Adsorber device for dialysate regeneration

Abstract

The present disclosure relates to a system using an adsorber device or to an adsorber device configured for dialysis treatment, such as extracorporeal blood treatment or peritoneal dialysis treatment.

Description

Technical Field

[0001] The present disclosure relates to a system using an adsorber device, or to an adsorber device configured for dialysis treatment such as extracorporeal blood treatment or peritoneal dialysis treatment. Background Art

[0002] Dialysis treatment is typically used to extract unwanted substances or molecules from a patient's blood and / or add needed substances or molecules to the blood. This treatment is used for patients who cannot effectively remove substances from their blood, such as when a patient has temporary or permanent kidney failure.

[0003] Extracorporeal blood treatment is accomplished by withdrawing blood from a patient's body and introducing the blood into a filtration unit (e.g., a dialyzer) where the blood is allowed to flow across a semipermeable membrane. Depending on the type of treatment (ultrafiltration (UF) treatment, hemofiltration (HF) treatment, hemodialysis (HD) treatment, hemodiafiltration (HDF) treatment, etc.), the semipermeable membrane selectively allows substances in the blood to pass from the main chamber through the membrane into the secondary chamber and also selectively allows substances in the secondary chamber to pass through the membrane into the blood in the main chamber.

[0004] Peritoneal dialysis treatment is accomplished by filling a patient's peritoneal cavity with a dialysis fluid solution and draining the dialysis fluid solution from the patient after a dwell phase. Peritoneal dialysis treatment and extracorporeal blood treatment (e.g., hemodialysis) are different treatments, but the concepts are still similar: on one side is the patient's blood and on the other side is the dialysis fluid. The membrane separating the blood side from the dialysis fluid side is the peritoneal membrane or the dialyzer membrane.

[0005] Dialysis treatment is widely performed in medical centers where healthcare personnel operate the dialysis system and ensure safe treatment. However, an increasing number of treatments are being performed at home and the patient is not always accompanied by healthcare personnel. Therefore, the operation of the dialysis system must be simplified or facilitated in order to limit the risk of incorrect preparation or actions or the risk of contamination of the sterile fluid components by the system.

[0006] In addition, a large amount of dialysis solution is consumed to dialyze a patient during a single treatment, for example approximately 120 liters for hemodialysis therapy.

[0007] Due to the large amount of dialysis fluid solution to be managed, one solution is to recycle or regenerate the dialysis fluid in progress during treatment, for example once the dialysis fluid solution has been used. This solution allows only a few liters (approximately 5L for hemodialysis therapy) to be used. To regenerate the dialysis fluid, the system may include an adsorber device. Summary of the Invention

[0008] Several features of the adsorber device are disclosed herein. Each feature may be claimed in an independent claim.

[0009] The first aspect of the present disclosure relates to an adsorber cartridge, which may include a compressible layer (such as, but not limited to, foam) in an adsorber column. This configuration may allow for:

[0010] · Overcoming manufacturing challenges arising from imperfect cartridge packaging due to variations in adsorber density,

[0011] · Avoiding the formation of cavities and non-uniformities in the adsorber column during transportation, and

[0012] · Allowing flexibility in using different adsorber configurations in the same housing (e.g., filling void spaces with foam to ensure perfect packaging).

[0013] In one possible embodiment, the adsorber cartridge includes:

[0014] · A cartridge body,

[0015] · A lid,

[0016] · A first port (which may optionally be arranged on the cartridge body),

[0017] · A second port (which may optionally be arranged on the lid),

[0018] · An internal compartment through which the dialysate solution flows from the second port to the first port,

[0019] · An adsorber column having at least one layer of cleaning material stored in the internal compartment, and

[0020] · A compressible layer in at least a partially compressed state.

[0021] The cartridge may be constructed and arranged such that the dialysate solution entering the cartridge contacts the compressible layer before contacting the adsorbent column (or other layers such as the urease layer and / or the adsorption layer). Even though the compressible layer may be arranged anywhere in the adsorber cartridge, it may be preferred to arrange the compressible layer at the end of the cartridge (particularly at the end of the internal compartment (e.g., at the top end and / or at the bottom end of the internal compartment)).

[0022] The compressible layer may include at least one of flexural behavior and elastic behavior.

[0023] The compressible layer may be configured to act as a spring on the adsorber column.

[0024] The adsorber column may include a set of particles arranged in the cartridge body and held by the compressible layer. The compressible layer may exert a force on the adsorber column to prevent any free movement of the particles or to maintain the integrity of the adsorber column.

[0025] The compressible layer can be compressed to about 10 - 90%, or about 50%.

[0026] The compressible layer can include an open - cell sponge - type material that allows a dialysate solution to pass therethrough. The compressible layer can be configured to evenly disperse / distribute / share the liquid across the entire surface of the adsorber column.

[0027] The adsorber cartridge can further include a filter disposed between the compressible layer and the adsorber column or between the lid and the compressible layer.

[0028] The compressible layer can be compressed to compensate for density fluctuations of the adsorber column or volume changes of the adsorber column.

[0029] The compressible layer can be disposed in the inner compartment against the lid upstream of the adsorber column. The pore size of the compressible layer can be between 30 ppi and 100 ppi (pores per inch), between 40 ppi and 90 ppi, between 40 ppi and 50 ppi, or between 70 ppi and 90 ppi. The compressible layer can include a biocompatible material.

[0030] The cartridge body can include a generally conical shape, and the compressible layer is disposed at the wider portion of the cartridge body.

[0031] A second aspect of the present disclosure relates to an adsorber device that can include an inner wall having a specific shape configured to enhance the uniformity of the dialysate flow through the adsorber device. This configuration can allow:

[0032] · Avoiding dialysate adsorber bypass at the cartridge wall

[0033] · A combination of smaller and larger steps provides a uniform effect throughout the cartridge and facilitates cartridge manufacturing (molding)

[0034] In one possible embodiment, the adsorber cartridge includes:[[]]

[0035] · A cartridge body having an inner compartment, a first end, a second end, a first port (which can optionally be disposed on the first end), and a second port (which can optionally be disposed on the second end), and

[0036] · An adsorber column having at least one layer of cleaning material stored in the inner compartment

[0037] The cartridge body may further include an inner wall extending from the first end to the second end. The inner wall may include a first series of steps and a second series of steps disposed on at least one step of the first series of steps to control the flow of the dialysate solution near the inner wall.

