JPS6317922B2 - - 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

[Detailed description of the invention]

This invention relates to an improved method for producing cellulose acetate semipermeable hollow fibers suitable for use in artificial kidneys. Cellulose esters, including cellulose acetate, have traditionally been spun into semipermeable hollow fibers for use in various processes such as desalination of seawater, ultrafiltration of aqueous and non-aqueous solutions, ion exchange processes, concentration of salts, and waste steam processing. It has been used as a separation membrane in purification, etc. The preparation of permeable separation membranes from film-forming cellulose esters is described in a number of US patents, the most relevant to the applicant's knowledge being US Pat. Nos. 3,532,527 and 3,494,780
This is the number. U.S. Patent No. 3,532,527 and
No. 3,494,789 describes a process for melt-spinning cellulose esters, particularly cellulose triacetate and cellulose acetate, from melt-spinning compositions, which are described, for example, in U.S. Pat.
a compatible plasticizer of the tetramethylene sulfone type as described in US Pat. 0.66:1 to about 5:
1, preferably in the range of about 0.8:1 to 1.3:1. It is stated that the purpose of changing the relative proportions of these materials is to improve the ability of the fibers to separate salt from seawater. US Patent No. 3532527
Although the fibers produced by the methods of No. 1 and No. 3,494,780 are effective for desalinating seawater, they are not satisfactory for use as hollow fibers in artificial kidneys for hemodialysis. Beginning in the mid-1960s, the National Institute of Health
Institutes of Health) and Offices of Health)
Saline Water (the Office of Saline)
Various types of cellulose acetate membranes have been extensively researched with financial support from the Water Institute. In addition, the National Institute of Arthritis and Metabolic Disease
and Metabolic Diseases) is also sponsoring research to improve known cellulose acetate hollow fibers and evaluate their potential for use in artificial kidneys. This type of three-year project is aimed at developing an artificial kidney made of cellulose acetate hollow fibers.
NIH Contract No. 70− from 1971 to 1973
2302, the Dow Chemical Company's Western Division Research Laboratory
Chemical Company, Western Division
Research Laboratories). In this contract, a mixture of cellulose acetate and triethylene glycol was melt spun to produce cellulose acetate fibers, and some of the produced fibers were used in artificial kidneys for clinical use in hemodialysis. Although the best artificial kidney produced in this three-year project was a success in the sense that it could be safely used for dialysis in many clinical trial patients, it nevertheless The properties of moving them simultaneously for removal were not as good as in the cellulose hollow fiber artificial kidneys used at the time. Problems with these kidneys were that the rate of water removal was too high and the ratio of blood solutes to water removed was too small, so this three-year project was abandoned. Since the early 1970s, when the first artificial kidneys were commercially available from Cordis Dow Corp. in the United States, the hollow fibers used in such commercially available artificial kidneys were almost exclusively cellulose fibers. These fibers were produced either by the copper ammonia process or by the Lipps process of US Pat. No. 3,546,209. To date, cellulose hollow fibers have been widely accepted by the market as the best semipermeable membrane for artificial kidneys, but there are many challenges involved in melt spinning such fibers and manufacturing them into leak-free artificial kidneys. It is clear to those skilled in the art that there are problems. For example, the tensile strength of fibers is relatively low;
And when the fibers break during fiber processing and dialysis chamber assembly, the process becomes complicated and difficult. Due to the above-mentioned difficulties of cellulose capillary fibers, it is economical, easy to melt-spun and processed into artificial kidneys on a commercial scale, and the solutes in the blood, such as urea, creatinine, uric acid and water, can be easily removed from the current cellulose capillary fibers. There is a continuing need for semipermeable capillaries that can be removed at a rate greater than The primary object of this invention is to provide novel cellulose acetate hollow fibers which are improved compared to currently known cellulose esters and cellulose hollow fibers, and which enable the production of artificial kidneys incorporating the fibers. A method for producing novel cellulose acetate hollow fibers with selectively adjustable osmotic properties and superior water and solute