DD159527A5 - DIALYSEMEMBRANE FROM CELLULOSE - Google Patents

Abstract

1. A process for the production of a dialysis membrane of regenerated cellulose in the form of flat films, tubular films or hollow filaments, characterized in that a mixture of from 7 to 25 % by weight of cellulose, from 93 to 50 % by weight of tertiary amine oxide, optionally up to 25 % by weight of a diluent which does not dissolve the cellulose and up to 10 % by weight of standard additives, based in each case on the weight of the spinning solution, is dissolved in less than 8 minutes at temperatures of from 80 to 150 degrees C in a mixing unit, in that the solution is degassed, extruded through a wide slot die, annular slot die or hollow filament die into a precipitation bath, washed and, after addition of plasticizer, is dried without shrinkage at temperatures of from 50 to 110 degrees C and wound into roll form.

Description

Berlin, the 4.11. 1981 AP B 01 D / 230 698/4 59 293 11

Dialysis membrane made of cellulose

Field of application of the invention .

The invention relates to regenerated cellulose dialysis membranes in the form of flat films, tubular films or hollow fibers, in which flat films, tubular films or hollow fibers are formed by extruding a spinning solution consisting essentially of cellulose and a tertiary amine oxide into a non-solvent.

Character istik of the known technical solutions

From CH-PS 191 822 it is known that cellulose can be dissolved in tertiary amine oxide, and that the cellulose can be regenerated by introducing such a solution in an aqueous precipitation bath. Another method for dissolving cellulose in tertiary amine oxides is described in German Auslegeschrift 3,447,939.

DE-OS 28 30 683, DE-OS '28 30 684 and DE-OS 28 30 685 describe processes for dissolving cellulose in tertiary amine oxide, v / ei ίί-methyl-morpholine is preferred amine oxide and the tertiary amine oxide may not containing diluent ..

The storage-stable product obtained can be used immediately for extrusion into an insoluble solvent, forming films or threads of regenerated cellulose.

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Regenerated cellulose dialysis membranes in the form of flat films, tubular films or hollow fibers have long been known, wherein the regeneration of the cellulose by the Cuoxam process, after the. Depending on the method used and the process conditions, membranes with different dialysis shells, such as, for example, ultrafiltration performance, permeability for different molecular sizes, water retention capacity and different ratios of several such properties, are obtained. hydrodynamic permeability in a certain ratio to the diffusive permeability ·

For example, in DE-OS 28 23 985, a cellulose membrane, which is produced by the Cuo:%; m.verfahren claimed, which has a greater hydrodynamic permeability (ultrafiltration performance), than is otherwise achieved in the Cuoxam process · Such membranes play a role in the treatment of hypertensive patients in which a membrane with increased hydrodynamic permeability is desired for reinfusion of larger quantities of human blood into the human circulation, which also has a sufficiently high diffusive permeability as that regenerated by the cuoxam method Cellulose is achieved ·

Regenerated cellulose dialysis membranes regenerated by the cuoxam process lose their dialytic permeability, while respecting the ultrafiltration performance of 1 × 10 -5 ml / min- Έ, to such an extent that they serve as membrane for the Dialysis, especially for hemodialysis are no longer usable «

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In GB-PS 1 144 759, which describes the regeneration of cellulose from spinning solutions consisting essentially of cellulose and tertiary amine oxides, mention is also made of the possibility of using the so-regenerated cellulose in dialysis membranes, but without the various related ones To even cut problems ·. , ·

Object of the invention ·

The aim of the invention is to provide a novel regenerated cellulose dialysis membrane having sufficient strength and hitherto unknown dialysis properties.

Presentation of the invention

The invention is based on the problem of producing dialysis proteins from regenerated cellulose in which the vitamin B bi2 permeability is significantly higher than in the case of known dialysis membranes.

This object is achieved by a membrane of the type mentioned, which is characterized in that the adjustable depending on the ultrafiltration performance dialytic permeability 'for vitamin B12, measured at 20 ⁰ C, equal to or greater than that from the linear regression equation ^DL yitamin B12 ^{= 5} * ³ *

calculable value, the ultrafiltration power being from 0 to 10.10 * "* ml / min · IT"

The dialysis membrane according to the invention thus has a markedly higher vitamin B12 permeability than the hitherto known dialysis membranes from regenerated _A.

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Cellulose In particular, it is advantageous that now dialysis membranes are available which still have a considerable vitamin B12 permeability. when virtually no ultrafiltration performance is measured anymore.

Excellent dialysis membranes according to the invention are those which consist entirely or partly of substituted cellulose, the degree of substitution of the substituted cellulose preferably being between 0.1 and 0.7.

