SIMPLIFIED REGENERATION OF APHERESES COLUMNS

Description

[0001] The present invention relates to an apheresis device (1) for the extracorporeal removal of CRP from a patient's blood, wherein the apheresis device can be connected to the patient's bloodstream. The blood is pumped via a part of the extracorporeal circulation system (2) of the apheresis device (1) according to the invention to a cell separator (7) for separating the blood into blood plasma and cellular components. Via a first outlet of the cell separator (7), the separated blood plasma is conveyed via a plasma line (8A) to an apheresis column (4) for the affinity chromatographic removal of CRP from the blood plasma. After the removal of the CRP from the patient's blood plasma, this now treated blood plasma is combined with the cellular components of the blood via a plasma line (8B).Furthermore, the apheresis device (1) according to the invention comprises a bypass line (12) that leads from the plasma line (8A) to the plasma line (8B), bypassing the apheresis column (4). The apheresis device (1) according to the invention also comprises a regeneration line (14) that opens into the plasma line (8A) or directly into the apheresis column (4).

[0002] Additionally, a non-stressed method for simplified regeneration of an apheresis tube is described. Background of the invention

[0003] According to the World Health Organization (WHO), approximately 17 million people died from cardiovascular diseases in 2008. This makes cardiovascular diseases the leading cause of death among non-communicable diseases, accounting for roughly one-third of all deaths worldwide each year. This number is estimated to rise to approximately 23 million deaths per year by 2030.

[0004] Thus, cardiovascular diseases are and remain not only the leading cause of death worldwide, but also incur enormous medical costs for national healthcare systems and health insurance companies. Two of the most common and damaging manifestations of cardiovascular diseases are the development of arteriosclerosis and thrombosis, which in turn are among the causes of heart attacks and strokes.

[0005] Significant progress has been made in the treatment of cardiovascular diseases in recent years. This progress has been enabled not only by growing knowledge of disease-causing mechanisms but also by the early identification of high-risk patients. Indeed, identifying disease risks and addressing them early are key features of modern medical practice. Over the past 25 years, a multitude of factors and clinical parameters have been identified that correlate either with the current state of the disease or with the future likelihood of developing cardiovascular disease. Such risk factors can include measurable biochemical or physiological parameters, such as serum cholesterol, HDL, LDL, and fibrinogen levels, as well as behavioral patterns such as obesity and smoking.In cases where a risk factor not only indicates a disease or its development, but is actually causally involved in its development, therapeutic intervention in this risk factor can influence the course of the disease or reduce the risk of its development.

[0006] CRP is an acute-phase protein that is part of the innate immune system. It is produced in the liver during inflammatory reactions and released into the blood. CRP production is primarily induced by cytokines expressed during an acute or chronic inflammatory response. The most potent stimulus for CRP production is interleukin-6 (IL-6). Therefore, blood levels of CRP, as well as IL-6, are indicators of a local or systemic inflammatory response. Chronic inflammation is suspected to be one of the underlying and supporting pathological phenomena in cardiovascular diseases. It is increasingly assumed that CRP is not only predictive of cardiovascular diseases, but also causally involved in their development and can influence their progression.

[0007] Yeh (Clin Cardiol., 2005, 28: 408-412) shows that CRP levels can be used to predict cardiovascular disease risk, that CRP is also an indicator of inflammatory responses, and that inflammation promotes all stages of atherosclerosis. Zoccali et al. (Semin. Nephrol., 2005, 25: 358-362) show that CRP levels are predictive of cardiovascular mortality risk in patients with end-stage renal disease. According to Nurmohamed et al. (Neth. J. Med., 2005, 63: 376-381), CRP levels are predictive of cardiovascular mortality risk in hemodialysis patients.

[0008] Sola et al. (J. Card. Fail., 2005, 11: 607-612) demonstrated that statin therapy can be used to lower CRP levels, thereby reducing mortality and morbidity caused by cardiovascular disease. However, this form of therapy is insufficient to significantly reduce the high CRP levels (up to 1000 times above normal) that occur after a heart attack or the high CRP levels in the blood of dialysis patients.

[0009] Slagman et al. 2011 (Specific Removal of C-Reactive Protein by Apheresis in a Porcine Cardiac Infarction Model, Blood Purif 2011;31:9-17), Sheriff et al. 2014 (C-Reactive Protein-Adsorber therapies: new ideas and concepts; LECTURE NOTES OF THE ICB SEMINAR: ADVANCES IN MEMBRANE AND ADSORBER TECHNOLOGY IN LIFE SCIENCES, Warsaw, April 2014), Sheriff et al. 2015 (Selective Apheresis of C-Reactive Protein: A New Therapeutic Option in Myocardial Infarction? Journal of Clinical Apheresis 30:15-21 (2015))

[0010] Consequently, there is increasing interest in therapeutic methods to reduce CRP levels in the blood of patients.

[0011] WO 90 / 12632 discloses a method and apparatus for the extracorporeal treatment of biological fluids for the removal of CRP and anti-phosphocholine antibodies from these biological fluids for the treatment of cancer. The phosphocholine-containing matrix used for this purpose can consist, for example, of silica, Sepharose, acrylic beads, or agarose, wherein the phosphocholine binds both CRP and anti-phosphocholine antibodies.

[0012] WO 2007 / 076844 discloses a method for reducing the risk to a patient caused by elevated CRP levels in the blood through extracorporeal CRP removal from blood plasma by means of apheresis. According to the invention, a column containing a matrix is ​​used to which phosphocholine derivatives are bound to bind CRP and remove it from the plasma, thereby treating and / or preventing autoimmune diseases, cardiovascular diseases, diabetes, and renal insufficiency.

[0013] The normal value for CRP in human blood varies from person to person, but the median is approximately 0.8 mg CRP per liter of blood. However, in cases of acute or chronic inflammatory reactions (e.g., bacterial infections, atherosclerosis, after a heart attack), this value can rise to well over 100 mg CRP per liter of blood. Since the half-life of CRP in the blood (approximately 19 hours) is constant and thus independent of the patient's health status, the synthesis rate of CRP alone is responsible for regulating the CRP level in the blood (Pepys & Hirschfield, J. Clin. Invest., 2003, 111: 1805-1812). The greatly increased synthesis of CRP in acute pathological conditions therefore places special demands on therapeutic approaches for CRP removal from patients (at-risk or acute patients), since a significant amount of CRP must be removed to reduce the CRP level in the blood to normal values.Therefore, there is a need for particularly efficient devices for removing CRP from the blood of patients.

[0014] DE 102005061715 A1 discloses a method for treating the risk of elevated levels of C-reactive protein (CRP) by performing extracorporeal perfusion of blood plasma through a device, such as a column, containing adsorbable matrix material, including lipids, peptides, polypeptides, phosphocholine (PC), or PC derivatives, to remove C-reactive protein. The possibility of regenerating the column is not disclosed.

[0015] Reusable adsorbers are known from the prior art. These consist of a housing filled with a carrier substance and a binding factor coupled to it. Reusable adsorbers are generally regenerable because, after passing through a quantity of plasma dependent on the concentration of the substance to be adsorbed, the adsorber is "saturated" and no further binding of the substance can occur. Two adsorbers are usually used for a single treatment. While plasma is being pumped through one adsorber, the second adsorber is being regenerated simultaneously. During regeneration, the adsorber is flushed with various regeneration solutions to remove the bound substances and is thus prepared for re-plasming. The permissible number of regenerations is specified by the manufacturers. The reusable adsorber may only be used on the same patient.To prevent bacterial growth in the adsorbers, they must be filled with a preservative fluid at the end of each treatment, which must then be rinsed out before each new therapy. However, significant costs could be saved through reuse. Operating the existing devices (a combination of two or more medical devices) is very complex and highly demanding. Furthermore, the devices are generally used infrequently.

[0016] German patent DE 102005019406 A1 discloses a method and a device for the automatic drainage of rinsing fluid during apheresis treatment. The disclosure also covers the use of auxiliary equipment, wherein two adsorbers are alternately and repeatedly loaded and rinsed. This auxiliary equipment has its own peristaltic pumps, hose clamps, and control elements. While these devices and methods are efficient, a disadvantage is the simultaneous operation of two devices, which, as mentioned above, are not used regularly due to their complexity. According to the disclosure in DE 102005019406 A1, the objective was to reduce switching operations between fluid drainage and fluid recirculation during treatment in order to enable direct adsorber operation without an additional device on a cell separator.DE 102005019406 A1 discloses a combination of collection containers and backflow preventers to enable, for example, a change in the loading from a first adsorber to a second absorber by means of a 3-way valve in the supply tubing system. Thus, DE 102005019406 A1 discloses an alternative device with two apheresis columns. The disadvantage of the increased costs due to the second apheresis column, which can also only be used for the same patient, is not eliminated by the disclosure of DE 102005019406 A1.

[0017] WO 2012 / 143103 discloses a device for extracorporeal blood treatment and for monitoring the fluid flow therein, wherein the fluid flow is switched between treatment mode and filling and rinsing mode by means of a changeover clamp. During the filling and rinsing mode, the rinsing solution is collected in a collection bag, whereas during the treatment mode, it must be ensured that the purified plasma does not enter the collection bag. Therefore, monitoring the correct function of the changeover clamp is necessary. The fluid flow is monitored by detecting a change in the weight of the collection bag. An evaluation unit for monitoring the change in the weight of the collection bag is taught as an additional feature in WO 2012 / 143103 and contributes to the complex structure of the disclosed device.The specialist personnel operating the disclosed device must set a predetermined time interval such that the tubing of the fluid system can be completely filled with rinsing fluid. An increase in the weight of the collection bag is only to be expected when the tubing of the fluid system is completely filled with fluid. In doing so, the specialist personnel must pay attention to the various acoustic and / or optical signals generated by the control unit. The device taught in WO 2012 / 143103 therefore requires a very high level of training for clinical personnel. Furthermore, although WO 2012 / 143103 discloses a blood treatment unit (10) having one or more filters or adsorbers, it does not disclose which fluids are used to regenerate the blood treatment unit, nor whether the plasma flow is interrupted during regeneration.Therefore, the presence of a bypass line is neither taught nor suggested by WO 2012 / 143103.

[0018] German patent DE 4338858 C1 also discloses a device for regenerating an apheresis column. DE 4338858 C1 teaches the use of a storage unit in which the plasma is temporarily stored during the regeneration of the apheresis column. The regeneration of the apheresis column takes place using the prior art combination of glycine, NaCl solution, and PBS. Consequently, DE 4338858 C1 does not disclose the use of the anticoagulation solution or the plasma separator rinsing solution as a regeneration solution for the apheresis column according to the invention. Furthermore, DE 4338858 C1 does not disclose a bypass line that allows the plasma flow to be diverted around the apheresis column during its regeneration.

[0019] International patent application WO2012141697 A1 discloses an apheresis device for the extracorporeal removal of CRP from blood. The regeneration of the apheresis column during apheresis without stopping the treatment is not described.

[0020] European patent application EP 0834329 A1 is directed to a device for removing cholesterol from blood. It does not mention any specific columns or column materials. The removal of CRP is not taught. Columns for the affinity chromatographic removal of cholesterol do not exist. Cholesterol is generally removed via lipoprotein apheresis. This involves using columns that are only partially selective for LDL cholesterol, meaning that LDL cholesterol binds to the matrix in the apheresis column with higher affinity than other substances present in the blood. However, other substances are also removed from the blood or blood plasma in high percentages. The columns disclosed in EP 0834329 A1 are not suitable for the selective removal of CRP from blood. European patent application EP 0111696 A2 discloses a device for removing anti-factor VII or IX antibodies.The removal of CRP is not taught. Therefore, in particular, apheresis columns for the affinity chromatographic removal of CRP are not disclosed; that is, CRP does not bind to the matrix in the apheresis column with a higher affinity than other substances present in the blood, but rather that there is a specificity for antibodies. The columns disclosed in EP 0834329 A1 are not suitable for the selective removal of CRP from blood.

[0021] Object of the present inventionThe object of the present invention is to provide a device for the simplified regeneration of apheresis columns, minimizing the disadvantages of devices known from the prior art. In other words, the object of the present invention is to provide a device for the simplified regeneration of apheresis columns, and in particular an apheresis column for the selective removal of CRP from blood, which can be operated with reduced training effort, and thus with reduced personnel costs and lower overall costs.

[0022] This problem is solved by the teaching of the independent claims. Further advantageous embodiments emerge from the description, the examples, and the appended patent claims.

[0023] Surprisingly, it was found that by providing a regeneration line that either flows directly into the apheresis column or into the plasma line before the apheresis column but after the bypass line, a simplified regeneration of the apheresis column is possible, minimizing the disadvantages of the known state of the art. Description of the invention

[0024] The present invention relates to an apheresis device (1) for the extracorporeal removal and preferably for the extracorporeal selective removal of CRP from a patient's blood, wherein the apheresis device can be connected to the patient's bloodstream. The blood is pumped via a part of the extracorporeal circulation system (2) of the apheresis device (1) according to the invention to a cell separator (7) for separating the blood into blood plasma and cellular components. Via a first outlet of the cell separator (7), the separated blood plasma is passed via a plasma line (8A) to an apheresis column (4) for the affinity chromatographic removal of CRP from the blood plasma. After the removal and preferably after the selective removal of CRP from the patient's blood plasma, this now treated blood plasma is combined with the cellular components of the blood via a plasma line (8B).Furthermore, the apheresis device (1) according to the invention comprises a bypass line (12) that leads from the plasma line (8A) into the plasma line (8B), bypassing the apheresis column (4). Furthermore, the apheresis device (1) according to the invention comprises a regeneration line (14) that opens into the plasma line (8A) or directly into the apheresis column (4) at or after, preferably after, the bypass line (12).

[0025] Additionally, a non-stressed method for simplified regeneration of an apheresis tube is described. device

[0026] The present invention relates to an apheresis device (1) for the extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood, wherein the extracorporeal circulation system (2) comprises an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4) to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), and a central processing unit (10) for controlling the apheresis device (1),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), a waste line (13) branches off directly from the apheresis column (4) or branches off from the plasma line (8B) in the flow direction before the confluence of the bypass line (12), and at least one regeneration line (14) which branches off from the at least one liquid container (F) or the at least one connecting line (11) and leads in the flow direction at or after the branching of the bypass line (12) to the plasma line (8A) or opens directly into the apheresis column (4).

[0027] As already explained above, the apheresis device (1) according to the invention for the extracorporeal removal of CRP from blood can be connected to the bloodstream of a patient. From a vascular access on the patient (usually a venous access), the blood is pumped via a part of the extracorporeal circulation system (2) of the present invention to a cell separator (7). The part of the extracorporeal circulation system (2) that directs the blood from the patient and to the cell separator (7) directs the blood away from the patient and thus also from their heart and is therefore referred to as "arterial line" (5).

[0028] The patient's blood is drawn into the cell separator (7) through an inlet and separated into blood plasma (sometimes simply referred to as "plasma") and the cellular components of the blood. It should be noted that the separation into blood plasma and cellular components is not complete; rather, preferably 10 to 90% of the total blood plasma is separated from the cellular components. The separated blood plasma is then conveyed via a plasma line (8A) through a first outlet of the cell separator (7) to the apheresis column (4) for the affinity chromatographic removal of CRP from the blood (or blood plasma). After the removal or reduction of CRP in the patient's blood plasma, this now treated blood plasma (also called plasmapheresis) is used for further analysis. "depleted blood plasma"via a plasma line (8B) to point (P1). Via a second outlet of the cell separator (7) and a subsequent line (the so-called cell line (9)), the cellular components of the blood are guided past the apheresis column (4) and to point (P1). There, the cellular components are combined with the depleted blood plasma. After the cellular components have been combined with the depleted blood plasma, the now treated blood is returned to the patient via another part of the extracorporeal circulation system (2) of the present invention. The part of the extracorporeal circulation system (2) that carries the treated blood from point (P1) of the extracorporeal circulation system (2) back to the patient carries the blood to the patient and thus also to their heart and is therefore referred to as "venous conduction" (6).

[0029] In an alternative embodiment of the present invention, it is possible that the cellular components are also supplied directly to the patient again via the second output on the cell separator and a subsequent line after separation from the plasma, and only the treated plasma is supplied to the patient via the venous line.

[0030] In order to prevent blood clotting in the extracorporeal circulation system or to enable flushing or pre-rinsing of the extracorporeal circulation system (e.g. with a physiological saline solution), the apheresis device according to the invention comprises at least one line (the so-called connecting cable(11)), which enables the connection of at least one liquid container (F) and thus the introduction of the liquid contained in this at least one liquid container (F) (e.g., an anticoagulant or a physiological saline solution) into the extracorporeal circulation system. In this context, it is also said that the connecting line (11) for connecting at least one liquid container (F) is in fluidic connection with the extracorporeal circulation system, i.e., a liquid from a liquid container can be introduced into the extracorporeal circulation system via the connecting line (11). In preferred embodiments of the present invention, the at least one connecting line (11) opens into the extracorporeal circulation system (2) upstream of the cell separator (7), i.e., into the arterial line (5), or directly into the cell separator (7).

[0031] It is obvious to the person skilled in the art that the liquid container(s) (F) themselves do not need to be part of the apheresis device according to the invention, since these are usually disposable items, e.g. in the form of common infusion bags, which are connected to the connecting line by the operating personnel (e.g. the attending physician or a nurse) according to the specific application.

[0032] According to the invention, it is possible to have a single connecting line (11) for connecting a liquid container. However, it is equally conceivable that a single connecting line (11) is provided to which two, three, or preferably more liquid containers can be connected. Likewise, embodiments of the apheresis device according to the invention with two, preferably three, or preferably more connecting lines (11', 11", 11‴, etc.) for connecting at least one liquid container each are possible, wherein it is preferred that these two, preferably three, or preferably more connecting lines can lead independently of one another into the arterial line (5) or directly into the cell separator (7)."Independent of each other" in this context means, for example, that in one embodiment of the apheresis device according to the invention with two connecting lines (11', 11"), one connecting line (11') can lead into the arterial line (5) and the other connecting line (11") can lead directly into the cell separator (7), but also that both connecting lines (11', 11") can lead into the arterial line (5) or that both connecting lines (11', 11") can lead directly into the cell separator (7).

[0033] According to one embodiment of the present invention, it is particularly preferred if the apheresis device (1) according to the invention has two connecting lines (11', 11") for connecting at least one liquid container each, wherein the connecting lines (11', 11") open independently of one another into the arterial line (5) or directly into the cell separator (7). Consequently, both connecting lines (11', 11") open into the arterial line (5), or both connecting lines (11', 11") open directly into the cell separator (7), or, particularly preferably, one connecting line (11') opens into the arterial line (5) and the other connecting line (11") opens directly into the cell separator (7). This makes it possible for the two connecting lines (11', 11") to be connected to different liquid containers. It is particularly preferred if one of the two connecting lines (e.g. 11') is connected to a liquid container containing a physiological saline solution (e.g.NaCl solution), while the second of the two connecting lines (e.g. 11") is connected to a liquid container containing a citrate solution.

[0034] It is therefore particularly preferred if the apheresis device (1) has a connecting line (11') for connecting a liquid container (F1) and a connecting line (11") for connecting a liquid container (F2) and the connecting line (11') opens into the arterial line (5) or into the cell separator (7) and the connecting line (11") opens into the arterial line (5) or into the cell separator (7) or into the connecting line (11') and thus ultimately also into the arterial line (5) or into the cell separator (7).

[0035] The present invention therefore also relates to an apheresis device (1) for the extracorporeal removal and preferably for the selective removal of CRP from blood, comprising: an extracorporeal circulation system (2) for blood, means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood, wherein the extracorporeal circulation system (2) has an arterial line (5) to the cell separator (7) for separating the blood into blood plasma and cellular components, a plasma line (8A) from the cell separator (7) for separating the blood into blood plasma and cellular components to the apheresis column (4) for affinity chromatographic removal of CRP, and a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4) to a point (P1).The device comprises a cell conduit (9) for the separated cellular components from the cell separator (7) for separating the blood into blood plasma up to point (P1) and a venous conduit (6) extending from point (P1), a central processing unit (10) for controlling the apheresis device (1), two connecting lines (11', 11") for connecting at least one fluid container each to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), a waste line (13) extends directly from the apheresis column (4) or from the plasma line (8B) in the direction of flow upstream of the bypass line (12), and at least one regeneration line (14) extends in the direction of flow to or, preferably, after the branch of the bypass line (12). to the plasma line (8A) or directly into the apheresis column (4).

[0036] A significant advantage of the apheresis device according to the invention is that the apheresis column, which is naturally limited in its cleaning capacity, regenerated during operation can be performed without stopping the blood collection and supply or the cell separator. Bypass line(12, also referred to as a "shunt"), which enables a redirection of the plasma flow, bypassing the apheresis column (4). This bypass line (12) enables a temporary decoupling of the apheresis column (4) from the plasma flow and thus the regeneration of the apheresis column (4) without having to interrupt the blood or blood plasma flow in the device according to the invention. The bypass line branches off from the plasma line (8A), with the point in the plasma line (8A) from which the bypass line branches off being referred to as point (P2), and preferably opens into the plasma line (8B), with the point in the plasma line (8B) into which the bypass line (12) opens being referred to as point (P6). In an equally possible embodiment, the bypass line (12) does not lead into the plasma line (8B), but into the cell line (9), with the point in the cell line (9) into which the bypass line (12) leads being referred to as point (P3).

[0037] The regeneration solution required for the regeneration of the apheresis column is fed into the extracorporeal circulation system (2) via the regeneration line (14), whereby the regeneration line (14) either opens directly into the apheresis column (4) or (in the direction of flow) before the apheresis column (4) but (in the direction of flow) after the branch of the bypass line, i.e. after point (P2) into the plasma line (8A).

[0038] To ensure that the regeneration solution can be removed from the system after flowing through the apheresis column (4) (and is not administered to the patient), the Waste pipe(13), which branches off from the plasma line (8B), the point in the plasma line (8B) from which the waste line (13) branches off being referred to as point (P4). In embodiments in which the bypass line (12) opens into the cell line (9), point (P4) is preferably located in a region from the apheresis column (4) to point (P1). In embodiments in which the bypass line (12) opens into the plasma line (8B), point (P4) is preferably located in a region from the apheresis column (4) to point (P6). A collection container, for example, can be connected to said waste line (13). A physiological sodium chloride solution, TRIS glycine solution, or a citrate solution, for example, can be used as a regeneration solution.

[0039] In addition to the regeneration solution, a rinsing solution can also be used. The rinsing solution can, but does not have to, serve to regenerate the apheresis column (4). Its primary function is to displace the blood plasma from the plasma line (8A) in the area from point P2 to the apheresis column (4), from the apheresis column (4), and from the plasma line (8B) from the apheresis column (4) to point P4 before the regeneration solution is introduced. After passing through the apheresis column (4), the regeneration solution is then discarded via the waste line (13). The rinsing solution, on the other hand, can be administered to the patient, either partially or completely, and does not have to be discarded, at least not as long as it does not yet contain any regeneration solution. A physiological saline solution is preferably used as the rinsing solution.It is even more preferred to use a physiological NaCl solution as the rinsing solution if a citrate solution is used as the regeneration solution.

[0040] The present invention therefore also relates to an apheresis device (1) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for the affinity chromatographic removal of CRP from the blood, wherein the extracorporeal circulation system (2) comprises an arterial line (5) to the cell separator (7) for separating the blood into blood plasma and cellular components, a plasma line (8A) from the cell separator (7) for separating the blood into blood plasma and cellular components to the apheresis column (4) for the affinity chromatographic removal of CRP, a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4) to a point (P1),a cell conduit (9) for the separated cellular components from the cell separator (7) for separating the blood into blood plasma up to point (P1) and a venous conduit (6) extending from point (P1), a central processing unit (10) for controlling the apheresis device (1), at least one connecting line (11) for connecting at least one fluid container to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), a waste line (13) extends directly from the apheresis column (4) or from the plasma line (8B) in the direction of flow upstream of the inlet of the bypass line (12), and at least one regeneration line (14) in a region from the branch of the bypass line (12) at the plasma line (8A) to to the apheresis column (4) into the extracorporeal circulation system (2).

