DE19917522A1 - Blood purification process, comprises separating out the non-cellular components and then subjecting the blood to further cleansing. - Google Patents

Abstract

A process for cleansing the blood of a patient comprises sepg out the non-cellular components and then subjecting the blood to further cleansing. The liquid obtain is fed through a housing containing filters. The housing has partially or fully flexible or elastic walls, and contains particles.

Description

The invention relates to a method and an apparatus for cleaning Media, especially blood.

Diseases treated with extracorporeal detoxification procedures are medically and economically significant. In this Group of diseases, drug treatment alone is common insufficient. For this reason, new treatments are constantly being developed searched. Extracorporeal supplements come as a supplement to drug therapy Blood purification procedures are used as they remove disease allow relevant factors. The theoretical basis for the use of blood purification methods defined diseases consists in the removal of the disease-mediating Substances from the blood or plasma.

Adsorption (binding, enrichment of substances at an interface between neighboring phases, in this case solid and liquid) of substances plays an important role today in addition to convection and diffusion at the Removal of disease-relevant substance classes. In the past, adsorbers have been used for acute poisoning, but also for a variety of other diseases, for the direct removal of harmful Substances have been used.

In the conventional adsorption process, patient plasma, which was previously obtained by plasma operation on an adsorption column directed, whereby a protein class or ideally only extracts the pathogen becomes. After a defined saturation of the column, the plasma flow is reduced to a passed second adsorption column and regenerated the first loaded column. During the regeneration process, the rinsing liquids are removed from a reservoir passed over the adsorber column to be regenerated, which is the most  substances in the regenerating adsorber material are removed again and thus allowed another adsorption process using this column. The Flushing liquids are collected after the regeneration process container (waste container).

The process of loading and regeneration can be repeated until the desired target concentration of the components to be removed in the patient is reached.

Another way is through disposable articles in adsorption technology followed. Without regeneration and / or flushing, an adsorbent is due the capacity flows in circulation and after a single use discarded.

The z. Z. usual adsorber columns consist of a plastic or glass housing with connections for the media inlet and outlet. The adsorber material is usually between two sieve filters at the inlet and outlet connection Housing packed or enclosed loose (EP 056977 A1). Another variant is that the medium in the housing via a drip plate is passed and thus evenly over that located on a filter plate Adsorber material should run.

The problem here is the most effective use of the Adsorption process taking into account a small medium fading.

A major problem arises in the phase of switching between adsorption and Regeneration process and vice versa.

To return patient-damaging regeneration fluids to the Avoid the patient's blood circulation and change processes with To minimize the medium loss, use a saline solution (NaCl) worked.  

The saline solution is fed into the interior of the adsorber and washes the medium from the adsorber. Partial mixing occurs between the medium and saline. The medium then passes with part of the Saline back to the patient. The actual regeneration process then takes place, in which acid is added to the Adsorber housing and thus the adsorbent is regenerated. In order to neutralize the adsorber material, a buffer solution is placed over the Adsorber column directed, the actual regeneration process is complete. Before the medium can flow again through the adsorber housing, the Column washed again with saline so as not to contain any harmful substances to let the patient cycle come. Finally, the medium is again sent over the column, it washes the Saline solution from the adsorber housing, a partial occurs again Mixing between medium and saline on the Adsorption process begins.

If the adsorber housing has a large internal volume, the volume fraction is Mixing between the medium and the saline solution was greater, more was achieved Saline in the patient's circulation, which does not exceed a certain amount is absolutely advantageous for the patient.

There is a possibility to change the amount of saline in the Patients manage to keep low in part of the mixed substance Medium and saline is discarded. The time of switching, between the line of the mixed substance to the patient, or to the waste container, consists of a compromise Medium rejection and saline supply to the patient.

Another possibility is to create an adsorber housing in which the adsorber material is in the packed state. This path represents a good alternative to solving the task Media loss, as well as the amount of saline supply to the patient to be kept as low as possible.  

This creates an adsorber volume that is almost the same as the volume of the adsorber material, the difference between the two volumes is very high low, and thus only a small proportion of medium can be in it Get inside the adsorber. As a result, the change between the rinsing and adsorption process becomes one resulting, mixing between medium and saline, only one low proportion of medium affected by the compromise solution.

However, such an arrangement is disadvantageous in that there are channels on the one hand form between the adsorber material, through which the medium preferably flows and on the other hand points of contact between the packed Adsorber particles occur which the medium cannot reach and where no adsorption process takes place. A disadvantage of this channel formation is that the percentage is low Adsorber particles that are in contact with the flow channel quickly with the adsorbent substances are loaded. Since the medium to be cleaned still preferably flows through the existing channels, is an adsorption with the help of the adsorber material almost no longer possible, although a large proportion is not yet saturated with adsorber particles. To continue removing the immunologically relevant factors from the medium To be able to switch to the regeneration process faster.