[0038] The inner wall may be configured to create turbulence near the inner wall such that the dialysate solution flows substantially uniformly through the adsorber column.

[0039] The steps of the first series of steps may be larger than the steps of the second series of steps. At least one of the first series of steps and the second series of steps may be configured in such a way that the second end has an average diameter greater than that of the first end.

[0040] The first series of steps may include at least two steps and / or the second series of steps may include at least two steps. Each step of the first series of steps may include the second series of steps. The first series of steps may include evenly spaced steps and / or the second series of steps may include evenly spaced steps.

[0041] A third aspect of the present disclosure relates to the composition of the adsorber device or a system using such an adsorber device.

[0042] For example, the adsorber device may include a layer having a mixture of urease and activated carbon. This layer may not include any zirconium phosphate or zirconium oxide. This configuration may allow:

[0043] · To increase the stability and shelf life of urease through the unexpected stabilizing effect of activated carbon

[0044] · To facilitate the cartridge assembly process by directly using urease in its manufactured form

[0045] For example, the adsorber device may include a homogeneous mixture of at least one of ZP (zirconium phosphate), HZO (hydrous zirconium oxide), AC (activated carbon), and a Na source, but no urease. This configuration may allow:

[0046] · To avoid waste of urease in layers where urease activity is not required

[0047] · To avoid leaching of urease from the upper layer in the adsorber (increase biocompatibility)

[0048] · To eliminate the risk of premature ammonia leaching in cartridges with insufficient urease activity (mitigate the effects of incorrect storage or incorrect use) (this problem may occur in cartridges where urease is part of the (homogeneous) absorption layer (second layer))

[0049] For example, the system can include at least one of a dialysate circuit line, an adsorber device, and a supply line, the supply line being configured to add a bicarbonate equivalent salt (such as lactate or acetate) to the dialysate circuit line. This configuration can allow:

[0050] · An increased release of bicarbonate equivalents to the patient

[0051] · Compensation for the condition of patient acidosis

[0052] For example, the system can include at least one of a dialysate circuit line, an adsorber device, and a supply line, the supply line being configured to add an Na salt (which can include at least one of chloride, lactate, or acetate) to the dialysate circuit line. This configuration can allow:

[0053] · Prevention of excessive removal of Na from the patient (such as having a very low urea concentration)

[0054] In one embodiment, the adsorber cartridge includes a urease layer and an adsorption layer, the urease layer including a mixture of urease and activated carbon, and the adsorption layer including zirconium-based ion exchange particles. The components of the adsorption layer interact with the fluid by adsorption or absorption.

[0055] The cartridge can be configured such that the used dialysate contacts the urease layer before contacting the adsorption layer.

[0056] The urease layer may not include any ion exchange particles (such as group IV transition metal-based ion exchangers), or any cation exchange particles or any anion exchange particles. The adsorption layer may not include urease. The adsorption layer may include activated carbon. In one embodiment, the urease layer does not include any cation exchangers.

[0057] The zirconium-based ion exchange particles can include at least one of cation exchange particles and anion exchange particles. The zirconium-based ion exchange particles can include zirconium phosphate, acid zirconium phosphate, sodium zirconium phosphate, zirconia, zirconium hydroxide, zirconium oxyhydroxide, hydrated zirconia, hydrous zirconia, anhydrous hydrous zirconia, or a combination thereof. The zirconium-based ion exchange particles can include a homogeneous mixture of zirconium phosphate and hydrated zirconia.

[0058] The adsorption layer may further include a sodium source. The sodium source can include sodium carbonate and / or sodium bicarbonate.

[0059] The adsorber cartridge may further include an inlet port and an outlet port. The urease layer may be disposed near the inlet, while the adsorption layer is disposed near the outlet.

[0060] The urease in the urease layer can be immobilized.

[0061] In a possible embodiment, a device for performing dialysis treatment includes an adsorber cartridge and a dialysate circuit in fluid communication with the adsorber cartridge. The dialysate circuit may be configured such that used dialysate passes through the adsorber cartridge to clean the used dialysate. The adsorber cartridge may include a urease layer and an adsorption layer, the urease layer including a mixture of urease and activated carbon, and the adsorption layer including zirconium-based ion exchange particles.

[0062] The cartridge may be configured such that the used dialysate contacts the urease layer before the used dialysate contacts the adsorption layer.

[0063] The urease layer may not include any ion exchange particles (e.g., group IV transition metal-based ion exchangers), or any cation exchange particles or any anion exchange particles. The adsorption layer may not include urease. The adsorption layer may include activated carbon. In one embodiment, the urease layer does not include any cation exchangers.

[0064] The urease layer may further include glucose. The adsorption layer may further include glucose. This can be used as an osmotic agent to control the osmolality of the dialysate during priming. The advantage may be that this allows the use of glucose-free priming dialysate. Thus, the priming solution for the dialysate circuit may include a glucose-free dialysate solution, or the dialysate solution may be generated during the priming process, as described in PCT / IB2023 / 060957 filed on October 31, 2023 in the name of Nextkidney, the entire disclosure of which is incorporated herein by reference.

[0065] The zirconium-based ion exchange particles may include at least one of cation exchange particles and anion exchange particles. The zirconium-based ion exchange particles may include zirconium phosphate, acid zirconium phosphate, sodium zirconium phosphate, zirconium oxide, zirconium hydroxide, zirconium oxyhydroxide, hydrated zirconium oxide, hydrous zirconium oxide, hydrated zirconium oxide, anhydrous zirconium oxide, or a combination thereof. The zirconium-based ion exchange particles may include a homogeneous mixture of zirconium phosphate and hydrated zirconium oxide.

