DE3101159A1 - METHOD AND DEVICE FOR CLEANING BLOOD - Google Patents

Description

Method and device for purifying blood

The invention relates to a method for purifying Blood through extracorporeal elimination of special Urinary Bubetanzen via diffusion (hemodialysis) and convective tranaport (hemofiltration) of these substances through a semipermeable membrane, according to the arterial blood along a string (blood side) of the membrane and OialyaaflUseigkait while maintaining it ain transmission pressure on the other side

or direct current

(Filtrate side) of the Mambran in countercurrent / to each other and the resulting filtrate is withdrawn from the mambran and discarded.

Ea is known to be the symptoms of renal insufficiency in acute or chronic kidney disease with the help of treat extracorporeal hemodialysis. With this dialyaing procedure, the retention products or Toxins eliminated by diffusion processes. They diffuse in from the blood through a semipermeable membrane the OialyaeflUaaigkeit. The rate of diffusion depends on the ratio of pore size of the membrane / molecular size of the substance to be eliminated and on the Blood / dialysis fluid concentration gradient. Yes smaller the case of concentration and the greater the molecular

the weight of a substance, the slower it becomes eliminated by dialysis.

The process of hemodialysis has the disadvantage that for Maintaining a high concentration gradient, the provision of large amounts of dialysis fluid is necessary is. In order to carry out the process, extensive installations are therefore required to facilitate mobility of the system in terms of use as a portable artificial one Set kidney limits. Another major disadvantage of hemodialysis is that it only contains substances with relatively small molecules (molecular weight <£ 5000 Dalton) can be removed, since the elimination of the substances from the blood takes place via a pure diffusion process.

In contrast to the dialysis process, the metabolic products are in the natural kidney through filtration processes, i.e. eliminated with the help of corrective transport. In the years 1967-69 one of the modes of operation of the A procedure based on the natural kidney developed in which the elimination of the urinary substances exclusively through convective transport in the course ultrafiltration through a highly permeable membrane

as
he follows. In this process, known as "hemofiltration", ultrafiltrate is removed from the patient using hydrostatic pressure, which is then replaced by an infusion solution. An advantage over the process

the dialysis predecessor lies in the fact that within «in ·· through the pore diameter of the membrane and the filtrate * * fluB limited range of all substances, regardless of Molecular weight and size, can be eliminated at the same rate. It can therefore be used with this Processes also substances with a larger molecular weight (up to 1,000,000 tons and more) and especially large amounts of water remove. The disadvantage of this method is that to compensate for the withdrawal of liquid from the blood this again a relatively expensive substitution solution must be supplied and that the process related to the removal of low molecular weight substances is not particularly effective because the elimination takes place exclusively via convective transport.

To improve the removal of low molecular weight substances in a hemofiltration process, Combined procedures have already been proposed that involve both hemodialysis and one Make use of hemofiltration (A.W. Leber, V. Wiezemann and F. Techert, Art. Organs, 4 (4), 19Θ0, p. 10β). These Processes correspond to the procedure mentioned at the beginning. Here, on the filtrate side, the semipermeable Membrane dialysis fluid passed by. On the membrane thus both convective transport and a diffusion process take place, so that this process

remove both low and medium to large molecular weight substances. The filtrate withdrawn from the membrane is completely discarded. The process has the disadvantage that precise control of the rate of filtration is associated with difficulties and that large amounts of dialysis fluid and substitution solution are also required here. As a result, this method also has limited "mobility" * ¹ and appears hardly suitable for use in the farm of a portable artificial kidney.

The invention is based on the object of a method to create blood entrainment, with which both substances with low as well as medium and high molecular weight can be removed without this large amounts of Need dialysis fluid and substitution fluid. The method should also be in the form of a simply constructed and portable device, for example a portable artificial kidney.

This task is according to the invention in a method of the type described in the introduction in that only a tail of the filtrate withdrawn from the membrane is discarded while the other part of the filtrate is continuously passed through an adsorption system in which the filtrate by removing at least a portion of the blood from the blood absorbed substances is regenerated, and the filtrate is regenerated in the circuit to the filtrate side of the membrane returned and there all dialya fluid again

is used.

