Patent Publication Number: US-2021162109-A1

Title: Membrane catheter

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 15/768,705 filed Apr. 16, 2018, pending, which is the U.S. national phase of PCT International Application No. PCT/EP2016/074776 filed Oct. 14, 2016 which designated the U.S. and claims priority to European Patent Application No. 15189777.4 filed Oct. 14, 2015, the entire contents of each of which are hereby incorporated by reference. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     (NOT APPLICABLE) 
     BACKGROUND 
     The invention relates to a device for the exchange or replacement of substances from the blood or into the blood. 
     The field of application of the invention in general is the examination or treatment of the human or animal body. In detail, in this connection the transport of certain substances either from the blood of the body to the outside of the body or—vice versa—from the outside of the body into the blood of the body is enabled. In particular diagnostic methods which are based on evidence of certain substances in the blood or also on the quantitative measuring of certain substances in the blood fall within said general field of application. Furthermore, the field of application of the invention also includes functions which support or replace the activity of organs in the body, in particular of the lung, the kidneys or the liver. Eventually, the invention can also be used for the administration of non-endogenous substances, in particular drugs or medicaments. Especially promising fields of application concern a long-time support of the pulmonary function or of the renal function (Continuous Renal Replacement Therapy, CRRT). 
     To the above field of application there also belongs for instance an extracorporeal blood purification (ECBP) which refers to the removal of endogenous or exogenous toxins or of dissolved substances from the blood and also comprises various therapies like hemodialysis, hemofiltration, or hemodiafiltration. The main idea is the withdrawal of blood from the patient, the removal of the substance in an external filtering unit (“purification”) and the return of purified blood via a venous access. 
     GB 2 004 092 A shows a device for measuring the content of glucose in the blood by means of an intravascular membrane catheter. In this connection, in a circuit a measuring liquid is guided past a membrane forming the outer side of the catheter and is transferred out of the body, where first of all oxygen is added to the liquid. Then the measuring liquid is supplied to an enzyme reactor, and the concentration of glucose in the blood is determined from the partial pressure of oxygen at the outlet of the reactor. Here, in this design, the surface of the membrane is limited by the dimensions of the catheter so that only a comparably low amount of the blood comes into contact with the membrane and participates in the exchange with the measuring liquid. 
     WO 2008/046630 A1 shows devices for the continuous monitoring of the concentration of a substance in the blood by means of microdialysis. Here a tubular membrane which is surrounded by blood and through which a perfusate flows can be used. Such a tubular membrane, naturally, has no blood inlet or blood outlet. As an alternative to the tubular membrane, a planar membrane is described, wherein blood and a carrier medium are pumped—obviously in an extracorporeal manner—through lines provided respectively on opposing sides of the planar membrane and extending in meanders. 
     Furthermore, in the field of the invention it has already been known to support the pulmonary function of a patient by means of ECMO (Extra Corporeal Membrane Oxygenation) systems or ECCO2R (Extra Corporeal CO2 Removal) systems. Such systems usually comprise cannulas, an impeller pump, a tube system, a membrane oxygenator, safety systems, and a heat exchanger, and they are reliable and easy to handle. They do, however, have several limitations with regard to a wide distribution and frequent use—they are very expensive, quite large in size and make patients immobile, which means that the patient has to be immobilized (sedated) during the treatment as there is the risk that the cannulas can become dislocated due to movements of the patient. Furthermore, in the common systems a conducting of the blood out of the body via one or several catheters and a return of the blood—to which oxygen has been added and from which CO2 has been removed—into the body are required. 
     Therefore, a lot of patients with an acute and chronic respiratory increase of CO2 (hypercapnia) would benefit from the availability of a mobile form of the ECCO2R reduced in size—with all advantages to be expected—as thereby they can be mobilized at an earlier point of time, they do not need long-lasting or further sedations, and said therapy could also be used already at an early phase of the disease. In extenso, a complete avoidance of a mechanical ventilation is conceivable, as a major part of the patients requires ventilation only due to the respiratory exhaustion and the hypercapnia as a result of the increased breathing work. 
     Already marketable intravascular membrane oxygenators had undergone clinical trials in the past and were approved for use with patients. Said techniques primarily had the object to improve the shortage of oxygen in the blood by an intravascular membrane oxygenation or to guarantee a sufficient availability of oxygen. In order to achieve said object, a large contact surface between the blood and the gas phase as well as a supply of gases into the catheter in the vascular system is required which potentially increases the risk of a gas embolism severely. The problem of the required large minimum surface was solved by the introduction of unfoldable webs of hollow fibres which were flushed extracorporeally with high gas flows. Said technique has several limitations, among them a low gas transfer for oxygen (O2), a high thrombogenicity of the fibre system having a turbulent flow therethrough, the susceptibility of the hollow fibres to breaking, and the obligatory size of the catheter with all of the associated risks of injuries. For this reason, said technology could not achieve acceptance in hospitals. 
     Intravascular membrane oxygenators are known in different design variants from patent literature. For instance WO 2004/016300 A2 discloses an intravenous oxygenator in the form of a catheter for oxygenating the blood, said oxygenator comprising a fibre bundle, said fibres being respectively connected by a first connection to a gas supply and by a second connection to a gas outlet. The fibre bundle is twisted about the longitudinal axis of the oxygenator during operation by a relative rotation of the first connection of the fibres in relation to the second connection of the fibres. Consequently, the fibres extend over the entire length of the fibre bundle as continuous gas conduits. During operation of the oxygenator, oxygen is supplied which flows via the first connection into the fibres at the surfaces of which a diffuse gas exchange with the blood takes place. Thereby an enrichment of the blood with oxygen and a simultaneous removal of CO2 is obtained. Therefore, at the second connection there is present a gas mixture of oxygen and carbon dioxide in the fibres, said gas mixture flowing through a discharge chamber in a tube and through the tube out of the body of the patient. The blood flowing into the oxygenator flows through the twisted fibre bundle and gets to a pump where the blood is transported in the flow direction of the vein and leaves the oxygenator through an outlet. Therefore, the drop in pressure of the blood is compensated for by the pump so that the pressure at the outlet once again has the physiological pressure. An effective exchange of oxygen for carbon dioxide requires a very large membrane surface of the hollow fibres which is hardly realizable in a catheter, and which, in turn, further increases the risk of the event of a gas embolism. 
     US 2010/0258116 A1 deals with different methods for the removal of carbon dioxide and in particular with blood oxygenators. Therein, however, there cannot be found any detailed explanations with regard to certain exchange devices, and there are mentioned extracorporeal exchange devices as well as intravascular catheters. The structure of the catheter is not described in detail. There is in particular not shown any catheter with a blood inlet and a blood outlet. Furthermore, with regard to catheters only the supply of gas as an exchange medium is mentioned. 
     U.S. Pat. No. 4,631,053 A discloses an intravascular membrane oxygenator. As an exchange medium there is exclusively disclosed the use of oxygen which is gaseous under standard conditions. A carrier medium is apparently not used, as only a supply line for the oxygen and no return for a possible carrier medium is shown. 
     In GB 2 505 068 A there is shown an extracorporeal drive which is connected via a shaft with a catheter pump for supporting the heart function. Obviously, due to its size the disclosed drive unit is unsuited for being used as a part of an intravascular catheter. 
     The pump shown in US 2013/053623 A1 is used for the support of the heart function and, thus, refers to a completely different field of application than the present device. The shown pump, naturally, does not comprise a membrane in the sense of the device according to the invention, i.e. for the exchange of substances. 
     SUMMARY 
     Based on the mentioned disadvantages of the known devices and methods it is an object of the invention to provide a device or a method by means of which substances can be transported efficiently out of the blood or into the blood. Furthermore, said device shall meet the criteria of minimally invasive surgeries and shall affect the patient and his/her blood circulation as little as possible. In particular, the disadvantages of an extracorporeal circuit or circulation and unnecessary surface contacts of the blood shall be reduced. Furthermore, the removal of toxic substances from the blood shall be improved in contrast to methods currently in use. For instance, by the system according to the invention the risk of a gas embolism shall be reduced and at the same time the performance of the exchange device, in particular with regard to the ratio between the rate of exchange of the membrane and the size of the catheter required to achieve this, shall be improved. 
     Consequently, the present invention refers to a device comprising a catheter for intravascular use, wherein the catheter has a blood inlet and a blood outlet, and comprises a membrane, wherein a first side of the membrane is in contact with a carrier medium and wherein the membrane is arranged in the catheter in such a way that at least one part of the blood flowing into the catheter via the blood inlet during operation comes into contact with a second side of the membrane lying opposite the first side thereof, before the blood leaves the catheter via the blood outlet, wherein the membrane allows an exchange of at least one substance to be exchanged between the carrier medium and the blood. In particular, in the respective device the catheter can comprise a conveying device which is configured to at least partially compensate for a pressure difference between the blood inlet and the blood outlet. 
