FR2459674A1 - DIALYSEUR WITH HOLLOW FIBER MEMBRANE AND METHOD FOR MANUFACTURING THE SAME - Google Patents

Abstract

DIALYZER WITH HOLLOW FIBER MEMBRANE AND ITS MANUFACTURING PROCESS. IN THIS PROCESS, THE SECTION SURFACES OF THE MEMBRANES IN HOLLOW FILAMENTS ASSEMBLED INTO BUNDLES WHICH HAVE THEIR ENDS COATED IN POLYURETHANES AND SECTIONED TO HAVE A TUBULAR PLATE AND WHICH, ON THE DIALYSATE SIDE, ARE CONSTITUTED BY A LAYER CONTAINING LIKE ACTIVE CARBON, AND THE PRODUCT SIDE RETAINED BY A LAYER OF REGENERATED CELLULOSE, ARE EQUIPPED WITH A SEALING HAVING A THICKNESS OF 0.2 TO 2MM BY SPRAYING ON THEM A POLYURETHANE SOLUTION WHICH, IN ADDITION TO THE SOLVENT STILL CONTAINS A THINNER HAVING AN EVAPORATION INDEX OF 2 TO 25 AND POSSIBLE A SPREADING AGENT. WITH THIS DIALYZER, USED IN HEMODIALYSIS FOR EXAMPLE, THE CLOGGING OF THE CHANNELS BY THE ADSORBENT PRODUCT IS AVOIDED.

Description

1. "Dialyzer with hollow fiber membrane and its process

Manufacturing."

  The present invention relates to dialyzers with multi-component hollow filaments bound as members

  branes which consist of at least two layers,

  of a regenerated cellulose layer which represents the actual membrane and a layer which contains adsorbent particles such as activated carbon or

aluminum oxide.

  It is known to use in the dialyzers

  two-component hollow filaments in the form of

  Regenerated lulose formed from two layers firmly adhering

  to one another, one being of regenerated cellulose

  and possibly a cellulose derivative while the other layer is regenerated cellulose which contains 1 to

  % by weight of adsorbent particles uniformly distributed

  incorporated particles having an average size of up to 40 μm.

  Membranes of this kind are described, for example, in German Offenlegungsschrift No. 2,627,858. In the structure of a suitable dialyzer, hollow filaments of this kind are assembled into bundles and their ends are

  coated in a mass, in particular polyurethane, se-

  in the classical processes. After curing the coating mass the filaments are cut at their ends so that a tubular plate is formed leaving open

the orifices of the hollow filaments.

  For dialysis the dialyser fluid can then

  pour the hollow filaments. So the constituents to separate

  can diffuse through the wall of the cellulosic layer

  than. The adsorbent material is able to adsorb at the same time

time some products.

  It has been found that, by cutting the coated filaments, the adsorbent particles are removed from their coating and are placed on the cut surface or fall into the hollow channels. During dialysis it is possible that

  such particles hinder because they clog, for example,

fill the hollow filaments.

  By using such a dialyzer for hemodialysis it can be done in addition that particles of coal for example reach the blood circuit and there can

  cause serious damage, endangering the health of the patient.

  Efforts have already been made to overcome such difficulties by first eliminating such fines.

  as the dust of the coal particles used. Toute-

  This is only possible to a certain extent; fina-

  It has not been possible to avoid that, as a result of the cutting, the coal particles are again finely divided and

  that the smaller particles come off.

  It has therefore become necessary to have a device that does not have the drawbacks mentioned above as well as an advantageous method for the manufacture of dialyzer

Of this genre.

