CH632536A5 - HOLLOW FIBER OF CELLULOSE ACETATE AND PROCESS FOR ITS MANUFACTURE. - Google Patents

Description

The present invention relates to a hollow and semi-permeable fiber of cellulose acetate, useful in artificial kidneys, as well as its method of production.

Cellulosic esters, and in particular cellulose acetate, have already been put in the form of hollow semi-permeable fibers, and have been used as separation membranes in various processes including desalination of seawater, ultrafiltration. aqueous and non-aqueous solutions, ion exchange operations, concentration of salts, purification of spent streams and the like. Permeable separation membranes prepared from film-forming cellulose esters are described, for example, in numerous patents from the United States of America, the most interesting of which appear to be United States patents Nos. 3532527 and 3494780. The aforementioned patents describe a process for spinning in the melt state of cellulose esters, in particular of triacetate and acetate, from a spinning composition in the melt state which contains a compatible plasticizer of the tetramethylenesulfone type, described by example in United States patents Nos. 2219006,2451299 and 3423491, and a polyol whose molecular weight is between about 62 and 20,000. The weight ratio of the sulfolane plasticizer to the polyol in the mixture is indicated as varying between about 0.66 / 1 and 5/1 and, preferably, between about 0.8 / 1 and 1.3 / 1. The role indicated by the variation in the relative proportions of the materials is the modification of the ability of the fibers to separate salt from sea water.-Such fibers, prepared by implementing the methods of the aforementioned patents Nos. , although useful for the desalination of seawater, are not satisfactory in hemodialysis in the form of hollow fibers in artificial kidneys.

Cellulose acetate membranes in various shapes have been the subject of extensive research, funded by The National Institutes of Health and The Office of Saline Water since the mid-sixties. The National Institute of Arthritis and Metabolie Diseases has also funded research into the modification of known hollow fibers of cellulose acetate to assess the potential for use in artificial kidneys. A three-year study of this type, with the primary objective of developing an artificial kidney containing hollow fibers of cellulose acetate, was carried out by The Dow Chemical Company, Western Division Research Laboratories in 1971-1973 , under the NIH contract N ° 70-2302. As part of this contract, cellulose acetate fibers were prepared by melt spinning a mixture of cellulose acetate and triethylene glycol, and some of the fibers obtained were incorporated into artificial kidneys and studied clinically in hemodialysis. The best artificial kidneys that have been made as part of this project, although they are satisfactory because they can be safely used for dialysis of a number of patients in a clinic, during trials, n '', however, have not been satisfactory because their transport properties by circulation in the same direction, when removing water and low molecular weight solutes such as urea and creatinine, are not as good as those of artificial kidneys at present. available and having hollow cellulose fibers; the problem with these kidneys is that the rates of water withdrawal are too high and the ratio of blood solute to water withdrawn is too low, so the study was abandoned.

Since the early 1970s, when hollow fiber artificial kidneys were first marketed by Cordis Dow Corp. in the United States of America, the hollow fibers of these artificial kidneys were formed almost exclusively of cellulosic fibers. Fibers are the product formed either by the cuproammonium process or by the process described in United States Patent No. 3546209. Although hollow cellulose fibers have an important market because they currently constitute the best form of semi-permeable membranes for artificial kidneys, specialists know that many production problems return during the spinning in the molten state of such fibers and their incorporation in artificial kidneys without leaks. Thus, the tensile strength of the fibers is relatively low, and the breaking of the fibers makes handling during the treatment of the fibers and assembly in a dialysis chamber both complex and difficult. Given these difficulties presented by cellulose capillary fibers, one always seeks semi-permeable capillary fibers which are inexpensive, of easy spinning from molten materials and which can form artificial kidneys on an industrial scale, these fibers having to be able to remove solutes from the blood such as urea, creatinine, uric acid and water, with flow rates higher than those which characterize the cellulose hair fibers currently used.

The invention therefore relates to a hollow fiber of cellulose acetate having better properties than the hollow fibers of cellulose and of cellulose ester of known type, having selectively adjustable permeability characteristics which make possible the production of artificial kidneys containing such fibers, and giving discharges of water and solutes which are greater than those which characterize the current artificial kidneys of the trade containing hollow cellulose fibers. The invention also relates to a process for producing such cellulose acetate fibers.

