Sorbents for renal therapy

Abstract

A sorbent cartridge for a portable wearable renal therapy system and methods of use thereof are provided. The sorbent cartridge includes an inlet and an outlet, the inlet configured to receive process fluid from a renal therapy device and the outlet configured to discharge treated process fluid; a hydrogel configured to absorb and adsorb toxins from the process fluid without using dialysate to purify the process fluid. The inlet and the outlet are each configured to be releasably coupled to the renal therapy device to remove the sorbent cartridge.

Description

[0001] Cross Reference to Related Applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 830,239, filed April 5, 2019, which is incorporated by reference in its entirety. TECHNICAL FIELD

[0003] The present disclosure relates generally to fluid treatment systems and methods for kidney therapy, and more particularly to systems and methods including a sorbent for removing toxins and / or water from a fluid. BACKGROUND

[0004] More than 2.5 million patients worldwide utilize some form of dialysis, such as hemodialysis (HD) or peritoneal dialysis (PD), as a life-saving treatment. However, current dialysis therapies still have many shortcomings when used to replace the function of a normal kidney. The most important shortcoming of the current HD method is its intermittency, which causes large fluctuations in the internal electrolyte environment and patient fluid volume compared to the regulation that can be achieved with a normal kidney. PD provides more continuous dialysis, but has a relatively lower clearance of uremic toxins compared to HD. The PD method often fails in the long term for patients, primarily due to damage to the peritoneum from peritonitis infections, and the high concentration of intraperitoneal glucose required for use in removing the osmotic fluid.

[0005] The overall impact of the shortcomings of current kidney therapies means that these patients have a much lower long-term survival rate compared to the general population. Longer and more frequent treatment methods can improve the survival rate and quality of life for these patients. The use of current kidney therapy technology in a home environment to allow longer and more frequent treatment has had some success in improving outcomes compared to treatment center HD treatment methods, but is limited by economic factors, logistical issues, and space for the patient’s home, such that only a relatively small percentage of patients use home HD treatment methods. Another disadvantage of current home HD treatment methods is that the patient is connected to large medical equipment and water treatment systems for long periods of time, severely impacting mobility. Conventional HD assemblies weigh up to 60 kg. In addition, conventional HD assemblies require additional equipment at a fixed location to purify approximately 120 liters of water each time. This equipment cannot be easily moved to other locations, thus limiting the daily mobility and travel capabilities of home HD patients. SUMMARY

[0006] Disclosed herein are kidney therapy methods using at least one sorbent or sorptive material in a device for removing toxic substances and excess water from a patient’s blood or other bodily fluids, and using sorbent or sorptive materials suitable for use in the device and other hemodialysis and peritoneal dialysis systems for removing toxic substances from blood and other bodily fluids. The patient can be a human or an animal.

[0007] In one aspect, the disclosure describes a sorbent cartridge for a portable wearable renal therapy system. The sorbent cartridge includes an inlet configured to receive process fluid from the renal therapy system and an outlet configured to discharge treated process fluid; a hydrogel configured to absorb and adsorb toxins from the process fluid without using dialysate to purify the process fluid. The inlet and the outlet are each configured to be releasably coupled to the renal therapy device to remove the sorbent cartridge.

[0008] In another aspect, the disclosure describes a sorbent cartridge for a renal therapy system. The sorbent cartridge is loaded with a hydrogel configured to absorb or adsorb toxins from process fluid, and the sorbent cartridge is configured to be releasably coupled to the renal therapy system for easy removal.

[0009] In one embodiment, the hydrogel is configured to release at least one of an electrolyte, a buffer, a mineral, a vitamin, or an anticoagulant to the process fluid. In one embodiment, the buffer is sodium bicarbonate. In one embodiment, the anticoagulant is at least one of heparin and citrate.

[0010] In one embodiment, the hydrogel is formed into a plurality of water beads located in a reservoir of the sorbent cartridge configured to receive process fluid flowing through the sorbent cartridge, the sorbent cartridge including a filter to prevent the plurality of water beads from entering circulation of the process fluid.

[0011] In one embodiment, the sorbent cartridge is configured such that the hydrogel is in direct contact with the process fluid.

[0012] In one embodiment, the sorbent cartridge is configured such that the hydrogel is in indirect communication with the process fluid through a membrane.

[0013] In one embodiment, the hydrogel is configured to absorb toxins from the process fluid into the hydrogel without changing electrolyte levels outside of a physiological range that is harmful to a user of the renal therapy system.

[0014] In one embodiment, the hydrogel is configured to absorb 1-100 grams of urea from the process fluid in 24 hours without changing electrolyte levels outside of a physiological range that is harmful to a user of the renal therapy system.

