SE428221B - HALFIBER OF CELLULOSA ACETATE AND WAY TO MAKE IT - Google Patents

Abstract

The invention provides cellulose acetate hollow fibers suitable for use in artificial kidneys which provide superior water and solute clearances. The cellulose acetate hollow fibers of this invention may be made from a molten mixture of 41-50% cellulose acetate, 30-57% polyethylene glycol (MW150-600) and 2-20% glycerine, the resultant fibers being cold drawn by 2-20% and then leached to remove the polyethylene glycol and glycerine. The hollow fibers of the invention have an internal diameter of 100 to 350 microns, a wall thickness of 20 to 60 microns, and ultra-filtration coefficient of 2 to 6 millilitres per hour per square meter per millimeter of mercury and a urea coefficient of 0.015 to 0.045 centimeters per minute.

Description

? so7s1e-5 10 15 20 25 30 .35 2 ning in artificial kidneys. A three-year project of this type, with the main purpose of developing an artificial kidney based on cellulose acetate hollow fibers, was led by The Dow Chemical Company, Western Division Research Laboratories during the period 1971-1973, under NIH Contract No. 70-2302.

During this project work, cellulose acetate fibers were prepared by melt spinning a mixture of cellulose acetate and triethylene glycol, and some of the I fibers obtained were incorporated into artificial kidneys and clinically tested by hemodialysis. The best artificial kidneys produced during this project were successful in that they had a safe function in the dialysis of a number of test patients in a clinic, but their transport properties for removing water and low molecular weight exhibiting substances, such as urea and creatinine α were not as favorable as in artificial kidneys available at the time, which included cellulose hollow fibers. The problem with these kidneys was that the water removal rates were too high and that the ratio between the removal of blood-soluble substances and water was too low, which is why the project gave up.

Since the early 1970s, when artificial kidneys with hollow fibers were first commercialized by Cordis Dow Corp; in the United States, the hollow fibers for use in such commercial artificial kidneys have consisted exclusively of. cellulose fibers. These fibers have been the product of the copper ammonium process of U.S. Pat. No. 3,546,209. Although cellulosic hollow fibers have been widely accepted as the best form of semipermeable membrane for use in artificial kidneys, those skilled in the art know that there are many recurring production problems. by melt-spinning such fibers and by incorporating them into leak-proof artificial kidneys.

For example, the tensile strength of the fibers is relatively low, and fiber breakage makes handling during fiber treatment and assembly into a dialysis chamber both complex and difficult. Due to such difficulties with capillary cellulose fibers, there is a continuing need for such semipermeable capillary fibers which are inexpensive, easy to melt spin and further process into artificial kidneys on a commercial scale, and which have the ability to remove blood solutes. such as urea, creatinine, uric acid and water at rates higher than currently present capillary cellulosic fibers.

The main object of the invention is to provide such a new cellulose acetate half-fiber which is better than the hitherto known cellulose ester and cellulose hollow fibers in that it has selectively controllable permeability properties which enable the production of artificial kidneys with better clearance. "values with respect to water and solids other than those which currently characterize commercial artificial kidneys containing cellulose half-fibers. A related object is to provide a method for producing the improved cellulose acetate fibers of the invention.

The invention creates novel semipermeable cellulosic acetate hollow fibers which have a combination of permeability and "clearance" properties with respect to water and blood-soluble substances of less than about 1400 molecular weight, which are variable relative to each other and controllable to achieve of optimized operating conditions when used in artificial kidneys for hemodialysis. Optimal operating conditions for an artificial kidney relate to a high "clearance" value - for blood-dissolved slag products in relation to the rate of water removal, thereby enabling blood purification in a minimum of time.

