DE2650588A1 - HOLLOW FIBER DIALYZER - Google Patents

Description

Patent attorneys: a. grunecker

DlPL-INGt

H. KINKELDEY

W. STOCKMAlR

Dn-INCl-AaElCAUHX

K. SCHUMANN

Dn HER NAT. · OPL-PHYS

P. H. JAKOB

G. BEZOLD

DR FER. NAT. CXPL-CHEM.

8 MUNICH 22

MAXIMILIANSTRASSE 43

M-. November 1976 P 10 978

EXTEACOEPOEEAL MEDICAL SPECIALTIES, 'INC., Eoyal and Eoss Eoads, King of Prussia, Pennsylvania, Y.St.A.

Hollow fiber malyser

The invention relates to dialysis, in particular it relates to the dialysis of liquids such as blood.

There have been many proposals for improving dialysis machines, especially those made from artificial ones Kidney type, made. There are a large number of so-called snake type artificial kidneys in use in which the dialysis element is an ear many centimeters in diameter, but flattened and spirally wound with a spacer to keep the turns of the winding apart to separate. An artificial kidney made in this way is relatively large and smaller constructions have already been made with bundles of thousands of hollow fibers, each

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a very narrow tube that functions like a dialysis element has been proposed, but problems still arise with this modified construction. An example for a hollow fiber apparatus is described in US Pat. No. 3,444-2 and a fiber which has recently been used for hollow fiber dialyzers is used is the deacetylated cellulose acetate fiber described in U.S. Patent 3,54-5,209. In general, these fibers must be kept wetted with water at all times after the deacetylation. their dialytic Maintain permeability. This leads to inconvenience during shipping and storage of Dialyzers based on hollow fibers in which the fibers are filled with water and in which the water is formaldehyde contains to prevent microbial growth from developing. All formaldehyde must then be used before each use be flushed out.

The aim of the present invention is, inter alia, to ver. to develop improved hollow fiber dialyzer designs.

The above object, as well as other objects, features, and advantages of the invention will become apparent from the more detailed below Description of several preferred embodiments of the invention, referring to the accompanying Drawings is referred to. Show:

Fig. 1 is an elevational view, partly in section and partly broken away, of a hollow fiber dialyzer according to the invention;

2, 3 and 4 · cross-sectional views of the construction according to FIG Figure 1 is taken along lines 2-2, 3-3 and 4-4, respectively;

5 shows a view similar to FIG. 6 of a modified hollow fiber dialyzer according to the invention;

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Figures 6, 7 and 8 are cross-sectional views of the structure of Figure 5 taken along lines 6-6, 7-7 "and 8-8, respectively;

FIGS. 9, 10, 11 and 12 are views similar to FIGS. 1, 2, 3 and 4 x another modified dialyzer typical of the present invention;

FIG. 13 is a cross-sectional view of a cover device suitable for use in the construction of FIG suitable; and

FIGS. 14, 15 and 16 are views similar to FIGS. 1, 2 and 3 another embodiment of the invention.

In one aspect, the present invention relates to a Hollow fiber dialyzer with an elongated tubular housing with ends with a larger inner diameter (a larger clear width) than in the central section, the central section being a subdivision extending in the longitudinal direction which divides its interior into a plurality of generally parallel passages, the housing ends dialysate flow branching and -guiding devices for the reception of the dialysate from a storage container for it, which it from one end of the housing through one of the passages to the other end and successively through the successive passages direct and finally direct the dialysate outwards through a discharge opening, and have bundles of parallel Hollow dialysis fibers are present in at least all of the passageways are pressed into which the steering devices direct the dialysate flow in the same direction.

The examples given below illustrate very advantageous ways of producing the hollow fiber dialyzers according to the invention, however, the invention is not restricted thereto is·

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example 1

First, a dialysis case 10, as indicated in FIG. 1, is through. Molded or glued together from a polycarbonate or polystyrene resin. This case has a total length of about 19 _? 0 cm (7 »5 inches) with a central section 12 having an inner diameter of 3.5 cm (1 3/8 inches) with each end 14-, 16 having an enlarged opening about 4-, 8 cm (1st quarter) inside diameter 7/8 inches). The length of the inside of the housing is divided into three individual passages 21, 22, 23 by an axial stiffener 26 with three webs 31, 32 and 33. An inlet pipe opens into the widened end 14 and a discharge pipe 38 leads away from the end 16.

