Adsorbent regeneration cartridge for dialysis

Abstract

To provide a regenerative cartridge for adsorbents used in dialysis. [Solution] An adsorbent regeneration system for use in a dialysis machine is described. The adsorbent regeneration cartridge may include a layer of urease, a layer of acidic zirconium phosphate, and a layer of sodium zirconium phosphate. The apparatus for performing dialysis may include the adsorbent cartridge and a dialyzer in fluid communication with the adsorbent cartridge, wherein used dialysate moves from the dialyzer to the adsorbent cartridge and passes through it, and the adsorbent cartridge includes a layer of urease, a layer of acidic zirconium phosphate, and a layer of sodium zirconium phosphate. The urease may be immobilized or bound to a carrier.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority and benefit of U.S. Provisional Application No. 63 / 194,843, filed on 28 May 2021, which is expressly incorporated herein in its entirety by reference for all purposes.

[0002] Background of the Invention This invention relates to cartridges useful for dialysis. In particular, the invention generally relates to the regeneration or purification of dialysate after use. The invention further relates to a method for performing dialysis using a specific cartridge, and a method for manufacturing a cartridge. [Background technology]

[0003] In the United States, it is estimated that more than two out of seven adults (approximately 15 out of 15 American adults) suffer from chronic kidney disease (or renal disease). In people suffering from chronic kidney disease, their kidneys no longer cleanse their blood as effectively as healthy kidneys. Therefore, toxic waste and excess fluid accumulate in the body. Dialysis is a procedure to remove waste products and excess fluid that accumulate in the blood as a result of kidney failure. Chronic renal failure is when kidney function deteriorates to about 25% of normal. This deterioration causes significant changes in blood chemistry, and it is around this time that people begin to feel unwell and seek medical attention. If medical treatment is sought at this stage, the progression can be slowed. Late chronic renal failure is when kidney function has decreased to 15%. End-stage renal failure is when kidney function is 5% of normal. At this point, the probability of death is highest if treatment is not provided.

[0004] Currently, there is no cure for kidney disease, but there are several forms of treatment. One treatment is transplantation, in which a human kidney is surgically placed in the body and connected to the bladder. After transplantation, daily medication is required to prevent the transplanted kidney from being rejected by the body. Another treatment is peritoneal dialysis (PD). In this procedure, a dilute saline solution containing dextrose and electrolytes, called dialysate, is introduced into the peritoneal cavity. Concentrated blood is supplied to this peritoneal cavity, so urea and other toxins from the blood and fluids are transferred to the dialysate, thereby purifying the blood. Next, the dialysate is drained from the peritoneum. Then, "fresh" dialysate is introduced back into the peritoneum.

[0005] Another form of treatment is hemodialysis. This is a method of blood purification in which blood is continuously drawn from the body and passed through a dialyzer (artificial kidney) where metabolic waste and excess water are removed and the pH and acid / base balance are normalized. At the same time, the blood is returned to the body. The dialyzer is a small, disposable device consisting of a semipermeable membrane. The membrane allows waste, electrolytes, and water to pass through, but restricts the passage of large molecular weight proteins and blood cells. Blood is pumped from one side of the membrane, and similarly, dialysate is pumped from the opposite side of the membrane in the opposite direction. Dialysis is highly purified water to which salts and electrolytes have been added. The machine is a control unit that pumps the blood and dialysate and controls their pressure, temperature, and electrolyte concentration. The average length of a single hemodialysis treatment is approximately 3.5 hours.

[0006] There are several types of hemodialysis, including single-pass systems and adsorbent systems. Single-pass hemodialysis is the most common treatment for kidney disease. These methods are called single-pass because the dialysate (clean fluid) passes through the blood in the dialyzer only once and is then discarded. Single-pass dialysis machines generally have: (1) a water supply capable of delivering at least 1000-1500 ml / min (assuming a 50% removal rate by a reverse osmosis (RO) system) The system requires: (2) a water purification system sufficient to supply purified water at a continuous flow rate of 500-800 ml / min; (3) an electrical circuit of at least 15 amps for pumping 500-800 ml of water / min for treatment; and (4) a floor drain or any other container capable of holding at least 500 ml of used dialysate / min, as well as water removed from the RO system.

[0007] The adsorbent dialysis system continuously regenerates small amounts of dialysate and incorporates a water treatment system within the machine, eliminating the need for a continuous water supply, a separate water purifier, or a floor drain. Therefore, the adsorbent system is portable. The adsorbent system can use 5-7 liters of sterile water, standard saline, semi-concentrated saline, or dialysate from which dialysate is prepared or regenerated throughout the entire procedure. The adsorbent system uses an adsorbent cartridge, which removes uremic toxins without removing most of the salts, allowing for efficient regeneration of used dialysate into fresh dialysate. An infusion system works with the adsorbent system to maintain proper electrolyte balance in the regenerated dialysate.