     The invention also refers to a device comprising a catheter for intravascular use, wherein the catheter has a blood inlet and a blood outlet, and comprises a membrane, wherein a first side of the membrane delimits a lumen for the reception of a carrier medium, and wherein the membrane is arranged in the catheter in such a way that at least one part of the blood flowing into the catheter via the blood inlet during operation comes into contact with a second side of the membrane lying opposite the first side thereof, before the blood leaves the catheter via the blood outlet, wherein the membrane allows an exchange of at least one substance to be exchanged between a carrier medium received in the lumen during operation and the blood, and wherein the catheter comprises a conveying device which is configured to at least partially compensate for a pressure difference between the blood inlet and the blood outlet during operation. 
     Furthermore, the invention refers to a method for removing at least one substance from venous blood for diagnostic purposes using one of the above-mentioned devices, wherein the substance to be removed corresponds to the substance to be exchanged through the membrane of the catheter of the device. 
     Furthermore, the invention refers to a method for the treatment of a human or animal body by replacing or exchanging at least one substance from the blood or into the blood using one of the above-mentioned devices. 
     Correspondingly, according to the invention it is provided that the carrier medium is a carrier liquid in which the substance to be exchanged can be dissolved. That means that the carrier medium is in a liquid state of matter during operation (in case of standard conditions). Due to the use of a liquid as a carrier medium, the removal and supply of substances can be performed in a substantially more controlled and more efficient manner; thereby for instance the risk of a gas embolism is reduced significantly. Furthermore, there is only a slight risk of the development of thromboses. As the blood is not conducted out of the patient, the necessity of a systemic anticoagulation with the bleeding complications associated therewith is eliminated. Apart therefrom, by the use of suitable carrier liquids and a faster/higher circulation, a in general higher exchange of the substance to be exchanged through the membrane, i.e. through a membrane which is suitable for liquids (in short: “liquids membrane”), can be achieved, and, thus, the required membrane surface can be reduced which results in a reduced pressure difference in the catheter. If the catheter comprises a conveying device, the conveying rate of the conveying device required for the adaptation of the lower pressure difference is also reduced accordingly, which, in general, allows for a reduction in size of the conveying device and, hence, of the catheter as a whole. In case of a catheter without any conveying device, a reduction of the cross-section of the catheter can be carried out due to the comparatively lower pressure difference. By the possibility of the reduction in size of the entire system, which is associated with the present invention, the application is facilitated, and thereby, in the end, the risk of complications is reduced. By using components already available on the market, the entire system can be dimensioned such that it is portable and that the extracorporeal circuit with or at the console even fits into a bag. 
     Owing to the use of a carrier liquid as a carrier medium, the membrane of the device is a membrane which is suitable for liquids, i.e. which is configured and designed for the exchange of substances between two liquids. Even if with such a membrane also an exchange of substances between a liquid and a gas could be achieved or can be achieved to a certain degree, from the configuration of the membrane as a whole and above all from the provided contact surface and/or from the mechanical stability it results that the membrane is not designed for the use with a gaseous carrier medium. 
     In a particularly small and, hence, advantageous type of construction, the conveying device comprises a drive unit for the generation of a torque and a pump rotor or impeller connected to the drive unit for transmitting a torque. In this connection, the torque is preferably transmitted along a shaft the axis of which is arranged substantially in parallel to a longitudinal axis of extension of the catheter. Here, the pump rotor corresponds to the impeller of an axial-flow pump. 
     A simple control of the conveying device, in particular of the rotational speed of the rotor, can be achieved if the conveying device comprises an electric motor. In this connection, the reliability of the conveying device is substantially limited by the reliability of the electric motor. 
     Alternatively, the conveying device can comprise a turbine element around which the carrier medium flows during operation. In such a conveying device, a part of the flow energy of the carrier medium is transferred onto the delivered blood. In the simplest and most reliable case, the turbine element is directly coupled to the pump rotor so that the two elements will run with the same rotational speed during operation. In this connection, a driving relationship can be determined by means of the shape, i.e. the surface, the form and the arrangement, of the respective blades. Said type of drive has the additional advantage that no separate power supply, in particular no electrical connection, of the drive unit from outside of the body is required. Thereby the reliability as well as also the operating safety of the device are improved. 
     In connection with the drive unit it is favourable if the pump rotor is connected to the drive unit via a magnetic coupling, wherein the magnetic coupling comprises two coupling parts for the transmission of the torque along an axis of rotation being rotatable relative to each other and each including a permanent magnet. As a magnetic coupling there can for instance be used a concentric ring coupling or a disc coupling. When compared to a continuous mechanical connection, for instance in the form of a continuous shaft, a magnetic coupling has the advantage that the transmitted torque is limited. Thereby, in particular in case of an error, unplanned states can be excluded; for instance, even in case of a blockade of one element, the respectively coupled other element can still remain movable—with certain restrictions. If for instance the drive of the pump rotor fails or blocks, after overcoming the torque maximally transmitted by the magnetic coupling the pump rotor can run almost freely, whereby, in comparison with a blocking pump rotor, the blood flow is subjected to a smaller flow resistance so that the risk of complications as for instance of thromboses due to the blood coagulation (activated at external or foreign surfaces) is reduced. Moreover, by the limitation of the torque it is also possible to counteract a damaging of the pump. 
     Furthermore, the impeller or rotor of the pump thus formed can also be supported preferably in a suspended manner. There can for instance be provided a bearing in accordance with the heart support system INCOR of the “Berlin Heart” company. 
     In order to be able to transmit a desired torque also in a particularly compact magnetic coupling, it has proven favourable if one of the coupling parts comprises an at least partially ferromagnetic guiding element which is non-rotatably connected to the permanent magnet of the coupling part, wherein one part of the guiding element is disposed radially outside of the permanent magnet of the other coupling part. This means that the magnetic coupling comprises two coupling parts which can be rotated relative to each other, wherein a drive-side coupling part comprises a drive-side permanent magnet and wherein an output-side coupling part comprises an output-side permanent magnet that lies opposite and at a distance from the drive-side permanent magnet along the axis of rotation, wherein one of the coupling parts comprises an at least partially ferromagnetic guiding element which is non-rotatably connected to the permanent magnet of the coupling part, wherein one part of the guiding element is disposed radially outside of the opposite permanent magnet. When compared to conventional concentric ring couplings, said design has the advantage that the manufacturing thereof is easier and more economical, and that, on the whole, less coupling surface is required, as a part of the torque is transmitted via the front face of the coupling parts. When compared to conventional disc couplings, said design has the advantage that only smaller radial dimensions are required for the transmission of a certain torque. The guiding element may be shaped as a cup or a hollow cylinder—comparable to the outer coupling part of a concentric ring coupling—and may surround the respective other coupling part circumferentially, i.e. it preferably extends radially outside of both permanent magnets. In this connection, the guiding element may be formed as a thin-walled hollow cylinder, for example, so that with unchanged dimensions the magnetised volume of the disc coupling is retained to the greatest possible extent and, at the same time, a transmittable torque in a size comparable to that of a concentric ring coupling may be obtained between the guiding element and the opposite permanent magnet at a distance therefrom. The direction of magnetisation of the permanent magnets is preferably oriented perpendicularly to the axis of rotation, i.e. the poles of the magnets extend circumferentially from south to north and are—at least in a two-pole design—diametrically opposite each other with respect to the axis of rotation. By means of the guiding element, magnetic field lines extending radially from the permanent magnets are bundled, and due to the ferromagnetic material of the guiding element the magnetic force between the coupling parts is further increased. The magnetic force for transmitting the torque is raised by compressing the magnetic field lines in the ferromagnetic material. Advantageously, due to the larger volume of the permanent magnets when compared to concentric ring couplings with equal dimensions of the couplings, a shorter axial extension and, thus, lower radial transverse forces on the bearings of the coupling parts can be achieved. 
     The permanent magnets of the magnetic coupling can be 2-, 4-, or 6-pole permanent magnets, respectively. They are preferably each of a two-pole design with two half-cylindrical magnetic poles, respectively. The guiding element may comprise at least one diamagnetic separation parting the guiding element into at least two ferromagnetic sections in order to avoid a magnetic short circuit. In addition to the radial outer arrangement, the guiding element can also extend at a rear side of the non-rotatably connected permanent magnet, which rear side is facing away from the opposite permanent magnet. Alternatively or additionally, the guiding element can comprise a substantially H-shaped longitudinal section, with a cross web disposed perpendicularly to the axis of rotation and with cup-shaped recesses formed on both sides, wherein a permanent magnet is received and non-rotatably connected in one of these recesses. This means that the guiding element can comprise a hollow cylindrical jacket and can preferably be designed with an intermediate base arranged substantially at half height of the jacket. 