[0015] In one embodiment, the hydrogel is configured to absorb electrolytes into the hydrogel to lower a specific electrolyte level of the process fluid.

[0016] In one embodiment, the sorbent cartridge is configured to be releasably coupled to the renal therapy system, wherein the renal therapy system is a portable wearable system.

[0017] In one embodiment, the sorbent cartridge includes a first compartment including a membrane configured to remove water from the process fluid, and a second compartment including a membrane configured to remove toxins.

[0018] In one embodiment, the hydrogel is attached to the membrane in the sorbent cartridge, wherein the membrane is a hollow fiber membrane.

[0019] In one embodiment, the sorbent cartridge includes a temperature sensor configured to send a temperature signal to the controller, and at least one of a heating element and / or a cooling element configured to receive an output signal from the controller.

[0020] In one embodiment, the sorbent cartridge includes an electrically conductive member configured to couple with the cooling element to create a temperature gradient along a distance between the electrically conductive member and the membrane.

[0021] In one embodiment, the sorbent cartridge includes a vibration element configured to vibrate the hydrogel.

[0022] In one embodiment, the hydrogel forms a hydrogel layer having a thickness greater than or equal to about 1 mm.

[0023] In one embodiment, the hydrogel forms a hydrogel layer having a thickness of 1-3 mm.

[0024] In one embodiment, the hydrogel forms a hydrogel layer having a thickness greater than or equal to 3 mm.

[0025] Embodiments can include combinations of the above features.

[0026] In another aspect, the disclosure describes a renal therapy system including the sorbent cartridge of any of the above embodiments. The renal therapy system is at least one of a hemodialysis system, a peritoneal dialysis system, a hemoperfusion system, a hemofiltration system, or a hemodiafiltration system.

[0027] In one embodiment, the system is a portable wearable system.

[0028] In one embodiment, the renal therapy system includes a cooling element to create a temperature gradient along a length of the hydrogel.

[0029] In one embodiment, the renal therapy system includes a vibration element configured to vibrate the hydrogel.

[0030] Embodiments can include combinations of the above features.

[0031] In another aspect, the present disclosure describes use of any of the above sorbent cartridges for renal therapy of a user.

[0032] In another aspect, the present disclosure describes a method of removing a toxic substance from a process fluid. The method includes providing a sorbent cartridge comprising a hydrogel; moving the process fluid through the sorbent cartridge in communication with the hydrogel, the process fluid containing the toxin; absorbing or adsorbing the toxin into the hydrogel from the process fluid to provide a treated process fluid.

[0033] In one embodiment, the method includes heating the process fluid to about 37°C.

[0034] In one embodiment, the method includes absorbing water into the hydrogel from the process fluid.

[0035] In one embodiment, the method includes releasing at least one of an electrolyte, a buffer, a mineral, a vitamin, or an anticoagulant from the hydrogel into the process fluid.

[0036] In one embodiment, the method includes moving the process fluid through a hollow fiber membrane, the process fluid being in indirect communication with the hydrogel through the hollow fiber membrane.

[0037] In one embodiment, the method includes vibrating the hydrogel.

[0038] In one embodiment, the method includes cooling the hydrogel to create a temperature gradient along a length of the hydrogel.

[0039] Embodiments can include combinations of the above features.

[0040] In another aspect, the present disclosure describes use of a hydrogel in a renal therapy system, the hydrogel comprising an interpenetrating network of polymer chains, monomers of the polymer chains having hydrophilic functional groups.

[0041] In one embodiment, the monomers include at least one of polyacrylamide, acrylic acid, alginate, or chitosan.

[0042] In one embodiment, the hydrogel is formed to have a specific surface area of at least 0.1 m 2 / m 3 of a plurality of water beads.

[0043] In one embodiment, the hydrogel is attached around a hollow filtration fiber.

[0044] In one embodiment, the hollow filtration fiber has an internal surface area of 0.1 to 1.0 m 2 / m 3

[0045] ​In one embodiment, the hydrogel is a colloidal gel in which water is the dispersion medium.

[0046] In one embodiment, the polymer chains are functionalized with chemicals or biological elements to facilitate sorption of water and toxins in the hydrogel.

[0047] Embodiments can include combinations of the above features.