[0066] The adsorption layer may further include a sodium source. The sodium source may include at least one of sodium carbonate, sodium bicarbonate, and sodium hydroxide.

[0067] The adsorber cartridge may include an inlet port and an outlet port, the urease layer may be disposed near the inlet, and the adsorption layer may be disposed near the outlet.

[0068] The urease of the urease layer may be immobilized.

[0069] The device may further include a dialyzer in fluid communication with the adsorber cartridge, and the dialysate circuit is configured such that used dialysate flows from the dialyzer to the adsorber cartridge. The dialysate circuit may include a circuit that includes the dialyzer and the adsorber cartridge.

[0070] This application claims the priority of EP 22205023.9, EP 22205027.0, EP22205030.4, EP 22205036.1, EP 22205040.3, and EP22205043.7, filed on November 2, 2022, and the benefit of the priority of PCT / IB2023 / 060957, filed in the name of Nextkidney on October 31, 2023, the entire disclosures of which are incorporated herein by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0071] The present disclosure will be better understood from the following detailed description, which includes non-limiting examples illustrated by the following drawings.

[0072] Figure 1 A potential architecture of the system is shown.

[0073] Figure 2 The normal operation of the dialysate circuit during treatment is shown.

[0074] Figure 3 An embodiment of the adsorber device is shown.

[0075] Figure 4 A cross-sectional view of an embodiment of the adsorber device is disclosed.

[0076] Figure 5a and 5b The general flow pattern of the dialysate solution through the chamber of the adsorber device is shown.

[0077] Figure 6a 、 6b 、6c and 6d show cross-sectional views of embodiments of the adsorber device.

[0078] Figure 7 A cross-sectional view of an embodiment of the adsorber device is disclosed.

[0079] Figure 8a 、 8b 、8c, 8d; and Figure 8e The performance of different configurations of the adsorber in the adsorber device is shown.

[0080] Figure 9 The urease activity of a urease layer including urease and activated carbon is compared with that of a urease layer including urease but not including activated carbon.

[0081] Figure 10 An exploded view of an embodiment of the adsorber device is disclosed.

[0082] Figure 11a And 11b A cross-sectional view of an embodiment of the adsorber device is disclosed.

[0083] List of components

[0084] 1 Fluid circuit of the system

[0085] 2 Blood circuit

[0086] 3 Dialysate circuit

[0087] 4 First filter (e.g., dialyzer)

[0088] 5 Blood cartridge

[0089] 6 Dialysate cartridge

[0090] 10 First bag (e.g., weighing bag)

[0091] 11 Second bag (e.g., additive bag)

[0092] 12 Second filter (e.g., adsorber device)

[0093] 13 First pump

[0094] 14 Second pump

[0095] 15 Third pump

[0096] 16 Fourth pump

[0097] 17 Valve or clamp

[0098] 18 First sensor (e.g., pressure sensor)

[0099] 19 Second sensor (e.g., air sensor)

[0100] 20 Third sensor (e.g., level sensor)

[0101] 21 Fourth sensor (e.g., temperature sensor)

[0102] 22 Fifth sensor (e.g., ammonia sensor)

[0103] 23 Airflow device

[0104] 24 Connector

[0105] 25 Arterial line

[0106] 26 Venous line

[0107] 27 Drip chamber

[0108] 29 Dialysate circuit pipeline

[0109] 31 Supply pipeline

[0110] 32 Patient

[0111] 100 System

[0112] 101 Reusable part

[0113] 102 Disposable part

[0114] 103 Sensor

[0115] 104 Sensing area

[0116] 105 Actuator (such as valve actuator, pumping device, etc.)

[0117] 106 Actuating area (such as valve, pumping head, etc.)

[0118] 107 User interface device

[0119] 108 Patient

[0120] 109 Processor

[0121] 200 Adsorber device

[0122] 201 Body

[0123] 202 Chamber

[0124] 203 Inner wall

[0125] 204 Cover

[0126] 205 Inlet

[0127] 206 Outlet

[0128] 207 From dialyzer / peritoneal cavity

[0129] 208 To dialyzer / peritoneal cavity

[0130] 209 Foam

[0131] 210 Chemical component

[0132] 211 First layer

[0133] 212 Second layer

[0134] 213 First tube

[0135] 214 Second tube

[0136] 215 First connector

[0137] 216 Second tube

[0138] 217 Filter

[0139] 218 First Series of Steps

[0140] 219 Second Series of Steps Detailed Implementation Manner

[0141] The following detailed description includes references to the accompanying drawings, which form a part of the detailed description. The accompanying drawings illustrate, by way of example, specific embodiments in which the present disclosure may be practiced. These embodiments, also referred to herein as "examples," are described in sufficient detail to enable those skilled in the art to practice the present disclosure. 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. Accordingly, the following detailed description should not be considered limiting in nature, and the scope of the present disclosure is defined by the appended claims and their equivalents.

[0142] All scientific and technical terms used herein have the meanings commonly used in the art, unless otherwise specified. The definitions provided herein are for the purpose of facilitating the understanding of certain terms frequently used herein and are not intended to limit the scope of the present disclosure.

[0143] As used in this specification and the claims, the singular forms "a," "an," and "the" cover embodiments having a plurality of referents, unless the context clearly dictates otherwise.

[0144] As used in this specification and the claims, any direction mentioned herein, such as "top," "bottom," "left," "right," "upper," "lower," and other directions or orientations, are described herein for the purpose of clearly referring to the accompanying drawings and are not intended to limit the actual device or system, unless the context clearly dictates otherwise. The devices and systems described herein may be used in several directions and orientations.

[0145] As used in this specification and the claims, "have," "having," "include," "including," "comprise," "comprising," etc. are used in their open-ended sense and generally mean "including but not limited to."

[0146] As used in this specification and the claims, the term "or" is generally used in its meaning that includes "and / or," unless the context clearly dictates otherwise.

[0147] As used in this specification and the claims, phrases such as "at least one of A, B, and C", "at least one of A, B, or C", "selected from A, B, C, and combinations thereof" are used in their open-ended sense, including "only A, or only B, or only C, or any combination of A, B, and C", unless the context clearly dictates otherwise.