[0008] Several types of multilayer adsorbent cartridges are used in dialysis machines to remove uremic toxins from a patient's blood and reuse the dialysate solution through recirculation. However, these earlier adsorbent dialysis systems did not efficiently remove uremic toxins without significant trade-offs in sodium, pH control, procedure reproducibility, total urea capacity, and adsorbent cartridge size. [Overview of the project] [Problems that the invention aims to solve]

[0009] Therefore, in the field of dialysis, it would be beneficial to create adsorbent cartridge systems with a higher capacity to remove uremic toxins and sodium within the cartridge. [Brief explanation of the drawing]

[0010] [Figure 1A] Figures 1A to 1E are schematic diagrams of adsorbent cartridges based on various embodiments. [Figure 1B] Figures 1A to 1E are schematic diagrams of adsorbent cartridges based on various embodiments. [Figure 1C] Figures 1A to 1E are schematic diagrams of adsorbent cartridges based on various embodiments. [Figure 1D] Figures 1A to 1E are schematic diagrams of adsorbent cartridges based on various embodiments. [Figure 1E] Figures 1A to 1E are schematic diagrams of adsorbent cartridges based on various embodiments. [Modes for carrying out the invention]

[0011] Abstract This document describes adsorbent cartridges that can be used to regenerate the dialysate used in dialysis systems.

[0012] In many embodiments, the adsorbent cartridge includes a layer of urease, a layer of acidic zirconium phosphate, and a layer of zirconium phosphate. In some embodiments, in the urease layer, the urease may be immobilized or bound to a carrier. In some embodiments, the urease is attached to a carrier such as silica, diatoms (e.g., diatomaceous earth), alumina, activated carbon, metal hydroxides (based on iron, titanium, and zirconium), metal phosphates (primarily composed of iron, titanium, zirconium, or cerium), high surface area metal oxides (primarily composed of iron, titanium, zirconium, and cerium), anion, or cation exchange polymer. It may be conjugated with a polymer or a high-surface-area polymer-based adsorbent.

[0013] In many embodiments, a device for performing dialysis includes an adsorbent cartridge and a dialyzer in fluid communication with the adsorbent cartridge, where spent dialysate moves from the dialyzer to and through the adsorbent cartridge, and where the adsorbent cartridge includes a layer of immobilized urease, a layer of acidic zirconium phosphate, and a layer of sodium-form zirconium phosphate.

[0014] Detailed Description In a dialysis procedure, for patients without a healthy kidney to perform those tasks, a dialysis machine functions as an artificial kidney to remove uremic toxins, maintain the balance of ionic molecules, and balance the pH. When a large amount of water is replaced in a multi-layer cartridge, the cartridge is involved not only in removing uremic toxins but also in maintaining the balance of ionic salts and pH.

[0015] A hemodialysis system incorporating a dialysate generator is described in US2021 / 0128807, which is hereby expressly incorporated by reference in its entirety for all purposes. Various embodiments of an adsorbent regeneration system, including an adsorbent cartridge, described herein may be incorporated into the system described in US2021 / 0128807 in place of the dialysate generator.

[0016] As shown in FIG. 1A, the cartridge 200 may include multiple components for purifying the dialysate. The cartridge 200 may include layers of urease 204, activated carbon 206, zirconium hydrogen phosphate 208, sodium zirconium phosphate 210, and zirconium hydroxide 212, or combinations thereof. Each layer may be separated by a filter, such as filter paper. During regenerative dialysis, the used dialysate moves upward through the layers of the cartridge 200. Urease 204 converts urea to ammonium carbonate. Activated carbon 206 absorbs the patient's organic metabolites, such as creatinine, uric acid, and nitrogenous metabolic wastes, as well as chlorine and chloramine from water. Next, ammonia and ammonium ions are removed by exchange with H + and Na + ions by the layers of zirconium hydrogen phosphate 208 and sodium zirconium phosphate 210. Next, bicarbonate (HCO3 - ) and carbon dioxide (CO2) are formed by urea hydrolysis. HZO adsorbs HCO3 - , PO4 - and other anions and releases hydroxide. CO2 bubbles are exhausted from the cartridge.

[0017] It should be understood that although the layers of the cartridge are described in an exemplary order in FIGS. 1A - 1E, they may be arranged in any other possible order or arrangement. For example, the cartridge may be configured such that the activated carbon layer 206 contacts the used dialysate after either or both of the zirconium phosphate layers 207, 208, 209, 210. The activated carbon layer 206 may be after the zirconium oxide 212 layer. The activated carbon layer 206 may also be before the urease layer 204.