[0048] Further details of the above and other aspects of the present principles will become apparent from the detailed description and drawings included below. BRIEF DESCRIPTION OF DRAWINGS

[0049] Reference is made to the accompanying drawings, in which:

[0050] Figure 1 An exploded view of an embodiment sorbent cartridge is shown;

[0051] Figure 2 is an embodiment implementation of a sorbent cartridge in a hemoperfusion system;

[0052] Figure 3 is an embodiment implementation of a sorbent cartridge in a hemofiltration system; and

[0053] Figure 4 is an embodiment implementation of a sorbent cartridge in a hemodialysis system;

[0054] Figure 5 is an embodiment implementation of a sorbent cartridge in a peritoneal dialysis system;

[0055] Figure 6 A portion of an embodiment sorbent cartridge is shown at the interface of the first and second compartments of the sorbent cartridge;

[0056] Figure 7 An embodiment experimental setup to test an embodiment sorbent cartridge is shown; and

[0057] FIG. 8A shows a perspective view of an embodiment sorbent cartridge. FIG. 8B shows a cross-sectional view of an embodiment sorbent cartridge along line A-A of FIG. 8A with a hollow fiber membrane. Figure 8C FIG. 8C shows a cross-sectional view of an embodiment sorbent cartridge along line A-A of FIG. 8A with a substantially flat or corrugated membrane. DETAILED DESCRIPTION

[0058] Described herein are systems and methods that use a hydrogel as a sorbent to detoxify blood directly or indirectly through a membrane, such as in hemoperfusion or to remove toxins from ultrafiltrate and dialysate, for hemofiltration, hemodialysis, or peritoneal dialysis, etc. These fluids can be regenerated and reused.

[0059] Although terms such as "maximizing," "minimizing," and "optimizing" can be used in the present disclosure, it should be understood that such terms can be used to refer to improving, adjusting, and refining, which should not be strictly limited to the greatest, least, or best.

[0060] The term "connected" or "coupled to" can include both direct coupling (in which two elements that are directly connected to one another contact one another) and indirect coupling (in which at least one additional element is located between them).

[0061] As used herein, the term "substantially" can be used in connection with any quantitative representation, which can allow for minor variations without causing a change in the basic function to which it is related. For example, a drive shaft having a circular cross-section is disclosed herein, and within the scope of the invention, a slightly non-circular cross-section can be allowed if its rotational drive capability is not materially altered.

[0062] As used herein, the term "sorption" refers to adsorption and absorption. Adsorption is the process of forming a thin film of molecules or atoms (adsorbate) when a gas or liquid or solute (called the adsorbate) accumulates on the surface of a solid or, less commonly, a liquid (the adsorbent). It is different from absorption, which is the diffusion of a substance into a liquid or solid to form a "solution". The term sorption encompasses both processes, while desorption is the reverse process.

[0063] As used herein, the term "small size molecules" refers to molecules with a molecular weight below 500 Da, such as uric acid, urea, guanidine, ADMA, creatinine.

[0064] As used herein, the term "medium size molecules" refers to molecules with a molecular weight between 500 and 5000 Da, such as end products from peptides and lipids, amines, amino acids, compounds bound to proteins, cytokines, leptin, microglobulin, and some hormones.

[0065] As used herein, the term "ionic solutes" refers to constituents such as phosphates, sulfates, carbohydrates, chlorides, ammonia, potassium, calcium, sodium.

[0066] As used herein, the term "process fluid" refers to dialysate fluid, blood, or plasma.

[0067] As used herein, "nanosize" refers to a size of about 1 to 1000 nm, more preferably, 1 to 100 nm.

[0068] An "electrolyte" is a substance that, when dissolved in, for example, water, produces an electrically conductive solution by dissociating into positive and negative ions. For example, sodium chloride (salt) dissociates into sodium ions and chloride ions. Other electrolytes are bicarbonates, potassium, and phosphates.

[0069] A "buffer" solution is one that resists a change in pH from the addition of acidic or basic substances. The equilibrium between a weak acid and its conjugate base imparts its resistance to a change in pH. Bicarbonate is one example of a buffering substance. Bicarbonate has two equilibrium reactions with bicarbonate ion and carbonic acid.

[0070] The implementation of a wearable kidney treatment device that combines continuous or daily blood purification while maintaining high efficiency removal of uremic toxins can provide an improved method of treatment for patients with kidney disease, including end-stage renal disease.

[0071] More continuous and efficient removal of uremic solutes and water, as well as control of electrolytes, is a major advantage of a wearable device, one of the main challenges of which is the removal of urea. A relatively large amount of urea, up to 24 grams, needs to be removed daily. Existing sorption methods have proven difficult to remove urea. Existing wearable kidney treatment devices based on sorbent and enzyme technology that allow for regeneration of dialysis fluid have been used in some prototypes, but have some problems in terms of safety, control, size, weight, and cost of consumable components. Electro-oxidation methods have also been used. The problem with electro-oxidation is that oxidation of chloride can lead to the formation of reactive chlorine species, such as chloramines.

