JPH035847B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to membranes for semipermeable plasma export methods in the form of hollow fibers, tubular sheets or planar sheets made of cellulose esters.

Plasma transport membranes are used for plasma separation, ie for separating plasma from cellular components as well as for further separating plasma components by molecular weight.

Plasma evacuation methods have already been carried out for a long time using membrane filters, and later centrifugation was used for this purpose. However, recently the law has gone back to normal. One of the reasons for this is that membrane filters can be used in sufficient quantities and at low cost because the manufacturing method of membrane filters has been able to be strongly mechanized.

US Pat. No. 1,421,341 describes a filter made of cellulose ester, such as cellulose acetate, having pores suitable for separating bacteria, and a method for producing the same. Filters of this description can be dried without destroying the pores.

The filter is manufactured by pouring a solution of cellulose ester in a solvent mixture and evaporating the solvent at low temperature in a humid atmosphere. An amount of water is added to the solvent such that the mixture still dissolves the cellulose ester. Pore size is affected by the amount of water. The resulting membrane is washed in water, stretched wet and dried by heat treatment in hot water or steam.

German Patent No. 843 088 describes a method for producing ultrafiltration membranes and diaphragms made of plastics, in which the porosity is determined by the plastics suitable for producing the membranes themselves. mixing the solution with a salt or other substance soluble therein that is miscible without reacting with the plastic solution, and then drying the mixture;
This is accomplished by eluting the admixed substances from the membrane thus produced with a solvent that does not dissolve the plastic.

West German Patent Publication No. 1017596 states that working temperatures of 20°C to 40°C and relative humidity of 50% to 70% in a ventilated room.
A method is described for producing cellulose acetate membranes by a phase inversion method by pregelling.

US Pat. No. 2,783,894 describes a similar method for making microporous membrane filters made of nylon.

West German Patent Publication No. 1156051 includes the above-mentioned US Patent No. 1421341 or US Pat.
A method is described in which the membrane produced according to that patent is applied in a special manner onto a hollow body provided with perforations. This microporous coating has an effective diameter of less than about 10 μm and a total of 80% of the total volume of the filter material.
It has pores that occupy more volume than the pores.

West German Patent No. 2257697 discloses that cellulose acetate having a degree of acetylation of 20 to 65.5% is dissolved in an organic solvent at a weight ratio of 5 to 40% to the solvent, and the boiling point is higher than the boiling point of the organic solvent. Adding a highly diluent solvent and adding to the solution a metal component having an ionic radius of less than 1.33A and being an element of group ~~ of the periodic system, and a ratio of 20 to 200% by weight relative to the acetate ester. by adding a metal salt with a homogeneous solution, applying this homogeneous solution on a polished flat surface to obtain a thin film, and evaporating the solvent contained therein from this thin film. The porous membrane was produced by removing the thin film, converting it into a gel state by microscopic phase separation, and then finally eluting the metal salts contained in the lie to form a porous membrane. A cellulose acetate symmetric membrane filter is described.

The pore diameter is 0.01 to 10 μm, and 70 to 81 μm.
% porosity is stated.

In the case of the above membrane, an electron microscope with a magnification of 6000x
When considered from the surface, it shows a mat-like structure consisting of irregularly overlapping and juxtaposed threads arranged in loops projecting from common points of intersection. The fracture points indicate that the internal structure of the membrane is a loose but still uniformly dense material.

West German Patent Publication No. 2606244 describes hollow membrane fibers made of synthetic or semi-synthetic chain-like polymers that form filaments during spinning; The cylindrical wall has a pore ratio of at least 55% within a closed area whose cross section appears as an annular band.
has a three-dimensional network of fine channels as an active zone, and in this case the active points of the channels determine the minimum cross-section of the channels for passing the substance contained in the liquid. It happens that it is divided by at least an active band, and the dimensions of this cross section are approximately equal. When such films are examined under an electron microscope at 3,000 to 10,000 times magnification, the obvious structure is reminiscent of coral colonies. The membrane formation appears to be composed of numerous corallily branched stalks. On the outer surface of the hollow fibers, the branched stalks intertwine and intertwine with each other on the grain surface with pores aligned parallel to the longitudinal direction.

