GB2069925A - Plasmaphoresis membrane - Google Patents

Abstract

A process for the production of a membrane which comprises forcing a spinning solution comprising from 8 to 25%, by weight, of one or more cellulose esters, from 55 to 92%, by weight, of one or more solvents and optionally up to 20%, by weight, of one or more other additives through a spinning jet immersed in a precipitation bath, exposing the jet of solution to the coagulating effect of the precipitation bath at the boundaries of the jet over a section of precipitation bath which is at least 30 cm long, guiding the coagulated material out of the precipitation bath, washing with water until free from solvent, impregnating with plasticiser solution and drying is disclosed. The present invention also relates to a membrane which comprises distinct, substantially parallelepipedic closed cells juxtaposed to form a honeycomb-like structure all the cell walls having a plurality of holes as pores.

Description

SPECIFICATION Plasmaphoresis membrane This invention relates to a plasmaphoresis membrane, more particularly in the form of hollow filaments, tubular films or flat films of cellulose esters.

Plasmaphoresis membranes are used for plasma separation, i.e. for separating the blood plasma from cellular constituents and also for separating plasma constituents according to molecular weight.

After plasmaphoresis had been carried out for some time by means of membrane filters, centrifuges were subsequently used for this purpose. More recently, however, filtration processes have been taken up again. One reason for this is that, in the meantime, it has been possible to automate the processes for producing the membrane filters to a greater extent so that they are inexpensively available in sufficient numbers.

US Patent No. 1,421,341 describes a filter and a process for the production thereof. The filter in question consists of a cellulose ester, for example cellulose acetate, and has pores which are suitable for the separation of bacteria. The described filters may be dried without the pores collapsing.

The filters are produced by casting a solution of the cellulose ester in a solvent mixture and evaporating the solvent in a moist atmosphere at a low temperature. Water is added to the solvent in such a quantity that the mixture still dissolves the cellulose ester. The size of the pores is influenced by the quantity of water. The resulting membrane is washed in water, stretched while wet and dried after a heat treatment in hot water or steam.

German Patent No. 843,088 described a process for the production of ultrafilters and diaphragms of plastics in which porosity is obtained by adding to a plastics solution which is basically suitable for forming a thin skin either salts which are soluble therein or other substances in a solution which is miscible without reacting with the plastics solution, subsequently evaporating the mixture to dryness and then dissolving the added substance out of the thus-formed skin by means of a solvent which does not dissolve the plastics material.

German Auslegeschrift No. 1,01 7,596 describes a process in which a cellulose acetate membrane is produced by the phase inversion process by pre-gelation in a ventilation chamber at a working temperature of from 20 to 400C and at a relative air humidity of from 50 to 70%.

US Patent No. 2,783,894 describes a similar process for the production of a microporous membrane filter of nylon.

German Auslegeschrift No. 1,156,051 describes a process in which membranes produced in accordance with the above-mentioned US Patent Nos. 1,421,341 or 2,783,894 are applied in a particular way to a perforated hollow body. The microporous films have pores of which the effective diameter is smaller than about 10 Mm and which in all take up more than 80% of the total volume of the filter material.

German Patent No. 2,257,697 describes porous symmetrical cellulose acetate membrane filters, which have been produced by dissolving cellulose acetate having a degree of acetylation of from 20 to 65.5% in an organic solvent in a ratio, by weight, of from 5 to 40% to the solvent and adding a dilute solvent, the boiling point of which is higher than that of the above-mentioned organic solvent, and also a metal salt, the metal component of which has an ionic radius of less than 1.33 A and is a member of Groups I to Ill of the Periodic Table, in a ratio of from 20 to 200%, by weight, to the acetate, to the solution so as to form a homogeneous solution which is applied to a flat polished surface to form a thin film from which the solvent contained therein is removed by evaporation and which is converted by microphase separation into its gel state, after which and finally the metal salt present therein is dissolved out to form the porous membrane.

The pore diameter is between 0.01 and 10 lim and porosities of from 70 to 81% are quoted.

Magnification of a membrane of this type 6000 times under an electron microscope reveals a structure which, viewed from the surface, is similar to a mat of filaments in which the looped filaments which project from common crossing points lie irregularly over and adjacent one another. In the fractured state, the structure shows a loose, but nevertheless uniformly dense mass inside the membrane.