In the method according to the invention, the blood becomes aozuaagan in the ultrafilter (aemipermeable membrane) against its own regenerated filtrate "dialyzed". Through the on the The negative pressure maintained on the filtrate side of the membrane will also reduce the rate of filtration the circulation speed of the Filtrata is controlled. When if the negative pressure on the filtrate side increases, the rate of filtration increases. Daa procedure preferably runs in such a way that there is always only a lot of filtrate is discarded that an approximately constant fluid circulation can be maintained. To the invention The process begins to start, a relatively small amount of dialysis fluid is required (approx. 3-5 l), which is far below the amounts of dialysis fluid which can be reacted using conventional hemodialysis have to. The negative pressure on the filtrate side of the membrane is generated with the aid of a filtrate pump. When the pressure on the filtrate side a positive value is assumed, ao this means that through the filter more liquid is in is introduced into the filtrate circuit rather than withdrawn from the circuit. Ea must then dia deductible windigkait be increased in order to build up a negative pressure again on the filtrate side of the membrane and an approximately constant pressure Maintain fluid circulation. This can be done by

opening a valve happen.

The main advantages of the method according to the invention are that none large amounts of dialysis fluid and substitution fluid are required ι with only a relatively small proportion of the filtrate is discarded from the treating Can be determined by a doctor and is necessary for draining the patient. This means that to carry out the invention Processed also no voluminous devices for storing the dialysis fluid or the discarded Filtrates are needed. The method can therefore be implemented in a simple and inexpensive manner, one being very high "mobility" is given.

With regard to the elimination of substances, both those with a low molecular weight can be used in an in Remove in a manner comparable to conventional hemodialysis as well as substances with medium or higher molecular weight in a manner comparable to hemofiltration. The inventive method combined thus the advantages of the two known methods without, however, the large amounts of dialysis fluid and need substitution fluid.

If the inventive method in the sense of an artificial If the kidney is to work, the adaortion system for regenerating the filtrate is set so that predominantly Urea, creatinine and uric acid are removed from the filtrate,

However, the method according to the invention is not only based on these Scope of application restrictedi This means that other In particular, remove toxic substances from the blood, so that the process can also be used, for example, in the case of drug or drug abuse. Poisonous patients and generally in immunotherapy can be used. The method is therefore much more versatile than the known methods of hemodialysis and hemofiltration or their combinations, since the adsorption system is adjusted to the specific application can be, i.e. such an adsorption system be used, which binds the corresponding substances to be eliminated from the blood * As mentioned, this is when used as an artificial kidney a predominantly urea,

and
Creatinine / uric acid binding system. In other cases, an adsorption system can be used that binds the corresponding substance to be eliminated.

Such a possibility of removing very special substances from the blood exists with the known methods not. In hemodialysis and hemofiltration, only the size of the molecules plays a role in the substances to be removed Rolle, i.e. all substances below a certain molecular weight are removed from the blood, regardless of whether they have "toxic properties" or not. According to the invention however, it is possible to selectively remove a very special substance by simply tapping on it special substance-matched adsorption system used will.

In addition to the state of the art, it should be noted that that ea is already known, a hemoperfusion with a To couple ultrafiltration (T.U.S. Chang, E. Chirito, P. Barre, C. Cole, C. Lister, and E. Resurreccion, Long-term Clinical Assessment Combined ACAC Hemoperfusion-Ultrafiltration in Uremia, Artificial Organs 3 (2), 1979, p. 127). Here blood is passed directly over an activated charcoal column and then an ultrafiltration using a semipermswblen Membrane subjected, wherein the withdrawn filtrate is completely discarded. Although this procedure is relative is easy to implement, it has the disadvantage that the Blood comes into direct contact with the activated carbon filter, which can destroy blood cells. A very special type of activated charcoal must be used here, which is in microcapsules made from cellulose nitrate is included. The method according to the invention has do not have these disadvantages, since here only the filtrate separated from the blood via an adsorption system (activated carbon filter) is performed, i.e. the adsorption system is not in direct contact with the Blood.