Furthermore, DE 28 45 797 A1 describes anisotropic synthetic membranes having a multilayer structure, each layer acting as a molecular sieve for accurate and precise molecular weight separation.

Characteristic of all known membranes is a more or less pronounced pore diameter asymmetry due to the rigid support surface used during production and at least partial evaporation of the solvent. Some are not readily shelf-stable in the dry state and the pores are very easily destroyed even with careful handling. Many of the known membranes are
It shows a broad spectrum of pore diameter distribution and therefore no clear exclusion limits. Known methods for producing membranes generally have only low production rates, excluding the effect on the membranes of the process. Recovery of solvent from air-solvent mixtures is expensive and results in higher losses and environmental pollution.

The object of the present invention is to provide hollow fibers with a novel membrane wall structure, in which, for example, plasma export filtration can be carried out at higher rates and the pore diameter can be adjusted depending on the production conditions, resulting in a clear exclusion limit. , to produce membranes in the form of tubular sheets or planar sheets. In this case, the disadvantages associated with known membranes should be avoided to the greatest extent possible.

Along with a clear exclusion limit, the filtration properties of plasmapheresis membranes can be characterized by the sieving coefficient.

In this case, the sieving coefficient is: S=C _F /C _B C _F = Concentration of substance X in the filtrate C _B = Concentration of substance This can be done by If S=1, complete transparency prevails, and if S is less than 1, partial transparency prevails. The currently freely used membranes already have a sieving coefficient for albumin that is less than 0.8.
This means that the components to be separated are removed only to a small extent:
Therefore, longer processing times are required. Also, one has to work with higher reinjection volumes or use significantly larger membranes, which leads to significant disadvantages. This is because the membrane model then has a significantly higher extracorporeal capacity.

According to the present invention, this problem is solved by extruding a casting stock solution containing cellulose ester through a molding nozzle, subjecting the jetting flow of the stock solution to the coagulation effect of a precipitation bath,
In the case of semipermeable plasmapheresis membranes in the form of hollow systems, tubular sheets or planar sheets made of cellulose esters, produced by a process consisting of drawing them out of a precipitation bath and washing to remove the bath agent. , the membrane is composed of substantially rectangular closed cells arranged next to each other in a honeycomb-like manner without preferential direction, all the cell walls are penetrated by a large number of pores as pore passages, and 5
The casting solution with a viscosity of ~200 Pa.s contains 8-25% by weight of cellulose esters, 55-92% by weight of solvent and optionally up to 20% by weight of viscosity-controlling additives, but not pore-forming metal salts. The stock solution is extruded directly into the precipitation bath, and the membrane is washed with acetone 50~
The problem is solved by impregnating with a plasticizer solution after washing away the solvent consisting of 90% by weight, 5-25% by weight of monohydric alcohol and 5-25% by weight of plasticizer and finally drying.

The precipitation bath can be mixed with the solvent of the casting stock solution in any ratio, but a liquid that does not dissolve or chemically change the cellulose ester is suitable.

Suitable plasticizers are those known for cellulose esters, which are capable of preventing the residual water content after drying from falling below 3 to 15% by weight, based on the weight of the membrane. Polyhydric alcohols and esters have proven particularly effective as such plasticizers.

In the case of hemodialysis, in particular tubular sheets and hollow fibers have proven to be excellent membrane types. In the case of plasma export membranes, this type has already proven to be superior. In order to construct well-structured cavities with the desired internal diameter cross-section, membranes in the form of hollow fibers or tubular sheets are produced by introducing a settling bath inside the flowing casting solution. ing. As a result, the boundary surface of the jetting flow of the raw solution existing inside is also subjected to the coagulation effect of the settling bath.