More specifically, the invention relates to hollow and semi-permeable fibers of cellulose acetate having a combination of permeability and discharge characteristics, for water and blood solutes whose molecular weight is less than about 1400, which are variable with respect to each other and adjustable in order to give the optimal operating characteristics when they are used in an artificial kidney, during hemodialysis. The

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Optimal operating characteristics for an artificial kidney are a high rate of discharge of the solutes of the blood used compared to the rate of withdrawal of water, so that the purification of the blood which protects health can be carried out in a minimum time.

The new fibers according to the invention are prepared from a new spinning composition in the molten state. This composition allows the dry spinning of cellulose acetate, air cooling and winding on rollers without prior extraction of materials. This composition is a mixture of cellulose acetate, of certain proportions of polyethylene glycol, having a molecular weight of between approximately 150 and 600, and glycerin; this composition can be spun in the molten state in the form of hollow fibers whose mechanical strength and ease of use in artificial kidneys are superior to the corresponding properties of cellulose fibers, with however a favorable combination of characteristics of permeability of the water and blood solutions. These permeability characteristics are further improved and optimized by treatment of the fibers spun during certain treatment stages, adjusted according to the spinning. The permeability of these fibers can be modified and regulated by modifying the relative amounts of each of the three constituents of the composition, and the optimization of the ratio of discharges of the low molecular weight solute from blood and water is obtained when the composition is adjusted as a function of controlled cooling and a controlled degree of cold drawing or elongation of the spun fiber immediately after cooling and before the spun fiber is removed from the glycerin or polyethylene glycol from the cooled fiber. Dry spinning, in air, at room temperature and the appropriate setting of cold drawing, as well as the careful selection of the amounts of each of the constituents in the composition make it possible to form cellulose acetate fibers having a selected combination of discharge properties and increased ratios of solute and water discharges compared to those of currently known hollow fibers of cellulose acetate.

The family or spectrum resulting from fibers constitutes a product according to the invention.

The method of the invention comprises steps ensuring the adjustment and the correlation of the melt spinning composition and the cooling of the spun fibers, with the importance of cold drawing and the conditions of separation and drying, so that the cellulose acetate fibers have the desired permeability.

Other characteristics and advantages of the invention will emerge more clearly from the description which follows, given with reference to the appended drawings in which:

fig. 1 is a ternary diagram representing the proportions of the three constituents combined in the compositions according to the invention, as indicated by the area indicated by the points A, B, C and D, and FIG. 2 is a block diagram illustrating the various steps used for the treatment of the compositions corresponding to the area indicated in FIG. 1, during the formation of a family of hollow cellulose acetate capillary fibers according to the invention.

We first consider the spinning composition in the molten state.

This composition contains, in weight percentages, 41 to 50% approximately of cellulose acetate, 2 to 20% approximately of glycerin and the remainder of polyethylene glycol whose molecular weight is between approximately 150 and 600. As indicated in fig. 1, this family or spectrum of compositions with three constituents is found in the area delimited by the extreme values giving the area indicated by points A, B, C and D. Any composition comprising an amount of each of the three constituents corresponding to the zone A, B, C, D of fig. 1 is suitable for spinning in the molten state in the form of hollow capillary fibers; after cooling, separation, by water, of glycol and glycerin and put in the form of an artificial kidney of known type, the fibers have a behavior as good or even better than that of the cellulose fibers currently used and formed by implementation of the cuproammonium process or of the process described in the aforementioned United States patent No. 3546209. Particularly advantageous compositions for optimizing the operating characteristics, for certain patients undergoing intermittent dialysis, are indicated in fig. 1 by zone E, F, G, H.

The three constituents, cellulose acetate, ethylene glycol and glycerin, have long been used separately in membranes, and cellulose acetate has been combined with a polyol, such as glycols, in compositions which also contain a plasticizer or solvent for cellulose acetate, for example of the sulfolane type, as indicated in the aforementioned patent of the United States of America No. 3532527. However, it was not known that glycerin, which is not a solvent for cellulose acetate at room temperature, could be used, in combination with selected glycols of low molecular weight, for the formation of resistant hollow fibers having modified permeability characteristics compared to those obtained in the presence of a sulfolane type solvent; similarly, it was not known that certain proportions of glycerin in these compositions allowed the modification and regulation of the transport of the low molecular weight solute through the wall of the fiber, compared to the transport of water through the same wall.

