the sealant. Further, the potting agent contracts 
after curing, so it is feared that the dialytic solution leaks into a 
space between the potting agent and the end closure member through the gap 
between the inner sleeve and the potting agents. 
An object of the present invention, therefore, is to provide a medical 
device for the transfer of substances which is provided with a highly 
reliable, safe sealing structure. 
SUMMARY OF THE INVENTION 
The object described above is accomplished by a medical device for the 
transfer of substances, comprising a cylindrical housing, a hollow fiber 
bundle of a plurality of hollow fiber membranes for transfer of the 
substances and inserted within the housing, a first substance transfer 
chamber defined by the outer surfaces of the hollow fiber membranes and 
the inner wall surfaces of the housing, a first substance transferring 
inlet and outlet both communicating with the first substance transfer 
chamber, partitions supporting opposite ends of the hollow fiber membranes 
fixed in position and separating them from the first substance transfer 
chamber, and a second substance transferring fluid inlet and outlet 
communicating with the interior spaces of the hollow fiber membranes and 
formed with flow path forming members attached to opposite ends of the 
housing and provided each with an annular protuberance, which device is 
characterized by having the flow path forming members and the partitions 
fastened to each other by sealing the interfacial gaps therebetween with a 
packing material applied to the outer edges of the protuberances of the 
flow path forming members, so as to contact the packing material with the 
partitions. 
In a preferred embodiment of the invention, the protuberances of the flow 
path forming members are continous raised strips which are held fixed to 
the flow path forming members, and the packing material is applied to fill 
up the gaps formed by the strips, the portions of the flow path forming 
members excluding the strips, and the partitions. The packing material is 
injected into the gaps through at least two holes bored in each of the 
flow path forming members so as to communicate with the gaps formed 
between the flow path forming members and the partitions. The packing 
material now filling the gaps is left standing until complete cure. The 
packing material is made of a homogeneous, substance especially the same 
substance as the potting material which is used in the formation of the 
partitions. The flow path forming members are made preferably of 
polycarbonate.

PREFERRED EMBODIMENT OF THE INVENTION 
FIG. 1 represents a hollow fiber type artificial lung as a typical medical 
device for the transfer of substances according to the present invention. 
That is to say, the hollow fiber type artificial lung of this invention 
has a housing 1, and the housing 1 is provided, at opposite ends of a 
cylindrical main body 2 which forms a part of the housing, with annular 
male screw thread fitting covers 3, 4. Inside the housing 1, a 
multiplicity, specifically on the order of 10,000 to 60,000 in total, of 
gas-exchange hollow fiber membranes 5 are parallelly arranged, while 
mutually separated, longitudinally to full capacity. Inside the annular 
fitting covers 3, 4, the opposite ends of the gas-exchange hollow fiber 
membranes 5 are water-tightly supported in position by a first partition 6 
and a second partition 7 in such a manner that the openings of the 
individual membranes may not be blocked. The partitions 6, 7 define and 
enclose an oxygen chamber 8 in conjunction with the outer surfaces of the 
hollow fiber membranes 5 and the inner wall surfaces of the housing 1. The 
partitions further separate the oxygen chamber 8 from cavities or interior 
spaces formed inside the gas-exchange hollow fiber membranes 5 for passage 
of blood (not shown). 
The annular fitting cover 3 is provided with an inlet 9 for supply of 
oxygen which is a first fluid for transfering a substance, and the other 
annular fitting cover 4 is provided with an outlet for discharge of 
oxygen. 
