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Patent 1184716 Summary

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(12) Patent: (11) CA 1184716
(21) Application Number: 371435
(54) English Title: PLASMA PHORESIS MEMBRANE
(54) French Title: MEMBRANE DE PLASMAPHORESE
Status: Expired
Bibliographic Data
(52) Canadian Patent Classification (CPC):
  • 18/25
  • 18/597
(51) International Patent Classification (IPC):
  • C08J 9/28 (2006.01)
  • A61M 1/16 (2006.01)
  • C08J 5/22 (2006.01)
  • D01D 5/24 (2006.01)
  • D01D 5/247 (2006.01)
  • D01F 1/08 (2006.01)
  • D01F 2/20 (2006.01)
  • D01F 2/28 (2006.01)
(72) Inventors :
  • BANDEL, WERNER (Germany)
  • DUNWEG, GUSTAV (Germany)
(73) Owners :
  • AKZO N.V. (Netherlands (Kingdom of the))
(71) Applicants :
(74) Agent: NORTON ROSE FULBRIGHT CANADA LLP/S.E.N.C.R.L., S.R.L.
(74) Associate agent:
(45) Issued: 1985-04-02
(22) Filed Date: 1981-02-20
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): No

(30) Application Priority Data:
Application No. Country/Territory Date
P 30 06 880.5 Germany 1980-02-23

Abstracts

English Abstract






ABSTRACT OF THE DISCLOSURE


A plasmapheresis membrane in the form of hollow
threads, tubular foil, or flat foil, produced by a method
in which a spinning solution made of cellulose ester is
pressed through a spinneret immersed in a precipitation bath,
is washed free of solvent with water, is impregnated with a
plasticizer-solution, and is dried.


Claims

Note: Claims are shown in the official language in which they were submitted.



The embodiments of the invention in which an exclusive pro-
perty or provilege is claimed are defined as follows.

1. A membrane, in the form of hollow filaments or
fibres, tubular foil, or flat foil, made of a cellulose ester,
which comprises closed cells arranged in rows in the manner
of a honeycomb, said cells being substantially rectangular
or prismatic, all of the cell walls of said cells being
pierced with a plurality of holes forming pore passages,
produced by a method in which a spinning solution containing
8 to 25%, by weight, of cellulose ester, 55 to 92%, by weight
of a solvent mixture, said mixture comprising 50 to 90%, by
weight, of acetone, 5 to 25%, by weight, of monovalent
alcohol, and 5 to 25%, by weight, of plasticizer, is
immersed as a jet of solution in a precipitation bath, the
jet of solution being exposed, along a section of the
precipitation bath measuring at least 30 cm, at the
boundaries of said jet, to the coagulating action of the
precipitation bath, is removed from said precipitation bath,
is washed free of solvent with water, is impregnated with
a plasticizer solution, and is dried.


2. A membrane according to claim 1, wherein said
plasticizer of said spinning solution and of said
plasticizer solution is a polyvalent alcohol.


3. A membrane according to claim 2, wherein the
polyvalent alcohol is glycerine.


4. A membrane according to claim 1, wherein the

cellulose ester is cellulose acetate.


5. A membrane according to claim 4, wherein the
cellulose acetate has a degree of substitution of between
2.0 and 2.7.

-21-

6. A membrane according to claim 5, wherein the
degree of substitution is between 2.3 and 2.5.


7. A method for producing a membrane, in the form of
hollow filaments or fibres, tubular foil, or flat foil, made
of a cellulose ester, which comprises immersing a jet of a
spinning solution containing 8 to 25%, by weight, of
cellulose ester, 55 to 92%, by weight, of a solvent mixture,
said mixture comprising 50 to 90%, by weight, of acetone,
5 to 25%, by weight, of a monovalent alcohol, and 5 to 25%,
by weight, of plasticizer, in a precipitation bath, exposing
a jet of solution along a section of the precipitation
bath measuring at least 30 cm, at the boundaries of said
jet, to the coagulating action of the precipitation bath,
removing the coagulated product from said precipitation
bath, washing the coagulated product free of solvent with
water, impregnating the product with a plasticizer solution,
and drying the product.


8. A method according to claim 7, wherein said jet
of solution is pressed through a spinneret immersed in said
bath.


9. A method according to claim 7, including intro-
ducing a precipitation bath into the interior of the emerging
spinning solution to produce hollow filaments or fibres or
tubular foils.


10. A method according to claim 9, wherein the

internal and external precipitation baths are of the same
composition.