[0041] Likewise, the present invention is directed to an apheresis device (1) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood or blood plasma, comprising: an extracorporeal circulation system (2) for blood or blood plasma connectable to the blood circulation of a patient, means (3) for generating and regulating a flow of blood or blood plasma in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood or blood plasma, wherein the extracorporeal circulation system (2) comprises an arterial line (5) from the patient to the cell separator (7), a plasma line (8A) extending from the cell separator (7) for the separated blood plasma in fluidic connection with the apheresis column (4) for affinity chromatographic removal of CRP, a plasma line (8B) extending from the apheresis column (4) for the CRP-depleted blood plasma, and a outgoing cell line (9) for the separated cellular components,which opens into the plasma conduit (8B) at a point (P1), and includes a venous conduit (6) from the point (P1) to the patient; a central computing unit (10) for controlling the apheresis device (1), at least one connecting line (11) for connecting at least one liquid container in fluidic connection with the extracorporeal circulation system (2), characterized in that the apheresis device (1) further comprises: a bypass line (12) leading from a point (P2) in the plasma line (8A) to a point (P3) in the cell line (9) or to a point (P6) in the plasma line (8B), a waste line (13) branching off from a point (P4) in the plasma line (8B), at least one regeneration line (14) opening into the extracorporeal circulation system (2) in a region from point (P2) to the apheresis column (4), and point (P4) being arranged upstream of points (P1) and (P6) or point (P4) coinciding with point (P6).

[0042] Likewise, the present invention is directed to an apheresis device (1) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood or blood plasma, comprising: an extracorporeal circulation system (2) for blood or blood plasma connectable to the blood circulation of a patient, means (3) for generating and regulating a flow of blood or blood plasma in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood or blood plasma, wherein the extracorporeal circulation system (2) comprises an arterial line (5) from the patient to the cell separator (7), a plasma line (8A) extending from the cell separator (7) for the separated blood plasma in fluidic connection with the apheresis column (4) for affinity chromatographic removal of CRP, a plasma line (8B) extending from the apheresis column (4) for the CRP-depleted blood plasma, and a outgoing cell line (9) for the separated cellular components,which opens into the plasma conduit (8B) at a point (P1), and includes a venous conduit (6) from the point (P1) to the patient; a central computing unit (10) for controlling the apheresis device (1), two connecting lines (11', 11") for connecting at least one liquid container each in fluidic connection with the extracorporeal circulation system (2), characterized in that the apheresis device (1) further comprises: a bypass line (12) leading from a point (P2) in the plasma line (8A) to a point (P3) in the cell line (9) or to a point (P6) in the plasma line (8B), a waste line (13) branching off from a point (P4) in the plasma line (8B), at least one regeneration line (14) opening into the extracorporeal circulation system (2) in a region from point (P2) to the apheresis column (4), and point (P4) being arranged upstream of points (P1) and (P6) or point (P4) coinciding with point (P6).

[0043] According to one embodiment of the present invention, it is therefore preferred if the apheresis device (1) according to the invention has at least two connecting lines (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7).

[0044] Furthermore, embodiments of the apheresis device (1) are preferred in which the apheresis device (1) has at least two connecting lines (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), and wherein a regeneration line (14) exists for each liquid container (F) which leads from the respective liquid container (F) or its connecting line (11) and which lead into the plasma line (8A) or directly into the apheresis column (4).

[0045] It is also possible that the at least two connecting lines (11) merge before their junction, i.e., converge into one line. It is also possible that the regeneration lines (14) merge before their junction, i.e., converge into one line.

[0046] When the present application describes a device feature as being located in, or opening into, or branching off from a region extending from a first position in the device to a second position in the device, this is to be understood as including both the first position and the second position, as well as the section between them. This is illustrated by the following example: The statement that "the regeneration line (14) opens into the extracorporeal circulation system (2) in a region from point (P2) to the apheresis column (4)" means that the regeneration line (14) opens into a region of the extracorporeal circulation system (2) that includes not only the section between point (P2) and the apheresis column (4), but also point (P2) itself, which is also the apheresis column (4).The regeneration line (14) can lead to point (P2) or to the apheresis column (4) or to the section of the plasma line (8A) that lies between point (P2) and the apheresis column (4).

[0047] The point ( P1 ) is the node in the extracorporeal circulatory system (2) where the plasma conduit (8B) transitions into the venous conduit (6). The point ( P2 ) is the node in the extracorporeal circulation system (2) where the bypass line (12) branches off from the plasma line (8A). The point ( P3 ) is the node in the extracorporeal circulation system (2) where the bypass line (12) connects to the cell line (9). The point ( P4 ) is the node in the extracorporeal circulation system (2) where the waste line (13) branches off from the plasma line (8B). The point ( P5) is the node in the extracorporeal circulation system (2) where the regeneration line (15) connects to the connecting line (11). The point ( P6 ) is the node in the extracorporeal circulation system (2) where the bypass line (12) connects to the plasma line (8B).

[0048] Likewise, the present invention is directed to an apheresis device (1) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood or blood plasma, comprising: an extracorporeal circulation system (2) for blood or blood plasma connectable to the blood circulation of a patient, means (3) for generating and regulating a flow of blood or blood plasma in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood or blood plasma, wherein the extracorporeal circulation system (2) comprises an arterial line (5) from the patient to the cell separator (7), a plasma line (8A) extending from the cell separator (7) for the separated blood plasma in fluidic connection with the apheresis column (4) for affinity chromatographic removal of CRP, a plasma line (8B) extending from the apheresis column (4) for the CRP-depleted blood plasma, and a outgoing cell line (9) for the separated cellular components,which opens into the plasma conduit (8B) at a point (P1), and includes a venous conduit (6) from the point (P1) to the patient; a central processing unit (10) for controlling the apheresis device (1), at least one connecting line (11) for connecting at least one liquid container to the arterial line (5) or the cell separator (7), characterized in that the apheresis device (1) further comprises: a bypass line (12) leading from a point (P2) in the plasma line (8A) to a point (P3) in the cell line (9) or to a point (P6) in the plasma line (8B), a waste line (13) branching off from a point (P4) in the plasma line (8B), at least one regeneration line (14) opening into the plasma line (8A) or directly into the apheresis column (4) after point (P2), and point (P4) is located before points (P1) and (P6) or point (P4) coincides with point (P6).

[0049] According to a preferred embodiment of the present invention, the connecting line (11) opens into the arterial line (5). According to a further preferred embodiment of the present invention, the connecting line (11) opens directly into the cell separator (7).

[0050] As already stated, the apheresis device according to the invention comprises at least one line (the so-called Regeneration line(14)), which enables the feeding of a regeneration solution (e.g. a citrate solution, a TRIS-glycine solution or a NaCl solution) into the extracorporeal circulation system, preferably shortly before the apheresis column (4) or directly into the apheresis column (4). In this context, it is also said that the regeneration line (14) for connecting at least one liquid container (F) is in fluid communication with the extracorporeal circulation system, ie a liquid from a liquid container can be introduced into the extracorporeal circulation system via the regeneration line.

[0051] According to a preferred embodiment of the present invention, the regeneration line (14) opens into the plasma line (8A) at point (P2), i.e., between point (P2) and the apheresis column (4). According to a further preferred embodiment of the present invention, the regeneration line (14) opens into the plasma line (8A) at point (P2). According to a further preferred embodiment of the present invention, the regeneration line (14) opens directly into the apheresis column (4).

[0052] It is obvious to the person skilled in the art that a liquid container (F) for connection to the regeneration line itself does not have to be part of the apheresis device according to the invention, since these are usually disposable items, e.g. in the form of common infusion bags, which are connected to the connecting line by the operating personnel (e.g. the attending physician or a nurse) according to the specific application.

[0053] According to the invention, a single regeneration line (14) for connecting a fluid container (F) is possible. For example, it is conceivable that a separate fluid container, e.g., an infusion bag with NaCl solution, can be connected to the regeneration line (14). However, it is equally conceivable that the end of the regeneration line (14) that allows the connection of a fluid container is located in close proximity to the end of a connecting line (11) that allows the connection of a fluid container, so that a fluid container (with at least two connection options or a corresponding adapter) can be connected to both the connecting line (11) and the regeneration line (14).

[0054] According to the invention, the presence of a single regeneration line (14) is possible, and one or two regeneration lines are particularly preferred. Likewise, embodiments of the apheresis device according to the invention with two, three, or more regeneration lines (14', 14", 14'', etc.) are possible, wherein these two, three, or more regeneration lines can open independently of one another into the extracorporeal circulation system (2) in a region from the branch of the bypass line (12) at the plasma line (8A) (i.e., from point P2) to the apheresis column (4).In this context, "independent of one another" means, for example, that in an embodiment of the apheresis device according to the invention with two regeneration lines (14', 14"), one regeneration line (14') opens into the plasma line (8A) between point (P2) and the apheresis column (4) and the other regeneration line (14") opens directly into the apheresis column (4), but also that both regeneration lines (14', 14") can open into the plasma line (8A) between point (P2) and the apheresis column (4). It is also possible for one regeneration line (14') to open into the other regeneration line (14"). However, in the presence of two or more regeneration lines (14', 14", 14"', etc.), it is particularly preferred if all regeneration lines (14', 14", 14"', etc.) open into the extracorporeal circulation system (2) at the same point in the area from point (P2) to the apheresis column (4), even more preferably if all regeneration lines (14', 14", 14"', etc.) at point (P2) into the extracorporeal circulation system (2).

[0055] According to the invention, it is particularly advantageous if a connecting line (11) and a regeneration line (14) use the same fluid source, as this not only saves space but also minimizes the effort required for operation and maintenance of the apheresis device according to the invention. In this way, existing apheresis systems can also be modified or supplemented without having to connect a separate, additional large device. In preferred embodiments of the present invention, the regeneration line (14) therefore branches off from the connecting line (11), with the point in the connecting line (11) from which the regeneration line (14) branches off being referred to as point ( P5 ) is called.

[0056] It is therefore preferred according to some embodiments of the present invention that the at least one regeneration line (14) leading into the plasma line (8A) or directly into the apheresis column (4) starts from a point (P5) in the at least one connecting line (11).

[0057] In embodiments in which more than one connecting line (11', 11", 11‴ etc.) is present and a regeneration line (14) is connected to several connecting lines (11', 11", 11‴ etc.), the nomenclature of the branching points (P5', P5", P5‴ etc.) is based on the nomenclature of the connecting line (11', 11", 11‴ etc.). This means, for example, that in the case of a regeneration line (14) which opens into two existing connecting lines (11', 11") or creates a connection to them, the point at which the regeneration line (14) opens into the connecting line (11') is referred to as point (P5') and the point at which the regeneration line (14) opens into the connecting line (11") is referred to as point (P5").

[0058] A preferred apheresis device (1) is wherein the apheresis device (1) has two connecting lines (11', 11") for connecting each of a liquid container (F1, F2) to the arterial line (5) or the cell separator (7), and wherein two regeneration lines (14', 14") extend from the two liquid containers (F1, F2) or the two connecting lines (11', 11") and lead into the plasma line (8A) or directly into the apheresis column (4).

[0059] Likewise, embodiments are conceivable in which a regeneration line (14), which leads into the plasma line (8A) or directly into the apheresis column (4) and which originates from a point (P5) in which at least one connecting line (11) extends, has at least one additional connection for a liquid container (see Fig. 7 ).

[0060] In embodiments with more connecting lines than regeneration lines, where each regeneration line connects to at least one connecting line, it is possible for each regeneration line to be connected to a respective connecting line, and the surplus connecting line(s) to be connected only to the arterial line or the cell separator, or for the more numerous connecting lines to converge onto the regeneration lines, i.e., multiple connecting lines are connected to one regeneration line. Mixed forms are also possible.

[0061] There are several ways to regulate the flow rates in the section of the connecting line (11) downstream of point (P5) and in the regeneration line (14). This could be achieved, for example, by using separately controllable pumps in the section of the connecting line (11) downstream of point (P5) and in the regeneration line (14). Another possibility would be a pump located in the connecting line (11) upstream of point (P5), where the distribution of the flow rates downstream of point (P5) is either fixed by the diameters of the regeneration line (14) and the connecting line (11) or can be regulated by appropriate means (clamps, valves) (e.g., by varying the respective pipe diameters). Regulating the flow rates is, of course, particularly important when a solution (e.g., a citrate solution) needs to be introduced into the system via the connecting line (11).for blood anticoagulation) and simultaneously must be fed into the apheresis column via the regeneration line (14) (for regeneration). Such mechanisms can, for example, keep the solution feed via the connecting line (11) constant (e.g., for consistent anticoagulation), even if solution is diverted in phases via the regeneration line (14) for regeneration of the apheresis column.

[0062] Compared to other systems, the apheresis device (1) requires a maximum of 8, preferably 7, more preferably 6 and most preferably 5 pumps.

[0063] Therefore, the present invention is also directed to an apheresis device (1) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood or blood plasma, comprising: an extracorporeal circulation system (2) for blood or blood plasma connectable to the blood circulation of a patient, means (3) for generating and regulating a flow of blood or blood plasma in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood or blood plasma, wherein the extracorporeal circulation system (2) comprises an arterial line (5) from the patient to the cell separator (7), a plasma line (8A) extending from the cell separator (7) for the separated blood plasma in fluidic connection with the apheresis column (4) for affinity chromatographic removal of CRP, a plasma line (8B) extending from the apheresis column (4) for the CRP-depleted blood plasma, and a outgoing cell conduction (9) for the separated cellular components,which opens into the plasma conduit (8B) at a point (P1), and includes a venous conduit (6) from the point (P1) to the patient; a central processing unit (10) for controlling the apheresis device (1), at least one connecting line (11) for connecting at least one liquid container in fluid communication with the extracorporeal circulation system (2), characterized in that the apheresis device (1) further comprises: a bypass line (12) leading from a point (P2) in the plasma line (8A) to a point (P3) in the cell line (9) or to a point (P6) in the plasma line (8B), a waste line (13) branching off from a point (P4) in the plasma line (8B), at least one regeneration line (14) starting from a point (P5) in the at least one connecting line (11) and opening into the extracorporeal circulation system (2) in a region from point (P2) to the apheresis column (4),and point (P4) is located before points (P1) and (P6), or if the bypass line (12) terminates at point (P3), point (P1) coincides with point (P4), or if the bypass line (12) terminates at point (P6), point (P4) coincides with point (P6).

[0064] Likewise, the present invention is directed to an apheresis device (1) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood or blood plasma, comprising: an extracorporeal circulation system (2) for blood or blood plasma connectable to the blood circulation of a patient, means (3) for generating and regulating a flow of blood or blood plasma in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood or blood plasma, wherein the extracorporeal circulation system (2) comprises an arterial line (5) from the patient to the cell separator (7), a plasma line (8A) extending from the cell separator (7) for the separated blood plasma in fluidic connection with the apheresis column (4) for affinity chromatographic removal of CRP, a plasma line (8B) extending from the apheresis column (4) for the CRP-depleted blood plasma, and a outgoing cell line (9) for the separated cellular components,which opens into the plasma conduit (8B) at a point (P1), and includes a venous conduit (6) from the point (P1) to the patient; a central processing unit (10) for controlling the apheresis device (1), at least one connecting line (11) for connecting at least one liquid container to the arterial line (5) or the cell separator (7), characterized in that the apheresis device (1) further comprises: a bypass line (12) leading from a point (P2) in the plasma line (8A) to a point (P3) in the cell line (9) or to a point (P6) in the plasma line (8B), a waste line (13) branching off from a point (P4) in the plasma line (8B), at least one regeneration line (14) starting from a point (P5) in the at least one connecting line (11) and ending after the point (P2) in the plasma line (8A) or directly in the apheresis column (4), and the point (P4) is arranged upstream of the points (P1) and (P6) or in the case,that the bypass line (12) ends at point (P3), the point (P1) coincides with the point (P4) or in the case that the bypass line (12) ends at point (P6), the point (P4) coincides with the point (P6). ,

[0065] In embodiments of the present invention with multiple connecting lines (11', 11", 11‴, etc.) and multiple regeneration lines (14', 14", 14'', etc.), it is possible for each connecting line to be connected to a regeneration line, which in turn leads to the plasma line (8A) or directly to the apheresis column (4) after point (P2). Each regeneration line can lead independently of other regeneration lines to the plasma line (8A) or directly to the apheresis column (4) at a point after point (P2). However, it is preferred if all regeneration lines lead to the plasma line (8A) or directly to the apheresis column (4) at the same point after point (P2), even more preferably directly to the apheresis column (4), and most preferably at point (P2). Such an exemplary embodiment is illustrated by reference to Fig. 6explained: Here, the apheresis device (1) has a first connecting line (11'), which firstly leads into the arterial line (5) and from which, secondly, a first regeneration line (14') branches off at point (P5'). The apheresis device (1) also has a second connecting line (11"), which firstly leads directly into the cell separator (7) and from which, secondly, a second regeneration line (14") branches off at point (P5'). In this embodiment, both regeneration lines (14', 14") open into the extracorporeal circulation system (2) at point (P2).

[0066] A preferred apheresis device (1) is therefore apheresis device, wherein the apheresis device (1) has two connecting lines (11', 11") for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), and wherein the at least one regeneration line (14), which leads into the plasma line (8A) or directly into the apheresis column (4), connects to the connecting line (11') at one point (P5') and to the connecting line (11") at one point (P5").

[0067] Thus, embodiments of the apheresis device (1) are particularly preferred, wherein the apheresis device (1) has two connecting lines (11', 11") for connecting at least one liquid container (F1, F2) to the arterial line (5) or the cell separator (7), and wherein the at least one regeneration line (14), which leads into the plasma line (8A) or directly into the apheresis column (4), connects to the connecting line (11') at one point (P5') and to the connecting line (11") at another point (P5"), and wherein a regeneration line (14') leads from the liquid container (F1) or from the connecting line (11') extending from the liquid container (F1) to the apheresis column (4) or to the plasma line (8A), and a regeneration line (14") leads from the liquid container (F2) or from the connecting line (11") extending from the liquid container (F2) to the apheresis column (4) or to the plasma conduit (8A) or into the regeneration conduit (14').

[0068] Preferably, the liquid container (F1) contains a physiological NaCl solution and the liquid container (F2) contains a citrate solution.

[0069] It is therefore particularly preferred if the apheresis device (1) has a connecting line (11') for connecting a liquid container (F1) and a connecting line (11") for connecting a liquid container (F2), and the connecting line (11') opens into the arterial line (5) or into the cell separator (7), and the connecting line (11") opens into the arterial line (5) or into the cell separator (7) or into the connecting line (11') and thus ultimately also into the arterial line (5) or into the cell separator (7), and a regeneration line (14') leads from the liquid container (F1) or from the connecting line (11') to the apheresis column (4) or to the plasma line (8A), and a regeneration line (14") leads from the liquid container (F2) or from the connecting line (11") to the apheresis column (4) or to the plasma line (8A). or leads into the regeneration line (14').

[0070] Preferably, the liquid container (F1) contains a physiological NaCl solution and the liquid container (F2) contains a citrate solution.

[0071] Embodiments of the apheresis device (1) are therefore particularly preferred in which the apheresis device (1) has a connecting line (11') for connecting a liquid container (F1) to the arterial line (5) or the cell separator (7) and a connecting line (11") for connecting a liquid container (F2) to the arterial line (5) or the cell separator (7), and wherein a regeneration line (14') extends from the liquid container (F1) or the connecting line (11') and leads in the direction of flow to or preferably after the branch of the bypass line (12) into the plasma line (8A) or directly into the apheresis column (4), and a regeneration line (14") extends from the liquid container (F2) or the connecting line (11") and leads in the direction of flow to or preferably after the branch of the bypass line (12) into the plasma line (8A) or into the Regeneration line (14') or directly into the apheresis column (4).

[0072] Particularly preferred is therefore an apheresis device (1) for extracorporeal removal and preferably for selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood, wherein the extracorporeal circulation system (2) comprises an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4) to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), and a central processing unit (10) for controlling the apheresis device (1),a connecting line (11') for connecting a liquid container (F1) to the arterial line (5) or the cell separator (7) and a connecting line (11") for connecting a liquid container (F2) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), a waste line (13) branches off directly from the apheresis column (4) or branches off from the plasma line (8B) in the flow direction before the opening of the bypass line (12),and a regeneration line (14') branches off from the liquid container (F1) or the connecting line (11') and leads in the direction of flow to or preferably after the branch of the bypass line (12) into the plasma line (8A) or directly into the apheresis column (4), and a regeneration line (14") branches off from the liquid container (F2) or the connecting line (11") and leads in the direction of flow to or preferably after the branch of the bypass line (12) into the plasma line (8A) or into the apheresis column (4), or joins with the regeneration line (14').

[0073] Preferably, the liquid container (F1) is a container for a physiological sodium chloride solution and the liquid container (F2) is a container for a citrate solution.

[0074] In other words, according to one embodiment, an apheresis device (1) is preferred, wherein the apheresis device (1) has two connecting lines (11', 11") for connecting at least one liquid container each to the arterial line (5) or the cell separator (7), and wherein the at least one regeneration line (14), which leads into the plasma line (8A) or directly into the apheresis column (4), establishes a connection at point (P5') to the connecting line (11') and at point (P5") to the connecting line (11"). This is to be understood in such a way that the one regeneration line (14) represents the connecting element between the connecting lines (11', 11") on the one side and the plasma line (8A) or the apheresis column (4) on the other side.A liquid from one of the liquid containers (F) connected to one of the two connecting lines (11', 11") could therefore flow via the regeneration line (14) to point (P2) into the plasma line (8A) or directly into the apheresis column (4).

[0075] Therefore, the present invention is also directed to an apheresis device (1) for the extracorporeal removal of CRP from blood or blood plasma comprising: an extracorporeal circulation system (2) for blood or blood plasma connectable to the blood circulation of a patient, means (3) for generating and regulating a flow of blood or blood plasma in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood or blood plasma, wherein the extracorporeal circulation system (2) comprises an arterial line (5) from the patient to the cell separator (7), a plasma line (8A) extending from the cell separator (7) for the separated blood plasma in fluidic connection with the apheresis column (4) for affinity chromatographic removal of CRP, a plasma line (8B) extending from the apheresis column (4) for the CRP-depleted blood plasma, and a outgoing cell conduction (9) for the separated cellular components,which opens into the plasma line (8B) at a point (P1), and includes a venous line (6) from the point (P1) to the patient; a central computing unit (10) for controlling the apheresis device (1), two connecting lines (11', 11") for connecting at least one fluid container each in fluid-technical connection with the extracorporeal circulation system (2), characterized in that the apheresis device (1) further comprises: a bypass line (12) leading from a point (P2) in the plasma line (8A) to a point (P3) in the cell line (9) or to a point (P6) in the plasma line (8B), a waste line (13) branching off from a point (P4) in the plasma line (8B), at least one regeneration line (14),which opens into the extracorporeal circulation system (2) in an area from point (P2) to the apheresis column (4) and which establishes a connection at point (P5') to the connecting line (11') and at point (P5") to the connecting line (11"), and point (P4) is located upstream of points (P1) and (P6), or in the case that the bypass line (12) opens into point (P3), point (P1) coincides with point (P4), or in the case that the bypass line (12) opens into point (P6), point (P4) coincides with point (P6).