When using a settling bath that is introduced inside and has a different composition from the settling bath that acts on the interface of the raw liquid jet flow that exists outside (this may lead to non-uniform solidification rates). ) have different effects on the porosity of the internal and external surfaces.

If the precipitation bath contains a larger amount of solvent,
Precipitation baths produce small pore passages, and precipitation baths with low solvent content produce large pore passages. However, the solvent concentration in the precipitation bath must not exceed 20% by weight. Membranes such as those produced by having both precipitation baths having the same composition exhibit good agreement in the surface structure of the membrane.

The membrane according to the invention exhibits a new class of cell structures: at the fracture point, i.e. in the cross-section of the wall, there is already a magnification
At 100x magnification, a clearly pronounced bubble structure reminiscent of a honeycomb can be seen. The interfaces of closed cells do not really have a consistent shape. The shape of the bubble former is approximately a rectangular parallelepiped, and the rectangular parallelepipeds are always juxtaposed without preferential direction and smoothly connected to adjacent bubbles. The cell wall has a large number of pores. This pore passage through the outer wall and the cell wall forms a sieve plate through which the ultraliquid permeates (see FIG. 1).

Regarding the structural configuration of the membrane and the applicability of the membrane, the composition of the casting solution is particularly important. In this case, the chemical composition and physical properties of the casting stock influence the arrangement and size of the cells and cell walls in a complex manner.

One factor is the solvent in the casting stock. Examples of such solvents include acetone,
These include dioxane, dioxolane, methyl acetate or nitromethane or methylene chloride.

Acetone is generally preferred. It is particularly advantageous to use the mixture as a solvent in the casting concentrate, since the properties of the membrane and the structure of the membrane can be controlled over a wide range. A mixture consisting of 50-90% by weight of acetone, 5-25% by weight of monohydric alcohol and 5-25% by weight of plasticizer has proven advantageous. The cell structure consists of a monohydric alcohol (or optionally as a mixture of alcohols) having 1 to 3 carbon atoms.
and the plasticizer content, glycerin being preferred as plasticizer if the membrane is used for medical purposes. The use of myristyl myristate as a plasticizer in the casting solution provides a structure that is important for industrial purposes of the membrane.

The precipitation bath also has a significant influence on the properties of the membrane, in which case water without admixtures produces very large pore passages, and when small pore passages are desired, aqueous solutions are advantageous as precipitation baths. Depending on the selected working conditions, the membrane according to the invention has a diameter of
It can have pore passages with a diameter of 0.01 μm to 50 μm.

In the case of previously known plasmapheresis membranes, nitrocellulose was more important than acylcellulose. Since nitrocellulose has problems in handling, acylcellulose has generally been given priority.
This acylcellulose can also be used for the membranes according to the invention in the same way as nitrocellulose.
Mixtures of various acylcelluloses, such as acetylcellulose and propionylcellulose and butyrylcellulose, can also be processed into membranes according to the invention. Cellulose acetate is preferred because of its already good availability.

Membranes consisting of pure cellulose triacetate are reasonably hydrophobic for most use cases of membranes according to the invention. In one embodiment of the invention, the plasmapheresis membrane consists of cellulose acetate with a degree of substitution of 2.0 to 2.7. The degree of substitution of the cellulose acetate used in the casting stock solution corresponds to the degree of substitution of the membranes cast therefrom. Preferably the degree of substitution is between 2.3 and 2.5.

A physical property of the casting solution that has a particular effect on the structure of the membrane is viscosity. Thus, a high viscosity casting stock produces thin cell walls in the membrane, which does not result in a reduction in the resistance to mechanical stresses, especially when at the same time the cell structure is constructed with low symmetry. The viscosity of the casting concentrate can be adjusted in part by the cellulose ester content, but also by viscosity-modifying solvents or additives. For example, a solvent containing isopropanol as the monohydric alcohol has a higher viscosity than a solvent containing methanol. The viscosity can also be reduced, for example, by adding halogenated hydrocarbons, such as trichlorotrifluoroethane. The viscosity of the casting stock solution is between 5 and 200 Pas, preferably 10
~100 Pas.

