Adsorption device for regeneration of dialysate

Abstract

The present disclosure relates to systems that use adsorption devices or adsorption devices configured for dialysis therapy, such as extracorporeal blood therapy or peritoneal dialysis therapy.

Description

[Technical Field]

[0001] TECHNICAL FIELD

[0001] The present disclosure relates to systems that use adsorption devices or adsorption devices configured for dialysis treatments, such as extracorporeal blood treatments or peritoneal dialysis treatments. [Background technology]

[0002] Dialysis treatments are typically used to extract undesirable substances or molecules from a patient's blood and / or add desired substances or molecules to the blood. Such treatments are used when a patient is unable to effectively remove substances from their blood, such as when the patient suffers from temporary or permanent kidney failure.

[0003]

[0003] Extracorporeal blood therapy is accomplished by withdrawing blood from a patient and introducing the blood into a filtration unit (e.g., a dialyzer) where the blood can flow through a permeable membrane that selectively allows substances in the blood to cross the membrane from the primary chamber into the secondary chamber, and also selectively allows substances in the secondary chamber to cross the membrane into the blood in the primary chamber, depending on the type of treatment (ultrafiltration (UF) treatment, hemofiltration (HF) treatment, hemodialysis (HD) treatment, hemodiafiltration (HDF) treatment, etc.).

[0004]

[0004] Peritoneal dialysis treatment is accomplished by filling a patient's peritoneal membrane with a dialysate solution and, after a dwell phase, draining the dialysate solution from the patient. Peritoneal dialysis treatment and extracorporeal blood treatment (such as hemodialysis) are different treatments, but the concept remains similar: the patient's blood on the one hand and dialysate on the other. The membrane separating the blood side from the dialysate side is either the peritoneal membrane or the dialyzer membrane.

[0005] Dialysis treatments are widely performed in medical centers, where caregivers operate the dialysis system and ensure safe treatment. However, an increasing number of treatments are performed at home, where patients are not always accompanied by a caregiver. Therefore, simplifying or facilitating the handling of dialysis systems is essential to limit the risk of incorrect setup or operation, or the risk of contamination of sterile fluid elements from the system.

[0006] Furthermore, to dialyze a patient, a large amount of dialysis solution is consumed during one treatment, for example, in the case of hemodialysis therapy, approximately 120 liters.

[0007]

[0007] Because the volume of dialysate solution to be administered is large, one solution is to reuse or regenerate the dialysate during the course of the treatment, for example, as the dialysate solution is used. This solution makes it possible to use only a few liters (approximately 5 liters in the case of hemodialysis therapy). To regenerate the dialysate, the system may be equipped with an adsorption device. Summary of the Invention

[0008]

[0008] This specification discloses several features of the adsorption device, each of which may be claimed in an independent claim.

[0009] A first aspect of the present disclosure relates to a sorbent cartridge that may include a compressible layer (such as, but not limited to, foam) within the sorbent column. Overcoming manufacturing challenges due to sorbent density variations resulting in imperfect cartridge packing; Avoiding the formation of cavities and inhomogeneities in the adsorbent column during transport; Allowing flexibility to use different sorbent configurations within the same casing (e.g., foam fills void spaces, thereby ensuring complete packing) This may make it possible.

[0010] In one possible embodiment, the sorbent cartridge comprises: The cartridge body and Lid and a first port (which may optionally be located on the cartridge body); and a second port (which may optionally be located on the lid); an internal compartment through which the dialysate solution flows from the second port to the first port; an adsorbent column having at least one layer of purified material stored in an internal compartment; a compressible layer that is at least partially compressed; Equipped with.

[0011]

[0011] The cartridge may be constructed and arranged so that the dialysate solution entering the cartridge contacts the compressible layer before contacting the sorbent column (or other layers, such as the urease layer and / or adsorption layer). Although the compressible layer may be located anywhere within the sorbent cartridge, it may be preferable to locate the compressible layer at the ends of the cartridge, particularly at the ends of the internal compartments (e.g., at the top and / or bottom of the internal compartments).

[0012] The compressible layer may include at least one of a flexible behavior and an elastic behavior.

[0013] The compressible bed may be configured to act as a spring on the adsorbent column.

[0014] The sorbent column can include a set of particles disposed within the cartridge body and held by a compressible layer, which can exert a force on the sorbent column to prevent free movement of the particles or to maintain the integrity of the sorbent column.

[0015] The compressible layer may be compressed to about 10-90%, or to about 50%.

[0016] The compressible layer may include an open-cell sponge-type material to allow passage of the dialysate solution through the open-cell sponge-type material. The compressible layer may be configured to distribute / share the liquid evenly across the surface of the sorbent column.

[0017] The sorbent cartridge may further include a filter disposed between the compressible layer and the sorbent column or between the lid and the compressible layer.

[0018] The compressible bed may be compressed to compensate for density variations in the adsorbent column or volume changes in the adsorbent column.

[0019] The compressible layer may be disposed within the interior compartment upstream of the adsorbent column and against the lid. The pore size of the compressible layer may be between 30 and 100 pores per inch (ppi), between 40 and 90 ppi, between 40 and 50 ppi, or between 70 and 90 ppi. The compressible layer may comprise a biocompatible material.

[0020]

[0020] The cartridge body may include a generally conical shape, with the compressible layer disposed in a wider portion of the cartridge body.

[0021] A second aspect of the present disclosure relates to an adsorption device that may include an inner wall having a particular shape configured to improve the uniformity of dialysate flow through the adsorption device. Avoiding bypass of dialysate sorbent at the cartridge wall It is possible to The combination of smaller and larger steps provides a uniform effect across the entire cartridge, making it easier to manufacture (mold) the cartridge.

[0022] In one possible embodiment, the sorbent cartridge comprises: a cartridge body having an internal compartment, a first end, a second end, a first port (which may optionally be located on the first end), and a second port (which may optionally be located on the second end); an adsorbent column having at least one layer of purified material stored in an internal compartment; Equipped with.

[0023] The cartridge body may further include an inner wall extending from the first end to the second end, and the inner wall may include a first step and a second step disposed on at least one of the first steps to control the flow of dialysate solution adjacent the inner wall.