[0018] Layer 204, containing urease and a carrier, serves the purpose of converting urea to ammonium (e.g., 2 molecules of ammonium for 1 molecule of urea), and the ammonium is adsorbed to other layers of the cartridge. Layer 204 contains either immobilized urease or free urease bound to an adsorbent carrier. When the urease is covalently bonded, it maintains the urease active and stable for a longer period compared to layers where the urease is not covalently bonded to alumina. Furthermore, it has been found that alumina leaches aluminum into the dialysis system, resulting in unacceptably high levels of aluminum. The urease can be covalently bonded to silica or diatoms coated with a primary amine via glutaraldehyde, thereby preventing alumina from being incorporated into the adsorbent cartridge. The primary amine coating is APTES Urease may result from the treatment of silica or diatoms with ((3-aminopropyl)triethoxysilane) or APTMS (3-aminopropyltrimethoxysilane) or (3-aminopropyl)silanetriol. Alternatively, urease can adsorb and bind to materials with a lower risk of leaching of toxic metals such as titanium, cerium, iron, or zirconium oxides, hydroxides, or phosphates. The urease layer 204 may contain about 100g to about 400g, or about 100g to about 300g, or about 150g to about 250g of urease, for example, in the form of urease conjugated with silica.

[0019] In some embodiments, the urease layer 204 may contain a mix of silica, diatoms, titanium dioxide, iron oxide, iron phosphate, titanium phosphate, or cerium oxide. This mix may or may not be mixed with zirconium phosphate in various hydrogen-to-sodium ratios.

[0020] In some embodiments, the urease layer 204 may contain urease in combination with one or more other components. As seen in the cartridge 250 of FIG. 1D, the urease layer 204 may include urease and iron oxide. As seen in the cartridge 260 of FIG. 1E, the urease layer 204 may include urease and a mix of sodium zirconium phosphate and hydrogen (acidic) zirconium phosphate.

[0021] The activated carbon layer 206 may be disposed after or downstream of the urease and removes specific uremic toxins such as middle molecules, uric acid, oxidants, and creatinine, as well as any toxins from the water / dialysate such as heavy metals and organic molecules. In some embodiments, the activated carbon may be the final layer within the cartridge (see, e.g., FIGS. 1D and 1E). The activated carbon layer 206 may also capture unwanted enzymes and proteins leached from the layer 204. Activated carbon can also be used as a filter medium for binding heavy metals, oxidants, and chloramines. The activated carbon layer 206 may contain from about 100 g to about 400 g, or from about 100 g to about 300 g, or from about 150 g to about 250 g of activated carbon. The particle size of the activated carbon may be from about 50 μm to about 600 μm, or from about 75 μm to about 550 μm, or from about 80 μm to about 550 μm, or from about 75 μm to about 550 μm, or from about 90 μm to about 550 μm, or from about 90 μm to about 500 μm, or from about 100 μm to about 500 μm. The activated carbon layer 206 may be disposed either before or after any of the zirconium phosphate layers 208, 210 or the hydrated zirconium oxide layer 212.

[0022] Either the layer of hydrogen acid zirconium phosphate 208 and sodium zirconium phosphate 210 may be disposed after the activated carbon layer 206 or before the activated carbon layer 206 and the zirconium oxide layer. Zirconium phosphate in sodium or hydrogen form functions as a cation exchanger and ammonium (NH4 + )、calcium (Ca +2 )、potassium (K + )、and magnesium (Mg +2It can absorb cations such as sodium (Na). Instead of absorbing these cations, zirconium phosphate absorbs two other cations, sodium (Na). + ) and hydrogen (H + ) releases ). Hydrated zirconium oxide acts as an anion exchanger. Therefore, hydrated zirconium oxide releases phosphate (PO4) instead. - ) and fluoride (F - It can bind to anions such as hydroxides.

[0023] The hydrogen (acid) zirconium phosphate layer 208 may contain approximately 200g to 1200g, or approximately 200g to 800g, or approximately 200g to 750g, or approximately 300g to 700g, or approximately 300g to 650g of hydrogen (acid) zirconium phosphate. The pH of the hydrogen (acid) zirconium phosphate in layer 208 may be approximately 1 to 4, or approximately 1 to 3, or approximately 1 to 2, or approximately 1.2 to 1.8, or approximately 1.5 to 1.8, or approximately 1.0, or approximately 1.1, or approximately 1.2, or approximately 1.3, or approximately 1.4, or approximately 1.5, or approximately 1.6, or approximately 1.7, or approximately 1. The pH may be 0.8, or about 1.9, or about 2.0. Zirconium phosphate may be equilibrated with hydrogen to a specific pH in order to achieve the desired pH. The particle size of hydrogen (acidified) zirconium phosphate may be about 20 μm to about 150 μm, or about 20 μm to about 130 μm, or about 30 μm to about 120 μm, or about 30 μm to about 110 μm, or about 40 μm to about 110 μm, or about 30 μm to about 100 μm, or about 40 μm to about 100 μm.