The stiffener 26 has 14, 16 flow control devices at each end arranged so that the liquid (fluid) entering through inlet 36 is in an upward direction flows from the end 14- through the passage 21 to the end, then at the end 16 from the upper end of the Passage 21 to the upper end of passage 22, then moved down through passage 22 to the lower end 14, where it is then transferred into the lower section of the passage 23, in which it extends upwards to the end 16 moved through outlet 38 for discharge. I'm this flow control to achieve is a web 31 as a barrier seal with respect to the outer wall of the housing over the entire length of the lower end 14 and over the entire length of the central section 12, but not arranged at the upper end 16. Instead, the web 31 is cut out at this upper end, as indicated at 4-0, to achieve a flow-through cavity 4-1 which extends between the upper ends of the passages 21 and 22 opens.

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The web 32 is similarly shaped in the opposite sense, so that it forms an edge 5 ° on its lower section, which has a distance from the lowest point of the housing end 14- to achieve a flow cavity 51 between the lower ends of the passages 22 and 23.

A batch of hollow, regenerated cuprammonium cellulose fibers having a wall thickness of about 12 + 2 microns and an inner diameter of about 200 + 50 microns is preferably unwound from a plurality of spools in the form of parallel strands, to a length of about 22.9 cm (9 inches) cut and carefully cleaned. In their generally available form, these fibers are made by extruding a euprammonium cellulose solution through an annular nozzle into a regeneration bath while introducing a water-immiscible liquid into the interior of the hollow extrudate. A typical liquid that is insoluble in water is isopropyl myristate. After the regeneration has ended, this liquid is removed by careful washing with isopropanol. The interior of the fibers can then be wetted with a plasticizer, such as glycerine, preferably about 5 % of the plasticizer, based on the weight of the clean fiber, remaining therein. This softening is not essential, but it does protect the fibers from breakage or damage during subsequent handling and does not affect the effectiveness with which the fibers are enclosed in the housing 10.

Then a bundle of 2,000 to 3,000 fibers made in this way is made is inserted into one of the passages 21, 22, 23 and further bundles are inserted into each of the remaining passages. These Insertion can be accelerated by first sliding a conical polyethylene sleeve over the bundle. then first insert the filled casing with the narrow end into one of the passages and finally remove the casing from the

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led bundle pulls down. At the narrow end of the cone, the fibers are arranged so that they protrude from the sheath, so that they can be grasped (held in place) to facilitate peeling of the sleeve from the other ends of the fibers.

When all the passageways are filled with fibers, potting can begin. At each end of the housing Each "bundle of fibers" stands a short distance in front of each of these protruding ends is dipped in molten carnauba wax, which is then allowed to solidify after the carnauba wax penetrated a very short distance into all individual fibers. The housing is then placed lengthways between pouring heads clamped, which are in communication with a casting compound container, as shown in FIG. 19 of the US patent 3 442 002, and centrifuged, as is also indicated in this patent, while the non-hardened, liquid, freshly mixed pouring mixture is poured into the potting compound container. With this mixture can it is a polyurethane prepolymer resin with a chain extender or an epoxy adhesive blend as described in US Pat. No. 3,442,002, or a curable one Act polysiloxane fluid or other curable resin.

When a curable Polysiloxanflussigkeit with a curing agent, such as chloroplatinic acid, is used, the centrifugation is conducted g at about 350, while the mixture is heated, and after about 1/2 hour at 66 ⁰ C. (150 ⁰ F) the Eingießmischung until hardened to such a point that it no longer flows. The Vergießköpfe are then removed and the curing is completed by (F ⁰ 150) holds the dialyzer for 2 hours at 66 ⁰ C in an air oven ·. Then the potting mixture is a solid that can be cut cleanly and a sharp metal knife is used.