     A particularly high concentration of magnetic field lines within the guiding element of the magnetic coupling may be achieved if a diamagnetic shielding element is arranged at a rear side of the permanent magnet non-rotatably connected to the guiding element which rear side is facing away from the opposite permanent magnet. In this way, field lines running outside of the coupling parts may be avoided, and thus losses related thereto may be reduced. 
     Furthermore, it has proven favourable if, in the magnetic coupling, a diamagnetic shielding element is arranged at a front side of the permanent magnet non-rotatably connected to the guiding element which front side is facing the opposite permanent magnet, in particular in a region centred around the axis of rotation, which shielding element adjoins the guiding element preferably circumferentially or radially on the outside. Such a shielding makes it possible to guide and divert the magnetic field to regions located at larger radial distances from the axis of rotation so that the torque transmitted at a given magnetic force is increased. 
     In order to reliably avoid a transition of the carrier medium to the blood, it is also favourable for the two coupling parts to be hermetically separated. Such a hermetic separation may be obtained, for instance, by a hermetic wall between the two coupling parts of the magnetic coupling, which wall should be non-conductive both magnetically and electrically. In particular, at least one of the coupling parts can be accommodated in a substantially non-magnetic and electrically non-conductive housing so that it is possible to avoid losses due to a reversal of magnetism of the housing and/or induced eddy currents in the housing. 
     An application which profits in a particularly high extent from the advantages of the invention is the use for the removal of CO2 from the blood, i.e. wherein the substance to be exchanged is CO2. In this connection, the carrier liquid may have a solubility of at least 140 ml CO2, in particular of at least 180 ml CO2, in 100 ml of the carrier liquid at 37° C. In comparison therewith, the solubility of CO2 in arterial blood at 40 mmHg (approximately 5332.88 Pa) (dissolved physically) is approximately 2.6 ml/100 ml and at 90 mmHg (11998.98 Pa) it is approximately 0.3 ml/100 ml. 
     The carrier liquid can be a perfluorocarbon or an albumin solution and/or an electrolyte solution, in particular enriched with specific proteins or glucose derivatives, or it can be a commercially available dialysate which preferably was additionally processed via an ion exchanger, activated carbon or another adsorber. 
     Preferably, the invention can be used with a dialysis liquid as a carrier medium, which comprises or consists of demineralized water including various electrolytes as well as bicarbonate in an identical concentration as the physiological extracellular liquid. During operation, the blood and the dialysis liquid can be guided in a counterflow along a semipermeable membrane which is permeable to low-molecular substances (&lt;5-15 kDa or kilodaltons; related to the atomic mass unit Dalton) (uraemic toxins, electrolytes). Thereby a maximum concentration gradient can be obtained only for the excess uraemic toxins but not for the electrolytes. If additionally a liquid shall be separated, a pressure gradient can be generated which presses a solution off the blood. Thus, the invention can for instance be used in case of heavy metal poisonings and alcohol poisoning. 
     In connection with the exchange of CO2 or the removal of CO2 from the blood, a perfluorocarbon has turned out to be a particularly favourable carrier liquid. This means that the carrier liquid preferably is a liquid of the family of perfluorocarbons (PFC) which is in a liquid state under physiological conditions and at ambient temperature. PFC has a reception capacity for CO2 which is ten times higher than that of blood (the solubility of CO2 in PFC is 210 ml/dl, that of O2 is 53 ml/dl). Apart from perfluorocarbons, in particular other blood substitutes, like for instance a haemoglobin based oxygen carrier, are suitable. The suitable perfluorocarbons further have a low surface tension and easily spread on surfaces due to their high spreading coefficient. Said properties and their large potential for the transport of CO2 make said liquids particularly suitable for the use for flowing through a membrane of hollow fibres in order to remove above all a part of the continuously formed carbon dioxide for the relief of the breathing work during a spontaneous or mechanically supported ventilation under low blood flows. Therefore, the hollow fibre membrane will be preferably designed in such a way that the minimum exchange surface for an efficient CO2 transfer is available which, for patients of normal weight and under blood flow rates of approximately 300 ml per minute (through the catheter/in conventional methods through the catheter—in the invention actually only contact equivalence time), lies in the order of magnitude of at least 0.84 m 2 . 
     For the exchange of protein-bound toxins, the carrier liquid may preferably comprise albumin. In this case, the invention can be used for carrying out an albumin dialysis. In this connection, a membrane is used which is only permeable to toxins bound to the albumin and also is permeable to water-soluble small molecules. The concentration gradient of toxins on the blood circulation side is larger than on the side with the albumin-containing carrier liquid. Due to the concentration gradient and the permeability of the membrane to the albumin-bound toxins, said toxins pass through the membrane (diffusion) and are bound by the free albumin in the carrier liquid. Via a circuit, the albumin together with the toxins can travel on the dialysis side to different detoxification stations. As a first detoxification station there can for instance be provided a complete dialysis apparatus which, however, rather filters out the molecules dissolved in water (toxins) and checks the electrolyte level. As a second detoxification station there can be provided an activated carbon filter which filters toxins which are not anionic. Anionic toxins can leave the circuit via an anion filter. The albumin thus purified can then once again absorb toxins at the membrane. Thus, the albumin will become free again on the blood circulation side and can transport new toxins. The blood will be detoxified. As an alternative to the described reprocessing, the carrier liquid with the albumin can also be discarded after passing the membrane. 
     Furthermore, special carrier liquids (e.g. dialysates, physiological saline) can be prepared or mixed which are used for instance for the treatment of electrolyte disorders (hyperkaliemia) or for the transport of blood glucose, pathological glucose molecules (for the treatment of glycogen storage diseases), lipids (for the treatment of dyslipidoses), urea or creatinine, or in general for a therapeutic apheresis. In this connection, membranes, for instance semipermeable membranes, which are configured specifically for the exchange of the respective substance(s) can be used. Particularly preferred carrier liquids are, apart from perfluorocarbon, in particular albumin solutions and/or electrolyte solutions or commercially available dialysates which were additionally processed via an ion exchanger, activated carbon or another adsorber. 
     The invention can for instance be used as an artificial pancreas, wherein the blood can absorb insulin from the carrier liquid through the membrane and can pass on glucagon to the carrier liquid. The membrane can for instance be made of poly-urethane. 
     When the above-mentioned carrier liquids are used, the invention enables that hypercapnia can be avoided in that a part of the continuously generated carbon dioxide is removed through a liquid, in particular a perfluorocarbon, for the relief of the breathing work during a spontaneous or mechanical ventilation. Perfluorocarbons show a high solubility not only for CO2 but also for all respiratory gases and, therefore, also for O2, N2, and NO. Consequently, the surface for the exchange of gases of the membrane used does not have to be as large as it is required for conventional intravascular membrane oxygenators. Thereby the catheter can be implemented in the size of a conventional dialysis catheter or a single port ECMO catheter. By the use of liquid perfluorocarbon, which has a gas binding capacity which is by far higher than that of oxygen used so far in conventional intravascular membrane oxygenators, for the achievement of a gas binding effect of similar quality a much smaller contact surface of the membrane with the blood is required in order to guarantee an efficient removal of CO2. 
     Moreover, the invention can be used with a carrier liquid which includes decoupler substances. In general, toxins can be displaced by substances which have a higher affinity for the specific binding sites at the protein or at the lipid than the toxin. Said substances are called decoupler substances. As decoupler substances there are principally preferred physiological substances but, if necessary, also non-physiological substances which are regarded as toxicologically safe can be used. Said substances have a higher specific binding affinity to the binding sites of the toxin so that a shift of the chemical equilibrium is effected, and the toxins are released. Then the released toxins can be removed from the blood or from the blood components (enzymatically, adsorptively, membrane process). 
     For the removal of the released toxins from the carrier liquid there can be preferably used an ultrafiltration process. In this connection, solutions consisting of several components can be separated according to the molecular weight. Said process is suitable in particular for the separation of low-molecular substances. The exclusion limit, i.e. the molecular weight of the substances which are retained up to approximately 90%, is determined by the chosen membrane. The driving force is here a pressure difference between the two membrane sides. The obtained ultrafiltrate primarily contains the low-molecular substances, i.e. in general the toxin. There can, however, also be present small amounts of protein (approximately 1%) in the filtrate. In the ultrafiltration and the dialysis a distinction has to be made between the single passage and the recirculation. 
