DE2827100C2 - Cellulose acetate hollow fibers and process for their manufacture - Google Patents

Description

5. The method according to claim 4, characterized in that that the cooled hollow fibers are cold-drawn by 10 to 15% of their length.

6. Use of the cellulose acetate hollow fibers according to any one of claims 1 to 3 in artificial ones Kidneys.

The invention relates to semipermeable hollow fibers made of cellulose acetate with an inner diameter in the range from 100 to 350 μm and a wall thickness in the range of up to 60 μm. The invention also relates to a method of making such fibers. .

Fibers of the type described above and a process for their production by mixing Cellulose acetate, glycerine and polyethylene glycol, melt spinning de *! Mixture to hollow fibers, Cooling of the hollow fibers, leaching of the hollow fibers to remove the polyethylene glycol and glycerine and drying of the fibers are known from DE-AS 14 94 579. In this publication is also the The use of such hollow fibers for the production of permeability-selective membranes is described. The membranes should be particularly well suited for the separation of constituents Gas mixtures, liquid mixtures and solutions, with particular emphasis on the separation of hydrogen from gas mixtures and the extraction of oxygen from seawater is pointed out

The invention is based on the object of cellulose acetate hollow fibers to create the improved properties in terms of their selective permeability against blood-soluble components.

This object is achieved by cellulose acetate hollow fibers of the type described at the outset, which are characterized according to the invention by a selective permeability of the wall during hemodialysis for water to be removed from the blood and dissolved matter with an ultrafiltration coefficient Kufr in the range from 1.5 to 4.6 ml / h / mVmbar and a urea coefficient. ^ Urea in the range of 15 χ 10 ^-3 to 45 χ 10 ^-3 cm / min.

The fiber according to the invention is distinguished from the known fiber essentially in that it improved permeability properties with respect to other substances dissolved in the blood, such as Urea, creatinine, vitamin B 12 etc, has Das Relationship between the permeability coefficient for these substances and the permeability coefficient for water (ultrafiltration coefficient) is therefore particularly high in the case of the fiber according to the invention. Of decisive importance The importance here is the urea coefficient. The cellulose acetate hollow fibers according to the invention are therefore particularly suitable for artificial kidneys

The reason for this high ratio is, on the one hand, the composition of the fiber according to the invention and on the other hand their special treatment. As already mentioned, DE-AS 14 94 579 is a Process for the production of cellulose acetate hollow fibers by mixing cellulose acetate and glycerin Polyethylene glycol, melt spinning the mixture into hollow fibers, cooling the hollow fibers, leaching the Hollow fibers for removing the polyethylene glycol and glycerol and drying the fibers are known. That In contrast, the method according to the invention is characterized in that

(1) 41 to 50 wt% cellulose acetate, 2 to 20 wt% Glycerine and 30 to 57% by weight of polyethylene glycol with a molecular weight of 150 to 600 mixed;

(2) cold drawn the cooled hollow fibers about 2 to 20 of their length; and

(3) the leached fibers are plasticized again with glycerine.

In a preferred method, the cooled hollow fibers become about 10 to 15% of their size Cold drawn length

The invention will now be explained in more detail with reference to the drawing

F i g. 1 is a three-component diagram in which the proportions of the three components in the melt spinning mixture are shown by the hatched areas A, B, C and D; and

F i g. 2 shows a schematic representation of the sequence of the individual process steps.

The mixture used for melt spinning consists of 41 to 50% by weight of cellulose acetate, 2 to 20% by weight of glycerol and the remainder to 100% by weight of polyethylene glycol with a molecular weight of 150 to 600. As in FIG. As shown in Fig. 1, this family of mixtures lies in the area defined by the extreme values of each of the three components that make up the area A, B, QD

form, is limited. Each of the specific mixtures, which consists of an amount of each of the three components in the area A, B, QD of FIG. 1, is suitable for melt spinning into hollow fibers or capillary fibers se fibers are used with excellent success in artificial kidneys of conventional construction. Preferred mixtures, which are particularly well suited for optimizing the operating properties of the dialysis, are in the range enclosed by the letters E, F, G and H in FIG.