-22-


11. A method according to claim 7, wherein said
spinning solution additionally contains up to 20%, by
weight, based on the weight of the spinning solution of
at least one conventional additive.


12. A method according to claim 11, wherein said
additive is selected from the group consisting of pigments
and viscosity lowering agents.


13. A method according to claim 7, 8 or 9, wherein
the monovalent alcohol has 1 to 3 carbon atoms.


14. A method according to claim 7, wherein said
plasticizer of said spinning solution and of said
plasticizer solution is a polyvalent alochol.


15. A method according to claim 14, wherein said
polyvalent alcohol is glycerine.


16. A method according to claim 7 or 8, wherein said
precipitation bath comprises an aqueous solution.


17. A method according to claim 7 or 8, wherein
said precipitation bath is water.



18. A method according to claim 7, wherein the
cellulose ester is cellulose acetate.


19. A method according to claim 18, wherein the
cellulose acetate has a degree of substitution of between
2.0 and 2.7.

-23-

20. A method according to claim 19, wherein the
degree of substitution is between 2.3 and 2.5.


21. A method according to claim 7, wherein the
viscosity of the spinning solution is between 5 and
200 Pas.


22. A method according to claim 21, wherein the
viscosity of the spinning solution is between 10 and 100
Pas.


23. A method according to claim 22, including a
step of adjusting the viscosity of the spinning solution
by including a viscosity controlling additive in the
spinning solution.


24. A method according to claim 7, wherein after
passing along said section of the precipitation bath
measuring at least 30 cm, the jet is passed around a
deflecting element, and is removed from the precipitation
bath at an angle of between 15 and 60° to the surface of
said bath.


25. A method according to claim 24, wherein said
jet of solution is pressed through a spinneret immersed
in said bath, and said deflecting element is disposed
downstream of said spinneret.



26. A method according to claim 25, wherein the
spinneret forms an acute angle with the surface of the
precipitation bath.


27. A membrane according to claim 1, in the form of
a plasmapheresis membrane.

-24-


28. A membrane according to claim 1 or 27, formed
from a cellulose acetate.


29. A membrane according to claim 1 or 27, wherein
said pore passages have a diameter of 0.01 to 50 µm.


30. In a plasmaphoresis device comprising a membrane
for separating blood plasma, the improvement wherein said
membrane is a membrane as defined in claim 1, 4 or 5.


31. In a plasmaphoresis device comprising a membrane
for separating blood plasma, the improvement wherein said
membrane is a membrane as defined in claim 7 or 27.

-25-

Description

Note: Descriptions are shown in the official language in which they were submitted.


7~

The invention relates to a membrane, more particu-
larly for plasmapheresisl and more especially to a membrane
in the form of hollow threads, or fibres, tubular foil or
flat foil, made of cellulose esters.
Plasmapheresis membranes are used in plasma separa-
tion, that is, the separation of blood plasma from its cel-
lular constituents and the further separation of plasma
constituents according to molecular weight.
After plasmapheresis had been carried out for a long
time with membrane filters, centrifuyes were used for the
purpose. In recent times there has been a trend bac~ to
~iltration processes, one of the reasons for this being
that the production of membrane filters has in the meanwhile
become more highly mechanized, so that they can now be pro-
duced in adequate quantitites at reasonable prices.
UOS~ Patent 1,4~1,341 describes a filter and a
production methocl, the filter being made ~f a cellulose ester,
for example cellulose acetate, which comprises pores suitable
for separating bacteria. The filters described may be dried
without collapsing the pores.
The filters are produced b~ pouring a solution of
the cellulose ester into a solvent mixture and evaporating
the solvent in a moist atmosphere at a low temperature.
Enough water is added to the solvent to ensure that the mix-
ture dissolves the cellulose ester. The amount of water
governs the size of the pores. The membrane thus obtained is
washed in water, is stretched in a wet condition and, after
a heat treatment, is dried in hot water or steam.
German Patent 8~3,088 describes a method for pro-

ducing ultra filters and diaphragms out of synthetic materialsrIn this case, porosity is achieved by adding to a plastic


