NL8006491A - IMPROVED SEMI-PERMISSIBLE HOLLOW CELLULOSE FIBERS AND METHOD OF MANUFACTURING THE SAME - Google Patents

Description

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Improved semipermeable hollow cellulose fibers and method for their manufacture.

The invention relates to semipermeable hollow cellulose fibers of the type useful for dialysis, osmosis or ultrafiltration type separation cells, more particularly cells useful in blood detoxification by hemodialysis or hemofiltration. The invention also relates to an improved method of manufacturing the new fibers.

In the past, the largest amount of hollow cellulose fibers used in hemodialysis artificial kidneys have been produced by melt extrusion of a cellulose ester, such as cellulose triacetate, in a continuous process such as the process of US Pat. No. 3,5 ^ 6,209. Another part of the hollow cellulose fibers was manufactured according to the cupronium cellulose regeneration process of the type disclosed in an improved form in US Pat. No. 3,888,771. Although these in principle uneven processes provide cellulose fibers, which have commercially acceptable water permeability (ultrafiltration) and urea permeability (cleaning) properties for use in artificial kidneys, however, the fibers do not have optimal combination permeabilities. For example, cellulose fibers made by the method of U.S. Pat. No. 3, 5-6,209 have lower water permeability than desired in fibers, which have acceptable cleaning properties for urea, creatinine, vitamin, and other low molecular weight impurities. In addition, the continuous manufacture of cellulose fibers from melt-extruded cellulose acetate fibers involves the chemical conversion of the thermoplastic polymer cellulose acetate to the non-thermoplastic polymer cellulose by hydrolysis or saponification in an aqueous alkali bath. During this hydrolysis, the thin-walled fibers of small size are particularly sensitive to contact and brittle. Successful fabrication with minimal efficiency to be commercial depends on maintaining sufficient tensile strength in the fibers during the wet process steps to prevent breakage or damage. Thus, it will be highly desirable to improve the tensile properties of the fiber, especially its wet strength during hydrolysis, or conversion from cellulose ester to cellulose, before drying and storage and assembly in hemodialysis machines or hemofilters.

The insight to manufacture semipermeable hollow fibers by melt spinning a plasticized polymer composition was developed in the early 1960s and is first described in U.S. Pat. No. 3,123,391; various types of polymers are described there, including cellulose esters, and suitable plasticizers are discussed for use in forming the melt spinning compositions with different types of thermoplastic polymers. The cellulose ester class of polymer developed into the commercial polymer of choice, especially cellulose acetates, and tetramethylene sulfone, commonly referred to as sulfolane, is commonly used as the plasticizer to make the melt spinning composition for use in melt spinning cellulose acetate fibers. U.S. Pat. Nos. 3, 9, 780, and 3,532,527 disclose improvements in the sulfolan cellulose acetate melt spinning process of extruding cellulose acetate fibers, whereby either after spinning, the spun fiber is immersed in a bath containing a mixture of sulfolan and a polyol with contains a molecular weight below 10000, or wherein for spinning the fiber the sulfol plasticizer is modified by incorporating a small amount of a polyol having a molecular weight below about 20,000. These patents also disclose that polyols are considered insufficient for use only as the plasticizer to form melt spinning compositions with cellulose esters, especially the cellulose acetates.

8 00 6 49 1 3

This invention is based on the unexpected discovery that cellulose ester melt spinning compositions, which are sulfolane-free and which contain only certain low molecular polyols or mixtures thereof, can be melt spun into fibers, which can be hydrolyzed into cellulose fibers, which surprisingly have greatly improved wet strength. during the conversion of cellulose ester to cellulose. The omission of the sulfolane, hitherto considered necessary, is key to obtaining the much improved fibers of the invention. The obtained cellulose ester fibers according to the invention have sufficiently high intrinsic tensile strengths in their freshly spun form and, moreover, retain the spun fibers, and in some cases increase in their intrinsic tensile strengths during the polyol leaching and hydrolysis, or deacetylation steps which convert the cellulose ester fiber into a cellulose fiber.

Thus, the invention provides an improved semipermeable hollow cellulose fiber, which is melt-extruded from a cellulose ester melt spinning composition, which is sulfolane-free and contains only low molecular polyols, and the melt-spun fibers have significantly improved intrinsic tensile strengths during the wet process steps, removing the polyol and the fibers are hydrolyzed to cellulose. The obtained cellulose fibers are characterized by a significantly increased water permeability and improved cleaning capabilities for separating low molecular impurities from blood such as urea, creatinine and the like. The improved hollow cellulose fibers of the invention are characterized by a 1 * intrinsic wet tensile strength of about 2 X 10 to about k 11 X 10 g intrinsic fiber tensile strength per gram of cellulose polymer, a water permeability or ultrafiltration coefficient in the range of 2 - 200 millimeters per hour per square meter per millimeter of mercury pressure across the semipermeable wall of the fiber, and a urea cleaning coefficient KyREA in the range of about 15 X 10-3 to about 1 * 5 X 10 3 centimeters per minute at 37 ° C. These functional properties qualify such fibers for use in blood detoxification processes, including hemodialysis 800649 1 + and hemofiltration. The invention also provides an improved method of manufacturing the new fibers of the invention.