[0076] Likewise, the present invention is directed to an apheresis device (1) for the extracorporeal removal of CRP from blood or blood plasma comprising: an extracorporeal circulation system (2) for blood or blood plasma connectable to the blood circulation of a patient, means (3) for generating and regulating a flow of blood or blood plasma in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood or blood plasma, wherein the extracorporeal circulation system (2) comprises an arterial line (5) from the patient to the cell separator (7), a plasma line (8A) extending from the cell separator (7) for the separated blood plasma in fluidic connection with the apheresis column (4) for affinity chromatographic removal of CRP, a plasma line (8B) extending from the apheresis column (4) for the CRP-depleted blood plasma, and a outgoing cell line (9) for the separated cellular components,which opens into the plasma conduit (8B) at a point (P1), and includes a venous conduit (6) from the point (P1) to the patient; a central processing unit (10) for controlling the apheresis device (1), two connecting lines (11', 11") for connecting at least one liquid container to the arterial line (5) or the cell separator (7), characterized in that the apheresis device (1) further comprises: a bypass line (12) leading from a point (P2) in the plasma line (8A) to a point (P3) in the cell line (9) or to a point (P6) in the plasma line (8B), a waste line (13) branching off from a point (P4) in the plasma line (8B), at least one regeneration line (14) opening into the plasma line (8A) or directly into the apheresis column (4) after point (P2) and establishing a connection at point (P5') to the connecting line (11') and at point (P5") to the connecting line (11"),and point (P4) is located before points (P1) and (P6), or if the bypass line (12) terminates at point (P3), point (P1) coincides with point (P4), or if the bypass line (12) terminates at point (P6), point (P4) coincides with point (P6).

[0077] According to one embodiment of the present invention, it is preferred that the apheresis device (1) according to the invention has two connecting lines (11', 11"), wherein the first connecting line (11') is connected to the arterial line (5) for connecting at least one liquid container (preferably a liquid container for or containing a NaCl solution) (i.e. fluidically connected) and a second connecting line (11") is connected directly to the cell separator (7) for connecting at least one liquid container (preferably a liquid container for or containing a citrate solution) (i.e. fluidically connected).In addition, it is preferred if the apheresis device (1) according to the invention has a single regeneration line (14) which opens into the plasma line (8A) or directly into the apheresis column (4) after point (P2), and which, however, originates from or is connected to both the first connecting line (11') and the second connecting line (11") (see . Fig. 5The regeneration line (14) is connected at point (P5') to the first connecting line (11') and at point (P5") to the second connecting line (11"), and then leads to point (P2) into the plasma line (8A) or directly into the apheresis column (4). Using appropriate valves or hose clamps, fluid can be directed as needed via the regeneration line (14) from the fluid reservoir connected to the first connecting line (11') into the apheresis column (4) or to point (P2) into the plasma line (8A), or fluid can be directed from the fluid reservoir connected to the second connecting line (11").

[0078] Such embodiments with two (or even more) connecting lines are ideally suited for using different regeneration solutions to regenerate the apheresis column (4) and for successively introducing them into the apheresis column (4). For example, such a device is ideally suited for first introducing an NaCl solution to displace the plasma contained in the apheresis column, followed by a citrate solution for efficient and rapid regeneration of the adsorber, and finally again by an NaCl solution to displace the citrate solution contained in the apheresis column, before plasma is then introduced back into the apheresis column.

[0079] Therefore, a particularly preferred embodiment of the present invention relates to an apheresis device (1) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood or blood plasma, comprising: an extracorporeal circulation system (2) for blood or blood plasma connectable to the blood circulation of a patient, means (3) for generating and regulating a flow of blood or blood plasma in the extracorporeal circulation system (2), a cell separator (7) for separating the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from the blood or blood plasma, wherein the extracorporeal circulation system (2) comprises an arterial line (5) from the patient to the cell separator (7), a plasma line (8A) extending from the cell separator (7) for the separated blood plasma in fluidic connection with the apheresis column (4) for affinity chromatographic removal of CRP, a plasma line (8B) extending from the apheresis column (4) for the CRP-depleted blood plasma, and a outgoing cell line (9) for the separated cellular components,which opens into the plasma line (8B) at a point (P1), and comprises a venous line (6) from the point (P1) to the patient; a central processing unit (10) for controlling the apheresis device (1), a first connecting line (11') for connecting at least one fluid container to the arterial line (5) and a second connecting line (11") for connecting at least one fluid container directly to the cell separator (7), characterized in that the apheresis device (1) further comprises: a bypass line (12) leading from a point (P2) in the plasma line (8A) to a point (P3) in the cell line (9) or to a point (P6) in the plasma line (8B), a waste line (13) branching off from a point (P4) in the plasma line (8B), at least one regeneration line (14),which leads from point (P2) into the plasma line (8A) or directly into the apheresis column (4) and which establishes a connection at point (P5') to the connecting line (11') and at point (P5") to the connecting line (11"), and point (P4) is located before points (P1) and (P6).

[0080] In embodiments of the apheresis device according to the invention, in which the bypass line (12) leads to the point (P6) in the plasma line (8B), it is preferred if the point (P6) is arranged (in the direction of flow) upstream of the point (P1) (see Fig. 1 - 3 ).

[0081] According to a preferred embodiment of the present invention, the connecting line opens into the arterial line. According to a further preferred embodiment of the present invention, the connecting line opens directly into the cell separator.

[0082] According to a preferred embodiment of the present invention, the regeneration line (14) opens into the plasma line (8A) after point (P2), i.e., between point (P2) and the apheresis column (4). According to a further preferred embodiment of the present invention, the regeneration line (14) opens directly into the apheresis column (4).

[0083] In order to keep the dead volume of the system as low as possible, it is particularly preferred according to the invention if, in the apheresis device (1) according to the invention, the at least one regeneration line (14) opens into the extracorporeal circulation system (2) at point (P2). In embodiments in which more than one regeneration line (14', 14", 14‴, etc.) is present, it is particularly preferred if all existing regeneration lines (14', 14", 14"', etc.) open into the extracorporeal circulation system (2) at point (P2) or open into the plasma line (8A) at point (P2).

[0084] The present invention is therefore also directed to an apheresis device (1) according to the invention, wherein the bypass line (12) leads from a point (P2) in the plasma line (8A) to a point (P6) in the plasma line (8B), and the waste line (13) branches off from a point (P4) from the plasma line (8B), and the at least one regeneration line (14) opens into the plasma line (8A) at point (P2).

[0085] To further reduce the dead volume of the system, it is even more preferred if not only the regeneration line (14) connects to the plasma line (8A) at the point (P2) where the bypass line (12) branches off from the plasma line (8A), but also if the waste line (13) branches off from the same point in the plasma line (8B) where the bypass line (12) connects. In other words, it is preferred if the point (P6) where the bypass line (12) connects to the plasma line (8B) and the point (P4) where the waste line (13) branches off from the plasma line (8B) coincide, i.e., if P4 = P6 (see also [reference to be added]). Fig. 2 and Fig. 3 )

[0086] The present invention is therefore also directed to an apheresis device (1) according to the invention, wherein the bypass line (12) leads from a point (P2) in the plasma line (8A) to a point (P6) in the plasma line (8B), and the waste line (13) branches off from a point (P4) from the plasma line (8B), and the at least one regeneration line (14) opens into the plasma line (8A) at point (P2), wherein point (P6) and point (P4) are identical.

[0087] In the device according to the invention, a Cell separatorThe device incorporates a separator that divides the patient's blood (via arterial lines) into blood plasma and cellular components, and conveys these fractions via the corresponding lines, namely the plasma line and the cell line. As already mentioned, it must be taken into account that the separation into blood plasma and cellular components by the cell separators used is not complete, but rather preferably separates only 10 to 90% of the total blood plasma from the cellular components. When using centrifugal cell separators, preferably 70% to 90%, and more preferably 80% to 87% of the total blood plasma is separated from the cellular components. When using membrane cell separators, preferably 10% to 30%, more preferably 13% to 25%, and even more preferably 15% to 20% of the total blood plasma is separated from the cellular components.

[0088] Possible types of cell separators that can be used in connection with the present invention include centrifugal cell separators, membrane cell separators such as membrane cell separators with semipermeable membranes, and membrane cell separators with rotating membranes.

[0089] The present invention is therefore also directed to an apheresis device for the extracorporeal removal of CRP from blood, wherein the cell separator (7) is either a centrifugal cell separator or a membrane cell separator.

[0090] In the present application, the position of one or more components of the apheresis device according to the invention in relation to another component of the apheresis device according to the invention is defined by the terms "before" or "after"(or "in the direction of flow before" and "in the direction of flow after"), this refers to the general direction of flow of the blood or blood plasma in the apheresis device according to the invention. "Before" in relation to a component of the device according to the invention therefore means in contrast to the general flow direction of the blood or blood plasma, and "towards" in relation to a component of the device according to the invention consequently means with the general flow direction of the blood or blood plasma. It is preferred that the flow direction in the apheresis device does not reverse or is not reversed by the means for generating and regulating a flow.

[0091] According to the present invention, the apheresis device according to the invention for the extracorporeal removal of CRP from blood comprises an apheresis column (4) for affinity chromatographic removal of CRP from the blood or blood plasma, the function of which consists in binding CRP which is located in the blood or blood plasma of a patient and which is passed through the apheresis column (4).

[0092] The term "affinity chromatographic"In relation to the removal of CRP, as used in the present application, this means that the removal of CRP occurs through a specific binding between CRP and components of the apheresis column (4). In this context, one can also speak of "selective removal of CRP" or "selective CRP apheresis." Such specific binding between CRP and components of the apheresis column (4) is based on the structural properties of the CRP protein and includes, for example, the characteristic binding of CRP to phosphocholine and its derivatives, or the binding of CRP to antibodies directed against a CRP epitope. The selective or molecule-specific removal of CRP implies that CRP binds to the matrix in the apheresis column (4) with a higher affinity than to other structures / molecules.CRP also binds to the matrix in the apheresis column (4) with a higher affinity than other substances present in the blood; that is, the matrix has a specificity for CRP. The matrix, preferably a phosphocholine-modified solid phase, preferably binds CRP selectively, meaning that almost exclusively CRP is bound and no other blood components such as LDL cholesterol, antibodies, or uremic toxins are bound. Thus, the "removal of CRP" as disclosed herein preferably means the selective removal of CRP.

[0093] The basic design and construction of such an apheresis column (or cartridge) is part of the prior art and is described, inter alia, in EP 0237659 B1. The exact dimensions of the cartridge, column, or cartridge used according to the invention (as a device for the selective removal of CRP) depend significantly on the intended use of the device according to the invention. The apheresis column (4) for the affinity chromatographic removal of CRP generally comprises a housing, e.g., in the form of a cartridge, which is connected to the extracorporeal circulation system via at least one inlet and at least one outlet and contains a matrix for the affinity chromatographic or adsorptive removal of CRP.

[0094] The matrix for the affinity chromatographic (or adsorptive) removal of CRP comprises a matrix substrate material, to which compounds are bound that have the property of specifically binding CRP. According to a preferred embodiment of the present invention, the matrix is ​​integrated into or immobilized in the apheresis column (4) for the affinity chromatographic removal of CRP in such a way that it cannot be flushed out of the column with the blood plasma flow. Depending on the embodiment, this can be implemented, for example, in the form of filters at the inlet and outlet of the device.

[0095] In principle, all inert chromatography or column materials are suitable as matrix substrate materials for the production of the matrix, provided that they do not react with blood or blood plasma, nor alter or contaminate blood or blood plasma in such a way that the blood or blood plasma cannot be returned to a patient after contact with the matrix. The suitable matrix substrate materials according to the invention therefore include, but are not limited to, eupergite, polyvinylpyrrolidone, methacrylate, methacrylate resins, agarose, Sepharose, acrylic beads, cellulose matrices, ceramic matrices, glass beads, and / or solid-state silica or mixtures and / or derivatives of these substances.The solid-phase silica matrix can include virtually any form of particulate silica, including amorphous silicas such as colloidal silica, silica gels, precipitated silicas, and fumed or pyrogenic silicas; microcrystalline silicas such as diatomaceous earth; and crystalline silicas such as quartz. According to the invention, the compounds bound to the matrix substrate materials, which have the property of specifically binding CRP, are selected from the group comprising or consisting of lipids, lysophospholipids, lysophosphatidylcholine, peptides, peptides with charged amino acids, peptides containing the sequence ArgProArg, polypeptides, antibodies, monoclonal antibodies, antibody fragments, manipulated antibodies, phosphocholine, derivatives of phosphocholine, DNA, DNA derivatives, RNA, RNA derivatives, L-ribonucleic acid aptamers, such as Spiegelmers ®< (an RNA-like molecule consisting of L-ribose units) and aptamers. Ca 2+< -dependent ligands for CRP

[0096] As already mentioned several times, for the affinity chromatographic removal of CRP from biological fluids, e.g., blood or blood plasma, a column material containing phosphocholine and / or its derivatives is used, which makes a Ca 2+< -dependent binding of CRP to the said functionalized column material possible.

[0097] For this purpose, phosphocholine and / or its derivatives are immobilized on a column material. This is usually done via an organic linker group, through which the phosphocholine or its derivatives are adsorptively or, more preferably, covalently bound to the column material. This results in a so-called "functionalized column material", wherein the chemical group responsible for the Ca 2+< -dependent binding of CRP is exposed to the outside, so that CRP, which is in a biological fluid, also has access to said chemical group.

[0098] In other words, the term "functionalized column material", As used herein, a column material for affinity chromatography, modified with a functional chemical group, is defined. This functional chemical group can be linked to the column material via adsorptive or ionic interactions, but preferably via a covalent bond. It is essential that the functional chemical group is linked to the column material in such a way that it remains active and exposed, thus preserving its functionality. This allows the group attached to the column material (here: ω-phosphonooxyalkylammonium group and / or ω-ammonium alkoxy-hydroxyphosphoryloxy group) to interact with or bind to a ligand (here: CRP) from the sample (here: biological fluid such as blood or blood plasma).

[0099] Depending on whether the phosphocholine or its derivative is linked to the column material via an organic linker through the ammonium group or the phosphate group, a distinction is made between a column material that has been functionalized with an ω-phosphonooxyalkylammonium group (linking via the ammonium group) and a column material that has been functionalized with an ω-ammonium alkoxy-hydroxy-phosphoryloxy group (linking via the phosphate group).

[0100] The linkage with the column material (possibly via an organic linker) is described in the formulas listed below ( I ) and ( II ) about a dashed line either represented at the nitrogen atom of the ammonium group or at the oxygen atom of the phosphate group.

[0101] The term "ω-Phosphonooxyalkylammonium group"as used herein can be used synonymously with "omega-phosphonooxyalkylammonium" and describes compounds of the following general formula ( I ) where n is selected from 2 and 3; R 1< and R 2< are independently selected from: -H, -CH 3 , -C 2 H 5 , -C 3 H 7 , -C 4 H 9 , -C 5 H 11 , -C 6 H 13 , or R 1< and R 2< together with the nitrogen atom to which they are attached may form a heterocycle selected from: where one or more hydrogen atoms can be replaced by one or more fluorine atoms.

[0102] Preferred ω-phosphonooxyalkylammonium groups include compounds of the general formula ( I ) where n = 2 or 3; R1< and R2< can be selected independently from: -H, -CH3, -C2H5, -C3H7 or R1< and R2< together with the nitrogen atom to which they are bonded can form a heterocycle, which is selected from:

[0103] Particularly preferred ω-phosphonooxyalkylammonium groups include compounds of the general formula ( I ) where n = 2; R1< and R2< are selected from: -H, -CH3, -C2H5, and particularly preferably from -CH3 and -C2H5, or R1< and R2< together with the nitrogen atom to which they are bonded can form a heterocycle selected from:

[0104] Preferred compounds containing an ω-phosphonooxyalkylammonium group as described above and suitable for functionalizing a corresponding column material include, for example: 2-[2-(2-Aminoethoxy)ethyl-diethyl-ammonio]ethyl hydrogen phosphate, 2-[4-[2-(2-Aminoethoxy)ethyl]morpholine-4-ium-4-yl]ethyl hydrogen phosphate, 2-[1-[2-(2-Aminoethoxy)ethyl]piperidin-1-ium-1-yl]ethyl hydrogen phosphate, 2-[2-(2-Aminoethoxy)ethyl-dimethyl-ammonio]ethyl hydrogen phosphate, 2-[3-Aminopropyl-(dimethyl)ammonio]ethyl hydrogen phosphate, 2-[Dimethyl(4-sulfanylbutyl)ammonio]ethyl hydrogen phosphate, 2-[4-Azidobutyl(dimethyl)ammonio]ethyl hydrogen phosphate, 2-[Dimethyl(pent-4-ynyl)ammonio]ethyl hydrogen phosphate, 2-[3-(6-aminohexanoyl-amino)propyl-diethyl-ammonio]ethyl hydrogen phosphate, 2-[1-[2-[2-(6-aminohexanoyl-amino)ethoxy]ethyl]piperidin-1-ium-1-yl]ethyl hydrogen phosphate, 2-[4-[2-[2-[3-(6-Aminohexanoylamino)propanoylamino]ethoxy]ethyl]morpholin-4-ium-4-yl]ethyl hydrogen phosphate,2-[1-[2-[2-[6-(6-Aminohexanoylamino)hexanoylamino]ethoxy]ethyl]pyrrolidin-1-ium-1-yl]ethyl-hydrogenphosphat, 2-[2-Allyloxyethyl(dimethyl)ammonio]ethyl-hydrogenphosphat, 2-[2-Allyloxyethyl(diethyl)ammonio]ethyl-hydrogenphosphat, 2-[4-(2-Allyloxyethyl)morpholin-4-ium-4-yl]ethyl-hydrogenphosphat, 2-[1-(2-Allyloxyethyl)piperidin-1-ium-1-yl]ethyl-hydrogenphosphat, 2-[2-[2-(6-Aminohexanoylamino)ethoxy]ethyl-dimethyl-ammonio]ethyl-hydrogenphosphat, 2-[2-[2-[3-(6-Aminohexanoylamino)propanoylamino]ethoxy]ethyl-dimethyl-ammonio]ethyl-hydrogenphosphat, 2-[3-Azidopropyl(dimethyl)ammonio]ethyl-hydrogenphosphat, 2-[Dimethyl-[2-[2-(prop-2-ynoxycarbonylamino)ethoxy]ethyl]ammonio]ethyl-hydrogenphosphat, 2-[2-[2-(Allyloxycarbonylamino)ethoxy]ethyl-dimethyl-ammonio]ethyl-hydrogenphosphat, 2-[2-[2-[6-(Allyloxycarbonylamino)hexanoylamino]ethoxy]ethyl-dimethyl-ammonio]ethyl-hydrogenphosphat, 2-[2-(6-Aminohexanoylamino)ethyl-dimethyl-ammonio]ethyl-hydrogenphosphat,2-[Dimethyl-[3-[6-(prop-2-ynoxycarbonylamino)hexanoylamino]propyl]ammonio]ethyl hydrogen phosphate, and 2-[3-(6-aminohexanoylamino)propyl-dimethyl-ammonio]ethyl hydrogen phosphate.,

[0105] The term ω-ammoniumalkoxy-hydroxy-phosphoryloxy groups" as used herein, can be used synonymously with "omega-ammonium alkoxy-hydroxy-phosphoryloxy groups" and describes compounds of the following general formula ( II ) where n is selected from 2 and 3; R 1< , R 2< and R 3< are independently selected from: -H, -CH 3 , -C 2 H 5 , -C 3 H 7 , -C 4 H 9 , -C 5 H 11 , -C 6 H 13 , or R 1< and R 2< together with the nitrogen atom to which they are attached may form a heterocycle selected from: and R 3< is selected from: -H, -CH 3 , -C 2 H 5 , -C 3 H 7 , -C 4 H 9 , -C 5 H 11 , -C 6 H 13 , and preferably -H; where one or more hydrogen atoms may be replaced by (a) fluorine atom(s).

[0106] Preferred ω-ammoniumalkoxy-hydroxy-phosphoryloxy groups include compounds of the general formula ( II ) where n is selected from 2 and 3; R1<, R2< and R3< are selected independently from: -H, -CH3, -C2H5, -C3H7, or R1< and R2< together with the nitrogen atom to which they are bonded can form a heterocycle, which is selected from: and R 3< = -H is.

[0107] Within the scope of the present invention, it is particularly preferred if the ω-ammonium alkoxy-hydroxy-phosphoryloxy group is a ω-trialkylammonium alkoxyhydroxy-phosphoryloxy group.

[0108] Therefore, particularly preferred ω-ammoniumalkoxy-hydroxy-phosphoryloxy groups include compounds of the general formula ( II ) where n = 2; and R 1< , R 2< and R 3< are selected from: -H, -CH 3 , -C 2 H 5 and especially preferably from -CH 3 and -C 2 H 5 .

[0109] It is therefore particularly preferred if the ω-ammonium alkoxy-hydroxy-phosphoryloxy groups are ω-trimethylammonium ethoxy-hydroxy-phosphoryloxy groups or ω-trimethylammoniupropoxy-hydroxy-phosphoryloxy groups.

[0110] Preferred compounds containing an ω-ammonium alkoxy-hydroxy-phosphoryloxy group as described above and suitable for functionalizing a corresponding column material include, for example: p-aminophenylphosphocholine (APPC), 4-[[Hydroxy[2-(trimethylammonio)ethoxy]phosphinyl]oxy]-benzenediazonium (p-diazonium phenylphosphocholine) or p-nitrophenyl-6-(O-phosphocholine)hydroxyhexanoate.

[0111] In one possible embodiment of the present invention, the ω-ammonium alkoxy-hydroxyphosphoryloxy group is linked via a phosphoester bond to a hydroxyl group of a glycerol molecule (as an organic linker), the resulting glycerol ester then being linked to the column material via a second hydroxyl group of the glycerol. In such an embodiment, it is also possible that the remaining third hydroxyl group of the glycerol is either esterified with a fatty acid or with a second ω-ammonium alkoxy-hydroxyphosphoryloxy group. Furthermore, the position of the respective esterification on the glycerol molecule can vary. The usual saturated, monoolefinic, polyolefinic, monoacetylenic, unsaturated linear and / or branched fatty acids with 8 to 28 carbon atoms can be used as fatty acids. Preferred fatty acid residues are palmitic acid, arachidonic acid, oxovaleric acid, glutaric acid, epoxyisoprostane and stearic acid. Column material

[0112] In principle, all inert chromatography or column materials are suitable for the production of column material functionalized with ω-phosphonooxyalkylammonium groups and / or with ω-ammonium alkoxy-hydroxy-phosphoryloxy groups, provided that these materials do not react with blood or blood plasma or alter or contaminate blood or blood plasma in such a way that the blood or blood plasma cannot be injected into a patient after contact with the column material.The column materials suitable according to the invention therefore include, but are not limited to: Eupergit®, polyvinylpyrrolidone (PVP), polysulfone (PS), polyethersulfone (PES), polyarylethersulfone (PAES), polyacrylate, methacrylate, methacrylate resins such as poly(methyl methacrylate) (PMMA) and poly(glycidyl methacrylate) (PGMA), poly(hydroxy methacrylate), polystyrene (PS), polytetrafluoroethylene (PTFE), polyacrylamide, polyacrolein, acrylonitrile butadiene styrene (ABS), polyacrylonitrile (PAN), polyurethane (PU), Sepharose®, acrylic beads, agarose, cellulose matrices, polyethylene glycol (PEG), alginate, carrageenan, chitin, starch, nitrocellulose, ceramic matrices, glass beads and / or solid-phase silica or mixtures and / or derivatives of these substances.The solid-state silica matrix can comprise virtually any form of particulate silica, including amorphous silicas such as colloidal silica, silica gels, precipitated silicas, and fumed or pyrogenic silicas; microcrystalline silicas such as diatomaceous earth; and crystalline silicas such as quartz. The silica should have a particle size in the range of approximately 45 to 120 mesh (corresponding to approximately 345 µm to 125 µm), preferably in the range of approximately 45 to 60 mesh (corresponding to approximately 345 µm to 212 µm).