removal than artificial kidneys with conventional cellulose hollow fibers is provided. This invention has a combination of solute and water removal properties and permeability in blood with a molecular weight of about 1400 or less and is interrelatedly variable and adjustable in an artificial kidney for hemodialysis. Provided is a method for producing novel cellulose acetate semipermeable hollow fibers that exhibit optimal handling properties when used in The optimal handling characteristics of an artificial kidney are such that the rate of removal of solutes from waste blood is high compared to the rate of water removal, so that health-protecting blood purification takes place in the shortest possible time. That is, the present invention provides a method for producing polyethylene glycol and glycerin-modified cellulose acetate hollow fibers, comprising: a) 41 to 50 weight percent of cellulose acetate, 2 to 20 weight percent of glycerin, and 30 to 57 weight percent of polyethylene glycol having a molecular weight in the range of 150 to 600; b. Producing hollow fibers from the molten mass of the mixture; c. Cooling the fibers; d. Cold drawing the fibers in a range of 2% to 20% based on the cooled fiber length. e) subjecting the fibers to a leaching step to remove polyethylene glycol and glycerin from the fibers; and f) replasticizing the fibers with glycerin followed by drying. The novel fibers obtained by the method of this invention are produced from novel melt-spinning compositions. Using this composition, cellulose acetate can be wound onto a reel without leaching after dry spinning and air cooling. This novel melt-spun composition comprises cellulose acetate and a proportion of molecular weight from about 150 to 600.
Polyethylene glycol and a certain proportion of glycerin can be melt-spun into hollow fibers that are stronger than cellulose fibers and easier to process into artificial kidneys. The hollow fibers have a favorable combination of water and blood solute permeability properties, which are further increased and optimized when the spun fibers are subjected to certain controlled post-spinning processing steps. The permeability of such fibers can be varied and controlled by adjusting the relative amounts of each of the three components in the melt-spun composition, and by adjusting the composition, further adjusting the cooling, immediately after cooling and Adjusting the cold stretching or elongation of the glycerin or polyethylene glycol component in the chilled fibers prior to leaching from any spun fibers provides an optimal ratio of low molecular weight blood solute and water removal. By dry spinning in air at room temperature, and by properly controlling the degree of cold drawing, and by carefully selecting the amounts of each component in the melt-spinning composition, the solute removal efficiency is better than that of previously known cellulose acetate hollow fibers. It is possible to produce cellulose acetate fibers with high water removal ratios and preselected combinations of removal properties. The spectra or systems of the fibers were examined and were found to be improved products of this invention. The improved method of this invention comprises the steps of controlling and correlating the melt-spun composition and selecting the degree of cold drawing and leaching conditions to cool the spun fibers and drying the spun fibers to form a novel cellulose. This imparts the desired permeability to the acetate fibers. The novel and improved cellulose acetate fibers of the present invention described above are illustrated in FIGS. 1 and 2, respectively, and are further characterized and described with respect to the melt spinning compositions and methods of the present invention. FIG. 1 is a three-component system phase diagram in which the proportions of the three components used in the melt-spinning composition of the present invention are at points A,
It is indicated by the compositional region surrounded by B, C and D. FIG. 2 shows the process of processing the melt-spinning composition of FIG.
1 is a schematic illustration of a process for producing an improved system of hollow capillary cellulose acetate fibers of the present invention; FIG. The melt spinning compositions of this invention contain about 41 to about 50% by weight cellulose acetate, about 2 to about 20% by weight glycerin, and the balance having a molecular weight of about
Contains polyethylene glycol ranging from 150 to about 600%. As shown in Figure 1, the system or spectrum of a ternary composition is within the region surrounded by the extreme values of each of the three components occurring in the composition region surrounded by A, B, C, and D. It is in. Specific compositions of the three components in amounts in the ABCD composition range of FIG.