[0024] The inner wall may be configured to generate turbulence adjacent the inner wall so that the dialysate solution flows substantially uniformly through the sorbent column.

[0025]

[0025] The steps of the first staircase may be larger than the steps of the second staircase, and at least one of the first staircase and the second staircase may be configured such that the second end has a larger average diameter than the first end.

[0026]

[0026] The first staircase may include at least two steps, and / or the second staircase may include at least two steps. Each step of the first staircase may include a second staircase. The first staircase may include equally spaced steps, and / or the second staircase may include equally spaced steps.

[0027] A third aspect of the present disclosure relates to the configuration of an adsorption device or a system that uses such an adsorption device.

[0028] For example, the adsorption device may comprise a layer having a mixture of urease and activated carbon. This layer may not contain zirconium phosphate or zirconium oxide. This configuration: -Increasing the stability and shelf life of urease due to the unexpected stabilizing effect of activated carbon; Facilitating the cartridge assembly process by using urease in its directly manufactured form This may make it possible.

[0029] For example, the adsorption device may include a homogeneous mixture of at least one of ZP (zirconium phosphate), HZO (zirconium hydroxide), AC (activated carbon), and a Na source, but does not include urease. avoiding the depletion of urease in layers where urease activity is not required; - Avoiding leaching of urease from the upper layers within the adsorbent (enhancing biocompatibility); Eliminate the risk of premature ammonia leaching in cartridges with insufficient urease activity (mitigating the effects of incorrect storage or incorrect use) (this problem can occur in cartridges where the urease is part of the (homogeneous) absorbent layer (second layer)) This may make it possible.

[0030] For example, the system may include at least one of a dialysate loop line, an adsorption device, and a supply line configured to add a bicarbonate equivalent salt (such as lactate or acetate) in the dialysate loop line. Increased delivery of bicarbonate equivalents to the patient; and Compensating for the patient's acidotic state and This may make it possible.

[0031] For example, the system may include at least one of a dialysate loop line, an adsorption device, and a supply line configured to add Na salts (which may include at least one of chloride, lactate, or acetate) in the dialysate loop line. Preventing excessive removal of sodium from patients (e.g., with very low urea levels) This may make it possible.

[0032] In one embodiment, the sorbent cartridge comprises a urease layer comprising a mixture of urease and activated carbon, and a sorbent layer comprising zirconium-based ion exchange particles, wherein the components of the sorbent layer interact with the fluid either by adsorption or absorption.

[0033] The cartridge may be configured so that the spent dialysate contacts the urease layer before it contacts the adsorbent layer.

[0034] The urease layer may be free of ion exchange particles (e.g., Group IV transition metal-based ion exchangers), or cation or anion exchange particles. The adsorption layer may be free of urease. The adsorption layer may include activated carbon. In one embodiment, the urease layer does not include a cation exchanger.

[0035] The zirconium-based ion exchange particles may comprise at least one of cation exchange particles and anion exchange particles. The zirconium-based ion exchange particles may comprise zirconium phosphate, acid zirconium phosphate, sodium zirconium phosphate, zirconium oxide, zirconium hydroxide, zirconium oxide hydroxide, hydrous zirconium oxide, hydrous zirconium oxide, hydrated zirconium oxide, unhydrated zirconium oxide, or a combination thereof. The zirconium-based ion exchange particles may comprise a homogeneous mixture of zirconium phosphate and hydrous zirconium oxide.

[0036] The adsorption bed may further comprise a sodium source, which may comprise sodium carbonate and / or sodium bicarbonate.

[0037] The sorbent cartridge may further include an inlet port and an outlet port. The urease layer may be disposed near the inlet and the adsorbent layer disposed near the outlet.

[0038] The urease in the urease layer may be immobilized.

[0039] In one possible embodiment, a device for performing dialysis therapy includes a sorbent cartridge and a dialysate circuit in fluid communication with the sorbent cartridge. The dialysate circuit can be configured so that spent dialysate passes through the sorbent cartridge for purifying the spent dialysate. The sorbent cartridge can include a urease layer including a mixture of urease and activated carbon and a sorbent layer including zirconium-based ion exchange particles.

[0040] The cartridge may be configured so that the spent dialysate contacts the urease layer before it contacts the adsorbent layer.

[0041] The urease layer may be free of ion exchange particles (e.g., Group IV transition metal-based ion exchangers), or cation or anion exchange particles. The adsorption layer may be free of urease. The adsorption layer may include activated carbon. In one embodiment, the urease layer does not include a cation exchanger.

[0042] The urease layer may further include glucose. The adsorption layer may further include glucose, which may be used to function as an osmotic agent to control the osmotic pressure of the dialysate during priming. An advantage may be that this allows for the use of a priming dialysate that does not contain glucose. Thus, the priming solution of the dialysate circuit may include a glucose-free dialysate solution, or a dialysate solution may be generated during the priming process as described in PCT / IB2023 / 060957, filed October 31, 2023, in the name of Nextkidney, the entire disclosure of which is incorporated herein by reference.

[0043] The zirconium-based ion exchange particles may comprise at least one of cation exchange particles and anion exchange particles. The zirconium-based ion exchange particles may comprise zirconium phosphate, acid zirconium phosphate, sodium zirconium phosphate, zirconium oxide, zirconium hydroxide, zirconium oxide hydroxide, hydrous zirconium oxide, hydrous zirconium oxide, hydrated zirconium oxide, unhydrated zirconium oxide, or a combination thereof. The zirconium-based ion exchange particles may comprise a homogeneous mixture of zirconium phosphate and hydrous zirconium oxide.

[0044] The adsorption bed may further include a sodium source, which may include at least one of sodium carbonate, sodium bicarbonate, and sodium hydroxide.

[0045] The sorbent cartridge may include an inlet port and an outlet port, the urease layer may be located near the inlet, and the adsorbent layer may be located near the outlet.

[0046] The urease in the urease layer may be immobilized.

[0047] The device may further include a dialyzer in fluid communication with the sorbent cartridge, and the dialysate circuit may be configured to transfer spent dialysate from the dialyzer to the sorbent cartridge. The dialysate circuit may include a loop circuit including the dialyzer and the sorbent cartridge.