[0113] Often, for functionalization with ω-phosphonooxyalkylammonium groups and / or with ω-ammonium alkoxy-hydroxy-phosphoryloxy groups, a column material is used that has already been "pre-functionalized", i.e., provided with a chemical group which then in turn enables the covalent attachment of the ω-phosphonooxyalkylammonium groups and / or the ω-ammonium alkoxy-hydroxy-phosphoryloxy groups.

[0114] Such "pre-functionalization" of a column material is achieved by methods that are well known to a person skilled in the art (Chin J Chem 2012, 30, 2473; Polym Int 2013, 62, 991). In addition, some pre-functionalized column materials are commercially available, such as: Toyopearl ®< AF-epoxy, Toyopearl ®< AF-amino, Toyopearl ®< AFtresyl, TSKgel ®< tresyl, epoxy-activated Sepharose ®< 6B (GE Healthcare Life Sciences), CNBr-activated Sepharose ®< 4 fast flow (GE Healthcare Life Sciences), ECH Sepharose ®< 4B (GE Healthcare Life Sciences), NHS-activated Sepharose ®< 4 fast flow (GE Healthcare Life Sciences), terminal vinylsulfone activated Sepharose ®< 4 fast flow (Affiland), aldehyde Separopore ®< (Agarose) 4B, ECH Separopore ®< (Agarose) 4B (Separopore), agaroses from Sterogene Bioseparations, Inc., e.g. Epoxy-Ultraflow-4 Agarose (Sterogene Bioseparations, Inc.), Epoxy-Ultraflow-6 Agarose (Sterogene Bioseparations, Inc.), Agaroses from empBiotech GmbH, Epoxy-Ultraflow-4 Agarose ( emp Biotech GmbH), Epoxy-Ultraflow-6 Agarose ( emp Biotech GmbH), activated agaroses with any degree of cross-linking. In principle, columns for the selective removal of cholesterol (LDL cholesterol) and anti-factor VII or -IX antibodies are not suitable and cannot be used for the affinity chromatographic removal of CRP, and especially not for the selective affinity chromatographic removal of CRP from blood.

[0115] Columns consisting of protein A bound to a matrix substrate material are suitable for affinity chromatographic purification of antibodies, i.e., the column is specific for antibodies but not for CRP.

[0116] A well-known example of a matrix for the affinity chromatographic removal of LDL cholesterol is polyacrylamide beads, to whose surface polyacrylic acid is covalently bound (also known under the trade name Dali Beads, where DALI stands for "direct adsorption of lipids"). Due to their size, only the small proteins (lipoproteins such as LDL with a diameter of 25 nm) diffuse through the pores (diameter 100-200 nm) into the interior of the sponge-like structure of the beads. Pump

[0117] According to the present invention, the apheresis device according to the invention for the extracorporeal removal of CRP from blood includes means for generating and regulating a flow of blood (or blood plasma) in the extracorporeal circulation system. For this purpose, one or more pumps or pump systems are generally used, which enable a controllable flow of blood (or blood plasma, or also of the regeneration solution or anticoagulation solution) through the extracorporeal circulation system and the fluid-technically connected components of the device according to the invention.

[0118] The preferred flow direction according to the invention within the extracorporeal circulation system and the components of the device according to the invention that are fluidically connected thereto runs from the access on the patient through which the blood enters the device according to the invention, via the arterial line of the extracorporeal circulation system to the venous line of the extracorporeal circulation system and to the access on the patient at which the treated blood is returned to the patient.

[0119] The means used according to the invention for generating and regulating a flow in the extracorporeal circulation system are preferably pumps in the form of peristaltic pumps (also known as hose pumps), piston pumps, pneumatic pumps, hydraulic pumps, or other pump types known to those skilled in the art. Consequently, the terms "means for generating and regulating a flow" and "pump" can be used synonymously herein.

[0120] According to the invention, it is preferred if the means used for generating and regulating a flow of blood (or blood plasma, or also the regeneration solution or anticoagulation solution) in the extracorporeal circulation system do not have direct physical contact with the blood (or blood plasma, or also the regeneration solution or anticoagulation solution) in the device according to the invention. This is particularly advantageous for hygienic reasons and prevents the contamination of complex mechanical components, such as a pump, by blood, as well as of the blood itself by the means used for flow generation.

[0121] In a particularly preferred embodiment of the present invention, the means for generating and regulating a flow in the extracorporeal circulation system are therefore one or more peristaltic pump(s).

[0122] The exact position of the means for generating and regulating flow in the extracorporeal circulation system, i.e., the one or more pumps, is not essential to the present invention. Embodiments of the present invention using only one pump are possible, in which the pump is located in the region of the arterial line of the apheresis device according to the invention for the extracorporeal removal of CRP from blood, i.e., upstream of the cell separator. If, according to the invention, several means for generating and regulating flow in the extracorporeal circulation system are provided, i.e., several pumps, it is preferred if these can be controlled and regulated independently of one another (e.g., by the CPU). Depending on the specific application, different flow rates within the extracorporeal circulation system may be desired or required.It is also conceivable that during a specific application different flow rates are desired in different components of the device according to the invention.

[0123] According to the invention, several means for generating and regulating a flow (i.e., pumps) can also be integrated into the apheresis device according to the invention. Thus, it is possible for means for generating and regulating a flow to be located in the arterial line (5) and / or in the plasma line (8A) and / or in the plasma line (8B) and / or in the venous line (6) and / or in the bypass line (12) and / or in the cell line (9) and / or in the connecting line (11) or connecting lines (11', 11", 11", etc.) and / or in the regeneration line (14) or regeneration lines (14', 14", 14'', etc.). As already indicated above, according to an embodiment of the present invention in which the regeneration line (14) branches off from the connecting line (11) at point (P5), it is preferred that a means for generating and regulating a flow (of inorganic salt solutions) in the connecting line (11) is provided upstream of point (P5).

[0124] According to a further embodiment of the present invention, in which the regeneration line (14) branches off from the connecting line (11) at point (P5), it is preferred that a means for generating and regulating a flow in the connecting line (11) is provided after point (P5) and a means for generating and regulating a flow in the regeneration line (14).

[0125] Furthermore, the apheresis device (1) preferably has at least one particle filter which is provided in the flow direction behind the apheresis column (4) in the plasma line (8B) or the venous line (6).

[0126] Furthermore, the apheresis device (1) preferably has at least one bubble catcher, which is provided in the flow direction behind the apheresis column (4) in the plasma line (8B) or the venous line (6).

[0127] In the case of a centrifuge as cell separator (7), the apheresis device (1) preferably has at least one plasma reservoir which is provided in the plasma line (8A) downstream of the centrifuge (7) and upstream of the apheresis column (4) in the flow direction.

[0128] In further embodiments, the apheresis device according to the invention can be used for the extracorporeal removal of CRP from blood or blood plasma, comprising one or more Pressure sensorsThe device comprises sensors that serve to measure or monitor the pressure in a specific section of the device according to the invention. This serves not only to monitor and adjust the operating parameters of the apheresis device according to the invention, but is also advantageous in that, in the event of a malfunction (e.g., a blockage of a tube or filter of the device), operation can be stopped to prevent harmful consequences for the patient. The exact function and installation position in the device according to the invention are part of the prior art and are known to those skilled in the art. In a preferred embodiment of the present invention, at least one pressure sensor is arranged in the arterial line of the apheresis device according to the invention, as well as at least one pressure sensor in the venous line of the apheresis device according to the invention.In a further preferred embodiment of the present invention, such pressure sensors are integrated into the means used for generating and regulating a flow in the extracorporeal circulation system of the apheresis device according to the invention.

[0129] To control the flow direction at the nodes of the extracorporeal circulation system, i.e., at the points where several lines converge or branch off, means are preferably provided to determine the flow of the solution (e.g., blood, plasma, or regeneration solution). These means can be valves, multi-way valves, clamps, or valves in the form of shut-off valves, check valves, pressure valves, directional control valves, or other valve types known to those skilled in the art, which allow flow in one direction and block it in another. Preferably, such flow control means (e.g., valves) are located at point (P1) and / or point (P2) and / or point (P3) and / or point (P4) and / or point (P5) and / or point (P6). Furthermore, it is possible, for example, to connect two or more valves in series at a single point to enable more complex flow control.

[0130] It is also particularly preferred if the means for flow regulation (e.g. valves) are electronically controllable, i.e. their position can be controlled by the central computing unit (10).

[0131] The present invention is therefore also directed to an apheresis device for the extracorporeal removal of CRP from blood, wherein electronically controlled valves are attached at points (P1), (P2), (P4), (P5), (P6), (P7) and (P8).

[0132] It is also conceivable and in accordance with the invention if valves are not located directly at the branching points (P1, P2, P4, P5, P6, P7 and P8), but rather in the upstream and / or downstream lines, thus controlling the flow of solutions in the extracorporeal circulation system. Hose clamps can also be used for this purpose. It is particularly preferred if these valves or hose clamps are electronically controlled.

[0133] A further advantage of the present invention, related to the fact that apheresis and the regeneration of the apheresis column are realized in a single device, is that the entire device can be controlled by a single central processing unit (CPU). Thus, the different programs during an apheresis session—for example, normal operation, in which the blood plasma is passed through the apheresis column, and regeneration operation, in which the blood plasma is passed past the apheresis column through the bypass line and the apheresis column is rinsed with regeneration solution—can be controlled by a single processing unit or the software located on it. This facilitates the automation of many processes and thus reduces the scope for operating errors on the part of the staff.In contrast, state-of-the-art devices require the combination of different complex systems (primary system for separating blood into plasma and cellular components; and secondary system for apheresis and regeneration), with each system having to be controlled separately.

[0134] The present invention is therefore also directed to an apheresis device for the extracorporeal removal of CRP from blood, wherein the entire device is controlled only by means of the one central computing unit (10).

[0135] Another aspect of the present invention relates to an apheresis device, wherein a second apheresis column (4") is connected to the bypass line or the bypass line comprises a second apheresis column. Preferably, the second apheresis column (4") is contained within the bypass line. Therefore, the apheresis devices described herein for the extracorporeal removal of CRP from blood can include a second apheresis column (4"), wherein the second apheresis column (4") is contained within the bypass line. An apheresis column (4") is contained within the bypass line if a section of the bypass line (12') opens into the second apheresis column (4") and a further section of the bypass line (12') leads away from the outlet of the apheresis column (4").

[0136] Therefore, another aspect of the present invention comprises an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from the blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1) includes a central computing unit (10) for controlling the apheresis device (1),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), and the bypass line (12) comprises the second apheresis column (4"), a waste line (13) branches directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow upstream of the inlet of the bypass line (12), and at least one regeneration line (14) which branches off from the at least one liquid container (F) or the at least one connecting line (11) and leads in the direction of flow at or downstream of the branch of the bypass line (12) to the plasma line (8A) or opens directly into the apheresis column (4'), and wherein a second apheresis column (4") is parallel to the first apheresis column (4') is switched and both apheresis columns (4', 4") can only be operated alternately,This means they cannot be used simultaneously with CRP removal.

[0137] The above-mentioned embodiments of the apheresis device (1) according to the invention are to be transferred to the apheresis device (II) according to the invention.

[0138] With the aid of this apheresis device (II) according to the invention, it is possible to remove CRP from blood more efficiently with the same treatment duration than with devices from the prior art. By using two apheresis columns connected in parallel, which can only be used alternately for CRP removal, one apheresis column can be used for the removal of CRP from the blood with the apheresis device according to the invention, while the second apheresis column can either be replaced by another apheresis column or regenerated during the ongoing apheresis session. This also allows a high clinical throughput to be achieved with a single apheresis device. Furthermore, the use of the apheresis device according to the invention is not limited by the dead volume.Typically, oversized apheresis columns, as well as those connected in series, are severely limited in their use for apheresis due to their large dead volume. Furthermore, the volume of an apheresis device, and thus the volume or number of apheresis columns connected in series, is determined by the human blood flow rate. Apheresis devices with parallel apheresis columns used simultaneously cannot be used efficiently and without risk to the patient for the removal of CRP from blood due to the large dead volume. Therefore, the bypass line (12) can be used as a plasma line.

[0139] An apheresis device (II) according to the invention described herein is characterized in that a second apheresis column is connected in parallel to a first apheresis column (4'). "Parallel" in this context means that several circuits are present side by side within the extracorporeal circulation system (2), i.e., that, for example, a first apheresis column (4') with the plasma line (8A) for the separated plasma and with the plasma line (8B) for the CRP-depleted plasma constitutes a first circuit of the extracorporeal circulation system (2), and a second apheresis column (4") with the bypass line section (12') of the bypass line (12) and the bypass line section (12") of the bypass line (12) constitutes a second circuit of the extracorporeal circulation system (2). "Parallel" also means that the two apheresis columns are not connected in series, i.e.The outflow from the first apheresis column is not directed sequentially into the second apheresis column. Due to the parallel arrangement of the apheresis columns, their capacities do not add up.

[0140] This is to be distinguished from the serial connection of the apheresis columns, which is not according to the invention. "Serial" means that several apheresis columns are located in only one circuit of the extracorporeal circulation system (2), i.e., that, for example, the first apheresis column (4') and the second apheresis column (4") together with the plasma line (8A) and the plasma line (8B) form only one circuit of the extracorporeal circulation system (2), i.e., would be connected or arranged in series.

[0141] According to the invention, the two apheresis columns (4', 4") connected or arranged in parallel can only be operated alternately. "Alternatively" means that the separated blood plasma is passed either through apheresis column (4') or through apheresis column (4"), but not simultaneously through both apheresis columns (4', 4"). "Alternatively" operation refers to therapeutic CRP removal. Both apheresis columns (4' and 4") cannot be used simultaneously for CRP removal. Of course, one of the two apheresis columns can be regenerated while the other is used for CRP removal. Simultaneous therapeutic operation of both apheresis columns for CRP removal is the only limitation.

[0142] The following scenarios are therefore possible. Blood plasma is passed through one apheresis column to remove CRP. Simultaneously, the second apheresis column is ready for use, and the plasma flow can be diverted to this second column as soon as the capacity of the first column is exhausted, or other problems arise with the first column, or the second column has already been used for CRP removal and needs to be replaced or regenerated, or the second column is being regenerated while the first column is removing CRP.

[0143] In embodiments of the present invention, the apheresis device (II) with two apheresis columns is therefore designed such that the apheresis columns can only be operated alternately.

[0144] Thus, according to one embodiment of the apheresis device (II) according to the invention, the blood plasma can be conducted simultaneously either only through the first apheresis column (4') or only through the second apheresis column (4"). In further embodiments of the device according to the invention, the apheresis device is thus configured such that the blood plasma can be conducted simultaneously either only through the first apheresis column (4') or only through the second apheresis column (4").

[0145] One embodiment of the present invention therefore relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from the blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1) includes a central computing unit (10) for controlling the apheresis device (1),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), and the bypass line (12) comprises the second apheresis column (4"), a waste line (13) leads directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line (12), and at least one regeneration line (14) which leads from the at least one liquid container (F) or the at least one connecting line (11) and leads in the flow direction at or after, preferably after the branching of the bypass line (12) to the plasma line (8A) or opens directly into the apheresis column (4'), and wherein a second apheresis column (4") is parallel to first apheresis column (4') is switched on and both apheresis columns (4', 4") can only be operated alternately,and wherein the blood plasma is simultaneously conductable either only through the first apheresis column (4') or only through the second apheresis column (4").

[0146] During the alternating operation of the two apheresis columns (4', 4"), no blood plasma is passed through either column (4') or column (4"). This allows for the replacement of one of the two apheresis columns from the apheresis device while the device is operating. "Replacement" in this context means either replacing one of the two apheresis columns with a new one or regenerating one of the two apheresis columns. Regeneration can be achieved, for example, by flushing with a citrate solution. The use of a citrate solution is preferred for regenerating the apheresis columns. "During operation" in this context means that the removal of CRP from the blood continues.

[0147] One embodiment of the apheresis devices (II) described herein relates to an apheresis device in which a first apheresis column (4') is interchangeable during the operation of a second apheresis column (4") and the second apheresis column (4") is interchangeable during the operation of the first apheresis column (4').

[0148] Likewise, embodiments are conceivable in which a first apheresis column (4') is regenerable during the operation of a second apheresis column (4") and the second apheresis column (4") is regenerable during the operation of the first apheresis column (4').

[0149] Thus, in one embodiment of the present invention, the apheresis device (II) is designed such that a first apheresis column (4') is replaceable or regenerable during the operation of a second apheresis column (4") and the second apheresis column (4") is replaceable or regenerable during the operation of the first apheresis column (4').

[0150] An embodiment of the present invention further relates to an apheresis device (II) for extracorporeal removal and preferably for selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from the blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1) includes a central computing unit (10) for controlling the apheresis device (1),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), and the bypass line (12) comprises the second apheresis column (4"), a waste line (13) leads directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line (12), and at least one regeneration line (14) which leads from the at least one liquid container (F) or the at least one connecting line (11) and leads in the flow direction at or after, preferably after the branching of the bypass line (12) to the plasma line (8A) or opens directly into the apheresis column (4'), and wherein a second apheresis column (4") is parallel to first apheresis column (4') and both apheresis columns (4',4") can only be operated alternately at the same time, and wherein the first apheresis column (4') is replaceable or regenerable during the operation of the second apheresis column (4") and the second apheresis column (4") is replaceable or regenerable during the operation of the first apheresis column (4').

[0151] The present invention also relates to an apheresis device (II) for the extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from the blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1) includes a central computing unit (10) for controlling the apheresis device (1),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), and the bypass line (12) comprises the second apheresis column (4"), a waste line (13) leads directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line (12), and at least one regeneration line (14) which leads from the at least one liquid container (F) or the at least one connecting line (11) and leads in the flow direction at or after, preferably after the branching of the bypass line (12) to the plasma line (8A) or opens directly into the apheresis column (4'), and wherein a second apheresis column (4") is parallel to first apheresis column (4') and both apheresis columns (4',4") are not usable simultaneously with CRP removal, and one of the apheresis columns (4', 4") can be regenerated simultaneously with CRP removal by the other apheresis column.

[0152] Therefore, according to one embodiment of the present invention, the apheresis device (II) is designed such that the first apheresis column (4') is replaceable during the operation of the second apheresis column (4") and the apheresis column is designed in such a way that it is regenerable and the second apheresis column (4") is replaceable during the operation of the first apheresis column (4') and the apheresis column (4") is designed in such a way that the apheresis column (4") is regenerable.

[0153] The second apheresis column (4") connected in parallel to the first apheresis column (4') can be integrated into the bypass line, i.e. the bypass line (12) consists of a bypass line section (12') and a bypass line section (12"), with the second apheresis column (4") located between said bypass line sections.

[0154] The present invention therefore also relates to an apheresis device (II) for the extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from the blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4'), and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13) branches off directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow upstream of the inlet of the bypass line (12), and at least one regeneration line (14) that branches off from the at least one liquid container (F) or the at least one connecting line (11) and extends in the direction of flow at or after, preferably after, the branch of the bypass line. (12) leads to the plasma conduit (8A) or directly into the apheresis column (4'),and wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal. ,

[0155] One embodiment of the present invention therefore relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from the blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least two connecting lines (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), and the bypass line (12) comprises the second apheresis column (4"), a waste line (13) branches directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow upstream of the inlet of the bypass line (12), and at least one regeneration line (14) which branches off from the at least one liquid container (F) or the at least two connecting lines (11) and leads in the direction of flow to or preferably after the branch of the bypass line (12) to the plasma line (8A) or opens directly into the apheresis column (4'), and wherein a second apheresis column (4") is parallel to the first apheresis column (4') and both apheresis columns (4',4") cannot be used simultaneously with CRP removal (i.e., they can only be operated alternately).

[0156] According to one embodiment of the present invention, it is particularly preferred if the apheresis device (II) according to the invention has two connecting lines (11', 11") for connecting at least one liquid container (F) each, wherein the connecting lines (11', 11") open independently of one another into the arterial line (5) or directly into the cell separator (7). Consequently, both connecting lines (11', 11") open into the arterial line (5), or both connecting lines (11', 11") open directly into the cell separator (7), or, particularly preferably, one connecting line (11') opens into the arterial line (5) and the other connecting line (11") opens directly into the cell separator (7). This makes it possible to connect the two connecting lines (11', 11") to different liquid containers. It is particularly preferred if one of the two connecting lines (e.g. 11') is connected to a liquid container containing a physiological saline solution (e.g.The first of the two connecting lines (e.g., 11") is connected to a container of liquid containing a citrate solution.

[0157] A further embodiment of the present invention is an apheresis device (II) for extracorporeal removal and preferably for selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1) comprises a central computing unit (10) for controlling the apheresis device (II), two connecting lines (11',11") for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), and the bypass line (12) comprises the second apheresis column (4"), a waste line (13) branches off directly from the apheresis column (4') or branches off from the plasma line (8B) in the flow direction before the confluence of the bypass line (12), and at least one regeneration line (14) which branches off from the at least one liquid container (F) or the at least one connecting line (11) and leads in the flow direction at or after, preferably after the branching of the bypass line (12), to the plasma line (8A) or opens directly into the apheresis column (4'), and wherein the second apheresis column (4") is parallel to the first apheresis column (4') is switched on and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal,ie can only be operated alternately.

[0158] According to a further embodiment of the present invention, the apheresis device (II) contains a waste line (13') which leads directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the bypass line section (12") of the bypass line joins the plasma line (8B) and a waste line (13") which leads directly from the apheresis column (4") or from the bypass line section (12") in the flow direction before the join to the plasma line (8B).

[0159] The present invention therefore also relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4') and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13') leads directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line section (12") of the bypass line (12), a waste line (13") which leads directly from the apheresis column (4") or from the plasma line (8B) in the flow direction before the opening of the Bypass line section (12") of the bypass line into the plasma line (8B) and a waste line (13"),which branches directly from the apheresis column (4") or from the bypass line section (12") in the direction of flow upstream of the confluence with the plasma line (8B), and at least one regeneration line (14) which branches off from the at least one liquid container (F) or the at least one connecting line (11) and leads in the direction of flow to or, preferably, after the branch of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') or opens directly into the apheresis column (4') or apheresis column (4"), wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal, i.e., they can only be operated alternately.

[0160] According to a further embodiment of the present invention, the apheresis device (II) further comprises at least one regeneration line (14) which extends from the at least one liquid container (F) or the at least one connecting line (11) and leads into the plasma line (8A) or into the bypass line section (12') of the bypass line (12), or opens directly into the apheresis column (4') or directly into the apheresis column (4"). According to a further embodiment of the present invention, the apheresis device (II) further comprises at least one regeneration line (14) which opens into the bypass line section (12') in a region between point (P2) and the apheresis column (4'), or into the plasma line (8A) in a region between point (P2) and the apheresis column (4"), or directly into the apheresis column (4') or directly into the apheresis column (4").

[0161] In a particularly preferred embodiment of the present invention, the apheresis device (II) comprises a waste line (13') that leads directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow upstream of the bypass line section (12") of the bypass line (12) and at least one regeneration line (14) that leads from the at least one liquid container (F) or the at least one connecting line (11) and leads into the bypass line section (12') or into the plasma line (8A) or directly into the apheresis column (4') or directly into the apheresis column (4").

[0162] Particularly preferred is an apheresis device (II) for extracorporeal removal and preferably for selective extracorporeal removal of CRP from blood or blood plasma comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for the affinity chromatographic removal of CRP from blood plasma, wherein the extracorporeal circulation system (2) comprises an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), a venous line (6) starting from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4'), and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13) branches off directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow upstream of the bypass line (12), and at least one regeneration line (14),which branches off from the at least one liquid container (F) or the at least one connecting line (11) and leads in the flow direction at or after, preferably after the branching of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or opens directly into the apheresis column (4') or directly into the apheresis column (4"), and wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal.