The improved semipermeable hollow cellulose fibers of the invention are manufactured by melt spinning a cellulose ester melt spinning composition consisting of about 35-80% by weight of a selected cellulose ester, or mixtures thereof, and a polyol or mixtures thereof, having an average molecular weight in the range from 106 - 900.

Suitable cellulose esters include the cellulose mono-, di- and triacetates and mixtures thereof, cellulose acetate propionate, cellulose acetate butyrate, cellulose propionate and cellulose butyrate and mixtures of two or more thereof. The acetates are preferred, in particular cellulose diacetate and mixtures advantageously contain at least a small amount of one or more of the other cellulose acetates.

Polyols are not suitable for blending with the selected cellulose ester to an acceptable melt spinning composition, but rather the polyols which are sufficient are limited to those low molecular weight polyols having an average molecular weight in the range of 106-900. Attempts to single polyol having a molecular weight above about 600 with cellulose acetate have failed because the composition could not be melt spun. However, sufficient melt spinning compositions have been prepared using blends of polyols, wherein one of the polyols in the blend had an average molecular weight significantly greater than 900, for example, a molecular weight of 11 + 50; a mixture of two polyethylene glycols with 30 molecular weights of 200 and 11 + 50, respectively, to obtain an average molecular weight of 902 has been successfully used for a cellulose acetate melt spinning composition which was spun into hollow fibers, which exhibited the improved tensile strengths of the fibers of the invention characteristics. Mixtures of poly-35 ethylene glycols with polyols, for example, a mixture of polypropylene glycol with an average molecular weight of 1 + 00 and 800 6 49 1 5 glycerol provide a spinnable composition, whereas polypropylene glycol alone with an average molecular weight of 1 + 00 does not success could be spun. Mixtures of polyethylene glycols and ethylene glycol are sufficient and mixtures of two or more low molecular weight polyethylene glycols can be used with or without glycerol.

It has also been found that pure polyethylene glycols, or pure polypropylene glycols of too high molecular weight to form a spinnable cellulose ester composition, can be modified by adding glycerol, a recognized non-solvent for cellulose esters, to thereby form a composition that successfully can be spun like the improved fibers of the invention. The amount of glycerol required for this purpose varies with the molecular weight of the pure polyethylene or propylene glycol chosen and also with the cellulose ester or mixture thereof present.

Generally, the amount of glycerol required increases with the average molecular weight of the pure glycol above about 600; the glycerol concentration should also increase with the amount of cellulose ester which is mixed with cellulose diacetate or for melt spinning compositions prepared from cellulose propionate or cellulose butyrate or mixtures thereof. As a general guideline, amounts of glycerol in the range of about 5-35 wt% can be used. of the cellulose ester melt spinning composition 25 satisfactorily. Polyols with at least two hydroxyl groups in the molecule that are sufficient for use include diethylene glycol, triethylene glycol, tetraethylene glycol, the mono-, di- and tripropylene glycols, and mixtures of one or more of the propylene and ethylene glycols or glycols 30 with ethylene-propylene chains in the glycol molecule, and mixtures of any one or more polyethylene or polypropylene glycol with glycerol in an amount less than 50 vol. of the glycol-glycerol mixture.

The process of the invention consists of the steps of mixing the selected cellulose ester and selected polyol to form a melt spinning composition, melt spinning hollow fibers and cooling them to a gelled self-supporting state, hydrolyzing or deacetylating from the hollow cellulose ester fiber to substantially a cellulose fiber, ie hydrolysis of a substantial portion of the ester groups back to the cellulose hydroxyl group. Complete hydrolysis is usually not achieved and is not necessary, but it is desirable for the best overall permeability properties and their maintenance during storage and transportation to effect or achieve substantially complete hydrolysis, for example above about 90%. The polyol contained in the freshly spun cellulose ester fiber is usually leached from the fiber during hydrolysis or deacetylation; on the other hand, the polyol can be removed in a separate step prior to hydrolysis.

