DD200311A5 - SEPARATION DEVICE FOR HAEMODIALYSIS AND HAEMOFILTRATION OF BLOOD - Google Patents

Abstract

The invention relates to a separation device for hemodialization and hemofiltration of blood. The aim of the invention is to improve the cleaning ability of such devices for the removal of impurities, such as urea, creatine, as well as the improvement of the wet tensile strength of the cellulose hollow fibers used in these devices. In the inventive separation device hollow fibers are used with an ultrafiltration coefficient K & ind UFR! from about 2 to 200 ml / h / m & exp2! / mm Hg; a urea coefficient K & ind urea! from about 15x10 & exp-3! up to 45x10 & exp-3! cm / min and an intrinsic wet tensile strength of about 2 to 11 g / g cellulose polymer. They are made by: a) melt spinning from a melt spinning composition consisting essentially of about 35 to 80 weight percent cellulose ester and the balance polyol with a molecular weight of 106 to 900; b) hydrolyzing the cellulose ester hollow fiber into a cellulose hollow fiber; c) replastifying the cellulose fiber with a water-soluble plasticizer; and d) drying the plasticized fiber.

Description

Berlin, May 25, 81 Excretion from AP B Ol D / 226 098 (58 534 12) 59 179 12

Separator for hemodialyzing and hemofiltration of blood . _L , »

The invention relates to a separation device for hemodialyzing and hemofiltration of blood, it is used as an artificial kidney for the detoxification of blood,

Separating means for Hämodialysieren and hemofiltration of blood are known They are equipped with a pair of blood chambers _c which is arranged through an intervening Dialysst "chamber ^ which is integrally connected to the blood chambers, _o vverden kept at a distance A bundle of hollow fibers terminate at their opposite ends in a tube plate made of plastic «. The tubesheet bond the fibers to each other and also create an annular part _e aer outside the scope of the fibers in the bundle. " The part serves * to connect the tubesheet to the end sections of the dialysate chamber and the plutkair chambers and thereby to enclose the blood chambers and the dialysate chamber with the fibers in the dialysate chamber so that the chambers are isolated from each other in fluid tight connection stand*

The water permeability of the semipermeable used in the known separating devices or "artificial kidneys"! Celluldse 'Hohifassrn does not meet the requirements for the cleaning effect of artificial kidneys,

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Another disadvantage of the fibers used in the known separation devices is their low tensile strength, in particular wet tensile strength _f which caused high economic losses

Most of the cellulosic fibers "used in artificial kidneys for hemodialysis" have hitherto been prepared by melt-spinning a cellulose ester * such as cellulose triace- tate _t in a continuous process, as disclosed, for example, in US Pat. No. 3,546,209. * Another part the cellulose hollow fibers were prepared by the copper-ammonia method; an improved process is described in U.S. Patent No. 3,888,771 * During be obtained cellulose fibers in these fundamentally different method "; which have acceptable water permeability (ultrafiltration) and urea permeability (clearance) for use in artificial kidneys, their permeabilities are generally not optimal. For example, cellulosic fibers produced by the process of U.S. Patent 3,546,209 have lower water permeability than is desired with fibers * have acceptable clearance properties for urea, Greatinine, Vitamin B. "and other low molecular weight blood contaminants."

Moreover, the continuous production of cellulosic fibers from melt-spun cellulose acetate fibers involves the chemical transformation of the thermoplastic cellulose acetate into the non-thermoplastic cellulose polymer by hydrolysis under saponification in an aqueous alkaline bath. During the hydrolysis, the thin-walled, small diameter fibers are extremely sensitive

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to touch and break easily "Successful manufacture at just a sufficient grade: to be commercialized depends on maintaining enough tear strength in the fiber during the manufacturing stage where moisture is maintained to break or damage to avoid"

The concept of producing semi-permeable hollow fibers "by melt spinning a plasticize polymer composition has been developed in the early 60 Oahren and first disclosed in U.S. Patent No. 3,423,491 In the patent, various types of polymers are described _for including Celluloseester and suitable plasticizers for use in the formation of [0002] The Cellulose Polymer Esters Discussed Thermoplastic Polymer Spun Compositions * Polymeric cellulose esters were developed into inexpensive commercial polymers, especially cellulose acetate, and tetramethylenesulfone usually referred to as sufolfolide was normally used as a plasticizer for the melt spinning composition to make cellulose acetate fibers. US Pat * 3,494,780 and 3,532,527 disclose improvements to the sulfolane cellulose acetate melt spinning web after which cellulose acetate fibers are extruded, including either dipping the spun fiber ch in a OeAD _e includes spinning the 'a mixture of sulfolane and a polyol having a molecular weight under 4000th ,, modifying the SuIfClan plasticizer or-under by including a small amount of a polyol having a molecular weight prior to u m spinning of the fiber about 20 000 .., These patents can also be seen that Polyoley alone as a plasticizer in egg formulation of melt spinning compositions with cellulose esters _β particular cellulose acetate

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"unsatisfactory"

The object of the invention is to provide a separation device for hemodialyzing and hemofiltration of blood having improved cleanability for separating impurities such as urea, creatinine and the like.

Darlegunq the essence of the invention

H l-l! ) ilM i ii IT h -Iib-ΓΛ 'ι ~ ΓΙ "ιτ1πι ~ ΠΓπ - ΊΤιτ ~ ίΐ I, ίι" ^ Ct'IMfiiIIi -ii ¹ HIHiPfT IJMIi BIn λΛ * II BTlr Ii ib Πι ill """ill"Λ ^ Τμ

The invention is based on the object "the chemical-physical properties of the semipermeable cellulose hollow fibers used in the separator and the tensile strength of the fibers _e in particular the wet strength during the hydrolysis or the conversion of cellulose ester into cellulose before drying _f storage and incorporation in Hemedialysatoren or to improve hemofilter «.