Substituted celluloses, which in the context of the invention lead to good dialysis membranes having the high vitamin B 12 permeability with comparatively low ultrafiltration performance, are carboxyalkyl cellulose, alkylated cellulose, such as methyl cellulose, ethyl cellulose, but also mixed substituted, such as, for example, hydroxypropylmethyl cellulose.

The invention also provides a process for the preparation of the dialysis membrane according to the invention, which is characterized in that a mixture of 7 wt .-% to 25 wt .-% cellulose, 93 to 50 wt .-% tertiary amine oxide, optionally up to 25 wt . ~% Mchtlösungsmittel and up to 10 percent by "-% customary additives, all based on the weight of the spinning solution in einem.ItLschorgan in less than 8 · min and at temperatures between 80 and 150 ⁰ C is brought to the solution, the solution was degassed , is washed extrudierti through a slot die, or hollow Ringschlitζdüse * "Thread nozzle in a Pällbad and dried, and after addition of Y / calibration wheeler under SGhrumpfbehinderung at temperatures between 50 and 110 ⁰ C wound ··

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As tertiary amine oxides, for example, iriäthylaminoxid, Dimethylcyclohexylaminoxid,. Dimethylethanolamine oxide, dimethylbenzylamine oxide, methylpiperidine oxide * methylpyrrolidine oxide, pyridino xid. proved to be suitable. However, preference is given to N-methyl-morpholine-N-oxide. Optionally, the spinning solution contains from 10 to 25% by weight of an insoluble solvent. As non-solvent come in embossing: water, low mono- and polyhydric alcohols, dimethylformamide, dimethyl sulfoxide, higher-boiling amines, in particular the amine corresponding to the tertiary amine oxide. ·

A parameter which influences the ultrafiltration performance in the dialysis membrane is the concentration of cellulose in the spinning solution, where a lower concentration leads to higher ultrafiltration performances. Higher cellulose concentrations lead to high viscosities, which impairs the spinnability.

If appropriate, the spinning solution is admixed with up to 10 % by weight of additives. As such, for example, viscosity-influencing additives, stabilizers and / or plasticizers come into question. Stabilizers prevent too great a reduction in the degree of polymerization and other damage which results in a discoloration of the regenerated oil cellulose. So far have proved successful for this purpose, for example, • citric acid and / ode ⁰ r glucose. As additives, it is also possible to use inorganic and / or organic salts, which are soluble in the spinning solution, in order thereby to influence, for example, the pore structure.

While in the previously known Dialysememb.ranen as cellulose always-, a'high-quality cellulose with high

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^ Sp ^ w_ ·? &>> 43 * · ► * D "*

Used vmrde polymerization, such as cotton linters, it is in the inventive dialysis membrane readily possible, celluloses with- a lower degree of polymerization use · For toxicological reasons, only has to be ensured that no on-going blood substances remain in the cellulose, d "h. one should pay attention to resin and Hemicellulosefreiheit.

The temperature in the extruder should be set as high as possible because it can reduce the residence time, and the processability is improved due to the lower viscosity - for example, degassing, higher cellulose concentration and thus lower ultrafiltration performance with excellent dialysis permeability for vitamin Bi2.

Up to temperatures of 150 ^° C., the mixture for the spinning solution could still be processed without serious damage to the cellulose, especially when, for example, 3 % citric acid had been added as stabilizer to the mixture. The working temperature must in any event be above the melting temperature of the selected tertiary amine oxide · the melting point of most tertiary candidate amine oxides is reduced sufficiently by admixtures of Mchtlösungsmitteln that temperatures suffice to 80 ⁰ C, to prepare the spinning solution ·

Suitable precipitation baths are liquids and solutions which are miscible with the tertiary amine oxide. Water, lower monohydric and polyhydric alcohols, ketones, amines and, in particular, aqueous solutions may be mentioned here. The substances mentioned may be used alone or in a mixture.

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In order to influence the coagulation, the coagulation bath preferably contains from 1 to 25% by weight of tertiary amine oxide.

Optionally, salts, such as, for example, sodium sulfate or ifetrium acetate, may be added to the precipitation bath in order to limit the swelling of the regenerated cellulose during coagulation. ·

In general, the precipitation bath temperature is at room temperature. Higher precipitation bath temperatures should be avoided in order to avoid a reduction in the diisocyanate performance of the membrane.

Under the conditions mentioned, a residence time in the precipitation bath of 2.Min "aus.'Das washing out of the residues of tertiary Aininoxid and optional additives in a conventional manner in countercurrent with water from 12 to 40 ⁰ G and requires sufficient in most cases a residence time for a maximum of 2 to 4 minutes

To counteract keratinization and embrittlement on drying, a plasticizer is added to the washed and still wet dialysis membrane. This can be done by immersion in an aqueous and / or alcoholic solution of a plasticizer or by spraying or printing such a solution. For the purposes of hemodialysis are generally only those compounds in question - which can be used toxicologically ^ without restriction »have proven to be suitable: glycerol, polyethylene glycols, 1,3-butanediol, glucose and mixtures of the substances mentioned. , , '.