[0048]

[0048] This application claims the benefit of priority from EP22205023.9, EP22205027.0, EP22205030.4, EP22205036.1, EP22205040.3 and EP22205043.7 filed on November 2, 2022, the entire disclosures of which are incorporated herein by reference, and from PCT / IB2023 / 060957 filed in the name of Nextkidney on October 31, 2023.

[0049]

[0049] The present disclosure will be better understood in light of the following detailed description, including non-limiting examples illustrated by the following figures. [Brief explanation of the drawings]

[0050] [Figure 1] FIG. 1 illustrates a potential architecture of the system. [Figure 2] FIG. 1 illustrates normal operation of the dialysate circuit during treatment. [Figure 3] FIG. 1 shows an embodiment of an adsorption device. [Figure 4] FIG. 1 is a cross-sectional view of one embodiment of an adsorption device. [Figure 5a] FIG. 1 illustrates the general flow pattern of dialysate solution through the cavity of an adsorption device. [Figure 5b] FIG. 1 illustrates the general flow pattern of dialysate solution through the cavity of an adsorption device. [Figure 6a] FIG. 1 is a cross-sectional view of one embodiment of an adsorption device. [Figure 6b] FIG. 1 is a cross-sectional view of one embodiment of an adsorption device. [Figure 6c] FIG. 1 is a cross-sectional view of one embodiment of an adsorption device. [Figure 6d] FIG. 1 is a cross-sectional view of one embodiment of an adsorption device. [Figure 7] FIG. 1 is a cross-sectional view of one embodiment of an adsorption device. [Figure 8a] FIG. 1 shows the performance of one configuration of adsorbent in an adsorption device. [Figure 8b] FIG. 10 shows the performance of alternative adsorbent configurations in an adsorption device. [Figure 8c] FIG. 10 illustrates the performance of yet another configuration of adsorbent in an adsorption device. [Figure 8d] FIG. 10 illustrates the performance of yet another configuration of adsorbent in an adsorption device. [Figure 8e] FIG. 10 illustrates the performance of yet another configuration of adsorbent in an adsorption device. [Figure 9]FIG. 1 is a diagram comparing the urease activity of a urease layer containing urease and activated carbon with a urease layer containing urease but not activated carbon. [Figure 10] FIG. 1 is an exploded view of one embodiment of an adsorption device. [Figure 11a] FIG. 1 is a cross-sectional view of one embodiment of an adsorption device. [Figure 11b] FIG. 1 is a cross-sectional view of one embodiment of an adsorption device. DETAILED DESCRIPTION OF THE INVENTION

[0051] The following detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the present disclosure may be practiced. These embodiments, sometimes referred to herein as "examples," are described in sufficient detail to enable those skilled in the art to practice the present disclosure. The embodiments may be combined, other embodiments may be utilized, or structural, logical, and electrical changes may be made without departing from the scope of the present disclosure. Therefore, the following detailed description is not to be taken in a limiting sense, and the scope of the present disclosure is defined by the appended claims and their equivalents.

[0052]

[0051] All scientific and technical terms used herein have the meanings commonly used in the art unless otherwise specified. The definitions provided herein are intended to facilitate understanding of certain terms used frequently herein and are not intended to limit the scope of the present disclosure.

[0053]

[0052] As used in this specification and claims, the singular forms "a," "an," and "the" include embodiments with plural referents unless the content clearly dictates otherwise.

[0054]

[0053] As used in this specification and claims, any directions referred to herein, such as "top," "bottom," "left," "right," "upper," "lower," and other directions or orientations, are described herein for clarity with respect to the figures and are not intended to limit the actual device or system unless the content expressly states otherwise. The devices and systems described herein can be used in several directions and orientations.

[0055]

[0054] As used in this specification and claims, the words "have," "having," "include," "including," "comprise," "comprising," and the like are used in their open-ended sense and generally mean "including, but not limited to."

[0056]

[0055] As used in this specification and claims, the term "or" is generally used in its sense including "and / or" unless the content clearly dictates otherwise.

[0057]

[0056] As used in this specification and claims, "at least one of A, B, and C," "at least one of A, B, or C," "selected from the group consisting of A, B, C, and combinations thereof," etc., are used in their open-ended sense, including "A only, or B only, or C only, or any combination of A, B, and C," unless the content clearly dictates otherwise.

[0058] According to one embodiment of the present disclosure shown in FIG. 1, the system (100) may include a reusable portion (101) and a disposable portion (102). The disposable portion (102) may include elements that must be discarded after a predetermined number of uses, e.g., after one treatment. The operational life of the disposable portion (102) may be directly dependent on the number of treatments. These elements may be wetted by medical fluids (e.g., dialysis fluid) or by the patient's body fluids (e.g., blood).

[0059]

[0058] The reusable part (101) may comprise expensive elements, such as sensors (103), electronic components, user interface devices (107), valve or pump actuators (105), processors (109), or memories. The reusable part (101) is used continuously with several disposable parts (102). The reusable part (101) may comprise components that can be replaced when they become too worn, when they break, or after a predetermined period of time that is much longer than one treatment. The change of the reusable part may depend on the wear of the components.

[0060] The reusable portion (101) may be configured to be operably coupled to the disposable portion (102). The sensor (103) may be configured to be operably coupled to a sensing area (104) of the disposable portion. The actuator (105) may be configured to be operably coupled to an actuation area (106) of the disposable portion (102). The reusable portion (101) (e.g., a user interface device (107)) may be configured to provide information to and / or receive instructions from the patient (108). At least one of the sensor (103), the actuator (105), and the user interface device (107) may be connected to a processor (109). The disposable portion (102) may be connected to or in contact with the patient (108) at least during treatment.

[0061] Although the following description discloses a hemodialysis treatment system using an adsorption device, similar adsorption devices can be used for peritoneal dialysis treatment. The type of treatment should not be understood to limit the use of the adsorption devices disclosed herein.