German Offenlegungsschrift No. 2,606,244 describes a hollow fibre for membrane filtration of a synthetic or semi-synthetic, chain-like high polymer which forms filaments when spun, the cylindrical wall forming the hollow fibre, at least in a closed section looking like a circular band in cross-section, having a three-dimensional net-like structure of fine filter passages having a pore ratio of at least 55% as the active filter zone, the active points of the filter passages which determine the smallest crosssectional areas of the passages for the throughflow of substances contained in a filter liquid being randomly distributed at least over the active filter zone and these cross-sectional areas being substantially uniform in size. If such a membrane is examined under an electron microscope magnified from 300 to 10,000 times, the structure appearing is reminiscent of a coral colony.The membrane structure looks as if it is made up of numerous stems branched like coral. At the surface of the outside of the hollow fibres, the branches merge with one another in a pitted surface comprising elongate, parallel pore openings.

In addition, German Offenlegungsschrift No. 2,845,797 describes an anisotropic synthetic membrane having a multilayer structure, each layer acting as a molecular sieve for an exact, precise separation according to molecular weight.

A more or less pronounced pore diameter asymmetry is common to all known filter membranes on account of the firm supporting surface used during production and the at least partial evaporation of the solvent. Some cannot readily be stored in the dry state and the pore openings collapse very easily, even with careful handling. Some of the known membranes show a wide pore diameter distribution range and hence no definite exclusion limit. Apart from process-related effects on the membranes, known processes for the production of filter membranes generally have only a moderate production rate.

Recovery of the solvent from the air-solvent mixture is complicated and involves considerable losses and pollution of the environment.

An object of the present invention is to provide a filtration membrane in the form of hollow filaments, tubular films or flat films having a novel membrane wall structure by which it is possible, for example, to carry out plasmaphoresis filtrations at high speeds, the pore diameter representing a definite exclusion limit being infiuencable by the production conditions. The disadvantages attending known filter membranes are to be avoided as far as possible.

According to the present invention, this object is achieved in that the membrane is produced by a process in which a spinning solution of from 8 to 25%, by weight, of solvent and optionally up to 20%, by weight, of other additives is forced through a spinning jet immersed in a precipitation bath, the jet of solution is exposed to the coagulating effect of a precipitation bath at the boundaries of the jet over a section of precipitation bath which is at least 30 cm long, guided out of the precipitation bath and washed with water until free from solvent, impregnated with plasticiser solution and finally dried.

Suitable precipitation baths are liquids of the type which may be mixed with the solvent of the spinning solution in any ratio, but which do not dissolve or chemically affect the cellulose ester.

Suitable plasticisers are the known plasticisers for cellulose esters which enable the residual water content after drying to be maintained between 3 and 15%, by weight, based on the weight of the membrane. Polyhydric alcohols and esters have proved to be particularly suitable plasticisers.

In the dialysis of blood, tubular films and hollow filaments have proved to be particularly preferred membrane forms. There is also a preference for these forms in the case of membranes for plasmaphoresis. To obtain a well-developed interior with the required lumen cross-section, the hollow filament or tubular film membranes are produced by introducing a precipitation liquid into the interior of the issuing spinning solution. In this way, the internal boundary of the jet of solution is also exposed to the coagulating effect of the precipitation bath.

If a precipitation agent differing in its composition from the precipitation bath which has a coagulating effect on the outer boundary of the jet of solution used for the precipitation liquid introduced into the interior, which leads to unequal coagulation rates, different effects are obtained in the porosity of the inner and outer surfaces.

If the precipitation bath contains a relatively large quantity of solvent, smaller pores will be formed, while a precipitation bath of low solvent content will lead to larger pores. However, the concentration of the solvent in the precipitation bath should not exceed 20%, by weight. High consistency in the surface development of the membrane is shown by a membrane which has been produced using precipitation baths of the same composition.

The membrane according to the present invention shows a novel structure: In the fractured state, i.e. in the wall cross-section, a clearly pronounced cell structure reminiscent of honeycombs is observed even with only 100-fold magnification. Although the boundaries of the closed cells are not consistent in shape, the cells are reminiscent in shape of parallelepipeds which regularly adjoin one another and link smoothly with the adjacent cells. The cell walls have a plurality of holes. These pores by which the outer walls and the cell walls are permeated form sieve plates through which the ultrafiltrate permeates (cf. Figure 1 of the accompanying drawings).