For the above reasons, it is according to the invention Method also possible to work with relatively high blood flows (greater than 150 ial / min), wao in a human perfusion procedure due to a possible Damage to blood particles and the risk of embolism

not possible iat. In addition, it must be used in the case of the inventions Procedure daa adaorptionaeyatam also not ateriliaiert because bacteria and viruses cannot get through the ultrafilter *

As already mentioned, a method can be invented can also be used to detoxify drugs and remove toxins. In immunotherapy there is a need to Use removal of antigen-antibody complexes and other proteins. For these purposes, anateile an ultrafilter a membrane filter with a pore size of 0.1 to 0.5 µm is used, and it becomes a corresponding one Adsorption material used in the adsorption system.

The circulated filtrate is advantageous kept at about body temperature. If necessary, this can be achieved by heating the circulating filtrate, this preferably being carried out via a heat exchanger will.

The blood circulation on the blood side of the membrane is Carried out if possible without a blood pump by using the body's own pressure drop. This body's own pressure gradient is about 50-80 mm Hg, which pressure is sufficient to pass 200-250 ml of blood per minute through one to drive the usual ultrafilter. In the case of the method according to the invention, a filtration

rate between 10 to 50 ml / min worked, which is much lower than with a corresponding Haraofiltration method. If the procedure is being performed on a patient, large amounts of fluid will be added with a filtration rate higher than 50 ml / min worked. Of course, you can also work with a blood pump.

When the process is supposed to take over the function of an artificial kidney, it is advisable to work with a membrane with a cut-off between 100,000 and 100,000 Daltons. By using such a membrane, the aforementioned filtration rate of 10 to 50 ml / min can be achieved at a relatively low transmembrane pressure. Preferably, with a transmembrane pressure Δ ρ of ^ 200 mm Hg, in particular

80 mm Hg worked. Since this value is comparatively great is low, there is also the risk of the membrane rupturing and a corresponding transfer of blood into the filtrate circuit small amount.

In many applications, in particular as an artificial kidney, the method according to the invention is carried out with activated carbon worked in the Adsorptionssystara. In this way, a large part of the uramic substances can be removed from the filtrate. Although the binding capacity of activated carbon with respect to urea is relatively poor, it has not yet been better

Material has been suggested for this purpose. It has been shown, for example, that to remove 40 g Urea per treatment approx. 3 kg activated carbon and 3 ltr. removed Filtratflüsaigkeit are sufficient.

It is evident that the filtrate is not recirculating can be before the Filtratkreia is completely filled with liquid. An alternative to the invention The process is therefore started in such a way that the filtrate circle is initially filled with fresh dialysis fluid. if however, filling with dialysate is not desired the treatment can be started with another alternative of the procedure with a fast, pure ultrafiltration, until the filtrate circuit is filled. The filtrate is then used as dialysis fluid in the filtrate circuit. Through this no external dialysate is necessary.

According to the invention, one can work with an adsorption system divided into three or more small systems, which are used either parallel to one another or one after the other. With the latter variant for example, a saturated adsorption cartridge is replaced by a fresh adsorption cartridge in a simple manner replaced. This variant allows the method by means of perform a device that can be carried on the body. For example, if several adsorption cartridges are used in parallel with each other, care must be taken

bear that each cartridge has an identical pressure drop has, ao that everywhere the same flow ratios to rule.

The process according to the application is therefore in relation to the The formation of the Adsorptionaeystem is very flexible because the Number of cartridges used can be adapted to the respective requirements. The used cartridges can be regenerated very quickly. For example, an activated charcoal column can be regenerated using steam and used again for the same patient, making the treatment cheaper overall than other systems. This is for the cases of Advantage where no fresh cartridges are available. This also enables storage in fresh Cartridges are avoided.