[0062] According to one embodiment shown in FIG. 2, the system may include a fluid circuit (1). The fluid circuit (1) of the system may include a blood circuit (2), a dialysate circuit (3), and a first filter (e.g., a dialyzer) (4). The fluid-wetted elements of the fluid circuit may be part of a disposable portion (e.g., as disclosed above). The system may include at least one of a first sensor (18), a second sensor (19), a third sensor (20), a fourth sensor (21), a fifth sensor (22), and other sensors. These sensors may be part of a reusable portion (e.g., as disclosed above).

[0063] The blood circuit (2) may include at least one of a connector (24), an arterial line (25), a venous line (26), and a first pump (13). The arterial line (25) and / or the venous line (26) may be intended to be connected to a patient (32), for example, via a catheter (not shown here), for example, during treatment. The first pump may be configured to move fluid (e.g., the patient's blood) from the arterial line to the venous line during normal operation (e.g., during treatment) and from the venous line to the arterial line during reverse operation (e.g., during at least a portion of priming). The first pump may be controlled by a processor.

[0064]

[0063] The blood circuit (2) may further include at least one of a drip chamber (27), a pressure sensor (18), an air sensor (19), a level sensor (20), and a valve or clamp (17). The drip chamber (27) may include an air flow device (23). At least some of the above elements may be disposed within the blood cartridge (5).

[0065] The dialysate circuit (3) may include at least one of a dialysate loop line (29), a second pump (14), a third pump (15), a second filter (12) (e.g., an adsorption device), and a first bag (10) (also referred to as a metering bag). The dialysate circuit (3) may include at least one of a supply line (31) connected to the second bag (11). The supply line may include a fourth pump (16). The dialysate circuit may further include at least one of a pressure sensor (18), a temperature sensor (21), an ammonia sensor (22), a connector (24), and a valve or clamp (17). At least some of the above elements may be disposed within the dialysate cartridge (6).

[0066] The blood circuit (2) and the dialysate circuit (3) may be fluidly connected to a first filter (4), e.g., a dialyzer. The first filter may include a blood compartment connected to the blood circuit and a dialysate compartment connected to the dialysate circuit. Both may be separated by a permeable membrane.

[0067] The weighing bag (10) may be placed on a warmer and / or a weighing scale (not shown), which may be connected to a processor to determine the volume (or weight, or data related to weight or volume) of the fluid (liquid) stored in the weighing bag (10).

[0068] In one embodiment, a first bag may be configured to store the dialysate solution needed for treatment. A second pump (14) moves the solution from the first bag to a first filter. By passing through the first filter, the dialysate solution is considered spent and cannot be used again. A third pump (15) then moves the spent dialysate solution to a second filter (12) to "clean" it (e.g., to remove toxins such as urea). The cleaned dialysate solution is then returned to the first bag.

[0069] In some embodiments, the sorbent also removes some electrolytes (or essential ions) required for therapy, which must then be re-added or reconstituted. Thus, during therapy, the second pump (14) and the third pump (15) can be operated to move dialysate through the dialysate loop line, and the fourth pump (16) can be operated to infuse an additive solution into the dialysate loop line (29). The additive solution can be added to the dialysate loop line (29) between the second filter (12) and the first bag (10), e.g., upstream of the first bag (10) and / or downstream of the second filter (12). The additive solution can also be added between the first bag and the first filter, e.g., downstream of the first bag and upstream of the first filter.

[0070] The second bag (11) may initially store an additive solution, which may contain electrolytes (or essential ions) necessary to reconstitute the dialysate solution. The second bag may be configured to store a volume of fluid, for example, 2.5 L, comprised between 0.5 L and 5 L, preferably between 1 L and 4 L. The volume of this bag may depend on the duration of the treatment and the concentration of the electrolytes. The additive solution may contain water and electrolytes (such as, for example, at least one of magnesium, calcium, and potassium).

[0071] In one embodiment, the sorbent (12) may include at least one of activated carbon, an ion exchanger (such as zirconium phosphate and / or hydrous zirconium oxide), and one or more enzymes (e.g., urease). During treatment as described above, the sorbent may be configured to remove toxins (such as urea and others). Toxin removal may involve at least one of the following phenomena with components contained in the sorbent: (i) adsorption (or absorption), (ii) catalysis, and (iii) ion exchange. Toxin removal may result in the production of gases (such as CO2).

[0072]

[0071] Thus, in some embodiments, the first bag may be configured to store the dialysate solution and collect at least one of the purified dialysate, the additive solution, and the gas.

[0073] In one embodiment shown in FIG. 3 , a sorbent cartridge (200) (also referred to as a sorbent or adsorption device) may include at least one of a body (201), a lid (204), an inlet port (205), and an outlet port (207). The body may include a cavity (202) configured to store at least one chemical component used to purify the dialysate solution. The cavity may be defined by at least one interior wall (203) and may be closed by a lid (204). The inlet and outlet ports are configured to provide fluid communication to the cavity (also referred to as an internal compartment). The inlet port may be configured to allow delivery of dialysate (e.g., spent dialysate) to the sorbent, and the outlet port may be configured to allow discharge of dialysate (e.g., purified dialysate).

[0074] A sorbent cartridge may contain multiple layers with similar or substantially similar chemical compositions in each given layer. Flow distribution within a given cartridge layer of a sorbent cartridge may vary across that layer. Channeling may occur in peripheral regions of one or more cartridge layers of the cartridge located closer to the cartridge wall. Fluid flow may increase in peripheral regions of one or more layers at the expense of their central regions located further away from the cartridge wall. This is undesirable because it may result in separate regions of overused and unused (or underused) material within the same layer of the cartridge. This may lead to inefficient treatment performance, premature or premature wear of cartridge components, shortened useful cartridge life, unused material within a used cartridge, or a combination of these problems. Sorbent cartridge designs that can further reduce or prevent flow distribution variations from occurring in sorbent cartridges would be preferable.

[0075] 4, 11a and 11b show cross-sectional views of an adsorption device (200) comprising a conical body having a conical cylindrical shape (frustum of a cone). In this example, the body (201) may comprise an inner wall (203) subdivided by a first step (218) and a second step (219).

[0076] The first staircase may include at least one step, including a second step. FIG. 11a shows a cartridge body including a first staircase, each step of which includes a second step. In this example, the step height of the first set of steps is greater than the step height of the second set of steps, and the step depth of the first set of steps is greater than the step height of the second set of steps. Nevertheless, the depth and height of each step can be varied from step to step and / or step to step, and can be configured to achieve a desired purpose. FIG. 11b shows a zoom of the first staircase (218) including a second step (219).