Semipermeable hollow cellulose fibers made from a sulfolan acetate melt spinning composition by the method of US Patent 3,5 ^ 6,209 ° P on a commercial basis and as used intensively in artificial kidneys after about 1972 have typically had a water permeability coefficient of about 1.0 - 1.2 milliliters per hour per square meter of fiber surface area per millimeter of mercury pressure across the semipermeable fiber wall at 37 ° C, a urea -3 coefficient of about 28 to about 30 X 10 centimeters per minute and wet cellulose fiber strength after: 25 deacetylation of about 1.1¼ - 1.8g intrinsic fiber tensile strength per gram of cellulose polymer. The improved cellulose fibers of the invention have been significantly improved in each of these three major functional properties. The most surprising and significantly improved property is the increased intrinsic wet tensile strength. As indicated above, the wet tensile strength of the fibers is critically important for successful continuous production in a production train or line.

Typically, such a line uses a bundle of 16-30 fibers or a number of such strands, which pass from the spinnerets through air, gelling into a self-supporting fiber, and then through a series of liquids in treatment tanks 800 6 49 1 7 which successively leach the polyol from the cellulose ester fiber, hydrolyze the ester to cellulose, rinse the hydrolysis products and excess hydrolysis agent from the cellulose fiber and plasticize the cellulose fiber again. The plasticized product fibers are then taken up on receiving reels. During the wet treatment stages, the fibers are continuously subjected to a stretching or longitudinal force while undergoing drastic internal molecular rearrangements, especially those resulting from polyol removal and chemical changes during deacetylation of a cellulose ester to near a cellulose fiber. Fiber breakage or damage due to the inability of the polymer backbone in each fiber to withstand tensile or frictional forces during such a continuous process interrupts continuous operation and is highly undesirable.

It has been found that cellulose acetate fibers prepared from a melt spun composition of the invention, which is free of sulfolan, tend to retain a greater proportion of their freshly spun tensile strength during walking through the successive wet processing steps than those prepared from the sulfolane melt spinning compositions, that have been in commercial use for a long time. In addition, some of the improved fibers exhibit an unexpected increase in tensile strength from their newly spun state, and this increase occurs during the hydrolysis stages of the process. The cellulose fibers of the present invention exhibit an average intrinsic wet tensile strength after hydrolysis which is at least twice and at most about seven times higher than of hollow cellulose fibers made by the method of U.S. Pat. No. 3,56,209 As used herein. and in the claims, the term "intrinsic fiber tensile strength" as applied to wet cellulose fiber tensile strength measurements refers to the ultimate or breaking strength in grams per gram of polymer in a length of 5 cm of a single wet fiber required to break this fiber, when this is vertically suspended between gripping claws in an 800 6 49 1 8

Instron machine. In the tests done to obtain the wet intrinsic tensile strengths shown in Table A, the grams of polymer in a selected length of 5 cm of the fiber represent an average weight in grams determined for each 5 cm 5 individual sample of cellulose fiber by drying the adjacent 25 m fiber of the same strand to a constant weight and then weighing the 25 m long strand and dividing the total weight by 500 to thereby obtain an average weight, which is then used for the determined 5 cm piece , 10 which is subjected to the breaking strength test. This procedure effectively increases the accuracy of the tensile strength thus determined by substantially eliminating the potential error due to the fiber wall thickness variation along the continuous fiber. Furthermore, each tensile strength value represents the average of six determinations on individual 5 cm long samples. The increases in intrinsic tensile strength thus determined, which are obtained, are of commercial importance in that they greatly increase the overall manufacturing efficiency in the continuous manufacture of the fibers of the invention.

Although the above-described effects of increased wet tensile strength during fiber manufacturing are of great commercial importance, the increase in water permeability achieved in determining the fibers produced by the method of the invention is also very important; certain fibers have reached up to 80 times higher water permeability with respect to still available cellulose fibers made from cellulose acetate melt spinning compositions. Such an increase in water permeability means that the fiber's ability to separate water from a water-containing fluid, such as blood, has increased drastically and the practical benefit that arises is significant in that it allows for significant decreases in the requirement time per hemo-dialysis treatment, as will be apparent to experts.

The melt spinning composition can be formulated in any suitable manner with conventional mixing equipment, the main feature being that sufficient 800 6 49 1 9 mixing is obtained to obtain a thoroughly uniform mixture. For example, dry cellulose acetate powder is mixed with a weighed amount of selected polyol in a rubbing Hobart mixer; the mixed material is further homogenized and mixed by feeding a heated counter-rotating twin screw extruder and the molten extrudate is then forced through a spinneret, for example 16-30 holes of the type, with conventional gas feeders for injecting 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 gases. If desired, one can use a spinneret provided with means for injecting a liquid into the extrudate core, which is not a solvent for the cellulose ester and the polyol, for example a spinneret of the type described in U.S. Pat. No. 3,888,771. extrudate emerging from the spinneret is subjected to cooling, such as compressed air cooling of varying force and / or temperature, to cause gelation and solidification of the extrudate into solid self-supporting fibers.

The cellulose ester fiber can be satisfactorily hydrolyzed by any of the currently known deacetylation techniques.