  The present invention therefore aims to provide a

  dialyzer with multicomponent filaments as membrane

  which on the section surfaces does not have any

  freely moving adsorbent particles, which has

  these smooth on the tubular trays and which is long-lasting and has no toxicological disadvantages and can be used in particular for hemodialysis without penetrating particles of the adsorbent in the blood. This object is realized, according to the present invention, by

  a dialyzer with the membrane of hollow filaments with

  a plurality of bundled components having a layer containing the adsorbent particles on the dialysate side and consisting of the product side retained by a regenerated cellulose layer and optionally a cellulose derivative and having their ends encased in hardened polyurethane and severed to form a tubular plate leaving the opening of the hollow filaments open, this dialyzer being characterized by sealing the sectional surfaces with the polyurethane having a thickness

  0.2 to 2 μm leaving open the orifices of the filaments.

  Preferably the sealing consists of polyurethanes

  rethanes that are obtained by reacting compounds

  di- and trihydroxylated with a di-isocyanate in a solvent.

  It has proved particularly advantageous to use trimethylolpropane as the trihydroxy compound for the constitution of the polyurethanes. As the dihydroxy compound dipropylene glycol is particularly suitable. A very suitable polyurethane is that obtained by reacting castor oil, trimethylolpropane,

  dipropylene glycol and diphenylmethane diisocyanate.

  As the dihydroxy compound it is also possible to use

  polyalkylene glycols, in particular polytetramethylene,

  glycol. It has proved particularly advantageous to use

  at the same time as the polyalkylene glycols also dipropylene glycol.

  Preferably the sealing consists of polyurethanes

  rethanes that have been obtained by reacting the compounds

  hydroxylated with di-isocyanates in a group report.

  OH to the NCO groups equal to 1 - 1.5, in particular equal to

1.25 - 1.4.

  To seal the sectional surfaces of the filaments

  multi-component hollow bundles, which serve as

  membrane in a dialyser and which on the dialysate side have a layer containing the adsorbent particles and the product side retained are constituted by a regenerated cellulose layer optionally a cellulose derivative and whose ends are embedded in hardened polyurethane and are cut to have a tubular tray

  leaving it open, we use a process that is

  characterized by spraying on the cross-section surfaces a 10% -20% by weight polyurethane solution having a viscosity of 8 to 15 mPa.s which, in addition to the solvent, contains a diluent having a evaporation of 2 to 25, and optionally a spreading agent. It has proved advantageous to use gel-free solutions. As the solvent is particularly suitable ethylglycol acetate;

  As the isopropanol diluent is particularly advantageous.

  It is favorable to spray on

  sectional areas heated to 40 '- 60-C.

  As spreading agent cellulose acetate butyrate

is particularly appropriate.

  It is very favorable to use polyurethane solutions

  rethanes having a viscosity of 10 to 11 mPa.s.

  The preparation of the polyurethanes takes place according to the procedure

  usually used in polyurethane chemistry.

  The reagents are dissolved in a solvent ethyl acetate

  glycol being mainly used as a solvent. Other suitable solvents are other acetic esters, for example

  ethyl acetate and others.

  It is advantageous to separately dissolve the hydroxyl compounds on the one hand and diisocyanate on the other hand and slowly add the di-isocyanate solution in a solution prepared in advance of the hydroxylated compounds. It is

  favorable to operate under a nitrogen atmosphere.

  The concentration of starting materials in the solu-

  It is adjusted to a sufficiently high value that a final concentration of 20% by weight of polyurethane can be obtained after the reaction by adding the agent.

  spreading and diluent. So the concentration of

  The starting point in the solvent is advantageously

  above 30% by weight; a favorable concentration is

  between about 40% by weight or even 60% by weight.

  The solution of the hydroxyl compounds prepared in advance can be heated, for example to 801C; during the addition

  of diisocyanate care must be taken that the temperature

  eradication does not rise too high; it must not exceed,

  as far as possible, 901C.

  During the reaction it is advantageous to stir; care must be taken that the addition of the di-isocyanate is not carried out too quickly, because as a result of the reaction

  Exothermic, the temperature should not rise too high.

  In general, the addition of the di-isocyanate lasts 20 to 30 minutes.

  Then it is still allowed to react at 90 ° C until a large

  part of the NCO groups reacted. This usually requires

  still another hour and a half to two hours.