[0077] The size of the steps of the first step may be between 0.5 and 2 mm (for example, 1 mm). The size of the steps of the second step may be between 10 and 500 μm (for example, 100 μm). One reason for these sizes may be that the small steps are of the same order of magnitude as the particle size in the adsorbent material.

[0078] For example, a first staircase may include seven evenly spaced larger steps, and each of the subdivided sections may further include a second staircase including three evenly spaced smaller steps. The interior wall may be subdivided by steps of uniform or varying step size. Each section subdivided by smaller steps may have a draft angle for ease of molding. The combined configuration of all steps may define an overall cone angle.

[0079]

[0078] In use, dialysate can enter the conical cartridge body through the large radius side and exit through the smaller radius side.

[0080] The radius and height of the cone can be selected so that the resulting volume is greater than or equal to the volume of the sorbent packing (sorbent column) and so that, in use, the pressure drop caused by the flow resistance of the dialysate through the sorbent column remains below the desired maximum pressure drop (e.g., 0.6 bar at 300 mL / min). The size of the small steps can be selected to be within the range of the average diameter of the sorbent particles (e.g., 50-150 μm), thereby preventing sorbent bypass along the inner cartridge wall. The presence of larger steps can induce areas of turbulence, thereby further preventing sorbent bypass and contributing to consistent flow mismatch.

[0081] In one embodiment, the section between the base of the cone (maximum radius) and the first large step may comprise a total of five small steps (for example), thereby providing additional volume to be used as excess volume. This facilitates the adsorbent loading process by providing extra volume.

[0082] In one embodiment, the sorbent cartridge includes at least one of a first layer and a second layer comprising components configured to purify spent dialysate. At least one layer may include a homogenous mixture of two components and / or may be disposed in a portion of a cavity comprising at least two major steps and / or at least two minor steps. For example, a homogenous layer may be disposed within the cavity and extend sufficiently to fill an area (of the interior wall) comprising at least two steps of the second step and / or at least two steps of the first step.

[0083] 5a and 5b show the difference in fluid flow patterns between an adsorption device with a smooth inner wall (FIG. 5a) and an adsorption device with an optimized inner wall shape (e.g., as disclosed above). In the absence of steps (FIG. 5a), the fluid flow along the inner wall is faster than the fluid flow within the body of the adsorbent column. This results in a more rapid advance of the fluid front near the wall and the subsequent adsorbent depletion front relative to the body of the adsorbent column. The adsorbent column may thereby be depleted more rapidly in areas along the inner wall, where toxin breakthrough occurs prematurely before most of the adsorbent within the body of the adsorbent column is depleted. Unused adsorbent is wasted, and the size of such an adsorption device must be increased to achieve the desired amount of toxin removal before toxin breakthrough. In the presence of steps, the flow along the inner wall is slowed to equalize with the flow within the body of the adsorbent column. Thus, toxin breakthrough occurs much later, when much more adsorbent within the inner area of ​​the adsorbent column has been used.

[0084] In one embodiment, the body may comprise a plastic part. The draft angles of the straight sections between the steps in the sidewalls may be selected to facilitate the molding process by allowing for easy tool removal. The body may comprise ABS, PC, PP, or any other suitable polymer material.

[0085] In one embodiment, during assembly, the body can be positioned with the open side of the larger radius of the cone facing upward. The adsorbent material can be filled from the top to the desired fill level. The lid can then be placed on the body. The lid (204) can be secured to the cartridge body, for example, by gluing or welding.

[0086] 6a and 6b show cross-sectional views of one embodiment of the adsorption device (200). In this embodiment, the adsorption device (200) may further comprise a foam (209). The foam may have flexible and / or elastic behavior. FIG. 6a shows the foam in an expanded form, and FIG. 6b shows the same foam but compressed. During assembly, the adsorption material (a component configured to purify spent dialysate) may be filled from the top to a desired filling level. The remaining free volume of the body is then filled with foam (209), which may protrude above the upper surface of the body (201). The protruding foam may then be pressed down, for example, with the lid (204), thereby compressing the foam (209). The lid may be fixed to the cartridge body, for example, by gluing or welding. The elasticity of the foam may exert a spring force on the sorbent fill, thereby compressing the sorbent fill and preventing the formation of loosely packed areas or cavities.

[0087] The foam can be cut into cylindrical shapes (discs) with a height of 10-40 mm (for example) and a radius equal to or greater than the larger radius of the cone. For example, the radius of the cylindrical disc may be 1 mm greater than the larger radius of the body, and the height may be 20 mm. During assembly, the foam can be compressed to about 10-90% or 20-80% of its uncompressed height. For example, the foam can be compressed to about 50% of its uncompressed height.

[0088]

[0087] The foam may comprise an open-cell sponge-type material that readily allows the passage of liquids. The foam may comprise a biocompatible polyurethane material.

[0089] In one embodiment, the force (spring force) exerted by the compressed foam on the sorbent material can prevent free movement of the sorbent particles (e.g., due to vibration or other agitation during transport), thereby maintaining the integrity of the sorbent column (sorbent packing). The foam can be located on the larger radius side of the cartridge body (casing), for example, on the dialysate inlet side.

[0090] Instead of using a single disc of resilient foam, two or more layers can be combined to obtain the desired total foam height, for example, two layers of 10 mm foam can be combined to give a total foam height of 20 mm.

[0091] In one embodiment, the foam may be separated from the adsorbent column by a filter (eg, filter paper) or may be in direct contact with the adsorbent column (chemical components).

[0092] The foam layer is configured to compensate for density variations in the chemical components, which may result in variations in the height of the chemical components within the cavity. These variations may result from normal, expected variations in the chemical components (e.g., introduced during the adsorbent manufacturing process).

[0093]

[0092] The foam layer may be configured to compensate for volume changes in the adsorbent column that result from shipping or storage, such as tighter packing due to vibration during shipping.