The process according to the invention for the production of membranes in the form of hollow fibers, tubular sheets or planar sheets, in particular for plasma export processes, consisting of cellulose acetate comprises 8 to 25% by weight of cellulose esters, 55 to 92% by weight of solvent and A casting stock solution, possibly consisting of up to 20% by weight of other additives, is extruded through a forming nozzle immersed in a precipitation bath, and the solution jet is joined to the solution jet interface with a settling bath section of at least 30 cm. It is characterized by subjecting it to the coagulating action of a precipitation bath, taking it out from the precipitation bath, washing it with water until the solvent is gone, impregnating it with a plasticizer solution, and finally drying it. Drying should be carried out under temperature conditions such that an average material temperature of 70°C is not exceeded.

An advantageous implementation of the process of the invention is to introduce a precipitation bath inside the exiting casting stock solution for producing hollow fibers or tubular sheets, in which case both precipitation baths preferably have the same composition. Preference is given to using mixtures as solvents. A good mixture is 50-90% acetone and 5-25% monohydric alcohol by weight.
and 5 to 25% by weight of a plasticizer, in which the monohydric alcohol preferably has 1 to 3 carbon atoms and the plasticizer used is a polyhydric alcohol, in particular glycerin in the scope of medical use. Ru.

Suitable settling baths include, in particular, water and aqueous solutions. Among the cellulose esters, preference is given to membrane-forming polymers, especially cellulose acetate, especially those having a degree of substitution of 2.0 to 2.7. Particularly preferred is a degree of substitution of 2.3 to 2.5. Failures during casting occur when the viscosity of the casting stock solution is 5 to 200 Pas,
This is advantageously avoided by being between 10 and 100 Pas.

The method is characterized in that, after passing through a settling bath section of at least 30 cm, the raw solution jet is led out of the settling bath around a deflection device arranged behind the spinning nozzle at an angle of 15 to 60° with the settling bath surface. It has been found that it can be carried out with good production rates.

In this case, it has proven advantageous to immerse the spinning nozzle in the precipitation bath in such a way that it forms an acute angle with the surface of the precipitation bath.

The membrane according to the invention is distinguished by its novel structure, in which the membrane is composed of substantially cuboid-shaped closed cells arranged next to each other in a pronounced honeycomb shape, with all the cell walls being narrowed. It is characterized by having a large number of holes passing through it as hole passages.

Generally, the membrane is constructed so that the closed cells do not have matching shapes and volumes. However, manufacturing often results in cell walls in which there is a point of symmetry approximately in the center of the wall. However, it is also possible to adjust the condition that the central cell wall extends in a serpentine manner through the cross section.

The cell structure as well as the pores penetrating all the cell walls have a significant influence on the selectivity of the membrane.

Of course, if desired, pigments can be loaded into the membrane in a known manner.

The invention will be illustrated in detail with reference to the following examples.

Example 1 Preparation of a casting stock solution consisting of cellulose acetate The following substances were fed one after another under stirring into a stirred vessel with a stirrer rotating at 800 rpm: 3000 g of methanol 4000 g of glycerin 2000 g of cellulose acetate (degree of substitution 2.48) 11000 g of acetone at room temperature After stirring for 2 hours, the cellulose acetate was dissolved. Subsequently, the solution was passed through a filter with an opening of 20 μm, degassed and
After some time, it was ready to be cast. The viscosity of the casting stock solution was 15 Pas.