According to the invention, the separation device is for hemodialyzing and hemofiltration of blood with a pair of blood chambers, which are held by an interposed, einstükkiges with them dialysate from each other at a distance. Bundle of H.phlfs which "ends at each of its ends in a tube-bottom" which is sealingly arranged between and fixed to the dialysate chamber and each of the two blood chambers, to connect the chambers in fluid-tight connection with the passages in the tubes Separating fibers, creating connections between the interior of the blood, chambers, such that the hollow fibers are a plurality of hollow fibers with an ultrafiltration

25 »5« 81 59 179 12

tion coefficient Isjpo of about 2 to about 200 ml / h / m / mm

jp

Hg; a urea coefficient K of about 15 χ 10 ~ to about 45 χ 1Q ~ cm / rain _e and an intrinsic wet tensile strength of about 2 to about 11 g / g of cellulose polymer and can be obtained by?

a) melt spinning a Celluloseester hollow fiber from a melt spinning composition% Celluloseester and the rest consists essentially of about 35 to about 80 percent by _e ~ to 100 by weight "~% of at least one polyol of an average molecular weight in the range of from about to about 900, ·

b) largely hydrolyzing the cellulose ester hollow fiber into a cellulose hollow fiber

c) Wiederplastifizieren the cellulose fiber while still wet ISTY with a water soluble substantially non-volatile plasticizer, and

d) Drying of the plasticized fiber «

The hollow fibers used in the separator of the present invention preferably have an outside diameter of about 200 to about 400 μm and a wall thickness of about 12 to 80 μm

The separating device according to the invention and. the hollow fibers present therein are sterile with gamma rays as a result of sterilization, the sterilized hollow fibers having an intrinsic intrinsic strength in the range of from about 5 χ 10 ^ to 9 χ 10 'g / g cellulose fibers. "

Particularly advantageous properties of the invention. Separator in dom case · when the hollow fibers in

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The apparatus comprises gamma-rays as dry replanted cellulose fibers containing about 2.0% glycerol, sterilized and the sterilized fibers have an intrinsic Na tear strength of about 9 × 10 g / g cellulose fibers *

The separator of the present invention also has very advantageous properties when the hollow fibers in the device have been sterilized with gamma rays while the fibers were wetted with a physiological saline solution, and the sterilized fibers have intrinsic wet tear fibers

trinsic wet tensile strength of about 5 × 10 g / g cellulose

The invention is based on the surprising discovery that Celluloseester-Schmelzspinnzusaramensetzungen _t the sul ~ are folanfrei and only certain polyols of low molecular weight or mixtures thereof include, can be melt spun into fibers which can be hydrolyzed to cellulose fibers, the wet strengths during the conversion of the The omission of sulfolane, which has previously been considered necessary, is the key change that enabled the production of the substantially improved fibers of the invention. The resulting cellulose ester fibers of the invention have satisfactorily high levels intrinsic wet strengths in their spun form and, moreover, the spun fibers retain their intrinsic tear resistance during polyol suction and hydrolysis or deacetylation, ie, the stages in which the cellulose ester fiber enters the cellulose fiber

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In some cases, even the intrinsic tear strength increases *

The semipermeable cellulosic hollow fibers used in the separator of the invention are prepared by melt spinning a cellulose ester melt spinning composition comprising about 35 to 80 weight percent of a selected cellulose ester or cellulose ester mixture and one or a mixture of polyols of average molecular weight in the range of about Contains 106 to 900.

Celluloseester suitable close> ay cellulose Mono ": _f di- and triacetate and mixtures thereof · _e cellulose acetate propionate \ Celluiose acetate butyrate" cellulose "propionate and cellulose butyrate and mixtures of two or more of these esters *. The acetates are preferred in particular cellulose diacetate, and mixtures preferably include at least a small proportion of one or more other cellulose acetates.

· For the production of an acceptable Schraelzspinnzusammen "reduction is the class of polyols suitable as such, but the polyols with lower molecular weight, for example, an average molecular weight in the range of about 106 900 * big attempts _e a single polyol. Using a molecular weight of about 600 with cellulose acetate failed because the composition is not spun . could _e Satisfactory melt spinning conglomerates. are jedoc'i when using Polyolgemischen.e in which one of the polyols having an average molecular weight substantially in excess of 90O _4, for example, .1400,., obtained wordenj. a mixture of two polyethylene »

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glycols "of which one had a molecular weight of 200 and the other had a molecular weight of 1450" so as to give an average molecular weight of 902 proved to be suitable in the preparation of a cellulose acetate carbon spun composition spun into hollow fibers having the improved tear strengths. which characterize the fibers in the separating device according to the invention. Genetic of polyethylene glycols with polyols _ff, for example, a mixture of polypropylene glycol of average molecular weight 400 and glycerin gave a spinnable composition, while polypropylene glycol of average molecular weight 400 alone gave no spinnable composition. Blends of polyethylene glycols and ethylene glycols were satisfactory and blends 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 _e have too high a molecular weight to form a spinnable Celluloseesterzusammensetzung, may be modified by addition of glycerol to obtain a known non-solvent for cellulose "ester * a * composition can be successfully spun into the improved fibers for use in the inventive apparatus _P the glycerol proportion required for this purpose will vary with the molecular weight of pure polyethylene or polypropylene glycol and also with the Celluloseester or Estergemisch "the vorliegte in general, the Amount of glycerol required is higher, if the average mo-