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The resulting dialysis membranes according to the invention are dried at temperatures between 50 and 110 ⁰ G in a similar manner, as it is • known from other regenerated cellulose dialysis membranes. Roll dryers, belt dryers or other types of dryers which ensure that drying takes place under shrinkage inhibition are suitable for this purpose. By shrinkage inhibition it is to be understood that measures are taken which largely rule out a reduction in dimension in the longitudinal and transverse direction. A reduction in thickness is permissible "In general, drying is started at a higher temperature and reduced towards the end of the drying section."

In a particular embodiment of the invention, the mixture for the spinning solution is brought to solution in less than 4 minutes, which is made possible in particular by a correspondingly higher temperature in the extruder.

However, the higher temperature in the extruder is only possible if the spinning solution already contains a stabilizer. "For spinning solvent mixtures without stabilizer, a temperature range of 90 to 110 ⁰ C in the extruder is preferred.

The dialysis membranes according to the invention have a high dialytic permeability in the so-called medium molecular weight range (500-5000 daltons) which is expressed as vitamin B12-C as a test molecule. This high dialytic permeability is also essentially retained when a post-treatment the hydraulic permeability for water (= ultrafiltration performance) is drastically reduced to the optimal value for hemodialysis · · '

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This post-treatment is carried out in such a way that the dialysis membrane i.before the addition of plasticizers in aqueous liquids 5 to 50 min., Preferably 10 to 20 min., At temperatures of 50 to 105 ⁰ G, preferably 60 to 80 ° _(is treated.

As the water-containing liquid in addition to water as such a 75 to 85 wt .-% aqueous hydrazine solution or a mixture of water and / or monohydric alcohols having 1-3 carbon atoms and glycerol are preferred. '-

As a mixing element with which particularly favorable short residence times have been achieved for mixing the spinning solution into a homogeneous degassed solution, a twin-screw extruder with degassing zone has proven particularly suitable. The screws in the twin-screw extruder preferably have the same direction of rotation.

embodiment

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

Example 1 . ·. '

In a twin-screw extruder with degassing zone and concurrent screw is continuously fed via a dosing with a 36 g / min mixture of 20 wt .-% beech sulfite cellulose having an average degree of polymerization of 795 anhydroglucose units (weight average), 68 wt .-% U-MethyImorpholin IT oxide and 12% V / asser supplied. The extruder was heated to 100 ^° C. (except for the feed zone). In the 'Degradation

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At 10 mbar the mixture is degassed, whereby air and a part of the water are removed. After a residence time of 4 minutes in the extruder, the resulting clear solution was filtered and fed to a spinneret by a metering pump. The nozzle with a slot width of 180 mm and a gap setting of 600 μm was heated to 130 ° and spaced 10 mm above the surface of the precipitation bath arranged · As coagulation bath / ater served V of 20 ⁰ C. in a take-off speed of 4 m / min and a coagulation bath in Verwe.ilzeit of 2.5 min, the membrane was precipitated, washed and after dipping in a softening bath whose inlet · sämmensetzung 35 wt * -% glycerol, 45 was wt .-% ethanol and 20% water, and pressing dried in a duo in a belt dryer at a chamber temperature of 65 ⁰ G under shrinkage prevention and wound The membrane thus obtained was transparent and had the following dialysis properties : '.

UFL = 3.2 χ 10 '

-4

ml

DL (vitamin B12) = 3.9 χ 10 '

min II

-3

cm

MM) * MH

min

The breaking load according to -DIU 53455 is 1836 cli in the longitudinal direction, the breaking elongation is 25.9 % · The thickness of the membrane in the dry state is 13 / um, the water content is 7.9%, the glycerin content is 25 % ·

Example 2 . , '

In an analogous manner, a spinning solution with a cellulose content of 14 % was processed into a membrane. The

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dried membrane gave the following values:

UI ¹ L = 5.3 x 10

-4

ml · min U

It B "12

= 6.1 χ 10 " ³

cm

min

Dl urea = 37.3 x 10 '

-3

^mn

Breaking load along a 1600 CN transverse - 500 cN Elongation at break along = 23 % cross = 140 % water content = 8 wt. glycerol content = 22 wt. J ⁰ Example 3

Instead of the slot die, a core-shell-symmetric heatable bicomponent nozzle was used. The outside diameter of the nozzle bore was 1100 μm, the core needle one 700 μm. A paraffin oil was used as the void-forming liquid. * The spinning solution had a cellulose concentration of 22 % " at a flow rate of 1.8 - ^ U-T per spinneret and a deduction of 15 hjr ~ j

hollow fiber were 300 to outer diameter and 20 to obtain wall thickness "Mach removing the internal liquid with methylene chloride and blow-drying, the hollow fiber was tested for its dialytic properties for:

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23

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The ultrafiltration rate was measured and, because of the better comparison strength, converted to ultrafiltration performance.