[0094] The foam layer can be configured to compensate for or be used as an adjustable, low-cost filler material to allow flexibility in adsorbent material fill levels, if desired, which allows the same body to be used for smaller, more economical cartridges, if desired.

[0095] In one embodiment, the location of the fluid inlet and / or outlet may be central to the body of the sorbent. The inlet and / or outlet may comprise a tube that may be attached to at least one of the body and the lid.

[0096] In one embodiment disclosed in Figure 4, the inlet tube can be positioned at least partially along and / or through the lid. The lid can include a recess in which the inlet tube can be positioned so that the inlet tube is not twisted or otherwise affected by the weight of the adsorption device. The width of the recess can be greater than the width of the inlet tube. The inlet tube can be secured to the lid by pinching, welding, and / or gluing.

[0097] In one embodiment, the adsorbent may be provided with flow distribution means having the shape of a spider web at the inlet and outlet. The foam may be in direct contact with the spider web, or there may be filter paper between the spider web and the foam. In one embodiment, the foam may be configured to provide flow instead of the flow supply means or to contribute to providing flow by the flow supply means.

[0098] In one embodiment, the lid may comprise a transparent material to allow for UV adhesion.

[0099] In one embodiment, the body and / or lid may include a skirt, a step / shoulder to allow for ultrasonic welding, and / or a stabilizing rib structure. The body may further include a rib structure to stabilize the step or shoulder.

[0100] In one embodiment, the adsorbent may include a handle for transporting the adsorbent. The body and / or lid may include a fastening means for fastening the handle to the adsorbent. The fastening means may include at least one of a clip and a mushroom head.

[0101] In one embodiment, the inlet may comprise a first tube (213) and a first connector (215) intended to be connected to a dialysate loop line (e.g., downstream of the dialyzer) at least during therapy. The outlet may comprise a second tube (214) and a second connector (216) intended to be connected to a dialysate loop line (e.g., upstream of the dialyzer) at least during therapy. During storage or transport, the first connector may be configured to be connectable to the second connector.

[0102] 7, the adsorbent may comprise at least one of a first layer of chemical components (211) and a second layer of chemical components (212). The first layer may be a urease layer and the second layer may be an adsorbent layer.

[0103]

[0102] The first layer may include at least one of urease and activated carbon. The first layer may include urease provided as a mixture with activated carbon particles. This may be obtained by blending urease with activated carbon particles. The activated carbon particles may be obtained from any common source, such as coconut shells. The urease may be in the form of urease particles. The urease particles may be immobilized urease. The ratio of urease to activated carbon may be, for example, 1:1 to 1:100. The urease layer may include covalently immobilized urease, for example, urease immobilized on cellulose. The urease may be mixed with activated carbon in a ratio of 1:8.

[0104] The combination of urease with activated carbon has the following advantages: -Stabilizing effect on urease, - Significant improvement in shelf life, Providing a substrate for urease to dilute the urease to a concentration that can be handled during production; and Reduced activity loss during manufacturing, sterilization (if performed), shipping, and storage (see, e.g., Figures 8e and 9) may provide at least one of:

[0105] This stabilizing effect may be related, at least in part, to the antioxidant properties of activated carbon. Activated carbon may provide a stabilizing environment for urease. Furthermore, if mixing of AC and IU is already performed as part of the IU manufacturing process, the cartridge assembly process may be facilitated by providing the immobilized urease product as a single layer (no further mixing and proportioning is required). Thus, the immobilized urease prevents leakage of urease and is mixed with activated carbon, stabilizing the enzyme.

[0106]

[0105] Such a homogeneous mixture is inherently equilibrated, reduces pressure drop, and is shape independent.

[0107] In one embodiment, the first layer does not include an ion exchange material or a cation or anion exchange material, such as zirconium-based cation or anion exchange particles, for example, the first layer does not include zirconium oxide, hydrous zirconium oxide, zirconium phosphate, or metals that form insoluble phosphates.

[0108] The first layer containing the mixture of immobilized urease and activated carbon can be separated from another layer (e.g., a second layer) that can contain ion exchange particles, e.g., zirconium-based ion exchange particles or other similar chemical elements. The first and second layers can be separated by a filter (e.g., a filter membrane such as filter paper). Each layer can be separated by a filter.

[0109] In one embodiment, the second layer comprises a homogenous mixture of ZP, HZO, and optionally may further comprise AC, and / or a Na source such as sodium carbonate or sodium bicarbonate. The second layer may be urease-free.

[0110] The first layer can be positioned near the inlet and the second layer can be positioned near the outlet. The first layer can be positioned adjacent to the second layer. The first layer can be positioned upstream of and / or near the second layer. For example, the first layer can be positioned so that the second layer follows it.

[0111]

[0110] Some of the advantages of excluding urease from the second layer may be as follows: Reduce cartridge manufacturing costs by avoiding the waste of urease in layers where urease function is neither needed nor desired. Ensures that all urea hydrolysis and conversion to ammonia is complete in this first layer before the dialysate reaches the second layer where ammonia binds. Prevents unwanted urea hydrolysis and ammonia formation in deeper (more downstream) layers of the sorbent column, which can lead to premature, slow depletion and unwanted premature release of ammonia to the patient. This scenario can occur in the case of an unexpected loss of urease activity due to excessive amounts of urea from the patient or errors in use, such as incorrect storage or incorrect use. In these scenarios, restricting urease to a separate, earlier layer results in only incomplete urea hydrolysis (less harmful), rather than premature release of ammonia (more harmful). · Limits or eliminates the risk of urease leakage to the patient, thus significantly improving the biocompatibility of the sorbent.

[0112]

[0111] As explained above, the second layer may further include a sodium source (such as, but not limited to, sodium bicarbonate). This addition may improve control of Na, HCO3, and PH.

[0113]

[0112] Figure 10 is a first layer (211) which may contain a homogeneous mixture of urease and activated carbon; A second layer (212) that may contain a homogeneous mixture of ZP, HZO, AC, and NaHCO3; 2 shows an example of a sorbent cartridge comprising a cartridge body (201) having a cavity in which the sorbent is housed.

[0114] The sorbent cartridge may further comprise foam (209). Figure 10 also shows a filter (217) that may be positioned upstream of the first layer (and foam), between the first and second layers, and / or downstream of the second layer.