[0148] According to one embodiment of the present disclosure as Figure 1 shown, system (100) may include a reusable portion (101) and a disposable portion (102). The disposable portion (102) may include components that must be discarded after a predetermined number of uses (e.g., after a single treatment). The working life of the disposable portion (102) may depend directly on the number of treatments. These components may be components that have been wetted by a medical fluid (such as dialysis fluid) or by a patient fluid (such as blood).

[0149] The reusable portion (101) may include expensive components such as sensors (103), electronic components, a user interface device (107), actuators (105) for valves or pumps, a processor (109), or a memory. The reusable portion (101) is used continuously with a number of disposable portions (102). The reusable portion (101) may include components that can be replaced when the components are too worn, damaged, or after a predetermined period of time but longer than a single treatment. Replacing the reusable portion may depend on the wear of the components.

[0150] The reusable portion (101) may be configured to be operatively coupled to the disposable portion (102). The sensor (103) may be configured to be operatively coupled to a sensing area (104) of the disposable portion. The actuator (105) may be configured to be operatively coupled to an actuation area (106) of the disposable portion (102). The reusable portion (101) (e.g., the user interface device (107)) may be configured to provide information to and / or receive instructions from a patient (108). At least one of the sensor (103), the actuator (105), and the user interface device (107) may be connected to the processor (109). The disposable portion (102) may be connected to or in contact with the patient (108) at least during treatment.

[0151] The following description discloses a hemodialysis treatment system using an adsorber device, but a similar adsorber device may be used for peritoneal dialysis treatment. The type of treatment should not be construed as a limitation on the use of the adsorber device disclosed herein.

[0152] According to one embodiment of the present disclosure as Figure 2In one embodiment shown, the system may include a fluid circuit (1). The fluid circuit of the system (1) may include a blood circuit (2), a dialysate circuit (3), and a first filter (such as a dialyzer) (4). The elements of the fluid circuit wetted by the fluid 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).

[0153] 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 used to connect to a patient (32) via, for example, a catheter (not shown here) during treatment. The first pump may be configured to move fluid (such as the patient's blood) from the arterial line to the venous line during normal operation (e.g., during treatment), and to move fluid from the venous line to the arterial line during reverse operation (e.g., during at least a portion of the priming). The first pump may be controlled by a processor.

[0154] 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 arranged in a blood cartridge (5).

[0155] The dialysate circuit (3) may include at least one of a dialysate circuit line (29), a second pump (14), a third pump (15), a second filter (12) (such as an adsorber device), and a first bag (10) (also referred to as a weighing bag). The dialysate circuit (3) may include at least one of a supply line (31) connected to a 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 arranged in a dialysate cartridge (6).

[0156] The blood circuit (2) and the dialysate circuit (3) may be fluidly connected to a first filter (4), such as a dialyzer. The first filter may include a blood compartment connected to the blood circuit and a dialysate compartment connected to the dialysate circuit. The two may be separated by a permeable membrane.

[0157] The weighing bag (10) can be arranged on a warmer and / or a weighing scale (not shown). The weighing scale can 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).

[0158] In one embodiment, the first bag can be configured to store a dialysis fluid solution required for treatment. A second pump (14) moves the solution from the first bag to a first filter. By passing through the first filter, the dialysis fluid solution is considered used and cannot be used a second time. Thereafter, a third pump (15) moves the used dialysis fluid solution to a second filter (12) in order to "clean" the used dialysis fluid solution (e.g., to remove toxins such as urea). The cleaned dialysis fluid solution is then moved back to the first bag.

[0159] In some embodiments, the adsorber (from the dialysis fluid solution) also removes some electrolytes (or essential ions) required for treatment, which must then be re-added or reconstituted. Thus, during treatment, the second pump (14) and the third pump (15) can be operated to move the dialysis fluid through the dialysis fluid circuit line, and the fourth pump (16) can also be operated to inject an additive solution into the dialysis fluid circuit line (29). The additive solution can be added, for example, upstream of the first bag (10) and / or downstream of the second filter (12) to the dialysis fluid circuit line (29) between the second filter (12) and the first bag (10). It can also be added between the first bag and the first filter, for example, downstream of the first bag and upstream of the first filter.

[0160] The second bag (11) can initially store an additive solution, which can include electrolytes (or essential ions) required to reconstitute the dialysis fluid solution. The second bag can be configured to store a fluid volume between 0.5 L and 5 L, preferably between 1 L and 4 L, such as 2.5 L. The volume of the bag can depend on the duration of the treatment and the concentration of the electrolytes. The additive solution can include water and electrolytes (such as at least one of magnesium, calcium, and potassium).

[0161] In one embodiment, the adsorber (12) can include at least one of activated carbon, an ion exchanger (such as zirconium phosphate and / or zirconium hydrous oxide), and one or more enzymes (such as urease). During treatment as described above, the adsorber can be configured to remove toxins (such as urea, etc.). Toxin removal can involve at least one of the following phenomena: (i) adsorption (or absorption) at the (one or more) components included in the adsorber, (ii) catalysis, and (iii) ion exchange. As a result of toxin removal, a gas (such as CO2) can be produced.

[0162] Thus, in some embodiments, the first bag can be configured to store a dialysate solution and collect at least one of a cleaned dialysate, an additive solution, and a gas.

[0163] In one embodiment as Figure 3 shown, an adsorber cartridge (200) (also referred to as an adsorber or adsorber device) can include at least one of a body (201), a lid (204), an inlet port (205), and an outlet port (207). The body can include a cavity (202) configured to store at least one of chemical components for cleaning a dialysate solution. The cavity can be defined by at least one inner wall (203) and can be closed by a lid (204). The inlet port and the outlet port are configured to provide fluid communication with the cavity (also referred to as an internal compartment). The inlet port can be configured to allow supply of a dialysate (e.g., a used dialysate) to the adsorber, and the outlet port can be configured to allow discharge of the dialysate (e.g., a cleaned dialysate).

