DE19624250A1 - Haemodialysis appts - Google Patents

Abstract

Appts. to separate substances from blood has an intermediate circuit (6) for the dialysate between the dialysis machine (1) and a membrane filter (3). It takes the fluid from a separation filter stage (4) from the dialysis machine (1), and has a recirculation pump (5) to pass it through the membrane filter (3) and back to the separation filter stage (4).

Description

The invention relates to a device for eliminating substances up to one relative molar mass of 150,000 from blood, both dissolved in plasma water as also bound to carrier molecules present in the blood - preferably proteins can be and with conventional methods not or only insufficient can be eliminated.

The need to remove pathophysiologically relevant substances in the mentioned molar mass range from the blood results in the acute and chronic renal failure, acute and chronic liver failure, exogenous intoxications, the multi-organ failure, caused immunologically Diseases, etc. These substances cover a wide range of molecular weights, starting with very small molecules such as urea (relative molar mass = 60), protein-bound uremic toxins (indoxyl sulfate, furan carboxylic acid,...) or liver toxic substances (e.g. bilirubin, tryptophan,...), lipophilic substances (Phenols, indoles,...), Pathophysiologically relevant peptides and proteins up to one relative molecular weight from 150,000 (cytokines) to lipopolysaccharides such as Endotoxins (relative molar mass up to 150,000). You can either freely in the plasma water dissolved or on carrier molecules such. B. bound albumin. Conventional procedures for removing pathogenic substances from the blood are hemodialysis, hemofiltration, the combination of both methods for Hemodiafiltration, hemoperfusion via adsorber cartridges, and membrane Plasma separation (apheresis) and its combination with a specific one Adsorber (plasma sorption).

The conventional methods of hemodialysis (HD) as well as hemofiltration (HF) and hemodiafiltration (HDF) including on-line HF and on-line HDF (i.e. the on-line preparation of the substitution solution) have the following disadvantages:

• - Limitation of eliminable molecular sizes up to a maximum of 40,000 relative Molar mass.
• - lack of selectivity of elimination.
• - Exclusive removal of substances dissolved in the plasma water, d. H. no elimination of lipophilic substances or substances bound to proteins.

The membrane plasma separation process has the following disadvantages:

• - Unspecific removal of substances up to 2 · 10⁶ rel. Molecular weight, d. H. loss of physiologically valuable substances such as albumin, hormones, growth factors, etc.
• - Limited filtration rates due to the risk of hemolysis when using a Filtration pressure <100 mm Hg.

Hemoperfusion via adsorber cartridges is due to the lack of Biocompatibility of the available adsorber materials with whole blood hardly anymore applied. The way out, membrane plasma filtration with subsequent plasma perfusion (plasma sorption), eliminates this serious disadvantage, but is limited to a few substances for which selective adsorbers have been developed (e.g. LDL, immune, endotoxin adsorbers).  

In addition to the conventional methods mentioned, there are proposals that Effectiveness and / or selectivity of these processes by the combination of Increase hemodialysis with additives in the dialysate compartment. In this Regarding earlier, U.S. Patent Applications 3,963,613 (June 15, 1976) and 3,619,423 (Nov. 9, 1970). Both use recirculating dialysate with an enzyme additive for asparaginase therapy for certain forms of leukemia and keep the addition of other substances open. While in the patent 3,619,423 asked about the removal of the asparagine cleavage the resulting toxic ammonia remains unanswered, is described in patent 3,963,613 for this purpose a second dialyzer is inserted into the circuit. For both patents the small-pored membranes used at the time of registration, so that the Question of the removal of higher molecular weight and bound to carrier molecules Substances is not up for debate. Nor will the recirculating dialysate continuously replaced by fresh solution.

Also in the more recent patent application WO 93/15825 "Device and method for extracorporeal blood treatment "and the device Biologic DT® based thereon with the plate dialyzer used and the proposed adsorber Suspensions (activated carbon, cation exchangers, polyvinylpyrrolidone, "polyol flow inducing agent ") only the elimination of water-soluble substances from the blood possible. Likewise, there will be no regular replacement of the used dialysate solution and the adsorber provided.

In contrast, the patent WO 95/04559 "Arrangement for removing substances from liquids, in particular blood "is the basis for the presented invention. Here becomes a very fine cleaning suspension at high speed over the Rinsing solution compartment of a high-flux dialyzer pumped, so that by the positive and negative transmembrane pressures filtered Plasma water can be cleaned and filtered back.