[0024] The sodium zirconium phosphate layer 210 may contain approximately 200g to 1200g, or approximately 200g to 800g, or approximately 200g to 750g, or approximately 300g to 700g, or approximately 300g to 650g, or approximately 400g to 650g, or approximately 450g to 650g of sodium zirconium phosphate. The pH of the sodium zirconium phosphate in layer 210 may be approximately 2 to approximately 7, or approximately 3 to approximately 6.5, or approximately 3 to approximately 6.0, or approximately 3.5 to approximately 5.5, or approximately 4.5 to approximately 6.5, or approximately 4.0, or approximately 4.3, or approximately 4.5, or approximately 4.7, or approximately 5.0, or approximately 5.3, or approximately 5.5, or approximately 5.7, or approximately 6.0, or approximately 6.3, or approximately 6.5, or approximately 6.7. The particle size of the sodium zirconium phosphate may be approximately 20 μm to approximately 150 μm, or approximately 20 μm to approximately 130 μm, or approximately 30 μm to approximately 120 μm, or approximately 30 μm to approximately 110 μm, or approximately 40 μm to approximately 110 μm, or approximately 30 μm to approximately 100 μm, or approximately 40 μm to approximately 100 μm.

[0025] The hydrogen (acidified) zirconium phosphate layer 208 may bind to ammonium molecules converted from urea molecules while counteracting sodium ions by exchanging its hydrogen ions. While the hydrogen (acidified) zirconium phosphate layer alone utilizes ammonium capacity faster than sodium zirconium phosphate, the acidic layer 208 removes an excess of 10–35 mmol / L of sodium from the dialysate during the procedure. The sodium zirconium phosphate layer 210 can bind to ammonium molecules in a larger capacity than hydrogen zirconium phosphate. Layers 208 and 210 adsorb large amounts of sodium ions, and as more sodium is removed over time, the release of ammonium decreases. This design maximizes ammonium removal by zirconium phosphate, but also maximizes sodium removal. The removed excess sodium prevents excess sodium from re-entering the patient and allows for the re-equilibrium of the dialysate solution to a neutral pH.

[0026] In some embodiments, the cartridge may contain three or more layers of zirconium phosphate. As shown in Figure 1B, cartridge 220 may contain layers of hydrogen (acidic) zirconium phosphate 208, partially acidic / sodium zirconium phosphate 209, and sodium zirconium phosphate 210. Partially acidic / sodium zirconium phosphate 209 may be a mixture of sodium and the acidic form of zirconium phosphate. Partially acidic / sodium zirconium phosphate 209 is a salt / acidic solution of zirconium phosphate with some bonded H + or Na + Since it can be prepared by equilibrating with, the properties of layer 209 can be similar to those of the homogeneous mixed layer 207. For example, when acidic zirconium phosphate is mixed with deionized (DI) water, the pH is about 1.5, and when sodium zirconium phosphate is mixed with DI water, the pH is about 6-7, but various amounts of H + / NA + By exchanging the material, zirconium phosphate with a pH of approximately 5 in DI water can be obtained.

[0027] In other embodiments, as shown in Figure 1C, the cartridge 240 may contain layers of mixed sodium zirconium phosphate and hydrogen (acid) zirconium phosphate 207, for example, a homogeneous mixture, as well as a layer 210 of sodium zirconium phosphate. The relative ratio of thorium may be approximately 1:10 to 3:1, or approximately 0.2:3.0, or approximately 0.2:2.5, or approximately 0.2:2.0, or approximately 0.25:2.0, or approximately 0.3:2.0, or approximately 0.4:2.0, or approximately 0.5:2.0.

[0028] A multilayer of acidic zirconium phosphate 208 and partially hydrogenated (acidic) / sodium zirconium phosphate 209 (see Figure 1B), or a mixed layer of sodium zirconium phosphate and hydrogenated (acidic) zirconium phosphate 207, followed by sodium zirconium phosphate 210 (see Figure 1C), counteracts sodium ions and readjusts the pH of the dialysate, while providing a higher ammonium capacity of approximately 20-30%. Additional and / or continuous layers may have a higher capacity to bind ammonium compared to other adsorbent cartridges that contain only a mixture of acidic zirconium phosphate and sodium zirconium phosphate within their cartridges to maintain the pH equilibrium of the system.