     With regard to the membrane of the catheter it is favourable if the membrane is a selectively permeable membrane which is permeable at least to the substance to be exchanged. In dependence on the application, i.e. in particular in dependence on the substance to be exchanged and, thus, also in dependence on the carrier liquid, the design, the material and the structure of the membrane can be adapted correspondingly. As materials there are suitable for instance hydrophilic or hydrophilized copolymers and hydrophilic polymer mixtures. In detail, as a membrane material there can be used mixtures with one or several components of a group consisting of polyethylene, thermoplastic polyurethane, polysulfones (PSU), polyethersulfones (PES), polyacrylethersulfones (PAES), polyvinyl pyrrolidone (PVP), polymethylmethacrylate (PMMA), polyamide (PA), polyacrylnitrile (PAN), and/or ethylene vinyl alcohol copolymer (EVOH), as well as cellulose, cellulose triacetate (CTA), or cellulose nitrate. It is preferred to use membranes substantially consisting only of PSU or PSE, substantially of a mixture of PES, PVP and PA (PEPA), or substantially of a mixture of PAES, PVP, and PA. The size of the pores of the membrane can lie between 0.01 μm and 0.1 μm. Additionally, the membrane can be coated, for instance with heparin. 
     A particularly large contact surface in a small space can be obtained if the membrane is a hollow fibre membrane. Here, the actual contact surface is formed by the walls of the hollow fibres or capillaries. A hollow fibre membrane can comprise up to 20,000 individual capillaries or hollow fibres. The diameter of the individual hollow fibres lies between 0.01 mm and 1 mm, in particular between 0.1 and 0.5 mm. The entire surface of the membrane, which forms the contact surface for the exchange of substances, lies between 0.01 and up to 10 m 2 , preferably between 0.1 and 1 m 2 . The material from which the hollow fibres are made can be composed of one or several of the above-mentioned components, wherein PMP (polymethylpentene) has to be mentioned as being preferred. In connection with the performance according to the invention and, if applicable, with the conveying of the blood through the catheter during operation, the filigree hollow fibres of the membrane can be accommodated in a protective catheter sheath. The flow resistance caused by the large contact surface can at least partially be compensated for by the conveying device. 
     Further preferred membrane materials can comprise nanocapsules or microcapsules or they can be manufactured by using such capsules. Nanocapsules can be produced by interfacial polymerization from polymers like polyacrylates, preferably poly(n-butyl cyanoacrylate) (PACA), as well as poly(lactid coglycolide) (PLGA), albumin. Such nanocapsules are characterized by a very small wall thickness of 3-20 nm. They can be filled with perfluorocarbons (PFC). Alternatively or additionally, also magnetic particles as well as fluorescence dyes (e.g. Nile red) can be added to the nanocapsules during the production thereof, so that they can be specified and identified in a better manner. (Delphine Moinard-Checot, Yves Chevalier, Stephanie Briancon et al. “Mechanism of nanocapsules formation by emulsion-diffusion process”, Journal of Colloid and Interface Science 317 (2008) 458-468; Christian Erdmann, Christian Mayer, “Permeability profile of poly(alkyl cyanoacrylate) nanocapsules”, Journal of Colloid and Interface Science 478 (2016) 394-401). 
     Microcapsules can for instance be produced from silicone, in particular from UV-curing silicone, for instance Semicosil 949UV, by means of a double-capillary method. Such microcapsules comprise an outer shell made of silicone and a filling. The filling can include sodium carbonate, potassium carbonate, magnesium carbonate, sodium chloride, physiological NaCl solution, as well as mixtures of the mentioned materials. The filling can further include carbonic anhydrase or chemical equivalents thereof, like cyclen Zn (II). The filling can also consist of PACA nanocapsules (as defined above) accommodated in a carrier medium. Furthermore, the filling of the microcapsules can substantially consist of pure perfluorocarbons or of emulsions of PFC. Fluorescence dyes can be added to the capsule material and/or to the filling. Furthermore, to the filling there can for instance also be added colour indicators (e.g. thymol blue) which indicate a change in the pH value by a change in colour, in order to be able to monitor the saturation of the substances. (A. S. Utada, E. Lorenceau, D. R. Link, P. D. Kaplan, H. A. Stone, D. A. Weitz, “Monodisperse Double Emulsions Generated from a Microcapillary Device”, SCIENCE VOL 308 22 Apr. 2005; John J. Vericella, Sarah E. Baker,*, Joshuah K. Stolaroff et al., “Encapsulated liquid sorbents for carbon dioxide capture”, nature communications, 2015, DOI: 10.1038/ncomms7124). 
     Such nanocapsules and/or microcapsules can for instance be attached to the surface of membrane materials, like polymethylpentene (PMP), polypropylene (PP), or silicone, by means of polymers, cyanoacrylates, silicone (Loctite etc.). Thereby a chemical bond between the carrier material and the capsules is created which contributes to a surface enlargement and breaks the diffusion boundary layer by minimum turbulences. Correspondingly, the membrane of the present catheter can be provided with nanocapsules and/or microcapsules. 
     Alternatively or additionally, such nanocapsules and/or microcapsules can also be introduced into existing polymers like silicone in that they are for instance mixed or stirred thereinto. They spread out in the basic material and form for instance cavities filled with PFC which increase the permeability of the basic material. Alternatively, the nanocapsules and/or the microcapsules can be introduced between two thin polymer layers, preferably silicone (Silpuran). Thereby there are formed bubble foils. This increases the stability of the capsules. The materials thus produced are particularly suitable for the use as a membrane of the present catheter. 
     Furthermore, the microcapsules and/or nanocapsules can be bonded with each other, for instance by means of polymers, cyanoacrylates or silicone (Loctite etc.), and can thus be used for the production of foils or small hollow tubes, which foils and small hollow tubes can be used as a membrane of the present catheter. 
     The device according to the invention is particularly suitable for minimally invasive applications, for instance in the arm and leg veins. In this regard, the dimensions of the device according to the invention follow the dimensions which are used in the catheter technology (e.g. an outer diameter of 2.3 to 12.7 mm or 7 to 40 Fr). The design for the application in veins is preferred, wherein an outer diameter of the device of 10 mm or less, preferably of 8.7 mm or less, in particular of 8.0 mm or less, has proven to be especially well-suited in practice. Also the length of the device according to the invention preferably follows the standard vein catheter formats, i.e. approximately 100 to 400 mm, in particular 150 to 250 mm (in the blood vessel). The same applies to the materials which are used for the outer side; also here there shall be used the materials already known from the catheter technology. 
     In order to nevertheless keep the flow resistance and, thus, the output of the conveying device—which is required for the complete compensation—low, it is advantageous if the fibres of the hollow fibre membrane for the most part are arranged substantially in parallel to a longitudinal extension of the catheter. Here, the longitudinal extension of the catheter naturally corresponds to the main flow direction of the blood in the vessel surrounding the catheter during operation. 
     A simple possibility to provide the inflow and the outflow of the carrier medium at the same—preferably the distal—end of the catheter is that the membrane, in particular the hollow fibre membrane, is folded. With a folding by 180° at the opposing (proximal) end of the catheter, both ends of the hollow fibres are located at the same end of the catheter. 
     Even if principally also the use of a disposable catheter with a—apart from the membrane—closed reservoir for the carrier medium is conceivable and also enjoys the advantages according to the invention, it is favourable if the catheter has an inlet and an outlet for the carrier liquid which are connected with an extracorporeal exchange device for the formation of a circulation or circuit system with the exchange device, wherein the circulation system has a pump for the conveying of the carrier liquid. In this case it refers to a double-lumen catheter. Such exchange devices and circulation or circuit systems are principally known, wherein reference is made in particular to applications for the support of the pulmonary function (ECMO, ECCO2R) and dialysis applications. 
     In connection with the application as a lung support, it is favourable if the exchange device is a membrane oxygenator. The exchange device can, however, also be an absorber (for the removal of (32 microglobulin, rheumatoid factors, lipids, immunoglobulins, or endotoxins), e.g. activated carbon absorbers or resin absorbers, it can be membrane devices for the diffusion, ultrafiltration, and/or convection of substance from the carrier medium, or it can be other filter devices. 
     Preferably, such a device can be made available together with a catheter and an extracorporeal exchange device in a kit, wherein the kit comprises additionally at least one tube connected with the catheter and the exchange device for the transport of a carrier liquid between the catheter and the exchange device. In this connection the tube preferably has at least two channels or lines, wherein an entry channel for the supply of the carrier liquid to the catheter and an exit channel for discharging the carrier liquid from the catheter are installed. 
     A particularly simple and continuous application is facilitated if, in the kit, the exchange device is a portable exchange device, preferably with a carrying means. As a carrying means there can be provided for instance fastening elements for a wrist strap or for the fastening at a belt or at another piece of clothing. 