The preferred procedure is to use an aqueous sodium hydroxide bath. Suitable methods are described in a number of 25 books and technical journals, including, for example

Laidler, Chemical Kinetics, McGraw Hill Book Co., New York (1950), biz. 282-290; Howlett, et al., Technical Inst. J. 38, 212 (19 ^ 7);

Hiller, Jour, Polymer Science 10, 385 (1953) etc .. After rinsing to remove, or neutralize, the hydrolysis products and excess hydrolysis agent, the fibers are still plasticized again with an in water-soluble, substantially non-volatile plasticizer of U.S. Pat. No. 3,5 ^ 6,209. The term "substantially non-volatile" as used in this specification and in claims 35 is understood to mean that the plasticizer remains substantially in the cellulose fiber during the subsequent drying step and storage at 800649 ambient temperature.

Suitable plasticizers for the deacetylated cellulose fibers include those capable of swelling the fibers, probably due to such interactions as hydrogen-5 bonding or dipole-dipole reactions. Preferably, the water-soluble substantially non-volatile plasticizer is a hydroxyl-containing compound, and more preferably a polyol, such as polyalkylene oxides, glycols such as ethylene glycol, diethylene glycol, dipropylene glycol, tripropylene glycol, and the like; glycerol and the like.

10 Glycerol is a choice plasticizer.

After plasticizing, the fiber is then dried in any suitable manner such as vacuum drying, forced air drying at ambient or elevated temperature, microwave drying and the like. Elevated temperatures can be used as long as the temperature does not cause a significant loss of plasticizer. Accordingly, an increased drying temperature depends on the particular plasticizer used and a suitable temperature is easily determined.

The dried final product cellulose fibers of the invention are of capillary size and are in the range of about 200-100 microns external diameter and have a wall thickness in the range of 10-80 microns. For separation cells used in hemodialysis, the fibers preferably have a wall thickness in the range of 10-50 microns and a maximum outer diameter of about 230-320 microns.

The following examples illustrate the new process and the improved hollow cellulose fibers of the invention and contain the best mode of use. As used in this specification and claims, all composition percentages are by weight unless otherwise specifically indicated. Each of the specifically formulated melt spinning compositions is prepared using the above mixer and steps described, and the fibers are spun from a 16-hole spinneret using nitrogen injected into the fiber core. After gelation in air and removal of samples to determine the newly spun intrinsic fiber tensile strength according to the procedure described, the fibers are deacetylated in a caustic solution, typically aqueous sodium hydroxide in a range of 0.2-1.2 wt. $ at a temperature of 20-60 ° C.

The newly spun intrinsic tensile strengths are determined by weighing 15 m of adjacent fiber to determine the average weight of the selected 5 cm piece of each individual fiber subjected to the breaking test.

The obtained cellulose fibers are then thoroughly washed in water and samples are drawn to determine the wet tensile fiber strength according to the test procedure described above. The product fibers are also tested for water permeability KyFR, and urea purification or transport in a laboratory testing device. The tester consists of a fluid reservoir equipped with a magnetic stirrer, and a dialyzer test cup fitted with a magnetic stirrer, a top closure plate with compression fittings, and connectors for connecting the ends of the pot cuffs connected at each end of a bundle of fibers, containing 128 - Contain 178 fibers per bundle 20. The fiber bundle is bent into a U-shape and inserted into the cup and connected to the closure plate; one cuff is connected by a fluid conduit to a pump connected to a conduit to the reservoir and the other cuff is connected by a return conduit to the reservoir to allow fluid to be pumped from the reservoir under controlled pressure through the cavities of the fibers located in the dialysis cup.

The beaker is also provided with dialysate feed and drain connections and during testing the fibers are immersed in a surrounding stirred water bath for the test.

The water transport coefficient is determined by pumping pressurized water through the fibers and measuring the increase in water volume outside the fibers in the dialysis cup at 37 ° C.

The KyFR is then calculated for each test in milliliters per square meter per hour per millimeter of mercury differential pressure as shown in Table A.

The urea coefficient K is determined by providing urea 800649 1 12 with a water-urea solution in the storage reservoir and pumping it through the fiber pockets where the bath surrounding the fibers in the dialysis cup is initially pure water. Measurements are made to determine the urea concentration in the dialysate fluid intermittently.

The tests are performed at 37 ° C and there is no pressure difference over the fiber wall surface during the tests.

The urea coefficient K is determined by considering the urea shell in the concentrations of urea in the storage vessel and in the dialysis cup on the outside of the fibers as a function of time and the fiber area according to the equation: N = KA (C -C0), where N represents the flux across the membrane in moles per minute, the initial urea concentration, C ^ the final, or measured concentration, and 15 A the area of the fiber wall or membrane between the two solutions.

In a two-chamber system without a differential pressure or resulting ultrafiltration, the transfer of urea through the membrane wall can be integrated over a time interval of 20 t to obtain the further comparison: μ ^.