The invention also relates to a device for Implementation of the method described above with a first line system for production and maintenance an eMtracorporeal blood flow from an artery to a vein, one in the erate conduit system switched on hemofilter with a semipermeable membrane, along one side of which the blood is guided, and a second line system for conducting dialysis fluid while maintaining a transmembrane pressure along the other side of the membrane in the counter-atom

or direct current

/ to the bloodstream, ao dafl a · Hemodialyae and hemofiltration atattfinds, and to discharge or discard dea from the Membrane withdrawn filtrata.

Oieae device is characterized according to the invention, that there is a second line atromab from the hemofilter Branch point from which a line for dividing and maintaining a filtrate cycle back to the homofilter while another line to remove the filtrate that is used in the filtrate between Häraofiltar and branching point a filtrate pump aowie atromab from the branching point an absorption aayatera arranged iat and that there is an Abaperr or Doaiar valve in the line serving to discharge the filtrate

Regulation of the circulated Filtratmenga is located.

The device according to the invention draws aich by a simple structure and easy handling as well as great mobility as well. Oiea makes aie beaondera suitable for use as a künatlicha that can be worn on the body Kidney. By dividing the Abaperr- resp. Dosing valve ·, daa in the serving to discharge the filtrate

Line arranged iat, the circulated fiItrate volume or

in particular

The amount of filtrate discharged can be adjusted easily / manually. For the absorption system I offer one A number of possible variations, including in particular here a quick Auatauach and Eraatz from used ones

Allow adsorption elements that regenerate quickly can be.

Developments of the device according to the invention go out of the sub-reviews.

The device is now illustrated on the basis of an embodiment described in detail in connection with the drawing. The drawing shows the acheroatiachen structure designed as an artificial kidney according to the invention Contraption.

The device comprises a first line system 1 for producing and maintaining an extracorparal Blood atromes from an artery to a vein. In this Line system is a Hamofilter 2, which is from can be of a known type, for example an Amicon Qiafiiter, an Asahi haemofilter or an flP-6 haemofilter. The separation limit of the seraipermeable membrane of the filter can in the embodiment shown here as an artificial one Kidney can range up to a molecular weight of 100,000 Daltons. For other application cases are even higher Separation limits possible. In front of and behind the Hemofilter 2, a manometer 4, 21 is arranged. In the pipe system 1 there is also a bubble trap. The system described here usually comes without the Use of a blood pump in the line system 1 also, since the

Pressure drop across the hemofilters mentioned above is small. Ee sail also work with a relatively low tranamembrane pressure Δ p _ffl below 200 mm Hg, preferably around θ mm Hg. This further simplifies the system and does not damage the blood filter.

The device also has a second line system S on, in connection with a line 11 for the production and maintaining a filtrate cycle. Means this Filtratkreises S, 11 is that by diffusion and Convective transport, i.e. hemodialysis and hemofiltration, filtrate withdrawn from the blood via the semipermeable membrane circulated, whereby it is guided through an adsorption system 15 is regenerated. The blood is therefore "dialyzed" in the hemofilter 2 against its own regenerated filtrate. To the UmwälZMng a filtrate pump 13 is used for the filtrate, which controls both the filtration speed and the circulation speed specifies. The pump sucks the filtrate through the semipermeable membrane and pushes it through the adsorption system 15 through. To regulate the pressure drop in the filtrate circuit is between the adsorption system 15 and the hemofilter 2 a shut-off or metering valve 20 is provided.