The novel fibers of the invention are made from a novel spin melt composition. Thanks to this composition, cellulose acetate can be spun dry, cooled in air and taken up on rolls without prior leaching. The new spin-melt composition comprises a mixture of cellulose acetate and certain proportions of polyethylene glycol having a molecular weight of about 150-600 and certain proportions of glycerin; this composition can be melt-spun into semi-soft fibers and fibers which are stronger and easier to process into artificial kidneys than cellulosic fibers but nevertheless have a favorable combination of water and blood permeability properties. these permeability properties are further improved and optimized by subjecting the spun fibers to certain supervised process steps after spinning. The permeability of these fibers can be varied and controlled by adjusting the relative quantities of each of the 3 components of the melt spinning composition and optimizing the relationship between the results for the "clearance" values for low molecular weight blood-soluble substances and for water, when such compositional adjustments are made in connection with controlled or controlled cooling and a regulated or controlled degree of cold draft stretching, or stretching, of the spun fiber immediately after cooling and after leaching from the spun fiber of the glycerin or polyethylene glycol constituents of the cooled fiber; By dry spinning in air at ambient temperature and correct control of the degree of cold drawing and by careful selection of the amounts of each component in the melt spinning composition, it is possible to obtain such cellulose acetate fibers which have selected combination properties with respect to "clearance" and higher conditions. between "clearance" with respect to the solutes and "clearance" with respect to the water, than the hitherto known cellulose acetate hollow fibers. The resulting spectrum, or family, of fibers constitutes the improved product of the invention.

The improved method of the invention includes steps which control and correlate the melt spinning composition and cooling of spun fibers with the degree of cold drawing and with the conditions of leaching and drying to achieve the desired permeabilities in the new cellulose acetate fiber.

The invention is described in more detail below with reference to the accompanying drawings, in which Fig. 1 shows a three-component diagram illustrating the proportions of the three components combined in the melt-spinning composition according to the invention, as indicated by the field. as defined by points A, B, C and D, and Fig. 2 '5 schematically illustrates the steps performed in the treatment of the melt spinning compositions of Fig. 1 to provide the improved family of capillary cellulose acetate hollow fibers of the invention.

Melt spinning composition 10 e The melt spinning composition of the invention consists, by weight%, of about 41-50% cellulose acetate, about 2-20% glycerin and the remainder polyethylene glycol having a molecular weight of about 150-600. As shown in Fig. 1, this family or spectrum of three-component compositions lies within the range limited by the extreme values of each of these three components, which define the range A, B, C, D.

Each of the specific compositions comprising an amount of each of the three components within the range A, B, C, D in Fig. 1 is suitable for melt spinning into capillary half fibers. After cooling, water leaching of glycol and glycerin and assembling into an artificial nure with a conventional design, such fibers function as well or better than currently available cellulose fibers, produced by the copper ammonium process of U.S. Pat. No. 3,546,209. compositions which are particularly well suited for optimizing the operating properties of most intermittent dialysis patients are shown in Fig. 1 as the range E, F, G, H.