One solution would be to use a loose pack, but again that is already the case mentioned problem of an increased filling volume and thus a stronger one Mixing between medium and saline is a significant negative Would play a role.

Another option is single use and negation of flushing and regeneration through the development of highly effective adsorbents with good Compatibility and high adsorption capacity.

However, here too there are the same problems of capacity utilization as during flushing and regeneration.  

The inventive solution to these difficulties is achieved in that the Adsorber housing is expandable in its scope elastically or flexibly.

One way to accomplish this is to use plastics work. DE-OS 39 04 080 is a collapsible plastic film Containers known for holding liquid substances. This invention underlying task is for handling liquid To develop substances, in particular of dialysis concentrates, a container, the simple and sterile to use, easy to position and easy to is to be disposed of.

Furthermore, the patent DE 31 31 075 should be mentioned. This invention relates to a memory in a dialysis system for single-needle dialysis is arranged. The walls of the store are elastic on the outside expandable so that they are under tension when filled. After this Stopping the blood supply pump and opening a shut-off device The blood flows from the memory in a controlled manner via a dialysis membrane in which the Blood to be cleaned from the metabolites and excess fluid is released back to the patient. So a device is described in which both a pressure and Volume control is possible in which only one pump is used must and, if working with pressure control, an essentially constant pressure is applied to the dialysis membrane during blood passage and thus controlled non-pulsating blood flow is achieved.

Also in the more recent patent application WO 93/15825 "Device and method for extracorpreal blood treatment "by S.R. Ash use flexible parts. In this case a flexible membrane is used. Through that on this Patent based device BioLogic DT® is used with the Plate dialyzer and the proposed adsorber suspensions the elimination water-soluble substances from the blood possible.  

The elimination of water-soluble substances from the blood is carried out in the Counterflow principle through a chemical gradient along the membrane and influenced a pressure gradient between the blood and dialyzer side. A variable pressure gradient can be generated by means of a vacuum pump, which is the volume enclosed by the flexible membrane changed that you can work on the blood side without a pump.

An application of such flexible or elastic materials and of them resulting possibilities, such as the volume change, should be in our Invention find application.

With the help of the elastic wall, a variable adsorber housing volume is to be achieved, which has two advantages:
On the one hand, due to the reduction to the minimum adsorber housing volume, which is essentially determined by the adsorber particles remaining in the housing, only a minimal amount of liquid remains in the housing and thus any mixing of the rinsing liquid with the medium is reduced and thus the discarding of the medium is counteracted . And on the other hand, by setting the maximum volume, the possibility is created that the adsorber particles can be optimally flowed around and thus the adsorber effectiveness can be increased.

The invention is therefore based on the object, a method and a Device to eliminate substances from media, which at least one elastic and / or flexible outer and / or inner wall owns and therefore the substances to be removed with little media loss and high adsorption capacity removed.

According to the invention, this object is achieved by the features specified Claims 1-26 solved.

In our example a medical application is made for every patient a pair of Asorbers columns used.  

The elimination of pathophysiologically relevant substances from the patient's blood can be carried out with extracorporeal systems, using plasma separation and adsorption methods. Blood is drawn from the patient via an access and plasma is separated in the primary separation process. The separated plasma in the plasma separator ( Fig. 1) passes through an inlet valve through a filter into the interior of the adsorber housing, the volume in the housing can be varied by a flexible or elastic wall. The inlet valve is closed, the valves can be controlled with the aid of a pressure sensor or as a function of time. After the required amount of pathological substances has been bound to the adsorbent, the outlet valve is opened, the internal volume of the adsorber is reduced again to the minimum volume, the treated plasma emerges from the adsorber housing and returns to the patient with the high blood content (concentrate).

After a defined amount of plasma, the plasma flow over the other column passed and the first loaded regenerated. In this way, the columns are alternately loaded and regenerated. This process is repeated until all relevant substances, which were in the patient's blood to a certain extent were.

All with the biological fluid, preferably blood and plasma, in Parts coming into contact are preferably only for one-time consumption certainly.

The system according to the invention preferably also has Detectors to detect defects in the filters. To such detectors include photo-optical sensors, ultrasonic detectors, magnetic sensors that can determine magnetically active substances, and the like.

According to a further embodiment, an additional membrane filter downstream to pass through due to a defect  Adsorption particles securely from entering the patient's bloodstream prevent.

Furthermore, a magnetic field can be applied, which deflects and captures magnetically active substances, and so the magnetic ones Keeps particles in the adsorber housing. Advantageously, further magnetic traps are the adsorber connected in the event of a fault in the system feeding the particles in prevent the patient circulation.

The invention is explained in more detail using an example.