[0164] The adsorber cartridge can include multiple layers, each including similar or substantially the same chemical components in each given layer. The flow distribution in a given cartridge layer of the adsorber cartridge can vary across the layer. Channeling can occur in the peripheral region of the cartridge layer or in the cartridge layers closer to the cartridge wall. Fluid flow can increase in the peripheral regions of one or more layers, at the expense of the central regions thereof away from the cartridge wall. This is undesirable because it can lead to a separation region of overused material and unused (or underused) material in the same layer of the cartridge. This can result in inefficient treatment performance, early or premature depletion of cartridge components, shortened service life of the cartridge, unused material in the used cartridge, or a combination of these problems. An adsorber cartridge design that can further reduce or prevent variations in flow distribution in the adsorber cartridge would be preferred.

[0165] Figure 4 , 11a and 11b disclose cross-sectional views of an adsorber device (200) including a conical body having a frustoconical shape. In this example, the body (201) can include an inner wall (203) subdivided by a first series of steps (218) and a second series of steps (219).

[0166] The first series of steps can include at least one step that includes the second series of steps. Figure 11a Shown is a cartridge body including a first series of steps, where each step of the first series of steps includes a second series of steps. 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 depth of the steps in the first set of steps is greater than the height of the steps in the second set of steps. However, the depth and height of each step can vary between steps and / or between series and can be configured to achieve a desired objective.Figure 11b An enlargement of a first series of steps (218) including a second series of steps (219) is shown.

[0167] The dimensions of the steps of the first series of steps may be between 0.5 and 2 mm (e.g., 1 mm). The dimensions of the steps of the second series of steps may be between 10 μm and 500 μm (e.g., 100 μm). One reason for these dimensions may be that the small steps are of the same order of magnitude as the particle size in the adsorbent material.

[0168] For example, the first series of steps may include 7 evenly spaced larger steps, and each sub-section may also include a second series of steps, which includes 3 evenly spaced smaller steps. The inner wall may be subdivided by steps of uniform or varying step sizes. Each section subdivided by the smaller steps may have a draft angle to facilitate molding. The combined arrangement of all the steps may define a total cone angle.

[0169] When in use, the dialysate may enter the conical cartridge body through the large radius side and may exit through the smaller radius side.

[0170] The cone radius and height may be selected such that the resulting volume is greater than or equal to the volume of the adsorbent filling (adsorbent column), and such that, when in use, the pressure drop caused by the flow resistance of the dialysate through the adsorbent column remains below a desired maximum pressure drop (e.g., 0.6 bar at 300 mL / min). The size of the small steps may be selected to be within the range of the average size of the adsorbent particles (e.g., 50 - 150 μm), thereby preventing adsorbent bypass along the inner wall of the cartridge. The presence of the larger steps creates turbulent regions, thereby further preventing adsorbent bypass and contributing to smooth flow inconsistencies.

[0171] In one embodiment, the section between the cone base (maximum radius) and the first large step may include a total of 5 small steps (e.g.), thereby providing an additional volume that serves as an excess volume. This facilitates the adsorbent filling process by providing additional volume.

[0172] In one embodiment, the adsorbent cartridge includes at least one of a first layer and a second layer, the first layer and the second layer including components configured to clean the used dialysate. At least one layer may include a homogeneous mixture of two components and / or at least one layer may be disposed in a portion of a cavity including at least two large steps and / or at least two small steps. For example, the homogeneous layer may be disposed in the cavity and extend sufficiently to fill the region of (the inner wall) including at least two steps of the second series of steps and / or at least two steps of the first series of steps.

[0173] Figure 5a and 5b An adsorbent device with a smooth inner wall is shown (Figure 5a ) and the difference in the fluid flow pattern between the adsorber device having an optimized-shaped inner wall (such as disclosed above). In the absence of steps ( Figure 5a ), the fluid flow along the inner wall is faster than the fluid flow in the main body of the adsorber column. This causes the fluid front and subsequently the adsorber depletion front near the wall to advance faster relative to the main body of the adsorber column. As a result, the adsorber column will be depleted faster in the region along the inner wall, where toxin breakthrough will occur prematurely before most of the adsorbers in the main body of the adsorber column have been exhausted. The unused adsorbers are wasted, and the size of such an adsorber device must be increased in order to provide the required amount of toxin removal before toxin breakthrough. In the presence of steps, the flow along the inner wall slows down until it is flush with the flow in the main body of the adsorber column. Similarly, toxin breakthrough occurs much later when more adsorbers in the inner region of the adsorber column have been used.

[0174] In one embodiment, the main body can include a plastic part. The draft angle of the straight section between the steps at the side wall can be selected to facilitate the molding process by allowing easy tool release. The main body can include ABS, PC, PP, or any other suitable polymeric material.

[0175] In one embodiment, during assembly, the main body can be placed such that the open side of the cone with the larger radius faces upward. The adsorbent material can be filled from the top until the desired filling level is reached. After that, the lid can be placed on the main body. The lid (204) can be fixed to the cartridge main body, for example, by gluing or welding.

[0176] Figure 6a and 6b shows a cross-sectional view of one embodiment of the adsorber device (200). In this embodiment, the adsorber device (200) can further include a foam (209). The foam can have a flexible and / or elastic behavior. Figure 6a shows the foam in its expanded form, while Figure 6b shows the same but compressed foam. During assembly, the adsorbent material (the component configured to clean the used dialysate) can be filled from the top until the desired filling level. Then the remaining free volume of the main body can be filled with the foam (209), which can protrude above the top surface of the main body (201). Then the protruding foam can be pressed down, for example, with a lid (204), thereby compressing the foam (209). The lid can be fixed to the cartridge main body, for example, by gluing or welding. Due to the elasticity of the foam, a spring force can act on the adsorbent filler, thereby compressing it and preventing the formation of loosely filled regions or cavities.

[0177] The foam can be cut into a cylindrical shape (disc) with a height of 10 - 40 mm (for example), and a radius equal to or greater than the larger radius of the conical body. For example, the radius of the cylindrical disc can be 1 mm larger than the larger radius of the body, and the height can be 20 mm. During assembly, the foam can be compressed to about 10 - 90% or 20 - 80% of its uncompressed height. For example, it can be compressed to about 50% of its uncompressed height.