The composition of the spinning solution is of particular importance to the structural development of the membrane and its service properties. The chemical composition and physical quality of the spinning solution act in a complex fashion on the arrangement and size of the cells and cell walls.

One factor is the solvent in the spinning solution. Suitable solvents are, for example, acetone, dioxane, dioxolane, methyl acetate, nitromethane or methylene chloride. Acetone is generally preferred.

By virtue of the possibility of controlling the properties and structure of the membranes within wide limits, it is particularly preferred to use mixtures as solvents in the spinning solution. A mixture of from 50 to 90%, by weight, of acetone, from 5 to 25%, by weight, of monohydric alcohol and from 5 to 25%, by weight, of plasticiser has proved to be effective. By using monohydric alcohols containing from 1 to 3 carbon atoms, optionally in admixture, the cell structure may be influenced as it may by the amount of plasticiser present, glycerol preferably being used as the plasticiser when the membrane is to be used for medical purposes. By using myristyl myristate as the plasticiser in the spinning solution, it is possible to produce structures which are of interest for technical applications of the membrane.

The precipitation bath also has a considerable bearing upon the properties of the membrane, water on its own leading to very large pores, while aqueous solutions are preferably used for the precipitation bath when small pores are required. The membrane according to the present invention may have pores ranging from 0.01 to 50 ELm in diameter, depending upon the working conditions selected.

With the earlier known plasmaphoresis membranes, nitro-cellulose played a more important role than acyl celluloses. Since nitrocellulose may be problematical to handle, acyl celluloses have acquired greater significance in the meantime. Acyl celluloses are suitable for the membrane according to the present invention as nitrocellulose. Mixtures of different acyl celluloses may also be processed to form the membrane according to the present invention, for example acetyl celluloses, propionyl celluloses and butyryl celluloses. Cellulose acetate is preferred simply for its ready availability.

A filtration membrane of pure cellulose triacetate is too hydrophobic for many of the applications of the membrane according to the present invention. In one embodiment of the present invention, the plasmaphoresis membrane consists of a cellulose acetate having a degree of substitution of from 2.0 to 2.7. The degree of substitution of the cellulose acetate used in the spinning solution also corresponds to that of the membrane spun therefrom. The degree of substitution preferably amounts to between 2.3 and 2.5.

The physical property of the spinning solution which has the greatest effect on the structure of the membrane is its viscosity. Thus, spinning solutions of relatively high viscosity give relatively thin cell walls in the membrane which does not affect the ability of the membrane to withstand mechanical stressing, particularly when at the same time the cell structure is far from symmetrical. The viscosity of the spinning solution may be influenced, on the one hand, by the cellulose ester content or even by viscosity-altering solvents or additives. Solvents containing isopropanol, for example, as the monohydric alcohol have a higher viscosity than solvents containing methanol. Viscosity may be reduced, for example, even by the addition of halogenated hydrocarbons, for example trichlorotrifluoroethane.The spinning solution has a viscosity of from 5 to 200 Pas, preferably from 10 to 100 Pas.

The process according to the present invention for the production of a membrane, particularly for plasmaphoresis, in the form of hollow filaments, tubular or flat films of cellulose acetate is characterised in that a spinning solution of from 8 to 25%, by weight, of cellulose esters, from 55 to 92%, by weight, of solvent and optionally up to 20%, by weight, of other additives is forced through a spinning jet immersed in a precipitation bath, the jet of solution is exposed to the coagulating effect of a precipitation bath at the boundaries of the jet over a section of precipitation bath which is at least 30 cm long, guided out of the precipitation bath and washed with water until free from solvent, impregnated with plasticiser solution and finally dried.Drying should be carried out at such a temperature that the mean material temperature does not exceed 700 C.

Advantageous embodiments of the present invention are characterised in that, to produce hollow filaments or tubular films, a precipitation agent is introduced into the interior of the issuing spinning solution, both precipitation liquids preferably having the same composition. Mixtures are advantageously used as the solvent. One preferred mixture consists of from 50 to 90%, by weight, of acetone, from 5 to 25%, by weight, of monohydric alcohol and from 5 to 25%, by weight, of plasticisers, the monohydric alcohol preferably containing from 1 to 3 carbon atoms and polyhydric alcohols, particularly glycerol for medical applications, being used as the plasticiser.