The present invention has for its object to a device create with which the device according to patent WO 95/04559 with the conventional Dialysis procedures can be combined. This creates a possibility Remove substances from the blood that are both dissolved in the plasma water as well can be bound to carrier molecules.

According to the invention we solve this problem by the in the characteristic of Features specified resolved.

The advantageous embodiment of the invention is that

• - A membrane filter with an exclusion limit of 150,000 rel. molar mass is used,
• - Fresh dialysate is continuously fed by between one Dialysis machine and the membrane filter switched a dialysate intermediate circuit which receives liquid from a separation filter stage from the dialysis machine and back over the membrane filter by means of a recirculation pump Separation filter stage returns.

The invention is explained in more detail using several exemplary embodiments. It demonstrate:

Fig. 1 shows the simplest diagram of the combination of a Rezirkulationskreislaufes with a dialysis machine via a separating filter stage,

Fig. 2 combination of a dialysis machine with a recirculation circuit via 2 separation filter stages; in addition, inward and outward transfer of adsorber particles and monitoring of the blood for transferred adsorber particles,

Fig. 3 series circuit of a conventional dialyzer with the highly permeable membrane filter of Rezirkulationskreislaufes,

Fig. 4 series connection of 2 highly permeable membrane filters, one of which delivers defined amounts of filtrate into the recirculation circuit by means of an additional pump.

Fig. 1 shows the separation of the present invention supplied by a dialysis machine 1 2 dialysate from the membrane filter 3 via a separating filter Step 4. Membrane filter 3 and separating filter stage 4 together with a recirculation pump 5 form an intermediate dialysate circuit 6 , which is continuously supplied with fresh dialysate 2 from the dialysis machine 1 . In principle, the separating filter stage 4 is constructed like a high-flux dialyzer, ie, due to its high hydraulic permeability, it allows dialysate 2 to pass through, while large molecules and any particles present in the intermediate circuit 6 are retained. The separation filter stage 4 has a design-related high flow resistance on the side of the dialysis machine 1 , so that a sufficiently high dialysate flow (approx. 500 ml / min) can get into the intermediate circuit 6 . The membrane filter 3 is constructed like a high-flux dialyzer, but with a separation limit of 150,000 relative molar mass, so that due to the transmembrane pressure generated, the ultrafiltrate entering the intermediate circuit 6 contains molecules up to this molar mass from the blood. As usual in hemodialysis, the blood compartment of the membrane filter 3 is fed in countercurrent to the dialysate flow from an extracorporeal blood circuit 7 . The transmembrane pressure is generated by the recirculation pump 5 by creating negative pressure on the suction side of the recirculation pump 5 in the area where the dialyzer enters the blood. On the pressure side of the recirculation pump 5 in the area of the blood outlet of the membrane filter 3 , back-filtration takes place because of the positive pressure present there. Large molecules above the separation limit of separation filter stage 4 (approx. 40,000 relative molar mass) are returned to the blood with the back-filtration, while smaller molecules with the outflowing dialysate 2 can reach the outlet of the dialysis machine 1 .

Fig. 2 shows the use of two separation filter stages 4/1 and 4/2 , which are connected to each other on the side of the intermediate circuit 6 . As a result of this measure, the entire dialysate flow supplied by the dialysis machine 1 is available for the intermediate circuit 6 , as a result of which the separation performance (clearance) for the diffusive mass transfer via the membrane of the membrane filter 3 is increased. In order to achieve the necessary transmembrane pressure gradients for the convective mass transfer of large molecules, the recirculation pump 5 preferably runs with a flow between 1-3 l / min.

In order to bind larger molecules or molecules bound to carrier molecules from the filtrate, an adsorber suspension is introduced into the intermediate circuit 6 , which has a particle diameter of preferably 100-1000 nm. The adsorber suspension is introduced into the intermediate circuit 6 via a special structural unit 8 . In the event that the adsorber suspension is used up before the end of the therapy session, the possibility is provided to fix the adsorber particles to magnetic particles and to design the structural unit 8 by means of a magnetic coil for discharging and introducing the particles.

To increase safety, a particle detector 9 can be attached to the blood outlet of the membrane filter 3 , so that particles which may leak through a membrane leak can be detected and safety measures such as stopping the blood pump and separating the magnetic particles can be triggered.

Fig. 3 shows the possibility of, in addition to the highly permeable membrane filter 3 a conventional low-flux dialyzer 10 to be connected in series. The membrane filter 3 with a cut-off of 150,000 rel. Molar mass essentially serves to eliminate larger molecules by filtration, adsorption and back-filtration, while the low-flux dialyzer 10 is primarily responsible for the diffusive transport of small molecules.