[0178] The foam can include an open-cell sponge-like material that easily allows liquids to pass through. The foam can include a biocompatible polyurethane material.

[0179] In one embodiment, the force (spring force) exerted by the compressed foam on the adsorbent material can prevent any free movement of the adsorbent particles (e.g., due to vibration or other agitation during transportation), thus maintaining the integrity of the adsorbent column (adsorbent packing). The foam can be located on the larger radius side of the cartridge body (housing), e.g., on the dialysate inlet side.

[0180] As an alternative to using a single elastic foam disc, two or more layers can be combined to obtain the total desired height of the foam. For example, two 10 - mm foams can be combined to a total foam height of 20 mm.

[0181] In one embodiment, the foam can be separated from the adsorbent column by a filter (e.g., filter paper), or can be in direct contact with the adsorbent column (chemical component).

[0182] The foam layer can be configured to compensate for density fluctuations of the chemical component, resulting in fluctuations in the height of the chemical component within the cavity. These fluctuations may be caused by normal expected fluctuations of the chemical component (e.g., introduced during the manufacture of the adsorbent).

[0183] The foam layer can be configured to compensate for volume changes of the adsorbent column caused by transportation or storage, e.g., tighter packing due to vibration during transportation.

[0184] The foam layer can be configured to compensate for or serve as an adjustable low-cost packing material when needed, to allow flexibility in the filling level of the adsorbent material. This allows the same body to be used for smaller, more economical cartridges when needed.

[0185] In one embodiment, the location of the fluid inlet and / or outlet can be centered relative to the body of the adsorbent. The inlet and / or outlet can include a tube that can be glued to at least one of the body and the lid.

[0186] In Figure 4In one disclosed embodiment, the inlet tube may be disposed at least partially along and / or through the lid. The lid may include a recess through which the inlet tube may be disposed such that the inlet tube is not kinked or otherwise affected by the weight of the adsorber device. The width of the recess may be greater than the inlet tube. The inlet tube may be fastened to the lid by clamping, welding, and / or gluing.

[0187] In one embodiment, the adsorber may include a flow distribution device having a spider web shape at the inlet and outlet. The foam may be in direct contact with the spider web, or a filter paper may be present between the spider web and the foam. In one embodiment, the foam may be configured to distribute the flow instead of the fluid distribution device or to assist in distributing the flow with the fluid distribution device.

[0188] In one embodiment, the lid may include a transparent material in a manner that allows UV gluing.

[0189] In one embodiment, the body and / or the lid may include a skirt, a step / shoulder to allow ultrasonic welding, and / or a structure of stabilizing ribs. The body may also include a rib structure to stabilize the step or shoulder.

[0190] In one embodiment, the adsorber may include a handle for transporting the adsorber. The body and / or the lid may include fastening means for fastening the handle to the adsorber. The fastening means may include at least one of a clip and a mushroom head.

[0191] In one embodiment, the inlet may include a first tube (213) and a first connector (215) for connecting to a dialysate circuit line at least during treatment (e.g., downstream of the dialyzer). The outlet may include a second tube (214) and a second connector (216) for connecting to a dialysate circuit line at least during treatment (e.g., upstream of the dialyzer). During storage or transportation, the first connector may be configured to be connectable to the second connector.

[0192] In one embodiment as Figure 7 shown, the adsorber may include at least one of a first layer (211) of chemical components and a second layer (212) of chemical components. The first layer may be a urease layer and the second layer may be an adsorption layer.

[0193] 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 mixing 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 - 1:100. The urease layer may include covalently immobilized urease, such as immobilized on cellulose. The urease may be mixed with activated carbon in a ratio of 1:8.

[0194] A mixture of urease and activated carbon can provide at least one of the following advantages:

[0195] · A stabilizing effect on urease,

[0196] · A significant improvement in shelf life,

[0197] · Providing a matrix for urease to dilute it to a concentration that can be handled during manufacturing, and

[0198] · Reducing the loss of activity during manufacturing, sterilization (if performed), transportation, and storage (see, for example, Figure 8e and 9 ).

[0199] This stabilizing effect is at least partially related to the antioxidant properties of activated carbon. Activated carbon can provide a stable environment for urease. In addition, in cases where the mixing of AC and IU has been carried out as part of the IU manufacturing process, the cartridge assembly process can be facilitated by providing the immobilized urease product as is in a single layer (without further mixing and proportioning). Thus, the immobilized urease prevents urease leakage and stabilizes the enzyme when mixed with activated carbon.

[0200] Such a homogeneous mixture is inherently balanced, reduces pressure drop, and is independent of shape.

[0201] In one embodiment, the first layer does not include ion exchange materials, or any cation exchange materials or any anion exchange materials, such as zirconium-based cation or anion exchanger particles. For example, the first layer does not include zirconia, hydrated zirconia, zirconium phosphate, or metals that form insoluble phosphates, etc.

[0202] The first layer comprising a mixture of immobilized urease and activated carbon can be separated from another layer (e.g., the second layer), which can include ion exchange particles, such as zirconium-based ion exchange particles or other similar chemical elements. The first layer and the second layer can be separated by a filter (e.g., a filter membrane, such as filter paper). Each layer can be separated by a filter.

[0203] In one embodiment, the second layer can include a homogeneous mixture of ZP, HZO, optionally further including AC and / or a Na source, such as sodium carbonate or sodium bicarbonate. The second layer can not include urease.

[0204] The first layer can be arranged closer to the inlet, while the second layer can be arranged closer to the outlet. The first layer can be arranged adjacent to the second layer. The first layer can be arranged upstream of and / or close to the second layer. For example, the first layer can be arranged to be followed by the second layer.

[0205] Some of the advantages of excluding urease from the second layer can be:

[0206] ·Reduce cartridge manufacturing costs by avoiding waste of urease in layers where urease function is neither required nor desired.