[0072] A wearable device with an effective sorbent system can also be used to enhance the efficacy of PD by continuously regenerating peritoneal dialysis fluid to maintain a greater plasma-peritoneal dialysis fluid concentration gradient. This reduces the time spent by the patient to perform exchanges while still improving the rate of toxin clearance. In such a wearable PD device, the reduced exposure of the PD catheter to the environment can also extend the viability of the PD technology by reducing the risk of bacterial contamination, thereby reducing the risk of peritonitis. Continuous glucose infusion in a wearable PD device can reduce the functional deterioration of the peritoneum by slightly reducing the peak levels of glucose concentration needed to remove the osmotic fluid in regular intermittent infusion PD. Further, the provided portable dialysis device or artificial kidney allows the patient to perform normal daily activities while receiving an extended period of blood purification treatment, without frequent interruptions or limitations on what they can do.

[0073] A portable dialysis device can be enabled by a system that can remove most toxins from blood without using dialysate or using as little dialysate as possible. The feature of using no or as little dialysate as possible can require the use of one or more substances that can absorb and retain the toxins that need to be removed as well as control electrolyte levels and restore buffer solutions. Attempts have been made in the past to find such materials. Activated carbon has been found to be effective in removing most organic uremic organic toxins, middle molecular weight molecules, uric acid, creatinine, and heavy metals, with the notable exception of urea. Activated carbon has minimal impact on electrolyte levels and does not have the ability to modify or restore buffer levels. Other methods of regenerating dialysate for reuse are using urease to convert urea in the liquid to ammonium carbonate and then using zirconium compounds to remove it. These zirconium compounds can also convert ammonium carbonate to bicarbonate and remove electrolytes. The levels of electrolytes and buffers are restored to the desired levels and then a calibration fluid is perfused through the dialyzer again. This process, known as the REDY system, was effective and used from 1973 to 1993 in a recirculating home hemodialysis system that used 6 liters of dialysate, demonstrating that a sorbent-based system can provide adequate therapy. The main reason this process is no longer used in home hemodialysis is that it is more expensive overall compared to a single pass system that uses a larger volume of water. Patients also have some ongoing concerns about possible adverse reactions, if the system fails to successfully convert all of the ammonia, or if more volume than these compounds can be converted, some of the chemicals in the zirconium compounds can leach into the dialysate. This urease plus zirconium compound and activated carbon system has also been used in trials of wearable hemodialysis systems. Wearable systems require a smaller volume of dialysate. This smaller volume of dialysate also makes it more difficult to remove any air bubbles in the fluid that can contain ammonia. The overall size of multiple sorbent cartridges makes the system heavier, bulkier, and the high cost of the component materials can discourage its widespread adoption.

[0074] A hydrogel sorbent (also referred to herein as a "hydrogel") can include materials that can adsorb large amounts of urea that can also be infused with electrolytes and buffers so that it can provide all of the sorbent volume, electrolyte management, and buffer replacement functions needed when it is used in a wearable or portable kidney treatment system. When a hydrogel is used as a sorbent to regenerate dialysate for hemodialysis or peritoneal dialysis, the volume of dialysate can be kept very low. A hydrogel sorbent can also directly contact dialysate or indirectly through a membrane to adsorb toxins and modify the concentration of electrolytes and buffers without using dialysate to purify the blood filtrate for reinfusion in a hemofiltration system. A hydrogel can also directly pass through a membrane to adsorb toxins and modify the electrolyte and buffer concentration of blood without using dialysate in a hemoperfusion system. A hydrogel can be made from common, low-cost materials and can be made in a form in which toxic materials cannot leach out.

[0075] Hydrogels have been used for other biomedical applications, to absorb exudates from wounds, to slow the release of drugs and other compounds, and as structural materials. Hydrogels have been used for industrial applications, to adsorb nitrates, phosphorus, and metals from waste water. Hydrogels have been used for agriculture, to absorb and release water and fertilizers (e.g., urea, phosphorus, and other electrolytes, etc.) into the soil. Hydrogels have not been used as sorbents for urea and other toxins, or to modify electrolyte and buffer levels in biomedical applications.

[0076] The hydrogel material can be attached directly to the membrane structure or in a separate chamber, with dialysis fluid pumped through the compartment to regenerate the dialysate or backflush. The hydrogel can also be in smaller spheres or shredded form to reduce flow restrictions through the chamber and increase the exposed surface area of the hydrogel material.

