CA1184716A - Plasma phoresis membrane - Google Patents

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.

Description

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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.

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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 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~

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 .

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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.

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 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:

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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.

Production of a lasma heresis membrane in the P ~
~ form of a flat foil.
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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 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 .
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:

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 %

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.

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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:

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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 . . . _ 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.

, 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 ~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).

Claims (31)

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.

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.

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.

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.

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.