The three components cellulose acetate, ethylene glycols and glycerin are separately known membrane materials, and cellulose acetate has been combined with a polyol, such as glycols, in compositions which also contained a plasticizer, or solvent, for the cellulose acetate of e.g. sulfolane type However, prior to the advent of the present invention, it has not been known that glycerin, which is not a solvent for cellulose acetate at ambient temperature, could be used in combination with selected glycols with low 7807s16es. 6 molecular weight for the production of strong hollow fibers, which have modified permeability properties relative to those obtained in the presence of a sulfolane-type solvent. Furthermore, it was not known that certain proportions of glycerin in such compositions allow modification and control of the transport of low molecular weight solutes through the fiber wall relative to the water transport through the same wall. Cellulose acetate is referred to in this specification and in the claims for cellulose diacetate. Cellulose diacetate, as commercially available in the United States, is satisfactory for use in this invention and is preferred, although amounts of monoacetate and triacetate may be present, for example up to about 25%. Smaller amounts normally occur in commercial cellulose diacetate. When cellulose acetate is dissolved in a solvent such as dimethyl sulfoxide, sulfolane, triethylene glycol or other low molecular weight glycol which is liquid at ambient temperatures, and spun through a conventional spinneret into a fiber strand, the individual fibers tend to or welded together, when placed on a core. Such fibers, although cooled below the gelling point and allowed to solidify into a solid fiber form, retain a quantity of solvent which; obviously keeps surface areas soft enough to cause adhesion during winding. Hitherto, it has been necessary to collect solution flour from the spun and cooled fiber before winding, and a hot water leaching bath has been used for this purpose. However, it has been found that feeding capillary hollow fibers immediately after cooling to a leaching bath caused severe fiber pulsation and concomitant uneven wall thickness and uneven inner diameter. It has been found according to the invention that fiber agglomeration welding could be avoided without leaching before incorporation into cores by using a low molecular weight glycol as a solvent for the cellulose acetate, modified with the above-mentioned amounts of glycerin. Obviously, glycerin reduces the softening effect of the glycol, and the fibers can be wound, and even stretched and wound on cores in the tensioned state, without adhesion or welding. The obtained spun fibers show improved uniformity in the wall thickness and the inner diameter and can be stored indefinitely at room temperature on cores for future further processing into artificial kidneys. Furthermore, glycerin obviously has a modifying effect on the cellulose acetate gelation during cooling in such a way that the resulting porosity in the fiber wall changes. When glycerin is present in the spun melt composition defined above, a gelled fiber is obtained which has sufficient strength to maintain its integrity and substantially maintain its uniform wall thickness and inner diameter during stretching and cold drawing immediately after gelation or solidification, such as will be explained later in connection with the description of the cold drawing step. Surprisingly, such cold drawing further modifies the fiber wall porosity so that low molecular weight solutes in the blood pass more easily through the wall from the blood flowing inside the fiber to a dialysate solution flowing on the outside of the fiber. A significant increase in the transport of such substances dissolved in the blood, i.e. dissolved substances with low molecular weight up to 1400, including urea, creatinine, uric acid and others up to and including vitamin B 12, is achieved without increasing the ability of the fiber to transport water through the same wall. Although the mechanism of this change due to cold drawing is not fully understood, it has been found that the degree of cold drawing and the amount of glycerin present in the spun melt composition are interrelated and interdependent. In general, when using a spin-melt composition consisting of cellulose acetate dissolved in a polyethylene glycol, whose molecular weight is in the range of about 150-600, and of at least 2% glycerin, there is some increase in transport. of substances dissolved in the blood when the cold draw increases up to about 20% of the fiber length just spun. Such an increase continues with increasing glycerin content, but the relationship is not completely linear; when the proportions of glycerin in the spin-melt composition are between about 3% and 10%, and the cellulose acetate is between about 42% and 47%, the remainder being polyethylene glycol, there is an improvement in the ratio between transport of substances dissolved in the blood and transport of water, when the degree of cold drawing increases up to about 15% of the just spun fiber length, and at 42-45% cellulose acetate excellent results are achieved by about 10%. Maximum improvement of the just mentioned conditions is achieved with compositions selected from the preferred range of EFGH according to Fig. 1, and the optimal degree of cold drawing can be easily established for the selected composition by a few simple experiments.

Hole fiber process using melt spinning composition As shown in Fig. 2, the process or method includes. the steps of forming the melt-spinning composition described above, melt-spinning hollow fibers and cooling them to a gelled self-supporting state, and stretching or cooling the fibers. The stretched fibers can be stored, or a number of bundles consolidated into fiber bundles, for example 3000-30000 fibers, for further processing for assembly into artificial kidneys. The fibers again consolidated in bundled bundles are passed through a leaching tank to remove the glycol and glycerin, forming a bundle of semipermeable hollow fibers. The lacquered bundle is then softened with an aqueous glycerin solution, after which the excess glycerin is removed and the fibers are dried. The dried fibers constitute the improved product according to the invention.

The formation of the melt-spinning composition can take place in any suitable manner with conventional mixing equipment, the important thing being to ensure sufficient mixing to obtain an intimate, uniform mixture. For example, dry cellulose acetate powder is now mixed with a balanced amount of polyethylene glycol and glycerin in a high shear Hobart mixer; the mixed material is homogenized and further mixed by feeding it to a heated extruder with counter-rotating screws, whereupon the molten extrudate is forced through a spinneret, for example a 16-32 hole die of the type having conventional gas supply means for driving gas into the core of the extrudate. A preferred gas for this purpose is nitrogen, but other gases can be used satisfactorily, including carbon dioxide, air or other harmless gas. The extrudate exiting the die is subjected to cooling, such as compressed air cooling with varying pressure and / or temperature, in order to effect gelation and solidification of the extrudate into solid, self-supporting fibers. The fibers are typically of capillary size, ie their inner diameter is in the range of about 150-300 μm and their wall thickness is in the range of about 20-50 μm. Although the preferred fibers of the invention are particularly suitable for use in hemodialysis in artificial kidneys, the advantages of dry spinning and forming fibers which can be applied to support cores without prior leaching are equally applicable to fibers provided for other uses. such as ultrafiltration, etc. Such other fibers may, with satisfactory results, have an outer diameter in the range of about 350-400 μm and in wall thickness in the range of about 10-80 μm.