solution, suitable for producing a thin skin, salts soluble
therein or other substances, in a solution which is miscible
with the plastic solution but does not react therewith, where-
upon the mixture is dried, the substance added being dissolved
out of the skin thus obtained by means of a solvent which
does not dissolve the plastic.
German Auslegeschrift 1,017,596 describes a method
whereby a cellulose acetate membrane is produced by the phase
inversion process involving pre-gelling in an aerating
~hamber at an operating temperature of between 20 and 40C,
at a relative atmospheric humidity of between 50 and 70~/O.
U.S. Patent 2,783,894 describes a similar method
for producing a microporous membrane ~ilter from nylon.
German Auslegeschrift 1,156,051 describes a method
whereby membranes produced in accordance with the afore
mentioned U~S. Patents 1,421,341 and 2,783,89~ are applied,
in a special manner, to a hollow body provided with dis-
continuities r The pores in the microporous films are less
than about lO~m :in diameter and comprise, in all, more than
8~/o of the total volume of the filter materialO
German Patent 22 57 697 describes porous cellulose
acetate symmetr~-membrane filters produced by dissolving
cellulose acetate, with a 20-65.5% degree of acetylation,
in an organic solvent, the weight ratio being between 5 and
40/O of the solvent, and adding a diluting solvent; the
boiling point of which is higher than that of the organic
solvent; and furthermore adding a metal salt, the metal
component of which has an ion radius of less than 1.33 A,
is a member of Group I - III of the Periodic System, and has
a ratio of between 20 and 2000/o by weight to the acetate, to
the solution, so that a homogeneous solution is obtained.

A thin :~ilm of this solution is applied to a ~lat, polished
surface, the solvent therein being removed by evaporation.
Microphase separation converts this to a gel~ Finally, the
metal salts therein are dissolved out in order to form the
porous membrane.
The diameter of the pores is between 0.01 and 10~m
and porosity is said to be between 70 and 81%.
Under the electron microscope,a 6000 ~ enlargement
of such a membrane reveals a structure which, as seen from
the surface, resembles a mat of threads in which threads
arranged in loops and emerging at common intersections, lie
irregularly above and at the side of each other. As seen in
cross-section, the internal structure of the membrane appears
as a loose but ~niformly dense mass.
German Offenlegung~schrift(Published Patent Specifi-
cation) 26 06 244 describes a hollow fibre for membrane filtra-
tion made from a synthetic or semi synethetic, chain like high
polymer which forms threads when spun, the cylindrical wall
constituting the hollow fibre comprising, at least in a
closed area appearing cross-sectionally as an annular band,
a three dimensional, net like structure of fine filter
channels having a pore ratio of at least 55% of the active
filter area, the active points in the filter channels, which
determine the smallest cross sectional dimensions of the
channels for the passage of substances contained in a filtra-

.ti~n ~luid, being distributed at random at least over theactive filter zone, and these cross-sectional dimensions
being almost uniform. If a membrane of this ~indis observed
under 3000 to 10,000 x magnification, with an electron
microscope, the structure that emerges is reminiscent of a
coral colony consisting of a plurality of coral like branched


stems. At the surface of the exterior of the hollow fibre,
the branches merge into a grained surface with elongated
pore apertures running parallel with each other~
German Offenlegungschrift 28 45 797 describes an
anisotropic synthetic membrane having a multi-layer structure,
each layer acting as a molecular screen for accurate separa-
tion by molecular weightn
Common to all know filter membranes, because of
the fixed supporting surfaces used during production, and
the at least partial evaporation of the solvent, is a more
; or less pronounced pore diameter asymmetry. Some filters
cannot be stored dry and the pores collapse very easily, even
with careful handling. Many known membranes have a wide
range of pore diameter distribution, and thus no definite
rejection limit. Known methods for producing filter mem~
branes generally operate at moderate speeds, apart from the
effects on the membranes produced by production conditions.
Recovery of the solvent from air-solvent mixtures is costly,
involving heavy losses and envirol~metnal pollution.
~he present invention seeks to produce a filtra-
tion membrane in the form of hollow threads, tubular foil
or flat foil, with a novel membrane wall structure permit-
ting plasmapheresis filtration to be carried out at high
speed, for example, the pore diameter providing a specific
rejection limit. Moreover, the disadvantages of known filter
membranes are to be eliminated as far as possible.
According to the invention, there is provided a
method for producing a membrane, in the form of hollow threads
or fibres, tubular foil, or flat foil, made of a cellulose
ester which comprises immersing a jet of a spinniny solution
containing 8 to 25%, by weight, of cellulose ester, 55 to 92%,