The three components cellulose acetate, ethylene glycol and glycerine are by themselves not new to membranes, and cellulose acetate is already with υ a polyol, such as a glycol, in mixtures that too a plasticizer or a solvent, e.g. B. from Sulfolanlyp according to US-PS 35 32 527, contained, united been (DE-AS 14 94 579). It was not known, however, that glycerin, a non-solvent for cellulose acetate low molecular weight selected at room temperature in conjunction with polyethylene glycols can be used to make strong hollow fibers that have modified permeability properties relative to cellulose acetate fibers obtained in the presence of a sulfolane. Likewise, it was not known that certain amounts of the glycerine in such mixtures caused a modification the permeability properties of the low molecular weight solutes through the fiber wall relative to the permeability to water through the same wall.

The term cellulose acetate as it is used here in the description and in the claims, Cellulose acetate means cellulose diacetate as it is im Commercially available is suitable according to the invention and is preferred although amounts of monoacetate are also used and triacetate may be present, e.g. B. up to about 25%; are usually commercially available Cellulose diacetate contain minor amounts.

When cellulose acetate in a solvent such as dimethyl sulfoxide, sulfolane, triethylene glycol or a another low molecular weight glycol that is liquid at room temperature and dissolved by a conventional spinneret is spun into a fiber tow, the individual fibers tend to stick to each other, when they are wound on a spool. Such fibers even if they are below the gel point Chilled and hardened into solid fibers hold back a lot of solvent, which is what appears to be the Keeps surface areas soft enough to cause sticking during winding. Previously it was necessary to remove the solvent from the spun and cooled fibers prior to winding leach out; a hot water bath was used for this purpose. However, it has been found that the immediate transfer of the hollow capillary fiber after cooling into a leaching bath fiber pulsing causing uneven wall thicknesses and uneven inside diameters It is now it has been found that the fibers stick or fuse together without leaching prior to winding can be avoided if a low molecular weight glycol is used as a solvent for the cellulose acetate is modified with the amounts of glycerine given above. Apparently the glycerin sets the surface softening effect of the glycol, and the fibers can be wound and even just and wound on spools under tension without that there is a risk of sticking or welding. The spun fibers obtained have more uniform properties Wall thickness and inner diameter and can be used at room temperature on spools for later Can be stored indefinitely for use in artificial kidneys.

Glycerine apparently also modifies the gelation of the cellulose acetate during cooling in such a way that the resulting porosity of the fiber wall is changed. When glycerin is present in the mixture, a gelled fiber is obtained which is sufficiently strong to maintain its integrity and the uniformity of its wall thickness and inner diameter during stretching or cold drawing immediately after gelling or solidification. Surprisingly, the cold stretching also modifies the fiber wall porosity in such a way that substances of low molecular weight dissolved in the blood migrate more quickly from the blood flowing in the fiber through the wall to the dialysate solution flowing outside the fiber. A substantial improvement (increase) in the permeability of that dissolved in the blood, & h. solutes of molecular weight up to about 1400, such as urea, creatinine, uric acid, etc. up to and including vitamin B 12, is achieved without increasing the ability of the fiber to transport water through the same wall. Although the mechanism of this change is the result of the Cold drawing has not been fully understood, it has been found that the degree of cold drawing and the amount of glycerin present in the melt spinning mixture are interrelated and interdependent. Generally speaking, if a melt spinning mixture consisting of cellulose acetate dissolved in a polyethylene glycol with a molecular weight in the range from 150 to 600 and at least 2% by weight glycerol is used, a certain increase in the permeability of the blood dissolved takes place when the cold drawing is up to 20% % of the length of the spun fibers is stretched. The increase continues with increasing glycerol content, but the relationship is not linear. With quantities of glycerin in the melt spinning mixture between 3 to 10 wt .-% and cellulose acetate between 42 and 47 wt .-% and the remainder polyethylene glycol, an improvement in the ratio of the permeability of dissolved in blood to water takes place when the degree of cold drawing up to 15% fiber length increases and at 43 to 45% cellulose acetate excellent results are obtained at 10% cold draw. The maximum improvement in the ratio of the permeabilities of dissolved solids in the blood to water is obtained with mixtures derived from the preferred range E, F, G, // in FIG. 1 are selected and the optimal degree of cold stretch for a given blend can be determined by a few simple tests.