In the method according to the invention, the short period of time which follows immediately after the extrudate emerges from the nozzle openings is of extremely great importance for achieving the desired permeability of the obtained fibers. During this time period, the porosity, and thus the permeability, of the resulting fiber is determined as a combined function of the cooling rate and the cold drawing or stretching to which the fibers are subjected. The porosity, for a given melt spin composition, is increased, at each determined degree of stretching of the fibers, by a drastic cooling of the molten fiber 1 relative to the porosity obtained by a less drastic cooling or a slower gelation of the extrudate. to fibers. increasing porosity obtained in such a cooling process normally affects the ability of the fiber to transport water and can be used, as needed, to pre-select or modify the ultrafiltration rate of the resulting fiber, when used. for hemo-- dialysis. By increasing the flow rate of the air with ambient temperature across the extrudate, minor adjustments can be made in the obtained fiber porosity, whereby a similar effect can be achieved by lowering the temperature of the refrigerant, or both can be set to achieve optimal conditions. It is preferred to use air with ambient temperature for cooling, in which case commercially satisfactory results have been obtained without cooling to below ambient temperature. Cold drawing or stretching is carried out in a satisfactory manner by passing the extruded and solidified fibers over a series of rollers, or separate series of rollers, such as Godet rollers; wherein the desired degree of cold drawing can be obtained by controlling the rotational speed of the second roller, or the second group of rollers in the direction of movement of the fibers. Good correlation between the degree of fiber cold drawing and the preset, or measured, rotational speed of the downstream set of rollers is usually achieved and for a particular, desired cold drawing percentage value, it is only necessary to correctly control the rotational speed of the downstream set of rollers. rollers in relation to the upstream sets of rollers. Uptake or winding of the cold drawn or stretched fibers on cores or bobbins can be accomplished by commercially available winding devices, such as Leesona winding devices, whereby adequate care is taken to maintain a slight elongation of the fibers during winding.

In the preferred embodiment of the method, a plurality of cold drawing cores or rollers are mounted for feeding a plurality of fiber strands through a conventional collecting device to form a consolidated bundle, after which the consolidated fibers are leached to remove glycerin. and the polyethylene glycol components. The leaching treatment can be carried out by any conventional means and method, such as conducting the fiber bundle through a bath of selected solvent, or by semi-batch immersing the cores or rollers in such solvent. The leaching solvent may consist of any such solvent which is a good solvent for the plasticizer and glycerin and a bad solvent for cellulose acetate, with water being preferred. Aqueous solutions, alcohols and combinations thereof have been used with satisfactory results, for example methanol, ethanol, propanol and mixtures thereof, dilute aqueous solutions of sodium sulphate, magnesium sulphate and sodium chloride. Leaching can be performed at ambient or elevated temperatures, and ambient temperatures are recommended up to, for example, 80-90 ° C. The preferred leaching procedure is to use a primary and a secondary leaching bath, the first bath at an upper ambient temperature and preferably in the range of about 80-90 ° C for 5-30 seconds and the secondary leaching bath for 1-10 minutes, preferably 2-4 minutes. at ambient temperature. As a guide to the choice of optimal pre-leaching temperature for the production of fibers having the desired water transport rate, it has been found that when the percentage of cellulose acetate content increases between 41% and 50%, the water transport rate decreases. relative cellulose fibers, slower, when the leaching temperature increases from about 20 ° C up to about 80 ° C. The increase in leaching temperatures between about 50 ° C and 90 ° C tends to increase the transport permeability of the fibers to urea, creatinine and other low molecular weight solutes up to and including vitamin B12.