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turns to cut the potting compound ridges at the open ends 14, 16 of the housing. The in Pig 1, the potting compound is shown at 56 and 57. Then on the housing ends 14, 16 by welding or gluing covers 61, 62 placed, each with a flow connection 64, 65 are equipped, but if desired they can also be screwed tight. The structure is then ready and only needs to be rinsed to remove the water-soluble hardener To flush out the inside of the hollow fibers, the device was operated is put into operation. The dialyzers can be stored before or after washing out the plasticizer without significantly affecting their dialysis properties.

When the dialyzer is in use, it is generally held with the end 16 facing up, with the inlet 36 becoming a dialysate source connected ", the discharge 38 is connected to the Drain connected and a supply of blood to be dialyzed is connected to inlet 65 with a blood recirculation to outlet 64. In use, bubbles of air or other gases may form in the dialysate and these rise up to the top 16 of the dialyzer. TJm to prevent these bubbles from getting on the tops of the passageways 21 and 22 are held fast and gather there in a crowd, which could interfere with the dialysis is, as shown, a small one at the upper end of the stiffening web 32 Outlet 59 is provided. With a web with a wall thickness of 0.16 cm (1/16 inch) this can be done at the ends mentioned above Trapped gas through a round opening with a diameter of only 0.5 mm easily into the upper end of the passage 23 and from there escape to the outside through the discharge opening 38, without that the effectiveness of the dialysis is significantly reduced. The gas outlet can be even smaller be made, for example with a diameter of 0.3 µm,

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- fT -

The optimal width of the outlet is related to the thickness of the wall it crosses. For wall thicknesses greater than 0.16 cm (1/16 inch), the width of the outlet is preferred slightly larger than 0.5

One feature of the dialyzer assembly according to FIG. 1 is that such dialyzers can easily be manufactured with a more uniform analysis efficiency than corresponding ones Dialyzers in which there is no subdivision and the stiffener 26 is completely omitted. Still has Dialysate at the widened ends 14, 16, which act as dialysate branching points serve that the dialysate is in direct contact with the outer layers of the fibers in the fiber bundles bring about the tendency to flow through one end of the dialyzer to the other end by the easiest path and such To form a channel even if the fibers are quite tightly packed. -Through such channeling, the efficiency of the Dialysis greatly diminished, especially through the walls of such "fibers, which are at a certain lateral distance from the Channel. If this occurs with a dialyzer that has only a single dialysate passage, it will its efficiency is so poor that it generally has to be thrown away.

Such channeling is all the more likely to occur the more the wall thickness of the hollow fibers decreases and also the diameter of the fibers decreases. This makes the fibers more flexible so that it is easier for the dialysate to pass through Bending the fibers to create a canal. For effective Wall thicknesses of about 5 to about 20 microns are used suitable and thicknesses from about 10 to about 15 microns are preferred. Fibers having internal passageways no more than about 500 microns wide, preferably within the range from about 100 to about 300 microns are very effective. In the regenerated cuprammonium hollow used according to the invention

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fibers are relatively stiff fibers, especially when they are dry and they can therefore be grouped into a bundle for introduction into a dialyzer and very easy to use during the introduction itself.

In the case of the construction shown in FIG. 1, a decrease in effectiveness induced by the formation of eanals can also occur of the passage 21 occur, but if this is the case, the dialysate emerging from the passage 21 is less loaded with impurities so that it becomes more effective in the subsequent pass through passages 22 and 23.

In addition, each of the passages 21, 22 and 23 is narrower than without the use of the stiffener 26 and the channeling is narrower Passes less likely. Also, the total length of the fibers in the construction according to FIG. 1 with the Dialysate come into contact, three times the contact length if stiffener 26 were omitted, and the loss of effectiveness due to channeling decreases as that length increases ·

Because of the more reproducible, greater efficiency of the construction according to FIG. 1, dialyzers with a working length between the cast-in seals 56, 57 of only made about 15 cm lighter with the desired high quality will. This small size is particularly desirable, although in the. overall overall lengths of about 15 »2 to about 30.5 6 to 12 inches (cm) can be attractive for hospital use.

Example 2

Figures 5, 6, 7 and 8 illustrate a modified one according to the invention Dialyzer 110. In this dialyzer there are three parallel

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Dialyzer passages along the lines of the pig. 1 is present, but the flow of dialysate is arranged so that it is along its I-fiber contact path on the outside of the individual fibers in a direction countercurrent to the flow of blood or the flow of some other medium that is within the fibers is dialyzed, "moves.