In Fig. 2 are the individual steps of the invention Process listed The cold drawn fibers can be stored, or a variety of For example, cables can be in fiber bundles of 3,000 to 30,000 fibers for use in man-made Kidneys are compressed. The fibers in the compacted bundle are drained through a leach tank to remove the glycol and glycerin and a bundle of semi-permeable hollow fibers to build. The leached bundle is then softened again with a glycerine-water solution,

"Excess glycerin is removed and the fibers are dried.

The preparation of the melt spinning mixture can be carried out in any suitable manner using conventional mixing devices. It is essential that the mixture is sufficiently well mixed so that an intimate, uniform mixture is obtained. For example, dry cellulose acetate powder is mixed with a weighed amount of polyethylene glycol and glycerine in a high-shear Hobart mixer. The mixed material is further homogenized and further mixed by feeding it into a heated twin-screw extruder with counter-rotating screws. B. an IO to 32-hole nozzle \ 5 with gas feed for blowing gas into the core of the extrudate. A preferred gas for this purpose is nitrogen, but other gases can be used as well, including carbon dioxide, air, or another harmless gas. The extrudate emerging from the spinneret is then cooled, e.g. B. by forced air cooling of varying pressure and / or temperature to cause gelation and solidification of the extrudate into solid self-supporting fibers. The fibers typically have a capillary size, ie an internal diameter in the range from 150 to 300 μm and a wall thickness in the range from 20 to 50 μm.

In the method of the invention, the short period of time is immediately after the extrudate from the Spinning nozzles leaked is extremely important in terms of achieving the desired permeability of the finished fiber. During this period of time, the porosity and thus the permeability of the resulting Fiber determined as a joint function of cooling rate and cold drawing, to which the fibers are subjected. For a given melt spinning mixture, the porosity is a the given degree of tension of the fiber is increased by drastically cooling the molten fiber, in comparison less drastic cooling and slower gelation of the extrudate into fibers. Increased porosity resulting from such quenching usually affects the ability of the Fiber is used to transport water and can, if necessary, be used to increase the speed of ultrafiltration Select or modify the fiber when it is used for hemodialysis. By Increasing the flow rate of the air at room temperature through the extrudate you can make small modifications in the porosity of the finished fiber. The same effect can be achieved Lowering the temperature of the cooling medium can be achieved. By regulating the flow rate the air and lowering the temperature, optimal conditions can be achieved. It is preferred Use air at room temperature for cooling; economically satisfactory results are obtained without cooling below room temperature.

The cold stretching is satisfactorily effected by the extruded and solidified fibers over a series of rollers or spaced-apart rows of rollers, such as godet rollers, The desired degree of stretching can be achieved by controlling the speed of rotation of the second Roller or the second group of rollers are obtained in the direction of the fibers. Usually there will be a good correlation between the degree of cold stretching and the setting or dimensioning the speed of rotation of the downstream roller set, making it suitable for a specially Desired percentage cold stretching is only necessary, the rotational speed of the downstream Roller set to precisely control relative to the upstream roller set. Record or Winding up of the cold-drawn fibers on bobbins or reels can be done with commercially available winding devices, such as the Leesona winders, taking care that the fibers are somewhat taut during the pick-up.

In a preferred embodiment of the method according to the invention, a large number of cold stretching spools or rolls are attached in order to guide a large number of fiber cables through a conventional collecting device and to form a consolidated bundle. This fiber bundle is then leached to remove the glycerine and the polyethylene glycol. The leaching treatment can be carried out using conventional means, e.g. By passing the fiber bundle through a bath of the selected solvent or by semi-continuously dipping the spools or rollers in such a solvent. The leach solvent can be any that are good solvents for the plasticizer and glycerin, but not for cellulose acetate. Preferably, water is. Aqueous solutions, alcohols and mixtures thereof have been used with success, e.g. B. methanol, ethanol, propanol and mixtures thereof, dilute aqueous solutions of sodium sulfate, magnesium sulfate and sodium chloride. The leaching can be carried out at room temperature or at an elevated temperature. Elevated temperatures are recommended up to for example 80 to 90 ⁰ C. Preferably, a first and a second leach uses the first at a higher temperature than room temperature, preferably lake at 80 to 90 ° C for 5 to 30, and the second bath at room temperature for 1 to 10 minutes, preferably 2 to 4 minutes The following can be stated as a guide for the selection of the optimal first leaching temperature for producing fibers of the desired water transport rate: If the cellulose acetate content rises between 41 and 50% by weight, it falls the water transport speed related to cellulose fibers decreases to a lower speed when the leaching temperature is increased from 20 to 80 ° C. Increasing leaching temperatures between about 50 and 80 ° C increase the permeability of the fibers to urea, creatinine and other low molecular weight solutes, including vitamin B 12.