3546209, by melt-spinning into hollow capillary fibers and water leaching the glycol and glycerin after cooling, such fibers work in the current form of artificial kidneys. Suitable for manufacturing and good at the same time. Preferred compositions particularly suited for optimal properties for use with most patients undergoing intermittent dialysis are composition ranges E, F, G, and H in FIG. The three components of cellulose acetate, ethylene glycol and glycerin are separately traditional components in semipermeable membranes and contain plasticizers or cellulose acetate solvents of the sulfolane type, such as those described in U.S. Pat. No. 3,532,527. In the composition, cellulose acetate and polyol,
For example, glycols are used in combination. However, prior to the present invention, it was known that glycerin, which is not a solvent for cellulose acetate at room temperature, could be used with selected low molecular weight glycols to produce high strength hollow fibers with improved permeability over fibers obtained in the presence of sulfolane type solvents. was not publicly known. Similarly, it was not known that a proportion of glycerin in the above compositions could improve and control the movement of low molecular weight solutes through the fiber walls compared to the movement of water through the fiber walls. In this specification, the term cellulose acetate is used to mean cellulose diacetate. Cellulose diacetate is commercially available in the United States, and significant amounts, e.g., less than 25%, and usually much smaller amounts of monoacetate and diacetate, are present in commercially available cellulose diacetate but are satisfactory for use in the present invention. ,preferable. The cellulose acetate is dissolved in a solvent such as dimethyl sulfoxide, sulfolane, triethylene glycol or another glycol of low molecular weight that is liquid at room temperature and then spun into a tow of fibers through a conventional spinneret. Independent fibers tend to stick or weld when wound around a core. Even when cooled below the gelling temperature and hardened into solid fibers, such fibers retain a certain amount of solvent, softening the surface area and causing sticking during winding. is clear. Traditionally, it has been necessary to leach the solvent from the spun and cooled fibers before winding, and hot leach baths have been used for this purpose. However, introducing the hollow capillary fibers into the leaching bath immediately after cooling causes the fibers to pulse violently, resulting in non-uniform fiber wall thickness and, at the same time, non-uniform fiber inner diameter. According to the invention, by using a low molecular weight glycol as a solvent for cellulose acetate, improved by the above-mentioned specified amount of glycerin, welding of the fibers is avoided without leaching before winding onto a core. be able to. Glycerin clearly reduces the surface softening effect of glycols, allowing the fibers to be wound without sticking or welding of the fibers, and even to be wound under tension. The wall thickness and inner diameter of the spun fibers produced are improved and uniform;
It can be stored indefinitely at room temperature on a wick for future processing into artificial kidneys. Moreover, glycerin clearly improves the gelation of cellulose acetate upon cooling, in that it changes the porosity created in the fiber walls. As discussed below in connection with the cold drawing process, the glycerin present in the aforementioned melt spinning compositions allows the gelled fibers to retain their cohesive properties and to withstand tension or cold stretching immediately after gelling or solidification. It becomes strong enough to maintain uniformity of wall thickness and internal diameter dimensions during stretching. Furthermore, unexpectedly, cold stretching also improves the porosity of the fiber wall in that low molecular weight blood solutes pass from the blood flowing inside the fiber to the dialysate flowing outside the fiber. blood solutes,
That is, a substantial increase in the movement of other solutes, including solutes with molecular weights less than about 1400, such as urea, creatinine, uric acid, and vitamin _B12 , occurs without increasing the ability of the fiber to transport water through the fiber wall. Although the mechanism of this change as a result of cold stretching is not completely understood, it is likely that the degree of cold stretching and the amount of glycerin present in the melt-spun composition are correlated and mutually dependent. I understand. Generally speaking, the molecular weight is about 150 to about 600.
When using a melt-spun composition consisting of cellulose acetate dissolved in polyethylene glycol in the range of An increase in occurs. Although an increase in blood solute movement follows as glycerin content increases, the relationship is not completely linear. When the proportion of glycerin in the melt-spinning composition is about 3% to 10% and about 42% to 47% cellulose acetate with the remainder being polyethylene glycol, the improvement in the ratio of blood solute transfer to water transfer is The degree of room temperature drawing is approximately 15% of the spun fiber length.
When the cellulose acetate is 43% to 45%, the spun fiber length is about 10%.
Increased yields excellent results. In the case of a composition selected from the preferred composition range EFGH shown in FIG.