by weight, of solvent, and 0 to 20% by weight of at least one
additive in a precipitation bath, exposing the jet of solu-
tion along a section of the precipitation bath measuring at
least 3~ cm, at the boundaries of said jet, to the coagulating
action of the precipitation bath, removing the coagulated
product from said precipitation bath, washing the coagulated
product free of solvent with water, impregnating the product
with a plasticiser solution, and drying the product.
Suitably the jet of solution is pressed through a
spinneret immersed in the bath.
In another aspect of the invention there is provided
a membrane, particularly a membrane for plasmapheresis.
The precipitation bath may be made up of liquids,
which can be mixed in any proportions with the solvent of the
spinning solution, but which do not dissolve or chemically
alter the cellulose ester.
A plasticizer may be used, and in particular
known plastici~ers for cellulose ester, by means of which it
can be ensured that the residual water content after drying
does not drop below 3 to 15%, by weight, of the weight of the
membrane. Polyvalent alcohols and esters have been found
particularly satisfactory.
Tubular foils and hollow threads or fibres have
been found preferable for membranes used in blood dialysis.
They are also preferred for plasmapheresis membranes. In
order to obtain a well formed interior with the desired
lumen cross-section, membranes in the form of hollow threads
or fibres or tubular foil are produced by passing a precipi-
tation bath into the interior of the emerging spinning solu-

tion. In this way, the internal boundary of the jet ofsolution is also exposed to the action of the precipitation
bath.




~i~
,

7~

If the composition of the precipitation bath passed
into the interior differs from that of the precipitation bath
having a coagulating effect upon the external solution-jet
boundary, which leads to nonuniform coagulation velocities,
this produces varying effects upon the porosity of the
internal and external surfaces.
If the precipitation bath contains a large amount
of solvent, this results in smaller pores, while a precipi-
tation bath containing a small amount of solvent results in
larger pores. However, the concentration of solvent in the
precipitation bath should not exceed 20~/o, by weight.
Membranes haviny satisfactory surfaces properties are obtained
when the two precipitation baths are of the same composition.
The membrane according to the invention has a
novel cell structure.
The novel membranes of the invention are further
illustrated by reference to the accompanying drawings in
which:
Figure 1 is an electron microscope photograph of a
membrane of the invention in the form of a hollow thread or
fibre,
Figure 2 is a photograph showing the pores in
greater enlargement, and
Figure 3 is an electron microscope photograph
similar to Figure 1 but with greater enlargement.
A cross~section of the wall, even at a 100 x
enlargement, reveals a pronounced cell structure reminiscent
of a honeycomb, although the boundariesof the close cells
are not similar. The cells are approximately rectangular or
prismatic, arranged together in rows, and connected smoothly
to adjacent cells. The walls of the cells have large numbers



-- 6 --

7~

of holes. The pores in the outer walls and cell walls form
perforated elements through which the ultra filtrate perme-
ates as is shown in Figure 1.
The composition of the spinnin~ solution is of
special significance for the structural prop~rties of the
membrane and the purposes for which it may be used, the
chemical composition and physical characteristics having
comple~ effects upon the arrangement and dimension of the
cells and cell walls.
One factor is the solvent in the spinning solution,
for example acetone, dioxane, dioxolan, methyl acetate,
nitromethane and methylene chloride.
In general, acetone is preferred. Special prefer-
ence is given to the use of mixtures of solvents in the
spinning solution, because of the wide range of control this
gives over the properties and structure of the membrane. A
mixture of 50 to 9~/O by weight of acetone, 5 to 25% by weight
of monovalent alcohol, and 5 to 25% by weight of plasticizer
has been found particularly satisfactory. The use of mono-

valent alcohols hauing 1 to 3 carbon atoms, possibly inadmixture with the alcohols, affects the structure in the
same way as the amount of plasticizer, glycerine being the
preferred plasticizer in the case of membranes to be used
for medical purposes. The use of myristyl myristate as the
plasticizer in the spinning solution makes it possib~e to
produce structures of interest in industrial applications
of the membrane.
The precipitation bath also has a considerable
effect upon the properties of the membrane, water with no
admixture leading to very large pores, while precipitation
baths in the form of aqueous solutions are preferred when