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The molecular weight of pure glycol rises above about 600. The glycerol concentration should also be increased when the proportion of cellulose ester blended with the cellulose diacetate "increases, or in melt spinning compositions made from cellulose propionate or cellulose butyrate or mixtures thereof." As a general rule, glycerol is in the range of about 5 to 35 percent by _e -.%, based on the cellulose-Schmslzspinnzusammensetzung, can be used with success polyol © having at least two hydroxyl groups in the molecule ;, which are suitable _e include j diethylene glycol ·, triethylene "tetraethylene glycol _f mono- · -, di and tripropylene glycols and mixtures of one or more of the propylene and ethylene glycols or glycols with ethylene-propylene chains in the glycol molecule, and mixtures of any one or more polyethylene or polypropylene glycols with glycerine in an amount below 50% by volume of the glycol-glycerine mixture "

The process for producing the fibers used in the inventive apparatus comprises the aer Stufen.des mixing the selected Celluloseester and the polyol to form a melt-spinning composition, and melt-spinning the Hohlfa.sern-.Abkühlen them to a gel-like self-supporting state "or hydrolyzing the cellulose ester deacetylate Hchlfasern to substantially Celluloscfasern, d * 'h "Hydrolisieren a substantial portion of the ester groups with the formation of hydroxyl groups," Hir.e complete hydrolysis is usually not achieved and is not necessary, but to obtain best per meabiliiätseiigonschaften and during the

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Maintain storage and shipping, is substantially complete hydrolysis of for example, about 90% expedient "The Plyol _e is present which in the as-spun Celluloseesterfasern, is usually leached · from the fibers during the hydrolysis or deacetylation Alternatively, the polyol in a separate stage be removed after hydrolysis ©

Semipermeable cellulose hollow fibers _e which have been manufactured industrially from a sulfolane-acetate Schmeizspinnzusammensetzung by the method of US-PS 3,546,209 and used in known artificial kidneys in large quantities to about 1972 sind.y had, for example, a water permeability coefficient Kjipp of about 1.0 to 1.2 ml / h / m fiber surface area / mm Hg over the semipermeable fiber wall at 37 C, a urea coefficient K | _lor -. from

- 3 is about 28 to 30 χ 10 cm / min * and a Fasernaßfestigkeit after the deacetylation of about 1.4 to about 1.8 g intrinsic filament tenacity / g of polymeric cellulose ^ The improved cellulosic fibers _e which are used in the inventive separator werden- * Much better in all three important functionalities * The most surprising and most improved feature is the increased intrinsic wet tear strength. As noted above , the wet tensile strength of the fibers is exceptionally important for successful continuous production in the production line

For example, in a street, a cable of 16 to 30 fibers or a plurality of such thread cables _e runs from

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the spinneret are passed through air to become a self-supporting hollow fiber, then through a series of liquids in treatment tanks, which sequentially leach the cellulose ester fiber polyol, hydrolyze the ester to cellulose, rinse the hydrolysis product and remove excess hydrolysis agent from the cellulose fiber and Plasticize cellulose fiber again. The plasticize product fibers are then taken up by take-up rolls "During the NaSbehandlungsstufen the fibers are subjected to a stretching or there is a force acting in the longitudinal direction of force applied ^ while they are subject to strong intra-molecular rearrangements, in particular, those from the polyol removal and chemical changes during the deacetylation of Cellulose esters result in cellulose fiber breakage or damage due to the inability of the polymer skeleton of each fiber to withstand tensile or frictional forces during such continuous processing, interrupts continuous operation and is highly undesirable *

It has been found that cellulose acetate fibers, which tend from a Schrcelsspinnzusammensetzung according to the invention _f which is free from SuIfDianen _f to a greater proportion of their tensile strength _g - they after spinning have (as - spun tensile strength) _r during the 'A 'enes _β maintain through successive NaSbehandlungsstufen than the fibers that have been made of sulf oianhaltigen Schraelzspinnzusammensetzungen and "long commercial experience in addition to the improved fibers certain an unexpected increase in dsr tensile strength compared to the state after spinning, and this increase

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takes place during the hydrolysis stage of the process instead of * The cellulose fibers used in the inventive separator, have average intrinsic tear strengths in the wet state after the hydrolysis, are at least two to seven times higher than that of cellulose hollow fibers obtained by the method U.S. Patent No. 3,546,209 have been manufactured "in this specification and claims, the term" intrinsic tear strength ", applied to the tear strength measurements of the wet cellulose fiber, the breaking strength _t in g / g polymer of a 5.08 cm length of a single wet fiber and the force _s required to break the fiber when it is suspended vertically in an Instron between two jaws "the tests to preserve Oer intrinsic wet tensile strengths, which are reported in Table I, represent the grams of polymer a selected 5.08 cm fiber length is an average weight in g, which is f for each particular 5.08 cm sample of the cellulose fiber, by drying the adjacent 2540 cm fibers of the same strand to a constant weight, weighing 2540 cm in length and dividing the total weight by 500, thereby obtaining an average weight; this was then used for the particular 5.08 cm piece subjected to the Breaking Resistance Test. "Such action increases the accuracy of the tear strength determination by eliminating the potential error due to the fiber wall thickness change along the continuous fiber." Also, each tear strength value averages six determinations on different ones 5, o8 cm long samples. the thus determined increases in intrinsic tear strength has been made, is economically important _for since they greatly improved by a continuous production of the fibers according to the invention in terms of production capacity

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* 13 will.