(C1 - C2) t_0 V1 + V2A Λ t ln - = - urea. t ƒ 1 - ° 2) * J LV1 V2 25 where is the volume of the stock reservoir solution and the volume of the solution in the dialysis cup.

In the tests, the volumes and and the area A are measured separately so that a graph of the values on each side of the integrated equation yields a straight line, 30 from the slope of which the K can be calculated in units of urea centimeter per minute .

Example I

A thorough mixture of cellulose diacetate polymer and plasticizer is prepared as described above. The mixture 35 consists of 80% cellulose diacetate and 20% of a mixture of polyethylene glycols of molecular weights 200-150 Daltons to give 800649-113 an average molecular weight of the mixed polyethylene glycol plasticizer of 902 Daltons. The hollow cellulose diacetate fibers are then deacetylated into hollow cellulose fiber membranes in a 0.8% sodium hydroxide solution in water at 50 ° C. The hollow fiber membrane intrinsic tensile strengths, water permeabilities (K ^^) and urea transport rates (Kureum) are summarized in Table A column 2.

As shown in Table A, the wet cellulose fiber of this example has more than 2.5 times the wet intrinsic tensile strength of the reference fiber. The product cellulose fiber produced from this relatively high molecular weight polyol meltspin composition also exhibits superior performance properties for blood purification and higher water permeability. The water permeability (Kjjpp) is 1> 5 times that of the reference fiber. The urea transfer rate is also higher: K = 38 X 10 ~ cm per minute J urea compared to 30 X 10 ~ J cm per minute for the reference cellulose fiber membrane.

Such a mixture was prepared by mixing cellulose diacetate and the same mixture of polyethylene glycols having an average molecular weight of 902, but now using 3% cellulose diacetate instead of 80%. After melt spinning, the hollow cellulose acetate fibers are hydrolyzed or saponified in a Qtk% aqueous sodium hydroxide solution at 50 ° C. After testing, as above, the intrinsic wet tensile strength is 1.3 times that of the reference fiber. K is 26 compared to 30 for the reference fiber, but has increased dramatically to 86 times that of the reference fiber, or a value of 10 ^ millimeters per hour per square meter per millimeter of mercury. A comparison of these two melt spinning compositions shows that for a given polyol plasticizer, the decrease in cellulose ester concentration causes a significant decrease in water permeability at acceptable urea purification values. It can also be noted that a weaker hydrolysis solution has been used and stronger saponification solutions usually increase water permeability. Thus, the desired combination of intrinsic wet strength and properties can be modified to those specifically desired by such melt spinning composition changes, or by modifying the average molecular weight of the polyol as evidenced by comparisons that can be made with the examples following 5.

Example II

A thorough mixture of cellulose diacetate polymer and plasticizer is prepared using the procedures described above. The mixture consists of a mixture of cellulose diacetate and Yl% polyethylene glycol with an average molecular weight of H00 Daltons. The hollow cellulose diacetate fibers are tested after being deacetylated to hollow cellulose fiber membranes in an aqueous 0.1 + NaOH solution at 50 ° C for intrinsic tensile strengths, water permeability (Κ ^^) and urea transport (K _____) and the results are shown in Table A, column 3.

The wet intrinsic tensile strength of the product fiber is 2, b times that of the reference fiber, is 2.1 times higher and K is 32 X 10 3 3 in relation to 30 X 10 3 3 for the reference urea interest fiber. that during saponification from cellulose acetate to cellulose, the wet intrinsic tensile strength has increased to a value nearly double that of the newly spun state.

Another mixture is prepared with the same amounts of cellulose diacetate and polyethylene glycol, but now the average molecular weight of H00 Daltons at the glycol is achieved by mixing polyethylene glycol of average molecular weight 600 with glycerol of average molecular weight of 92 Daltons.

This change causes an improvement of all fiber-30 properties to a wet cellulose fiber intrinsic tensile strength of 3.7 times the reference, a KyFR of 3, times the reference and a Kureum of 33 X 10 ~ 3 compared to 30 X 10 ” 3 cm per minute for the reference.

Example III

A thorough mixture of cellulose diacetate polymer and plasticizer is prepared as described above. The mixture 800 6 49 1 15 consists of 1 + 3 $ cellulose diacetate and 51% polyethylene glycol with molecular weight 108 Daltons. The hollow cellulose diacetate fibers are then deacetylated into hollow cellulose fiber membranes in a 0.8% NaOH solution at 50 ° C. The hollow fiber membrane 5 intrinsic tensile strengths, water permeabilities and urea transport rates are shown in Table A, column 4.

As shown in Table A, the wet cellulose fiber of this example has 1.9 times the intrinsic tensile strength of the reference fiber. The water permeability KyFR is 1.8 times that of the reference fiber and K is 32 X 10 cm per minute in comparison. urea filling at 30 X 10 -3 cm per minute for the reference cellulose membrane.