Suitable precipitation agents are above all water and aqueous solutions. Of the cellulose esters used as the membrane-forming polymer, cellulose acetate is particularly preferred, particularly cellulose acetate having a degree of substitution of from 2.0 to 2.7. A degree of substitution of from 2.3 to 2.5 is more particularly preferred. Disturbances during spinning are largely avoided if the viscosity of the spinning solution is adjusted to between 5 and 200 Pas, preferably between 10 and 100 Pas.

It has been found that the process may be carried out at high production rates if, after passing through a section of the precipitation bath at least 30 cm long, the jet of solvent is deflected at a guide element following the spinning jet and is guided out of the spinning bath at an angle of from 1 5 to 600 with the surface of the precipitation bath.

In this connection, it has proved to be advantageous to immerse the spinning jet in the precipitation bath in such a way that the spinning jet forms an acute angle with the surface of the precipitation bath.

Membranes according to the present invention are distinguished by the novel structure thereof and are characterised in that the membrane is made up of distinct substantially parallelepipedic closed cells juxtaposed to form a honeycomb and all the cell walls are provided with a plurality of holes as pores.

In general, the structure of the membrane is such that the closed cells are not consistent either in shape or volume. In many cases, however, a cell wall lying substantially symmetrically in the middle of the wall is formed by the production process. However, it is also possible to establish conditions under which a central cell wall extends like a meander through the cross-section.

Not only the pore openings in all the cell walls, but also the cell structure influences the selectivity of the membrane to a considerable extent.

If desired, pigments may, of course, also be incorporated in the membrane in known manner.

The present invention is illustrated by the following Examples.

EXAMPLE 1 Production of a Spinning Solution of Cellulose Acetate The following ingredients were successively introduced, with stirring, into a stirrer-equipped vessel (stirrer speed 800 r.p.m.): 3000 g of methanol, 4000 g of glycerol, 200 g of cellulose acetate (degree of substitution 2.48) and 11,000 g of acetone. After stirring for two hours at room temperature, the cellulose acetate had dissolved. The solution was then filtered through a 20 ym mesh filter, deaerated and was ready for spinning after from 4 to 6 hours. The spinning solution had a viscosity of 15 Pas.

EXAMPLE 2 Production of a Membrane According to the Present Invention in Hollow Filament Form By means of a gear metering pump, 6 ml/min. of the spinning solution produced in accordance with Example 1 were delivered to a hollow-filament spinning jet of known type of which the outer annular slot had a diameter of 1300 ym and a width of 1 50 ,am. The central bore for delivering the liquid forming the follow space had a diameter of 600 pm. 4.5 ml/min. of germ-free water at from 20 to 220C was delivered as the liquid forming the hollow space, having a coagulating effect as the precipitation liquid for the inner boundary of the jet of solution.

The spinning jet was immersed to a depth of 12 mm in the precipitation bath which consisted of germ-free water at from 20 to 220C.

After passing through a 60 cm long section, the spinning solution with the internal liquid issuing downwards from the spinning jet was deflected at a roller arranged at the bottom of the spinning tank in such a way that it left the bath at an angle of 500 to the surface of the bath.

To remove residual solvent, the filament was guided through a water bath 120 metres long. This water bath was followed by a plasticiser bath containing a mixture of water (92%) and glycerol (8%).

The hollow filament was dried in a stream of hot air at from 60 to 700C."The speed of travel of the filament on leaving the installation was 20 metres/min. The thus-produced hollow filament was combined on a tension-controlled drum to form a strand having the required number of filaments, cut into individual lengths and processed to form filtration units.

The characteristics of the thus-produced hollow filaments were as follows: external diameter 700 Mm internal diameter 500 sum tensile strength 78 cN breaking elongation 9.1% pore volume 89.3% hydraulic permeability 2870 m/h ~ m2 - mm Hg retention capacity for albumin 2.3% at 0.6 bar (MW 69,000) maximum pore width 1.3 #m bursting point 1.6 bars Accompanying Figure 1 is a photograph taken using an electron microscope of the cross-section of the plasmaphoresis membrane according to the present invention in hollow filament form produced in accordance with this Example (magnified 450 times). The honeycomb-like cell structure is clearly discernible, the cell walls appearing dark and the cell voids light.Accompanying Figure 2 shows the pores magnified 6000 times. In this case, the pores are dark while the wall appears light.