[0163] In a particularly preferred embodiment of the present invention, the apheresis device (II) comprises a waste line (12') that extends directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow upstream of the bypass line section (12") of the bypass line, a waste line (13") that extends directly from the apheresis column (4") or from the bypass line section (12") of the bypass line (12) in the direction of flow upstream of the bypass line section (12') of the bypass line, and at least one regeneration line (14) that extends from the at least one liquid container (F) or the at least one connecting line (11) and leads into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4'). (4") leads to.

[0164] A particularly preferred embodiment of the underlying invention relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood, comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4') and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13') which branches off directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line section (12') of the bypass line (12), a waste line (13") which branches off directly from the apheresis column (14") or from the bypass line section (12") of the Bypass line (12) in the direction of flow upstream of the confluence of the bypass line section (12') of the bypass line (12), and at least one regeneration line (14),which branches off from the at least one liquid container (F) or the at least one connecting line (11) and leads in the direction of flow to or preferably after the branch of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') of the bypass line (12) or leads directly into the apheresis column (4') or directly into the apheresis column (4"), wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal.

[0165] Furthermore, embodiments of the apheresis device (II) according to the invention are possible, wherein at least one regeneration line (13) runs to a point (P7) and a line (14') leads from point (P7) to point (P2) or opens into the plasma line (8A) and a line (14") leads from point (P7) into plasma line (8A) (see Fig. 11 ).

[0166] In the event that the at least one regeneration line (14) for the rinsing solution opens into the plasma line (8A) between the point (P2) and the apheresis column (4') or in the event that the at least one regeneration line (14) opens into the bypass line section (12') of the bypass line (12) between the point (P2) and the apheresis column (4"), the rinsing solution can be used either only for the apheresis column (4') or for the apheresis column (4"). The regeneration line (14) is thus either selective to the apheresis column (4') or selective to the apheresis column (4").

[0167] Likewise, embodiments of the apheresis device (II) according to the invention are possible with two, three or more regeneration lines (14', 14", 14'', etc.), wherein these two, three or more regeneration lines can lead independently of one another into the plasma line (8A) [i.e. from point (P2) to the apheresis column (4')] or into the bypass line section (12') [i.e. from point (P2) to the apheresis column (4")] or into the apheresis column (4') or into the apheresis column (4").In this context, "independent of one another" means that in an embodiment of the apheresis devices according to the invention with two regeneration lines (14', 14"), one regeneration line (14') opens into the plasma line (8A) between the point (P2) and the apheresis column (4') and the other regeneration line (14") opens directly into the apheresis column (4'), but also that both regeneration lines (14', 14") can open into the plasma line (8A) between the point (P2) and the apheresis column (4'). Another possibility is that one regeneration line (14') opens into the extracorporeal circulation system (2) at point (P2) and the other regeneration line (14") opens into the bypass line section (12') of the bypass line (12) between point (P2) and the apheresis column (4").It is also conceivable that one regeneration line (14') connects to the extracorporeal circulation system at point (P2) and the other regeneration line (14") connects to the apheresis column (4"). It is also possible that one regeneration line (14') connects to the other regeneration line (14"). However, if two or more regeneration lines (14', 14", 14"', etc.) are present, it is preferable that all regeneration lines (14', 14", 14"', etc.) connect to the extracorporeal circulation system (2) at point (P2).

[0168] It is further preferred if one regeneration line (14') opens into the bypass line section (12') of the bypass line (12) between the point (P2) and the apheresis column (4') and the other regeneration line (14") opens into the bypass line section (12') of the bypass line (12) between the point P2 and the apheresis column (4"). It is further preferred if the regeneration line (14') opens into the apheresis column (4') and the other regeneration line (14") opens into the apheresis column (4"). In this case, the regeneration line (14') is selective to the first apheresis column (4') and the regeneration line is selective to the second apheresis column (4").

[0169] According to a particularly preferred embodiment of the present invention, the apheresis device (II) therefore further comprises a regeneration line (14') for a rinsing solution selectively to the first apheresis column (4') and / or further a regeneration line (14") for a rinsing solution selectively to the second apheresis column (4").

[0170] Therefore, one embodiment of the present invention relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and opens into the plasma line (8B), and the bypass line (12) comprises the second apheresis column (4"), a waste line (13) branches directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow upstream of the inlet of the bypass line (12), and a regeneration line (14') for a rinsing solution selectively to the first apheresis column (4') and / or a regeneration line (14") for a rinsing solution selectively to the second apheresis column (4"), and wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") are not can be used simultaneously with CRP removal, i.e., they can only be operated alternately.

[0171] As mentioned above, the regeneration solution required for the regeneration of the apheresis columns can be fed into the extracorporeal circulation system (2) via the regeneration line (14), and thus a regeneration solution (e.g. a citrate solution, a TRIS glycine solution, or a sodium chloride solution) can be used in addition to the rinsing solution.The rinsing solution can, but does not have to, serve to regenerate the first apheresis column (4') and / or apheresis column (4"). In addition to the function mentioned above, it has the task of displacing the blood plasma from the plasma line (8A) in the area from point (P2) to the apheresis column (4') and from the plasma line (8B) from the apheresis column (4') to point (P8), or the blood plasma from the bypass line section (12') of the bypass line (12) in the area from point (P2) to the apheresis column (4") and from the bypass line section (12") of the bypass line (12) from the apheresis column (4") to point (P8), thus returning it to the patient's bloodstream before the regeneration solution is used. After passing through one of the two apheresis columns (4', 4"), the regeneration solution then flows via the drainage line. (13', 13") is discarded.

[0172] Thus, it is conceivable that the parallel connected apheresis columns (4', 4") can not only be operated alternately, but also regenerated alternately.

[0173] In the apheresis devices (II) described herein according to the invention, the first apheresis column (4') can be replaced or regenerated during the operation of the second apheresis column (4") and the second apheresis column (4") can be replaced or regenerated during the operation of the first apheresis column (4').

[0174] One embodiment of the present invention is therefore directed to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood or blood plasma comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4') and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13') which branches off directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line section (12') of the bypass line (12), a waste line (13") which branches off directly from the apheresis column (14") or from the bypass line section (12") of the Bypass line (12) in the direction of flow upstream of the confluence of the bypass line section (12') of the bypass line (12), and at least one regeneration line (14),which branches off from the at least one liquid container (F) or the at least one connecting line (11) and leads in the flow direction at or after, preferably after the branching of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') of the bypass line (12) or opens directly into the apheresis column (4') or directly into the apheresis column (4"), and wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") can only be operated alternately, and wherein the first apheresis column (4') is replaceable or regenerable during the operation of the second apheresis column (4") and the second apheresis column (4") is replaceable or regenerable during the operation of the first apheresis column (4').

[0175] Furthermore, embodiments of the present invention are conceivable in which the apheresis device has a regeneration line (14) for each liquid container (F), which regeneration line (14) branches off from the respective liquid container (F) or its connecting line (11) and which leads into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4").

[0176] A particularly preferred embodiment of the underlying invention relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood, comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4') and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13') which branches off directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line section (12') of the bypass line (12), a waste line (13") which branches off directly from the apheresis column (14") or from the bypass line section (12") of the Bypass line (12) in the direction of flow before the confluence of the bypass line section (12') of the bypass line (12), and each liquid tank (F) contains a regeneration line (14),which branch off from the respective liquid container (F) or its connecting line (11) and lead in the direction of flow to or, preferably, after the branch of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') of the bypass line (12), or lead directly into the apheresis column (4') or directly into the apheresis column (4"), wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal.

[0177] Furthermore, embodiments of the apheresis device (II) are preferred in which the apheresis device (II) has at least two connecting lines (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), and wherein a regeneration line (13) exists for each liquid container (F) that leads from the respective liquid container (F) or its connecting line (11) and that lead into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4").

[0178] According to some embodiments of the present invention, it is preferred that the at least one regeneration line (14) leading into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4") starts from a point (P5) in the at least one connecting line (11).

[0179] The present invention therefore also relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4') and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13) branches directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow upstream of the inlet of the bypass line (12), and at least one regeneration line (14),which branches off from a point (P5) in the at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7) and leads in the direction of flow to or preferably after the branch of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') of the bypass line (12) or leads directly into the apheresis column (4') or directly into the apheresis column (4"), wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal.

[0180] A preferred apheresis device (II) is wherein the apheresis device (II) has two connecting lines (11', 11') for connecting each of a liquid container (F1, F2) to the arterial line (5) or the cell separator (7), and two regeneration lines (14', 14") extend from two liquid containers (F1, F2) or the two connecting lines (11', 11") and lead into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4").

[0181] A particularly preferred embodiment of the underlying invention relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood, comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1) comprises a central computing unit (10) for controlling the apheresis device (II), two connecting lines (11', 11") for connecting two liquid containers (F1,F2) to the arterial line (5) or the cell separator (7), characterized in that a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4') and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13') which branches off directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line section (12') of the bypass line (12), a waste line (13") which branches off directly from the apheresis column (14") or from the bypass line section (12") of the bypass line (12) in the flow direction before the opening of the Bypass line section (12') of the bypass line (12), and two regeneration lines (14', 14"), which are connected to the two liquid containers (F1, F2) or the two connecting lines (11',11") branch off and, in the direction of flow, leads to or preferably after the branch of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') of the bypass line (12), or leads directly into the apheresis column (4') or directly into the apheresis column (4"), wherein the second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal, i.e., they can only be operated alternately.

[0182] Likewise, embodiments are conceivable in which a regeneration line (14) leading into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4") and which has at least one additional connection for a liquid container from a point (P5) in which at least one connecting line (11) originates ( Fig. 16).

[0183] In embodiments of the present invention with multiple connecting lines (11', 11", 11‴, etc.) and multiple regeneration lines (14', 14", 14'', etc.) it is possible that each connecting line is connected to each regeneration line, which in turn leads after point (P2) into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4"). Each regeneration line can open independently of the other regeneration lines into the plasma line (8A), into the bypass line section (12') of the bypass line (12), or directly into the apheresis column (4') or directly into the apheresis column (4"). However, it is preferred that all regeneration lines open directly into the apheresis columns (4'; 4"), preferably at point (P2) into the extracorporeal circulation system (2). Such an exemplary embodiment is shown by reference to Fig. 7explained. Here, the apheresis device (II) has a first connecting line (11'), which firstly leads into the arterial line (5) and from which, secondly, a first regeneration line (14') branches off at point (P5'). The apheresis device (II) also has a second connecting line (11"), which firstly leads directly into the cell separator (7) and from which, secondly, a second regeneration line (14") branches off at point (P5'). In this embodiment, both regeneration lines open into the extracorporeal circulation system (2) at point (P2).

[0184] A preferred apheresis device (II) is therefore apheresis device, wherein the apheresis device (II) has two connecting lines (11', 11") for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), and wherein the at least one regeneration line (14), which leads into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4"), connects to the connecting line (11') at a point (P5') and to the connecting line (11") at a point (P5").

[0185] A preferred embodiment of the underlying invention relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1) comprises a central computing unit (10) for controlling the apheresis device (II), two connecting lines (11',11") for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4'), and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13') which branches off directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line section (12') of the bypass line (12), a waste line (13") which branches off directly from the apheresis column (14") or from the bypass line section (12") of the bypass line (12) in the direction of flow upstream of the confluence of the bypass pipe section (12') of the bypass pipe (12), and at least one regeneration pipe (14),which leads into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4"), connects at a point (P5') to the connecting line (11') and at a point (P5") to the connecting line (11"), which branches off from the at least one liquid container (F) or the at least one connecting line (11) and leads in the flow direction at or after, preferably after the branching of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') of the bypass line (12) or opens directly into the apheresis column (4') or directly into the apheresis column (4"), and wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and Both apheresis columns (4', 4") cannot be used simultaneously for CRP removal.

[0186] Thus, embodiments of the apheresis device are particularly preferred, wherein the apheresis device (II) has two connecting lines (11', 11") for connecting each of a liquid container (F1, F2) to the arterial line (5) or the cell separator (7), and wherein the at least one regeneration line (14), which leads into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4"),connects at a point (P5') to the connecting line (11') and at a point (P5") to the connecting line (11"), wherein a regeneration line (14') leads from the liquid reservoir (F1) or from the connecting line (11') leading from the liquid reservoir (F1) to the apheresis column (4') or to the apheresis column (4") or to the plasma line (8A') or to the plasma line (8A"), and a regeneration line (14") leads from the liquid reservoir (F2) or the connecting line (11") leading from the liquid reservoir (F2) to the apheresis column (4') or to the apheresis column (4") or to the plasma line (8A) or to the bypass line section (12') of the bypass line (12) or into the regeneration line (14').

[0187] Preferably, the liquid container (F1) contains a physiological solution and the liquid container (F2) contains a citrate solution.

[0188] Thus, it is particularly preferred if the apheresis device (II) has a connecting line (11') for connecting a liquid container (F1) and a connecting line (11') for connecting a liquid container (F2), and the connecting line (11') opens into the arterial line (5) or into the cell separator (7), and the connecting line (11") opens into the arterial line (5) or into the cell separator (7) or into the connecting line (11') and thus ultimately also into the arterial line (5) or into the cell separator (7), and a regeneration line (14') leads from the liquid container (F1) or from the connecting line (11') to the apheresis column (4') or to the apheresis column (4") or to the plasma line (8A) or to the plasma line (8A"), and a regeneration line (14") leads from the liquid container (F2) or from the connecting line (11") to the apheresis column (4') or to the apheresis column (4") or to the plasma line (8A') or to the bypass line section (12') of theBypass line (12) or into the regeneration line (14').

[0189] Embodiments of the apheresis device (II) are therefore particularly preferred in which the apheresis devices (II) have a connecting line (11') for connecting a liquid container (F1) to the arterial line (5) or the cell separator (7) and a connecting line (11") for connecting a liquid container (F2) to the arterial line (5) or the cell separator (7),and wherein a regeneration line (14') branches off from the liquid reservoir (F1) or the connecting line (11') and leads into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4') or directly into the apheresis column (4") and a regeneration line (14") branches off from a liquid reservoir (F2) or the connecting line (11") and leads into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or into the regeneration line (14') or directly into the apheresis column (4") or directly into the apheresis column (4").

[0190] A preferred embodiment of the underlying invention relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11') for connecting a liquid container (F1) to the arterial line (5) or the cell separator (7) and a connecting line (11") for connecting a liquid container (F2) to the arterial line (5) or the cell separator (7), characterized in that a bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and opens into the second apheresis column (4') and the bypass line section (12") of the bypass line (12") opens from the apheresis column (4") into the plasma line (8B), a waste line (13') which branches off directly from the apheresis column (4') or from the plasma line (8B) in the flow direction before the opening of the bypass line section (12') of the bypass line (12), a Waste pipe (13"),which branches directly from the apheresis column (14") or from the bypass line section (12") of the bypass line (12) in the direction of flow upstream of the junction of the bypass line section (12') of the bypass line (12), and a regeneration line (14') branches off from the liquid reservoir (F1) or the connecting line (11') and leads in the direction of flow to or, preferably, after the branch of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') of the bypass line (12) or leads directly into the apheresis column (4') or directly into the apheresis column (4"),and a regeneration line (14") branches off from a liquid container (F2) or the connecting line (11") and leads in the direction of flow to or, preferably, after the branch of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') of the bypass line (12), or opens directly into the apheresis column (4') or directly into the apheresis column (4"), wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal.

[0191] Preferably, the liquid container (F1) is a container for a physiological sodium chloride solution and the liquid container (F2) is a container for a citrate solution.

[0192] The present invention is therefore also directed to an apheresis device (II) according to the invention, wherein the plasma line (8A) and the bypass line section (12') of the bypass line (12) diverge from a point (P2), and the plasma line (8B) and the bypass line section (12") of the bypass line (12) converge at point (P6), and the waste line (13') branches off from a point (P4) from the plasma line (8B) and the waste line (13") branches off from a point (P8) from the bypass line section (12") of the bypass line (12), and the at least one regeneration line (14) opens into the extracorporeal circulation system (2) at point (P2).

[0193] A preferred embodiment of the underlying invention relates to an apheresis device (II) for the extracorporeal removal and preferably for the selective extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generating and regulating a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separating blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood plasma, the extracorporeal circulation system (2) having an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1), and a venous line (6) extending from the point (P1), a central processing unit (10) for controlling the apheresis device (II),at least one connecting line (11) for connecting at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a , Bypass pipe section (12') the bypass line (12) branches off from the plasma line (8A) and leads into the second apheresis column (4') and the Bypass pipe section (12") the bypass line (12") starting from the apheresis column (4") into the plasma line (8B), a waste line (13') that branches directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow before the confluence of the Bypass line section (12') branching off the bypass line (12), a waste line (13") branching directly off the apheresis column (14") or off the bypass line section (12") of the bypass line (12) in the direction of flow before the confluence of the Bypass line section (12') of theBypass line (12), wherein the plasma line (8A) and the bypass line section (12') of the bypass line (12) diverge from a point (P2), and the plasma line (8B) and the bypass line section (12") of the bypass line (12) converge at a point (P6), and at least one regeneration line (14) which branches off from the at least one liquid container (F) or the at least one connecting line (11) and leads in the flow direction at or after, preferably after the branching of the bypass line section (12') of the bypass line (12) to the plasma line (8A) or to the bypass line section (12') of the bypass line (12) or opens directly into the apheresis column (4') or directly into the apheresis column (4"), and the waste line (13') from a point (P4) of the Plasma line (8B) branches off and the waste line (13") branches off from a point (P8) of the bypass line section (12") of the bypass line (12),and which at least one regeneration line (14) opens into the extracorporeal circulation system (2) at point (P2), and wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal, i.e., they can only be used alternately.

[0194] To further reduce the dead volume of the system, it is even more preferred if not only the regeneration line (14) opens into the extracorporeal circulation system at the point (P2) where the plasma line (8A) and the bypass line section (12') of the bypass line (12) diverge, but also if the drain lines (13', 13") branch off from the same point (P6) where the plasma line (8B) and the bypass line section (12") of the bypass line (12) meet. In other words, it is preferred if the point (P6) at which the plasma lines (8B) and the bypass line section (12") of the bypass line (12) converge, the point (P8) at which the waste line (13") branches off and the point (P4) at which the waste line (13') branches off coincide, ie if P8 = P4 = P6 (see Fig. 12 and Fig. 13 ).

[0195] The present invention is therefore also directed to an apheresis device (II) according to the invention, wherein the plasma line (8B) and the bypass line section (12") of the bypass line (12) converge at a point (P6), and the waste line (13") branches off from a point (P8) from the bypass line section (12") of the bypass line (12), and the waste line (13') branches off from a point (P4) from the plasma line (8B), and the at least one regeneration line (14) opens into the extracorporeal circulation system (2) at point (P2), and wherein point (P6), point (P4), and point (P8) are identical.

[0196] According to the present invention, an embodiment of the apheresis device (II) for the extracorporeal removal of CRP from blood comprises two apheresis columns (4', 4") for affinity chromatographic removal of CRP from the blood or blood plasma, the function of which is to bind CRP which is located in the blood or blood plasma of a patient and which is passed through the apheresis column (4') or (4"). Proceedings

[0197] A non-claimed method for regenerating an apheresis column (4) for affinity chromatographic removal of CRP in an apheresis device (1) is described, wherein the method enables regeneration during operation and is characterized by the following steps: (A) Commencement of the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thereby stopping the introduction of the separated plasma from the plasma line (8A) into the apheresis column (4), (B) Commencement of the introduction of regeneration solution via at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (C) Commencement of the diversion of the fluid flow exiting the apheresis column (4) from the plasma line (8B) into the waste line (13), (D) Stopping of the introduction of regeneration solution and stopping the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thereby introducing the separated plasma from the plasma line (8A) into the apheresis column (4), (E) Closure of the waste line (13) and forwarding of the fluid exiting the apheresis column (4) Fluid flow into the venous line (6).

[0198] The term "stopping the introduction of the separated plasma" according to step (A) may, depending on the embodiment, be understood to mean the use of hose clamps, control elements, valves and / or peristaltic pumps to prevent the further flow of blood plasma into the plasma line (8A) or into the bypass line section (12') of the bypass line (12) or into the apheresis column (4') or (4").

[0199] The term "stopping the introduction of regeneration solution" according to step (D) can, depending on the embodiment, be understood to mean the use of hose clamps, control elements, valves, and / or peristaltic pumps to prevent the further flow of regeneration solution into the plasma line (8A) or into the apheresis column (4). It should be understood that in embodiments where only one regeneration solution is used, the introduction of that solution is stopped. In embodiments where several regeneration solutions are successively introduced, this means that the introduction of the last used regeneration solution is stopped, and thus the introduction of any regeneration solution is also terminated.

[0200] The term "closing the waste line (13)" according to step (E) can, depending on the embodiment, be understood to mean the use of hose clamps, control elements, valves and / or peristaltic pumps to prevent the further flow of the fluid exiting the apheresis column (4). It should be understood that in embodiments where only one regeneration solution is used, the introduction of this solution is stopped. In embodiments where several regeneration solutions are successively introduced, this means that the introduction of the last used regeneration solution is stopped, and thus the introduction of any regeneration solution is also terminated.By "forwarding the fluid flow exiting the apheresis column (4)" according to step (E), the separated plasma flows back into the plasma line (8B) after passing through the apheresis column (4) and from there through the venous line (6) back to the patient. Depending on the design, hose clamps, control elements, valves, and / or peristaltic pumps can be used to change the flow direction of the fluid flow exiting the apheresis column (4).

[0201] Furthermore, the present disclosure relates to a method for regenerating an apheresis column (4) for the affinity chromatographic removal of CRP in an apheresis device (1) as described herein, wherein the method enables regeneration during operation by switching from an apheresis mode to a regeneration mode, wherein in the apheresis mode, plasma separated from blood by means of the cell separator (7) is passed into the apheresis column (4) via the plasma line (8A) and the liquid stream emerging from the apheresis column (4) is passed into the venous line (6) via the plasma line (8B); and wherein the regeneration mode is characterized by the following steps: (A) Commencement of the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thus stopping the flow of the separated plasma from the plasma line (8A) into the apheresis column (4), (B) Commencement of the introduction of regeneration solution via at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (C) Commencement of the diversion of the fluid flow exiting the apheresis column (4) from the plasma line (8B) into the waste line (13), (D) Stopping of the introduction of regeneration solution and stopping the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thus stopping the flow of the separated plasma from the plasma line (8A) into the apheresis column (4), (E) Closure of the waste line (13) and forwarding of the fluid exiting the apheresis column (4) fluid flow into the venous line (6) and thus a switch back to apheresis mode.

[0202] With regard to the two aforementioned methods, the regeneration solution is preferably a saline solution or physiological NaCl solution.

[0203] Furthermore, methods are preferred in which step (C) is initiated after a total volume X of regeneration solution(s) has been introduced into the plasma line (8A) or directly into the apheresis column (4), wherein X corresponds to at least 75% of the volume of the device between the point where the regeneration line (14) opens into the extracorporeal circulation system (2) in the direction of flow, preferably after the branch of the bypass line (12), and the point where the waste line (13) originates from the extracorporeal circulation system (2). Here, the regeneration solution is, for example, a saline solution or a physiological saline solution.

[0204] Furthermore, methods are preferred in which step (E) is initiated after a volume Y of plasma has been introduced into the plasma line (8A) or directly into the apheresis column (4), wherein Y corresponds to at least 90% of the volume of the device between the point where the regeneration line (14) opens into the extracorporeal circulation system (2) in the direction of flow, preferably after the branch of the bypass line (12), and the point where the waste line (13) originates from the extracorporeal circulation system (2).

[0205] "In operation",As used herein, this means that the blood collection and supply, as well as the operation of the cell separator, do not need to be stopped to perform the procedure for regenerating an apheresis column (4). In other words, during the procedure for regenerating an apheresis column (4), the continuously collected plasma is combined with the cell components via the bypass line (12), bypassing the apheresis column (4), and then returned to the patient. During the time it takes for the plasma to be diverted via the bypass line (12), the apheresis column (4), which is usually reduced in capacity, is regenerated. Thus, the patient's circulatory system is not burdened because the continuously collected blood is returned to the patient without delay.