  In the still warm polyurethane solution, add

  then the spreading agent. The spreading agents,

  peeled yet equalizing agents, are additive products

  These are added to the many coating products, in particular lacquers, which accelerate the spreading of a paint, that is to say its ability to smooth out unevenness, scratches, blisters, etc. forming during the application. As spreading agents are suitable, the glycol and the glycol ethers, the esters, the ketones, the

  silicone oils, the polymers vi-

  nylics and other products. The spreading agent poses a problem here because when spraying on the surfaces of

  section, care should be taken that the desired sealing

  form on the adsorbent a thickness of 0.2 to 2 μm, but

  does not simultaneously form a skin that would close the ori-

  these hollow filaments. The spreading agent exerts an influence in particular on the superficial properties

  of the polyurethane solution used for sealing.

  The spreading agent can also be added at a time

  later, for example when the diluent is already added.

  As a spreading agent is appropriate especially in

  the scope of the present invention the cellulose acetoburyrate

  for example, a product which on the day of deposit of that

  Mande was sold commercially under the brand name "Cellit Bp 500" (Company BAYER AG, Leverkusen). The leveling agent is advantageously added in the form of a solution, the solvent already used in the manufacture of the polyurethane being

preference employed.

  In general, the amount of spreading agent added is from 3 to about 10% by weight (expressed as polyurethane solids). Preferably, about 4-6% is added

by weight of spreading agent.

  After adding the spreading agent, the diluent which serves to activate the evaporation of the solvent after the spraying is added. Suitable for this purpose are, inter alia, alcohols, such as methanol and low boiling acetic esters such as ethyl acetate. Preferably

  isopropanol is used as the diluent.

  When the diluent is added, the final concentration of the polyurethane is not usually adjusted yet, but

  gets a concentration that is still slightly higher than

  above the concentration with which the pul-

  vérisation. After the addition of the diluent,

  to remove the gel fraction or any other impure-

  possibly present. After the filtration by adding further diluent, which is advantageously used under

  form of a solution in a report of a part of di-

  luent for a portion of solvent, the final concentration is adjusted.

  To operate later with the solution it is important to

  setting it to a favorable viscosity which is in the range of 8 to 15 mPa.s, preferably in the range of 9 to 13 mPa.s. Suitable solutions of this type generally have a concentration of 10 to 20%

  by weight of polyurethane. The rest of the solution is

  1.5 killed by the solvent and the diluent as well as by the agent

  LEMENT. Of course, it goes without saying that the diluent and the sol-

  stand in a ratio measured one against

  the other, the amount of solvent is generally not less than

  than the amount of diluent, otherwise it may

  produce a precipitate. Possibly after the second addi-

  diluent is filtered once more, resulting in a spray solution which is free of gel and

all other foreign bodies.

  The viscosities mentioned are usually measured

  at 20C. For the constitution of the polyurethane

  reads di- and trihydroxy compounds as well as diiso-

  cyanate. In addition to trimethylolpropane, castor oil is

preferably used.

  As dihydroxy compounds, the dipro-

  pylèneglycol. By adding trimethylolpropane, the crosslinking reaction is particularly favorably controlled, which has a particularly favorable influence on the mechanical properties.

sealing.

  The dipropylene glycol must, among other things, dissolve the polyurethane in the solvent-diluent mixture and thus ensure good sprayability and formation.

  proper sealing. In addition, as another hy-

  can be used together with polytetramethylene

glycol,

  Instead of castor oil one can also use

  polyetherdiols such as polytetramethylene glycol or

polypropylene glycol.

  Spraying of the solution can be carried out at

  using typical spray devices. Thus the use

  of propellants such as CO2, hydrocarbons

  chlorofluorinated or compressed air is possible. He is also

  it is possible to operate with a simple

  bulding, the propellant air being supplied manually to

using a rubber pear.

  When spraying the section surfaces with the polyurethane solution, care must be taken not to spray the solution too much. It is therefore sufficient to spray on

  section surfaces in a very short time. The solvent evaporates

  pore relatively quickly. In general, it is sufficient to

  kill two sprays on the section surfaces.