After the fibers have been leached and the desired permeability has thereby been established, the conversion of the fibers to a dry form requires softening again with glycerin or its equivalent. Re-softening is preferably carried out with an aqueous / glycerin solution which may satisfactorily contain from about 30% to about 60% by weight of glycerin, with good results being obtained with 50% aqueous solution of glycerin. glycerin. For example, when the glycerin concentration in the softening solution is reduced below about 50%, the water transport rate also decreases. As indicated in Fig. 2, after softening, the fibers can be dried by passing them through a conventional drying oven or by some other means, such as by vacuum removal. A portion of the glycerin may, optionally, be removed by blowing with air, the fiber bundle being passed through or past a set of opposing air knives at such pressures and so many times that the glycerin content of the fiber is reduced.When the glycerin content is reduced by drying or vacuum or increasing air blowing pressures from about 6.9 kPa to about 41 kPa result in a reduction in the transport capacities of the resulting fibers with respect to both the water and the substances dissolved in the blood.Typically satisfactory drying conditions are about 40 ° C to ao ° c for 1-6 minutes, at longer drying times above 60 ° C the transport speeds of the solutes decrease, so that re temperatures should be used to optimize the ratio between abducted substances and abducted water during intermittent hemodialysis. The improved cellulose acetate fibers of the invention, which can be prepared from the above-described melt-spin compositions using the described process steps and the described selected conditions during these steps, possess such a combination of properties with respect to the transport of water and dissolved substances which distinguish them from the hitherto known cellulose acetate hollow fibers. The properties of the fibers according to the invention are most suitably expressed as coefficients. The water transport permeability is expressed as the ultrafiltration coefficient, KUFR, and is in the range of about 2-6 mm / h m2 mm Hg pressure difference between the opposite sides of the membrane wall. The KUFR coefficient gives a number that is representative of the ability of the semipermeable fiber to pass water per unit of the pressure gradient across the effective membrane area. The effective membrane area is the exposed part of the surface area of the semipermeable wall of the hollow fibers, which part is in contact with the fluid and through which part water transport can take place, for example per m2 or other selected area.

The transport permeability of solids is expressed as the total diffusive mass transport or dialysis coefficient of the membrane, Km. The dialysis coefficient 10 Km gives a number representative of the ability of the semipermeable cellulose acetate fiber to separate a dissolved component, or solute in a fluid on one side of the semipermeable wall of the fiber and transport or pass this component to another fluid. in contact with the opposite side of the same wall surface, f as a function of the effective area of the semipermeable membrane and the concentration of the dissolved substance in the two fluids on the opposite sides of the semipermeable wall. Although the rate at which solute is transported from the blood to the dialysate is V critical as it is the limiting variable which determines the minimum time required for complete hemodialysis with an artificial kidney containing the cellulose acetate fibers of the invention, and this. Rate can be determined by "clearance" for each solute expressed in ml of solute per minute, Km gives a number indicating the ability of the fiber to pass solutes as a function of the molecular size, wk, or weight. of the solute, and the units for Km are cm per min. "Clearance" refers to the number referred to as KIU, for renal urea clearance, or KrCr, for renal creatinine clearance, in ml / min, as defined in Chapter 41 by Frank A. Gotch in volume II of the dissertation "The Kidney". For the improved fibers of the invention, the membrane coefficient of urea, Kurea, is in the range of about 0.015-0.045 cm / min; membrane coefficient for creatinine, Ccreatinine 0.013-0.027 cm / min; and the membrane coefficient for vitamin, is in the range of about 7sovs16-s 10 10 25 25 Bö 14 2, is in the range of about 0.02-0.05 cm / min. The ratio B 12, KB 10 0 between the dialysis coefficient of the membrane, Km, and the ultrafiltration coefficient, KUFR, is above about 3: 1, based on the above-mentioned ranges of coefficients and on the above-mentioned units. For hemodialysis, the preferred combination of the ability to transport water and solute is a KUFR value in the range of about 3-5 ml / h m2 mm Hg, a Kurea value above about 0.020 cm / min and a ratio of On; Kurea / KUFR tion of artificial kidneys of the general type exceeding 5: 1. Such fibers can be engineered by Cordis Dow Corporation, which significantly reduce the time required for hemdialysis treatment and provide flexibility and convenient monitoring during hemodialysis, compared to artificial kidneys with commercial semipermeable cellulose fibers, made in accordance with U.S. Pat. No. 3,546,209. In relation to such artificial kidneys, which typically give a KUFÉ value of less than about 1 ml / h m2 mm Hg when operating at ambient temperature, the rate of water removal from blood, which is dialyzed with artificial kidneys, has the same effective area for the the new cellulose acetate fibers of the invention under similar conditions are two to six times as high. Although a KUFR value of - ~ over 6 may require replacement of some of the removed water.before the treatment reaches its preselected water content at the end of the hemodialysis, a higher water removal rate offers some advantages in terms of ease and flexibility and monitoring. during dialysis. In addition, artificial kidneys, which use cellulose acetate fibers with the coefficients defined above with respect to solute, per m2, allow faster removal of blood-soluble substances, such as urea, creatinine, uric acid, etc. For example, artificial kidneys with .. 1 mg effective area of the cellulose acetate fibers of the invention, which fibers have coefficients in the above range, typically a urea "clearance" in the range of about 100-165 ml / min, a creatinine "clearance" in about council about 80-135 ml / min and a B12 clearance within the range of about 15-45 ml / min.