The ratio of blood solute transfer to water transfer is maximally improved. Two or three simple tests then readily determine the optimum degree of cold stretching for a selected composition. As is clear from FIG. 2, the method of the present invention includes the steps of producing the above melt-spinning composition, melt-spinning hollow fibers, cooling the hollow fibers to a self-supporting gel state, and It consists of a process of pulling or drawing the fiber at room temperature. The tension-treated fibers may be stored or multiple tows of fibers may be bundled (eg, 3000 to 30000 fibers) and further processed to produce an artificial kidney. The fiber bundle is passed through a leaching bath to remove glycol and glycerin, producing a semipermeable hollow fiber bundle. The leached fiber bundle is then replasticized with an aqueous glycerin solution, excess glycerin is removed, and the fibers are dried. This dry fiber is an improved product of this invention. The preparation of the melt-spun composition can be performed using any method using conventional mixing equipment, the important point being to ensure sufficient mixing to obtain a homogeneous new mixture. For example, weighed amounts of polyethylene glycol and glycerin and dry cellulose acetate are mixed in a high shear Hobart mixer, the mixed materials are further homogenized and mixed in a heated reversing twin screw extruder, and then the melt extrudate is A type of spinneret with conventional gas supply means for injecting gas into the core, e.g.
The melt extrudate was forced through 16 to 32 spinnerets. The preferred gas for this purpose is nitrogen, but other gases including carbon dioxide, air or other non-hazardous gases may be used satisfactorily. The extrudate emerging from the spinneret is cooled, for example with forced air at various indentation forces and/or temperatures, to gel and solidify the extrudate into a self-supporting solid fiber. Typically, the fibers are capillary, ie, have an inner diameter in the range of about 150 to about 300 microns and a wall thickness of about 20 microns.
to 50 microns. Although the preferred fibers of this invention are particularly suitable for use in artificial kidneys and for use in hemodialysis, the advantages of dry spinning and manufacturing the fibers and winding them onto a supporting core without pre-leaching are other It can also be applied as a fiber for use in ultraviolet applications, etc. In such cases, fibers having an outside diameter of about 350 to 400 microns and a wall thickness of about 10 to about 80 microns are satisfactory to use. In the process of this invention, the short period of time immediately after the extrudate exits the spinneret opening is very important to achieve the desired degree of permeability of the textile product. The porosity of the textile product, as a joint effect of the cooling rate of the fiber and cold stretching or tension during this short period of time,
The permeability is thus determined. In certain melt-spinning compositions, the melt fibers are drastic.
When the fibers are quenched to any given degree, the porosity of the fibers increases compared to when the extrudate is quenched into fibers less thoroughly or when gelling is slow. The increased porosity as a result of such quenching usually has a negative effect on the fiber's ability to transport water, so the ultra-supervelocity of the fiber should be pre-selected or improved as necessary for use in hemodialysis. By increasing the velocity of the room temperature air flow forced through the extrudate, the porosity of the textile can be adjusted to a lower level, and a similar effect can be obtained by lowering the temperature of the cooling medium. And if both are done, the optimum conditions can be achieved. It is preferable to use air at room temperature for cooling, and industrially satisfactory results can be obtained even without cooling below room temperature. Cold drawing or drawing can be effected satisfactorily by passing the extruded and solidified fiber through a series of rolls, or a series of spaced apart rolls, such as godet rolls. The desired degree of cold drawing can be achieved by adjusting the rotational speed of the second roll or second group of rolls in the fiber feeding line. A good correlation between the degree of cold drawing of the fiber and the preset or measured speed of downward rotation of the rolls is usually obtained, and for a particular desired percentage of cold drawing a series of upward rolls is obtained. In comparison, it is necessary to precisely adjust the rotational speed of the series of downward rolls. To wind the cold drawn or tensile fibers onto a core or reel, use commercially available winding equipment;
For example, a Leesona winder may be used, and appropriate care must be taken to maintain a slight tension in the fibers during winding. In a preferred form of the method of the invention, a plurality of cold-drawn cores or reels are attached to feed a plurality of tows of fibers through conventional gathering equipment to form a cohesive fiber bundle, and the fiber bundle is then leached. Glycerin and polyethylene glycol components are removed. The leaching process can be carried out in any conventional equipment, for example by passing the fiber bundle through a selected solvent bath or by semi-batch immersing the core or roll in the solvent. The leaching solvent can be any solvent that is a good solvent for the plasticizer and glycerin and does not act as a solvent for cellulose acetate, with water being preferred. aqueous solution,
Alcohols and mixtures thereof are satisfactory solvents, such as methanol, ethanol, propanol and mixtures thereof, and dilute aqueous solutions of sodium sulfate, magnesium sulfate and sodium chloride. Leaching can be carried out at room temperature or at elevated temperatures, such as temperatures below 80°C to 90°C. A preferred leaching method uses a first bath and a second bath, with the first bath being leached at a temperature above room temperature, preferably in the range of about 80°C to 90°C, for about 5 to 30 seconds, followed by a second bath at room temperature. 1 to 10 in the bath
It is a method of steeping for 2 to 4 minutes, preferably 2 to 4 minutes.