After the fibers have been leached and the desired permeability has been established, the transfer of the fibers to a dry state requires a softening again Glycerin. The re-softening is preferably carried out with a water-glycerin solution which contains about 30 to 60 wt .-% glycerol Good results are achieved with a 50% aqueous Glycerin solution obtained.

When the glycerin concentration of the replasticizer solution is below about 50%, the water transport is reduced As in FIG. 2 shown the fibers can be re-softened by passing them through a conventional drying

oven or other drying device such as vacuum drying devices. If desired, part of the glycerol can be removed by blowing it away with compressed air, for which purpose the fiber bundle is passed through or past a set of opposing air brushes at pressures and temperatures which are suitable for reducing the glycerol content. If the glycerol content is reduced from about 0.07 to about 0.42 bar by drying or vacuum or by increasing the pressure of the air stream, the water transport capacity and the transport capacity for substances dissolved in the blood are reduced. Examples of good drying conditions are around 40 to 80 ^° C and 1 to δ min With longer drying times above 60 ° C., the transport speed of dissolved solids decreases, and therefore lower temperatures should be used in order to optimize the ratio of the permeabilities of dissolved solids and water during hemodialysis.

The cellulose acetate hollow fibers produced by the method described above have a ratio of the permeability to water and to that dissolved in the blood, which differs from that of the known cellulose acetate hollow fibers.The water transport permeability is expressed as the ultrafiltration coefficient, Kufr, and is in the range of 1 , 5 to 4.6 ml / h / m ² / mbar pressure difference between the opposite sides of the membrane wall. The Kufr coefficient is a number representative of the ability of the semipermeable fiber to allow water to pass per unit of pressure gradient across the effective membrane area Liquid is and through which the water transport can take place, z. B. per m ² or some other selected area.

The permeability for dissolved solids in the blood is expressed by the dialysis coefficient Km of the membrane.The dialysis coefficient Km is a number that is representative of the ability of the semipermeable cellulose acetate fibers to separate solids in a liquid on one side of the semipermeable wall of the fiber and this component to become one to transport another liquid with which the opposite side of the same wall surface is in contact. For the present fibers, the membrane coefficient for urea / ^ urea is in the range of 0.015 to 0.045 cm per minute; the membrane coefficient for crcainin trcaünin in the range from 0.013 to 0.027 cm per minute and the membrane coefficient for vitamin B 12 K ^ ₂ in the range from 0.002 to 0.005 cm per minute. The ratio of the dialysis coefficient of the membrane Km to the ultrafiltration coefficient Kufr is over 3.9: 1 based on the specified ranges and units.

For hemodialysis, the preferred material has the following coefficients: Kufr from 23 to 3.8 ml / h / m ² / mbar, / ^ urea over 0.020 cm / min and Khaknxtoff / Kufr over 6.5: 1. Such fibers make the construction of artificial kidneys possible, which in comparison to the use of the known semipermeable cellulose fibers significantly shortens the time required for hemodialysis, creates flexibility and enables easy regulation during dialysis. which, for example, have a Kufr below 0.8 ml / h / m ² / mbar when operated at room temperature, the rate of water removal from blood dialyzed with artificial kidneys using the new cellulose acetate fibers under the same working conditions is 2 to 6 times as big. Although a kufr above about 4.6 may require the replacement of some of the removed water before treating the preselected water level at the end of hemodialysis a higher water removal rate has certain advantages over a lighter and more flexible one Regulation during dialysis with it. They also make artificial kidneys with such Cellulose acetate fibers enable faster removal of substances dissolved in the blood, such as urea, creatinine, uric acid, etc. Artificial kidneys with 1 m ² effective surface of the new cellulose acetate fibers with coefficients in the range given above create a urea cleanse in the range of about 100 to about 165 ml per minute, a creatinine cleanse in the range of about 80 to 135 ml per minute and a B-12 purge in the range of about 15 to about 45 ml per minute.