This invention provides an area for spin compositions and variable process parameters in the production of the fibers according to the invention, which compositions and parameters make it possible to select and produce cellulose acetate fibers with optimal KUFR and Km values relatively easily and to produce artificial fibers with the aid of these fibers. kidneys, which are adapted to special patient needs. By using special melt spinning compositions and by selecting suitable process parameters, it is relatively easy to produce cellulose acetate fibers according to the invention at any desired rate of removal of water and solutes within the ranges indicated above. Thus, it should be apparent that the improved cellulose acetate fibers of the invention provide a convenient means of easily and conveniently producing a family of artificial kidneys which offer monitored and preselected rates for simultaneous removal of water and solutes during hemodialysis. The following examples specifically illustrate the presently best method of preparing the novel cellulose acetate fibers of the invention and also serve to further exemplify the effects on KUFR and Km 2 as a function of the melt spin composition, and the degree of cold drawing to which the fibers are subjected during treatment. - lingen; these examples also illustrate typical fiber transport properties which characterize the improved cellulosic fibers of the invention.

Examples 1-9 Three batches of cellulose acetate fibers were prepared using different melt spinning compositions. The first composition contained, by weight, 43% cellulose acetate and 57% polyethylene glycol having a molecular weight of about 400; the second composition contained 43% cellulose acetate, 50% polyethylene glycol having a molecular weight of about 400 and 7% glycerin; and the third melt spinning composition contained 43% cellulose acetate, 39% polyethylene glycol with a molecular weight of about 400 and 18% glycerin. The same cellulose acetate material was used in each of the three melt spinning compositions and was obtained from Eastman 'Chemical Products, Inc., Kingsport, Tennessee, designated CA-400-25, which cellulose acetate has an approximate ethylene content of 39.92; according to Asim Method _ D-871-72 and a viscosity, measured with falling ball, of 17-35 s according to ASTM Method D-1343. The polyethylene glycol in each of the melt spinning compositions was USP Grade PEG E-400 from The Dow Chemical Company and the glycerin was USP Grade from The Dow Chemical Company, Midland, Michigan. Each batch was prepared by carefully mixing the powdered cellulose acetate with the polyethylene glycol) and with the glycerin, in a standard Hobart laboratory mixer by slowly adding the liquid ingredients while rotating the mixer. After uniform mixing, the mixture is introduced into the feed zone of a heated extruder maintained at about 199 DEG C., and the extruded mass is forced through a multi-hole spinneret equipped to supply air through the center of each spinneret. thus forming hay fibers. i i g Three spools of fiber were prepared from each batch. by varying the uptake conditions between the spinnerets and the flushing. A first spool of non-cold formed or stretched fibers was formed by passing the fibers through air to a first and a second set of whales or reels, which had the same speed. A second spool of fibers was formed by controlling the speed of the second set of rollers so that they rolled 10% faster than the first set of rollers and a third spool of fibers was formed by the second set of rollers 20% faster. rotate than the first set. The nine fiber coils thus obtained were used to determine the water and urea transport coefficients in a laboratory test apparatus for the fibers as follows. The test apparatus consisted of a fluid reservoir provided with a magnetic stirrer, and a dialyzer test cup, provided with a magnetic stirrer, and a top closure plate with pressure couplings and connections for receiving the ends of the casting sleeves, which were attached to each end of a fiber bundle containing between 160 and 192 fibers per bundle. The fiber bundle was bent into a U-shape and inserted into the beaker and connected to the closure plate; one sleeve was connected by means of a fluid line to a pump * connected by one line to the reservoir, and the other sleeve was connected by means of a return line to the reservoir, so that fluid could be pumped from the reservoir under adjustable test pressure through the openings in the fibers, which were placed in the dialysis cup l5. The beaker was also provided with dialysate inlet and dialysate outlet connections, and during the experiments the fibers were immersed in a surrounding stirred pool of either water for the KUF K test. urea The water transport coefficient KUFR, was determined by the R-test or by water-urea solution to pump water under pressure through the fibers and measure the increase in the volume of water outside the fibers in the dialysis beaker, the test being performed at 21 ° C. KUFR was then calculated for each test, using the fibers identified in Table I - 25, in ml / m2 h mm Hg according to Table II.