The term cellulose acetate used herein refers to cellulose diacetate. This, as it is commercially available in the United States of America, is suitable for use according to the invention and it is advantageous although certain amounts of monoacetate and triacetate may be present, for example up to about 25%, smaller amounts being normally present in commercial cellulose diacetate.

When cellulose acetate is dissolved in a solvent such as dimethylsulfoxide, sulfolane, triethylene glycol or other low molecular weight glycols which are liquid at room temperature, and when it is spun by a conventional die by forming a wick of fibers, individual fibers tend to stick or weld when taken from a core. Such fibers, even when cooled below the gelling point and hardened as solid fibers, retain a certain amount of solvent which apparently maintains superficial areas sufficiently soft to stick during the sampling. Hitherto, the solvent has had to be removed from the spun and cooled fiber before removal, and a hot water bath has been used for this purpose ensuring leaching or separation of the solvent. However, it is found that the hollow capillary fibers, transmitted just after cooling in a leaching bath, subject the fibers to large pulses and cause a defect in uniformity of the thickness of the walls and of the internal diameter. It is further noted, according to the invention, that the welding of the fibers can be avoided, without leaching before removal from cores, by the use of a low molecular weight glycol in the form of an acetate solvent cellulose, modified by the specified amounts of glycerin. Apparently, the glycerin reduces the surface softening effect of the glycol and the fibers can be wound and even stretched and wound on tensioned webs without gluing or welding. The resulting spun fibers have excellent uniformity in wall thickness and internal diameter and can be stored indefinitely at room temperature on cores for further processing in artificial kidneys.

Glycerin also apparently alters the gelling of cellulose acetate upon cooling, so that the resulting porosity of the fiber wall is altered. When the glycerin is present in the spun composition, as indicated above, a gelled fiber is formed and has sufficient strength to maintain its integrity and, practically, its uniformity in wall thickness and internal diameter during elongation or cold drawing immediately after gelation or solidification, as described in detail below with reference to cold drawing. It is noted that, surprisingly, this cold drawing also modifies the porosity of the wall of the fiber so that the blood solutes, having a low molecular weight, pass more easily through the wall, coming from the blood circulating at inside the fiber, to a dialysate solution flowing outside the fiber. A significant increase of one

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such transport of solutes, that is to say solutes whose molecular weight can reach 1400 and which cover urea, creatinine, uric acid and other bodies such as vitamin B12 and other vitamins , is obtained without increasing the transport of water through the same fiber wall. Although the mechanism of this modification, following cold drawing, is not perfectly understood, it can be seen that the importance of cold drawing and the amount of glycerin present in the spinning composition are related and depend on each other. In general, when using a composition which contains cellulose acetate dissolved in a polyethylene glycol of molecular weight between about 150 and 600, with at least about 2% glycerin, an increase in the transport of solutes blood appears when cold drawing increases to 20% of the length of the spun fiber. This increase continues as the glycerin content increases, but the relationship is not perfectly linear; when the proportions of glycerin in the composition are between 3 and 10% and when those of the cellulose acetate are between about 42 and 47%, the polyethylene glycol forming the remainder, the improvement of the transport ratio of the solute and of water is obtained when the cold drawing increases to 15% of the length of the spun fibers and, for 43 to 45% of cellulose acetate, excellent results are obtained for approximately 10%. The maximum increase in the ratio of solute and water transport is obtained with the compositions included in the advantageous zone E, F, G, H of FIG. 1, and the optimum cold drawing can be easily determined for the composition chosen from a few simple tests.

We now consider the treatment of hollow fibers using the spinning composition in the molten state.

As shown in fig. 2, the method comprises the formation 10 of the aforementioned composition, the spinning in the molten state of hollow fibers and their cooling 12 in the gelled and coherent state, then the elongation or cold drawing 14 of the fibers. These can be stored or several wicks can be consolidated into a bundle of fibers having, for example, 3000 to 30,000 fibers, for further processing before mounting in artificial kidneys. The fibers of a consolidated bundle pass through a leach tank 16 which removes the glycol and glycerin, with the formation of a bundle of semi-permeable hollow fibers. The attacked bundle is then replastized at 18 with a solution of glycerin in water, the excess glycerine is removed at 20 and the fibers are dried 22. The dried fibers constitute the product 24 according to the invention.