[0029] Excess sodium zirconium phosphate in the cartridge can leach excess sodium ions into the dialysate, exchanging them for hydrogen in the acidic zirconium phosphate. This reduces the cartridge's capacity and increases the sodium concentration beyond the normal range. To maintain sodium ion equilibrium, the ratio of acidic zirconium phosphate can be adjusted to 50% or higher. To offset the decrease in sodium concentration while maintaining an optimal cartridge configuration, sodium carbonate injection can be controlled in various proportions through a modified program.

[0030] The cartridge may also contain a layer 212 of zirconium oxide or hydrated zirconium oxide or hydrated zirconium hydroxide to remove phosphate ions and any trace heavy metals that may have passed through the activated carbon layer from the patient's body and previous layers of the cartridge. Layer 212 may be the last layer of the cartridge or may be located ahead of the fluid flow path.

[0031] The zirconium oxide layer 212 may contain about 100g to about 600g, or about 100g to about 500g, or about 200g to about 500g, or about 200g to about 450g, or about 200g to about 400g of zirconium oxide or other transition metal oxides. In some embodiments, instead of zirconium oxide, layer 212 may contain titanium oxide, iron oxide, or any other transition metal oxide. In other embodiments, the transition metal oxide may also be in a hydrated form. The transition metal oxide can be equilibrated to a suitable pH in solution. The pH of the transition metal oxide, for example, zirconium oxide in layer 212, may be approximately 2.0 to approximately 7.0, or approximately 3 to approximately 7.0, or approximately 3.5 to approximately 7.0, or approximately 5.0 to approximately 8.0, or approximately 4.0 to approximately 7.0, or approximately 4.5 to approximately 7.0, or approximately 4.5 to approximately 6.5, or approximately 5.5 to approximately 6.5, or approximately 6.0 to approximately 7.0, or approximately 4.5, or approximately 5.0, or approximately 5.5, or approximately 6.0, or approximately 6.5, or approximately 7.0, or approximately 7.5, or approximately 8.0, or approximately 8.5. The particle size of the transition metal oxide may be approximately 10 μm to 150 μm, or approximately 10 μm to 130 μm, or approximately 10 μm to 120 μm, or approximately 20 μm to 110 μm, or approximately 20 μm to 105 μm, or approximately 20 μm to 100 μm, or approximately 25 μm to 100 μm.

[0032] Zirconium oxide may include, but is not limited to, many different forms, including zirconium oxide, zirconium hydroxide, zirconium hydroxide, hydrated zirconium oxide, hydrated or unhydrated zirconium oxide, or combinations thereof.

[0033] The zirconium oxide layer 212 is made of other metal oxides, such as iron oxide, titanium oxide, or acid It may be compatible with cerium oxide. Iron oxide may include, but is not limited to, iron oxide, iron hydroxide, iron oxide hydroxide, hydrated iron oxide, and hydrated iron oxide, and may include many different forms. Titanium oxide may include, but is not limited to, titanium oxide, titanium hydroxide, titanium oxide hydroxide, hydrated titanium oxide, and hydrated titanium oxide, and may include many different forms. Cerium oxide may include, but is not limited to, cerium oxide, cerium hydroxide, cerium oxide hydroxide, hydrated cerium oxide, and hydrated cerium oxide, and may include many different forms.

[0034] Potential chemicals that may leach into the cartridge may include unwanted intermediate molecules, such as proteins and enzymes, as well as phosphates from the zirconium phosphate adsorbent layer. The activated carbon layer 206 of the cartridge represents binding unwanted intermediates in the dialysate. The zirconium oxide layer at the end of the cartridge may function to bind phosphate molecules that may leach from the zirconium phosphate as the layer loses its capacity for ammonium.

[0035] In consideration of and / or supplement to the embodiments described herein, various aspects of this subject matter are described below, with an emphasis on the interrelationships and interchangeability of the following embodiments. In other words, emphasis is placed on the fact that each feature of an embodiment can be combined with any other feature unless otherwise specified or is logically unbelievable. The embodiments described herein are further described and extended in the following paragraphs without express reference to the drawings.

[0036] In many embodiments, the adsorbent cartridge includes a layer of urease, a layer of acidic zirconium phosphate, and a layer of zirconium phosphate, where the urease is immobilized by covalent bonds, or free urease is bound to or adsorbed onto the adsorbent carrier.

[0037] In some embodiments, the cartridge is configured such that the used dialysate comes into contact with a urease layer before it comes into contact with either a layer of acidic zirconium phosphate or a layer of zirconium phosphate.