Such a mixture is made in the same manner, but now the polyethylene glycol has a molecular weight of 150. Saponification of the cellulose acetate to cellulose is done in a 0.1% NaOH aqueous solution at 50 ° C. The same fiber properties are measured as described above, and the wet intrinsic tensile strength is 6.6 times that of the reference fiber, while Kureum are substantially the same as those of the reference fiber. Comparing the wet intrinsic tensile strength of the cellulose fibers of Examples II and III shows that the best wet intrinsic tensile strength for a given cellulose ester concentration, 1 + 3 $ cellulose diacetate, is obtained with a polyglycol average molecular weight between 106 and 1 * 00 and seems to peak at about 150.

Example IV

A thorough mixture of cellulose diacetate polymer and plasticizer is prepared as described above. The mixture 30 consists of 1 + 3. wt.% cellulose diacetate and 57 wt.% polyethylene glycols of molecular weights 1 + 00 and 11 + 50 Daltons. The average molecular weight of the polyethylene glycol plasticizer is 713 Daltons. The hollow cellulose diacetate fibers are then deacetylated into hollow cellulose fiber membranes according to the previously described method. The fiber properties are summarized in Table A, column 5.

800 649 1 16

Table A shows that the wet intrinsic tensile strength has increased to more than twice that of the newly spun intrinsic tensile strength and to a wet cellulose intrinsic tensile strength of 3.2 times that of the reference fiber, -3 -3 5 with a K of X 10 at 30 X 10 cm per minute for the urea reference fiber, and one of U times that of the reference fiber.

Example V

A thorough mixture of cellulose diacetate-10 polymer and plasticizer is prepared as described above. The mixture consists of k3% cellulose diacetate and 51% polyethylene glycol with molecular weight 1 * 00 Daltons and glycerol with molecular weight 92 Daltons to form a polyol blend with an average molecular weight of 362 Daltons. The hollow cellulose diacetate fibers are then deacetylated into hollow cellulose fiber membranes in a 0.1% NaOH aqueous solution at 50 ° C. The cellulose hollow fiber membrane has intrinsic tensile strengths, and are summarized in Table A, column 6.

Table A shows that the wet intrinsic tensile strength 20 has increased by 2b2% during saponification to a cellulose fiber wet intrinsic tensile strength that is 5 * 8 times that of the reference fiber. The urea purification rate has significantly improved to k2 X 10 cm per minute or 1.3 times that of the reference fiber, while K ^ FR is 2.1 times higher than the reference fiber.

Another melt spinning mixture identical to the above-described polyethylene glycol glycerol mixture and cellulose diacetate is prepared, but now the glycerol is replaced with such amount, 7 vol., Of the ethylene glycol to form a polyol mixture having an average molecular weight of 358. Fibers spun and deacetylated under the same conditions; similar properties of the obtained cellulose fiber were determined in the same manner; the cellulose fibers had a wet intrinsic tensile strength which was 5 × 8 times that of the reference fiber -3: 35, one of 21 X 10 cm per minute and one which was 1.7 times that of the reference fiber.

800 649 1 17

Example VI

A melt spinning composition is formed by uniformly mixing 36% cellulose diacetate with 6% of a polyol blend consisting of polyethylene glycol having an average molecular weight of 5 600 Daltons and glycerol in amounts producing an average molecular weight of 1 * 21 for the mixture. Fibers are melt spun and deacetylated in a 0.1 * NaOH solution in water at 50 ° C and the properties are determined according to the procedures described above and are summarized in Table A, column 7. These cellulose fibers have a combination of high tensile strength, high 1 K.TT;) _ and high K values and sets

Ur π urea is a preferred form of the invention in that such fibers are satisfactory for use in hemodialysis or hemo-filters and are particularly desirable for hemofilter use. The wet intrinsic tensile strength is 3> 1 * times that of the reference fiber, the Κ .. „0 is 32 times higher than the reference fiber and K__

Urπ urea is U9 X 10'3 cm per minute.

Example VII

A thorough mixture of cellulose diester 20 (propionate / acetate) and softener is prepared as described above. The cellulose ester of this example can generally be considered as cellulose propionate since 96% of the ester groups are propionate and only 1% acetate.

The blend consists of 1 * 3 $ cellulose propionate and 57 $ 25 polyethylene glycol with average molecular weight 1 * 00 Daltons and glycerol with molecular weight 92 Daltons to form a polyol blend with an average molecular weight of 362 Daltons.

The hollow cellulose propionate fibers are then deacetylated into hollow cellulose fiber membranes in a 0.1% NaOH solution in water at 50 ° C. The hollow fiber membrane intrinsic tensile strengths, water permeabilities and urea transport rates are summarized in Table A, column 8.