EXAMPLE 3 Production of a Plasmaphoresis Membrane in the Form of a Tubular Film By means of a gear metering pump, 325 ml/min. of the spinning solution described in Example 1 are delivered to an annular slot die having an annulus diameter of 70 mm and a slot width of 300 ym.

The spinning jet was immersed to a depth of 10 mm in the precipitation bath and was vertically arranged. The precipitation bath consisted of sterilised water at from 20 to 220C. Sterilised water was pumped by means of a metering pump into the interior of the solvent film issuing from the spinning jet in tubular form. At the same time, a corresponding amount of this precipitation bath liquid was run off again from the interior by means of another metering pump. The water run off contained 50 g/l of acetone. 50 cm below the spinning jet, the tube formed was laid flat on an expander and guided over a guide roller at an angle of 400 to the surface of the bath.After passing through a washing bath, in which the tubular film was washed with sterilised water at from 20 to 220C and which was 72 metres long, the tubular film was passed through a plasticiser bath 7.20 metres long and dried using hot air at from 64 to 740C in a tunnel dryer. A solution of 8%, by weight, of glycerol in water was used as the plasticiser bath.

The rate of travel at the end of the dryer was 9.8 metres per minute. The following data were measured on the tubular film obtained.

width (laid flat) 53 mm wall thickness 105 #m tensile strength longitudinal 102 CN transverse 48 CN breaking elongation longitudinal 4.3% transverse 7.1% hydraulic permeability 1220 ml/h ~ m2 - mm Hg retention capacity for albumin 4.4% at 0.6 bar (MW 69,000) maximum pore diameter 1.3 y.m bursting point 1.6 bars In cross-section, the tubular film obtained has a relatively symmetrical arrangement of the central cell walls. This structure is particularly suitable for applications where an optimal filter action and high selectivity are essential.

EXAMPLE 4 Production of a Plasmaphoresis Membrane in the Form of a Flat Film By means of a gear metering pump, 450 ml/min. of the spinning solution described in Example 1 were delivered to a slot die 300 mm wide having a slot width of 270 ,um which was immersed to a depth of 1 5 mm in the precipitation bath. The precipitation bath consisted of sterilised water at 200 C.

The slot die was inclined at an angle of 300 to the direction of travel of the film. 1.40 metres below the slot die, the film which had largely solidified was deflected around a guide roller and guided through the bath at an angle of 300. The film was passed through a washing bath 62 metres long in which it was washed with sterilised water at from 20 to 220C. After passing through a plasticiser bath 6 metres long containing a solution of 8%, by weight, of glycerol in water, the adhering water was stripped off and, after passing through a 3 metres long air duct, the film was delivered to a dryer. Using a hot air duct for air temperatures of from 40 to 450C as the dryer, it was possible to obtain membranes as satisfactory as those obtained using a drum dryer in which the surface temperatures were between 62 and 720C.

The production rate at the winding stage was 10.3 metres/minute.

The following data were measured on the flat film obtained: width 216 mm wall thickness 1 10#m tensile strength longitudinal 82 CN transverse 38 CN breaking elongation longitudinal 5.6% transverse 11.2% hydraulic permeability 1510 ml/h m2 ~ mm Hg retention capacity for albumin 0.2% at 0.6 bar (MW 69,000) maximum pore diameter 1.3 jum bursting point 1.6 bars EXAMPLE 5 While it was shown in Examples 2, 3 and 4 that it is possible to produce membranes having the same pore sizes in the form of hollow filaments, tubular films and flat films, it is shown in the following how to produce membranes of small pore diameter in hollow filament form.

A spinning solution of the following composition was prepared in the same way as described in Example 1 : 16.3%, by weight, of cellulose acetate (degree of substitution 2.40), 1 6.3%, by weight, of acetone, 10.2%, by weight, of methanol and 10.2%, by weight, of glycerol.