[0038] In some embodiments, the cartridge is configured such that the used dialysate comes into contact with the layer of acidic zirconium phosphate before the layer of zirconium phosphate.

[0039] In some embodiments, the cartridge further includes a layer of activated carbon. In some embodiments, the cartridge is configured such that the used dialysate comes into contact with the activated carbon layer after it has come into contact with the urease layer.

[0040] In some embodiments, the cartridge includes activated carbon as the final layer.

[0041] In some embodiments, the cartridge is configured with a layer of activated carbon as the final layer.

[0042] In some embodiments, the cartridge further includes a layer of zirconium oxide. In some embodiments, the zirconium oxide in the zirconium oxide layer is zirconium oxide, zirconium hydroxide, zirconium hydroxide, hydrated zirconium oxide, hydrated zirconium oxide, hydrated zirconium oxide, unhydrated zirconium oxide, or a combination thereof. In some embodiments, the cartridge is configured such that the used dialysate comes into contact with a layer of zirconium oxide after it has come into contact with a layer of acidic zirconium phosphate. In some embodiments, the cartridge is configured such that the used dialysate comes into contact with a layer of zirconium oxide after it has come into contact with a layer of zirconium phosphate.

[0043] In some embodiments, the zirconium phosphate layer contains sodium zirconium phosphate.

[0044] In some embodiments, the urease in the urease layer is immobilized.

[0045] In some embodiments, in the urease layer, the urease is covalently bonded to silica.

[0046] In some embodiments, the urease layer comprises a mixture of urease and a metal oxide. In some embodiments, the metal oxide is iron oxide. In some embodiments, the metal oxide is selected from the group consisting of iron oxide, iron hydroxide, iron hydroxide, hydrated iron oxide, and hydrated iron oxide.

[0047] In some embodiments, the urease layer comprises a mixture of urease and at least one zirconium phosphate.

[0048] In some embodiments, the urease layer comprises a mixture of urease and at least two forms of zirconium phosphate. In some embodiments, the at least two forms of zirconium phosphate comprise sodium zirconium phosphate and acidic zirconium phosphate.

[0049] In some embodiments, the cartridge further includes an additional layer of zirconium phosphate. In some embodiments, the cartridge is configured such that the used dialysate comes into contact with the additional layer of zirconium phosphate after it has come into contact with the activated carbon layer, but before it comes into contact with the acidic zirconium phosphate layer.

[0050] In some embodiments, the acidic zirconium phosphate layer further contains zirconium phosphate to form a mixed zirconium phosphate layer. In some embodiments, the mixed zirconium phosphate layer has an acidic zirconium phosphate:sodium zirconium phosphate ratio of about 0.25:2.0.

[0051] In many embodiments, the apparatus for performing dialysis includes an adsorbent cartridge and a dialyzer in fluid communication with the adsorbent cartridge, wherein used dialysate moves from the dialyzer to the adsorbent cartridge and passes through it, wherein the adsorbent cartridge includes a layer of urease and carrier, a layer of acidic zirconium phosphate, and a layer of zirconium phosphate.

[0052] In some embodiments, the adsorbent cartridge is configured such that the used dialysate comes into contact with a urease layer before it comes into contact with either a layer of acidic zirconium phosphate or a layer of zirconium phosphate.

[0053] In some embodiments, the adsorbent cartridge is configured such that the used dialysate comes into contact with a layer of acidic zirconium phosphate before the layer of zirconium phosphate.

[0054] In some embodiments, the adsorbent cartridge further includes a layer of activated carbon. In some embodiments, the activated carbon layer is configured as the final layer. In some embodiments, the adsorbent cartridge is configured such that the used dialysate comes into contact with the activated carbon layer after it has come into contact with the urease layer.

[0055] In some embodiments, the adsorbent cartridge further includes a layer of zirconium oxide. In some embodiments, the zirconium oxide in the zirconium oxide layer is zirconium oxide, zirconium hydroxide, zirconium hydroxide, hydrated zirconium oxide, and water The adsorbent is zirconium oxide, hydrated zirconium oxide, unhydrated zirconium oxide, or a combination thereof. In some embodiments, the adsorbent cartridge is configured such that the used dialysate comes into contact with a layer of zirconium oxide after coming into contact with a layer of acidic zirconium phosphate. In some embodiments, the adsorbent cartridge is configured such that the used dialysate comes into contact with a layer of zirconium oxide after coming into contact with a layer of zirconium phosphate.

[0056] In some embodiments, the zirconium phosphate layer comprises sodium zirconium phosphate.

[0057] In some embodiments, the urease in the urease layer is immobilized.

[0058] In some embodiments, in the urease layer, the urease is covalently bonded to silica.