The urea coefficient, K, was determined by creating a pool of water in the supply reservoir and pumping it through the fiber orifices, the pool surrounding the fibers in the dialysis beaker initially being a water-urea solution. Measurements were performed to determine the urea concentration in the recirculating liquid at certain time intervals. The experiments were performed at 21 ° C and there was no pressure difference across the fiber wall surface during the experiments. The urea coefficient, K, was determined by taking into account the difference in the concentration of urea in the supply reservoir and in the dialysis cup on the outside of the fibers as a function of time and the fiber area in accordance with '? 8-0'7_51_6 ~ É 10 15 20 t 18 the following equation: Kl N> = KšREA. A (C1 - C2) where N represents the flune across the membrane in mol / min, C1 is the initial urea concentration, C2 is the final, or measured concentration and A is the area of the fiber wall or membrane between the two solutions.

In a two-chamber system without a pressure difference or resulting ultrafiltration, the transfer of urea across the membrane wall can be integrated over a time interval, t, according to the following equation: in (C1-C2) t = ° _ (V1 + V2) A Kg _ '"_ "_ (Cl _c2) 1 = (" "“ "" "_vl V2) uREA-t, where Vi is the volume of the solution in the supply reservoir .and V2 is the volume of the solution in the dialysis beaker.

In the tests or experiments, the volumes V1 and V2 As well as the area A are constant, so that a plot of the values on each side of the integrated equation gives a straight line, the slope of which enables the calculation of Kurea in cm / min. The values thus obtained for the nine fiber packages are given in Table II in the column designated KUREA, š% h'x 10-3. _7807516'5 19 Qåuouh fl wv Houoñmwnwdx fl fwå Nma, Soïmómmv Hmwwämmc fi øx fl wñ Nam. 8793148 m mm nam .ÄN mÄm www mHN Mon mmm * ÄH Huëæ fl om. Nme n un mumm G fi nwum fl wv Hmuoñwwc fi dx fl f fi NN: ëïwåmmv HouwEm fi âdxøwñ Now _ Sïooqëov m mm .ÄN maa qow m2 .. m2 m§m cøw mw fi uwa fi om Nmw Nvu uv mum f. QS m5 Hwe fi om Nmq. H »G wumm 33 9.3 2.3 sm." Xu fl xm fi Ißuo wa lxuo nu Ixoo Û | A193 9: a EE .. Tåb. Aaö 2.3 .. Tâu Aaš Aaš w fi cva fl m lnämüv .min .då 13295 .må .wïw ... nEuEv 6. » .wim mumm | wwm> xo al uoum zw al uouw | MWM> SSM fi Ucum xu fi uoum | wwm> Mm f uouw Mm f uouw do fi Åm ... Huwmä, nwmß f m Iuun f w l f uwwz uumnÉ ... nm al substance l fl wwuz nuwn f m L f wn f m lomäox fi øwmm H QAmE wm _ 780751645 20 mo.m m fi. AEH mm. <mm.m ~ m.ß ~ «om mß.mw« .- H @. <A flfl umoæ fi mv HuwwB.dx = fl E Nw fi ^ o ° «» m | wmmv H «¶@e.=x=ma Mmm 7 ^ m ~ | oo «| Qwaw fi om Nnq m ud wumm mm.m om.-« H. «mcwm mm ~« @. «@«. «@ ~ .m ~ w fi. m Ac fl nwuh fl wv HmwwE.cx:HE Nß ^ Qo« | m | ww ~ v H @ w @ s.øx: «a Non ^ m ~ | o °« | HUENHON NÜQ N Hc mumm «em w« .m mm.o Næ.m mm.- Ho. @ Aooqfwzummv HmuwE. : x: wa Nßm ^ m ~ | oo «| uwe flfi om Nm« H nu wumm MMDM .u: «øwmhn.NoN Må udm fi omk fi NCH mm EE NE s .HE MWDM MMDM dmmbz .pH-HE muo fi x1mw: mf wdwcwmu fi wo fl wo fl NE S then Mmø fl mumw co fl uwm | omEox = ø «mm HH¶qAwm <@