-- 7 --

7~

small pores are required. The membranes of the invention may
have pores between OoOl and 50~m in diameter, depending upon
the operating conditions selected.
In earlier known plasmapheresis membranes, nitro
cellulose was of greater importance than acyl celluloses.
Since the handling of nitrocellulose can produce problems,
acyl celluloses are now generally more important, and they
may be used in the same manner as nitrocellulose for the
membranes of the invention. Mixtures of different acyl
celluloses may also be processed into membranes of the inven-
tion, for example acetyl celluloses, propionyl celluloses and
butyryl celluloses. Cellulose acetate is preferred because
of its availa~ility~
A filtration membrane formed of pure cellulose
triacetate is too hydrophobic for many of the applic~tions of
the membrane of the invention. According to one configura-
tion of the invention, the plasmapheresis membrane is made
of a cellulose acetate with a substitution degree of
~etween 2~0 a~d 2.7. The degree of substitution of the
cellulose acetate used in the spinning solution also corres-
ponds to the membrane spun there~rom. The degree of
substitution preferably amounts to between 2.3 and 2.5.
In the spinning solution, the property having a
particular effect upon the structure of the membrane is
viscosity. Thus high-viscosity spinning solutions produce
membranes with thinner cell walls, which i5 not detrimental
to the mechanical properties if the cell structure is, at
the same time, less symmetrical. The viscosity of the
spinning solution may be controlled not only by the cellu-

lose ester content, but also by viscosity changing solventsor additives. Solvents containing a group, for example,


isopropanol as a monovalent alcohol, are of higher viscosity
than those containing methanol. The viscosity may be lowered,
for example, by the addition of halogenated hydrocarbons,
for e~ample trichlorotrifluoroethane. The viscosity of the
spinning solution is between 5 and 200, preferably between
10 and 100 Pas.
The drying is suitably carried out under temperature
conditions such that the average temperature of the material
does not exceed 70C.
In especially advantageous embodiments of the method
of the invention, for the purpose of obtaining hollow threads
or fibres or tubular foils, a precipitation bath is passed
into the interior of the emerging spinning solution. It is
desirable for both precipitation baths to be of the same
composition.
The solvents used are preferably in the form of
mixtures. One preferred mixture consists of 50 to 90/O~
by weight, of acetone, 5 to 25%, by weight, of monovalent
alcohol, and 5 to 25%, by weight, of plasticizer, the
monovalent alcohol preferably containing 1 to 3 carbon atoms
and the plasticizersbeing polyvalent alcohols, above all
glycerine in medical applications.
The precipitation baths used are in particular,
water and aqueous solutions. Among the cellulose esters
suitable for the membrane, preference is given in particular
to cellulose acetate, especially one with a degree of substi-
tution of between 2.0 and Z.7, more particularly between
2O3 and 2.5. Spinning problems may be largely avoided if the
viscosity of ~he spinning solution is between 5 and 200,
preferably between 10 and 100 Pas~
It has been found that a satis~actory production

_ g .

7~

velocity may be obtained particularly if the jet of solution,
after passing along a section of the precipitation bath
measuring at least 30 cm, is passed around a deflecting
element located after the spinneret, and is removed from the
precipitation bath at an angle of between 15 and 60 to the
surface of the said bath.
In this connection, it has been found desirable for
the spinneret to be immersed into the precipitation bath in
such a manner as to form an acute angle with the surface
thereof.
The membranes of the invention are noted for their
novel structure and are characterized in that each membrane
; is made out of a closed, stamped, substantially rectangular
or prismatic cells, arranged in rows as in a honeycomb, all
cell walls being pierced by a plurality of holes in the
form of pores.
Generally speaking, the design of the membrane is
such that the closed cells are not similar in shape or
volume. However, as a result of the production method, there
is often a cell wall located approximately symmetrically in
the middle of the wall, ~owever, conditions may often be
arranged to produce a central cell wall which meanders
through the cross section.
The selectivity of the membrane is affected not
only by the pores passing through all of the cell walls, but
also by the structure of the cells.
Pi~nents may, of course, be applied to the membrane
in known fashion, if desired.
The invention is illustrated in particular and
preferred embodiments in the following examples.


-- 10 --

EXAMPLE 1
Production of a spinnin~ solution from cellulose acetate
The following were introduced consecutively into
an agitator vessel, the stirring element of which was set
to 800 r.p.m.:
3,000 g of methanol
4,000 g of glycerine
2,000 g of cellulose acetate -
subst. degree 2.48
11,000 g of acetone
After stirring for two hours at room temperature,
the cellulose acetate was dissolved. The solution was then
passed through a 20~m mesh filter, was then aerated, and was
ready for spinning after 4 to 6 hours. The viscosity of
,~v the spinning solution was 15 Pas.
EXAMPLÉ 2
Production of a membrane accordinq to the invention _n
h~ll~v tbrr,ad ~r fibre form
A gear type metering pump was used to feed 6 ml~min~
of the spinning solution, pxoduced as in Example 1, to a
hollow thread or fibre spinneret of known design having an
outer annular slot 1.300~m in diameter and a slot 150~m in
width. The diameter of the centxal bore forming the cavity
was 600~m. The cavity forming liquid consisted of 4.5 ml~min.
of sterile water at between 20 and 22C., which has a
coagulating effect as the precipitation bath for the inner
boundary of the jet of ~olution~
The spinneret was immersed into the precipitation
bath to a depth of 12 mm, the said bath consisting of sterile
water at between 20 and 22C.