The UPR (measured at 20 ^° C.) is 3.5

that corresponds to one.

UFL of 4.3 x 10

ml

2 m h Torr

, -4

ml

min

it B 12

= 5.5 * 10

-3

cm min

Example 4

A membrane prepared analogously to Example 1 was acting before plasticizer addition 12 min at 75 ⁰ G = with water aftertreatment and then provided in conventional manner with plasticizer and dried · Thereby, a practically no longer measurable with a simultaneous UPL

^DL V

it B12

= ² > ⁶

¹⁰

measure up

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Claims (5)

4. 11. 1981 AP B 01 D / 230 698/4. 59 293 11 - 13 - Invention claim. 1. malysemembran regenerated cellulose in the form of Plachfolien, tubular films or hollow thread, wherein by extrusion of a dope consisting essentially of cellulose and a tertiary amine oxide, in a non-solvent flat films, tubular films or hollow thread are made, characterized in that the function of dialysis permeability adjustable for vitamin B12, measured at 20 ° C, which is adjustable by the ultrafiltration performance, is equal to or greater than the Δμs of the linear regression equation DLy + _anr ? _n -ri? ⁼ 5.3 (Ui ¹ L) + 2.3 · 10 "" 2 calculable value, the ultrafiltration performance being between Q and 10. 10 ml / min. , , 2 · Dialysemembrah according to item 1, characterized in that the cellulose consists wholly or partially of substituted cellulose. 3 · dialysis membrane according to item 2, characterized in that the degree of substitution of the substituted cellulose is 0.1 to 0.7. 4 * A method for the preparation of the dialysis membrane according to the points 1 to 3 »characterized in that a mixture of 7 wt .-% to 25 wt .-% cellulose, 93 to 50 wt .-% tertiary amine oxide, optionally up to 25 Gew _e - % Non-solvent and up to 10% by weight of customary additives, in each case based on the weight of the spinning solution, in a mixer, in less than 8 minutes and at temperatures between 80 and 150 ^° C., 4 * 11th 1981 AP B 01 D / 230 698/4 59 293 11 the solution is degassed, extruded through a slot die, annular slot die or hollow thread die into a precipitation bath, washed and dried and wound up after the addition of plasticizer with shrinkage inhibition at temperatures between 50 and 110 ^° C. 5. The method according to item 4, characterized in that the precipitation bath is a liquid or solution which is miscible with the tertiary amine oxide. « Method according to item 5, characterized in that the predominant portion of the liquid or solution is water, monohydric or polyhydric alcohol, ketone or amine or a mixture of these. Process according to items 5 to 6, characterized in that the precipitation bath contains 1.0 to 25% by weight of tertiary amine oxide. 8 _β process according to item 4 to 7 », characterized in that the spinning solution contains as an additive a stabilizer. 9 · Process according to point 4 to 8, characterized in that the spinning solution contains as additive a plasticizer · 10, process according to point 4 to 9, characterized in that the mixture for the 'spinning solution in less' than 4 minutes is brought to the solution 11. The method according to item 4 to 10, characterized in that the mixture for the spinning solution at temperatures'  '' - '' '~' - 15 - 4o 11 · 1981 AP B 01 D / 230 698/4 59 293 11h: between 90 to 110 ⁰ G is brought to the solution. 12 * Process according to items 4 to 11, characterized in that the dialysis membrane obtained is treated at temperatures of 50 ° to 105 ^° C. for 5 to 50 minutes before the addition of plasticizer in liquids which are obtained. 13 * Process according to item 12, characterized in that the water-containing liquid is a 75 to 85% by weight aqueous hydrazine solution » , Method according to item 12, characterized in that a mixture of water and / or monohydric alcohols and 1 to 3 C atoms and glycerol is used as the water-containing liquid. 15 * Method nach.-point '14, characterized in that the water-containing liquid contains 10 to 40 wt .-% glycerol · 16. Method according to items 12 to 15, characterized in that the treatment is carried out at temperatures of 60 ° to 80 ^° C. 17 · Method according to "Points 12 to 16, characterized by the fact that the duration of treatment is 1 ° to 20 minutes. 18 * Process according to points 4 to 17 *, characterized in that a twin-screw extruder with degassing zone is used as mixing element. 19 '' Method according to item 18, characterized in that the Screws in twin-screw extruder same direction of rotation. respectively" . '