A range of spin mixes and variable processing parameters have been proposed by the invention which make it relatively easy to select and manufacture cellulose acetate fibers having optimal Kufr and Km , and such fibers for to use artificial kidneys that meet certain requirements. Using certain blends and choosing suitable processing conditions, it is relatively easy to manufacture cellulose acetate fibers which at the same time make certain Water transport speeds and transport speeds for solutes within the above specified area. Thus, the novel fibers are a suitable means for easily and conveniently manufacturing a family of artificial kidneys, the regulated and preselected speeds for the removal of water and solutes during the Have dialysis.

The invention is explained in detail below on the basis of examples

Examples

Cellulose acetate fibers were made using various melt spinning mixtures first mixture contained 43 wt .-% cellulose acetate, 50% by weight polyethylene glycol of molecular weight from about 400 and 7 weight percent glycerin, and the second The mixture contained 43% by weight of cellulose acetate and 39% by weight of polyethylene glycol of one molecular weight from about 400 and 18 wt% glycerin. With both of them The same cellulose acetate material was used as the same cellulose acetate material that cellulose acetate has an acetyl content of about 393%, determined according to ASTM method D-871-72, and a falling ball viscosity of 17 to 35 seconds, determined by the ASTM method D-1343. The polyethylene glycol in the two blends was PEG E 400, USP grade, and the glycerin was also a USP grade product

Each mixture was made by carefully mixing the powdered cellulose acetate with the polyethy lenglycol and glycerine in a standard laboratory mixer (a Hobart mixer) made with the liquid ingredients slowly added, while the mixer was running. Having an even

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Mixture was prepared, it was converted into the filling opening of a hot extruder, the temperature was maintained at about 200 ⁰ C. The extruded mass was forced through a multi-hole spinning nozzle which was designed so that air is introduced through the center of each spinning hole, so that hollow fibers are formed.

Three fiber bobbins were produced from each mixture by varying the take-up conditions between spinnerets and bobbins. The first coil of fiber, without cold forming or drawing, was obtained by air passing the fibers to first and second sets of rollers rotating at the same speed. A second spool of fiber was obtained by passing the fibers over two sets of 5 rolls, the speed of rotation of the rolls of the second set being 10% faster than that of the first set. A third spool of fiber was obtained by passing the fibers over two sets of rollers, the rotation speed of the rollers of the second set being 20% faster than that of the first set. The fiber coils produced in this way were tested in a laboratory test apparatus to determine the water and urea permeability coefficients The ends of a fiber bundle each containing about 160 to 192 fibers were attached. The fiber bundle was bent into a U-shape and inserted into the cup and connected to the closure plate. A sleeve was connected by a liquid line to a pump which was connected to the container by a line. The other sleeve was connected to the container by a supply line so that the liquid from the container could be pumped under controlled pressure through the lumens of the fibers in the dialysis cup. The beaker was also provided with dialysate inlet and outlet connections, and during the test the fibers were placed in an ambient stirred amount of either water for the KuFR-Tsst or water-urea solution for the

The coefficient Kufr was determined by pumping the water under pressure through the fibers and measuring the increase in the volume of water outside the fibers in the dialysis cup. The tests were carried out at 21 ° C. Kufr was then used for each test using the fibers specified in Table I in ml / mVh / mbar pressure difference calculated as shown in Table II

The urea coefficient ^ urea was determined by providing an amount of water in the Feed tank and pumping the water through the fiber lumens. The amount of water that the fibers in the The dialysis cup was originally a water-urea solution. Measurements were taken to determine the urea concentration in the circulating liquid at time intervals.

The tests were carried out at 2ΓC, and above that There was no pressure differential across the fiber wall surface during the tests.

The urea coefficient / ^ urea was below Consideration of the difference in the urea concentrations in the feed container and in the dialysis cup on the outside of the fibers as a function of time and the fiber area according to the following equation calculated

N = / ^ UREA -A (Q- C ₂ ),

where means:

N is the flow rate through the membrane in moles per minute,

Ci the urea concentration at the beginning, C ₂ the urea concentration at the end or the

measured concentration and A the area of the fiber wall or membrane between the two solutions.