Preparation of the membrane according to the invention in the form of hollow fibers 6 ml/min of the spinning dope prepared according to Example 1 was
A metering gear pump was used to feed a hollow fiber forming nozzle of known construction with an outer annular slit having a diameter of 1.300μ and a slit width of 150μ. The central hole for supplying the cavity-forming liquid had a diameter of 600μ.
As a cavity-forming liquid, 4.5 ml/min of spore-free water at 20°C to 22°C was supplied, which acted as a coagulating bath for the boundary surface of the spouting flow of the internal stock solution. The molding nozzle is
12mm into a sedimentation bath consisting of crystal-free water at 20°C to 22°C.
It was immersed in the depth of. The spout of spinning solution exiting downward from the forming nozzle together with the internal liquid is diverted by a roll placed at the bottom of the spinning pot after passing through a 60 cm settling bath section, which is at an angle to the bath surface.
Come out of the bath again at 50 degrees.

Remove the filament to remove any remaining solvent.
The water bath was electrically connected over a 120 m section. This water washing device is followed by a plasticizer bath containing a water-glycerin mixture of 92% water and 8% glycerin. The hollow fibers were dried in a stream of hot air at 60°C to 70°C. The speed of the hollow fiber at the exit of the device was 20 m/min. The completed hollow fibers were collected into a rope with a desired number of threads on a tension control drum, cut into a desired length, and processed into a large unit.

The following characteristic values were measured for the manufactured hollow fibers: Outer diameter 700μm Inner diameter 500μm Tear strength 78cN Elongation at break 9.1% Porosity 89.3% Hydraulic permeability 2.870m/h・m ²・mlHg Albumin Retention capacity for (molecular weight 69000) 2.3% at 0.6 bar Maximum pore size 1.3 μm Blowing pressure 1.6 bar Plasma is used as test medium and the sieving coefficient of plasma proteins is determined using a laser nephelometer (Boehringer) did.

Albumin (molecular weight 69000) 0.82 IgM (molecular weight 980000) 0.72 β-lipoprotein (molecular weight 2400000) 0.64 FIG.
This is a magnified electric micrograph. A honeycomb-like bubble structure is clearly observed, and in this case the bubble walls are dark.
Bubble voids appear bright. Figure 2 shows the pore passages at 6000x magnification. In this case, the pores appear dark and the walls light.

Example 2 Production of a plasma transport membrane in the form of a tubular sheet A gear pump was used to feed 325 ml/min of the casting stock solution described in Example 1 into an annular slit nozzle with a ring diameter of 70 mm and a slit width of 300 μm. The nozzle is immersed in the precipitation bath to a depth of 10 mm and is arranged vertically. The settling bath consisted of spore-free water at 20°C to 22°C. A metering pump was used to pressurize the bud crystal-free water into the tube-shaped undiluted film. At the same time, a considerable amount of this settling bath liquid was withdrawn from the interior again using multiple metering pumps. The water taken out contained 50 g of acetone.
50 cm below the nozzle, the resulting tube was flattened with a width holding device and guided at an angle of 40° to the bath surface with turning rolls. After passing through a 72 m washing section in which the tubular sheet is washed with germ-free water at 20°C to 22°C, it is passed through a 7.20 m long plasticizer bath and heated in a tunnel dryer at 64°C to 74°C. Dry with hot air at ℃. A solution of 8% by weight glycerin in water was used as plasticizer bath.

The speed at the end of the dryer was 9.8 m/min. The following data were measured for the resulting tubular sheet: Width (flattened) 53 mm Wall thickness 105 μ Tear strength (longitudinal) 102 cN (transverse) 48 cN Elongation at break (longitudinal) 4.3% ( Transverse direction) 7.1% Hydraulic permeability 1220ml/h・m ²・mmHg Retention rate for albumin (molecular weight 69000) 4.4% at 0.6 bar Maximum pore diameter 1.3 μ Blowing pressure 1.6 bar Using plasma, sieving of plasma proteins The separation coefficient was measured (laser-nephelometer,
Boehringer).