As a guide for selecting the optimal leaching temperature of the first bath to produce fibers with the desired water transfer rate, the cellulose acetate content (percent) associated with cellulose fibers increases from 41% to 50%. As the water transfer rate decreases, the leaching temperature increases from about 20°C to about 80°C. The leaching temperature is about 50
Increasing from °C to 90 °C tends to increase the permeability of the fibers _for transporting urea, creatinine, and other low molecular weight solutes up to and including vitamin _B12 . After leaching the fibers and thereby obtaining the desired permeability, replasticization with glycerin or the like is necessary to convert the fibers into dry form. water/
Replasticization is preferably carried out using a container of glycerin, the solution containing from about 30% to about 60% by weight glycerin, with 50% glycerin.
Good results are obtained with aqueous solutions containing . As an indicator, when the glycerin concentration in the replasticizing solution is reduced below about 50%, the water transfer rate also decreases. After replasticization, the fibers may be dried by passing through a conventional drying oven or by another device, such as a vacuum dryer, as shown in FIG. If necessary, the glycerin portion may be removed by forced air blowing by passing the fiber bundle through a set of opposing air knives at a pressure and time that reduces the glycerin present in the fibers. good. Dry, vacuum or about 1 to about 6 pounds/
Reducing glycerin by increasing air blowing pressure per square inch reduces the fabric's ability to transport both water and blood solutes. Satisfactory drying conditions are typically about 40°C to 80°C for 1 to 6 minutes; A low temperature range must be used to optimize the ratio of blood solutes to water removed during dialysis. The improved cellulose acetate hollow fibers obtained by the process of this invention can be produced from melt-spun compositions using the methods and selection conditions described above and have water transport and solute transport capabilities that are distinguishable from previously known cellulose acetate hollow fibers. Possesses a combination of abilities. The limited properties of the fibers of this invention are most conveniently described in terms of coefficients. The water transfer permeability is expressed as the ultimate permeability coefficient K _UFR and ranges from about 2 to about 6 millimeters/hour/square meter/millimetre of the difference in mercury pressure between opposing membrane walls. The K _UFR coefficient is a number that expresses the ability of a semipermeable fiber to pass water per unit of pressure gradient across the active area of the membrane. The effective area of the membrane is the exposed part of the surface area of the semipermeable walls of the hollow fibers that is in contact with the fluid, through which a movement of water takes place, for example per square meter. Solute transport permeability is expressed as the coefficient of diffusive mass transport across the membrane, or dialysis, Km. dialysis coefficient
Km is the ability of a semipermeable cellulose acetate fiber to separate dissolved components, or solutes, in a fluid on one side of the fiber's semipermeable wall and transfer that component into another fluid on the other side of the same wall surface, i.e. It is a numerical value that represents the ability of a semipermeable membrane to pass through as a function of its effective area and the concentrations in the two fluids on either side of the membrane. The rate of solute transfer from the blood to the dialysate is clinically important as the limiting factor determining the minimum time to complete hemodialysis using the cellulose acetate hollow fiber artificial kidney of the present invention; The rate of movement is then determined by the removal of each solute and is expressed in milliliters of solute per minute. Km provides a numerical value that indicates the ability to pass a solute as a function of the size or molecular weight of the solute molecule, and the units of Km are centimeters per minute. Removal with respect to the numerical value expressed as KrU is renal urea removal, or KrCr
relates to the removal of creatinine and is in milliliters per minute. These numbers are discussed in Chapter 41 by Frank A. Gottsch in Volume 2 of his paper Kidney.