The formulation of the spinning composition can be carried out in any convenient manner using conventional mixing equipment, the important characteristic being that the mixing is sufficient to obtain great uniformity. For example, the dry cellulose acetate powder is mixed with a weighed amount of polyethylene glycol and glycerin in a Hobart mixer with high shear gradient; the mixture is then homogenized and remixed by introduction into a twin-screw extruder which is heated, the two screws rotating in opposite directions, the extruded molten material then being expelled by a die having for example 16 to 32 holes, of the type comprising a conventional gas supply device which is intended to inject a gas into the core of the extruded material. An advantageous gas for this purpose is nitrogen, but other gases can give satisfaction, in particular carbon dioxide,

air and other harmless gases. The extruded material from the die undergoes cooling, for example in an air stream of variable force and / or temperature, so that the extruded material undergoes gelling and solidification in the form of solid coherent fibers. For example, the fibers have a capillary dimension, that is to say that their internal diameter is between approximately 150 and 300 (x, and their wall has a thickness of 20 to 50 dd. Although the fibers according to l are particularly suitable for hemodialysis in artificial kidneys, the advantages of dry spinning and the formation of fibers which can be taken from support cores without prior leaching are also applicable to fibers intended for other applications such as than ultrafiltration, etc. These other fibers must have an external diameter of between approximately 350 and 400 µm, and a wall thickness of between approximately 10 and 80 (i.

During the process according to the invention, the short period following the exit of the material extruded from the orifices of the die is very important for obtaining the desired permeability in the fibers produced. During this period, the porosity and thus the permeability of the fiber are determined both by the cooling rate and by the cold stretching or drawing to which the fibers are subjected. The porosity, for a given composition, increases,

io for a given tension prevailing in the fiber, by a very significant cooling of the molten fiber, taking into account the porosity obtained after a less rapid cooling or a slower gelling of the extruded material in the form of fibers. The increase in porosity obtained by this cooling normally has an effect on the ability of the fiber to transport water and can be used, if necessary, for the modification or prior selection of the ultrafiltration rate of the fiber. resulting when used in hemodialysis. The increase in the air flow rate at room temperature over the extruded material allows small adjustments to the porosity of the fiber; similarly, a similar effect can be obtained by lowering the temperature of the cooling material, or both parameters can be adjusted so that the conditions are optimal. It is advantageous for cooling to be ensured by air at room temperature, and industrially satisfactory results are obtained without cooling below room temperature.

The elongation or cold drawing is carried out satisfactorily by passing the extruded and solidified fibers over a series of rollers, or distant series of rollers, for example Bucket rolls; the desired cold drawing can be obtained by adjusting the speed of rotation of the second roller or of the second group of rollers, along the axis of circulation of the fibers. A good correlation between the degree of cold drawing of the fibers and the measured or preset speed of rotation of the downstream set of rollers is usually obtained and, for a particular desired percentage of cold drawing, it is sufficient that the speed of rotation of the downstream set of rollers is precisely adjusted with respect to that of the upstream set of rollers. Sampling or winding of cold drawn or elongated fibers on webs or rollers can be carried out with commercially available .40 winders, such as Leesona winders, taking care that a slight tension is applied to the fibers during collection.

In an advantageous embodiment of the invention, several rolls or cores of cold-drawn fibers are mounted so that several strands of fibers pass through a conventional gathering device which forms a consolidated bundle, the consolidated fibers then undergoing leaching which removes glycerin and polyethylene glycol. The leaching treatment can be carried out in any convenient manner, for example by passing the bundle of 50 fibers through a bath of a chosen solvent, or by semi-continuous immersion of the cores or rolls in such a solvent. The leaching solvent can be chosen from the materials which constitute good solvents for the plasticizer and glycerin and bad solvents for cellulose acetate, water being advantageous. Aqueous solutions, alcohols or combinations, for example methanol, ethanol, propanol and mixtures thereof, dilute aqueous solutions of sodium sulfate, magnesium sulfate and sodium chloride are used satisfactorily . Leaching can be carried out at room temperature or higher, temperatures 60 above room temperature being recommended up to 80 to 90 ° C for example. The most advantageous leaching process uses a primary bath and a secondary leaching bath, the former having a temperature above room temperature and preferably between 80 and 90 ° C, the fibers remaining there 65 for 5 to 30 s, while the secondary leaching lasts 1 to 10 min and preferably 2 to 4 min at room temperature. As a guideline for the selection of the optimal temperature of the primary leaching intended to give fibers having the desired flow rate of water transport,