     With regard to the method according to the invention is particularly favourable if the substance to be withdrawn for diagnostic purposes is a disease indicator, whereby also endogenous substances the presence of which (e.g. antibodies) or the quantity of which (e.g. inflammatory proteins, cytokines, complement factors, etc.) is correlated with a disease or its course, are comprised, in particular for instance at least a pathogen or at least an antibody, a substance which is toxic to the body (e.g. glucose or electrolytes outside the physiological range, like potassium, calcium, etc.), a substance which can otherwise not be excreted by the body (see storage diseases regarding glucose, copper, etc.), or in general an endogenous substance the quality or quantity of which correlates with the course of a disease, in particular at least a protein which is specific to a disease, or a substance generated by the courses of diseases (e.g. complement, cytokines, interleukins, or antibodies). When the substance is for instance glucose, the method can for instance be part of a diagnosis method for measuring the blood glucose. 
     In the following, preferred embodiments of the device according to the invention and of the method according to the invention as well as preferred combinations thereof will be stated: 
     1. A device comprising a catheter for intravascular use, wherein the catheter has a blood inlet and a blood outlet, and comprises a membrane, wherein a first side of the membrane is in contact with a carrier medium and wherein the membrane is arranged in the catheter in such a way that at least one part of the blood flowing into the catheter via the blood inlet during operation comes into contact with a second side of the membrane lying opposite the first side thereof, before the blood leaves the catheter via the blood outlet, wherein the membrane allows an exchange of at least one substance to be exchanged between the carrier medium and the blood, and wherein the catheter comprises a conveying device which is configured to at least partially compensate for a pressure difference between the blood inlet and the blood outlet, characterized in that the carrier medium is a carrier liquid in which the substance to be exchanged can be dissolved. 
     2. The device according to embodiment 1, characterized in that the conveying device comprises a drive unit for generating a torque and a pump rotor connected with the drive unit for the transmission of a torque. 
     3. The device according to embodiment 2, characterized in that the drive unit comprises an electric motor. 
     4. The device according to embodiment 2, characterized in that the drive unit comprises a turbine element around which the carrier medium flows during operation. 
     5. The device according to anyone of embodiments 2 through 4, characterized in that the pump rotor is connected to the drive unit via a magnetic coupling, wherein the magnetic coupling comprises two coupling parts for the transmission of the torque along an axis of rotation being rotatable relative to each other and each including a permanent magnet. 
     6. The device according to embodiment 5, characterized in that one of the coupling parts comprises an at least partially ferromagnetic guiding element which is non-rotatably connected to the permanent magnet of the coupling part, wherein one part of the guiding element is disposed radially outside of the permanent magnet of the other coupling part. 
     7. The device according to embodiment 6, characterized in that the guiding element comprises at least one diamagnetic separation parting the guiding element into at least two ferromagnetic sections. 
     8. The device according to anyone of embodiments 5 through 7, characterized in that the two coupling parts are hermetically separated. 
     9. The device according to anyone of embodiments 1 through 8, characterized in that the substance to be exchanged is CO2, wherein the carrier liquid has a solubility of at least 140 ml CO2, in particular of at least 180 ml CO2, in 100 ml of the carrier liquid at 37° C. 
     10. The device according to anyone of embodiments 1 through 9, characterized in that the carrier liquid is a perfluorocarbon or an albumin solution and/or an electrolyte solution, in particular enriched with specific proteins or glucose derivatives, or that it is a commercially available dialysate which preferably was additionally processed via an ion exchanger, activated carbon or another adsorber. 
     11. The device according to anyone of embodiments 1 through 10, characterized in that the carrier liquid comprises a decoupler substance. 
     12. The device according to anyone of embodiments 1 through 11, characterized in that the membrane is a selectively permeable membrane which is permeable to at least the substance to be exchanged. 
     13. The device according to anyone of embodiments 1 through 12, characterized in that the membrane is a hollow fibre membrane. 
     14. The device according to embodiment 13, characterized in that the hollow fibres of the hollow fibre membrane for the most part are arranged substantially in parallel to a longitudinal extension of the catheter. 
     15. The device according to anyone of embodiments 1 through 14, characterized in that the membrane is folded. 
     16. The device according to anyone of embodiments 1 through 15, characterized in that nanocapsules or microcapsules are bonded with the surface of the membrane. 
     17. The device according to anyone of embodiments 1 through 16, characterized in that the membrane comprises nanocapsules or microcapsules, wherein the nanocapsules or the microcapsules are embedded in an otherwise homogeneous carrier material, or that the membrane consists of nanocapsules or microcapsules which are bonded with each other. 
     18. The device according to anyone of embodiments 1 through 17, characterized in that the catheter has an inlet and an outlet for the carrier liquid which are connected with an extracorporeal exchange device for the formation of a circulation system with the exchange device, wherein the circulation system has a pump for the conveyance of the carrier liquid. 
     19. The device according to embodiment 18, characterized in that the exchange device is a membrane oxygenator. 
     20. A kit comprising a device according to anyone of embodiments 18 or 19 and at least one tube connected with the catheter and the exchange device for the transport of a carrier liquid between the catheter and the exchange device. 
     21. The kit according to embodiment 20, characterized in that the exchange device is a portable exchange device, preferably with a carrying means. 
     22. A device comprising a catheter for intravascular use, wherein the catheter has a blood inlet and a blood outlet, and comprises a membrane, wherein a first side of the membrane de-limits a lumen for the reception of a carrier medium, and wherein the membrane is arranged in the catheter in such a way that at least one part of the blood flowing into the catheter via the blood inlet during operation comes into contact with a second side of the membrane lying opposite the first side thereof, before the blood leaves the catheter via the blood outlet, wherein the membrane allows an exchange of at least one substance to be exchanged between a carrier medium received in the lumen during operation and the blood, characterized in that the lumen for the reception of a carrier liquid in which the substance to be exchanged can be dissolved is designed as a carrier medium, and that the membrane allows an exchange between the carrier liquid and the blood during operation. 
     23. The device according to embodiment 22, characterized in that the membrane is a membrane which is suitable for liquids. 
     24. The device according to embodiments 22 or 23, characterized in that the membrane is designed for the use with a per-fluorocarbon or an albumin solution and/or an electrolyte solution, in particular enriched with specific proteins or glucose derivatives, or with a commercially available dialysate which preferably was additionally processed via an ion exchanger, activated carbon or another adsorber, as a carrier liquid. 
     25. The device according to anyone of embodiments 22 through 24, characterized in that the catheter comprises a conveying device which is configured to at least partially compensate for a pressure difference between the blood inlet and the blood outlet during operation. 
     26. A device comprising a catheter for intravascular use, wherein the catheter has a blood inlet and a blood outlet, and comprises a membrane, wherein a first side of the membrane is in contact with a carrier medium and wherein the membrane is arranged in the catheter in such a way that at least one part of the blood flowing into the catheter via the blood inlet during operation comes into contact with a second side of the membrane lying opposite the first side thereof, before the blood leaves the catheter via the blood outlet, wherein the membrane allows an exchange of at least one substance to be exchanged between the carrier medium and the blood, characterized in that the carrier medium is a carrier liquid in which the substance to be exchanged can be dissolved. 
     27. A method for removing at least one substance from venous blood for diagnostic purposes using a device or a kit according to anyone of embodiments 1 through 26, wherein the substance to be removed corresponds to the substance to be exchanged through the membrane of the catheter of the device. 
     28. The method according to embodiment 27, wherein the substance to be removed is a disease indicator, in particular at least a pathogen, at least an antibody, a substance which is toxic to the body, a substance which can otherwise not be excreted by the body, or an endogenous substance the quality or quantity of which correlates with the course of a disease, in particular at least a protein which is specific to a disease, or a substance generated by the courses of diseases. 
     29. A method for the treatment of a human or animal body by replacing or exchanging at least one substance from the blood or into the blood of the body using a device or a kit according to anyone of embodiments 1 through 26. 
     30. A use of the device according to anyone of embodiments 22 through 25 with a liquid carrier medium. 
     31. The use according to embodiment 30, characterized in that the liquid carrier medium is a perfluorocarbon or an albumin solution and/or an electrolyte solution, in particular enriched with specific proteins or glucose derivatives, or that it is a commercially available dialysate which preferably was additionally processed via an ion exchanger, activated carbon or another adsorber. 
     32. The use according to embodiments 30 or 31, characterized in that the liquid carrier medium comprises a decoupler substance. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the following, the invention will be explained still further by means of particularly preferred embodiments to which it shall, however, not be restricted, and with reference to the accompanying drawings. Individually, in the drawings: 
         FIG. 1  schematically shows a longitudinal section through a device with an intravascular catheter having a lateral blood inlet and a centrally arranged hollow fibre membrane; 
         FIG. 2  schematically shows a longitudinal section through a device with an intravascular catheter having a central blood passage, laterally arranged hollow fibre membranes, and a proximal reflux lumen; 
         FIG. 3  schematically shows a cross-section through the catheter along line III-III in  FIG. 2 ; 
         FIG. 4  schematically shows a longitudinal section through a device with an intravascular catheter having a central blood passage and laterally arranged hollow fibre membranes without a proximal reflux lumen; 
         FIG. 5  schematically shows a longitudinal section through a device according to  FIG. 4  with a motor-driven conveying de-vice at the distal end of the blood passage; 
         FIG. 6  schematically shows a longitudinal section through a device with an intravascular catheter having laterally arranged hollow fibre membranes, lateral blood inlets and a tur-bine-driven conveying device at the distal end of the catheter; 
         FIG. 7  shows a further design variant of an intravascular catheter with a twisted hollow fibre membrane; and 
         FIG. 8  schematically shows an extracorporeal circulation system for use with a catheter according to anyone of  FIGS. 1 through 7 . 