[0207] ● Ensure that all ureolysis and conversion to ammonia are completed in the first layer before the dialysate reaches the second layer where ammonia will bind.

[0208] ● Prevent unwanted ureolysis and ammonia formation in deeper (more downstream) layers of the adsorber column, which can lead to early slow depletion of ammonia and unwanted early release to the patient. This can occur in the case of excess urea from the patient or due to accidental loss of urease activity due to misuse (e.g., incorrect storage or incorrect use). In these cases, confining urease to a separate front layer will only result in incomplete ureolysis (low hazard), rather than premature release of ammonia (higher hazard).

[0209] · Limit or eliminate the risk of urease leakage to the patient, thus significantly improving the biocompatibility of the adsorber.

[0210] As described above, the second layer may also include a sodium source (such as but not limited to sodium bicarbonate). This addition can improve the control of Na, HCO3, and pH.

[0211] Figure 10 An example of an adsorber cartridge including a cartridge body (201) is shown, the cartridge body having a cavity in which are stored:

[0212] · A first layer (211), which may include a homogeneous mixture of urease and activated carbon, and

[0213] · A second layer (212), which may include a homogeneous mixture of ZP, HZO, AC, and NaHCO3.

[0214] The adsorber cartridge may also include a foam (209). Figure 10 A filter (217) is also shown, which may be arranged upstream of the first layer (and the foam), between the first and second layers, and / or downstream of the second layer.

[0215] Figure 8a 、 8b Figures 8c, 8d, and 8e show the performance of different configurations of the adsorber in the adsorber device. The dashed lines in the figures show the performance of an adsorber with a single homogeneous layer of the ZP - HZO - AC - urease mixture, as described elsewhere. The solid lines in the figures show the performance of the adsorber according to the present invention, which contains the same amount of individual adsorber components but separated into a first layer of a urease - AC mixture without ion - exchange particles and a second layer of a ZP - HZO - AC mixture without urease. As Figure 8a andFigure 8b As seen, the adsorber according to the present invention provides dialysate regeneration, with better control of sodium and bicarbonate in the regenerated dialysate. Starting from similar concentrations of sodium ( Figure 8a ) and bicarbonate ( Figure 8b ), the single-layer adsorber results in a greater increase in the concentrations of sodium and bicarbonate in the regenerated dialysate after 4 h, leading to a greater change. On the other hand, the dialysate chloride concentration ( Figure 8c ) remains roughly unchanged. Figure 8d Shows the effect on the degree of ammonia penetration. Although both adsorbers contain the same amount of urease and cation exchanger (ZP), the single-layer adsorber shows extensive ammonia penetration after 4 h, while the adsorber according to the present invention shows only minimal depletion and signs of ammonia penetration after 4 h. Thus, the two-layer adsorber configuration is more effective and more economical than the single-layer adsorber configuration.

[0216] According to an embodiment, the additive solution (e.g., stored in the second bag (11)) may include at least one of a chloride salt, MgCl2, CaCl2, and a weak acid salt (e.g., lactate or acetate 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. We assume that the patient can metabolize lactate ions to bicarbonate ions. One of the advantages of such an additive solution is that it can increase the amount of bicarbonate rather than chloride in the patient, thereby offsetting the effect of metabolic acidosis commonly present in dialysis patients. In addition, the release of lactate can increase the buffering capacity of the regenerated dialysate compared to chloride.

[0217] 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, sodium lactate, or sodium acetate. The Na salt may include sodium lactate. Adding sodium lactate to the clean dialysate can help prevent too low plasma Na concentration in the dialysate and the patient. In addition, it can increase the buffering capacity of the regenerated dialysate and offset the effect of metabolic acidosis.

Claims

1. An adsorber cartridge configured to clean a dialysate solution, the adsorber cartridge comprising: · Cartridge body · Lid · Second port · First port · Inner compartment through which the dialysate solution flows from the second port to the first port · Adsorber column having at least one layer of cleaning material stored in the inner compartment, and · Compressible layer in at least a partially compressed state 2. The adsorber cartridge according to claim 1, wherein The cartridge is constructed and arranged such that the dialysate solution entering the cartridge contacts the compressible layer before contacting the adsorption column 3. The adsorber cartridge according to any one of the preceding claims, wherein The compressible layer includes at least one of flexural behavior and elastic behavior 4. The adsorber cartridge according to any one of the preceding claims, wherein The compressible layer is configured to act as a spring on the adsorber column 5. The adsorber cartridge according to any one of the preceding claims, wherein The adsorber column includes a set of particles arranged in the cartridge body and held by the compressible layer 6. The adsorber cartridge according to claim 5, wherein The compressible layer applies a force on the adsorber column to prevent any free movement of the particles or to maintain the integrity of the adsorber column 7. The adsorber cartridge according to any one of the preceding claims, wherein The compressible layer is compressed to about 10 - 90% or about 50% 8. The adsorber cartridge according to any one of the preceding claims, wherein The compressible layer includes an open - cell sponge - type material that allows the dialysate solution to pass through it 9. The adsorber cartridge according to any one of the preceding claims, further comprising a filter disposed between the compressible layer and the adsorber column or between the lid and the compressible layer.