While the above-described effects of increased wet tensile strength during the fiber production of high economic value are, is the increase in water permeability which is achieved in particular fibers used in the inventive separation device is also extremely important. Certain fibers have up to 80 times higher water permeability compared to the hitherto available cellulosic fibers obtained from cellulose acetate melt spinning compositions. Such an increase in water-permeability means that the capacity of the fiber, water from a water-containing liquid such as blood to separate, is drastically increased, and the practical advantage resulting from this is significant, by the use of the separation device according to the invention a substantial Reduction of the required per hemodialysis treatment time is possible, which is understandable to the expert.

The formulation of the melt spinning composition can be done in any suitable manner using a conventional mixing apparatus, which is essential to ensure sufficient mixing and to obtain an intimately uniform mixture. Thus w.ird for example dry Ceiluloseacetaipulver with a weighed amount of the selected polyol at a S _c herwirkung engendering Ho "discloses mixer" The blended material is then further homogenized and mixed by filled it in a heated counter-rotating twin-screw extruder and the aeschmolzone extrudate then through a multi-hole

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Spinneret, for example a 16 to 30 hole nozzle, is pressed »The spinneret may be one that has conventional gas inlets to push gas into the core of the extrudate. A preferred gas for this purpose is nitrogen, but other gases may be used satisfactorily, such as carbon dioxide, air and other harmless gases. "If desired, a spinnerette may be used which has means for injecting a liquid into the extrudate core the liquid must not be a solvent for the Celluloseester and the polyol * such a spinneret is, for example, in U.S. Patent No. 3,888,771 discloses, "the emerging from the spinneret extrudate is subjected to cooling _e, for example by means of compressed air of different pressures and / or Temperature to cause gelation and solidification of the extrudate into a solid self-supporting fiber

The cellulose ester fiber can be hydrolyzed satisfactorily by any of the known deacetylation methods. The preferred method is to use an aqueous sodium hydroxide bath. Suitable techniques have been described in a variety of books and related journals, including, for example, Laidler, Chemical Kinetics _and McGraw Hill Book Co _,? New York (1950) * /. S * 282 -290 y Hewlett, et al., Technical Inst _{C c} 38, 212 (1947); Hiller, Oour, Polymer Science 10, 385 (1953). After rinsing to remove the hydrolysis products and excess hydrolyzate or neutralize them, the still wet fiber is treated with a water-soluble _B substantially nonvolatile plasticizer according to U.S. Patent 3,546,209 plasticized * By the term "im

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^ _ λγ

substantially volatile "is not meant in this specification and claims," that the plasticizer is substantially retained on the cellulose fiber during the subsequent drying step and storage at normal temperature.

Suitable plasticizers for deacetylated cellulose fibers include those that are able to swell the fiber, presumably by Zwischenvvirkungen as hydrogen bonding or dipole-dipole interactions © Preferably, the water-soluble, non-volatile substantially plasticizer is a hydroxyl-containing compound and in particular a Polyol such as polyalkylene oxides; Glycols such as ethylene glycol, diethylene glycol * dipropylene glycol "tripropylene glycol and the like; Glycerin and the like «Glycerol is a preferred plasticizer *

After plasticizing the fiber, it is dried by any of the known methods, for example, by vacuum drying, normal or elevated temperature air drying, microwave drying, and the like. "Elevated temperatures may be used as long as there is no substantial plasticizer loss." Consequently, the elevated drying temperature of each used plasticizer dependent; the suitable temperature can be easily determined.

The dried finished cellulose fibers after the. The invention has capillary diameters "The outside diameter is in the range of about 200 to 400 ^ a _s the wall thickness in the range of about 10 to 80, usi / For used in hemodialysis

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Separating cells according to the invention preferably have a wall thickness in the range of about 10 to 50 μm and a maximum outside diameter in the range of about 230 to 320 μm. "

embodiment

The invention will be explained in more detail below with reference to some examples.

The following examples also illustrate the process for preparing the improved cellulosic hollow fibers used in the separator of the present invention. In this specification and claims, unless otherwise stated, % by weight means each of the specially formulated melt spinning compositions was blended with the above-described blending apparatus and made according to the indicated process steps * The fibers were made from a 16 hole spinneret while blowing nitrogen into the core. After gelling in air, samples were taken to determine the intrinsic fiber tear after spinning. The fibers were turned into alkaline Solution entacetylated, for example in 0.2 to 1.2 wt .-% sodium hydroxide solution at a temperature in the range of 20 to 60 ° C _e

The intrinsic tensile strengths after spinning were determined by weighing 1524 cm of the adjacent fibers to determine the average weight of the selected 5.08 cm section of each individual fiber subjected to the test.

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The resulting fibers were then thoroughly washed in water and samples taken for determining the wet tensile strength after the front-described process "the product fibers were also tested for water permeability K _BB p and urea purity or transport"<y _RE A ⁱⁿ a laboratory test apparatus * The test apparatus consisted of a liquid reservoir equipped with a magnetic stirrer; and a dialysis test cup equipped with a magnetic stirrer, a cover closure plate with pressure fittings, and fittings for receiving the ends of the potting sleeves, each end of a fiber bundle of Figs. 128-178 Fibers were added «. The fiber bundle was bent in a U-shape, inserted into the cup and connected to the closure plate; a sleeve was connected via a fluid line to a pump connected to the reservoir via a conduit. The other sleeve was connected to a return line to the reservoir to pump fluid from the reservoir under controllable pressure through the lumens of the fibers in the dialysis cup "The beaker was also equipped with an oxy-ylate inlet" and outlet connections, and during the test, the fibers were dipped into a moving water pool surrounding it for the < _iicp test ».