Frank A. Gotch in Vol of the treatise
eutitled The Kidney ). Due to the improved fibers of this invention, the membrane coefficient of urea
Kurea ranges from about 0.015 to about 0.045 cm/min, the membrane coefficient for creatinine Kcreatinine ranges from about 0.013 to about 0.027 cm/min, and the membrane coefficient for vitamin _B12 K _B12
is in the range of about 0.002 to about 0.005 cm/min. The ratio of the dialysis coefficient Km of the membrane to the critical excess coefficient K _UFR is greater than about 3:1 based on the coefficient range and units described above. For hemodialysis, a preferred combination of water and solute transfer capacity has a K _UFR of about 3 to about 5.
ml/hour/square meter/mmHg,
Kurea is greater than about 0.02 cm/min, and
The ratio of Kurea/K _UFR is greater than 5:1. Using such fibers, Cordis
(Dow Corp.), compared to a commercially available hollow fiber artificial kidney made from semipermeable cellulose fibers made by the method described in Lipps U.S. Pat. No. 3,546,209. This substantially reduces the time required for the hemodialysis process, provides flexibility, and facilitates adjustments during hemodialysis. The novel cellulose acetate fibers of this invention have the same effective area and similar conditions of use compared to conventional artificial kidneys, which have a K _UFR of typically about 1 ml/hr/sq m/mmHg when operated at room temperature. The rate of water removal from the blood during dialysis using an artificial kidney is 2 to 6 times faster. At the end of hemodialysis, a K _UFR of about 6 or more is required for some of the removed water to be replaced before the process reaches the preselected water content;
The faster the rate of water removal, the more advantageous it is in terms of ease of control and flexibility during dialysis. Furthermore, an artificial kidney using cellulose acetate fibers having the above-mentioned solute coefficient can quickly remove blood solutes such as urea, creatinine, uric acid, etc.
For example, an artificial kidney with an effective surface area of 1 square meter of cellulose acetate fibers of the present invention having the predetermined coefficients described above typically has a urea removal rate of about 100 m2.
creatinine removal ranges from about 80 to about 135 ml/min and vitamin
B ₁₂ removal ranges from about 15 to about 45 ml/min. This invention provides a range of spinning compositions and the production of the fibers described above, as well as the production of cellulose acetate fibers with optimal K _UFR and Km properties and the production of artificial kidneys therefrom to meet specific patient requirements. Various processing parameters that are relatively easy to select in advance are provided for use in the process. Using specific melt-spinning compositions and selecting appropriate processing conditions, any specific water and solute removal rates within the above ranges are simultaneously exhibited. The cellulose acetate fiber of this invention can be produced relatively easily. Accordingly, the improved cellulose acetate fibers of this invention provide controlled, controlled water and solute removal during hemodialysis.
and provides an easy and convenient means of manufacturing an artificial kidney system exhibiting a preselected rate. The following examples demonstrate the best mode for making the novel cellulose acetate fibers of the present invention and demonstrate the K _UFR and Km as a function of the melt spinning composition and the degree of cold drawing the fibers undergo during processing. exemplify the effect it has. In the examples, typical fiber migration ability characterizing the improved cellulose fibers of the present invention was also shown. Examples 1-9 Three batches of cellulose acetate fibers were made using different melt spinning compositions. 43% by weight of cellulose acetate and 57% by weight of polyethylene glycol having a molecular weight of about 400 in the first composition; cellulose acetate in the second composition;
43% by weight polyethylene glycol, 50% by weight polyethylene glycol having a molecular weight of about 400 and 7% by weight glycerin; and in the third composition 43% by weight polyethylene glycol having a molecular weight of about 400;
% by weight and 18% by weight of glycerin.