Albumin (molecular weight 69000) 0.35 IgG (molecular weight 140000) 0.19 IgM (molecular weight 980000) 0.01 β-lipoprotein (molecular weight 2400000) 0.01 The resulting tubular sheet has a relatively symmetrical arrangement of central cell walls in cross section. This structure is suitable for applications where optimal overeffect and good selectivity are important.

Example 3 Manufacture of a plasma transport membrane in the form of a flat sheet A slit with a width of 300 mm and a width of 270 μm was immersed in a precipitation bath to a depth of 15 mm using a gear pump at 450 ml/min of the casting stock solution described in Example 1. It was supplied to a wide slit nozzle. The settling bath consisted of spore-free water at 20°C. This wide slit nozzle is
It was tilted at approximately 30 degrees with respect to the direction of sheet travel.
At a distance of 1.40m below this wide slit nozzle,
The fully finished sheet was turned around with turning rolls and passed through the settling bath at an angle of 30°. This sheet is passed through a 62 m long cleaning section, and within this section 20
The cells were washed with bud crystal-free water at a temperature of 22°C to 22°C. After passing through a 6 m long plasticizer bath in which a solution of 8% by weight of glycerin in water was present, the adhering water was removed and, after passing through a 3 m air section, it was fed into a dryer. It was possible to obtain a satisfactory film in the same way as when using a hot air tunnel with an air temperature of 40°C to 45°C as a dryer and a drum dryer with a surface temperature of 62°C to 72°C. The production rate was 10.3 ml/min with the winder.

The following data were measured from the obtained planar sheet: Width 216 mm Wall thickness 110 μm Tear strength (longitudinal direction) 82 cN (transverse direction) 38 cN Elongation at break (longitudinal direction) 5.6% (transverse direction) 11.2% Hydraulic permeability 1510ml/h・m ²・mlHg Retention rate for albumin (molecular weight 69000) 0.2% at 0.6 bar Maximum pore diameter 1.3 μ Blowing pressure 1.6 bar Using plasma as the test medium, the sieving coefficient of plasma proteins was determined. (laser-nephelometer).

Albumin (molecular weight 69000) 0.44 IgG (molecular weight 140000) 0.29 IgM (molecular weight 980000) 0.05 β-lipoprotein (molecular weight 2400000) 0.03 Example 4 In Example 1, Example 2, and Example 3, the membranes with the same pore diameter are hollow fibers. It is described below how membranes in the form of hollow fibers with small pore diameters can be produced, although they can be produced as tubular sheets and planar sheets.

Analogously to the description in Example 1, a casting stock solution with the following composition was prepared: Cellulose acetate (degree of substitution 2.40) 16.3% by weight Acetone 63.3% by weight Methanol 10.2% by weight Glycerin 10.2% by weight As in Example 1, acetone content 6.9 ml/min of casting stock solution was fed to a hollow fiber molding nozzle immersed to a depth of 15 mm in a precipitation bath consisting of water with a glycerin content of 18 g/min and a glycerin content of 10 g/min. A precipitation bath consisting of 50% by weight of isopropanol and 50% by weight of water was pumped into the interior of this hollow fiber molding nozzle at 6 ml/min. The jet stream of raw liquid flowing out from this nozzle
After passing through a 40 cm settling bath section, it was turned and a further 30 cm
After a period of m, the precipitation bath was removed. The hollow fibers produced were washed free of solvent with water, impregnated with a plasticizer solution consisting of an aqueous glycerin solution containing 100 g of glycerin and subsequently dried in a stream of hot air at 62 DEG C. The velocity of the hollow fiber at the exit of the device is
It was 20m/min.

The following properties were measured for the finished hollow fibers: Internal diameter: 580 μm Outside diameter: 700 μm Tear strength: 174 cN Elongation at break: 14.7% Blowing pressure: 10 bar Maximum pore diameter: 0.2 μm Hydraulic permeability: 372 ml/h·m ² ·mmHg Retention rate for albumin: 83.3% Plasma was used as the test medium and the sieving coefficient was determined (laser-nephelometer).