[0059] In some embodiments, the urease layer comprises a mixture of urease and a metal oxide. In some embodiments, the metal oxide is iron oxide. In some embodiments, the metal oxide is selected from the group consisting of iron oxide, iron hydroxide, iron hydroxide, hydrated iron oxide, and hydrated iron oxide.

[0060] In some embodiments, the urease layer comprises a mixture of urease and at least one zirconium phosphate.

[0061] In some embodiments, the urease layer comprises a mixture of urease and at least two forms of zirconium phosphate.

[0062] In some embodiments, at least two forms of zirconium phosphate include sodium zirconium phosphate and acidic zirconium phosphate.

[0063] In some embodiments, the cartridge further includes an additional layer of zirconium phosphate. In some embodiments, the cartridge is configured such that the used dialysate comes into contact with the additional layer of zirconium phosphate after it has come into contact with the activated carbon layer, but before it comes into contact with the acidic zirconium phosphate layer.

[0064] In some embodiments, the acidic zirconium phosphate layer further contains zirconium phosphate to form a mixed zirconium phosphate layer. In some embodiments, the mixed zirconium phosphate layer has an acidic zirconium phosphate:sodium zirconium phosphate ratio of about 0.25:2.0. For example, the present invention provides the following items: (Item 1) An adsorbent cartridge containing a urease layer, an acidic zirconium phosphate layer, and a zirconium phosphate layer. (Item 2) The cartridge according to item 1, wherein the used dialysate is configured to come into contact with the urease layer before it comes into contact with either the acid zirconium phosphate layer or the zirconium phosphate layer. (Item 3) The cartridge according to item 1, wherein the used dialysis fluid is configured to come into contact with the layer of acidic zirconium phosphate before the layer of zirconium phosphate. (Item 4) The cartridge described in item 1, further containing a layer of activated carbon. (Item 5) The cartridge described in item 4, in which an activated carbon layer is formed as the final layer. (Item 6) The cartridge according to item 4, wherein the used dialysate is configured to come into contact with the urease layer, and then the used dialysate comes into contact with the activated carbon layer. (Item 7) The cartridge described in item 1, further containing a layer of zirconium oxide. (Item 8) The cartridge according to item 7, wherein the zirconium oxide in the zirconium oxide layer comprises zirconium oxide, zirconium hydroxide, zirconium hydroxide, hydrated zirconium oxide, hydrated zirconium oxide, hydrated zirconium oxide, unhydrated zirconium oxide, or a combination thereof. (Item 9) The cartridge according to item 7, wherein the used dialysate is configured to come into contact with the layer of acidic zirconium phosphate, and then with the layer of zirconium oxide. (Item 10) The cartridge according to item 7, wherein the used dialysate is configured to come into contact with the zirconium phosphate layer, and then with the zirconium oxide layer. (Item 11) The cartridge according to item 1, wherein the zirconium phosphate layer contains sodium zirconium phosphate. (Item 12) The cartridge described in item 1, wherein the urease in the aforementioned urease layer is immobilized. (Item 13) The cartridge according to item 12, wherein the immobilized urease layer is covalently bonded to silica. (Item 14) The cartridge according to item 1, wherein the urease layer comprises a mixture of urease and a metal oxide. (Item 15) The cartridge described in item 14, wherein the metal oxide is iron oxide. (Item 16) The cartridge according to item 14, wherein the metal oxide is selected from the group consisting of iron oxide, iron hydroxide, iron hydroxide, hydrated iron oxide, and hydrated iron oxide. (Item 17) The cartridge according to item 1, wherein the urease layer comprises a mixture of urease and at least one zirconium phosphate. (Item 18) The cartridge according to item 1, wherein the urease layer comprises a mixture of urease and at least two forms of zirconium phosphate. (Item 19) The cartridge according to item 18, wherein the at least two forms of zirconium phosphate include sodium zirconium phosphate and acidic zirconium phosphate. (Item 20) The cartridge described in item 1, further comprising an additional layer of zirconium phosphate. (Item 21) The cartridge according to item 20, wherein the additional zirconium phosphate layer further comprises acidic zirconium phosphate to form a layer of partially acidic zirconium phosphate and sodium zirconium phosphate. (Item 22) The cartridge according to item 21, wherein the layer of partially acidic zirconium phosphate and sodium zirconium phosphate is disposed between the layer of acidic zirconium phosphate and the layer of zirconium phosphate. (Item 23) The cartridge according to item 20, wherein the used dialysate is configured to come into contact with an additional layer of zirconium phosphate after it has come into contact with a layer of activated carbon, and before it comes into contact with a layer of acidic zirconium phosphate. (Item 24) The