The cylindrical main body 2 of the housing 1 preferably is provided on the 
inner wall surface thereof with a constricting member 14 protruding at a 
position halfway along the axial length thereof. To be specific, the 
constricting member 14 is integrally formed with the cylindrical main body 
2 on the inner wall side of the main body, so as to squeeze the overall 
periphery of the hollow fiber bundle 15 comprising the multiplicity of 
hollow fiber membranes 5 inserted axially in the interior of the 
cylindrical main body 2. Thus, the hollow fiber bundle 15 is constricted 
at a point falling halfway along the axial length thereof as illustrated 
in FIG. 1 to form a squeezed portion 16. The packing ratio of the hollow 
fiber membranes 5 continuously varies in the axial direction thereof, 
reaching the maximum at the center. For a reason to be described later, 
the values of packing ratio at varying points are desired to be as 
follows. First, the packing ratio in the squeezed portion 16 at the center 
is about 60 to 80%, that inside the cylindrical main body 2 about 30 to 
60%, that at the opposite ends of the hollow fiber bundle 15, namely on 
the outside of the partitions 6, 7 about 20 to 40%. 
The hollow fiber membranes 5 are made of porous polyolefin resin such as, 
for example, polypropylene resin or polyethylene resin. Among other 
polyolefin resins, the polypropylene resin proves particularly desirable. 
These hollow fiber membranes 5 can be obtained in a form containing 
numerous pores interconnecting the inside and the outside of the 
partition. The inside diameter is about 100 to 1,000 .mu.m, the wall 
thickness is about 10 to 50 .mu.m, the average pore diameter is about 200 
to 2,000 .ANG., and the porosity is about 20 to 80%. In the hollow fiber 
membranes made of such a polyolefin resin, the resistance the membranes 
offer to the movement of a gas therein is small and the capacity of the 
membranes for gas exchange is notably high because the gas moves therein 
in a voluminal flow. Optionally, the hollow fiber membranes may be made of 
silicone. 
The hollow fiber membranes 5 made of porous polypropylene or polyethylene 
are not directly used in their unmodified form in the artificial lung but 
preferably have their surfaces, which are destined to contact blood, 
coated in advance with an antithrombotic material. For example, the 
surfaces may be treated with such a material as polyalkyl sulfone, ethyl 
cellulose or polydimethyl siloxane which excels in gas permeability, so as 
to be coated with a film of this material in a thickness of about 1 to 20 
.mu.m. In this case, possible dispersion of water vapor from the blood 
under treatment may be precluded by allowing the produced film of this 
material to cover the pores in the membranes to such an extent that no 
adverse effect will be exerted on the previousness of the hollow fiber 
membranes 5 to gases. Generally during the operation of the artificial 
lung, the pressure on the blood side is higher than that on the oxygen 
side. There are times when this relationship may be reversed for some 
cause or other. If this reversal occurs, there may ensue the possibility 
of microbubbles flowing into the blood. When the hollow fiber membranes 
have their pores coated with an antithrombotic material as described 
above, this possibility is completely avoided. Of course, this coating is 
also useful for preventing the blood from coagulation (occurrence of 
microclots). 
Now, the formation of the partitions 6, 7 will be described. As described 
above, the first and second partitions 6, 7 fulfil an important function 
of isolating the interiors of the hollow fiber membranes 5 from the 
ambience. Generally, the partitions 6, 7 are produced by centrifugally 
casting a high molecular potting agent of high polarity such as, for 
example, polyurethane, silicone or epoxy resin, in the inner wall surfaces 
at the opposite ends of the housing 1 and allowing the cast potting agent 
to cure in place. To be more specific, a multiplicity of hollow fiber 
membranes 5 of a length greater than the length of the housing 1 are 
prepared and, with their opposed open ends filled up with a highly viscous 
resin, disposed parallelly within the cylindrical main body 2 of the 
housing 1. Then, the opposite ends of the hollow fiber membranes 5 are 
completely concealed with mold covers of a diameter greater than the 
diameter of the fitting covers 3, 4. The high molecular potting agent is 
cast through the opposite ends of the housing 1 at the same time that the 
housing 1 is rotated about its own axis. After the resin has been cast and 
cured fully, the mold covers are removed and the outer surface portions of 
the cured resin are cut off with a sharp cutter to expose the opposite 
open ends of the hollow fiber membranes 5 to view. Consequently, there are 
formed the partitions 6, 7. 