As with the construction according to Pig. 1 shows the dialyzer Ί1Ο a central tubular section T12 with enlarged seams 114, 116 and with a dividing stiffener 126, which is inserted or molded into section 112. The stiffener 126 has webs 131, 132, 133, the are similar to the three webs of stiffener 26, and it also has two additional webs 134, 135 which provide additional passageways 124, 125 limit.

The hollow fiber bundles are in the passages 121, 122, 123 included, the passages 124, 125 are not filled so that they represent passages for the dialysate that flows through, while it is not in contact with the Pasers.

The dialysate flow is created by suitable shaping of the stiffening webs in the construction according to Pig. 5 controlled so that it first enters passage 121 and flows upward therein, then flows downward through passage 124, then flows back up through passage 122 and at this point through passage 125; · to the lower section returns and ultimately by an upward flow through passage 123 and through the discharge at outlet 138 completes dialysis. For this purpose, the upper ends of the webs 134 and 135 are spaced from the inner wall of the housing end 116 and the lower ends of the webs 131 and 132 are spaced from the inner surface of the housing end 114, like the Pig. Figures 7 and 8 show more clearly.

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In the construction according to Pig. 5 no gas outlet is provided, since the dialysate flow rate in the very narrow reversing passages 124-125 is quite high. on in this way, a flow rate of only about 30 cm (1 foot) per second is generally sufficient flush out the gas bubbles that "form" Flow rates, for example when the dialysate after a single pass through the dialyzer discarded and not from outlet 138 to inlet 136 is returned in the cycle, can in the construction according to Pig. 5 a gas outlet should be provided »

The gas outlet can be eliminated when the dialysate is used Reduction of gas evolution is treated, for example by boiling the same under reduced pressure before it is inserted into the dialyzer. This will remove almost all of the dissolved gases and maintain one Some pressure on the dialysate as it is pushed through the dialyzer acts as an additional means of prevention a gas evolution. ·

The dialyzer housings according to the invention do not need to have a circular cross-section, but can, if desired also oval, rectangular or triangular, both in terms of their external shape and in terms of the shape of the passages. Accordingly, they do not have to be completely linear in the longitudinal direction either.

Example 3

FIGS. 9 to 13 explain a dialyzer according to the invention 210, which is generally triangular in cross-section, particularly at its ends 214, 216. These ends face each has a mounting rib 217 that assists in positioning the end connector covers 262. Furthermore

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each rib 217 can be provided with a rib 219 which to be only about 0.38 to about 0.51 mm (15 "to 20 mils) high needs that the welding of the lid by sonic or ultrasonic vibrations of the attached lid to the, Hippe supports. With vibrations of this kind they merge Rib 'and the part of the lid in contact with the rib with each other as a result of the frictional heat generated at The vibration arises between them and they weld together forming a very effective liquid-tight Seal.

The construction and operation of the dialyzer according to FIGS Figures 9 to 13 generally correspond to those of the dialyzer 5 to 8 and corresponding parts such as the partition stiffener 226, the passages 221, 222 and 223 for the reception of the hollow fibers, the passages 224 and for the return of the dialysate and the connecting passageways 24-1, are identified by corresponding numbers. However, to better seal the blood or another To obtain dialysate against undesired cracks and the like, the covers 262 are each provided with an inner sealing lip which is shaped to adhere to the sprue seal 257 rests outside the fiber-containing zone. In this way, the dialysate is prevented from entering the gap 265 penetrate between the inner surface of the lid and the outer surface of the housing wall.

In order to improve this seal even further, the 'potting seal 257 can be arranged so that they are a short distance 267, for example 0.32 cm (1/8 inch) beyond the end of the housing.

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Example 4-

FIGS. 14, 15 and 16 also explain a dialyzer 412 a generally rectangular structure both in terms of its external appearance and in terms of its passageways. Such a structure makes better use of the hem and can contain more fibers than others Eonfigurations with the same overall dimensions.