[0206] "During operation" as used herein does not mean that continuous plasma collection must be interrupted to carry out the process for regenerating an apheresis column (4). Furthermore, it does not mean that CRP depletion takes place during the regeneration of the apheresis column.

[0207] Thus, in the two aforementioned methods and those generally disclosed herein, it is preferred that the introduction of regeneration solution comprises the introduction of a single regeneration solution or the successive introduction of multiple regeneration solutions.

[0208] It is perfectly clear to those skilled in the art that an initial flushing process of the adsorber or the entire system must have taken place before carrying out the method according to the invention. This involves pre-filling the entire tubing system. Additional connections may be present on the system for this purpose, enabling flushing of the entire system. After the patient has been disconnected from the tubing system, the adsorber can be preserved so that it can be reused for further treatment on the same patient.

[0209] In other words, the present disclosure also relates to a method for regenerating an apheresis column (4) for the affinity chromatographic removal of CRP in the apheresis device (1), wherein the method enables regeneration during operation and is characterized by the following steps: (A) Diverting the separated plasma from the plasma line (8A) into the bypass line (12), (B) Introducing at least one regeneration solution from a liquid container on the connecting line (11) via the regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (C) Diverting the liquid flow emerging from the apheresis column (4) from the plasma line (8B) into the waste line (13), (D) Diverting the separated plasma from the plasma line (8A) into the apheresis column (4) and stopping the introduction of regeneration solution, (E) Closing the waste line (13) and passing the liquid flow emerging from the apheresis column (4) into the venous line (6).

[0210] The term "diversion" as used herein refers to a change in the flow direction of the respective fluid. During the treatment mode, the separated plasma flows through the plasma line (8A) into the apheresis column (4). After leaving the apheresis column (4), the depleted plasma flows through the plasma line (8B) into the venous line (6).

[0211] By "diverting" the flow direction of the separated plasma according to step (A), the separated plasma no longer flows through the apheresis column (4), but bypasses it by being diverted into the bypass line (12).

[0212] The term "introduction" as used herein according to step (B) can, depending on the embodiment of the present invention, be understood to mean the injection of at least one regeneration solution (using or actuating hose clamps, control elements, valves and / or peristaltic pumps) into the plasma line (8A) or into the apheresis column (4).

[0213] By "diverting" the flow direction of the liquid stream exiting the apheresis column (4) according to step (C), the exiting liquid no longer flows into the plasma line (8B) but directly into the waste line (13). According to the invention, it is preferred that the waste line (13) branches off directly from or immediately after the apheresis column (4) in order to minimize the volume of regeneration solution required to regenerate the apheresis column (4). Within the meaning of the disclosure, the waste line (13) can also branch off from the plasma line (8B) and thus does not have to branch off directly from the apheresis column.

[0214] By "diverting" the flow direction of the separated plasma according to step (D), the separated plasma now flows again through the apheresis column (4) and no longer into the bypass line (12). In certain embodiments, a pump is provided in the bypass line (12), whereby the plasma present in the bypass line (12), after diversion according to step (D), is pumped into the plasma line (8B) and via the venous line (6) into the patient. Preferably, the plasma in the bypass line is displaced from the regeneration line (14) by a NaCl solution. Preferably, this is a 0.9% NaCl solution. It would also be conceivable to connect a separate fluid reservoir to the bypass line (12) through which the aforementioned NaCl solution is supplied for displacement.

[0215] Therefore, a particularly preferred embodiment relates to a method for regenerating an apheresis column (4) for affinity chromatographic removal of CRP in the apheresis device (1), wherein the method enables regeneration during operation and is characterized by the steps disclosed in the following method.

[0216] A method for regenerating an apheresis column (4) for affinity chromatographic removal and preferably for selective extracorporeal removal of CRP in an apheresis device (1) is therefore particularly preferred, wherein the method is characterized by the following steps: (A) Starting the diversion of the separated plasma from the plasma line (8A) into the bypass line (12) and thus stopping the flow of the separated plasma from the plasma line (8A) into the apheresis column (4), (B) Starting the introduction of a rinsing solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (C) Starting the diversion of the liquid flow exiting the apheresis column (4) from the plasma line (8B) into the waste line (13), (D) Stopping the introduction of the rinsing solution and transitioning to the introduction of a regeneration solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (E) Stopping the introduction of the regeneration solution and transitioning to the introduction of the rinsing solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4),(F) Stopping the introduction of rinsing solution and stopping the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thus diverting the separated plasma from the plasma line (8A) into the apheresis column (4); (G) Closing the waste line (13) and diverting the fluid flow exiting the apheresis column (4) into the venous line (6).

[0217] Alternatively, a method for regenerating an apheresis column (4) for affinity chromatographic removal and preferably for the selective affinity chromatographic removal of CRP in an apheresis device (1) is also particularly preferred, wherein the method is characterized by the following steps: (A) Commencement of the diversion of the separated plasma from the plasma line (8A) into the bypass line (12) and thus cessation of the flow of the separated plasma from the plasma line (8A) into the apheresis column (4), (B) Commencement of the introduction of a rinsing solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (C) Cessation of the introduction of the rinsing solution and transition to the introduction of a regeneration solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (D) Commencement of the diversion of the fluid flow exiting the apheresis column (4) from the plasma line (8B) into the waste line (13), (E) Cessation of the introduction of the regeneration solution and transition to the introduction of the rinsing solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4),(F) Closing the waste line (13) and directing the fluid flow exiting the apheresis column (4) into the venous line (6); (G) Stopping the introduction of rinsing solution and stopping the diversion of the separated plasma from the plasma line (8A) into the bypass line (12) and thus directing the separated plasma from the plasma line (8A) into the apheresis column (4).

[0218] In both of the aforementioned procedures, a rinsing solution is used in addition to the regeneration solution. The rinsing solution is preferably physiologically compatible and primarily serves to displace the blood plasma from the plasma line (8A) from point P2, from the apheresis column (4), and from the plasma line (8B) up to point P4. The rinsing solution serves less or not at all for the regeneration of the apheresis column (4). Therefore, the rinsing solution minimizes or even completely prevents plasma loss. Only when the blood plasma has been largely or completely displaced from the section of the apheresis device (1) to be flushed with the regeneration solution is the regeneration solution introduced to regenerate the apheresis column (4).After regeneration has taken place, rinsing solution is then fed into the section of the apheresis device (1) flushed with regeneration solution (i.e. in the direction of flow from point P2 through the apheresis column (4) to point P4) until the regeneration solution has been completely disposed of through the waste line (13). Only then is the bypass line (12) closed and blood plasma is again fed through the apheresis column (4). In the two aforementioned processes, steps (C) and (D) are interchangeable, ie they can be carried out in any order and at the same time, and can also be combined into one step. However, performing step (D) before step (C) is preferred.

[0219] In this procedure, the rinsing solution is preferably a physiological NaCl solution and the regeneration solution is a citrate solution.

[0220] The preferred embodiment of the method serves to carry out the procedure more efficiently without loss of blood plasma. Due to the simultaneous diversion of the separated plasma and the parallel introduction of the rinsing solution into the apheresis column (4), no loss or no significant loss of blood plasma occurs. Furthermore, the preferred embodiment is advantageous in that mixing of the regeneration solution and blood plasma is completely avoided. This ensures that no regeneration solution enters the patient and, conversely, that no loss of blood plasma occurs for the patient.

[0221] This is ensured by the sequential order of steps (B) to (E). Any dilution of the blood plasma, if it occurs at all, is solely due to the use of rinsing solution. Conversely, any mixing of blood plasma with regeneration solution is completely avoided.

[0222] The volume of rinsing solution according to step (B) preferably corresponds to 3 to 4 times the volume of the matrix of the apheresis column (4).

[0223] At a minimum, the volume of rinsing solution according to step (B) corresponds to the volume of the plasma line (8A) from point P2 to the apheresis column (4) plus the volume of the matrix of the apheresis column (4) and plus the volume of the plasma line (8B) from the apheresis column (4) to point P4.

[0224] The volume of regeneration solution according to step (C) preferably corresponds to 2 to 100 times the volume of the matrix of the apheresis column (4).

[0225] The volume of rinsing solution according to step (E) preferably corresponds to 2 to 4 times the volume of the matrix of the apheresis column (4).

[0226] At least the volume of rinsing solution according to step (E) corresponds to the volume of the plasma line (8A) from point P2 to the apheresis column (4) plus the volume of the matrix of the apheresis column (4) and plus the volume of the plasma line (8B) from the apheresis column (4) to point P4.

[0227] According to this even more preferred embodiment, plasma dilution is largely avoided and mixing with regeneration solution is completely prevented. The user is not confronted with excessive complexity regarding the operation of the apheresis device (1). In an alternative embodiment, the process steps can therefore also be operated manually without appearing or being too complex for the user.

[0228] The "volume of the apheresis column matrix," as used herein, refers to the volume of the solid phase within the column, which in turn comprises a matrix substrate material and compounds bound to it that have the property of specifically binding CRP. This is distinct from the "dead volume of the apheresis column," i.e., the space within the column available to the mobile phase (e.g., plasma). The "dead volume of the apheresis column" is the difference between the volume enclosed by the column casing and the volume occupied by the swollen matrix (i.e., the "volume of the apheresis column matrix").

[0229] A further aspect of the present disclosure is directed to a method for regenerating an apheresis column (4') for affinity chromatographic removal and preferably for selective affinity chromatographic removal of CRP during the ongoing operation of a second apheresis column (4") in an apheresis device (II), comprising the following steps: (A) Starting from the flow of blood plasma through the apheresis column (4"), the separated blood plasma is introduced via the plasma line (8A) into the apheresis column (4') and the CRP-depleted blood plasma is directed into the venous line (6), thus stopping the introduction of the separated plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4"), (B) the introduction of regeneration solution via at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (C) the diversion of the fluid flow exiting the apheresis column (4") from the bypass line section (12") of the bypass line (12) into the waste line (13") begins,(D) Start of the introduction of the separated blood plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4") and directing the CRP-depleted plasma into the venous line (6) and thus stopping the introduction of the separated blood plasma via the plasma line (8A) into the apheresis column (4'). (E) Closing the waste line (13") and starting the diversion of the liquid flow emerging from the apheresis column (4') from the plasma line (8B) into the waste line (13').

[0230] With regard to the two aforementioned methods, the regeneration solution is preferably a saline solution or physiological NaCl solution.

[0231] "In operation"As used in this context, this means that, in order to carry out the inventive method for regenerating an apheresis column (4') or regenerating an apheresis column (4"), the blood withdrawal and supply as well as the operation of the cell separator do not have to be stopped. Thus, the patient's circulatory system is not burdened because the continuously withdrawn blood is returned to the patient without delay.

[0232] In other words, in one embodiment, the present disclosure relates to a method for regenerating an apheresis column (4') for affinity chromatographic removal and preferably for selective affinity chromatographic removal of CRP during the ongoing operation of a second apheresis column (4") in an apheresis device (II), comprising the following steps: (A) Starting from the flow of blood plasma through the apheresis column (4"), the separated plasma is introduced via the plasma line (8A) into the apheresis column (4') and the CRP-depleted plasma is directed into the venous line (6), thus stopping the introduction of the separated plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4"), (B) at least one regeneration solution is introduced from a liquid container at the connecting line (11) via the at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (C) the fluid flow exiting the apheresis column (4") is diverted from the bypass line section (12") of the bypass line (12) into the waste line (13"),(D) Introducing the separated plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4") and directing the CRP-depleted plasma into the venous line (6) and thus stopping the introduction of the separated plasma via the plasma line (8A) into the apheresis column (4'). (E) Closing the waste line (13") and diverting the liquid flow emerging from the apheresis column (4') from the plasma line (8B) into the waste line (13').

[0233] Furthermore, the present disclosure relates to a method for regenerating two apheresis columns (4', 4") for affinity chromatographic removal and preferably for selective affinity chromatographic removal of CRP in an apheresis device (II), wherein the method enables regeneration during operation and is characterized by the following steps: (A) Starting from the flow of blood plasma through the apheresis column (4"), the separated plasma is introduced via the plasma line (8A) into the apheresis column (4') and the CRP-depleted plasma is directed into the venous line (6), thus stopping the introduction of the separated plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4"), (B) a rinsing solution is introduced via at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (C) the fluid flow exiting the apheresis column (4") is introduced from the bypass line section (12") of the bypass line (12) into the waste line (13"),(D) Stopping the introduction of the rinsing solution and switching to the introduction of the regeneration solution via the at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (E) Stopping the introduction of the regeneration solution and switching to the introduction of the rinsing solution via the at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (F) Starting the introduction of the rinsing solution into the plasma line (8A) via the apheresis column (4") and thus introducing the separated plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4"), (G) Closing the waste line (13") and forwarding the fluid flow exiting the apheresis column (4") into the venous line (6),(H) Commencement of the diversion of the fluid flow exiting the apheresis column (4') from the plasma line (8B) to the waste line (13'), (I) Stopping of the introduction of the rinsing solution and transition to the introduction of a regeneration solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4'). (J) Stopping of the introduction of the regeneration solution and transition to the introduction of the rinsing solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4').

[0234] In both of the aforementioned procedures, a rinsing solution is used in addition to the regeneration solution. The rinsing solution is preferably physiologically compatible and primarily serves to displace the blood plasma from the plasma line (8A) or the bypass line section (12') of the bypass line (12) from point P2, from the apheresis column (4') or apheresis column (4"), as well as from the bypass line section (12") of the bypass line (12) up to point P3, and from the plasma line (8B) up to point P4. The rinsing solution is of little or no use for regenerating the apheresis column (4') or the apheresis column (4"). Therefore, the rinsing solution minimizes or even completely prevents plasma loss. Only when the blood plasma has been largely or completely displaced from the section of the apheresis device (II) to be rinsed with regeneration solution is the regeneration solution introduced to regenerate the apheresis column (4') or the apheresis column (4").After regeneration has been completed, rinsing solution is then introduced again into the section of the apheresis device (II) that has been flushed with regeneration solution (i.e., in the direction of flow from point P2 through the apheresis column (4") to point P8) or through the apheresis column (4') to point P4) until the regeneration solution has been completely disposed of through the waste lines (13', 13").

[0235] In this procedure, the rinsing solution is preferably a physiological NaCl solution and the regeneration solution is a citrate solution.

[0236] The preferred embodiment of the method serves to carry out the process more efficiently without loss of blood plasma. Due to the simultaneous diversion of the separated plasma and the parallel introduction of the rinsing solution into the apheresis column (4"), no loss or no significant loss of blood plasma occurs. Furthermore, the preferred embodiment is advantageous in that mixing of the regeneration solution and blood plasma is completely avoided.

[0237] This ensures that no regeneration solution enters the patient and, conversely, that the patient does not experience any loss of blood plasma.

[0238] This ensures that no regeneration solution enters the patient and, conversely, that the patient does not experience any loss of blood plasma.

[0239] This is ensured by the sequential order of steps (B) to (E). Any dilution of the blood plasma, if it occurs at all, is solely due to the use of rinsing solution. Conversely, any mixing of blood plasma with regeneration solution is completely avoided.

[0240] The volume of rinsing solution according to step (B) preferably corresponds to 3 to 4 times the volume of the matrix of the apheresis column (4"). At a minimum, the volume of rinsing solution according to step (B) corresponds to the volume of the bypass line section (12') of the bypass line (12) from point P2 to the apheresis column (4") plus the volume of the matrix of the apheresis column (4") and plus the volume of the bypass line section (12') of the bypass line (12) from the apheresis column (4") to point (P3).

[0241] The volume of rinsing solution according to step (F) preferably corresponds to 3 to 4 times the volume of the matrix of the apheresis column (4'). At a minimum, the volume of rinsing solution according to step (B) corresponds to the volume of the plasma conduit (8A') from point (P2) to the apheresis column (4') plus the volume of the matrix of the apheresis column (4') and plus the volume of the plasma conduit (8B) from the apheresis column to point (P4).

[0242] The volume of regeneration solution according to step (D) preferably corresponds to 2 to 100 times the volume of the matrix of the apheresis column (4").

[0243] The volume of regeneration solution according to step (I) preferably corresponds to 2 to 100 times the volume of the matrix of the apheresis column (4').

[0244] The volume of rinsing solution according to step (E) preferably corresponds to 2 to 4 times the volume of the matrix of the apheresis column (4").

[0245] At least the volume of rinsing solution according to step (E) corresponds to the volume of the bypass line section (12') of the bypass line (12) from point P2 to the apheresis column (4") plus the volume of the matrix of the apheresis column (4") and plus the volume of the bypass line section (12') of the bypass line (12) from the apheresis column (4') to point P3.

[0246] The volume of rinsing solution according to step (J) preferably corresponds to 2 to 4 times the volume of the matrix of the apheresis column (4').

[0247] At least the volume of rinsing solution according to step (E) corresponds to the volume of the plasma conduit (8A) from point P2 to the apheresis column (4') plus the volume of the matrix of the apheresis column (4') and plus the volume of the plasma conduit (8B) from the apheresis column (4') to point P4. Regeneration solution

[0248] In particular, the regeneration solution is a citrate solution, a TRIS-glycine solution, a NaCl solution, a full electrolyte solution or an EDTA solution, preferably a citrate solution, a TRIS-glycine solution or a NaCl solution, more preferably a citrate solution or a NaCl solution and most preferably a citrate solution.

[0249] The present disclosure therefore also relates to a method for regenerating an apheresis column, wherein the regeneration solution is selected from the group comprising or consisting of: NaCl solution, NaCl solution with added citrate, citrate solution alone, TRIS-glycine solution and EDTA solution.

[0250] According to this embodiment, the anticoagulation solution already present in the system can be used as the regeneration solution. Consequently, regeneration can be carried out without additional fluids.

[0251] The term " Citrate solution ", as used herein, includes aqueous solutions containing at least one citrate compound.

[0252] The term " Citrate ", as used herein, refers to the citrate anion, that is, the salt of citric acid, or in other words, an organic tricarboxylate of the following chemical formula:

[0253] Citrate can occur in various forms (or compounds), for example as citric acid (in one- to three-fold protonated form), as a salt of citric acid in combination with other (unlike H+) inorganic cations (e.g., as a metal salt together with metal cations or as an ammonium salt together with ammonium ions), but also as a partial citrate ester. In this context, the term is also used here. "Citrate compound" used.

[0254] When the salt of citric acid, i.e., the citrate anion, is complexed with an inorganic cation, this is also referred to as " Citrate salt"as a special form of the citrate compound. Thus, the term "citrate compound", as used herein, includes both citric acid and its salts.

[0255] It is preferred if the citrate solution contains at least one of the citrate compounds from the group comprising or consisting of citric acid, sodium dihydrogen citrate, disodium hydrogen citrate, trisodium citrate, trisodium citrate dihydrate, potassium dihydrogen citrate, dipotassium hydrogen citrate, tripotassium citrate, lithium dihydrogen citrate, dilithium hydrogen citrate, trilithium citrate, ammonium dihydrogen citrate, diammonium hydrogen citrate, triammonium citrate, tricalcium dicitrate (calcium citrate), trimagnesium dicitrate (magnesium citrate) and / or partial citrate esters.

[0256] If the rather general term "sodium citrate" is used in this application, this term encompasses the various protonated forms of sodium citrate, i.e., the unprotonated (trisodium citrate), the singly protonated (disodium hydrogen citrate), or the doubly protonated form (sodium dihydrogen citrate). If the rather general term "potassium citrate" is used in this application, this term encompasses the various protonated forms of potassium citrate, i.e., the unprotonated (tripotassium citrate), the singly protonated (dipotassium hydrogen citrate), or the doubly protonated form (potassium dihydrogen citrate). If the rather general term "lithium citrate" is used in this application, this term encompasses the various protonated forms of lithium citrate, i.e., the unprotonated (trilithium citrate), the singly protonated (dilithium hydrogen citrate), or the doubly protonated form (lithium dihydrogen citrate).When the rather general term "ammonium citrate" is used in this application, this term includes the various protonated forms of ammonium citrate, i.e., both the unprotonated form (triammonium citrate), the singly protonated form (diammonium hydrogen citrate) and the doubly protonated form (ammonium dihydrogen citrate).

[0257] A citrate solution consisting of citric acid, trisodium citrate, D-glucose, and water is also known as Acid Citrate Dextrose Solution (ACD Solution) Preferred variants of the citrate solution used according to the invention relate to ACD solutions containing between 22.9 mM and 38.0 mM citric acid, between 44.9 mM and 74.8 mM trisodium citrate, between 74.2 mM and 123.6 mM D-glucose, and water. A particularly preferred variant of the citrate solution used relates to an ACD solution containing 38 mM citric acid, 74.8 mM trisodium citrate, 123.6 mM D-glucose, and water. This is also referred to as "ACD-A solution".

[0258] A citrate solution consisting of citric acid, trisodium citrate, sodium hydrogen phosphate, D-glucose, and water is also known as Citrate Phosphate Dextrose Solution (CPD) This is referred to as a CPD solution. A preferred variant of the citrate solution used is a CPD solution containing 15.6 mM citric acid, 89.4 mM trisodium citrate, 128.7 mM D-glucose, 16.1 mM sodium hydrogen phosphate, and water. A citrate solution consisting of citric acid, trisodium citrate, sodium hydrogen phosphate, D-glucose, adenine, and water is also referred to as a CPD solution. Citrate phosphate dextrose solution with adenine (CPDA)A preferred embodiment of the citrate solution used relates to a CPDA solution containing 15.6 mM citric acid, 89.4 mM trisodium citrate, between 128.7 mM and 160.9 mM D-glucose, 16.1 mM sodium hydrogen phosphate, 2 mM adenine, and water. A particularly preferred variant of the citrate solution used is a CPDA solution containing 15.6 mM citric acid, 89.4 mM trisodium citrate, 160.9 mM D-glucose, 16.1 mM sodium hydrogen phosphate, 2 mM adenine and water.

[0259] The term " NaCl solution "The term "NaCl" as used herein comprises aqueous solutions containing sodium chloride (i.e., NaCl, also known as table salt) as the main component. "Main component" here means that the molar concentration of sodium chloride in the NaCl solution is higher than the respective molar concentration of all other compounds within the NaCl solution, except for water. Preferably, the NaCl solution comprises 0.1 to 5 wt% sodium chloride, more preferably 0.9 wt%. The rinsing solution is preferably such an NaCl solution.

[0260] The term "TRIS-glycine solution," as used herein, encompasses aqueous solutions containing tris(hydroxymethyl)aminomethane (2-amino-2-(hydroxymethyl)propane-1,3-diol; TRIS) and glycine. Preferably, a "TRIS-glycine solution" is a TRIS-glycine buffer. Particularly preferably, the tri-glycine solution is a TRIS-glycine buffer with a pH of 8.3 consisting of TRIS (25 mM) and glycine (192 mM). More preferably, the tri-glycine solution is a TRIS-glycine buffer with a pH of 8.3 consisting of TRIS (25 mM), glycine (192 mM), and SDS (sodium lauryl sulfate) (0.1% w / v). Preferably, the pH value corresponds to the pH value at 25°C.

[0261] In a preferred specific embodiment, the rinsing solution is a saline solution or a physiological saline solution, or a PBS solution (phosphate buffered saline), or a combination of saline solution and PBS solution sequentially or simultaneously, and the regeneration solution is a citrate solution.