The cellulose acetate material used in all three melt-spinning compositions was the same material, manufactured by Eastman Chemical Co., Ltd., Kingsport, Tennessee.
Eastman Chemical Products
Inc., Kingsport, Tennessee) from CA−400−
25, this cellulose acetate has an acetyl content of 39.9% as determined by the ASTM D-871-72 method and an ASTM D
The falling ball viscosity measured by the −1343 method was 17 to 35 seconds. 3
The polyethylene glycol used in the seed melt spinning composition was manufactured by The Dow Chemical Company, Midland, Michigan.
USP grade PEG 400 from Midland, Michigan) and glycerin also from USP and Dow Chemical Company. Each batch was made by placing the cellulose acetate powder in a standard laboratory Hobart mixer and slowly adding the liquid ingredients polyethylene glycol and glycerin while rotating the mixer paddle before thoroughly mixing. After making a homogeneous mixture, the mixture is introduced into the feed zone of a heated extruder maintained at a temperature of about 390°C (about 199°C) and then extruded into a mass through a multi-opening spinneret with an air inlet in the center of each spinneret. was forcibly extruded to produce hollow fibers. Two fiber spools were produced from each batch by varying the winding conditions between the spinneret and the spool.
A first spool of fiber was produced by passing the fiber through air to a set of first and second rolls rotating at a constant speed, without cold forming or drawing. The rotational speed of the second roll set is
A second spool of fiber was produced by adjusting the rotational speed of the second roll set to be 20% faster than the first roll set, and a third spool was produced by adjusting the rotational speed of the second roll set to be 20% faster than the first roll set. The nine fiber spools thus produced were used to measure water and urea transfer coefficients using the fiber laboratory test equipment described below. The test equipment consisted of a liquid bath with a magnetic stirrer, a dialysis test beaker with a magnetic stirring device, a top closure plate with pressure fittings, and a dialysis test beaker with a magnetic stirring device, a top closure plate with pressure fittings, and a notepad attached to each end of a fiber bundle consisting of 160 to 192 fibers per bundle. Consists of a connector that receives the end of the sealing sleeve. Bend the first bundle into a U shape and put it in a beaker.
One sleeve is then connected by a fluid line to a pump connected to the closure plate and connected to the reservoir by a line, and the other sleeve is connected to the reservoir by a return line so that the adjustable Fluid is pumped from the bath under pressure through the fiber bundle in the dialysis beaker. The beaker also had connections for inlet and outlet of dialysate to immerse the fibers in a stirring pool during either the K _UFR test for water or the Kurea test for water-urea solutions. The water transfer coefficient, K _UFR , was determined by pumping water under pressure into the fibers and measuring the increase in volume of water outside the fibers in the dialysis beaker. This test
It was carried out at 21°C. The K _UFR for each test was then calculated using the fibers shown in Table 1 and the difference in ml/m ² /h/ml of mercury pressure as shown in Table 2.
It was displayed in The urea coefficient Kurea was determined by creating a pool of water in the feed tank and pumping water through the fiber bundle.
The pool surrounding the fibers in the dialysis beaker is initially filled with water.
It was a urea solution. Measurements determined the urea concentration in the recirculating fluid at regular time intervals. The test was conducted at 21°C and there was no pressure difference across the fiber wall surface during the test. The difference between the urea concentration in the feed tank and the urea concentration in the dialysis beaker outside the fibers is expressed as the urea coefficient Kurea as a function of time and fiber area according to the following formula: M=Kurea・A(C ₁ −C ₂ ). Decided. where N is the flux across the membrane (mol/min), C ₁ is the initial urea concentration,
C ₂ is the final or measured urea concentration and A
is the area of the fiber wall or membrane between the two solutions. 2 without pressure differential or consequent extremes
In a two chamber system, the movement of urea through the membrane wall can be calculated integrally from the time interval t:
It is expressed by the following formula: ln [(C ₁ −C ₂ ) ^t=0 / (C ₁ −C ₂ ) ^t ] = [V ₁ +V ₂ /V ₁ V ₂ ·A] Kurea. where V ₁ is the volume of the supply tank solution,
and V ₂ is the volume of solution in the dialysis beaker. In the test, V ₁ and V ₂ and area A are constant, so that the plot of the values in both terms of the integral equation is a straight line whose slope is
It can be calculated using the Kurea unit as cm/minute. The values obtained for nine fiber lots are shown in Table 2 in the column labeled Kureacm/min x 10 ^-3 .