The WassertransDortkoeffxzient K _{1, CO} was determined by water was pumped through the fibers and the Dpuck / increase in iVasservolumen outside the fibers in the D.taly "was measured sierbecher" The tests were conducted at 37 ⁰ C by

"K _{1 lrr} was then calculated for each test in ml / m" / h / mm Hg pressure differential _r as shown in Table I ",

The "urea coefficient!", Was provided by providing a

U 1 Lr (U

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Urea water solution in the feed reservoir and pumping the solution through the fiber lumens; the fibers surrounding the pool in the Oialysierbecher was initially pure water _e was the concentration of urea in the dialysate certain time intervals in the tests were performed at 37 ⁰ C and during the tests there was no pressure differential across the fiber wall surface "

The urea coefficient K was calculated from the difference between the urea concentration in the reservoir and in the Dialysierbecher on the outside of the fibers as a function of time and the fiber surface according to the following equation: N s ^K UPEA ^{A (C} l "" ^G 2 ^ ^{* wherein N} the flow through the membrane is in moles / min, C _{1 is} the initial concentration, C _{2 is} the final concentration or the measured concentration, and A is the area of the fiber wall or membrane between the two solutions.

In a two-chamber system without pressure differential or resulting ultrafiltration, the urea transition (transport) through the membrane may be integrated over a time interval t to give the following equation:

"( ⁰ I - ^q 2)

- ^C 2)

^V 1 + ^V 2 ^V 1 ^V 2

K

UREA _β t

where V is the volume of the solution in the reservoir and Vp is the volume of the solution in the dialysis cup »

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In the tests, the volumes V ^ and V ₂ and the area A are measured separately so that plotting the fourth of each side of the integrated equation gives a straight line whose slope allows K to be calculated in cm / min *

An intimate mixture (blend) of the cellulose diacetate polymer and plasticizer was, _t prepared as described above * The blend consisted of a mixture of 80% Cellu "losediacetat and 20% of a mixture of polyethylene glycols of molecular weights of 200 to 1450 Daltons, to an average Molecular weight of the mixed polyethylene glycol plasticizer of 902 daltons. The cellulose diacetate hollow fibers were then deacetylated in an aqueous sodium hydroxide solution at 50 ° C. to form cellulose hollow fibers. The intrinsic tear strengths of the cellulose hollow fiber membranes, water permeabilities (K.jp _R ) and urea transport rates (K) are listed in Table I, column 2. "

As can be seen from Table I, the wet cellulosic fiber of this example has an intrinsic wet tensile strength greater than 2 _# 5msl than the comparative fiber. The product cell fiber ₈ made from this pulp spin composition with the relatively high molecular weight polyol also has better performance characteristics for blood purification and higher WasGe-r permeability _s The water permeability. (IC ^ -) is l ^; , 5 times larger than that of the comparison fiber _A The velocity of the Harstofftransportes is also higher:

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3 -3

K = 38 χ 10 cm / min »compared to 30 χ 10 cm / min, urea / · ο /

the comparative cellulose fiber membrane «

A similar mixture was prepared by mixing cellulose diacetate and the same mixture of polyethylene glycols of 902 average molecular weight except that 43 % cellulose diacetate was used instead of 80 % . "After melt spinning, the cellulose acetate hollow fibers were dissolved in a 0.4% aqueous solution hydrolyzed sodium hydroxide solution at 50 ⁰ C or saponified * at what above described test a l, 3-fold higher intrinsic wet tensile strength than the comparative fiber, K yielded was 26 compared to 30 of the reference fiber, but 1 _<UF was "drastically at 86fache of l _<Uf -p-value of the reference fiber is increased, or a value of 104 ml / h / m / mm Hg "from the comparison of these two melt spinning compositions it can be seen that for a given polyol plasticizer, the decrease in Celluloseesterkonzentration a substantial increase in water permeability at acceptable urea cleaning values causes «It should au ch be noted that a weaker Hydrolisierlösung was used and that stronger Verseifungslösungen usually increase the water permeability "Thus, the desired combination of intrinsic Naßreißf estigkeit _f K ₁ and K .-- <properties are achieved by similar changes of Schmelzspinnzü ~ saramensetzung or by modifying the molecular weight of the polyol as shown in the example below

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An intimate mixture (blend) of cellulose diacetate polymer and plasticizer was prepared as described above. The mixture consisted of 43 % of a mixture of cellulose diacetate and 57 % polyethylene glycol having a molecular weight of 400 daltons which after deacetylation in an aqueous 0.4% sodium hydroxide solution at 50 ⁰ C cellulose hollow fiber membranes obtained from cellulose diacetate hollow fibers were tested for intrinsic tensile strength, water permeability (K 1 Fr 2) and urea transport (K _e ). The results are given in Table I, column C.

The intrinsic Na tear strength of the product fiber is 2 _f 4 times higher than the intrinsic wet tensile strength of the comparative fiber, K ₁₁₁ -D is 2, InIaI is higher and K ₁ is 32 χ 10 compared to 30 χ 10 ~ of the comparison fiber "It should be noted that during the saponification of cellulose acetate to cellulose the intrinsic wet tear strength has dropped to a value of nearly double the intrinsic tensile strength after spinning _c

Another mixture was prepared with the same proportions of cellulose diacetate and polyethylene glycol except that. The average glycol molecular weight of 400 ounces was prepared by mixing polyethylene glycol of average molecular weight 600 with glycerol of average molecular weight 92 daltons. This change brought about an improvement in all fiber properties. The intrinsic wet strength of the cellulose fiber was S times greater than that of the reference fiber <> _F ^ Ky ^vva i ~ 3.4 times greater than the

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same coefficient of comparison fiber and K- was 33 χ 10 compared to 30 χ 10 * "cm / min" of the comparative fiber.