[0262] Thus, a preferred specific embodiment relates to a method for regenerating an apheresis column (4) for affinity chromatographic removal and preferably for selective affinity chromatographic removal of CRP in an apheresis device (1), wherein the method is characterized by the following steps: (A) Commencement of the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thus stopping the flow of the separated plasma from the plasma line (8A) into the apheresis column (4), (B) Commencement of the introduction of a saline solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (C) Commencement of the diversion of the fluid flow exiting the apheresis column (4) from the plasma line (8B) into the waste line (13), (D) Stop the introduction of the saline solution and switch to the introduction of a citrate solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (E) Stop the introduction of the citrate solution and switch to the introduction of the saline solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4)(F) Stopping the introduction of saline solution and stopping the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thus diverting the separated plasma from the plasma line (8A) into the apheresis column (4); (G) Closing the waste line (13) and diverting the fluid flow exiting the apheresis column (4) into the venous line (6).

[0263] Alternatively, the preferred specific embodiment relates to a method for regenerating an apheresis column (4) for affinity chromatographic removal and preferably for selective affinity chromatographic removal of CRP in an apheresis device (1), wherein the method is characterized by the following steps: (A) Beginning the diversion of the separated plasma from the plasma line (8A) into the bypass line (12) and thus stopping the flow of the separated plasma from the plasma line (8A) into the apheresis column (4), (B) Beginning the introduction of a saline solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (C) Stopping the introduction of the saline solution and transitioning to the introduction of a citrate solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (D) Beginning the diversion of the liquid flow emerging from the apheresis column (4) from the plasma line (8B) into the waste line (13), (E) Stopping the introduction of the citrate solution and transitioning to the introduction of the saline solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4)(F) Closure of the waste line (13) and redirection of the fluid flow exiting the apheresis column (4) into the venous line (6); (G) Stopping the introduction of saline solution and stopping the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thus redirecting the separated plasma from the plasma line (8A) into the apheresis column (4).

[0264] In the two aforementioned methods, steps (C) and (D) are interchangeable, ie they can be carried out in any order and simultaneously and can also be combined in one step.

[0265] Preferably, the regeneration process is carried out such that the plasma is first displaced from the apheresis column (4) with a rinsing solution, such as saline or physiological saline, and returned to the patient until almost only saline is returned. Only then is the saline directed into the waste line (13), and regeneration solution, such as a citrate solution, is introduced in the direction of flow, preferably after the bypass line (12), into the plasma line (8A). This displaces the saline, regenerates the apheresis column (4), is completely discharged into the waste line (13), and discarded. After successful regeneration of the apheresis column (4) with several apheresis column volumes of regeneration solution, a rinsing solution, such as saline or physiological saline, is again introduced.Physiological saline solution is introduced until the regeneration solution is completely displaced from the apheresis device (1) and discarded. Only then is the waste line (13) closed, the rinsing solution returned to the patient, the bypass line (12) closed, and plasma reintroduced through the plasma line (8A) into the apheresis column (4) simultaneously or immediately one after the other, with the order of the steps being interchangeable.

[0266] A further preferred specific embodiment relates to a method for regenerating an apheresis column (4) for the affinity chromatographic removal and preferably for the selective affinity chromatographic removal of CRP in an apheresis device (1), the method being characterized by the following steps: (A) Commencement of the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thus stopping the flow of the separated plasma from the plasma line (8A) into the apheresis column (4), (B) Commencement of the introduction of a saline solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (C) Commencement of the diversion of the fluid flow exiting the apheresis column (4) from the plasma line (8B) into the waste line (13), (D) Stop the introduction of the saline solution and switch to the introduction of a citrate solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (E1) Stop the introduction of the citrate solution and switch to the introduction of the saline solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4)(E2) Stopping the introduction of the saline solution and switching to the introduction of a PBS solution via at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (E3) Stopping the introduction of the PBS solution and switching to the introduction of a saline solution via at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (F) Stopping the introduction of saline solution and stopping the diversion of the separated plasma from the plasma line (8A) into the bypass line (12) and thus diverting the separated plasma from the plasma line (8A) into the apheresis column (4); (G) Closing the waste line (13) and diverting the fluid flow exiting the apheresis column (4) into the venous line (6).

[0267] An alternative preferred specific embodiment relates to a method for regenerating an apheresis column (4) for affinity chromatographic removal and preferably for selective affinity chromatographic removal of CRP in an apheresis device (1), wherein the method is characterized by the following steps: (A) Commencement of the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thus stopping the flow of the separated plasma from the plasma line (8A) into the apheresis column (4), (B) Commencement of the introduction of a saline solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (C) Stop the introduction of the saline solution and switch to the introduction of a citrate solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (D) Commencement of the diversion of the fluid flow exiting the apheresis column (4) from the plasma line (8B) into the waste line (13), (E1) Stop the introduction of the citrate solution and switch to the introduction of the saline solution via the at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4)(E2) Stopping the introduction of saline solution and switching to the introduction of a PBS solution via at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (E3) Stopping the introduction of the PBS solution and switching to the introduction of a saline solution via at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4), (F) Closing the waste line (13) and directing the fluid flow exiting the apheresis column (4) into the venous line (6); (G) Stopping the introduction of saline solution and stopping the diversion of the separated plasma from the plasma line (8A) into the bypass line (12), thus directing the separated plasma from the plasma line (8A) into the apheresis column (4).

[0268] In the two aforementioned methods, steps (C) and (D) are interchangeable, ie they can be carried out in any order and simultaneously and can also be combined in one step.

[0269] Thus, the present disclosure relates to a method for regenerating two apheresis columns (4',4") for affinity chromatographic removal and preferably for selective affinity chromatographic removal of CRP in an apheresis device (II), wherein the method enables regeneration during operation and is characterized by the following steps: (A) Starting from the flow of blood plasma through the apheresis column (4"), the introduction of the separated plasma via the plasma line (8A) into the apheresis column (4') begins, and the CRP-depleted plasma is directed into the venous line (6), thus stopping the introduction of the separated plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4"). (B) The introduction of a saline solution via at least one regeneration solution (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (C) commencement of the introduction of the fluid flow exiting the apheresis column (4") from the bypass line section (12") of the bypass line (12) into the waste line (13"), (D) stopping the introduction of the saline solution and transition to the introduction of Citrate solutionvia at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (E) stopping the introduction of the Citrate solution and transition to the introduction of saline solution via at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (F) start of the introduction of the saline solution into the plasma line (8A) via the apheresis column (4') and thus introduction of the separated plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4"), (G) closure of the waste line (13") and forwarding of the fluid flow exiting the apheresis column (4") into the venous line (6), (H) commencement of the diversion of the fluid flow exiting the apheresis column (4') from the plasma line (8B) into the waste line (13'), (I) stopping of the introduction of the rinsing solution and transition to the introduction of a Citrate solution via at least one regeneration line (13) into the plasma line (8A) or directly into the apheresis column (4'), (J) stopping the introduction of the Citrate solution and transition to the introduction of saline solution via at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4').

[0270] The regeneration procedures are preferably carried out as follows: first, the plasma is displaced from the apheresis column (4") with a rinsing solution, such as saline or physiological saline, and returned to the patient until almost only saline is returned. Only then is the saline directed to the waste line (13"), and regeneration solution, such as a citrate solution, is introduced in the direction of flow at point P2 into the bypass section (12') of the bypass line (12). This displaces the saline, regenerates the apheresis column (4"), and is then completely discharged into the waste line (13") and discarded. After successful regeneration of the apheresis column (4") with several column volumes of regeneration solution, a rinsing solution, such as saline or physiological saline, is again introduced.Physiological saline solution is introduced until the regeneration solution is completely displaced and discarded from the apheresis device (II). Only then is the plasma line (8A) closed, the rinsing solution returned to the patient, and plasma reintroduced through the bypass line section (12') of the bypass line (12) into the apheresis column (4") simultaneously or directly one after the other.

[0271] Another preferred specific embodiment relates to a method for regenerating two apheresis columns (4',4") for affinity chromatographic removal and preferably for selective affinity chromatographic removal of CRP in an apheresis device (II), wherein the method enables regeneration during operation and is characterized by the following steps: (A) Starting from the flow of blood plasma through the apheresis column (4"), the introduction of the separated plasma via the plasma line (8A) into the apheresis column (4') begins, and the CRP-depleted plasma is directed into the venous line (6), thus stopping the introduction of the separated plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4"). (B) The introduction of a saline solution via the at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (C) starting the introduction of the liquid flow emerging from the apheresis column (4") from the bypass line section (12') of the bypass line (12) into the waste line (13"), (D) stopping the introduction of the saline solution and transition to the introduction of Citrate solutionvia at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (E1) stopping the introduction of the Citrate solution and transition to the introduction of saline solution via at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (E2) stopping the introduction of the saline solution and transition to the introduction of a PBS solution via the at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (E3) stopping the introduction of the PBS solution and transitioning to the introduction of a saline solution via the at least one regeneration line (14) into the bypass line section (12') of the bypass line (12) or directly into the apheresis column (4"), (F) starting the introduction of the saline solutioninto the plasma line (8A) via the apheresis column (4') and thus introduction of the separated plasma via the bypass line section (12') of the bypass line (12) into the apheresis column (4"), (G) closure of the waste line (13") and forwarding of the fluid flow exiting the apheresis column (4") into the venous line (6), (H) commencement of the diversion of the fluid flow exiting the apheresis column (4') from the plasma line (8B) into the waste line (13'), (I) stopping of the introduction of the rinsing solution and transition to the introduction of a Citrate solution via at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4'), (J) stopping the introduction of the citrate solution and switching to the introduction of the saline solution via at least one regeneration line (14) into the plasma line (8A) or directly into the apheresis column (4'). Examples Application example:

[0272] The term "matrix volume" (also abbreviated as MV), as used herein, refers to the volume of the matrix contained in the adsorber.

[0273] The term "adsorber volume" (also abbreviated as AV), as used herein, refers to the volume of the adsorber housing. Example 1: Apheresis with a bypass line and an apheresis column Preparation:

[0274] Into the apheresis device (1) for the extracorporeal removal of CRP from the blood of a patient according to Fig. 3 , with a plasma centrifuge as a cell separator (7), a suitable tubing system is inserted. A 5 L bag containing 0.9% NaCl solution and a 500 ml bag containing ACD-A solution are connected to the connecting line. Two 3 L waste bags are connected to the waste line (13) (e.g., via a 3-way valve).

[0275] The arterial (5) and venous (6) lines are connected to each other using an adapter. Similarly, the plasma lines (8A and 8B) are connected before and after the adsorber using an adapter (without an adsorber in between), thus creating a closed system.

[0276] By pre-flushing with 1 L of 0.9% NaCl solution (200 ml / min), the entire system is filled with NaCl solution; any air present is expelled into the first waste bag. Subsequently, a shaken CRP adsorber (MV 20 ml, AV 30 ml) is inserted into the plasma line (8A and 8B) in place of the adapter. The adsorber is pre-flushed with 1 L of NaCl solution (100 ml / min). The NaCl is also directed into the first waste bag.

[0277] As the final preparation step, the plasma centrifuge is pre-filled with 0.9% NaCl solution and a 1:15 dilution of ACD-A solution. The required volume comprises the volume of the tubing system in the plasma centrifuge (7), the connecting line (11) to the plasma centrifuge, and the plasma line between the plasma centrifuge and P2. The displaced NaCl is routed via P4 / P6 into the first waste bag. Apheresis:

[0278] 1. After preparation is complete, the system switches to the second waste bag. The patient is connected to the arterial (5) and venous (6) lines. At the start of apheresis, the blood is directed into the centrifuge (60–80 ml / min). Throughout the entire treatment, ACD-A is mixed with the blood at a ratio of 1:15 (1 ml ACD-A to 15 ml blood) via the connecting line (11). The displaced NaCl is directed via P2, the bypass line (12), and P4 / P6 into the second waste bag. Once plasma separation begins, after a volume corresponding to the tubing length from the plasma centrifuge to point P4 / 6 has been reached, the system switches so that the plasma flows back into the venous line (6) and thus back to the patient. After a constant plasma flow of approximately 30 ml / min has been achieved for 3 minutes, the first cycle can begin. 2. The bypass line (12) is closed and the plasma is passed over the adsorber (loading).The NaCl in the plasma lines (8A and 8B) and the adsorber is diverted via P4 / P6 into the second waste bag until it reaches a volume equal to the volume of the plasma lines (8A and 8B) plus the AV (adsorber volume). The adsorber is then loaded with 50–100 MV (1000–2000 ml) of plasma. Regeneration then begins. 3. For this, the plasma is returned to the patient via the bypass line (12). The adsorber is then flushed with 0.9% NaCl (30 ml / min) via the regeneration line (14) and the plasma lines (8A and 8B). The required volume is calculated from the AV and the volume of the plasma lines (8A and 8B). The plasma in the plasma lines (8A and 8B) and the adsorber is returned to the patient up to a volume consisting of the AV and 75% of the volume of the plasma lines (8A and 8B). Subsequently, P4 / P6 is switched so that the solutions are directed into the second waste bag.

[0279] In the next step, regeneration is carried out with 3 MV (60 ml) of 0.9% NaCl, followed by a 1:15 ACD-A solution (100 ml / min). This is followed by a rinsing with 0.9% NaCl (100 ml / min). The required volume is calculated from the AV, the volume of the regeneration line (14), and the plasma line (8A and 8B).

[0280] Then step 2 (loading) can be carried out again, followed by step 3. If necessary, the bag containing ACD-A solution must be replaced.

[0281] 4. After the final loading, a final regeneration is performed. At the same time, the arterial line (5) is closed. The blood from the plasma centrifuge (7) is expelled via the cell line (9) and the remaining plasma from the plasma line to P2 and the bypass line (12) via the connecting line (11) using 0.9% NaCl (30 ml / min) and returned to the patient. The volume required for this is the sum of the volume of the plasma centrifuge (7), the volume of the plasma line to P2, the bypass line (12), the cell line (9), and the arterial line (6). The patient can then be disconnected from the apheresis device.

[0282] 5. If desired, the NaCl bag can now be replaced with a bag containing a preservative solution (e.g., PBS with sodium azide). The adsorber is rinsed with 10 MV of preservative solution via the regeneration line (into the second waste bag). The adsorber is then removed, sealed, and stored. The tubing system is removed from the apheresis device and disposed of. Example 2: Alternating use of the parallel apheresis column Preparation:

[0283] Into the apheresis device (II) for extracorporeal removal of CRP from blood of a patient according to Fig. 13 , with a plasma centrifuge as a cell separator (7), a suitable tubing system is inserted. A 5 L bag containing 0.9% NaCl solution and a 500 ml bag containing ACD-A solution are connected to the connecting line. Two 3 L waste bags are connected to the waste line (13) (e.g., via a 3-way valve).

[0284] The arterial (5) and venous (6) lines are connected to each other using an adapter. Similarly, the plasma lines (8A and 8B) are connected before and after the adsorber using an adapter (without an adsorber in between), and the bypass line sections (12' and 12") of the bypass line (12) are connected before and after the adsorber using an adapter (without an adsorber in between), thus creating a closed system.

[0285] The entire system is filled with NaCl solution by pre-rinsing with 1 L of 0.9% NaCl solution (200 ml / min); any air present is displaced into the first waste bag. A shaken CRP adsorber (MV 20 ml, AV 30 ml) is then inserted into the bypass line sections (12' and 12") and the plasma line (8A and 8B) in place of the adapter. The adsorber is pre-rinsed with 1 L of NaCl solution (100 ml / min). The NaCl is also discharged into the first waste bag.

[0286] As the final preparation step, the plasma centrifuge is pre-filled with 0.9% NaCl solution and a 1:15 dilution of ACD-A solution. The required volume comprises the volume of the tubing system in the plasma centrifuge (7), the connecting line (11) to the plasma centrifuge, and the plasma line between the plasma centrifuge and P2. The displaced sodium chloride is routed via P8 / P4 / P6 into the first waste bag. Apheresis:

[0287] 1. After preparation is complete, the system switches to the second waste bag. The patient is connected to the arterial (5) and venous (6) lines. At the start of apheresis, the blood is directed into the centrifuge (60–80 ml / min). Throughout the entire treatment, ACD-A is mixed with the blood at a ratio of 1:15 (1 ml ACD-A to 15 ml blood) via the connecting line (11). The displaced NaCl is directed via P2, the bypass line section 12', and P8 / P4 / P6 into the second waste bag. Once plasma separation begins, after a volume corresponding to the tubing length from the plasma centrifuge to point P8 / P4 / P6 has been reached, the system switches so that the plasma flows back into the venous line (6) and thus back to the patient. After a constant plasma flow of approximately 30 ml / min has been achieved for 3 minutes, the first cycle can begin. 2.The plasma line (8A) in the section between the node (P2) and the adsorber (4') is closed, and the plasma is passed through the adsorber (4") (loading). During this process, the NaCl in the bypass lines (12' and 12") and the adsorber (4") is diverted to the second waste bag via P3 / P4 / P6 until it reaches a volume equal to the volume of the bypass lines (12' and 12") plus the AV. The adsorber (4") is then loaded with 50–100 MV (1000–2000 ml) of plasma. The blood plasma is then displaced from the adsorber (4") along with the sodium chloride solution. 3. The system switches to the second adsorber and closes the bypass line section (12') in the area between the node (P2) and the adsorber (4"). The plasma is then passed through the adsorber (4') (loading).The sodium chloride solution in the bypass line sections (12' and 12") and the adsorber (4') is drained via P8 / P4 / P6 into the second waste bag up to a volume consisting of the volume of the plasma line (8A and 8B) plus the AV. The adsorber (4') is then loaded with 50 - 100 MV (1000 to 2000 ml) of plasma. The blood plasma is then displaced from the adsorber (4') with the sodium chloride solution and delivered to the patient. Step 2 (loading) can then be repeated, followed by step 3. If necessary, the bag must be replaced with ACD-A solution. 4. After the last loading, a final regeneration is performed. At the same time, the arterial line (5) is closed. The blood is drained from the plasma centrifuge (7) via the cell line via the connecting line (11) at 0.9% NaCl (30 ml / min). (9) repressed and returned to the patient.The required volume consists of the volume of the plasma centrifuge (7), the volume of the cell line (9), and the arterial line (6). The patient can then be disconnected from the apheresis device. 5. If desired, the sodium chloride solution bag can now be replaced with a bag containing a preservative solution (e.g., PBS with sodium azide). The adsorber is flushed with 10 MV of preservative solution via the regeneration line (into the second waste bag). The adsorber is then removed, sealed, and stored. The tubing system is removed from the apheresis device and disposed of. Example 3: Alternating use of parallel apheresis columns (4', 4") and regeneration during operation Preparation:

[0288] Into the apheresis device (II) for extracorporeal removal of CRP from blood of a patient according to Fig. 5, with a plasma centrifuge as a cell separator (7), a suitable tubing system is inserted. A 5 L bag containing 0.9% NaCl solution and a 500 ml bag containing ACD-A solution are connected to the connecting line. Two 3 L waste bags are connected to the waste line (13) (e.g., via a 3-way valve).

[0289] The arterial (5) and venous (6) lines are connected with an adapter. Likewise, the bypass line sections (12' and 12") before and after the adsorber are connected with an adapter (without an adsorber in between), and the plasma lines (8A and 8B) before and after the adsorber are connected with an adapter (without an adsorber in between), creating a closed system.

[0290] By pre-flushing with 1 L of 0.9% NaCl solution (200 ml / min), the entire system is filled with NaCl solution; any air present is expelled into the first waste bag. Subsequently, a shaken CRP adsorber (MV 20 ml, AV 30 ml) is inserted into the bypass line sections (12' and 12") and into the plasma line (8A and 8B) in place of the adapter. The adsorber is pre-flushed with 1 L of NaCl solution (100 ml / min). The NaCl is also directed into the first waste bag.

[0291] As a final preparation step, the plasma centrifuge is prefilled with 0.9% NaCl solution and 1:15 diluted ACD-A solution. The required volume is composed of the volume of the tubing system in the plasma centrifuge (7), the connecting line (11) to the plasma centrifuge, and the plasma line between the plasma centrifuge and P2. The displaced sodium chloride is directed into the first waste bag via P8 / P4 / P6. Apheresis:

[0292] 1. After preparation is complete, switch to the second waste bag. The patient is connected to the arterial (5) and venous (6) lines. At the start of apheresis, the blood is fed into the centrifuge (60-80 ml / min). Throughout the treatment, ACD-A is mixed with the blood via the connecting line (11) in a ratio of 1:15 (1 ml ACD-A to 15 ml blood). The displaced NaCl is fed into the second waste bag via P2, the bypass line sections (12'), and P8 / P4 / P6. When plasma separation begins, after a volume corresponding to the tubing from the plasma centrifuge to point P8 / P4 / 6, switch is made so that the plasma flows into the venous line (6), and thus back to the patient. After a constant plasma flow of approximately 30 ml / min has been achieved for 3 minutes, the first cycle can begin. 2. The plasma line (8A) is closed and the plasma is passed over the adsorber (4") (loading).The NaCl contained in the bypass line sections (12' and 12") and the adsorber (4") is drained via P8 / P4 / P6 into the second waste bag up to a volume consisting of the volume of the bypass line sections (12' and 12") plus the AV. The adsorber is then loaded with 50 - 100 MV (1000 to 2000 ml) of plasma. The blood plasma is then displaced from the adsorber (4") with the sodium chloride solution. 3. Switch over to the second adsorber and close the bypass line section (12') in the area between the junction point (P2) and the adsorber (4"). The plasma is passed through the adsorber (4') (loading). The sodium chloride solution in the bypass line sections (12' and 12") and the adsorber (4') is passed through P8 / P4 / P6 into the second waste bag up to a volume consisting of the volume of the plasma line (8A and 8B) plus the AV.The adsorber (4') is then loaded with 50 - 100 MV (1000 to 2000 ml) of plasma. The blood plasma is then displaced from the adsorber (4') with the sodium chloride solution and delivered to the patient.

[0293] At the same time, the adsorber (4") is now flushed with 0.9% NaCl (30 ml / min) via the regeneration line (14) and the bypass line sections (12' and 12"). The volume required for this is calculated from the AV and the volume of the bypass line sections (12' and 12"). The plasma contained in the bypass line sections (12' and 12") and the adsorber (4") is also returned to the patient up to a volume consisting of the AV and 75% of the volume of the plasma line (8A and 8B). P4 / P6 are then switched so that the solutions are directed into the second waste bag.

[0294] In the next step, regeneration is carried out with 3 MV (60 ml) of 0.9% NaCl, followed by a 1:15 ACD-A solution (100 ml / min). This is followed by a rinsing with 0.9% NaCl (100 ml / min). The required volume is calculated from the AV, the volume of the regeneration line (14), and the plasma line (8A and 8B).

[0295] Step 2 (loading) can then be repeated, followed by step 3. If necessary, the bag containing ACD-A solution must be replaced.

[0296] 4. After the final loading, a final regeneration is performed. At the same time, the arterial line (5) is closed. The blood from the plasma centrifuge (7) is displaced via the connecting line (11) with 0.9% NaCl (30 ml / min) through the cell line (9) and returned to the patient. The required volume is the sum of the volume of the plasma centrifuge (7), the volume of the cell line (9), and the arterial line (6). The patient can then be disconnected from the apheresis device.