Fig. 4 shows a further possibility in which by the additional use of a pump 11 , which is connected exclusively via only one connection to a membrane filter 3/2 separated from membrane filter 3/1 , the exclusion limit identical to that of membrane filter 3/1 Separation limit of 150,000 rel. Molecular mass, the filtration of a defined by the pumping speed of the pump 11 amount of filtrate per unit time from the blood into the dialysate intermediate circuit 6 is made possible. The filtrate obtained is pumped into the intermediate circuit 6 according to FIGS. 1 and 2, in which the particles with a size of preferably 100-1000 nm, which serve to eliminate certain substances, are recirculated by means of pump 5 . The liquid cleaned by the particles of defined substances is filtered back into the blood circuit 7 by means of the pressure ratios generated by the pump 11 and transferred to the intermediate circuit 6 , preferably via the membrane filter 3/1 , with an additional internal filtration within the membrane filter 3/1 being possible can. The device described does not allow the particles used to come into contact with the membrane filter 3/2 , since the pumping direction of the pump 11 is fixed in the direction of the intermediate circuit 6 in accordance with FIG. 4.

Reference list

1 dialysis machine (volumetric balancing single pass device)
2 dialysate
3 membrane filters (cut-off 150,000 rel. Molecular weight)
3/1 membrane filter stage 1 (exclusion limit as 3 )
3/2 membrane filter stage 2 (exclusion limit as 3 )
4 separation filter stage
4/1 separation filter stage 1
4/2 separation filter stage 2
5 recirculation pump
6 intermediate circuit
7 extracorporeal blood circulation
8 Unit for the inward and outward discharge of adsorber particles
9 particle sensor
10 conventional low-flux dialyzer
11 filtration pump

Claims (10)

1. Device for eliminating substances up to a relative molar mass of 150,000 from blood, characterized in that a dialysate intermediate circuit ( 6 ) between the dialysis machine ( 1 ) and membrane filter ( 3 ) is connected, the liquid from a separating filter stage ( 4 ) receives from the dialysis machine ( 1 ) and returns via the membrane filter ( 3 ) by means of a recirculation pump ( 5 ) to the separating filter stage ( 4 ). 2. Device according to 1, characterized in that the separating filter stage ( 4 ) between the dialysis machine ( 1 ) and the intermediate circuit ( 6 ) consists of a filter. 3. Device according to 1, characterized in that the separating filter stage ( 4 ) between the dialysis machine ( 1 ) and the intermediate circuit ( 6 ) consists of 2 separating filters ( 4/1 , 4/2 ) on the side of the dialysate intermediate circuit ( 6 ) are interconnected. 4. Device according to claims 1-3, characterized in that the recirculation pump ( 5 ), preferably at a flow rate of 1-3 l / min, can recirculate the dialysate ( 2 ) present in the intermediate circuit ( 6 ) to provide additional filtration in the membrane filter ( 3 ) to be generated by the resulting pressure gradient. 5. Device according to claim 1-4, characterized in that particles are preferably introduced with a diameter of 100-1000 nm in the intermediate circuit ( 6 ) for the elimination of protein-bound or higher molecular weight substances. 6. Device according to claims 1-5, characterized in that the used adsorber particles can be discharged by means of a special structural unit ( 8 ) and fresh adsorber particles can be introduced. 7. Device according to claims 1-6, characterized in that the adsorber particles are magnetic and the structural unit ( 8 ) for introducing and discharging the adsorber particles is based on the magnetic attraction. 8. Device according to claims 1-7, characterized in that a particle sensor ( 9 ) is adapted to the blood outlet of the membrane filter ( 3 ) to increase the security against the penetration of adsorber particles in the bloodstream. 9. Device according to claims 1-8, characterized in that the membrane filter ( 3 ) is supplemented by a second membrane filter ( 10 ), the membrane filter ( 3 ) serving primarily the convective mass transfer by filtration and membrane filter ( 10 ) preferably the diffusive mass transfer . 10. Device according to claims 1-8, characterized in that the membrane filter ( 3 ) consists of 2 identical units ( 3/1 , 3/2 ), so that a membrane filter ( 3/2 ) exclusively by means of a pump ( 11th ) generated recovery of a defined amount of filtrate per unit of time from the blood into the dialysate intermediate circuit ( 6 ) and the other membrane filter ( 3/1 ) for the back-filtration of the primarily obtained filtrate, the elimination of defined substances using recirculating particles without these particles Have contact with the membrane filter 3/2 .