cartridge according to item 1, wherein the layer of acidic zirconium phosphate further comprises zirconium phosphate to form a mixed layer of zirconium phosphate. (Item 25) The cartridge according to item 24, wherein the mixed layer of zirconium phosphate has a ratio of acidic zirconium phosphate to sodium zirconium phosphate of approximately 0.25:2.0. (Item 26) An apparatus for performing dialysis, comprising an adsorbent cartridge and a dialyzer in fluid communication with the adsorbent cartridge, wherein used dialysate moves from the dialyzer to the adsorbent cartridge and passes through it, and the adsorbent cartridge comprises a layer of urease, a layer of acidic zirconium phosphate, and a layer of zirconium phosphate. (Item 27) The apparatus according to item 26, wherein the adsorbent cartridge is configured such that the used dialysate comes into contact with the urease layer before it comes into contact with either the acid zirconium phosphate layer or the zirconium phosphate layer. (Item 28) The apparatus according to item 26, wherein the adsorbent cartridge is configured such that the used dialysis fluid comes into contact with the layer of acidic zirconium phosphate before the layer of zirconium phosphate. (Item 29) The apparatus according to item 26, wherein the adsorbent cartridge further comprises a layer of activated carbon. (Item 30) The apparatus according to item 26, wherein the activated carbon layer is configured as the final layer. (Item 31) The apparatus according to item 29, wherein the adsorbent cartridge is configured such that the used dialysate comes into contact with the activated carbon layer after the used dialysate has come into contact with the urease layer. (Item 32) The apparatus according to item 26, wherein the adsorbent cartridge further comprises a layer of zirconium oxide. (Item 33) The apparatus according to item 32, wherein the zirconium oxide in the zirconium oxide layer includes zirconium oxide, zirconium hydroxide, zirconium hydroxide, hydrated zirconium oxide, hydrated zirconium oxide, hydrated zirconium oxide, unhydrated zirconium oxide, or a combination thereof. (Item 34) The apparatus according to item 32, wherein the adsorbent cartridge is configured such that the used dialysate comes into contact with the layer of zirconium oxide after the used dialysate has come into contact with the layer of acid zirconium phosphate. (Item 35) The apparatus according to item 32, wherein the adsorbent cartridge is configured such that the used dialysate comes into contact with the zirconium oxide layer after the used dialysate has come into contact with the zirconium phosphate layer. (Item 36) The apparatus according to item 26, wherein the zirconium phosphate layer comprises sodium zirconium phosphate. (Item 37) The apparatus according to item 36, wherein the urease in the urease layer is immobilized. (Item 38) The apparatus according to item 37, wherein the immobilized urease layer is covalently bonded to silica. (Item 39) The apparatus according to item 26, wherein the urease layer comprises a mixture of urease and a metal oxide. (Item 40) The apparatus according to item 39, wherein the metal oxide is iron oxide. (Item 41) The apparatus according to item 39, wherein the metal oxide is selected from the group consisting of iron oxide, iron hydroxide, iron hydroxide, hydrated iron oxide, and hydrated iron oxide. (Item 42) The apparatus according to item 26, wherein the urease layer comprises a mixture of urease and at least one zirconium phosphate. (Item 43) The apparatus according to item 26, wherein the urease layer comprises a mixture of urease and at least two forms of zirconium phosphate. (Item 44) The apparatus according to item 43, wherein the at least two forms of zirconium phosphate include sodium zirconium phosphate and acidic zirconium phosphate. (Item 45) The apparatus according to item 26, further comprising an additional layer of zirconium phosphate. (Item 46) The apparatus according to item 45, wherein the additional zirconium phosphate layer further comprises acidic zirconium phosphate to form a layer of partially acidic zirconium phosphate and sodium zirconium phosphate. (Item 47) The apparatus according to item 46, wherein the layer of partially acidic zirconium phosphate and sodium zirconium phosphate is disposed between the layer of acidic zirconium phosphate and the layer of zirconium phosphate. (Item 48) The apparatus according to item 45, wherein the cartridge is configured such that the used dialysate comes into contact with an additional layer of zirconium phosphate after the used dialysate has come into contact with the activated carbon layer and before the used dialysate comes into contact with the acid zirconium phosphate layer. (Item 49) The apparatus according to item 26, wherein the layer of acidic zirconium phosphate further comprises zirconium phosphate to form a mixed layer of zirconium phosphate. (Item 50) The apparatus according to item 49, wherein the mixed layer of zirconium phosphate has a ratio of acidic zirconium phosphate to sodium zirconium phosphate of approximately 0.25:2.0.

Claims

[Claim 1] The invention described in the specification.

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