The j~t of spinning solution emerging downwardly
from the spinneret, after travelling a distance of 60 cm, was
deflected around a roller arranged at the bottom of the
spinning vat in such a manner as to leave the bath at an
angle of 50 to the surface thereof.
In order to remove the remaining solvent, the
thread was passed through a water bath for a distance of
120 m. This bath is followed by a plasticizer bath contain-
ing a mixture of 92% of water and ~% of glycerine. The
hollow fibre was dried in a flow of hot air at between 60 and
70C. The rate of travel of the thread at ~he outlet from
the installation was 20m/min. The finished hollow thread
was made up into a skein of the desired number of threads on
a tension controlled drum, was Cllt to the desired lengths,
and processed into filtration units.
The hollow threads thus produced had the following
properties:
outside diameter 700 ~m
inside diameter 500 ~m
tensile strength 78 cN
elongation at rupture 9O1%
pore volume 89.3%

hydraulic permeability 2870 m~h . m2 .
mmHg
albumin retention
(MW 69000) 2~3% at 0.6 bar
maximal pore width 1O3 ~m
inflation or expansion
point 1.6 bars
Figure 1 is an electron microscope photograph at
450 x of the cross-section of the plasmaplleresis membrane in
the form of a hollow thread or fibre according to the



- 12 -

7~

invention, produced by this method. It shows quite clearly
the honeycomb cell structure, the walls of the cells appearing
dark and the cavities light. Figure 2 shows the pores in
6000 x enlargementu In this case the pores are dark while
the wall appears light.
; EXAMPLE 3
Production of a plasmapheresis membrane in the form
of a tubular foil
A gear type metering pump was used to ~eed, to an
annular slotted nozzle, having an annular diameter of 70 mm
and a slot width of 300 mm, 325 ml~minO of the spinning
solution described in Example 1. The nozzle was Lmmersed in
the precipitation bath to a depth of 10 mm and was arranged
vertically, the said bath consisting of sterile water at
; between 20 and 22C~ A metering pump was used to pump sterile
water into the interior of the film of solution emerging in
the form of tube~ A corresponding amount of this precipita-
tion bath liquid was simultaneously removed from the interior
by means of an additional metering pump. The water thus
removed contained 50 g~l of acetoneO At a distance of 50 cm
below the nozzle, the tube thus produced was flattened with
a spreader and was passed round a deflecting roller at an
angle of 40 to the surface of the bath. After passing
through a washing section 72 m in length, in which the tubu-
lar foil was washed with sterile water at between 20 and
22C, the foil was pas~ed through a plasticizer bath 7~20 m
in length and was then dried in a channel drier with hot air
at between 64 and 74C. A solution consisting of 8% by
weight of glycerine in water was used as the plasticizer bath.
The speed at the outlet from the drier was 9. 8 m~min.
The following data apply to the tubular foil thus obtained:



- 13 -
.

L7~

width (laid flat) 53 mm
wall thickness 105 ~
tensile strength ~ longitudinal 102 CN
- transverse 48 CN
elongation at rupture - longitudinal 4.3 %
- transverse 7.1 %
hydraulic permeability 1220 ml~h .
m . mmHga
albumin retention (MW 69000) 4.4 %
at 0.6 bar
maximal pore diameter 1.3 ~m
inflation or expansion point1.6 bars
The tubular foil obtained reveals, in cross-
section, a relatively symmetrical arrangement of the central
cell walls. This structure is particularly suitable for
applications requiring optimal filtration and good selectivity.
EXAMPLE 4
Production of a lasma heresis membrane in the
P ~
~ form of a flat foil.
~ . . .
A gear type pump was used to feed 450 ml/min. of
the spinning solution described in Example 1 to a wide
slotted nozzle 300 mm in width with 270 ~m slot width,
immersed in the precipitation bath to a depth of 15 mm. The
precipitation bath was sterile water at 20C. The wide
slotted nozzle was inclined at an angle of 30 to the direc-
tion of travel of the foil. At a distance of 1.40 m below
the nozzle, the largely solidified foil was deflected around
a roller and passed through the precipitation bath at an
angle of 30. Tha foil was then passed through a washing
section 62 m in length where it was washed with sterile water