The filtrate pump 13 is naturally downstream of the hemofilter 2 arranged and is located upstream of a branch point 6 in the line system at which the line 11 to form of the Filtratkreisee and a line 7 for discharge or

Discard dee branch off from the Uebran abgezo _B enes FiItrat ". In the line 7 lifc a further abaperr or dosing valve § virgiiiHeni raitteli led or discharged to the dluragewjilzte

ina ^ bBsöndere
PiitritlTiehQi / raonUSii can be regulated “'' ου iböi led filetake kihh, for example, be introduced into a container Ϊ0, in which“ it is stored and discarded at a later point in time. In the line 7 iat vbriüBiweiia iih Durchflußraeaäer Ö

The Filtratkreie 5, 11 contains the further here daröaiteileh Äu Führuhgebeiepial a Wärraatauechär IBs in order to dig the molten filtrate to about body temperature hold, a trap 19 for ventilation and a Durchfluflmeaeer 17. Im Kraie and the further manometer 12, 14, 16 ahöGSördheti

The device described above works in such a way that first the filtrate circle 5, 11 ill a usual one Dialysis fluid replenishes. Naturgemissdaa is here Valve § geachlaaeen, while valve 20 opened lit « When the filtrate circle is filled with dialysis fluid, If the filtrate pump 13 is put into action, whereby the Dialyaeflüeaigkeit or dig filtrate is circulated. Above The valves § and 20 now know that the flow rate is regulated so that only a lot of filtrate enters the container 10 is discharged that an approximately constant FlÜeaigkeiteünilauf is maintained. In other words,

BATH ORIGINAL

If the pressure in the filtrate circle on the filtrate circle of the membrane reaches a positive value, this means that the fluid leakage through the membrane into the filtrate circle is greater than the liquid discharge into the container 1Q. By readjusting the valve 9, the equilibrium can be easily restored and vice versa * This can be done by the patient himself after appropriate medical advice

In the execution examples described here, Removal of approx. 40 g urea per treatment approx. 3 kg activated carbon in the adsorption system and 3 liters » withdrawn filtrate required ρ the entire device weighs no more than 8 kg, whereby this includes the discharge fluid, the platinum pump, the valves, etc. includes. This means that the device is significantly lighter than known systems and can be carried on the patient's body will·

To regenerate the filtrate is described here at dam Application as an artificial kidney, preferably activated charcoal «This can be done in the form of cartridges, like that that a quick replacement of used cartridges with new ones is possible. You can also use several cartridges can be used in parallel or one after the other * Redy cartridges can also be used instead of activated charcoal can be used, but have the disadvantage that they need a larger amount of dialysis fluid »

BATH ORIGINAL

Case an initial filling daa Filtratkreiaaa with dialysis The treatment can also be used A quick, pure ultrafiltration can be started until the filtrate is filled against the regenerated filtrate.

The functioning of the device described above is confirmed by the following test! An Araicon HIxSO hollow fiber filter (930 cm ² surface area) was used as a hemofilter, and 120 g of extruded activated carbon, which had been thoroughly washed, were used to regenerate the filtrate · In this experiment, a urea and uric acid solution (1500 ml ) used »This solution was implemented with a speed vgn

themselves

200 ml / min circulated through the filter, so that a Filtratio negesoh windiness of 10 ml / min, along with maintain the circulation speed of 200 ml / min was · At regular intervals the "blood" in a container and the activated charcoal column leaving filtrate to determine the urea and uric acid content samples taken

The examinations showed that after a 60-minute Treatment time the uric acid concentration in the "blood tank" has been brought to a value of zero. The amount of Urnatoff removed was 1 g.

BATH ORIGINAL

Claims (1)