As in Example 2, 6.9 ml/min. of spinning solution were delivered to the hollow-filament spinning jet which was immersed to a depth of 15 mm in a precipitation bath of water containing 18 g/l of acetone and 10 g/l of glycerol. 6 ml/min. of a precipitation liquid consisting of 50%, by weight, of isopropanol and 50%, by weight, of water was pumped into the interior of the hollow-filament spinning jet. After passing through a 40 cm long section of precipitation bath, the jet of solution issuing from the spinning jet was deflected and left the precipitation bath after another 30 metres. The hollow filament formed was washed free from solvent with water, impregnated with plasticiser solution consisting of an aqueous glycerol solution containing 100 g/l of glycerol and then dried in a stream of hot air at 620C.

The rate of travel of the filament on leaving the dryer was 20 metres/min.

The following data were measured on the thus-produced hollow filament: internal diameter 580 #m external diameter 700 #m tensile strength 174 cN breaking elongation 14.7% bursting point 10 bars maximum pore diameter 0.2 ym hydraulic permeability 372 ml/h ~ m2 - mm Hg retention capacity for albumin 83.3% In cross-section, the membrane structure of the hollow filament obtained shows a symmetrical arrangement of the honeycomb-like cells. Membranes of this type have particularly good tensile strength and breaking elongation. They may be used for application involving corresponding mechanical stressing.

EXAMPLE 6 Membranes having extremely large pores may also be produced in accordance with the present invention, as shown in the following: The membrane was produced in the form of a hollow filament in the same way as in Examples 2 and 5. The spinning solution had the following composition: 8.5%, by weight, of cellulose acetate (degree of substitution 2.40), 46.5%, by weight, of acetone, 20.0%, by weight, of methanol and 25.0%, by weight, of glycerol. The precipitation baths consisted of pure water at 200 C. The spinning jet was immersed in the precipitation bath at such an angle that the issuing jet of solution formed an angle of about 100 with the surface of the bath. After travelling a distance of 3 metres in the precipitation bath, the jet of solution was deflected and guided out of the precipitation bath. The hollow filament obtained was washed free from solvent with water, treated with 5% glycerol solution and dried in a stream of hot air at 700C. The rate of travel of the filament on leaving the installation was 22 metres per minute.

The following data were measured: external diameter 700 Mm internal diameter 495 Mm tensile strength 32 cN breaking elongation 4.2% hydraulic permeability 4200 ml/h. m2, mm Hg bursting point 0.05 bar maximum pore diameter 40 ym retention capacity for albumin 0 EXAMPLE 7 The spinning sclution used in this Example had a viscosity of only 6 Pas for a low cellulose acetate content through the addition of a viscosity-reducing additive to the spinning solution.The spinning solution had the following composition: 8.5%, by weight, of cellulose acetate, 48.5%, by weight, of acetone, 10.0%, by weight, of methanol, 18.0%, by weight, of glycerol and 1 5.0%, by weight, of trichlorotrifluoromethane. 1 8 ml/min. of this spinning solution were delivered to the hollow-filament spinning met described in Example 2. At the same time, 6.6 ml/min. of water as the liquid forming the hollow space and also as the precipitation agent for the inner boundary of the jet of solution were pumped into the interior of the issuing jet of solution. The spinning jet was immersed to a depth of 20 mm in the precipitation bath for the outer boundary of the jet of solution which also consisted of water.The jet of solution was deflected 60 cm below the spinning jet and, after leaving the precipitation bath, was washed with water until free from solvent. After treatment with 10% glycerol solution, the hollow filament was dried in a stream of air at 620C.

The following data were measured: external diameter 780 Mm internal diameter 608 ym tensile strength 90 cN breaking elongation 15.6% hydraulic permeability 2450 ml/h ~ m2 ~ mm Hg bursting point 0.4 bar maximum pore diameter 5 Hm retention capacity for albumin 2.4% Accompanying Figure 3 shows (magnified 1000 times) part of the cross-section of this hollow filament examined under an electron scan microscope. It shows a large number of closed cells and a slightly asymmetrical arrangement of the cells. The differences in the sizes of the cells are more clearly pronounced than in the case of the membrane shown in Figure 1. As in Figure 2, all outer and cell walls are permeated by a plurality of pores.

EXAMPLE 2 The membranes according to the present invention differing widely in the properties thereof may be produced without difficulty so that, on the one hand, membranes permeable to the entire blood plasma, retaining only the cellular constituents, may be produced, while, on the other hand, it is also possible to produce membranes the exclusion limit of which is at a molecular weight of the order of 100,000 so that they are permeable to albumin, but retain the other plasma proteins.