     
    
    
     DETAILED DESCRIPTION 
     In  FIG. 1  there is schematically shown a device  1  with an intravascular catheter  2  in a longitudinal section. The catheter  2  is provided for being inserted through a vein and being positioned in the inferior or superior vena cava. The catheter  2  can in principle be of a usual design and has those properties which are required for its use or application. The catheter  2  comprises a catheter tube  3 . The catheter tube  3  has a cross-section which is substantially circular in the relaxed state. The diameter of the catheter tube  3  is adapted to a vein, in particular it is smaller than the diameter of a vein in which the catheter shall be used. The catheter tube  3  consists of an elastic material which is commonly used for catheters, for instance of a biocompatible polyurethane. In the catheter tube  3  a membrane  4 ′, in particular a hollow fibre membrane  4 , extending lengthwise of the catheter tube  3  is arranged. For the sake of simplicity, the hollow fibre membrane  4  is only represented with one individual hollow fibre  5 , and, in practice, it comprises a plurality of semipermeable hollow fibres consisting of one of the preferred membrane materials mentioned at the beginning. When, in the following, the function of the hollow fibre  5  is described, the respective explanations equally apply to a second and each further hollow fibre of the hollow fibre membrane  4 . The hollow fibre membrane  4  is designed such that at the distal end  6  of the catheter  2  the carrier liquid can be introduced into the hollow fibre membrane  4  via an inlet  7  for a carrier liquid, said carrier liquid passing through the hollow fibre  5  of the hollow fibre membrane  4 , and that the carrier liquid can be discharged via an outlet  8  for the carrier liquid. Therefore, the carrier liquid passes through the hollow fibre membrane  4  or its hollow fibre  5  between the inlet  7  and the outlet  8 . Hence, the inner side of the hollow fibre  5  forms a first side of the hollow fibre membrane  4  which is in contact with the carrier liquid. The ends  9  of the hollow fibre  5  are fixed by an embedding mass  11  in a connecting area  10  and are connected with the embedding mass  11 , for instance an epoxy resin. In the region of a proximal end  12  of the catheter, the hollow fibre  5  has a bend  13  so that the hollow fibre  5  has a continuous loop-like extension between the inlet  7  and the outlet  8 . 
     The intravascular catheter  2  is further designed such that blood can flow around it and can pass through it. For this purpose, the catheter tube  3  has at least one lateral blood inlet  14  just outside the connecting area  10  at the distal end  6 . At the proximal end  12  the catheter tube  3  is opened so that the opening forms a blood outlet  15 . The blood flow in the catheter  2 , into the catheter  2  and out of the catheter  2  is indicated by direction arrows  16 . In this connection, the blood flows around the hollow fibre  5  of the hollow fibre membrane  4  starting from the lateral blood inlet  14  so that at least one part of the blood flowing into the catheter  2  via the blood inlet  14  during operation comes into contact with an outer side of the hollow fibre  5 , which outer side forms a second side of the hollow fibre membrane  4  lying opposite to the first side thereof. Due to the material of the hollow fibre  5 , said hollow fibre  5  and, thus, the hollow fibre membrane  4  as a whole allow an exchange of at least one substance to be exchanged between the carrier liquid inside the hollow fibre  5  and the blood surrounding it. 
     The inlet  7  and the outlet  8  are connected in a connection region  17  with a feeding tube  18 . The feeding tube  18  has a coaxial inner tube  19 . In the embodiment represented in  FIG. 1 , the channel formed inside the inner tube  10  serves as a supply channel  20 , and the channel formed between the inner tube  19  and the outer jacket of the feeding tube  18  serves as a discharge channel  21  for the carrier liquid. The feeding tube is connected with the catheter  2  in the connection region  17  by means of an elastic connecting mass  22 , for instance polyurethane. 
     In  FIGS. 2 and 3  there is schematically shown a further embodiment of a device  22  with an intravascular catheter  23  having a central blood passage  24 . The basic design of the catheter  23  with one catheter tube  25  corresponds to the catheter  2  and the catheter tube  3  described in connection with  FIG. 1 , unless it will be described differently in the following. 
     The central blood passage  24  extends as an open channel along a longitudinal axis in the centre of the catheter  23 . Thus, the blood passage  24  connects a central blood inlet  26  at the distal end  27  of the catheter  23  and a central blood outlet  28  at the proximal end  29  of the catheter  23  in parallel to the catheter tube  25 . 
     In the catheter  23  there is arranged a substantially cylindrical hollow fibre membrane  30 , wherein the semipermeable hollow fibres  31 ,  32  are arranged around the central blood passage  24  and substantially in parallel to the longitudinal extension of the catheter  23 . For the sake of simplicity, the hollow fibre membrane  30  is only represented with two individual hollow fibres  31 ,  32 , and, in practice, it comprises a plurality of semipermeable hollow fibres consisting of one of the preferred membrane materials mentioned at the beginning. The first hollow fibre  31  is connected to a supply channel  33  of a feeding tube  34  at the distal end  27  of the catheter  23 . The second hollow fibre  32  is connected to a discharge channel  35  of the feeding tube  34  at the distal end  27  of the catheter  23 . When, in the following, the function of the first or second hollow fibre  31 ,  32  is described, the respective explanations equally apply to each of a first part of all further hollow fibres of the hollow fibre membrane  30  in accordance with the first hollow fibre  31  or of a second part of all further hollow fibres of the hollow fibre membrane  30  in accordance with the second hollow fibre  32 . 
     In correspondence with the catheter  2  in  FIG. 1 , the first ends of all hollow fibres  31 ,  32  are fixed in a first ring-shaped connecting area  36  at the distal end  27  of the catheter  23  by an embedding mass  37  and they are connected with the embedding mass  37 , for instance an epoxy resin. At the proximal end  29  of the catheter  23  there are fixed the second ends of all hollow fibres  31 ,  32  in a second ring-shaped connecting area  38  also by means of an embedding mass  39  and they are connected with the embedding mass  39 , for instance an epoxy resin. The hollow fibres  31 ,  32  are connected to a reflux lumen  40  at their second ends, said reflux lumen  40  being formed at the distal end  29  of the catheter  23  as a ring-shaped channel within the catheter tube  25 . Thus, the hollow fibre membrane  30  is designed in such a way that a carrier liquid introduced at the distal end  27  of the catheter  23  via an inlet  41  into the hollow fibre membrane  30  passes through the first hollow fibre  31  of the hollow fibre membrane  30 , changes at the proximal end  29  of the catheter over to the reflux lumen  40 , is guided to the second hollow fibre  32 , passes through the second hollow fibre  32  and is discharged via an outlet  42 . 
     Thus, the inner side of the hollow fibres  31 ,  32  forms a first side of the hollow fibre membrane  30  which is in contact with the carrier liquid. The blood flow in the catheter  23 , into the catheter  23  and out of the catheter  23  is indicated by direction arrows  43 . In this connection, the blood flows around the hollow fibres  31 ,  32  of the hollow fibre membrane  30  starting from the central blood passage  24  so that at least one part of the blood flowing into the catheter  23  via the blood inlet  26  during operation comes into contact with an outer side of the hollow fibres  31 ,  32 , which outer side forms a second side of the hollow fibre membrane  30  lying opposite the first side thereof. Due to the materials of the hollow fibres  31 ,  32 , said hollow fibres and, thus, the hollow fibre membrane  30  as a whole allow the exchange of at least one substance to be exchanged between the carrier liquid inside the hollow fibres  31 ,  32  and the surrounding blood. 
     In  FIG. 4  there is shown another alternative design variant of the device according to the invention with a catheter  44 . The basic design of the catheter  44  with a catheter tube  45  corresponds again to the catheter  2  or  23  described in connection with  FIGS. 1 to 3 , unless it will be described differently in the following. 