Dr. Udipi Ramakrishna Shettigar
Melatansr Str. 33
0-5100 Aachen Dn-247
January 1981 Claims 1. Procedure for purifying blood by extracarporals Elimination of special urinary substances via oiffuaion (hemodialysis) and convective tranaport (Hemofiltration) of these substances through a semipermeable membrane, according to the arterial blood along one side (slut side) of the membrane and dialyaeflüasigkeit i j while maintaining a transmembrane pressure along j or direct current of the other side (filtrate side) of the membrane in counter-anatromic flow are fed to each other and the filtrate formed is drawn off from the membrane and discarded, thereby characterized in that only a portion of the filtrates withdrawn from the membrane is discarded, while the other Part of the filtrate continuously through an adsorption system is performed, in which the filtrate is taken up by removing at least a portion of the blood Substances is regenerated, and the regenerated filtrate is recycled to the filtrate side of the membrane and there it is used again as dialysis fluid. 3Ί0Ί159 The method according to claim 1, characterized in that only ao much filtrate is discarded so that an approximately constant liquid circulation can be maintained. 3. Method according to claim 1 or 2, characterized in that that the circulated filtrate is kept at about body temperature, if necessary by heating. 4. The method according to any one of the preceding claims, characterized characterized in that a filtration rate between 10 and SQ «l / min is used. 5. The method according to any one of claims 1 to 3, characterized characterized by operating at a filtration rate higher than 50 ml / min when the process is carried out on a patient, the large amounts of fluid are fed. 6 · Method according to one of the preceding claims, characterized in characterized in that a membrane is used whose cut-off limit is at a molecular weight between 5000 and 100000 OaIton. 7. The method according to any one of the preceding claims, characterized in that one works with a tranamembrane pressure Δ ρ of <200 mm Hg _1, in particular of 60 nra Hg θ. Method according to one of the preceding claims, characterized in that the blood circulation on the blood side the membrane is carried out without a blood pump by utilizing the body's own pressure gradient. 9. V / experience according to one of the preceding claims, characterized characterized in that the process is started by filling the filtrate circle with fresh dialysis fluid will. 10. The method according to any one of claims 1 to Θ, characterized characterized in that the process is started with a rapid, pure ultrafiltration until the filtrate circle is filled, after which hemodialysis is started against the regenerated filtrate. 11. The method according to any one of the preceding claims, characterized characterized in that an adsorption system divided into three or more small systems is used, which are used either parallel to one another or one after the other. Device for carrying out the method according to one of Claims 1 to 11 with a first line system for the production and maintenance of an extracorporeal Blood flow from one artery to one vein, one into the first line system switched on with hemofilter an aeraipermeable membrane along which one string there is blood, and a second conduit system for keeping dialye fluid in place a "tranmembrane pressure" along the other side of the membrane in counter current or direct current to the bloodstream, so that hemodialysis and hemofiltration takes place, and for discharging or discarding the filtrate withdrawn from the membrane, characterized in that the second pipe system (5) has a branching point (6) downstream of the Hümofilter (2) has, of which a line (11) for production and Maintaining a filtrate circuit to the hara filter (2), while another line (7) serves to discharge the filtrate, so that in the filtrate circuit (S, 11) between the hemofilter (2) and the branch point (6) Filtrate pump (13) and downstream of the branch point (6) an adsorption system (15) is arranged, and that in the line (7) used for discharging the filtrate in particular a shut-off or metering valve (9) for / manual regulation the circulated amount of filtrate is located. 13. The device according to claim 12, characterized in that in particular that in the filtrate circuit [5, 11J for manual regulation of the pressure drop in the Adsorptionsaystem (15) nachgeordnates Shut-off or metering valve (2Q) is provided. 14 device according to claim 12 or 13, characterized in that that aie ala formed an artificial kidney that can be worn on the body iat. 15. Device according to one of claims 12 bia 14, characterized
characterized in that daa absorption aayatem (1S) aiindeatena comprises an activated carbon eaa'ule or cartridge. 16 * Device according to claim 15, characterized in that several activated carbon columns or cartridges parallel to one another or arranged in series. 17. The device according to Anepruoh 14, characterized in that daa hemofilter (2) has a separation limit for a molecular weight between 5000 and 100000 Dal ton. 1B. Device according to another claim · 12 to 17, thereby characterized in that a heat exchanger (16) is arranged in the filtrate circuit (5, 11). 19. Device according to one of claims 12 to 18, characterized
characterized in that the filtrate pump (13) is a miniature pump. -for- 20. Apparatus according to claim 19, characterized in that that the miniature pump is a miniature rolling pump or Miniature mambranpumpa is. 21. Device according to one of the preceding claims, characterized in that the adsorption system consists of composed of different specifically acting adsorbers is.