[0115] Figures 8a, 8b, 8c, 8d, and 8e show the performance of different sorbent configurations in an adsorption device. The dotted line in the figures shows the performance of a sorbent with a single homogeneous layer of ZP-HZO-AC-urease mixture, as described elsewhere. The solid line in the figures shows the performance of a sorbent according to the present invention, containing the same amounts of individual sorbent components but separated into a first layer of urease-AC mixture without ion exchange particles and a second layer of ZP-HZO-AC mixture without urease. As can be seen in Figures 8a and 8b, the sorbent according to the present invention provides dialysate regeneration with better control of sodium and bicarbonate in the regenerated dialysate. Starting with similar concentrations for sodium (Figure 8a) and bicarbonate (Figure 8b), the single-layer sorbent results in a larger increase in sodium and bicarbonate concentrations in the regenerated dialysate after 4 hours, thereby resulting in a larger change. Meanwhile, the dialysate chloride concentration (Figure 8c) remains nearly unchanged. Figure 8d shows the effect on the extent of ammonia breakthrough. Although both sorbents contain the same amount of urease and cation exchanger (ZP), the single-layer sorbent shows extensive ammonia breakthrough after 4 hours, whereas the sorbent according to the present invention shows only minimal signs of depletion and ammonia breakthrough after 4 hours. Thus, the two-layer sorbent configuration is more efficient and economical than the single-layer sorbent configuration.

[0116] According to one embodiment, the additive solution (e.g., stored in the second bag (11)) may include at least one of chloride (KCl), MgCl2, CaCl2, and a salt of a weak acid (such as a lactate or acetate salt of Ca, Mg, and / or K). The additive solution may include a mixture of at least one of calcium lactate, magnesium lactate, and potassium chloride. Alternatively, the additive solution may include a mixture of at least one of calcium lactate, magnesium lactate, and potassium lactate. It is assumed that the patient can metabolize lactate ions to bicarbonate ions. One advantage of such an additive solution is that it increases the amount of bicarbonate rather than chloride in the patient, thereby countering the effects of metabolic acidosis commonly present in dialysis patients. Furthermore, the release of lactate may increase the buffering capacity of the regenerated dialysate with respect to chloride.

[0117] In one embodiment, the additive solution (e.g., stored in the second bag (11)) may further include a soluble Na salt. The Na salt may include at least one of NaCl, Na lactate, or Na acetate. The Na salt may include Na lactate. The addition of Na lactate to the purified dialysate may help prevent excessively low plasma Na concentrations in the dialysate and in the patient. Furthermore, the addition may increase the buffering capacity of the regenerated dialysate, countering the effects of metabolic acidosis. [Explanation of symbols]

[0118] 1. System fluid circuit 2 Blood circuit 3 Dialysate circuit 4. First filter (e.g., dialyzer) 5 Blood Cartridges 6 Dialysis fluid cartridges 10 First bag (e.g., weighing bag) 11 Second bag (e.g., additive bag) 12 Second filter (e.g., adsorption device) 13 First Pump 14 Second Pump 15 Third Pump 16 Fourth Pump 17 Valve or Clamp 18 First sensor (e.g., pressure sensor) 19 Second sensor (e.g., air sensor) 20 Third sensor (e.g., level sensor) 21 Fourth sensor (e.g., temperature sensor) 22 Fifth sensor (e.g., ammonia sensor) 23 Airflow Device 24 connectors 25 Arterial Line 26 Intravenous line 27 Drip Chamber 29 Dialysis fluid loop line 31 Supply Line 32 patients 100 systems 101 Reusable parts 102 Disposable Part 103 Sensors 104 Detection Area 105 Actuators (e.g., valve actuators, pump devices, ...) 106 Working areas (e.g. valves, pump heads, ...) 107 User Interface Devices 108 patients 109 processors 200 Adsorption Device 201 Main Unit 202 Cavity 203 Interior wall 204 Lid 205 Entrance 206 Exit 207 Dialysis Machine / Peritoneal Cavity 208 Dialysis machine / to the peritoneal cavity 209 Foam 210 Chemical Composition 211 First Layer 212 Second Layer 213 First Tube 214 Second Tube 215 First Connector 216 Second Tube 217 filters 218 First Staircase 219 Second Staircase

Claims

1. 1. A sorbent cartridge configured to purify a dialysate solution, comprising: A cartridge body; The lid and a second port; and a first port; an interior compartment through which the dialysate solution flows from the second port to the first port; an adsorbent column having at least one layer of cleaning material stored in the interior compartment; a compressible layer in an at least partially compressed state; A sorbent cartridge comprising:

2. the cartridge is constructed and arranged so that the dialysate solution entering the cartridge contacts the compressible layer before contacting the sorbent column; The sorbent cartridge of claim 1 .

3. the compressible layer comprises at least one of a flexible behavior and an elastic behavior; 3. The sorbent cartridge of claim 1 or 2.

4. the compressible layer is configured to act as a spring on the adsorbent column; The adsorbent cartridge according to any one of claims 1 to 3.

5. the sorbent column is disposed within the cartridge body and includes a set of particles retained by the compressible layer; The adsorbent cartridge according to any one of claims 1 to 4.

6. the compressible layer exerts a force on the adsorbent column to prevent free movement of the particles or to maintain the integrity of the adsorbent column; The sorbent cartridge of claim 5.

7. the compressible layer is compressed to about 10-90%, or about 50%; The adsorbent cartridge according to any one of claims 1 to 6.

8. the compressible layer comprises an open-cell sponge-type material, allowing passage of the dialysate solution through the open-cell sponge-type material; The sorbent cartridge according to any one of claims 1 to 7.

9. further comprising a filter disposed between the compressible layer and the adsorbent column or between the lid and the compressible layer; The sorbent cartridge according to any one of claims 1 to 8.

10. the compressible layer is compressed to compensate for density variations in the adsorbent column or volume changes in the adsorbent column; The sorbent cartridge according to any one of claims 1 to 9.

11. the compressible layer is disposed within the interior compartment against the lid, upstream of the adsorbent column; The sorbent cartridge according to any one of claims 1 to 10.