The mixture contained 43 % of cellulose diacetate mixture and 57 % of polyethylene glycol of 108 daltons molecular weight. The cellulose diacetate hollow fibers were then dissolved in 10 ml of Seiger sodium hydroxide solution at 50 ° C deacetylated to cellulose hollow fibers "The intrinsic tensile strengths of the hollow fiber membrane, water permeability and urea transport rate are summarized in Table I, column D,

As can be seen from Table I, the wet cellulosic fiber of this example has 9.1 times better intrinsic tensile strength than the comparative _fiber. The water permeability K _{llt = n} is _1.8 times higher than that of the _{control fibers}

3 ~ "ζ

^{Un K .. K} > oo ^is 32 x 10 cm / min »compared to 30 χ 10

cra / min _{e of} the comparative cellulose membrane *

A similar mixture was prepared in the same way, except that the polyethylene glycol had a molecular weight of 150. The saponification of the cellulose acetate to cellulose was carried out in a 0% 4% aqueous sodium hydroxide solution at 50 ° C. The same fiber properties were determined as above described ". The intrinsic wet strength was 6. _# 6 ^times the comparison ^fiber "while ^K UFR ^unc * - ^k urea ^{in the Λ7Θ3θη1:} · ^Ί ^ ^{οηοη were} equal to the values of the ^{control fiber} ," A comparison of the intrinsic wet tensile strength. "

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strengths of the cellulosic fibers of Example 2 and Example 3 shows that the best wet strengths at a given cellulose ester concentration, 43 % cellulose diacetate, at an average molecular weight of the polyglycol is between 106 and 400, with a peak at a molecular weight of about 150 *.

An intimate mixture of cellulose diacetate polymer and plasticizer was prepared as described above. The mixture consisted of 43 % of a mixture of cellulose diacetate and 57 % of a mixture of polyethylene glycols of molecular weights 400 and 1450 DaItons "The average molecular weight of the polyethylene glycol plasticizer was 713 Daltons. The cellulose diacetate hollow fibers were then _s described to cellulose hollow fiber membranes as above deacetylated "Fiber properties are listed in Table I, Column E

It can be seen from Table I that the intrinsic wet tensile strength increased to over twice the intrinsic tenacity after spinning and to an intrinsic cellulose wet tensile strength of 3.2 times that of the comparative fiber _f at a K of 34 χ 10 ™ against

- -3 above a value of χ 0O IO cm / min _e OCE reference fiber and a K, dor was 2.4 times than that of the V ER- orößer

U i ~ i

gle.ichsf sser,

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An intimate mixture of cellulose diacetate polymer and plasticizer was prepared as described above. The mixture contained 43 % of a mixture of cellulose diacetate and 57 % of a mixture of polyethylene glycol of molecular weight 400 Daltons and glycerol of molecular weight 92 Daltons "so that the polyol mixture had an average molecular weight of 362 Daltons." The cellulose diacetate hollow fibers were in an o, 4% aqueous sodium hydroxide solution at 50 C to cellulose hollow fiber membranes entacetylated. The intrinsic tear strengths,

K values of the cell urea

Column F listed «

K values of the cellulose hollow fiber membrane are shown in Table I,

It can be seen from Table I that the intrinsic wet tear strength during saponification increased by 242 % to give a cellulose fiber whose intrinsic wet tear strength was 5.8 times that of the comparative fiber. The urea clearance rate was significantly increased to 42 × 10 -5 cm / min, or 1.3- fold over the reference fiber , while Kypo 2 was 1-fold higher than the comparative fiber _e

Another melt spinning composition, such as the above-described mixture of polyethylene glycol-glycerol mixture and cellulose diacetate, was prepared except that the glycerin was replaced by an equal amount, 7% by volume, of ethylene glycol to a polyol mixture of 358 average molecular weight The same properties were attributed to the resulting cellulose

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loose fibers had a wet tensile strength which was 5.8 times that of the comparative fiber, a K value of 21.times.10.sup.-1 cm./min, and an IC.sub.i value which was 1.7 times the value of the reference fiber.

Example 6

A melt spinning composition was prepared by uniformly mixing 36 % cellulose diacetate and 64 % of a polyol mixture consisting of a mixture of polyethylene glycol of average molecular weight 600 daltons and glycerol in such amounts as to give an average molecular weight of 421 for the mixture melt-spun fibers, and in a 0.4% aqueous sodium hydroxide solution at 50 ⁰ C deacetylated ₆ the same characteristics as described, determined and summarized in Table 1, column G "This Ceilulosefasern have a combination of high wet tensile strength, high '" γιρρ - filters and high K value, and, a preferred embodiment for use in hemodialysis or Hämofilterrif in particular for use in the separation device according to the invention is haemofilters * the intrinsic wet tensile strength is the 3 _f 4 times the reference fiber, K .. _cr> is 32 times higher than'de r value of the comparison fibers and K -. '·' ..

. ··. . · -. ^ ₇ '. · · · -V · · urea

is 49 x · lCT " ¹ cm / min _e .

An intimate mixture (blend) of cellulose diester (propionate / acetate) and plasticizer was prepared as described above. The cellulose ester of this example can be used extensively.