Show it:

Fig. 1 Treatment scheme

Fig. 2 Scheme of the plasma circuit,

Fig. 3 scheme of the control of the plasma flow over the flexible adsorber.

Fig. 1 shows the essential elements of the invention. In the primary circuit 9 , the venous or arterial blood of the patient 1 is passed through a tube 2 to the plasma separator 4 , where the blood is separated into plasma and a cell-rich blood part (concentrate). Pumps 3 can be provided to maintain or increase the flows. The plasma separated in the plasma separator passes via the valve 5 through the filter 7 into the interior of the adsorber housing 8 , the volume in the housing being a minimum volume, which is essentially determined by the adsorber particles in the housing, through a flexible or elastic wall, increased to a defined maximum volume. The valve 5 is closed, and the control of the valves 5 and 6 can take place with the aid of a pressure sensor or as a function of time. After the required amount of pathological substances has been bound to the adsorbent, the valve 6 is opened, the interior volume of the adsorber is reduced again to the minimum volume, the treated plasma can emerge from the adsorber housing 8 and reaches the patient with the concentrate.

Pumps can also be provided in the plasma circuit 10 to maintain or increase the flow ( FIG. 2) or the plasma flow is controlled via the flexible adsorber housing ( FIG. 3).

In order to ensure the safety of the patient, adsorber particles should be prevented from entering the patient's bloodstream in the event of a fault in the system. This can be achieved with a filter that prevents the particles from entering the patient's bloodstream. Or a detector 12 can be provided in the plasma circuit 10 in order to be able to switch off the device via a terminal 13 . This detector can either be photo-optically sensitive or can be designed in a manner known per se for the detection of inhomogeneities in the blood using ultrasound.

Another option for filtering out adsorber particles (crosslinked magnetic particles or crosslinked dead magnetic bacteria, claims 23-26) are magnetic traps 11 . Such a safety device can be provided in the primary as well as in the plasma circuit.

In FIG. 2, an embodiment of the system according to the invention with regeneration ability of the adsorbent is listed. In contrast to FIG. 1, two separate connections on the adsorber housing are used here. A pair of columns is used for each patient during treatment. Blood is drawn from the patient via an access and 4 plasma is separated in the primary separation process. This plasma is fed into the first housing 8 via a valve 3 (preferably a roller pump) via the valve 5 . The housing fills up and the elastic or flexible walls increase the internal volume. The pathophysiological substances are bound to the adsorbent. Via a control by means of pressure sensor 20 , or after a defined time, valve 6 is opened, the housing 8 is emptied, the elastic or flexible walls reduce the internal volume and the detoxified plasma is returned to the bloodstream via pump 21 . After a defined amount of plasma, the plasma flow is passed over the other housing 22 and the first loaded housing 8 is regenerated. During the regeneration process, the rinsing liquid from the reservoirs 23-25 reaches the housing 8 with the help of the pump 26 via the valve 27 . The internal volume of the housing increases. After the adsorbent has been cleaned, the rinsing liquid is pumped out via the valve 28 as waste 30 with the aid of the pump 29 .

To return patient-damaging regeneration fluids to the Avoid patients and reduce the plasma loss as little as possible shape, is between the change between adsorption and Regeneration process and vice versa, with a physiological saline solution rinsed.

The adsorber particles in the housings are in this way alternately loaded and regenerated.  

This process is repeated until the desired toxic reduction reached on the patient.

In Fig. 3 is shown the possibility of controlling the plasma flow in the system via the flexible adsorber instead of pumps in the plasma circuit according to the invention.

In this case, the volume in the intermediate space 33 between the outer housing 34 and the adsorber housing 8 is changed cyclically via a fluid (preferably saline solution) or air reservoir 31 by means of a pump 32 such that the adsorber housing simultaneously functions as a pump. According to the invention, the adsorber wall 8 is elastic or flexible and, since the outer housing wall 34 is rigid, compensates for the pressure generated by the pump 32 by changing the volume enclosed by the adsorber wall 8 . With the help of a pressure sensor 20 , or as a function of time, the valves 5 and 6 support the process in such a way that when the fluid or the air is sucked out of the intermediate space 33, the valve 5 is open and thus an inflow of the plasma into the adsorber column 8 by a Negative pressure is guaranteed. The valve 6 is closed during this process. After the process is completed, valve 5 is closed. If the desired toxic reduction is achieved, an excess pressure is generated in the intermediate space 33 by means of the fluid or the air via the pump 32 , and the valve 6 (possibly with a time delay) is opened. This reduces the volume of the adsorber 8 and the detoxified plasma passes from the adsorber housing back into the bloodstream.

When using such a system for the safety of the Patients additional detectors can be integrated into the process. You have the Task in the event of a fault in the system, penetration of drive air or Drive fluids, preferably saline, into the patient's bloodstream to prevent.  