12. the compressible layer comprises a biocompatible material; The sorbent cartridge according to any one of claims 1 to 11.

13. the pore size of the compressible layer is comprised between 30 and 100 ppi, between 40 and 90 ppi, between 40 and 50 ppi, or between 70 and 90 ppi; The sorbent cartridge according to any one of claims 1 to 12.

14. the cartridge body comprises a generally conical shape, and the compressible layer is disposed in a wider portion of the cartridge body; The sorbent cartridge according to any one of claims 1 to 13.

15. 1. A sorbent cartridge configured to purify a dialysate solution, comprising: a cartridge body having an internal compartment, a first end, a second end, a first port, and a second port; an adsorbent column having at least one layer of cleaning material stored in the interior compartment; Equipped with the cartridge body further comprising an inner wall extending from the first end to the second end; the inner wall includes a first step and a second step disposed on at least one step of the first step to control the flow of the dialysate solution adjacent the inner wall; Sorbent cartridge.

16. the inner wall is configured to generate turbulence adjacent the inner wall so that the dialysate solution flows substantially uniformly through the sorbent column.

16. The sorbent cartridge of claim 15.

17. The first staircase step is larger than the second staircase step; A sorbent cartridge according to claim 15 or 16.

18. At least one of the first step and the second step is configured such that the second end has a larger average diameter than the first end. The sorbent cartridge according to any one of claims 15 to 17.

19. the first staircase includes at least two steps and the second staircase includes at least two steps; The sorbent cartridge according to any one of claims 15 to 18.

20. Each step of the first staircase includes the second staircase; The sorbent cartridge according to any one of claims 15 to 19.

21. the first staircase includes equally spaced steps; The sorbent cartridge according to any one of claims 15 to 20.

22. the second staircase includes equally spaced steps; A sorbent cartridge according to any one of claims 15 to 21.

23. A sorbent cartridge comprising a urease layer comprising a mixture of urease and activated carbon and a sorbent layer comprising zirconium-based ion exchange particles.

24. the cartridge is configured so that the spent dialysate contacts the urease layer before contacting the adsorbent layer; 24. The sorbent cartridge of claim 23.

25. the urease layer does not contain ion exchange particles, or cation exchange particles or anion exchange particles; 25. A sorbent cartridge according to claim 23 or 24.

26. The adsorption layer does not contain urease. The sorbent cartridge according to any one of claims 23 to 25.

27. the adsorption layer comprises activated carbon; The sorbent cartridge according to any one of claims 23 to 26.

28. the zirconium-based ion exchange particles comprise at least one of cation exchange particles and anion exchange particles; A sorbent cartridge according to any one of claims 23 to 27.

29. the zirconium-based ion exchange particles comprise zirconium phosphate, acid zirconium phosphate, sodium zirconium phosphate, zirconium oxide, zirconium hydroxide, zirconium oxide hydroxide, hydrous zirconium oxide, hydrous zirconium oxide, hydrated zirconium oxide, unhydrated zirconium oxide, or a combination thereof; A sorbent cartridge according to any one of claims 23 to 28.

30. the zirconium-based ion exchange particles comprise a homogeneous mixture of zirconium phosphate and hydrous zirconium oxide; A sorbent cartridge according to any one of claims 23 to 29.

31. the adsorption bed further comprises a basic sodium source; The sorbent cartridge according to any one of claims 23 to 30.

32. the sodium source comprises at least one of sodium carbonate, sodium bicarbonate, and sodium hydroxide; A sorbent cartridge according to any one of claims 23 to 31.

33. further comprising an inlet port and an outlet port, the urease layer being disposed proximate the inlet and the adsorbent layer being disposed proximate the outlet. A sorbent cartridge according to any one of claims 23 to 32.

34. The urease in the urease layer is immobilized. A sorbent cartridge according to any one of claims 23 to 33.

35. 1. An apparatus for performing dialysis therapy, comprising: a sorbent cartridge; and a dialysate circuit in fluid communication with the sorbent cartridge, 1. An apparatus in which spent dialysate passes through the sorbent cartridge to purify the spent dialysate, the sorbent cartridge comprising a urease layer comprising a mixture of urease and activated carbon and a sorbent layer comprising zirconium-based ion exchange particles.

36. the cartridge is configured so that the spent dialysate contacts the urease layer before contacting the adsorbent layer; 36. The apparatus of claim 35.

37. the urease layer does not contain ion exchange particles, or cation exchange particles or anion exchange particles; 37. Apparatus according to claim 35 or 36.

38. The adsorption layer does not contain urease.

38. Apparatus according to any one of claims 35 to 37.

39. the adsorption layer comprises activated carbon; 39. Apparatus according to any one of claims 35 to 38.

40. the zirconium-based ion exchange particles comprise at least one of cation exchange particles and anion exchange particles; 40. Apparatus according to any one of claims 35 to 39.

41. the zirconium-based ion exchange particles comprise zirconium phosphate, acid zirconium phosphate, sodium zirconium phosphate, zirconium oxide, zirconium hydroxide, zirconium oxide hydroxide, hydrous zirconium oxide, hydrous zirconium oxide, hydrated zirconium oxide, unhydrated zirconium oxide, or a combination thereof; Apparatus according to any one of claims 35 to 40.

42. the zirconium-based ion exchange particles comprise a homogeneous mixture of zirconium phosphate and hydrous zirconium oxide; 42. Apparatus according to any one of claims 35 to 41.

43. the adsorption bed further comprises a basic sodium source; 43. Apparatus according to any one of claims 35 to 42.

44. the sodium source comprises at least one of sodium carbonate and sodium bicarbonate; 44. Apparatus according to any one of claims 35 to 43.

45. the sorbent cartridge further comprises an inlet port and an outlet port, the urease layer being disposed proximate the inlet and the adsorbent layer being disposed proximate the outlet; 45. Apparatus according to any one of claims 35 to 44.

46. The urease in the urease layer is immobilized.

46. ​​Apparatus according to any one of claims 35 to 45.

47. a dialyzer in fluid communication with the sorbent cartridge, wherein spent dialysate is transferred from the dialyzer to the sorbent cartridge; 47. Apparatus according to any one of claims 35 to 46.

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