25 »5, 81 59 179 12

be regarded as cellulase propionate, since 96 % of the ester groups are propionate and only 4 % acetate »

The mixture consisted of 43 % of a mixture of cellulose propionate and 57% of a mixture of polyethylene glycol of average molecular weight 400 daltons and glycerol of molecular weight 92 daltons so that the polyol mixture had an average molecular weight of 362 daltons. The cellulose propionate hollow fibers were subsequently deacetylated in a 0.4% aqueous sodium hydroxide solution at 50 ° C. The intrinsic wet tensile strength of the hollow fiber, the water permeability and the urea transport rates are listed in Table I, column H *

As can be seen from Table I, the wet cellulosic fiber of this example has a 3.5 times higher intrinsic tear strength than the control fiber. The water permeability, ^K uFR ^{f is} ^ ^{38 2} * ^{4 | C acne} ^ ^er comparison ^fiber and the rate of urea transport, Κ, is 33 χ 10 * "cm / min,

It became a melt spinning composition by intimately mixing 43 % of cellulose diacetate and 57 % . Polyol · mixture consisting of a mixture of polypropylene glycol having an average molecular weight of 400 daltons and glycerol. * So that the average molecular weight of the polypropylene glycol / glycerin mixture was 297. "Cellulose fibers were made therefrom as described _s with deacetylation using

25 * 5ο 81 59 179 12

a 0.4% sodium hydroxide solution at 50 C. The determined properties are listed in Table I, column I,

Example 9

Separators of this invention were prepared using artificial kidneys marketed under the name C-DAK and using cellulosic fibers obtained on an industrial scale by the method of Example 5 using a melt spinning composition consisting of 43 % cellulose diacetate and 57 % of a mixture of polyethylene glycol having a molecular weight of 400 daltons and glycerol such that the polyol blend had an average molecular weight of 362 daltons. "Wet tensile strength was determined to be 11 x 10 g / g cellulose fiber."

After the cellulose fibers had been rinsed with water, replicated with an approximate glycerol / water solution and dried, they contained about 20 % glycerol. The intrinsic tear strength of these fibers was determined by a single fiber refraction test on the Instron apparatus as follows described above in connection with the dry cellulose acetate fiber, with the following modifications; A fiber cable of 360 'fibers and one meter in length was weighed, the glycerine extracted and the pure cellulose fiber weighed. * The average molecular weight of a 5.08 cm long section was then calculated on a 100 % polythene fiber basis. The tear resistance values represent the average of six separate

25. 5 * 81 59 179 12

Testing on six 5.08 cm long fibers from the glycerin-free fiber cable. The intrinsic dry tensile strength was 20 × 10 g / g cellulose fiber ·

2 One of the separators of this invention, containing 1.5 År of cellulosic fiber surface, was dry sterilized using 2.5 MRAD gamma rays. After sterilization, the separator was opened, fiber samples were taken and subjected to the intrinsic wet tear test. It was found that the fibers have an average intrinsic tear strength of 8.6 × 10 g / g cellulose.

Two loose fibers were made. Another 1.5 m separator was prepared by sterilizing the cellulosic fibers with 2.5 MRAD gamma rays while the separator was being filled with physiological saline. Fibers from this wet gamma sterilized separator had an intrinsic wet tear strength of 5 , 2 × 10 g / g of cellulosic fibers.

In comparison, in known artificial kidneys containing 1.5 m of cellulosic fibers prepared by the method of US Pat. No. 3,546,209, the following values were found in the same way:.

Intrinsic Dry Tensile Strength of Cellulose Fiber -

, 7.5 χ 10 ⁴ g / g |

Intrinsic wet tensile strength of the cellulose fiber - j

1.6 X ΙΟ ⁴ g / g. , , j

Intrinsic wet tensile strength of cellulose fiber after sterilization with gamma rays in dry

25. 5. 81 59 179 12

Condition - 1.53 χ ΙΟ ⁴ g / g

Intrinsic wet tensile strength of the cellulose fiber after sterilization with gamma rays in a wet state (physiological saline) -

1.28 x 10 ⁴ g / g.

Clinical evaluations of two 1.5m separators of the invention containing the improved cellulosic fibers of this example were performed on two hemodialysis patients at an average blood flow rate of 200 ml / min, and a dialysate flow rate of 500 ml / min _e for times of 3 , 5 and 4.1 hours performed The K .. _p "value was

ml

2.1 "-" .---- at 37 C. The K ₁ 'value was 31.6 cm / min _e hm .mm Hg ^a

at 37 ° C _e

In comparison, commercially available artificial

Kidneys containing 1.5 m cellulose fibers, made according to US PS

3,546,209, used in three hemodialysis patients, with average values for K ,, _cn of 'ml ^UFR '

0.89 - α- ~ - at 37 C and a K value of 29.6 cm /

hr.nr.ram Hg ^urea

min _e . was obtained at 37 ^° C. «·

Of marketed artificial kidney used in this example are devices with a pair ßlut- kamnie rn, which is arranged by one therebetween dialysate. chamber that err with the blood comb. is integrally connected, kept at a distance _e A bundle of hollow fibers, normal

25. 5, 81 59 179 12

Often consisting of many thousands of individual fibers, for example 6000 to 15 000 fibers, terminate at their opposite ends in a tube sheet made of plastic, for example polyurethane. The tubesheet connect the fibers to each other and also provide an annular portion located outside the perimeter of the fibers in the bundle. The portion serves to connect the tubesheet to the end portions of the dialysate chamber and the blood chambers and thereby into one the blood chambers and the dialysate chamber Unit with the fibers in the dialysate chamber so that the chambers are isolated from each other in fluid-tight connection. The open ends of the hollow fibers terminate in the plane of the outer end of each tube bottom and the passages in the hollow fibers provide connections between the interior of the spaced blood chambers "