[0077] In one aspect, when dialysate is to be recirculated into the dialyzer, the artificial kidney includes dialysis and regeneration through the dialysate to extract urea and other molecules from the blood. Regeneration is accomplished by means of a sorbent cartridge, prior to which regeneration is enabled by the addition of activated carbon. Activated carbon has the ability to adsorb a variety of uremic toxins, including urea. U.S. Patent No. 3,463,728 (incorporated by reference in its entirety) describes a method of using activated carbon slurry to augment the ability of the dialysate in a recirculating dialysate system. However, activated carbon is not a highly efficient adsorber of urea, and the amount of urea that would need to be adsorbed to effectively clear urea in hemodialysis would require more than 20 kg of activated carbon per day. U.S. Patent No. 4,581,141 (incorporated by reference in its entirety) describes a specific method of using urease to clear urea from the dialysate, and the use of carbon and zeolite to manage other electrolytes. U.S. Patent No. 2010 / 0078387 (incorporated by reference in its entirety) describes further improvements to these methods, which utilize zirconium phosphate (ZrP) particles and hydrous zirconium oxide (HZO) particles to help manage bicarbonate levels. Urease is expensive, and there is a risk of ammonia breakthrough and the problem of bubble generation in the dialysis fluid. U.S. Patent No. 9,682,184 (incorporated by reference in its entirety) describes a sorbent cartridge that uses a non-enzymatic urea-binding material in place of urease. U.S. Patent No. 20110171713 (incorporated by reference in its entirety) describes another sorbent that includes a layer of immobilized uremic toxin-treating enzyme particles mixed with cation exchange particles. European Patent Publication No. EP 1935441 Al (published June 25, 2008), incorporated by reference in its entirety, describes another alternative sorbent material that utilizes montmorillonite, nanoclay, layered double hydroxides, and modified biopolymers.

[0078] In one aspect, the principle of an artificial kidney can be based on ultrafiltration or hemofiltration of the plasma fraction of blood. During hemofiltration, the patient's blood is passed through a set of tubes (the filtration circuit) via a machine to a semipermeable membrane (filter) where waste and water are removed. A substitution fluid is added and the blood is returned to the patient. Like dialysis, hemofiltration involves the movement of solutes across a semipermeable membrane. However, compared to the membranes used in most hemodialysis treatment methods, the membranes used in hemofiltration are more permeable to fluids and instead of using dialysate, the positive hydrostatic pressure drives water and solutes across the filtration membrane where they are removed as filtrate. An isotonic substitution fluid is added to the blood resulting from the filtration to replace the volume of fluid and valuable electrolytes. The blood and substitution fluid are then returned to the patient. Thus, in the case of a substitution of circulating fluid for hemofiltration, a key aspect is the separation of urea and other toxins from other components (e.g., salts) in the ultrafiltrate through the membrane, but they must be re-incorporated into the blood to keep its electrolyte composition essentially constant. U.S. Patent No. 5,211,850 (incorporated by reference in its entirety) describes a sorbent system for purifying plasma ultrafiltered from blood so that it can be returned to a replacement solution. A combination of the two systems described above has also been proposed. U.S. Patent No. 8,029,454 (incorporated by reference in its entirety) describes a hemodiafiltration system that uses a sorbent for fluid regeneration for both the hemodialysis and hemofiltration aspects.

[0079] A direct hemoperfusion system or a system that adsorbs toxic substances directly from blood without ultrafiltration has also been proposed. U.S. Patent No. 4,169,051 (incorporated by reference in its entirety) describes carbon sorbent spheres coated with a membrane material to reduce coagulation of blood in contact with it. Other examples use different sorbent materials coated with a membrane. In general, hemoperfusion systems have not been widely used in artificial kidney systems due to the higher cost and lower efficiency of urea removal. In general, hemoperfusion systems are directed to specific toxins that are not well removed by conventional hemodialysis or hemofiltration. These systems are generally not used for kidney replacement therapy, but rather as an adjunct to another kidney replacement therapy to improve the clearance of the target molecule. U.S. Patent No. 6,878,269 (incorporated by reference in its entirety) describes a sorbent column containing cellulose acetate spherical hydrogel particles for removing beta2-microglobulin and chemokines. As noted above, the sorbent used to regenerate dialysate or ultrafiltrate is typically activated carbon. However, other sorbents for removing substances from dialysis fluid or ultrafiltrate have been proposed. U.S. Patent No. 3,874,907 (incorporated by reference in its entirety) describes microcapsules composed of a cross-linked polymer containing sulfonic acid groups and coated with a polymer containing quaternary ammonium groups for regenerating dialysate. Examples of the sulfonated polymer include sulfonated styrene / divinyl benzene copolymers and examples of the coating polymer include polymers obtained by polymerization of, for example, vinyl dimethyl amine monomers.

[0080] The above disclosures relate to dialysis, ultrafiltration, and hemoperfusion devices in which various materials can be used as sorbents. The disclosures also include issued patents for using specific sorbent materials for kidney treatment devices. However, the problem with the above disclosed systems is that due to the limited sorption capacity of the materials, they are still too large, have the risk of eluting toxic chemicals (e.g., ammonia or chlorine), or are not efficient, or all of the above, which motivates small, benchtop, or wearable dialysis and ultrafiltration systems. The raw material costs for these systems are also high. This limits their ability to provide a low cost solution to the expensive existing kidney treatment methods.