Claims (10)

10 15 20 25 30 7807516-5 21 PATENT REQUIREMENTS Cellulose acetate hollow fiber, for use, for example, in artificial kidneys, characterized in that it has an inner diameter of about 100-350 μm and a wall thickness of about 20-60 μm, which wall has a selective permeability in hemodialysis for water. and solutes to be removed from blood, which permeability is represented by an ultrafiltration coefficient in the range of about 2-6 ml / h m2 mm Hg and a urea coefficient in the range of about 0.015-0.045 cm / min. Fiber according to claim 1, characterized in that the selective permeability is also represented by a creatinine coefficient in the range of about 0.013-0.027 cm / min. Fiber according to claim 2, characterized in that the selective permeability t e c k n a d is also represented by a vitamin B 12 coefficient in the range of about 0.002-0.005 cm / min. The fiber of claim 1, wherein the ultrafiltration coefficient is about 5-6 and the urea coefficient is in the range of about 0.030-0, 4s. The fiber of claim 2, wherein the creatinine coefficient is in the range of about 0.020-0.027. Fiber according to any one of claims 1-5, characterized in that it is prepared from a melt-spinning composition, which consists essentially of about 41-50% by weight of cellulose acetate, preferably mainly cellulose diacetate, about 2-20% by weight of glycerin and the remainder polyethylene glycol having a molecular weight of about 150-600. Fiber according to claim 6, characterized in that it is produced from a melt-spinning composition consisting essentially of about 42-47% by weight, most preferably 42-44% is within the range of the specification -% by weight. , cellulose acetate, about 3-10 weight, preferably 6-a vixtí, 10- 15 _20 vso? s1e-s _. - 22 glycerin and the remainder polyethylene glycol with a molecular weight 0 in the range about 150-600. 8. A method of making cellulosic acetate hollow fibers, having the following steps: (1) providing an intimate mixture of about 41-50% by weight of cellulose acetate, about 2-20% by weight of glycerin, and about 30% by weight. 57% polyethylene glycol with a molecular weight in the dm range about 150-600. (2) that half-fibers are produced from a molten mass of said mixture, (3) that the fibers are cooled, (4) that the fibers are cooled to an extent which is in the range of about 2-20% of the cooled fiber length, (5) that the fiber is leached for removal from that of the polyethylene glycol and glycerin, and (6) the fiber is softened again with glycerin and then dried. of 9. A method according to claim 8, characterized in that the cellulose acetate in the mixture constitutes about 42-47% by weight. 0 10. A method according to claim 9, characterized in that the cold drawing amounts to about 10-152 of the length of the cooled fiber.