  For spraying at least one uses

  shovel the cross-spray technique; for this the surface receives a rapid spray from left to right and from top to bottom. In general the spraying time is very short. It only takes a fraction of a second, for example a quarter of a second. With longer spraying times, the hollow filaments may be plugged. The distance from the sprayer to the tubular plate must be understood

between about 20 and 30 cm.

  By heating the formation of the sealing is accelerated, so it is favorable that the tubular trays spray coating have a temperature of about

406 to 606C.

  It is advantageous to seal in a room

  this without dust especially when the dialyzers are

  used for hemodialysis, or any other medical

Dicale.

  The evaporation index is a measure used to determine

  the speed with which a liquid evaporates into the air below its boiling point at a temperature

  determined. This index is determined according to DIN 53170.

  It is quite surprising that according to the present

  If it is possible to achieve surface areas of

  in sealed polyurethane, which leaves open the origi-

  hollow filaments, but do not allow penetration of

  adsorbent particles within the hollow filaments.

  Thus it is possible to obtain by a simple spray waterproof sealing, without the orifices of the filaments

hollow are clogged.

  The section surface obtained is very united, so

  there is no sealing problem during dialysis.

  The sealing is very elastic, resistant to the

  most liquids, particularly with respect to blood and ab-

  solutely safe for human blood, that is, non-human

  toxic. The required spraying times are very short; in general spraying once or twice on the cross-sectional surfaces is sufficient to obtain a continuous sealing layer. With the help of the sealing

  can plug holes that may also be present

  in the polyurethane coating.

  The sealing also serves to avoid dead zones on the tubular plate, which for the quality of the purified blood is of utmost importance. Thanks to the sealing

  it prevents a turbulent circulation of blood.

  The dialyser according to the present invention is particularly suitable in hemodialysis for the purification of blood in liver diseases, poisoning, schizophrenia, etc. The present invention is illustrated by the examples

  descriptive and nonlimiting below.

EXAMPLE 1

  73.95 g of castor oil, 86.3 g of dipropylene glycol and 27.35 g of trimethylolpropane are dissolved in 322.45 g of ethylglycol acetate and placed in an apparatus equipped with a

  agitator (three-necked flask with stirrer, thermostatic

  meter, reflux condenser). By a regulated dropping funnel

  at a temperature of 80 ° C, a solution is added dropwise

  314.4 g of diphenylmethane diisocyanate (4,4 ') in 540.65 g of ethylglycol acetate are

  minutes. After allowing to react for about 2 hours

  At 2.5 hours, 20.1 g of "Cellit BP 500" dissolved in 180.9 g of ethylglycol acetate was added and stirred for about 10 minutes. 1044 g of isopropanol are then added and stirring is continued. This gives a solution containing 20% by weight of solid matter. After filtration, the viscosity is adjusted to 10.5 mPa.s by addition of isopropanol dissolved in the same amount of ethylglycol acetate. The solution thus obtained can be sprayed immediately.

EXAMPLE 2

  21.5 g of polytetramethylene glycol (molecular weight

  1000), 17.3 g of dipropylene glycol and 5.5 g of trimethylol-

  propane are dissolved in a mixture of 14.8 g of ethylglycol acetate and 14.8 g of ethyl acetate to obtain a 60% by weight solution, then placed in a container provided with

  an agitator. Then a solution is added dropwise

  54.4 g of diphenylmethane diisocyanate (4,4 ') in

  a solvent mixture comprising 18.1 g of ethyl acetate

  glycol and 18.1 g of ethyl acetate. After about 2 to 3 hours, 158 g of ethylglycol acetate and then 158 g of isopropanol are added first. The solution is adjusted to a viscosity of 11 mPa.s after filtration by adding isopropanol without addition of spreading agent. The solution thus obtained

  can be sprayed immediately.