[0081] It is an object of the present invention to overcome the problems associated with the existing devices and to provide a small and efficient sorption system for hemodialysis and peritoneal dialysis systems, portable kidney treatment systems, and wearable kidney treatment systems.

[0082] Various aspects of the detailed description are described with reference to the accompanying drawings.

[0083] Figure 1 An embodiment sorption cartridge (100) is shown. In one embodiment, the sorption cartridge 100 is configured for removing water and / or waste, such as toxic substances, from hemodialysis, hemofiltration, and peritoneal fluid, allowing for little or no dialysate volume, allowing for a small, benchtop, or wearable hemodialysis, hemofiltration, or peritoneal dialysis system. The sorption cartridge of the present disclosure can be in the form of a cartridge, including a rigid or flexible housing (30), which includes a sorbent material, such as a hydrogel sorbent. An inlet end (32) and an outlet end (28) can be removable, allowing for optional addition of membranes to separate the blood path from the hydrogel sorbent in the reservoir (29). The reservoir (29) can also be divided into one or more compartments, as described below. The sorption cartridge (100) includes an absorbent, adsorptive, and / or ion exchange material composed of a hydrogel sorbent. The hydrogel material can adsorb or absorb, or both, water, small molecules (e.g., uremic toxins), and middle molecules, and can also control electrolyte and buffer levels in process fluids (e.g., blood, plasma, or dialysis fluid). The hydrogel sorbent can be attached, for example, within the reservoir (29), or can include hydrogel beads. The cartridge cover (31) can be removable from the cartridge housing (30) to allow for placement of the hydrogel sorbent material and optional membranes, heating elements, and sensors. In one embodiment, the sorption cartridge can have a 10 cm x 10 cm x 3 cm footprint. The reservoir can include approximately 300 ml of hydrogel (approximately 300 grams in weight) and the total weight of the sorption cartridge, including the container, is approximately 500-700 grams.

[0084] The sorbent cartridge 100 can include a membrane configured to remove water and waste (e.g., small and medium molecules) from the process fluid. The membrane can be shaped as a hollow fiber, as generally flat, as generally corrugated, or other suitable shape to separate water and waste from the process fluid. The membrane can define a flow path through the sorbent cartridge, for example, a hollow fiber membrane can be configured to convey the process fluid through the cartridge, including defining a flow path through the hydrogel within the cartridge. Examples of flat membranes include Spectrum Technologies, Inc. Spectrum / Par™ 1-4 Standard RC flat sheet dialysis membranes, having manufacturing numbers SML132677, SML132686, SML132723, SML132712, respectively. Examples of hollow fiber dialysis membranes include the Elisio™-H membrane provided by Nipro Corporation (e.g., model number: ELISIO V11H or ELISIO V15H), the Polynephron™ membrane provided by Nipro Corporation, the Asymmetric Tri-Acetate (ATA) membrane provided by Nipro Corporation, the Membrana™ Purema™ H capillary membrane provided by 3M Company, and the Membrana™ Diapes™ capillary membrane provided by 3M Company. In one particular embodiment, the hollow fibers of the hollow fiber membrane have a thickness of less than 0.5 mm. In another particular embodiment, the hollow fibers of the hollow fiber membrane have a thickness of less than 200 microns.