Albumin (molecular weight 69,000) 0.10 IgG (molecular weight 140,000) 0.03 The membrane structure of the obtained hollow fiber exhibits an asymmetric arrangement of honeycomb-like bubbles, as is clear from the cross section. Membranes of this type have particularly good tear strength and elongation at break. This membrane should be used where significant mechanical stresses are expected.

Example 5 According to the invention it is also possible to produce membranes with significantly larger pore passages as shown below.

The membrane was prepared in the same manner as in Examples 2 and 5 using hollow fibers. The casting stock solution had the following composition: Cellulose acetate (degree of substitution 2.40) 8.5% by weight Acetone 46.5% by weight Methanol 20.0% by weight Glycerin 25.0% by weight The precipitation bath consisted of pure water at 20 °C. . The molding nozzle was immersed in the precipitation bath at an angle so that the outflowing raw solution jet formed an angle of about 10° with the surface of the precipitation bath. After passing through a 3 m settling bath section, the raw solution jet was diverted and led out of the settling bath. The obtained hollow fibers were washed with water until the solvent disappeared, and 5%
glycerin solution and dried in a hot air stream at 70°C. The velocity of the hollow fiber at the exit of the device is 22
m/min.

The following properties were measured: Outer diameter 700 μm Inner diameter 495 μm Tear strength 32 cN Elongation at break 4.2% Hydraulic permeability 4200 ml/h・m ²・mmHg Blow pressure 0.05 bar Maximum pore diameter 40 μm Retention for albumin 0 Plasma was used as the test medium and the sieving coefficients of various proteins were determined (laser-nephelometer).

Albumin (molecular weight 69000) 0.95 IgM (molecular weight 980000) 0.93 β-lipoprotein (molecular weight 2400000) 0.95 Example 6 In this example, when the cellulose acetate content is low, viscosity-lowering additives can be added to the spinning dope. Use a casting stock solution with a viscosity of 6 Pas. This casting stock solution had the following composition: Cellulose acetate 8.5% by weight Acetone 48.5% by weight Methanol 10.0% by weight Glycerin 18.0% by weight Trichlorotrifluoroethane 15.0% by weight This casting stock solution at 18 ml/min was used in Example 2. It was supplied to the hollow fiber forming nozzle as described. At the same time, 6.6 ml/min of water was pumped into the outflowing raw solution jet as a settling bath for the cavity-forming liquid and the interface of the raw solution jet existing inside. The nozzle was immersed to a depth of 20 mm into a settling bath also consisting of water to the external raw solution jet interface. The raw solution jet was diverted 60 cm below the spinning nozzle and washed free of solvent with water after exiting the settling bath. After treatment with a 10% glycerin solution, the hollow fibers were dried at 62°C in a stream of air.

The following property values were measured: Outer diameter: 780 μm Inner diameter: 608 μm Tear strength: 90 cN Elongation at break: 15.6% Hydraulic permeability: 2450 ml/h・m ²・mmHg Blow pressure: 0.4 bar maximum pore Diameter: 5 μm Retention rate for albumin: 2.4% Blood was used as the test medium and the sieving coefficients of various proteins were determined (laser-nephelometer).

Albumin (molecular weight 69000) 0.92 IgM (molecular weight 980000) 0.81 β-lipoprotein (molecular weight 2400000) 0.78 Figure 3 shows a portion of the cross section of the above hollow fiber examined with a mesh screen electron microscope at a magnification of 1000x. The photo is shown. This shows a large number of closed cells and a slightly asymmetrical arrangement of the cells. The difference in bubble size is clearly much more pronounced than in the case of the membrane illustrated in FIG. All outer walls and cell walls are pierced by numerous pore passages similar to FIG.