'tale I ¹

^r asereiqsnschaften

(A) Trockenreißfestig ~ ness dor cellulose acetate fiber 'before the deacetylation: g intrinsic tear strength / g Cellu loseacetat-polymer of a single fiber in a 5.08 he ?. length

  (A)

Comparative Example Commercially available cellulose hollow fiber according to US Pat. No. 3,546

Ex. - Ex. Ex. Ex. Ex. No 1 No 2 No 3 No _e 4

7.2 χ

7 _t 4xl0 ⁴ 2, OxIO ⁴ 4,4XlO ⁴ 2,3xlO ⁴

(B) Wet tensile strength of cellulose fiber after deacetylation: g intrinsic tear strength / g cellulose polymer

1.6 x 4.2xlO ⁴ 3.9xlO ⁴

5, Ixio

Commercially available fiber properties

Hollow fiber according to US Pat. No. 3,546

Comparative Example Example Example Example Example

No I No * 2 No * 3 No * 3

from a single fiber in a 5.8 cm sample

(C) Change in fiber tear strength during conversion about -78 % from the spun cellulose acetate fiber to the final semi-permeable _: wet. cellulose fiber

-43 %

+ 195 % -20 %

+ 222 %

i "ro η σι

(D) water permeability of the finished '. , moist cellulose

Fasoreigenschaften

; i oh one fas e rm em b 'r ^ n

mm Hg at 37 ° C

Comparative Example Example Example Example Example In Trade Received No. 1 No. * 2 No. 3 No. * 4

cellulose hollow fiber according to US Pat. No. 3,546

1.0 -1.2

1.3

2.5

2.1

, S

(E) Horristoff cleaning rate cior finished wet cellulosic hollow fiber membrane

^K urea

37 ⁵ C

in .. "at

28-30 X

38X10

-3

32x10 *

32xlO

~ ³

34xlO

" ³

Ui

vj Ui UD ·

I- * CO

Table I

fiber properties

(F) · (G) (H) (I) Example Example Example Example

, 5

No. 7

(A) Dry tensile strength of cellulose acetate fiber before deacetylation: g intrinsic tear strength / g cellulose acetate polymer from a single fiber in 5.08 cm length

No. ₈ 8

3 »8xlO ⁴ 3> 7xiO ⁴ 5,7xlO ⁴ 5,9xlQ ⁴

(B) Na tear resistance. the cellulose fiber according to the Entacet.ylierung: g intrinsic tear strength / g cellulose polymer of a single fiber in a 5 "08 cm sample 9,2xlO ⁴ 5,5xlO 5,6xlO ^{4 4 4} 3,6XlO

I- * CO

(C) Changing the fiber tear strength during the conversion, from the spun cellulose acetate fiber to the final semi-permeable wet cellulosic fiber

+ 149 % - 2 %

- 39 %

Fasereigenschäften

(D) Water permeability of the finished wet cellulosic hollow fiber membrane

Example Example Example Example Mr, 5 No., 6 No. 7 No.

2 2

/ h / m /

mm Hg at 37 ° C

2.5 38.0

2.9

(E) Clearance Rate of Clearance of Finished Wet Cellulose 42x10 "Hollow Fiber Membrane K. 49x10

33x10

, -3

urea

cm / min., at 37

3.5

44x10

-3

Claims (4)

Separator for hemodialyzing and hemofiltration of blood having a pair of blood chambers spaced from each other by a dialysate chamber disposed therebetween, a bundle of hollow fibers terminating at both ends in a tube sheet interposed between the dialysate chamber and each of the tubes both blood chambers are sealingly arranged and fixed to them to separate the chambers in fluid-tight connection with the passages in the fibers, creating connections between the interior of blood chambers, characterized in that the hollow fibers comprise a plurality of hollow fibers having an ultrafiltration coefficient K ₁₁ Co of from about 2 to about 200 ml / hr / m / hr Hg; a urea coefficient K of from about 15 x 10 -5 to about 45 x 10 -5 cm-1 and an intrinsic wet tensile strength of from about 2 to about 11 g per gram of cellulosic polymer and are obtained by j a) melt spinning of a cellulose ester hollow fiber a melt spinning composition consisting essentially of from about 35 to about 80% by weight of cellulose ester and the remainder to 100% by weight of at least one polyol of average molecular weight in the range of about 10 6 to about 900; · '. - b) largely hydrolyzing the cellulose ester hollow fiber into a cellulose hollow fiber; c) replastifying the cellulose fiber while it is still wet, with a water-soluble, largely non-volatile plasticizer and d) drying the plasticized fiber. 25. 5, 81 g 59 179 12 2 «Device according to item 1, characterized in that the hollow fibers are a plurality of hollow fibers having an outer diameter of about 200 to about 400, um and a wall thickness of about 12 to about 80, _e Have 3 * The apparatus of item 1, characterized in that the device and the hollow fibers therein are sterile as a result of sterilization aer device with gamma rays, and the sterilized hollow fibers have an intrinsic wet tensile strength in the range of about 5 χ 10-9 χ 10 g / g of cellulose fibers " Ao device according to item 3, characterized in that the hollow fibers in the device have been sterilized with gamma rays as dry replastered cellulose fibers containing about 20 % glycerol and the sterilized fibers have an intrinsic wet tensile strength of about 9 x 10 g / g cellulose fibers. " 5 _ff separating device according to item 3, characterized in that the hollow fibers have been sterilized with gamma rays in the device while the fibers moistened with a physiological saline solution, were, and 'sterilized fibers have an intrinsic wet tear strength 4- ' from about 5 χ .10. g / g cellulose fibers "