[0085] In one particular embodiment, a sorbent cartridge according to the present disclosure can include one or more compartments. In one embodiment, the sorbent cartridge can have two compartments. The first compartment can be configured for removal of water and the second compartment can be configured for removal of medium and / or small size molecules, such as uremic toxins. The first compartment configured for removal of water can include a membrane as described above, which can remove water and other solutes (e.g., waste) from the process fluid by ultrafiltration through the membrane to an ultrafiltrate. The second compartment configured for removal of toxins (e.g., urea) can include a membrane as described above, which can be embedded in a hydrogel sorbent. Figure 6A portion 600 of the adsorption cassette according to the present disclosure is shown at the interface between a first compartment 601 and a second compartment 602. As shown, the first and second compartments 601, 602 are connected in series such that process fluid 604 flows from one compartment through a membrane 607 to the other compartment. The interface 603 between the first compartment 601 and the second compartment 602 may be defined by a wall, a permeable barrier, or allow direct contact between compartments 601, 602. A portion of the membrane 607 in the first compartment 601 can be used for ultrafiltration to separate water molecules, medium-sized molecules, and / or small-sized molecules, wherein the ultrafiltrate 605 can be pumped away. In one embodiment, the ultrafiltrate 605 may comprise a dialysate. The compartment 602 according to the present disclosure may comprise a hydrogel adsorbent that interfaces with the membrane 607 at the membrane-hydrogel interface. Figure 6 As shown, a membrane 607 in compartment 602 is embedded in hydrogel 606 such that the outer surface of the membrane 607 intersects with the hydrogel 606. Small molecules, including toxins such as urea, can be absorbed by water within the hydrogel 606 and / or adsorbed onto the hydrogel. The arrangement of the compartments is not limited to the illustrated embodiment and can be reversed. Similarly, the illustrated embodiment shows the membrane 607 as a hollow fiber membrane embedded in a hydrogel, with the hydrogel surrounding the membrane; however, other types and shapes of membranes can also be used. In one embodiment, the first compartment 601 may be configured as a blood filter and the second compartment 602 may comprise hydrogel, such that each compartment is defined in a single housing having a single structure. Continuing with this embodiment, the portion of the fiber in the first compartment not covered by the hydrogel adsorbent can be used to provide the desired ultrafiltration and fluid removal, which is pumped from the cartridge to another container. In another embodiment, the adsorption cartridge according to the present disclosure may have only one compartment, which includes Figure 6 The components of compartment 602 shown.

[0086] In one embodiment, the hydrogel disclosed herein can be configured to release supplementary feedstocks, such as electrolytes, buffers, minerals, vitamins, and / or other substances, into a process fluid. For example, the hydrogel may also include sodium bicarbonate for bicarbonate ion control and / or anticoagulants (e.g., heparin or citrate) to aid in anticoagulation, each of which can be released from the hydrogel into the process fluid. The hydrogel in the adsorbent cartridge may be pre-loaded with supplementary feedstocks, such that the supplementary feedstocks are desorbed into the process fluid upon use.

[0087] In one embodiment, the membrane-hydrogel interface can be functionalized by promoting the movement of water and / or toxins from the process fluid through the membrane for absorption into or adsorption onto the hydrogel. In one embodiment, the molecular structure of the monomers of the polymer chains, which make up the polymeric structure of the hydrogel, can have hydrophilic functional groups that impart hydrophilicity to the hydrogel to promote the absorption of water by the hydrogel through the membrane. In another embodiment, chemicals and / or biological elements can be added to the hydrogel to attract toxins in the process fluid. The membrane can also be modified by chemicals to promote the passage of toxins through the membrane-hydrogel interface into the hydrogel.

[0088] The hydrogels described herein can be attached to the membrane, and / or can have the membrane embedded within the hydrogel, such that the hydrogel has a thickness. The thickness of the hydrogel can be configured to provide a concentration gradient to absorb toxins from the process fluid. In one embodiment, the thickness of the hydrogel layer is greater than or equal to about 1 mm. In another embodiment, the thickness of the hydrogel layer is between 1 and 3 mm. In another embodiment, the thickness of the hydrogel layer is greater than or equal to 3 mm.

[0089] In another embodiment, the reservoir (29) of the sorbent cartridge 100 can include a plurality of hydrogel sorbents in the form of water droplets. The process fluid, such as blood, plasma, or dialysate fluid, can be configured to come into direct contact with the water droplet hydrogel sorbents as it flows through the sorbent cartridge. In one embodiment, each water droplet hydrogel can have a diameter greater than or equal to about 1 mm. In another embodiment, each water droplet hydrogel can have a diameter between 1 and 3 mm. In another embodiment, each water droplet hydrogel can have a diameter between 3 and 10 mm.

[0090] The sorbent cartridges of the present disclosure differ from existing devices in that they utilize hydrogels with high sorption capacity for urea to allow for a small form factor that is wearable. The sorption system (i.e., the ability of the hydrogel to adsorb and / or absorb) and optional release system (i.e., the ability of the hydrogel to release electrolytes, buffers, minerals, vitamins, or other substances to blood, plasma, or dialysis fluid) of one or more sorbent cartridges described herein can be temporarily used until it reaches its maximum sorption capacity. The contents of the hydrogel sorbents can be customized to the needs of an individual patient. The sorbent cartridges according to the present disclosure can form disposable and replacement components of a renal therapy system, and can be replaced with new sorbent cartridges, for example, when they have become saturated with toxic substances, or if one or more of the constituents to be supplemented to the plasma have been used up.

[0091] The sorbent cartridges of the present disclosure can be used to filter or purify the blood of a patient with (developing) kidney failure. In one embodiment, the sorbent cartridges can be used in a wearable artificial kidney device, but can also be included in a benchtop device or applicable hemodialysis or peritoneal dialysis equipment.