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it is noted that, when the percentage of cellulose acetate goes from 41 to 50%, the water transport rate, compared to the cellulose fibers, decreases more slowly when the temperature of the leaching material goes from about 20 at about 80 ° C. Increasing the leaching temperature between about 50 and 90 ° C tends to increase the permeability of fibers to transport urea, creatinine and other low molecular weight solutes, up to 'with vitamin B12 included.

When the fibers have been leached and when the desired permeability has been established, the conversion of the fibers to dry form requires further plasticization with glycerine or an equivalent compound. This new plasticization is preferably carried out with a solution of water and glycerin which can contain, satisfactorily, about 30 to 60% of glycerin by weight, good results being obtained with an aqueous solution of 50% of glycerin.

For example, as a guideline, when the glycerin in the replastification solution has a concentration that decreases below about 50%, the water transport rate also decreases. As shown in fig. 2, after replastification, the fibers can be dried by passing them through a conventional drying oven or in any other way, for example by vacuum removal. A part of the glycerin can also possibly be removed by forced circulation of air, the bundle of fibers passing through a clearance of the air core placed opposite, at pressures and for times which cause the reduction of the glycerin content present in the fiber. When the glycerin is reduced by drying, or under vacuum, or by increasing the supply air pressure from approximately 0.07 to 0.42 bar, there appears to be a reduction in the water and solute transport capacities in the resulting fibers. For example, satisfactory conditions for drying are approximately 40 to 80 ° C, for 1 to 6 min; for longer drying times, above 60 ° C, the solute transport rates decrease and therefore lower temperatures must be used so that the ratio of solute transport to water removed during hemodialysis by intermittence is optimal.

The hollow fibers of cellulose acetate according to the invention, which can be formed using the above-mentioned melt spinning compositions, during the indicated steps and with the conditions indicated, have a combination of transport properties water and solute transport which distinguishes them from the known hollow fibers of cellulose acetate. The determining properties of the fibers according to the invention are most conveniently indicated in the form of coefficients. The permeability of water transport is expressed in the form of the ultrafiltration coefficient KUFR, and this coefficient is between approximately 2 and 6 mm / h • m2 • Torr of pressure difference between the two faces of the membrane. The KUFR coefficient represents a number corresponding to the ability of the semi-permeable fiber to transmit water per unit pressure of the gradient in the effective area of the membrane. This effective zone represents the exposed part of the semi-permeable wall of the hollow fibers in contact with the fluid and which allows the transport of water, for example, per square meter or any other surface unit.

The transport permeability of the solute is expressed by the overall mass transfer coefficient by diffusion or dialysis of the membrane Km. This coefficient is a number representative of the ability of the semi-permeable cellulose acetate fiber to separate a constituent dissolved, or solute, in a fluid placed on one side of the semi-permeable wall of the fiber, and to transport or allow this constituent to pass to another fluid which is in contact with the other face of the same wall, as a function of the effective surface of the semi-permeable membrane and of the concentration of the solute in the two fluids placed on either side of the wall. Although the transport rate of the solute from the blood to the dialysate is extremely important as a limiting parameter which determines the minimum time necessary for complete hemodialysis with the artificial kidney containing the hollow fibers of cellulose acetate according to the invention, and although the flow can be determined from the discharges of each solute,