Example 7 Membranes according to the invention with very different properties can be produced without difficulty, so that it is possible to produce membranes that are permeable to any plasma, retaining only the bubble component on one side, On the other hand, it is also possible to produce membranes with an exclusion limit of about 100,000 molecular weight, so that these membranes are permeable to albumin, but other plasma proteins are retained.

Producing a plasma transport membrane in the form of hollow fibers according to Example 5,
It was installed in a membrane model with a membrane area of 0.01 ^m2 .

Another plasma transport membrane in the form of hollow fibers with similar data to Example 2 was manufactured and installed in a membrane model with a membrane area of 0.01 m ² .

Blood taken from the patient is collected and the membrane permeation pressure is 100 mm.
Hg was passed through the first membrane model at 3 ml/min,
In this case, 0.5 ml/min of liquid I was produced. The retained fraction contained all the foam components. Continuing,
This liquid was passed through a second model at a differential pressure of 30 mmHg and filtered using the dead-end method.

The filtrate produced in this case contained, after fractionation, only 83% of albumin, 56% of IgG and 5% of IgM or β-lipoprotein, based on the amount of protein originally present in each 200 ml of plasma.

The membrane according to the invention thus allows the body's own albumin to be reinfused together with the blood cell fraction. This eliminates the need for expensive and poorly tolerated injections of foreign albumin.

[Brief explanation of drawings]

FIG. 1 is an electron micrograph at a magnification of 450 times of a cross section of a plasma transport membrane according to the invention in the form of hollow fibers;
Figure 2 is an electron micrograph of the pore passages of the same plasma transport membrane at 6000x magnification, and Figure 3 is an electron micrograph of the same plasma transport membrane at 6000x magnification.
This is a mesh screen electron micrograph of a part of the cross section of the hollow fiber at 1000 times magnification.

Claims (1)

[Claims] 1. Extruding a casting stock solution containing cellulose ester through a molding nozzle, subjecting the jetting flow of the stock solution to the coagulating action of a precipitation bath, drawing it out from the precipitation bath, and washing to remove the bath agent. A semipermeable plasma transport membrane in the form of a hollow system, a tubular sheet or a planar sheet, manufactured by a method comprising substantially It is composed of closed cells in the shape of a rectangular parallelepiped, and all the cell walls are penetrated by many pores as pore passages.
A casting solution with a viscosity of 200 Pa.s contains 8-25% by weight of cellulose esters, 55-92% by weight of solvent and optionally up to 20% by weight of viscosity-controlling additives, but no pore-forming metal salts. The stock solution was extruded directly into the precipitation bath, and the membrane was washed with acetone 50-90%.
% by weight, 5-25% by weight of monohydric alcohol and 5-25% by weight of a plasticizer, which is impregnated with a plasticizer solution after washing and removal, and finally dried. . 2. Semipermeable plasma transport membrane according to claim 1, used as cellulose acetate ester having a degree of substitution of 2.0 to 2.7. 3. A semipermeable plasmapheresis membrane according to claim 1, wherein the monohydric alcohol has 1 to 3 carbon atoms. 4. The semipermeable plasma transport membrane according to claim 1, which uses polyhydric alcohol as a plasticizer. 5. The semipermeable plasma transport membrane according to claim 4, wherein glycerin is used as the polyhydric alcohol. 6 Semi-permeable molding solution containing cellulose ester is extruded through a molding nozzle, the ejected solution is subjected to the coagulation effect of a precipitation bath, and is drawn out from the precipitation bath and washed to remove the solvent. In the method for manufacturing plasma transport membranes, a casting solution having a viscosity of 5 to 200 Pa.s is mixed with a cellulose ester of 8 to 25 Pa.s.
wt%, solvent 55-92 wt% and sometimes 20
% by weight of viscosity-controlling additives, but no pore-forming metal salts; A process for producing semipermeable plasmapheresis membranes, characterized in that they are washed to remove the solvent, impregnated with a plasticizer solution and finally dried.