10. The adsorber cartridge according to any one of the preceding claims, wherein The compressible layer is compressed to compensate for density fluctuations of the adsorber column or volume changes of the adsorber column 11. The adsorber cartridge according to any one of the preceding claims, wherein The compressible layer is arranged in the inner compartment against the lid upstream of the adsorber column 12. The adsorber cartridge according to any one of the preceding claims, wherein The compressible layer includes a biocompatible material 13. The adsorber cartridge according to any one of the preceding claims, wherein The pore size of the compressible layer is between 30 ppi and 100 ppi, between 40 ppi and 90 ppi, between 40 ppi and 50 ppi, or between 70 ppi and 90 ppi 14. The adsorber cartridge according to any one of the preceding claims, wherein The cartridge body has a generally conical shape, and the compressible layer is arranged at the wider part of the cartridge body 15. An adsorber cartridge configured to clean a dialysate solution, comprising: · Cartridge body having an inner compartment, a first end, a second end, a first port, and a second port, and · Adsorber column having at least one layer of cleaning material stored in the inner compartment wherein the cartridge body further includes an inner wall extending from the first end to the second end wherein the inner wall includes a first series of steps and a second series of steps arranged on at least one step of the first series of steps to control the flow of the dialysate solution near the inner wall 16. The adsorber cartridge according to claim 15, wherein, The inner wall is configured to create turbulence near the inner wall such that the dialysate solution flows substantially uniformly through the adsorber column 17. The adsorber cartridge according to any one of the preceding claims 15 to 16, wherein, The steps of the first series of steps are larger than the steps of the second series of steps 18. The adsorber cartridge according to any one of the preceding claims 15 to 17, wherein, At least one of the first series of steps and the second series of steps is configured such that the second end has an average diameter greater than that of the first end 19. The adsorber cartridge according to any one of the preceding claims 15 to 18, wherein, The first series of steps includes at least two steps, and the second series of steps includes at least two steps 20. The adsorber cartridge according to any one of the preceding claims 15 to 19, wherein, Each step of the first series of steps includes the second series of steps 21. The adsorber cartridge according to any one of the preceding claims 15 to 20, wherein, The first series of steps includes evenly spaced steps 22. The adsorber cartridge according to any one of the preceding claims 15 to 21, wherein, The second series of steps includes evenly spaced steps 23. An adsorber cartridge comprising a urease layer and an adsorption layer, the urease layer comprising a mixture of urease and activated carbon, and the adsorption layer comprising zirconium-based ion exchange particles.

24. The adsorber cartridge according to claim 23, wherein, The cartridge is configured such that the used dialysate contacts the urease layer before contacting the adsorption layer 25. The adsorber cartridge according to any one of the preceding claims 23 to 24, wherein, The urease layer does not include any ion - exchange particles, or any cation - exchange particles, or any anion - exchange particles 26. The adsorber cartridge according to any one of the preceding claims 23 to 25, wherein, The adsorption layer does not include urease 27. The adsorber cartridge according to any one of the preceding claims 23 to 26, wherein, The adsorption layer includes activated carbon 28. The adsorber cartridge according to any one of the preceding claims 23 to 27, wherein, The zirconium-based ion exchange particles include at least one of cation exchange particles and anion exchange particles.

29. The adsorber cartridge according to any one of the preceding claims 23 to 28, wherein, The zirconium-based ion exchange particles include zirconium phosphate, acid zirconium phosphate, sodium zirconium phosphate, zirconium oxide, zirconium hydroxide, hydroxozirconium oxide, hydrated zirconium oxide, hydrous zirconium oxide, hydrous zirconium oxide with water, anhydrous hydrous zirconium oxide, or a combination thereof.

30. The adsorber cartridge according to any one of the preceding claims 23 to 29, wherein, The zirconium-based ion exchange particles include a homogeneous mixture of zirconium phosphate and hydrous zirconium oxide.

31. The adsorber cartridge according to any one of the preceding claims 23 to 30, wherein, The adsorption layer further includes an alkaline sodium source.

32. The adsorber cartridge according to any one of the preceding claims 23 to 31, wherein,The sodium source includes at least one of sodium carbonate, sodium bicarbonate, and sodium hydroxide.

33. The adsorber cartridge according to any one of the preceding claims 23 to 32 further comprises an inlet port and an outlet port, wherein, The urease layer is disposed near the inlet, and the adsorption layer is disposed near the outlet.

34. The adsorber cartridge according to any one of the preceding claims 23 to 33, wherein, The urease in the urease layer is immobilized.

35. A device for performing dialysis treatment, comprising an adsorber cartridge and a dialysate circuit in fluid communication with the adsorber cartridge, wherein, Used dialysate passes through the adsorber cartridge to clean the used dialysate, and wherein the adsorber cartridge includes a urease layer and an adsorption layer, the urease layer includes a mixture of urease and activated carbon, and the adsorption layer includes zirconium-based ion exchange particles.

36. The device according to claim 35, wherein, The cartridge is configured such that the used dialysate contacts the urease layer before the used dialysate contacts the adsorption layer.

37. The device according to any one of the preceding claims 35 to 36, wherein, The urease layer does not include any ion exchange particles, or any cation exchange particles, or any anion exchange particles.

38. The device according to any one of the preceding claims 35 to 37, wherein, The adsorption layer does not include urease.

39. The device according to any one of the preceding claims 35 to 38, wherein, The adsorption layer includes activated carbon.

40. The device according to any one of the preceding claims 35 to 39, wherein, The zirconium-based ion exchange particles include at least one of cation exchange particles and anion exchange particles.

41. The device according to any one of the preceding claims 35 to 40, wherein, The zirconium-based ion exchange particles include zirconium phosphate, acid zirconium phosphate, sodium zirconium phosphate, zirconium oxide, zirconium hydroxide, hydroxozirconium oxide, hydrated zirconium oxide, hydrous zirconium oxide, hydrous zirconium oxide with water, anhydrous hydrous zirconium oxide, or a combination thereof.

42. The device according to any one of the preceding claims 35 to 41, wherein, The zirconium-based ion exchange particles include a homogeneous mixture of zirconium phosphate and hydrous zirconium oxide.

43. The device according to any one of the preceding claims 35 to 42, wherein, The adsorption layer further includes an alkaline sodium source.

44. The device according to any one of the preceding claims 35 to 43, wherein, The sodium source includes at least one of sodium carbonate and sodium bicarbonate.

45. The device according to any one of the preceding claims 35 to 44, wherein, The adsorber cartridge further includes an inlet port and an outlet port, the urease layer is disposed near the inlet, and the adsorption layer is disposed near the outlet.

46. The device according to any one of the preceding claims 35 to 45, wherein, The urease in the urease layer is immobilized.

47. The device according to any one of the preceding claims 35 to 46 further comprises a dialyzer in fluid communication with the adsorber cartridge, wherein, Used dialysate flows from the dialyzer to the adsorber cartridge.

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