In the embodiment described above, since the hollow fiber bundle 15 is 
constricted at the central portion by the constricting member 14 and 
expanded toward the opposite ends thereof, the packing ratio of hollow 
fiber membranes 5 is increased in the squeezed portion 16 and, at the same 
time, the individual hollow fiber membranes 5 are uniformly dispersed 
inside the cylindrical main body 2. Consequently, the oxygen gas is 
allowed to form a uniformly dispersed, stable current as compared with a 
hollow fiber bundle which lacks the squeezed portion 16. This means that 
the efficiency of exchange of oxygen for carbon dioxide gas is improved. 
Further, since the internal cross section of the housing 1 is suddenly 
changed in the squeezed portion 16 at the center, the flow rate of the 
oxygen gas in this portion is suddenly changed. Thus, the constriction of 
the hollow fiber bundle 15 is effective in increasing the flow rate of the 
oxygen gas and heightening the speed of movement of the carbon dioxide gas 
as well. 
The packing ratio of hollow fiber membranes 5 in the squeezed portion 16 is 
preferably fixed in the range of about 60 to 80% for the following reason. 
If the packing ratio is less than about 60%, part of the hollow fiber 
membranes 5 are not squeezed by the constricting member 14. Consequently, 
the performance of the hollow fiber membranes is impaired because they are 
unevenly distributed to an extent of inducing the phenomenon of 
channeling. Further, there is posed a problem that the hollow fiber bundle 
15 cannot be accurately disposed at the center of the cylindrical main 
body with ease. If the packing ratio is more than about 80%, those of the 
hollow fiber membranes 5 held in direct contact with the constricting 
member 14 are depressed so powerfully as to be crushed. Consequently, 
blood fails to flow through the crushed hollow fiber membranes, lowering 
the overall efficiency of the hollow fiber bundle and inducing the 
phenomenon of blood stagnation. Moreover, during the assembly of the 
artificial lung part, the constricting member 15 permits no easy passage 
of the hollow fiber bundle 15, making the work very difficult. 
The packing ratio of hollow fiber membranes inside the cylindrical main 
body 2 has been fixed in the range of about 30 to 60% for the following 
reason. If the packing ratio is less than about 30%, the hollow fiber 
membranes 5 are deviated to one side in the interior of the cylindrical 
main body 2 and, consequently, the efficiency of exchange of oxygen gas 
for carbon dioxide gas is degraded. The work involved also becomes 
difficult. If the packing ratio is more than about 60%, mutual contact of 
hollow fiber membranes 5 occurs and exerts an adverse effect upon the 
performance of the hollow fiber bundle. 
The packing ratio of hollow fiber membranes outside the partitions 6, 7 has 
been fixed in the range of about 20 to 40% for the following reason. If 
this packing ratio is less than about 20%, the uniformity of the 
distribution of hollow fiber membranes 5 at the opposite open ends tends 
to be degraded by reason of workmanship. Consequently, such problems as 
nonuniform blood flow distribution and blood clotting ensue. If the 
packing ratio is more than about 40%, mutual contact of hollow fiber 
membranes 5 occurs and prevents the potting agent, the materials for the 
first and second partitions 6, 7, from being evenly cast throughout the 
entire inner wall surfaces at the opposite ends of the cylindrical main 
body. Consequently, the produced partition 6, 7 will suffer from leakage. 
In the embodiment so far described, only the constricting member 14 is 
partially projected from the inner wall surface of the housing 1. This is 
not necessarily the sole means of imparting required constriction upon the 
hollow fiber bundle. It may be otherwise obtained by separately forming a 
ring-shaped constricting member and fitting it in position on the interior 
of the cylindrical main body. It may be obtained by forming an annular 
recess at the center of the cylindrical main body. Optionally, the 
cylindrical main body may be gradually converged inwardly from the 
opposite ends thereof so that the inside diameter thereof reaches its 
minimum at the center and its maximum at the opposite ends. 