The construction and operation of this embodiment, as well as the numbering of its parts, are similar to those of FIG. 1 to 4, but with the exception that their cover 462 and the Lid fastening correspond to those of FIGS. 9 to 13 without the inner sealing lip. The inner seal is in 14 thereby causes their end covers (lids) 462 to be in tight contact with the outer edge of the potting seal stand. Instead of passageways 421, 422 and 423 around housing 410 generally in the circumferential direction these passages are arranged in a simple row, all of which are in the same thick plane.

The fiber bundles can be inserted into the dialyzer without the use of a sheath Passages are introduced, especially when the walls of one end of the housing gradually taper from their wide inner opening downwards to the smaller opening of the central section 12 or 112. Alternatively, the bundles be provided with a sleeve and the sleeves can be left in place around the bundles in the dialyzer. This alternative is particularly advantageous when the sheaths have a relatively thin wall, i.e. about 0.76 mm (3 mils) are thick so that they do not take up much space

The introduction of the fiber bundles is also facilitated by the fact that it is carried out when the housings are hot the heat expands the housing and something like this is created

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more space for easier introduction of the bundle to the right place, then the housing cools down and tightly encloses the fibers, which improves efficiency will. Instead of an elongated sheath to support the introduction of the fibers, a single sheath can also be used narrow piece of plastic or even wire wrapped around a bundle of fibers near one end and attached to the Fibers attached or wrapped around them are underneath Formation of an end piece for the bundle. The bundle can then be pulled through a passage by first the end piece leads through the passage and then pulls on this end piece.

It is generally useful to clean the hollow fibers for dialysis by treating them with a volatile Solvent washes or rinses off, especially if the internal passages (openings) in the fibers contain a liquid that must not come into contact with the dialysate.

The advantages of the subdivision are achieved if the dialyzer is subdivided so that only two parallel dialysis passages can be obtained. A very simple structure of this type has inlet and outlet pipes 36,38 on top of one another opposite sides of the upper housing 16 on with a single central stiffener extending longitudinally Extends over the entire length of the housing, which, however, is provided with an opening in its lower section.

The subdivision can also be even more divided than shown in the drawings to generate 4 or 5 parallel Dialysis passages that use more subdivisions, however, occupy part of the tree that is responsible for the fibers is determined so that the housing must be enlarged in order to maintain the dialysis efficiency.

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Due to the subdivision according to the invention, the mechanical Simplified handling in the manufacture of the dialyzer. The reduced width (diameter) of the individual passages, e.g. 1 to 3 cm, compared to an undivided one Dialyzer reduces the number of fibers per passage and thereby simplifies the production of the individual bundles. For example, making a 6000 fiber bundle for an undivided dialyzer is more difficult than that Manufacture of three 2000 fiber bundles for use in the dialyzer according to Fig. 1 or 5 or 9 ·

The fiber-containing passageways can also be double-tapered, as shown at 211 in FIG. 9, so that they are in their central portion have a constriction. Such a narrowing from about 0.5 to about 1 mm tends to hold (grasp) the fibers and prevent them from passing through the Current will be deflected around them, reducing the tendency to channel formation. ·

Another feature of the invention is that the various compartments of the dialyzers described above need not be used for the same function. One of the compartments can, for example, be used to hold a Absorbents, such as activated carbon or the like, can be used instead of fibers so as to remove impurities or others absorb unwanted components in the dialysate. Different types of Fibers are used to contribute to various dialysis effects to achieve the dialysate when it passes through the dialyzer. For example, some of the passes, such as the Passage 124 · to be filled with an absorbent for the treatment of the dialysate when it passes through the dialyzer moved, and for better pretreatment of the dialysate for its passage through the remaining passages containing fibers .

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The casting (embedding) of the fiber ends can also be carried out using methods other than those described above will. For example, the fibers can previously be converted into melted waxes modified with a resin or into thermoplastic waxes Resins, or in bulk, which cure to form thermosetting resins, are immersed around their internal openings to close. The pouring mixture itself can be used, for example, as a shallow pre-immersion bath which is followed by a deeper pouring (embedding). By being in the non-closed paser openings maintains a slightly higher pressure than the pressure above the pouring mixture into which the uncapped Fiber ends are immersed, the pouring mixture (embedding compound) is also kept at a low level within these inner openings and the previous immersion in order to close these openings can be completely can be omitted. The inner openings can also be closed by melting the fiber ends, if they are fusible, thus making prior immersion unnecessary.