Related list

1

patient

2nd

tube

3rd

pump

4th

Plasma separator

5

Inlet valve

6

Exhaust valve

7

filter

8th

Adsorber housing

9

Primary circuit

10th

Plasma cycle

11

magnetic traps

12th

detector

13

Clamp

20th

Pressure sensor

21

pump

22

Adsorber housing

2nd

23

reservoir

24th

reservoir

25th

reservoir

26

pump

27

Inlet valve flushing liquid

28

Flush liquid outlet valve

29

pump

30th

Waste bin

31

Fluid or air reservoir

32

pump

33

Space

34

Outer housing wall

Claims (26)

1. A method for blood purification, in which the non-cellular blood components of a patient are separated by methods known per se and are then fed to a further purification, characterized in that the liquid thus obtained is closed by a filter with a housing having a partial or completely flexible or elastic wall filled with particles which adsorb the components of the liquid to be removed. 2. The method according to claim 1, characterized in that the obtained Liquid, preferably with controllable overpressure, brought in and is brought out again with negative pressure. 3. The method according to claim 1-2, characterized in that the obtained Substrate for further treatment with adsorbers, filters or others Devices is supplied before it is known per se Safety devices for detecting and trapping air or Particles are returned to the patient circuit. 4. The method and arrangement according to claims 1-3, characterized in that the change in the volume of the housing throughout Adsorption process takes place cyclically. 5. The method according to claim 1-3, characterized in that the change of the interior volume of the housing after a completed adsorption process or takes place after a completed rinsing process. 6. The method according to claim 1-5, characterized in that the different pressure controls at the inlet and outlet of the housing preferably by predeterminable different pump speeds are caused.   7. The method according to claim 1-6, characterized in that pressure sensors regulate the pump speeds so that the pressure in the housing does not exceed or fall below predetermined limits, and the time of the Alternating between filling and emptying the housing with the cell-free Determine blood components and irrigation fluids. 8. The method according to claim 1-7, characterized in that when used of regenerable adsorber particles with the inlet and outlet for the housing the adsorber particles either with the liquid circuit or Rinsing device are connected. 9. The method according to claim 1-8, characterized in that at discontinuous extraction of the non-cellular blood components temporal coupling for filling and emptying the housing takes place. 10. The method according to claim 1-9, characterized in that the discontinuous processes for the extraction of non-cellular Blood components are associated with a single-needle procedure. 11. The method according to claim 1-10, characterized in that for detection of system defective sensors are present, which are a warning, control, Possibility to correct or switch off the system. 12. The method according to claim 1-11, characterized in that by a Control of the inflow and outflow speeds a loosening of the Adsorber particles and flushing the filter can be achieved. 13. The method according to claim 1-12, characterized in that the necessary Pressure difference on the filters of the housing for filling and emptying the Housing, for mixing the adsorber particles with the liquids and for flushing the filter of settled adsorber particles by one of targeted positive pressure or negative pressure acting on the outside of the housing wall and corresponding valve positions on the inlets and outlets of the housing is achieved.   14. The method according to claim 1-13, characterized in that this pressure is a hydrostatic pressure. 15. The method according to claim 1-13, characterized in that this pressure is an aerostatic pressure. 16. The method according to claim 1-13, characterized in that this pressure is a mechanical pressure. 17. The apparatus for performing the method according to claim 1-16, characterized characterized in that the housing is preferably made of transparent material is. 18. The apparatus according to claim 17, characterized in that the housing at least one flexible or elastic wall and / or outer wall owns. 19. The apparatus according to claim 17-18, characterized in that the housing with flexible or elastic wall by one or more semipermeable filters with such a pore size are separated so that the Do not get adsorber particles into the liquid circuit. 20. The apparatus according to claim 17-19, characterized in that the housing with the adsorber particles are only provided with a filter through which the Liquid and the rinsing fluids alternate according to a predefined regime step in both directions. 21. The apparatus according to claim 17-19, characterized in that at Using non-regenerable adsorber particles designed the housing are that an exchange of the adsorber particles even during treatment of the patient is possible.   22. The apparatus of claim 17-21, characterized in that the Adsorber arbitrary particles whose diameter is larger than the pore size are the input and output filters. 23. The device according to claim 17-22, characterized in that the Adsorber particles are also cross-linked magnetic particles. 24. The device according to claim 17-23, characterized in that the Adsorber particles also crosslinked dead magnetic bacteria are adsorbent compounds on the surface. 25. The device according to claim 17-24, characterized in that at Using magnetic particles the magnetic traps feeding the Prevent particles from entering the patient circuit. 26. The apparatus according to claim 17-25, characterized in that at Use magnetic particles to feed the magnetic sensors Monitor particles in the patient circuit.