expressed in cubic centimeters of solute per minute, the coefficient Km represents a number indicating the ability of the fiber to transmit solutes according to their mass or their molecular size, Km being expressed in centimeters per minute. The discharge represents a KrU number in the case of renal urea discharge, or KrCr for the renal creatinine discharge, in cubic centimeters s per minute, as indicated in chapter 41 in volume 2 of the book by Frank A. Gotch, "The Kidney". In the case of the excellent fibers according to the invention, the coefficient of the membrane for urea (Kurée) corresponds to a range of approximately 0.015 to 0.045 cm / min, the coefficient of the membrane for creatinine (Kreatinine) is included. between about 0.013 and 0.027 cm / min, and the membrane coefficient for vitamin B12 (KBi2) is between about 0.002 and 0.005 cm / min. The ratio of the dialysis coefficient of the membrane Km to the ultrafiltration coefficient KUFR exceeds approximately 3/1, given the ranges indicated for the aforementioned coefficients 15 and the units given for each.

In the case of hemodialysis, the most advantageous combination of water and solute transport properties corresponds to a Kufr value of between approximately 3 and 5 cm3 / h • m2 • Torr, with a Kurée coefficient greater than approximately 0.20 cm / min and a Kurée / 20 Kufr ratio greater than 5/1. Such fibers make possible the construction of artificial kidneys of the general type manufactured by Cordis Dow Corp. which significantly reduces the time required for hemodialysis treatment, and provides great flexibility and ease of adjustment during hemodialysis compared to commercial hollow fiber artificial kidneys having fibers of the type manufactured by the process described in the aforementioned patent of the United States of America No. 3546209. Compared to such artificial kidneys which give a KUFR coefficient of less than 1 mm / h • m2 • Torr, when operating at room temperature, the flow of the withdrawal of water from the dialyzed blood by the artificial kidneys, for the same effective surface and with the cellulose acetate fibers according to the invention, under analogous conditions, is greater by 2 to 6 times. Although a KUFR coefficient greater than about 6 may require replacement of some of the water removed before treatment reaches the predetermined water content at the end of hemodialysis, an increase in the rate of withdrawal of Water has certain advantages in terms of ease and flexibility of adjustment during dialysis. In addition, artificial kidneys with cellulose acetate fibers, whose solute transport coefficients have the values indicated per square meter, 40 allow faster removal of solutes from the blood such as urea, creatinine, l uric acid, etc. For example, the artificial kidneys having 1 m2 of effective surface area of cellulose acetate fibers according to the invention, having the coefficients included in the range indicated, give for example a discharge of urea of between approximately 100 45 and 165 cm 3 / min, a creatinine discharge of between approximately 80 and 135 cm3 / min and a vitamin B12 discharge of between approximately 15 and 45 cm3 / min.

The invention relates to a whole range of spinning compositions and variable processing parameters in the stages used for the manufacture of the fibers, so that the prior selection and manufacture of the cellulose acetate fibers having optimal coefficients Kufr and Km are relatively easy, the fibers being able to form artificial kidneys of predetermined value, satisfying the particular criterion posed by the treatment of patients. The use of 55 particular melt spinning compositions and the selection of suitable processing conditions allow the relatively easy formation of the cellulose acetate fibers according to the invention, simultaneously having the desired flow rates of water withdrawal and of solute, in the ranges indicated above. Thus, the fibers according to “c the invention allow the easy and convenient manufacture of a family of artificial kidneys having regulated and predetermined flow rates ensuring the removal of water and solute during hemodialysis.

The examples which follow relate to the cellulose acetate fibers according to the invention and indicate the effects on the KUFR 65 and Km coefficients of the spinning composition, as well as of the cold drawing to which the fibers are subjected during the treatment. . These examples also indicate the fiber transport properties which characterize the fibers according to the invention.

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Examples 1 to 9:

Three batches of cellulose acetate fibers are prepared with different melt spinning compositions. The first composition contains, in percentages by weight, 43% of cellulose acetate and 57% of polyethylene glycol having a molecular weight of approximately 400, the second composition contains 43% of cellulose acetate, 50% of polyethylene glycol having a molecular weight about 400 and 7% glycerin, and the third composition contains 43% cellulose acetate, 39% polyethylene glycol of molecular weight of the order of 400 and 18% glycerin. The same material based on cellulose acetate is used for the three compositions, this material being available from Eastman Chemical Products, Inc., Kingsport, Tennessee, under the reference CA-400-25, this cellulose acetate having a content in approximate acetyl of 39.9%, determined according to standard ASTM D-871-72, the viscosity determined by falling of a ball being from 17 to 35 s, according to standard ASTM D-1343. The polyethylene glycol of each of the compositions is of USP PEG E-400 quality from The Dow Chemical Company, and the glycerin is of USP quality of The Dow Chemical Company, Midland, Michigan.