at between 20 and 22C. After passing through a plasticizer


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7~;

bath 6 m in length, containing an ~/O by weight solution of
glycerine in water, the strip was wiped free of water, passed
through an air section 3 rn in length, and then to a drier.
Using a hot air channel with an air temperature of between
40 and 45C as a drier, the membranes obtained were as
satisfactory as those obtained with a drum drier having
surface temperatures between 62 and 72C. Production velo-
city at the winding unit was 10.3 m/min.
The following data apply to the flat foil obtained:
width 216 mm
wall thickness 110 ~m
tensile strength - longitudinal82 CN
- transverse38 C~
elongation at rupture - longitudinal 5~6 %
- transverse 11.2 %
hydraulic permeability1510 ml~h .
m2 ~nH
albumin retention (MW 69000) 0.2%
at 0.6 bar
maximal pore diameter 1.3 ~m
inflation or expansion point 1.6 bars
EXAMPLE 5
.
Whereas in Examples 2, 3 and 4, it was shown that
membranes with the same pore dimensions may be produced as
hollow threads, or fibres, tubular foils or flat foils, a
description will now be given of how to produce membranes
with small diameter pores in the form of hollow threads.
As described in Example 1, a spinning solution of
the following composition was prepared:




- 15 -

16.3% by weight of cellulose acetate - subst.
degree 2.40
63~/o by weight of acetone
10.2% by weight of methanol
10.2% by weight of glycerine
As in Example 2, 6.9 ml/min. of the spinning solu-
tion were fed to the hollow thread spinneret which was
immersed, to a depth of 15 mm, in a preciptiation bath consis-
ting of water containing 18 g/l of acetone and 10 g/l of
glycerine. 6 ml/min~ of a precipitation bath, consisting of
5~/O by weight of isopropanol and ~0% by weight of water, were
pumped into the interior of the hollow thread spinneret.
After passing through a precipitation bath section measuring
40 cm in length, the jet solution emerging from the nozzle
was deflected and left the bath after passing through another
section 30 m in length.
The hollow thread thus obtained was washed frae of
solvent with water, was impregnated with a plasticiæer solu-
tion consisting of an aqueous glycerine solution with 100 g~l
of glycerine, and was then dried in a 1OW of hot air at
62C. At the outlet from the installation, the speed of the
thread was 20 m/min.
The following data apply to the finished hollow
thread:
- inside diameter 580 ~m
outside diameter 700 ~m
tensile strength 174 c~
elongation at rupture 14.7 %
inf lation point 10 bars
maximal pore dimension 0.? ~m
hydraulic permeability 372 ml/hm2 . mmHg
albumin retention 83.3 %


- 16 -

The membrane structure of the hollow thread thus
obtained, as seen in cross-cection~ reveals an asymmetrical
arrangement of honeycomb type cells. Membranes of this kind
have particularly high tensile strength and elongation at
rupture. They are for uses where corresponding mechanical
stresses are to be expected.
EXAMPLE 6
~ . .
It is also possible, according to the invention
to produce membranes having unusually large pores, as
indicated hereinafter.
A membrane was produced in the form of a hollow
thread, as in Examples 2 and 5. The composition of the
spinning solution was as follows:
8.5% by weight of cellulose~acetate subst.
degree 2.40
46~50/o by weight of acetone
~0.0/O by weight of methanol
25~00/o by weight of glycerine
The precipitation baths consisted of pure water
at 20C. The splnneret was immersed in the precipitation
bath at an angle such that the emerging jet solution formed
an angle of about 10 with the surface of the bath. After
travelling for a distance of 3 m through the precipitation
bath, the jet solution was deflected out of the bath. The
hollow thread thus obtained was washed free of solvent with
water, was treated with a 5.8% glycerine solution, and was
dried in a flow of hot air at 70C. `At the outlet from the
installation the speed of the thread was 22 mjmin~
The following properties were determined:

7~

outside diameter 700 ~m
inside diameter 4g5 ~m
tensile strength 32 cN
elongation at rupture 4.2%
hydraulic permeability 4200 ml~h. m . mmHg
inflation point 0.05 bar
maximal pore dimension 40 ~m
albumin retention 0
EXAMPLE 7
. . . _
In this example, a spinning solution is used which,
as a result of the inclusion of a viscosity lowering addi-
tive, had a viscosity of only 6 Pas with a low cellulose-
acetate content. The composition of this spinning solution
W2S as follows:
8O5% by weight of cellulose-acetate
48.5% by weight of acetone
lG~/o by weight of methanol
18~C% by weight of glycerine
15.0% by weight of trichlorotrifluoroethane
18 ml/min. of this spinning solution were fed to
the hollow thread spinneret described in Example 2. At the
same time, 6~6 ml~min,of water were pumped simultaneously
into the interior of the emerging jet solution as a cavity
forming liquid and as a precipitation bath for the internal
boundary of the jet solution. The spinneret was immersed
to a depth of 20 mm into the precipitation bath, also con-
sisting of water, for the external boundary of the jet solu-
tion. At a distance of 60 cm below the spinneret, the jet
solution was deflected and, after leaving the bath, was
washed free of solvent with water. ~fter treatment with
a l~/o glycerine solution, the hollow thread was dried in a
flow of air at 62C.
~ 18


The following properties were determined:
outside diameter780 ~m
inside diameter608 ~lm
tensile strength 90 c~
elongation at rupture15.6 %
hydraulic permeability 2450 ml/h . m2 . mmHg
inflation point0O4 bar
maximal pore dimension 5 ~m
albumin retention2.4 %
Figure 3 shows a 1000 x enlargement of a cross-
section of this hollow thread, investigated with a screen
electron microscope. It shows a large number of closed cells
in slightly asymmetrical arrangement. The differences in
cell size are much morë pronounced than in the membrane
illustrated in Figure 1. As in Figure 2, all external and
cell walls are pierced with a plurality of pores.
EXAMPLE 8
,
Membranes according to the invention having widely
varying properties may be produced without difficulty. On
the one hand it is possible to make membranes permeable to
the whole blood plasma, xetaining only the cellular compo-
nents. On the other hand it is possible to make membranes
the rejection limits of which lie at a molecular weight of
about 100,000, so that they are permeable to albumin but
hold back the other plasma proteins.
A plasmapheresis membrane according to Example 6
was produced in the form of a hollow thread and incorporated
into a membrane module having an area of 0.01 m2.
Another plasmapheresis membrane, having prope~ties
similar to those in Example 3, was produced in the form of a
hollow thxead and incorporated in a membrane module having



-- 19 --

~4~f~6

an area of 0.01 m .
Blood taken from a patient was first passed through
the first module at a transmembrane pressure of 100 mmHg
at a rate of 3 ml/min., which produced a filtrate I of
0.5 mlJmin~ The fraction retained contained all of the
cellular components. The filtrate was then passed through
the second module at a pressure differential of 30 mmHg.
The resulting filtrate II contained almost the total albumin,

.. . .
whereas the higher molecula~ weight protein components
remained predominantly in the residue of filtrate I,
Thus the membranes according to the invention
permit reinfusion of bodily albumin with the blood cell
fraction. This e]iminates the need to infuse costly and less
compatlble foreign albumin.
The patent specifications referred to herein are
further identified below:
Federal Republic o~ Germany Patent 22 57 697, granted
September 28, 1978, Kenj Kamide et al, (corresponds to U.S.
Patent 3,883,626).
Federal Republic of Germany Offenlegungsschrift
26 06 244, filed February 13, 1976, open to public inspection
on August 26, 1976, Mahahiro Mishiro et al (corresponds to
U.S. Patents 4,234,431 and 4,340,481.
Federal Republic of Germany Offenlegungsschrift
28 45 797, filed October 20, 1978, open to public inspection
on May 3, 1979, Michael Lefebvre et al, (corresponds to U.E~.
Patent Specification 2,006,643).




20 -

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Administrative Status

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Administrative Status

Title Date
Forecasted Issue Date 1985-04-02
(22) Filed 1981-02-20
(45) Issued 1985-04-02
Expired 2002-04-02

Abandonment History

There is no abandonment history.

Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Application Fee $0.00 1981-02-20
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
AKZO N.V.
Past Owners on Record
None
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Drawings 1993-10-31 1 56
Claims 1993-10-31 5 135
Abstract 1993-10-31 1 11
Cover Page 1993-10-31 1 19
Description 1993-10-31 20 862