In a two-chamber system without a pressure difference or resulting ultrafiltration, the Transport of the urea through the membrane over a time interval f can be integrated as follows To get equation:

(C ₁ -C ₂ ) '

in which:

· [■

k ₁

Λ ^ UREA "' ,

Vi is the volume in the solution in the feed container and V _{2 is} the volume of the solution in the dialysis cup.

In these tests, the volumes Vi and V ₂ and the region A were constant, so that a plot of the values on each side of the integrated equation yields a straight line from the inclination / (^ urea in cm / minute can be calculated. The values thus obtained for the six fiber gobs are given in Table II as urea cm / minute χ 10 ^-3 .

Table I. Spinning mixture

Wt%

Inner Outer Average Inner Outer Average Inner Outer Average Fiber through Fiber through Wall thickness Fiber through Fiber through Wall thickness Fiber through Fiber through Wall thickness knife knife Membrane thickness knife knife Membrane thickness knife knife Membrane thickness

μιη

μιη

μηι

μιη

μπι

μιη

μιη

Mixture No. 1
43% polymer (CA-400-25)

50% plasticizer (PEG-E-400)

7% plasticizer (glycerine)

Mixture No. 2

43% polymer (CA-400-25)

39% plasticizer (PEG-E-400)

18% plasticizer (glycerine)

185

37.5

193

273

40.0

274

39.5

174

39.5

213

282

34.5

297

36.5

K)

Table II 0% stretched
ml / h / m ² / mbar ^ urea ^ urea
cm / min _v
X 10 " ^{3 KuFR} 10% stretched
ml / h / m ² / mbar ^ UREA ^ UREA
cm / min _v
X 10 " ^{3 KuFR} 20% stretched
ml / h / m ² / mbar ^ UREA ^ UREA P.
cm / min _v
χ 10 " ^{3 KuFR} 1 - t 28 27 100 Spinning mixture Mixture No. 1 3.98 23.29 5.84 3.57 25.3 7.09 3.18 22.90 7.20 43% polymer
(CA ^ OO-25) 50% plasticizer
(PEG-E-400)
7% plasticizer
(Glycerine)
Mixture No. 2 3.55 17.48 4.93 3.88 17.92 4.62 3.79 18.19 4.80 ti. * ,. L. ■. ⁽ .-iiiwVi; J, '>. ii .. · .- = 43% polymer
(CA-400-25) 39% plasticizer
(PEG-E-400) Here 18% plasticizer
(Glycerine) for 2 sheets of drawing O
3

Claims (4)

Patent claims: 1. Cellulose acetate hollow fibers with an inner diameter in the range from 100 to 350 μm and a wall thickness in the range from 20 to 60 μm, characterized by a selective permeability of the wall during hemodialysis for water and solutes to be removed from the blood with an ultrafiltration coefficient Kufr in the range from 1.5 to 4.6 ml / h / m ² / mbar and a urea coefficient. ^ Urea in the range from 15 × 10 ^-3 to 45 χ 10 ^-3 cm / min. 2. Cellulose acetate hollow fibers according to claim 1, characterized by a creatinine coefficient is .Kcre »tinhi in the range of 13 χ 10 ^-3 to 27 χ ΙΟ- ³ cm / min. 3. Cellulose acetate hollow fibers according to claim 1 or 2, characterized by a vitamin B-12 coefficient Kb \ 2 in the range of 2 χ IO- ³ to 5 χ IO- ³ cm / min. 4. Process for the production of cellulose acetate hollow fibers according to one of the preceding claims by mixing cellulose acetate, glycerin and polyethylene glycol, melt-spinning the mixture to hollow fibers, cooling the hollow fibers, leaching the hollow fibers to remove the Polyethylene glycol and glycerol and drying the fibers, characterized in that one 30th (1) 41 to 50% by weight cellulose acetate, 2 to 20% by weight glycerin and 30 to 57% by weight Polyethylene glycol mixed with a molecular weight of 150 to 600; (2) the cooled hollow fibers cold drawn 2 to 20% of their length; and (3) the leached fibers are plasticized again with glycerine.