As shown in Table A, the wet cellulose fiber of this example has 3.5 times the intrinsic tensile strength of the reference fiber. The water permeability is 2.1 * times that

of the reference fiber and the rate of urea transfer, K.

* urea 8 00 6 49 1 -3 18 is 33 X 10 cm per minute.

Example VIII

A melt spinning mixture is formed by thorough mixing of 1 + 3 # cellulose diacetate and 57 # of a polyol consisting of a mixture of polypropylene glycol having an average molecular weight of 1 + 00 Daltons and glycerol to give an average molecular weight for the polypropylene glycol / glycerol Mixture of 297 · Cellulose fibers are manufactured and tested according to the above-described methods wherein the deacetylation 10 is carried out in a 0.1 + NaOH solution at 50 ° C. The properties are listed in Table A, column 9

Example IX

Artificial kidneys of the type marketed by Cordis Dow Corp. under the trade mark C-DAK artificial kidneys 15 are manufactured using cellulose fibers, manufactured in commercial quantities according to the method described in example V above, using the melt-spinning composition consisting of 1 + 3 # cellulose diacetate and 57 # of a mixture of polyethylene glycol with a molecular weight of 20 1 + 00 Daltons and glycerol to form a polyol mixture with an average molecular weight of 3β2 Daltons. The determination of the wet intrinsic tensile strength yields 11 X 10 g per gram of cellulose fiber.

After the cellulose fibers are rinsed with water and plasticized again in an approximately 10% glycerol water solution and then dried, the fibers retain about 20% glycerol. The intrinsic tensile strength of these fibers is determined according to the single fiber breaking test on the Instron machine, as described above, in connection with the tests on dry cellulose acetate fibers with the following variations. A bundle 30 consisting of 360 fibers of one meter long is weighed, the glycerol extracted and the pure cellulose fiber weighed. The average weight of a 5 cm long part is then calculated on a 100% polymer fiber base. The tensile strength results represent the average of six separate runs on six 5 cm long fibers 35 from the glycerol-free bundle. The dry intrinsic tensile strength is k 20 X 10 g per gram of cellulose fiber.

8 00 6 49 1 19 One of the artificial kidneys, the 1.5 m cellulose fiber area

is sterilized dry using 2.5 MRAD

gamma rays. After sterilization, the kidney is opened and fiber samples are removed and subjected to the wet intrinsic tensile strength test and the fibers are found to have an average wet intrinsic tensile strength of 8.6 X 10 µg per gram of cellulose fiber. Another 1.5 m kidney made with the cellulose fibers of this example is sterilized while the kidney is filled with physiological saline using 2.5 MRAD gamma rays. Fibers from this wet gamma-sterilized kidney have a wet intrinsic tensile strength k of 5> 2 X 10 g per gram of cellulose fiber.

For comparison, commercial production artificial kidneys from Cordis Dow Corp. containing 1.5 m of cellulose fibers manufactured according to the method of U.S. Pat. No. 3,5 ^ 6,209 were tested in the same manner as the fibers described above and were appear to have the following properties:

Dry intrinsic cellulose fiber tensile strength - 7.5 X 10 g 20 per gram. . Xk

Wet intrinsic cellulose fiber tensile strength - 1.6 X 10 g per gram

Wet Cellulose Fiber Intrinsic Tensile Strength After Dry ... K Gamma Radiation Sterilization - 1.53 X 10 g per gram Intrinsic Tensile Strength of Wet Cellulose Fiber After Wet (Physiological Saline) Gamma Radiation Sterilization - 1.28 X 10 g per gram.

. . ... 2

Clinical evaluations on two 1.5 m artificial kidneys containing the improved cellulose fibers of this example were made in two interrupted hemodialysis patients at an average blood flow rate of 200 ml per minute and a dialysate flow rate of 500 ml per minute for 3.5 and 3.5 ml respectively. U »You, 1 hour. The KyFR was 2.1 ml per hour m mm of mercury at 37 ° C. The K was 31.6 cm per minute at 37 ° C.

For comparison, commercial Cordis Dow artificial kidneys, .2 containing 1.5 m of cellulose fibers, manufactured in accordance with the method of U.S. Pat. No. 3,5 ^ 6,209 used in three interrupted hemodialysis patients, gave average values for o

KyFR of 0.89 ml per hour m mm of mercury at 37 ° C and a Kureum of 29.6 cm per minute at 3T ° C.