EXAMPLE 3

  9.25 g of polypropylene glycol (molecular weight 400), 17.26 g of dipropylene glycol and 5.47 g of trimethylolpropane are dissolved in 55 g of ethylglycol acetate and placed

  in an apparatus equipped with a stirrer. By a light bulb

  I then drop a solution of 62.88 g

  of diphenylmethane diisocyanate (4.4 ') in 108.1 g of

  Ethylglycolate in 20 to 30 minutes. After 2 to 3 hours, 3.79 g of "Cellit PB 500" dissolved in 34.1 g of ethylglycol acetate are added with stirring. 197.3 g of isopropanol are then added. After filtration, the solution containing 20% by weight of solid material is again diluted to

obtain a sprayable solution.

1.0

_ = E V E N D I C A T IO N S

- = == :: == == = = == = == - _ == ==

  1. Dialyzer with as membranes bundled multi-component hollow filaments which have a layer containing adsorbent particles placed on the dialysate side and which consist of the product product retained by a regenerated cellulose layer and optionally a cellulose derivative , and which have their ends encased in polyurethane hardened and cut to have a tubular plate leaving open the orifices of the hollow filaments, this dialyzer being characterized by sealing the cross-sectional surfaces with polyurethanes, 0.2 to

  2 m leaving the openings of the filaments open.

  2. Dialysis machine according to claim 1, characterized by

  sealing with polyurethanes which are obtained by

  to react dihydroxy and trihydroxy compounds with

a di-isocyanate in a solvent.

  3. Dialyzer according to claim 2, characterized in that the trimethylolpropane is used as trihydroxy compound.

  4. Dialysis machine according to claims 2 and 3, characterized

  rised by the fact that dipropylene glycol is used as

dihydroxy compound.

  5. Dialyzer according to any one of the claims

  2 to 4, characterized in that a polyurethane is used

  obtained by reacting castor oil, trimethylolpropane

  pane, dipropyleneglycol and 4,4'-diphenylmethanedioiso-

cyanate.

  6. Dialyzer according to any one of the claims

  2-4, characterized by simultaneously using

  polyalkylene glycols as dihydroxy compounds.

  7. Dialysis machine according to claim 6, characterized by

  the fact that polytetramethylene glycol is used simultaneously

col as polyalkylene glycol.

  8. Dialysis machine according to any one of the claims

  2-7, characterized in that a polyurethane obtained by reacting hydroxyl compounds with di-isocyanates in a ratio of OH groups to groups is used.

NCO from 1 to 1.5.

  9. The dialyzer according to claim 8, characterized in that the ratio of OH groups to NCO groups ranges from

1.25 to 1.4.

  10.- Process for sealing. the bundled multi-component hollow filament sectional surfaces which serve as membranes in a dialyser and which exhibit

  on the dialysate side a layer containing particles of ad-

  sorbent and which consist of the product side retained by a layer of regenerated cellulose and optionally a cellulose derivative, which have their ends embedded in hardened polyurethane and cut to have a tubular plate leaving their orifices open, this process being characterized by the fact that a section of 10-20% by weight polyurethane solution having a viscosity of 8-15 mPas is sprayed onto the cross-sectional surfaces which, in addition to the solvent, contains a diluent having an evaporation index of from 2 to 25

  and optionally a spreading agent.

11. Process according to claim 10, characterized by

  the fact that we use solutions without gel.

  12. Process according to claims 10 and 11,

  because the use of ethyl glycol acetate is

me solvent.

  13.- Method according to any one of the claims

  at 12, characterized by the fact that isopropanol is used

, diluent man.

  14.- Method according to any one of the claims

  13, characterized by the fact that the spraying is carried out

  on sectional surfaces heated to 40'-60'C.

  15.- Method according to any one of the claims

  10 to 14, characterized in that the acetobuty-

  spleen cellulose as spreading agent.

  16. A process according to any one of the claims

  at 15, characterized in that solutions are used

  of polyurethane having a viscosity of 10 to 11 mPa.s.