A plasmaphoresis membrane was produced in accordance with Example 6 in the form of a hollow filament and installed in a membrane module having a membrane surface of 0.01 m2.

Another plasmaphoresis membrane having similar data to Example 3 was produced in the form of a hollow filament and installed in a membrane module having a membrane surface of 0.01 m2.

The blood taken from a patient was first passed through the first module at a rate of 3 ml/min.

under a transmembranal pressure of 100 mm Hg, a filtrate I accumulating at a rate of 0.5 ml/min. The fraction retained contained all the cellular constituents. The filtrate was then passed through the second module at a pressure difference of 30 mm Hg.

The filtrate II formed contained almost all the albumin, while the protein constituents of higher molecular weight remained predominantly in the residue of filtrate I.

In this way, the membranes according to the present invention enable the body's own albumin to be reinfused together with the blood cell fraction. This eliminates the need to infuse expensive and less compatible foreign albumin.

Claims (24)

1. A process for the production of a membrane which comprises forcing a spinning solution comprising from 8 to 25%, by weight, of one or more cellulose esters, from 55 to 92%, by weight, of one or more solvents and optionally up to 20%, by weight, of one or more other additives through a spinning jet immersed in a precipitation bath, exposing the jet of solution to the coagulating effect of the precipitation bath at the boundaries of the jet over a section of precipitation bath which is at least 30 cm long, guiding the coagulated material out of the precipitation bath, washing with water until free from solvent, impregnating with plasticiser solution and drying.

2. A process as claimed in claim 1 in which a precipitation liquid is introduced into the interior of the issuing spinning solution.

3. A process as claimed in claim 1 or claim 2 in which precipitation agents of the same composition are used internally and externally.

4. A process as claimed in any of claims 1 to 3 in which mixtures are used as the solvents.

5. A process as claimed in claim 4 in which the solvent mixture comprises from 50 to 90%, by weight of acetone, from 5 to 25%, by weight, of monohydric alcohol and from 5 to 25%, by weight, of plasticiser.

6. A process as claimed in claim 5 in which the monohydric alcohol contains from 1 to 3 carbon atoms.

7. A process as claimed in any of claims 1 to 6 in which a polyhydric alcohol is used as the plasticiser.

8. A process as claimed in claim 7 in which glycerol is used as the polyhydric alcohol.

9. A process as claimed in any of claims 1 to 8 in which an aqueous solution is used as the precipitation agent.

10. A process as claimed in any of claims 1 to 8 in which water is used as the precipitation agent.

1 A process as claimed in any of claims 1 to 10 in which cellulose acetate is used as the cellulose ester.

12. A process as claimed in claim 11 in which the degree of substitution of the cellulose acetate is from 2.0 to 2.7.

13. A process as claimed in claim 12 in which the degree of substitution is from 2.3 to 2.5.

14. A process as claimed in any of claims 1 to 13 in which the spinning solution has a viscosity of from 5 to 200 Pas.

1 5. A process as claimed in claim 14 in which the spinning solution has a viscosity of from 10 to 100 Pas.

1 6. A process as claimed in any of claims 1 to 1 5 in which the viscosity of the spinning solution is adjusted by viscosity-influencing additions.

17. A process as claimed in any of claims 1 to 1 6 in which after passing through a section of the precipitation bath at least 30 cm long, the jet of solution is deflected at a guide member following the spinning jet and is guided out of the spinning bath at an angle of from 15 to 600 with the surface of the precipitation bath.

1 8. A process as claimed in claim 17 in which the spinning jet forms an acute angle with the surface of the precipitation bath.

19. A process as claimed in claim 1 substantially as herein described with particular reference to the Examples.

20. A membrane when produced by a process as claimed in any of claims 1 to 19.

21. A membrane which comprises distinct, substantially parallelepipedic closed cells juxtaposed to form a honeycomb-like structure, all the cell walls having a plurality of holes as pores.

22. A membrane as claimed in claim 20 or claim 21 in the form of hollow filaments, tubular films or flat films.

23. A membrane as claimed in claim 21 substantially as herein described with particular reference to the accompanying drawings.

24. A plasmaphoresis apparatus which comprises a membrane as claimed in any of claims 20 to 23.