The artificial kidneys used in this example and referred to above as the type marketed by Cordis Dow Corp. are devices with a pair of blood chambers separated from each other by an intermediate dialysate chamber which is integrally connected to the blood chambers. A bundle 10 of hollow fibers, usually consisting of thousands of individual fibers, for example six-fifteen thousand fibers, terminate with their opposite ends in a plastic tubular sheet, typically a polyurethane. The tubular sheet connects the fibers together and also provides an annular portion, which is outside the periphery of the fibers in the bundle, which serves to connect the tubular sheets to the end portions of the dialysate chamber and to the blood chambers and thereby confine the blood chambers and the dialysate chambers into a unit, the fibers within the dialysate chambers so that the chambers are insulated from each other in a liquid tight packing relationship. The open ends of the hollow fibers terminate in the plane of the outer end of each tubular sheet, and the passages in the hollow fibers provide communications between the interior of the spaced apart blood chambers.

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Claims (13)

1. Semipermeable hollow cellulose fiber, characterized in that it has an ultrafiltration coefficient in the range of 2 - 200 milliliters per hour per square meter per millimeter of 5 mercury, a urea coefficient K in the range of 15 to 1 + 5 X 10'J cm. per minute and a wet intrinsic tensile strength in the range of 2 - 11 g per gram of cellulose polymer and manufactured according to the method, (a) melting a hollow cellulose ester fiber spinning through a nozzle of a melt spinning composition consisting essentially of 35 - 80 given,% cellulose ester supplemented with at least one polyol having an average molecular weight between 106 - 900, (b) said cellulose ester fiber substantially hydrolyses into a hollow cellulose fiber, 15 (c) said cellulose fiber, while still wet, plasticizes again with a water-soluble substantially non-volatile plasticizer, and (d) said plasticized fiber dries. Semi-permeable hollow cellulose fiber according to claim 20 1, characterized in that the external diameter is in the range of 200 - 1 + 00 microns and the wall thickness in the range of 12 - 80 microns, 3. Semi-permeable hollow cellulose fiber according to claim 1, characterized in that said melt spinning composition consists of a mixture of polypropylene glycol and glycerol. 1+. Semi-permeable hollow cellulose fiber according to claim 1, characterized in that said cellulose ester comprises cellulose acetate propionate. Semipermeable hollow cellulose fiber according to claim 30 1, characterized in that said polyol consists essentially of a mixture of ethylene glycols with an average molecular weight of less than 600 and polyethylene glycols with an average molecular weight above 900 to form a mixed polyol with an average molecular weight below about 900. Process for the manufacture of a semipermeable hollow cellulose fiber with a wet intrinsic tensile strength in the 800649 1 2h range of 2 - 11 g per gram of cellulose polymer, characterized in that (a) a hollow cellulose ester fiber is melt spun through a nozzle from a melt spinning composition consisting essentially of 35 - 8θ wt.% cellulose ester supplemented with at least one polyol having an average molecular weight between 1θβ - 900, (b) said cellulose ester fiber substantially hydrolyses into a hollow cellulose fiber, (c) said cellulose fiber while still wet is again plasticized with a water-soluble, substantially non-volatile plasticizer, and (d) dries said plasticized fiber. Process according to claim 6, characterized in that said melt spinning composition contains 1 + 0 - 50% cellulose ester. Process according to claim 6, characterized in that said ester mainly consists of cellulose diacetate. Process according to claim 6, characterized in that said cellulose ester comprises cellulose acetate propionate. 10. A method according to claim 6, characterized in that the polyol consists of at least one polyol selected from the group consisting of polyethylene glycols, polypropylene glycols and glycerol. 11. Separation device for hemodialysis and hemofiltration of blood, characterized in that it consists of a pair of blood chambers, which are kept apart by an intermediate dialysate chamber, which is integrally connected thereto, a bundle of hollow fibers which ends terminate in a tubular sheet, said tubular sheets sealingly interposed between said dialysate chamber and each of said blood chambers and connected thereto so that said chambers are separated in a liquid-tight relationship, the passages in said fibers providing communications between the internals of said blood chambers, said hollow fibers consisting of a plurality of hollow fibers according to claim 1. Separating device according to claim 11, characterized in that said hollow fibers consist of a number of hollow 800 6 49 1 fibers according to claim 2. 13. Separation device according to claim 11, characterized in that said device and said hollow fibers therein are in a sterile state as a result of sterilization of said gamma-ray device and wherein said sterilized hollow fibers have a wet intrinsic tensile strength li in the range from 5 - 9 X 10 g per gram of cellulose fiber. 1U. Separating device according to claim 13, characterized in that said hollow fibers in said device are sterilized by gamma rays, said fibers being dry replasticated cellulose fibers with about 20% glycerol in them and said sterilized fibers being wet. . . You have intrinsic tensile strength of 9 X 10 g per gram of cellulose fiber. Separating device according to claim 13, characterized in that said hollow fibers in said device have been sterilized by gamma rays, while said fibers were wet with physiological saline and said sterilized fibers have a wet intrinsic tensile strength of about 20 X 10 g per gram of cellulose fiber . 800649 1