[0297] 5. If desired, the sodium chloride solution bag can now be replaced with a bag containing preservative solution (e.g., PBS with sodium azide). The adsorber is rinsed with 10 MV of preservative solution via the regeneration line (into the second waste bag). The adsorber is then removed, sealed, and stored. The tubing system is removed from the apheresis device and disposed of. Description of the characters

[0298] Fig. 1: Schematic drawingAn embodiment of the apheresis device (1) according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From this, the plasma line (8A) leads to the apheresis column (4) for the affinity chromatographic removal of CRP from the blood. From this, the plasma line (8B) leads to the node (P1). Another line, the cell line (9), leads from the cell separator (7) to the node (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the node (P1). In addition, there is a connecting line (11) for connecting a liquid container (F1), which opens into the arterial line (5) or alternatively leads directly into the cell separator (7) (dashed line).The bypass line (12) branches off from the plasma line (8A) at the junction point (P2) and flows into the plasma line (8B) at the junction point (P6). The waste line (13) branches off from the plasma line (8B) at the junction point (P4). In addition, the regeneration line (14) for connecting a liquid container (F2) flows into the plasma line (8A) in an area between the junction point (P2) and the apheresis column (4). Alternatively, the regeneration line (14) can also lead directly into the apheresis column (4) (not shown). For improved clarity, the central processing unit (10), which is also part of the apheresis device according to the invention, is not shown. Fig. 2: Schematic drawingAn embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From this, the plasma line (8A) leads to the apheresis column (4) for the affinity chromatographic removal of CRP from the blood. From this, the plasma line (8B) leads to the node (P1). Another line, the cell line (9), leads from the cell separator (7) to the node (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the node (P1). In addition, there is a connecting line (11) that flows into the arterial line (5) or alternatively leads directly into the cell separator (7) (dashed line).The bypass line (12) branches off from the plasma line (8A) at the junction point (P2) and flows into the plasma line (8B) at the junction point (P6). The waste line (13) branches off from the plasma line (8B) at the junction point (P6). Additionally, the regeneration line (14) flows into the plasma line (8A) at the junction point (P2). For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. Fig. 3: Schematic drawingAn embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From this, the plasma line (8A) leads to the apheresis column (4) for the affinity chromatographic removal of CRP from the blood. From this, the plasma line (8B) leads to the node (P1). Another line, the cell line (9), leads from the cell separator (7) to the node (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the node (P1). In addition, there is a connecting line (11) for connecting a liquid container (F), which opens into the arterial line (5) or alternatively leads directly into the cell separator (7) (dashed line).The bypass line (12) branches off from the plasma line (8A) at the junction point (P2) and flows into the plasma line (8B) at the junction point (P6). The waste line (13) branches off from the plasma line (8B) at the junction point (P6). In addition, the regeneration line (14), which branches off from the connecting line (11) at the point (P5), flows into the plasma line (8A) at the junction point (P2). For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. Fig. 4: Schematic drawingAn embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From this, the plasma line (8A) leads to the apheresis column (4) for the affinity chromatographic removal of CRP from the blood. From this, the plasma line (8B) leads to the node (P1). Another line, the cell line (9), leads from the cell separator (7) to the node (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the node (P1). In addition, there is a connecting line (11) that flows into the arterial line (5) or alternatively leads directly into the cell separator (7) (dashed line).The bypass line (12) branches off from the plasma line (8A) at the junction point (P2) and flows into the cell line (9) at the junction point (P3). The waste line (13) branches off from the plasma line (8B) at the junction point (P1). Additionally, the regeneration line (14), which branches off from the connecting line (11) at the point (P5), flows into the plasma line (8A) at the junction point (P2). For the sake of clarity, the central processing unit (10), which also forms part of the apheresis device according to the invention, is not shown. Fig. 5: Schematic drawingAn embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From this, the plasma line (8A) leads to the apheresis column (4) for the affinity chromatographic removal of CRP from the blood. From this, the plasma line (8B) leads to the node (P1). Another line, the cell line (9), leads from the cell separator (7) to the node (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the node (P1).In addition, there is a connecting line (11') that opens into the arterial line (5) but could also have opened directly into the cell separator (7), as well as a connecting line (11") that opens into the cell separator (7) but could also have opened into the arterial line (5). The bypass line (12) branches off from the plasma line (8A) at the junction point (P2) and opens into the plasma line (8B) at the junction point (P6). The waste line (13) branches off from the plasma line (8B) at the junction point (P6). In addition, the regeneration line (14), which is connected to the connecting line (11') at the point (P5') and is connected to the connecting line (11") at the point (P5"), opens into the plasma line (8A) at the junction point (P2). For improved clarity, the apheresis device according to the invention belonging to the central processing unit (10) is not shown. . Fig. 6: Schematic drawingAn embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From this, the plasma line (8A) leads to the apheresis column (4) for the affinity chromatographic removal of CRP from the blood. From this, the plasma line (8B) leads to the node (P1). Another line, the cell line (9), leads from the cell separator (7) to the node (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the node (P1).In addition, there is a connecting line (11') that opens into the arterial line (5) but could also have opened directly into the cell separator (7), as well as a connecting line (11") that opens into the cell separator (7) but could also have opened into the arterial line (5). The bypass line (12) branches off from the plasma line (8A) at the junction point (P2) and opens into the plasma line (8B) at the junction point (P6). The waste line (13) branches off from the plasma line (8B) at the junction point (P6). In addition, a first regeneration line (14') that branches off from the connecting line (11') at the point (P5') and a second regeneration line (14") that branches off from the connecting line (11") at the point (P5") both open into the plasma line at the junction point (P2). (8A). For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. Fig. 7: Schematic drawingan embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood as in Fig. 3 described, with the difference that there is an additional connection for a liquid container from the regeneration line (14). The connecting line (11) opens into the arterial line (5) and could also lead directly into the cell separator (7), which is indicated by the dashed line. This time the regeneration line (14) has an additional connection for a liquid container, whereby this connection is located behind the cell separator (7) in the direction of flow, so that liquid from this additional liquid container cannot be led into the cell separator (7) and cannot be led into the arterial line (5) in front of the cell separator (7), but only into the plasma line (8A) behind the cell separator (7) in the direction of flow or directly into the apheresis column (4). Fig. 8: Schematic representationa regeneration process. ( A ) In normal operation, the untreated blood (dark gray & dotted arrow) from the patient is separated in the cell separator (7) into the untreated plasma (dark gray arrow) and the cellular components (white & dotted arrow). The untreated plasma is fed via the plasma line (8A) into the apheresis column (4), where CRP is depleted. The treated plasma (light gray arrow) is fed via the plasma line (8B) to point (P1), where it is combined with the cellular components. The treated blood (light gray & dotted arrow) is returned to the patient via the venous line. ( B By switching the valve at point (P2), the untreated plasma is diverted into the bypass line (12), and regeneration solution (white arrow) is introduced into the apheresis column. The displaced plasma is largely delivered to the patient. ( C) Subsequently, by changing the valve at point (P6), the regeneration solution is diverted into the waste line (13) after flowing through the apheresis column (4) and thus discarded. ( D ) Subsequently, the introduction of regeneration solution is stopped by switching the valve at point (P2), and the untreated plasma is reintroduced into the apheresis column (4). The majority of the displaced regeneration solution is discarded via the waste line (13). Subsequent valve switching at point (P6) returns the system to normal operation (A). Fig. 9: Schematic drawingAn embodiment of the apheresis device (II) according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From there, the plasma line (8A) leads to the apheresis column (4') for the affinity chromatographic removal of CRP. The bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and leads to the apheresis column (4") for the affinity chromatographic removal of CRP from the blood. From the apheresis column (4"), the bypass line section (12") of the bypass line (12) for CRP-depleted blood plasma leads to the node (P1), and from the apheresis column (4') the plasma line (8B) for CRP-depleted blood plasma leads to the node (P1).Another line, the cell line (9), leads from the cell separator (7) to the junction point (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the junction point (P1). Additionally, there is a connecting line (11) for connecting a fluid container (F1), which opens into the arterial line (5) or, alternatively, leads directly into the cell separator (7) (dashed line). The plasma line (8A) and the bypass line section (12') of the bypass line (12) diverge at the junction point (P2), and the bypass line section (12") of the bypass line (12) and the plasma line (8B) converge at the junction point (P6). For the sake of clarity, the central processing unit (10), which also forms part of the apheresis device according to the invention, is not shown. Fig. 10: Schematic drawingAn embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From there, the plasma line (8A) leads to the apheresis column (4') for the affinity chromatographic removal of CRP. The bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and leads to the apheresis column (4") for the affinity chromatographic removal of CRP from the blood. From the apheresis column (4"), the bypass line section (12") of the bypass line (12) for CRP-depleted blood plasma leads to the node (P1), and from the apheresis column (4') the plasma line (8B) for CRP-depleted blood plasma leads to the node (P1).Another line, the cell line (9), leads from the cell separator (7) to the junction point (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the junction point (P1). Additionally, there is a connecting line (11) for connecting a fluid container (F1), which flows into the arterial line (5) or, alternatively, leads directly into the cell separator (7) (dashed line). The bypass line section (12') of the bypass line (12) and the plasma line (8A) diverge at the junction point (P2), and the bypass line section (12") of the bypass line (12) and the plasma line (8B) converge at the junction point (P6). The waste line (13") branches off from the bypass line section (12') of the bypass line (12) at the junction point (P8), and the waste line (13') branches off from the plasma line (8B) at the junction point (P4).In addition, the regeneration line (14) for connecting a fluid container (F2) opens into the extracorporeal circulation system (2) at the node (P2). For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. Fig. 11: Schematic drawingAn embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From there, the plasma line (8A) leads to the apheresis column (4') for the affinity chromatographic removal of CRP. The bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and leads to the apheresis column (4") for the affinity chromatographic removal of CRP from the blood. From the apheresis column (4"), the bypass line section (12") of the bypass line (12) for CRP-depleted blood plasma leads to the node (P1), and from the apheresis column (4') the plasma line (8B) for CRP-depleted blood plasma leads to the node (P1).Another line, the cell line (9), leads from the cell separator (7) to the junction point (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the junction point (P1). Additionally, there is a connecting line (11) for connecting a fluid container (F1), which flows into the arterial line (5) or, alternatively, leads directly into the cell separator (7) (dashed line). The bypass line section (12') of the bypass line (12) and the plasma line (8A) diverge at the junction point (P2), and the bypass line section (12") of the bypass line (12) and the plasma line (8B) converge at the junction point (P6). The waste line (13") branches off from the bypass line section (12") of the bypass line (12) at the junction point (P8), and the waste line (13') branches off from the plasma line (8B) at the junction point (P4).In addition, the regeneration line (14) leads to the connection of a liquid container (F2) up to the junction point (P7). Two lines (15', 15") branch off at the junction point (P7). Line (15') opens into the extracorporeal circulation system (2) at the junction point (P2), and line (15") opens in the area between the junction point (P2) and the apheresis column (4"). For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. Fig. 12: Schematic drawingAn embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From there, the plasma line (8A) leads to the apheresis column (4') for the affinity chromatographic removal of CRP. The bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and leads to the apheresis column (4") for the affinity chromatographic removal of CRP from the blood. From the apheresis column (4"), the bypass line section (12") of the bypass line (12) for CRP-depleted blood plasma leads to the node (P1), and from the apheresis column (4') the plasma line (8B) for CRP-depleted blood plasma leads to the node (P1).Another line, the cell line (9), leads from the cell separator (7) to the junction point (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the junction point (P1). Additionally, there is a connecting line (11) for connecting a fluid container (F1), which flows into the arterial line (5) or, alternatively, leads directly into the cell separator (7) (dashed line). The bypass line section (12') of the bypass line (12) and the plasma line (8A") diverge at the junction point (P2), and the bypass line section (12") of the bypass line (12) and the plasma line (8B") converge at the junction point (P6). The waste line (13) branches off from the extracorporeal circulation system (2) at the junction point (P6). In addition, the regeneration line (14) for connecting a liquid container (F2) opens into the extracorporeal circulation system (2) at the junction point (P2).For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. Fig. 13: Schematic drawingan embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), in which a means (3) for generating and regulating a blood flow (e.g. peristaltic pump) is located, leads the patient's blood to the cell separator (7, e.g. a centrifugal cell separator). From there, the plasma line (8A) leads to the apheresis column (4') for the affinity chromatographic removal of CRP. The bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and leads to the apheresis column (4") for the affinity chromatographic removal of CRP from the blood. From the apheresis column (4"), the bypass line section (12') of the bypass line (12) for CRP-depleted blood plasma leads to the node (P1) and from the apheresis column (4') the plasma line (8B) for CRP-depleted blood plasma leads to the node (P1).Another line, the cell line (9), leads from the cell separator (7) to the junction point (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the junction point (P1). Additionally, there is a connecting line (11) for connecting a fluid container (F), which flows into the arterial line (5) or, alternatively, leads directly into the cell separator (7) (dashed line). The bypass line section (12') of the bypass line (12) and the plasma line (8A) diverge at the junction point (P2), and the bypass line section (12") of the bypass line (12) and the plasma line (8B) converge at the junction point (P6). The waste line (13) branches off from the extracorporeal circulation system (2) at the junction point (P6). In addition, the regeneration line (14), which branches off from the connecting line (11) at the point (P5), flows into the extracorporeal circulation system (2) at the junction point (P2).For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. Fig. 14: Schematic drawingan embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), in which a means (3) for generating and regulating a blood flow (e.g. peristaltic pump) is located, leads the patient's blood to the cell separator (7, e.g. a centrifugal cell separator). From there, the plasma line (8A) leads to the apheresis column (4') for the affinity chromatographic removal of CRP. The bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and leads to the apheresis column (4") for the affinity chromatographic removal of CRP from the blood. From the apheresis column (4"), the bypass line section (12") of the bypass line (12) for CRP-depleted blood plasma leads to the node (P1) and from the apheresis column (4') the plasma line (8B) for CRP-depleted blood plasma leads to the node (P1).Another line, the cell line (9), leads from the cell separator (7) to the junction point (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the junction point (P1). There is also a connecting line (11') that flows into the arterial line (5) but could also have flowed directly into the cell separator (7), as well as a connecting line (11") that flows into the cell separator (7) but could also have flowed into the arterial line (5). The bypass line section (12') of the bypass line (12) and the plasma line (8A) diverge at the junction point (P2), and the bypass line section (12") of the bypass line (12) and the plasma line (8B) converge at the junction point (P6). The waste line (13) branches off from the extracorporeal circulation system (2) at the junction point (P6).In addition, the regeneration line (14), which is connected to the connecting line (11') at the point (P5') and to the connecting line (11') at the point (P5"), opens into the extracorporeal circulation system (2) at the junction point (P2). For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. Fig. 15: Schematic drawingAn embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), which contains a means (3) for generating and regulating blood flow (e.g., a peristaltic pump), carries the patient's blood to the cell separator (7, e.g., a centrifugal cell separator). From there, the plasma line (8A) leads to the apheresis column (4') for the affinity chromatographic removal of CRP. The bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and leads to the apheresis column (4") for the affinity chromatographic removal of CRP from the blood. From the apheresis column (4"), the bypass line section (12") of the bypass line (12) for CRP-depleted blood plasma leads to the node (P1), and from the apheresis column (4') the plasma line (8B) for CRP-depleted blood plasma leads to the node (P1).Another line, the cell line (9), leads from the cell separator (7) to the junction point (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the junction point (P1). There is also a connecting line (11') that flows into the arterial line (5) but could also have flowed directly into the cell separator (7), as well as a connecting line (11") that flows into the cell separator (7) but could also have flowed into the arterial line (5). The bypass line section (12') of the bypass line (12) and the plasma line (8A) diverge at the junction point (P2), and the plasma line (8B') and the plasma line (8B") converge at the junction point (P6). The waste line (12) branches off from the extracorporeal circulation system (2) at the junction point (P6).In addition, a first regeneration line (14'), which branches off from the connecting line (11') at the point (P5'), and a second regeneration line (14"), which branches off from the connecting line (11") at the point (P5"), both open into the extracorporeal circulation system (2) at the junction point (P2). For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. Fig. 16: Schematic drawingan embodiment of the apheresis device according to the invention for the extracorporeal removal of CRP from blood. The arterial line (5), in which a means (3) for generating and regulating a blood flow (e.g. peristaltic pump) is located, leads the patient's blood to the cell separator (7, e.g. a centrifugal cell separator). From there, the plasma line (8A) leads to the apheresis column (4') for the affinity chromatographic removal of CRP. The bypass line section (12') of the bypass line (12) branches off from the plasma line (8A) and leads to the apheresis column (4") for the affinity chromatographic removal of CRP from the blood. From the apheresis column (4"), the bypass line section (12") of the bypass line (12) for CRP-depleted blood plasma leads to the node (P1) and from the apheresis column (4') the plasma line (8B) for CRP-depleted blood plasma leads to the node (P1).Another line, the cell line (9), leads from the cell separator (7) to the junction point (P1). The venous line (6), which carries the treated blood back to the patient, also branches off from the junction point (P1). Additionally, there is a connecting line (11) for connecting a fluid container (F), which flows into the arterial line (5) or, alternatively, leads directly into the cell separator (7) (dashed line). The bypass line section (12') of the bypass line (12) and the plasma line (8A) diverge at the junction point (P2), and the bypass line section (12") of the bypass line (12) and the plasma line (8B) converge at the junction point (P6). The waste line (13) branches off from the extracorporeal circulation system (2) at the junction point (P6). In addition, the regeneration line (14), which branches off from the connecting line (11) at the point (P5), flows into the extracorporeal circulation system (2) at the junction point (P2).This time, the inlet line has an additional connection for a liquid container, wherein this connection is located behind the cell separator (7) in the direction of flow, so that liquid from this additional liquid container cannot be led into the cell separator (7) and not into the arterial line (5) in front of the cell separator (7), but only into the bypass line section (12') of the bypass line (12) or into the plasma line (8A) in the direction of flow behind the cell separator (7) or directly into the apheresis column (4') or directly into the apheresis column (4"). For improved clarity, the central processing unit (10), which also belongs to the apheresis device according to the invention, is not shown. List of reference symbols

[0299] 1 - Apheresis device 2 - Extracorporeal circulation system 3 - Means for generating and regulating a flow of blood (or blood plasma) in the extracorporeal circulation system (pump) 4 - Apheresis column for affinity chromatographic removal of CRP 4' - Apheresis column for affinity chromatographic removal of CRP 4" - Apheresis column for affinity chromatographic removal of CRP 5 - Arterial line 6 - Venous line 7 - Cell separator 8A - Plasma line (before the apheresis column) 8B - Plasma line (after the apheresis column) 9 - Cell line 10 - Central processing unit (CPU) 11 - Connecting line 12 - Bypass line 12' - Bypass line section of the bypass line 12" - Bypass line section of the bypass line 13 - Waste line 13' -Waste line 13" -Waste line 14 -Regeneration line 14' -Regeneration line 14" -Regeneration line F -Liquid tank F1 -Liquid tank 1 F2 -Liquid tank 2 P1 - Node point at which the plasma line (8B) merges into the venous line (6) or Node point at which the bypass line section (12") of the bypass line (12) or (8B) and the cell line (9) converge and merge into the venous line (6) P2 - Node point at which the bypass line (12) branches off from the plasma line (8A) or Node point at which the bypass line section (12') of the bypass line and the plasma line (8A) diverge P3 - Node point at which the bypass line (12) flows into the cell line (9) P4 - Node point at which the waste line (13) branches off from the plasma line (8B) or Node point at which the waste line (13') branches off from the plasma line (8B). P5 - Node point at which the Regeneration line (14) branches off from the connecting line (11) P5, P5' - node point at which the regeneration line (14) branches off from the connecting line (11) or (11').P6 - Node point at which the bypass line (12) flows into the plasma line (8B) or node point at which the bypass line section (12") of the bypass line (12) and the plasma line (8B) converge and run together as the bypass line section (12") of the bypass line (12) or (8B) to point P1. P7 - Node point in the regeneration line (14) from which the regeneration line (14) divides the lines (15') and (15"). P8 - Node point at which the waste line (13") branches off from the bypass line section (12") of the bypass line.

Claims

1. Apheresis device (1) for extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, means (3) for generation and regulation of a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separation of the blood into blood plasma and cellular components, at least one apheresis column (4) for affinity chromatographic removal of CRP from blood, wherein the extracorporeal circulation system (2) comprises an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4) to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1) and a venous line (6) starting from the point (P1), a central processing unit (10) for controlling the apheresis device (1), at least one connection line (11) for connection of at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and runs into the plasma line (8B), a waste line (13) goes off directly from the apheresis column (4) or from the plasma line (8B) in the direction of flow before the junction of the bypass line (12), and at least one regeneration line (14) which goes off from the at least one liquid container (F) or from the at least one connection line (11) and leads to the plasma line (8A) in the direction of flow at or after the branch of the bypass line (12) or runs directly into the apheresis column (4).

2. The device according to claim 1, wherein the at least one regeneration line (14) leading into the plasma line (8A) or directly into the apheresis column (4), starts from a point (P5) in the at least one connection line (11).

3. The device according to claim 1 or 2, wherein the apheresis device (1) has at least two connection lines (11) each for connection of at least one liquid container (F) to the arterial line (5) or the cell separator (7), and wherein there is a regeneration line (14) per liquid container (F) which go off from the respective liquid container (F) or its connection line (11) and which each lead into the plasma line (8A) or directly into the apheresis column (4).

4. The device according to any one of claims 1 - 3, wherein the apheresis device (1) has two connection lines (11', 11") each for connection of at least one liquid container (F) to the arterial line (5) or the cell separator (7), and wherein the at least one regeneration line (14) leading into the plasma line (8A) or directly into the apheresis column (4) connects to the connection line (11') at a point (P5') and to the connection line (11") at a point (P5").

5. The device according to any one of claims 1 - 4, wherein the apheresis device (1) has two connection lines (11', 11") each for connection of at least one liquid container (F1, F2) to the arterial line (5) or the cell separator (7), and wherein two regeneration lines (14', 14") go off from the two liquid containers (F1, F2) or the two connection lines (11', 11") and lead into the plasma line (8A) or directly into the apheresis column (4).

6. The device according to any one of claims 1 - 5, wherein the apheresis device (1) has a connection line (11') for connection of a liquid container (F1) to the arterial line (5) or the cell separator (7) and a connection line (11") for connection of a liquid container (F2) to the arterial line (5) or the cell separator (7), and wherein a regeneration line (14') goes off from the liquid container (F1) or the connection line (11') and leads into the plasma line (8A) in the direction of flow after the branch of the bypass line (12) or directly into the apheresis column (4) and a regeneration line (14") goes off from the liquid container (F2) or the connection line (11") and leads into the plasma line (8A) in the direction of flow after the branch of the bypass line (12) or into the regeneration line (14') or directly into the apheresis column (4).

7. The device according to any one of claims 1 - 6, wherein the bypass line (12) leads from a point (P2) in the plasma line (8A) to a point (P6) in the plasma line (8B) and the waste line (13) goes off from a point (P4) from the plasma line (8B) and the at least one regeneration line (14) runs into the plasma line (8A) at point (P2).

8. Apheresis device (II) for extracorporeal removal of CRP from blood comprising: an extracorporeal circulation system (2) for blood, a means (3) for generation and regulation of a flow of blood in the extracorporeal circulation system (2), a cell separator (7) for separation of the blood into blood plasma and cellular components, two apheresis columns (4', 4") for affinity chromatographic removal of CRP from blood, wherein the extracorporeal circulation system (2) comprises an arterial line (5) to the cell separator (7), a plasma line (8A) from the cell separator (7) to the apheresis column (4'), a plasma line (8B) for CRP-depleted blood plasma from the apheresis column (4') to a point (P1), a cell line (9) for the separated cellular components from the cell separator (7) to the point (P1) and a venous line (6) starting from the point (P1), a central processing unit (10) for controlling the apheresis device (II), at least one connection line (11) for connection of at least one liquid container (F) to the arterial line (5) or the cell separator (7), characterized in that a bypass line (12) branches off from the plasma line (8A) and runs into the plasma line (8B), and the bypass line (12) comprises the second apheresis column (4"), a waste line (13) goes off directly from the apheresis column (4') or from the plasma line (8B) in the direction of flow before the junction of the bypass line (12), and at least one regeneration line (14) which goes off from the at least one liquid container (F) or from the at least one connection line (11) and leads to the plasma line (8A) in the direction of flow at or after the branch of the bypass line (12) or runs directly into the apheresis column (4'), and wherein a second apheresis column (4") is connected in parallel to the first apheresis column (4') and both apheresis columns (4', 4") cannot be used simultaneously for CRP removal.