     In contrast to the above described catheters  2 ,  23 , according to  FIG. 4  the hollow fibre membrane  46  of the catheter  44 , which forms the membrane  4 ′ of the catheter, is arranged cylindrically around a central blood passage  24  like in  FIG. 2 , but the individual hollow fibres  47 ,  48  are formed loop-like—as in  FIG. 1 —with a bend  13  in the region of a proximal end  49  of the catheter  45 . Hence, the arrangement of the hollow fibre membrane  46  corresponds to a cylinder turned to the outside at half the height. The ends  50 ,  51  of the hollow fibres  47 ,  48  are fixed in a ring-shaped connecting area  52  by an embedding mass  53 , and they are connected with the embedding mass  53 , for instance an epoxy resin. The ends  50  of the hollow fibres  47 ,  48  which lie radially inside with respect to a central longitudinal axis of the catheter  45  lead into a ring-shaped inlet  54  of the hollow fibre membrane  46  for a carrier liquid. The ends  51  of the hollow fibres  47 ,  48  which lie radially outside with respect to a central longitudinal axis of the catheter  45  correspondingly lead into a ring-shaped outlet  55  of the hollow fibre membrane  46  for a carrier liquid, wherein said ring-shaped outlet  55  is arranged concentrically to the inlet  54  and radially outside thereof. The inlet  54  of the hollow fibre membrane  46  is connected with a supply channel  56  of a feeding tube  57 . The outlet  55  of the hollow fibre membrane  46  is connected with a discharge channel  58  of the feeding tube  57 . Otherwise, the feeding tube  57  is designed in a manner identical to that of the feeding tube  18  according to  FIG. 1 . 
     In the represented example, the channels  56 ,  58  of the feeding tube  57  end at two radially opposing locations in the ring-shaped inlet  54  and the ring-shaped outlet  55  so that the feeding tube  57  is bifurcated into two tube branches  60  at the connection region  59 . The carrier liquid introduced via the inlet  54  into the hollow fibre membrane  46  passes through the hollow fibres  47 ,  48  of the hollow fibre membrane  46  in parallel to the longitudinal extension of the catheter  45  up to the bend  13  of the hollow fibres  47 ,  48  and back to the distal end  61  of the catheter and is discharged via the outlet  55 . 
     Radially inside the inlet  54  of the hollow fibre membrane  46 , the catheter  45  has a central blood inlet  62  into the blood passage  24  at the distal end  61  thereof. At the proximal end  49 , the catheter tube  44  is opened so that the opening forms a blood outlet  15  as in  FIG. 1 . The blood flow in the catheter  45 , into the catheter  45  and out of the catheter  45  is indicated by direction arrows  63 . In this connection, the blood flows around the hollow fibres  47 ,  48  of the hollow fibre membrane  46  starting from the blood inlet  62  so that at least one part of the blood flowing into the catheter  45  via the blood inlet  62  during operation comes into contact with an outer side of the hollow fibres  47 ,  48 . In order to avoid repetitions, with regard to the exchange of substances with the blood reference is made to the respective explanations with respect to  FIGS. 1 and 2  and the membranes shown therein. 
     Since the devices in  FIGS. 1 to 4  have been shown and described without conveying devices for the sake of simplicity, now  FIGS. 5 and 6  each show a conveying device  64 ,  65  which can be used in particular in the catheters  23  or  44  as shown in  FIGS. 2 and 4 , preferably in the blood inlet  26  or  62 , respectively. Accordingly, the catheters  44  are represented in  FIG. 5  and  FIG. 6  only sketchily, and with regard to the design and the functioning of the catheter  44  as well as of the membranes arranged therein reference is made to the earlier explanations in connection with  FIGS. 1 to 4 . 
     The conveying device represented in  FIG. 5  comprises a pump rotor  66  and a drive unit  67  in the form of an electric motor  68 . During operation, the electric motor  68  transmits a torque via a shaft  69  to the pump rotor  66 . The shaft  69  is supported by means of an end  70  lying opposite the electric motor  68  in a stator  71 . The stator  71  is fastened in the catheter  44  in a connecting area  52  via wings  72 . Here, the wings  72  are arranged substantially in parallel or slightly angled to a flow direction (indicated by the direction arrows  73 ) of the blood entering through the lateral blood inlets (not shown) into the catheter  44 . The pump rotor  66  itself also has blades  74  which are arranged propeller-like for the axial transport of the blood located between the blades  74  during a rotation of the pump rotor  66 . 
     During operation, the pump rotor  66  is driven by the electric motor  68 —which forms a drive unit  85 ′—in such a way that an acceleration of the blood flow in the area of the blood inlets and, thus, an excess pressure at the distal end  61  of the catheter  44  are generated. In this connection, the rotational speed of the electric motor  68  is controlled via a control (not shown) such that the obtained excess pressure just compensates for a pressure difference between the blood inlets and the blood outlet  15  (see  FIG. 5 ). Thereby the flow resistance caused by the hollow fibres  47 ,  48  inside the catheter  44  is effectively compensated for. Thus, the amount of blood moved through the lumen of the catheter  44  corresponds to the same amount which would be moved through the hollow catheter tube  45  if the catheter had no membrane. 
     For the fixation with respect to the stator  71 , the electric motor  68  is embedded in an embedding mass  76  which connects the electric motor with the catheter tube  44 . 
       FIG. 6  shows a further, preferred embodiment for a conveying device  65 . The conveying device  65  forms the distal end  77  of the catheter  44 . The conveying device  65  comprises a pump rotor  78  which is rotatably arranged between a magnetic coupling  79  and a pump stator  80  and is rotatably supported with a shaft  81  in the pump stator  80 . The pump stator  80  is fastened via lateral wings  82  in a first connecting ring  83 . The first connecting ring  83  comprises an embedding mass  84  in which the hollow fibres  47 ,  48  of the hollow fibre membrane  46  are embedded and with which they are connected, wherein the hollow fibres  47 ,  48  extend through the first connecting ring  83  axially, i.e. in parallel to a longitudinal axis of the catheter  44 . The first connecting ring  83  is connected at a radial outer side to the catheter tube  45  of the catheter  44 . 
     The conveying device  65  further comprises as a drive unit  85 ′ a turbine element  85  which is supported in a turbine stator  86  such that it is rotatable around a shaft  87 . The shaft  87  forms a non-rotatable connection of the turbine element  85  with the magnetic coupling  79 , in particular with a drive-side coupling part  88 . The turbine stator  86  is arranged between the drive-side coupling part  88  and the turbine element  85  which acts as a turbine rotor, wherein the shaft  87  extends through the turbine stator  86 . The turbine stator  86  has lateral wings  89  by means of which it is fastened in a section  91  of the inner tube  92  of a feeding tube  93 , said section  91  being widened in the connecting area  90 . Correspondingly, the turbine element  85  is also arranged in the widened section  91 , and, thus, it is subjected to the flow of a carrier liquid  95  supplied through a supply channel  94  of the feeding tube  93 . As is indicated by the direction arrows  95 , the flow of the carrier liquid  95  leads out of the supply channel  94  into the widened section  91  via propeller-like blades  97  arranged at the turbine element  85  for the reception of a torque and past the wings  89  of the turbine stator  86  to the inlet  54  of the hollow fibre membrane  46 . 
     The ring-shaped inlet  54  and outlet  55  of the hollow fibre membrane  46  is formed at a second connecting ring  98  which—comparable to the connecting area  52  in  FIG. 4 —comprises an embedding mass  99  in which the ends  50 ,  51  of the hollow fibres  47 ,  48  are embedded so that they lead into the inlet  54  or into the outlet  55 . Between the second connecting ring  98  and the first connecting ring  83  which is arranged proximal of the second connecting ring  96 , the catheter  44  has lateral blood inlets  100 . 
     Apart from the drive-side coupling part  88 , the magnetic coupling  79  also comprises a corresponding output-side coupling part  101  which is non-rotatably connected to the pump rotor  78 . Due to the rotatable support via the separated shafts  81 ,  87  in the stators  80 ,  86 , the drive-side coupling part  88  is rotatably supported relative to the output-side coupling part  101 . The output-side coupling part  101  comprises an output-side two-pole permanent magnet  102  which is non-rotatably connected to the shaft  81  of the pump rotor  78 . The drive-side coupling part  88  comprises a drive-side two-pole permanent magnet  103  which is non-rotatably connected to the shaft  87  of the turbine element  85 . The output-side permanent magnet  102  is circumferentially surrounded by a substantially cup-shaped guiding element  104  having a hollow cylindrical jacket. In this connection, there is provided a clearance or gap between the output-side permanent magnet  102  and the guiding element  104  so that the output-side coupling part  101  is coupled to the drive-side coupling part  88  in a contact-free fashion. The guiding element  104  is mainly made of a ferromagnetic material. The jacket of the guiding element  104  is interrupted by a diamagnetic separation (not shown) only in a narrow angular region. Substantially, the separation parts the guiding element  104  into two ferromagnetic halves or half-shells. An intersecting plane running through the separation is thus perpendicular to a direction of magnetisation of the drive-side two-pole permanent magnet  103  that is connected to the guiding element  104 . Consequently, the ferromagnetic sections of the guiding element  104  defined by the separation are magnetised in accordance with the drive-side permanent magnet  103 . 