Each batch is prepared by thorough mixing of powdered cellulose acetate with polyethylene glycol and with glycerine, in a standardized Hobart laboratory mixer, with slow addition of the liquid ingredients when the paddle of the mixer is rotating. After uniform mixing, the material is introduced into the feed zone of a heated extruder, maintained at approximately 200 ° C., and the extruded mass is expelled in a die with numerous orifices mounted so that air is introduced through the center of each die, so that hollow fibers are formed.

Three spools of fibers are prepared from each of the batches by varying the sampling conditions during spinning and winding. A first spool of fibers, having no cold forming or elongation, is formed by passing the fibers through the air to a first and a second set of rollers rotating at the same speed. A second spool of fibers is formed by adjusting the speed of the second set of rollers to a value which is 10% higher than that of the first set of rollers, the third spool being formed when the second set of rollers has a higher speed of 20% to that of the first game.

The nine spools of fibers thus formed are used for the determination of the transport coefficients of water and urea in a laboratory test apparatus, from the fibers described. The testing apparatus includes a fluid reservoir having a magnetic stirrer, a dialyzer test beaker having a magnetic stirrer, an upper cover plate having connectors and pressure fittings intended to cooperate with the ends of the sleeves. closure attached to each end of a bundle of fibers containing 160 to 192 fibers per bundle. The beam is folded in a U, placed in the beaker and is connected to the closing plate; one sleeve is connected to a fluid line and to a pump which is itself connected to a line which joins the reservoir, while the other sleeve is connected by a return line to the reservoir, so that the fluid of this the latter can be pumped at an adjustable pressure through the lumens of the fibers found in the dialysis beaker. This beaker also has dialysate inlet and outlet connections and, during the test, the fibers are immersed in a stirred pool of water for the KUFR test or of a water / urea solution, placed around the filters for the Kurée test.

The KUFR coefficient of water transport is determined by pumping water under pressure in the fibers and measuring the increase in the volume of water outside the fibers in the beaker, the tests being carried out at 21 ° C. The KUFR coefficient is then calculated for each test, for the fibers indicated in Table I, in cubic centimeters per square meter per hour and per Torr of pressure difference, as indicated in Table II.

The Kurée coefficient for urea is determined by the arrangement of water in the supply tank and by pumping this water into the lumens of the fibers, the liquid surrounding the fibers in the dialysis beaker being initially a solution of urea in water. Measurements are made to determine the concentration of urea in the flowing fluid, at certain intervals.

The tests are carried out at 21 ° C. and there is no difference in pressure on either side of the wall of the fibers during the tests. The Kurée coefficient is determined taking into account the difference in the urea concentrations in the feed tank and in the beaker, outside the fibers, as a function of the time and the surface of the fibers, according to the equation:

N = KuréeA (C, -C2)

in which N represents the flow through the membrane, in mol / min, Ct represents the initial concentration of urea, C2 the final or measured concentration of urea and A the surface of the membrane or wall of the fibers between the two solutions.

In a two-chamber system, in the absence of a pressure difference or of a resultant ultrafiltration, the transfer of urea through the wall of the membrane can be integrated in a time interval t and there is the equation:

RCi-Qj) t = 0 ~ l R ^ + V,) J ^ (C.-Cjtj | _ (V, v2) 'A] Kurée in which V! Is the volume of the solution of the supply tank and V2 that of the solution in the dialysis beaker. During the tests, the volumes Vt and V2 and the surface A are constants, so that the reading of the values on both sides of the integrated equation gives a straight line, the slope allowing the calculation of Kuiée in centimeters per minute The values thus obtained for the nine batches of fibers are indicated in Table II, in the column giving Kurée.