【table】

[Table] Example 10 Four artificial kidneys of the type commercially available under the name "C-DAK artificial kidney" from Cordis Dow Corporation, the applicant of the present application, were made using cellulose acetate fibers, and these artificial kidney was evaluated in the laboratory and compared to four similar artificial kidneys used in clinical trials of hemodialysis patients. Cellulose acetate fibers were made from a melt-spun composition having the composition shown in Batch 2 of Table 2. A spinning composition was made using ingredients similar to those used to make the fibers of Examples 1-9, except that this composition was used in commercial equipment and as described in these Examples. A similar mixing process and spinning technique was used, and the cold draw of the spun fibers was from about 7% to about 12%, with an average of about 10%. Four artificial kidneys with the effective membrane area shown in Table 3 were first evaluated in the laboratory and then clinically tested on hemodialysis patients undergoing intermittent hemodialysis on similar artificial kidneys from the same production lot. It was evaluated as follows. Laboratory evaluation was performed in the same manner as described in Examples 1-9, and clinical evaluation of the artificial kidney was performed using an average blood flow rate of 200 ml/min and 500 ml/min.
The artificial kidney was operated with an average blood flow rate of 192.5 ml/min and a dialysate flow rate of 500 ml/min. In clinical evaluation, K _UFR shows the average value for the entire treatment time, and urea clearance is shown in subscript 1 of Table 3.
Measurements were taken at times indicated by ~4.
Normal clinical procedures were used and no abnormalities occurred during the hemodialysis treatment period shown in the clinical trials in Table 3. The data in Table 3 are from laboratory and clinical operations at 37°C.
On the other hand, the data in the table is based on operation at 21°C. Coefficient K _UFR shown in Example 10 and Table 2
In order to compare K UFR and K _UREA , calculations were made to determine the corrected K _UFR and K _UREA coefficients at 21°C, which are also shown in Table 3. To determine K _UFR at 21°C, the following equation for steady laminar flow of fluid: V = (n _f π D ⁴ △P) / 128 μL V : UFR in ml/sec D : Average pore diameter n _f : Number of pores △P: Pressure difference between membranes L: Pore length μ: Viscosity of fluid ℃)] V (37℃) was used to correct the experimentally determined K _UFR at 37℃. The influence of temperature on the rate of diffusive mass transfer can be evaluated using the following formula: D〓/T=C (constant) D: Diffusion coefficient (K _OV of the membrane) T: Temperature expressed as 〓. See Perry's Chemical Engineer's Handbook, 4th edition, pages 14-23. To find K _UREA at 21℃, use the following formula: K _OV (T) = [μ(37℃)/μ(T)] [T/310〓] K _UREA at 37℃ obtained experimentally has been corrected.

【table】 [Brief explanation of the drawing]

FIG. 1 is a ternary phase diagram of the melt spinning composition used in the present invention. FIG. 2 is a schematic diagram showing the method for producing hollow fibers according to the present invention.

Claims (1)

[Claims] 1. A method for producing polyethylene glycol and glycerin-modified cellulose acetate hollow fibers, comprising: a. 41 to 50 weight percent of cellulose acetate, 2 to 20 weight percent of glycerin, and 30 to 57 weight percent of polyethylene glycol having a molecular weight in the range of 150 to 600. b. Producing hollow fibers from the molten mass of said mixture; c. Cooling the fibers; d. Cold drawing the fibers in the range of 2% to 20% based on the cooled fiber length. A method comprising the following steps: e) subjecting the fibers to a leaching step to remove polyethylene glycol and glycerin from the fibers; and f) replasticizing the fibers with glycerin and drying. 2 Cellulose acetate in the mixture is 42 or more
47 percent by weight. 3. The method according to claim 1, wherein room-temperature drawing is carried out in a range of 10 to 15% based on the cooled fiber length.