     Due to the concact-free coupling there is provided a hermetic separation (not shown) between the drive-side coupling part  88  and the output-side coupling part  101 . The hermetic separation is formed by a foil sealingly connected with the radial inner side of the second connecting ring  98 . 
     During operation, by the flow of the supplied carrier liquid a torque is applied via the blades  97  to the turbine element  85 . The turbine element  85  transmits the torque via the shaft  87  to the drive-side coupling part  88  of the magnetic coupling  79 . By the magnetic forces between the coupling parts  88 ,  101 , the torque is transmitted from the drive-side coupling part  88  to the output-side coupling part  101 , wherein the power of the magnetic forces defines a certain maximum transmittable torque beyond which a “slipping” of the coupling parts  88 ,  101  relative to each other occurs. The output-side coupling part  101  transmits a torque exerted by the drive-side coupling part  88  via the shaft  81  to the pump rotor  78 . By means of lateral propeller-like blades  105 , the pump rotor  78  transports the blood located between the blades  105  from the blood inlets  100  in the direction of the blood passage  24  inside the catheter  44 . In this way, the conveying device  65  generates a pressure difference between the blood inlets  100  and the proximal end of the blood outlet  24  which preferably and substantially completely compensates for a pressure difference between the proximal and the distal end (not shown) of the catheter  44  which is due to the flow resistance of the hollow fibre membrane  46 . Here, the turbine element  85  and the pump rotor  78  are preferably tuned with each other such that an optimum ratio between the flow velocity of the carrier liquid in the hollow fibres  47 ,  48  and the flow velocity of the blood in the blood passage  24  is obtained. 
     In the above embodiments, the two conveying devices  64 ,  65  are arranged in a region of the distal end  27 ,  77  of the catheter  44 , respectively. As a matter of course, also arrangements at any location within the catheter  44  are conceivable, whereby, as expected, similar advantages can be achieved. Furthermore, of course also other arrangements than the shown arrangements of the respective rotors (pump rotor or turbine element) with regard to the respective stators or with several stators or altogether with only one stator are possible without leaving the functioning according to the invention and, thus, the scope of the invention. 
     Moreover, instead of a hollow fibre membrane also another type of membrane can be used in the catheter, wherein the person skilled in the art will adapt the conveying device  64 ,  65  to the pressure difference to be expected due to the different flow resistances of other types of membranes. 
       FIG. 7  shows another design variant of an intravascular catheter  106  which is provided for being inserted through a vein and for being positioned in the inferior or the superior vena cava. The catheter  106  can in principle be of a usual design and has those properties which are required for its use or application. Therefore, the catheter  106  comprises a catheter tube  107  formed in particular with a circular cross-section, the diameter of which is adapted to the diameter of the vein, in particular it is slightly smaller than the diameter of the vein. The catheter tube  107  consists of an elastic material which is commonly used for catheters, for instance of a biocompatible polyurethane. In the catheter tube  107  there is present a hollow fibre membrane module  108  extending lengthwise of the tube  107 , with a hollow fibre membrane having a plurality of hollow fibres being permeable to gas but impermeable to liquids and consisting of one of the materials mentioned at the beginning, for instance polyethylene or thermoplastic polyurethane. The hollow fibre membrane module  108  is designed such that at the distal end of the catheter  106  a medium which flows through the hollow fibres can be fed via a first catheter connection  109  into the hollow fibre membrane  108 , and that the medium can be discharged via a second catheter connection  110 . Therefore, the medium which will be explained in detail below passes through the hollow fibre membrane module  108  between the first catheter connection  109  and the second catheter connection  110 .  FIG. 7  shows a possible design variant of the hollow fibre membrane module  108  as a bundle of hollow fibres which extends between the first catheter connection  109  and the second catheter connection  110  in a kind of a loop form along the inside of the catheter. Thus, the one ends of the hollow fibres are connected with the first catheter connection  109  and the second ends are connected with the second catheter connection  100 . At the connecting areas, the hollow fibres can be cast or connected with each other by an epoxy resin or the like. The loop-like extending bundle of hollow fibres can additionally be twisted. Furthermore, the intravascular catheter  106  is designed such that blood can flow around it and can flow through it. For this purpose, the tube  107  can for instance be provided with a number of inflow openings  11  just outside the two catheter connections  109 ,  110  and can be provided with a number of outflow openings  112  in the region of its proximal end. 
     The hollow fibre membrane module  108  can be designed such that in one part of the hollow fibres the medium flows in a parallel flow with the blood and that in another part of the hollow fibres the medium flows in a counterflow to the blood. In the shown embodiment, the two catheter connections  109 ,  110  are shown such that they are coaxially positioned, but they can also be arranged next to each other in dependence on the design of the hollow fibre membrane module  108  (see  FIG. 1  or  FIG. 2 ). Furthermore, the catheter connections  109 ,  110  are connected with flexible tubes extending in particular coaxially over one section, to which tubes a feeding tube  113  connected to the first connection  109  and a discharge tube  114  connected to the second connection  5  belong. 
     The catheters  2 ,  23 ,  44 ,  106  described and shown so far in  FIGS. 1 through 7  can be a component of a larger device which, together with one of the catheters  2 ,  23 ,  44 ,  106 , forms a circulation or circuit system  115  to which further, extracorporeal components belong.  FIG. 8  schematically shows an embodiment of such extracorporeally provided components, namely a pump  116  which conveys a carrier liquid into the supply channel  117  of a feeding tube  118  and thus to the catheter (not shown in  FIG. 8 ) and through it. The pump  116  is connected with the feeding tube  118 . A further component is an oxygenator  119  in which the carrier liquid coming from the discharge channel  120  is introduced. The oxygenator  119  can be a conventional, standard membrane oxygenator  119 ′ having a gas supply  121  and a gas discharge  122 . In the extracorporeal part of the circuit there are further located for instance a heat exchanger  123  which heats the carrier liquid up to body temperature, as well as further components which are not shown, for instance pressure measuring devices, devices for the flow measurement, bubble detectors, etc. 
     During operation, in a vein the major part of the blood transported in the vein and enriched with CO 2  comes into contact with the hollow fibre membrane module  108  between the distal and the proximal end of the catheter  106 . In this connection, the respective application-specific carrier liquid is pumped through the hollow fibre membrane module  108 , wherein the carrier liquid of the hollow fibre membrane module  108  in part passes in the flowing direction of the blood and in part passes against the flowing direction of the blood. At the surfaces of the hollow fibres, for instance carbon dioxide (CO 2 ) transitions from the blood into the carrier liquid. The carrier liquid enriched with CO 2  leaves the hollow fibre membrane module  108  as well as the catheter  106  via the discharge channel  120  and is guided into the external oxygenator  119  where the carbon dioxide is passed over and oxygen is optionally added to the carrier liquid. In a simple embodiment, the external oxygenator  119  is supplied with ambient air. Through the gas exchange processes in the oxygenator  119 , the liquid also absorbs oxygen from the ambient air so that oxygen is passed over to the passing blood in the hollow fibre membrane module  108 . In an alternative embodiment of the invention, the liquid can be enriched with oxygen within the frame of its oxygen capacity by a supply of oxygen in the oxygenator  119 . The carrier liquid heated up to body temperature is added again to the hollow fibre membrane module  108  in the circuit. The efficiency of the gas transfer in the hollow fibre membrane module  108  is particularly high due to the fact that the carrier liquid is pumped in the flowing direction of the blood as well as also against the flowing direction of the blood through the hollow fibre membrane module  108 . 
     Analogously to the application for the exchange of CO 2 , the device can also be used for the removal of other substances, e.g. endotoxins, from the blood. In this connection, as a carrier liquid a correspondingly suitable liquid (e.g. commercially available) dialysate or its preparation by activated carbon/ion exchanger/adsorber, or an isotonic liquid enriched with endotoxin-neutralizing protein (ENP), or albumin can be provided. Instead of a closed circulation or circuit system, the dialysate can be drawn from a reservoir, it can be pumped through the catheter and then it can be accumulated in a separate reservoir for the disposal thereof. 
     As a further alternative, in the closed circulation system  115  there can be provided instead of the oxygenator  119  or in addition to the oxygenator  119  a filtering unit, e.g. with an adsorption filter, so that a substance to be exchanged is separated in the filtering unit from the carrier medium. 
     The device according to the invention can be designed as a portable, small unit which can be carried along by the patient, in particular in a design in which ambient air is supplied to the external membrane oxygenator  119 . The device according to the invention can furthermore be used in each conventional extracorporeal method as an additional device, above all also in conventional dialysis circuits. 
     While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.