Table I

Spinning composition

Fiber size: internal diameter fr)

Fiber size: external diameter (f *)

Average wall thickness

(V)

Lot N ° 1

43% polymer (CA-400-25)

57% plasticizer (PEG-E-400)

179

260

40.5

Lot N ° 2

43% polymer (CA-400-25)

50% plasticizer (PEG-E-400)

7% plasticizer (glycerin)

185

260

37.5

Lot N ° 3

43% polymer

(CA-400-25) 39% plasticizer (PEG-E-400)

18% plasticizer (glycerin)

174

253

39.5

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Table I (continued)

Spinning composition

Fiber size: internal diameter

(not)

Fiber size: external diameter w

Average wall thickness

W

Lot No 1

43% polymer (CA-400-25)

57% plasticizer (PEG-E-400)

180

261

40.5

Lot N ° 2

43% polymer

(CA-400-25) 50% plasticizer (PEG-E-400)

7% plasticizer (glycerin)

193

273

40.0

Lot No 3

43% polymer

(CA-400-25) 39% plasticizer (PEG-E-400)

18% plasticizer (glycerin)

213

282

34.5

Lot Noi

43% polymer (CA-400-25)

57% plasticizer (PEG-E-400)

180

264

42.0

Lot No 2

43% polymer

(CA-400-25) 50% plasticizer (PEG-E-400)

7% plasticizer (glycerin)

195

274

39.5

Lot No 3

43% polymer

(CA-400-25) 39% plasticizer (PEG-E-400)

18% plasticizer (glycerin)

224

297

36.5

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Table li

0% stretch

Draw 10%

20% stretch

Spinning composition

Kufr cm3

^ urea cm

^ urea kufr cm3

K-urjg cm

KUrea kufr cm3

r, "■ uree cm

Kurée cm3 / h-m2 -Torr min10 "3

kufr cm3 / h • m2 • Torr min10 "3

kufr cm3 / h-m2-Torr min10 "3

kufr

Lot N ° 1

43% polymer (CA-400-25)

57% plasticizer (PEG-E-400)

6.01

22.95

3.82

6.33

21.92

3.46

7.20

24.74

3.44

Lot No 2

43% polymer (CA-400-25)

50% plasticizer (PEG-E-400)

7% plasticizer (glycerin)

5.18

23.29

4.49

4.64

25.3

5.45

4.14

22.90

5.53

Lot No 3

43% polymer (CA-400-25)

39% plasticizer (PEG-E-400)

18% plasticizer (glycerin)

4.61

17.48

3.79

5.04

17.92

3.55

4.93

18.19

3.69

R

2 sheets of drawings

Claims (8)

632536 1. Hollow fiber of cellulose acetate, characterized in that it has an internal diameter between 100 and 350 (j. And a wall thickness between 20 and 60 u., The wall having a selective permeability when is used in hemodialysis, for water and solutions to be removed from the blood, represented by an ultrafiltration coefficient between 2 and 6 cm3 • h • m2 • Torr and a coefficient for urea between 0.015 and 0.045 cm / min. 2. Fiber according to claim 1, characterized in that the selective permeability is also represented by a creatinine coefficient between 0.013 and 0.027 cm / min. 2 3. Fiber according to claim 2, characterized in that the selective permeability is also represented by a vitamin B12 coefficient of between 0.002 and 0.005 cm / min. 4. Fiber according to claim 1, characterized in that the ultrafiltration coefficient is between 5 and 6, and the urea coefficient is between 0.030 and 0.045. 5. Fiber according to claim 2, characterized in that the creatinine coefficient is between 0.020 and 0.027 cm / min. 6. Method for producing hollow fibers of cellulose acetate according to claim 1, characterized in that it comprises the formation of an intimate mixture of 41 to 50% by weight of cellulose acetate, from 2 to 20% by weight of glycerin and from 30 to 57% by weight of polyethylene glycol having a molecular weight of between 150 and 600, the manufacture of hollow fibers from a melt of the mixture, the cooling of the fibers, the cold drawing of the fibers, in an amount between 2 and 20% of the length of the cooled fibers, the leaching of the fibers so that the polyethylene glycol and glycerin are removed therefrom, and a new plasticization of the fibers with glycerine, then their drying. 7. Method according to claim 6, characterized in that the cellulose acetate of the mixture is present in an amount of 42 to 47% by weight. 8. Method according to claim 6, characterized in that the cold drawing is carried out in an amount of 10 to 15% of the length of the cooled fibers.