The outer surfaces of the partitions 6, 7 are respectively covered with 
flow path forming members 11, 12 which are each provided with an annular 
protuberance. The flow path forming members 11, 12 are composed 
respectively of liquid distributing members 17, 18 and screw rings 19, 20. 
On the liquid distributing members 17, 18 along their peripheries, there 
are provided continuous raised strips 21, 22 in the shape of annular 
protuberances. By holding the edge faces of these continuous raised strips 
fixed against the aforementioned partitions and fastening the screw rings 
19, 20 through helical insertion to the fitting covers 3, 4, there are 
formed an inlet chamber 23 and an outlet chamber 24 for blood as a second 
substance transferring fluid. In the flow path forming members 11, 12, 
inlets 25, 26 for blood as the second substance transferring fluid, and 
holes for discharge of air are provided. 
The gaps formed round the peripheries of the partitions 6, 7 between the 
partitions 6, 7 and the flow path forming members 11, 12 are sealed by 
being filled up with packing agents 31, 32 introduced via at least two 
holes 29, 30 communicating with the gaps, so as to contact the partitions 
6, 7. 
The packing material to be used in the present invention must be in a 
liquid or some other similar state, so as to exhibit ample flowability 
when it is injected through the holes 29, 30 into the vacant portion. 
Thus, it is preferably made of rigid resin which exhibits high 
adhesiveness at least to the flow forming members 11, 12 and the 
partitions 6, 7. As the packing material, a potting agent of high polarity 
such as, for example, polyurethane, silicone or epoxy resin which is 
similar to the potting agent generally used to make the partitions 6, 7 is 
available. Particularly, polyurethane gives desirable results. Further, as 
the material for flow forming member 11, 12, polycarbonate is preferable. 
Among the different types of polyurethane adhesive agents, the prepolymer 
adhesive agent, the polyisocyanate adhesive agent and the 
isocyanate-modified polymer are advantageously used. Generally, the 
prepolymer adhesive agent is a preferred choice. A typical prepolymer 
adhesive agent is produced by mixing a prepolymer formed of 4,4'-diphenyl 
methane diisocyanate and a bifunctional caster oil derivative (such as, 
for example, polypropylene glycol ester of ricinoleic acid, having a 
molecular weight of 540) (with a NCO/OH ratio in the range of 1:1 to 
1:1.5) with a curing agent formed of a mixture of a bifunctional castor 
oil derivative, a polyfunctional polypropylene glycol (having a molecular 
weight of 2,000 to 3,000, and an amino alcohol (50-70:15-25:15-25 by 
weight ratio) in a weight ratio of 65:35 to 59:41, for example, so as to 
equalize substantially the numbers of functional groups involved. This 
prepolymer adhesive agent is capable of cold curing, possesses moderate 
elasticity, and excels in adhesiveness. 
In the preferred embodiment of FIG. 1, the openings are fitted with 
respective caps 33, 34, 35 and 36. 
FIG. 2 represents another preferred embodiment of this invention. Here, the 
annular protuberance formed on the liquid distributing member 17 along the 
periphery thereof comprises a continuous raised strip 21 and an O-ring 37 
formed outside the continuous raised strip 21. The sealing of the device 
is accomplished by filling with the packing material 31 the gap which is 
formed by the O-ring, the portion of the flow path forming member other 
than the O-ring, and the partition. The same numerical symbols found in 
FIG. 2 as those used in FIG. 1 denote like parts. 
FIG. 3 represents a further preferred embodiment of the present invention. 
In an artificial lung similar to the artificial lung illustrated in FIG. 