Although the centrifugal force acting on the liquid casting mixture (casting compound) ensures that this mixture thoroughly penetrates into all cracks and pores around the fibers and between the fibers and in this way a good one Ensures sealing of the dialysate chamber from the dialysate, a gas pressure above the liquid casting compound (casting compound) during casting (embedding) has a similar one Effect · Accordingly, one end of a fiber bundle can be potted (embedded) at a certain point in time without a centrifugal embedding device is required for this.

The cover 61, 62 can also be arranged so that they over snap into the molded ends of the dialyzer, such as shown in Fig. 5 at 161, 162. These lids

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can be relatively flexible and the cast Ends, over which they span, can be provided with ribs 163, which the snap-on lid in the hold in the correct position.

The dialysis described above differs from osmosis in that fibers are used in dialysis, the walls of which are extremely porous, far too porous for use in osmosis. This comparison is illustrated by the fact that a reverse osmosis process, for example for desalination of brackish water ^ the use of membranes made of a relatively non-porous material such as polyvinyl chloride, as well as the application of a drive pressure, which is greater than the osmotic pressure and as high as practical. Trying to do such Carrying out reverse osmosis with the regenerated cuprammonium cellulose described above would only result in that the brackish water quickly through the regenerated cellulose fibers is filtered and at the exit surface of the cellulose would exit in practically the same condition as introduced into the entry surface.

The dialyzer construction according to the invention can also be used in conjunction be applied with a dialysate that flows through the inner openings (passages) of the hollow fibers or itself moved along the outside of the fibers, although this arrangement is undesirable if blood is used as dialysate. With most osmosis fibers, however, the structural arrangement according to the invention for osmotic processes such as reverse osmosis, and in this use it is preferred to direct the liquid to be treated around the hollow fibers so that the high pressures that are exerted on such liquids (fluids) in reverse osmosis, -on the outer walls of the fibers act. This avoids a fiber break leading to a leak.

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The device according to the invention is suitable for use for gas separation, again with a suitable one Pasertyp, or for the gas treatment of liquids, as in the treatment of blood with oxygen, where silicone fibers are preferred.

Although the invention has been preferred with reference to FIG Embodiments explained in more detail, but it is it goes without saying for the person skilled in the art that "it is by no means restricted to this, but that it is in many respects can be changed and modified without this the scope of the present invention is departed from.

Patent claims:

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Claims (3)

Claims 1. Hollow fiber dialyzer, characterized by an elongated tubular housing (ΊΟ). in which the housing ends (14-, 16) have a larger diameter than its central section (12), the central section (12) having a longitudinally extending subdivision (26; 31, 32, 33) which its interior into a plurality divided by generally parallel passages (21, 22, 23), and the housing ends (14, 16) having dialysate flow branching and directing means for receiving dialysate from a reservoir therefor, the .es from one end of the housing through one of the passages (21, 22, 23) to the other end and backwards through the subsequent passages and finally direct the dialysate through a discharge opening (38) to the outside, and through bundles of parallel dialysis hollow fibers, which in at least all the passages are pressed in, in which the steering devices direct the Dia ^ sabstrom in the same direction. 2. hollow fiber dialyzer according to claim 1, characterized in that the dialysis hollow fibers in all passages (21, 22, 23) are pressed and the flow directing device at one end a gas bypass line between successive Has passages that allow the gas bubbles trapped at this end when the dialyzer operated with this end up, can be drained without being carried away by the dialysate to the other end will. 3. hollow fiber dialyzer according to claim 1 and / or 2, characterized characterized in that the housing (10) is about 15 »2 to about 30.5 cm (6 to 12 inches) long and that each contains fibers ORIGINAL 709820/0720 Passage (21, 22, 23) has a width (diameter) of no more than about 3 cm. 4, hollow fiber dialyzer according to at least one of the claims 1 "to 3" characterized in that the hollow fibers are made of Euprammonium Cellulose "consist. 709820/0720