1, the flow path forming member 11 is inserted in such a manner that the 
continuous raised strip 21 formed as an annular protuberance on the inner 
surface of the flow path forming member 11 along the periphery thereof, 
may come into contact with the partition 6 at one end of the cylindrical 
main body 2 instead of forming any screw thread on the inner surface of 
the ring part of the flow path forming member 11 composed integrally of a 
liquid distributing member and a ring member. The sealing of the device is 
accomplished by filling with the packing material 38 the gap formed by the 
flow path forming member 11, the partition 6, and the end part of the 
cylindrical main body 2. 
The filling of the gap with the packing material, when the packing material 
has high viscosity, may be accomplished by having the packing material 
applied in advance to the inner surface of the flow path forming member 11 
and inserting the flow path forming member 11 into the cylindrical main 
body 2. When the packing material has low viscosity, it may be 
accomplished by injecting the packing material into the gap through the 
hole 29 (or a gap 39 where the hole 29 is not formed) after the insertion 
of the flow path forming member 11 into the cylindrical main body 2. Then, 
the flow path forming member is set in its final position with the aid of 
a jig and the packing material now filling the gap is solidified by cold 
curing, hot curing, fusion with ultrasonic waves, or thermal fusion. The 
same numerical symbols found in FIG. 3 as those used in FIG. 1 denote like 
parts. 
The invention has been described as embodied in the artificial lung. When 
the artificial lung so embodying this invention is put to use with a heat 
exchanger coaxially connected thereto as proposed by Japanese Patent 
Application No. 115,868/1980, the flow path forming member to be used on 
the free end (the end opposite the end continuous with the artificial 
lung), can be similarly sealed as contemplated by this invention. 
By using hollow fiber membranes made of cellulose regenerated by the 
cuprammonium process, cellulose regenerated by the acetocellulose process, 
a stereo-complex of polymethyl methacrylate, polyacrylonitrile or 
ethylene-vinyl alcohol copolymer in a device for the transfer of a medical 
substance similar in structure to the artificial lung described above, 
there is obtained an artificial kidney. 
The device for the transfer of a medical substance constructed as described 
above according to the present invention is put to use as incorporated in 
an external circulation path for blood, for example, which is the second 
substance transferring fluid. In the case of the artificial lung, for 
example, the blood delivered by a blood pump (not shown) is introduced 
through the blood inlet 25, passed through the blood inlet chamber 23 and 
the interiors of the hollow fiber membranes. During this passage, the 
blood is impregnated with the oxygen gas introduced via the inlet 9 into 
the substance transfer chamber 16 and is divested of carbon dioxide gas. 
Then, the blood is forwarded via the blood outlet chamber 24 and 
discharged through the blood outlet 26. The oxygen within the substance 
transfer chamber 16 is discharged in conjunction with carbon dioxide gas 
through the outlet 10. The artificial kidney is operated on substantially 
the same principle, except that a dialytic fluid is used in the place of 
oxygen. 
Further, on one hand, blood can be introduced from the inlet 9 to the 
substance transfer chamber 16, and exhausted from the outlet 10. On the 
other hand the substance transferring fluid, e.g., oxygen can be 
introduced from the inlet chamber 23 into the hollow fibers 5 and 
exhausted from the outlet chamber 24. 
As described above, the present invention resides in sealing a medical 
device for the transfer of substances by filling the gaps formed round the 
peripheries of the flow path forming members, at opposite ends of the 
device, with a packing material thereby fastening the aforementioned flow 
path forming members to partitions at the end portions of the device. 
Thus, the packing material seals the device perfectly and precludes liquid 
leakage through lines or junction faces completely. This invention makes 
possible a notable cost cut because it permits omission of O-rings which 
have been indispensable components for the conventional device. It further 
offers an advantage that the packing material is not easily broken by 
shocks possibly exerted upon the screw ring, because the material remains 
concealed in the gap. Optionally, the liquid distributing member and the 
ring may be integrally formed to obviate the necessity of using a screw 
thread. This fact again contributes to cut costs.