[0092] The sorbent cartridge of the present disclosure can be combined with suitable equipment to expose it to toxins in blood to adsorb the toxins, to perform some of the functions that a human or animal kidney, which is capable of performing normal functions, is normally able to accomplish, more specifically, to filter blood and to control the regulation of the content of substances in the blood. The sorbent cartridge of the present disclosure includes a sorbent system for capturing toxic substances from blood and optionally a release system for releasing minerals, vitamins or other substances to the blood, and a filter for separating blood cells from plasma on the basis of a hemofilter.

[0093] The sorbent cartridge according to the present disclosure can be configured to remove urea and other toxic materials from blood, plasma or dialysis fluid. While urea is only toxic when it reaches high concentrations (more than 15 g / kg) in the body, and is neither acidic nor basic when dissolved in water, the body produces a large amount of urea as part of protein metabolism (more than 1800 mg per day) that should be removed, otherwise the concentration of urea would grow progressively. Urea is highly soluble in water, dissolving about 1079 g / L in water at 20°C. Urea is a molecular substance that does not decompose into ions, but becomes a solvate with water by forming hydrogen bonds, which can be formed in two ways: the hydrogen atom bonded to water aligns with the partially negatively charged area of the amine group; and / or the oxygen of the carbonyl group and the hydrogen bonded to the amine group can be attracted and associated to the oxygen end of the water molecule.

[0094] Because urea is soluble in water (it has a solubility of ~1000 g / L depending on the temperature), urea can easily diffuse through the membranes in standard hemodialysis. However, standard hemodialysis cannot take advantage of the high solubility of urea in water because the concentration of urea in the dialysate must always be kept lower than the concentration of urea in the blood to maintain the concentration gradient for the removal of urea from the blood.

[0095] Hydrogel sorbents include a three-dimensional network of cross-linked polymer chains. Hydrogel sorbents can have a high water content and can swell and shrink upon absorption or release of water. Hydrogel sorbents can include a network of polymer chains that can be hydrophilic. The molecular structure of the monomers of the polymer chains, which make up the polymeric structure of the hydrogel, can have hydrophilic functional groups that impart hydrophilicity to the hydrogel. The ability of the hydrogel to swell / expand is a function of the gel density and cross-linking. In one embodiment, the hydrogel sorbent can be a colloidal gel, in which water is the dispersion medium. In another embodiment, the hydrogel sorbent can include a three-dimensional solid that is created by cross-linking hydrophilic polymer chains together. Due to the inherent cross-linking, the structural integrity of the hydrogel network does not dissolve in high concentrations of water. Due to the high concentration of water, the hydrogel is able to absorb large amounts of water-soluble substances, such as urea. The hydrogel can also provide absorption by adsorbing electrolytes and uremic toxins into the gel matrix pore structure, such that the concentration of the fluid in contact with the membrane in contact with the blood can be maintained at a lower concentration than in the blood, thereby maintaining a concentration gradient that will continue to clear urea from the blood. The reaction of the sorbent material to the adsorption of toxins onto the hydrogel polymeric structure can include physical sorption, which is the physical entrapment of the toxin molecules within the solid pore structure. The sorbent material can be functionalized, which can exhibit improved sorption characteristics for toxic substances, such as urea, as compared to non-functionalized materials. In one embodiment, the sorbent material is a hydrogel that has a high water absorption capacity and an interpenetrating network of pores to create a large specific surface area. The hydrogel can have very high sorption efficiency, thereby enabling a small size, lightweight, and wearable device.

[0096] Hydrogels can be made from a variety of materials in different ways. Examples of suitable hydrogel materials include polyacrylamide, acrylic acid (e.g., polyacrylic acid), alginate, and chitosan. To expand the available surface area for adsorption, the hydrogel can have an interpenetrating network. Increasing the surface area can increase the rate and volume of toxin removal. The hydrogel can be formed into small hydrogel water beads, which in one embodiment have a specific surface area of at least 0.1 m 2 / m 3 . As described herein, the hydrogel can be disposed around a hollow filtration fiber, such as a hydrogel used in ultrafiltration. In one embodiment, the internal surface area of the hollow fiber is 0.1-1.0 m 2 / m 3 .

[0097] Other hydrogel properties that affect toxin removal and / or water removal include pore size, water volume, and monomer concentration.

[0098] The following are examples of methods of making hydrogels:

[0099] Synthesis of simple polyacrylamide (PAAm) hydrogels:

[0100] a. To synthesize polyacrylamide hydrogel, 2 g (28.1 mmol) of acrylamide (AAm) and 100 mg (0.65 mmol) of MBAAm were mixed in a dry 50 mL reaction flask. The concentration of AAm and MBAA can be varied based on the desired porosity and water absorption volume required for the hydrogel. The formulation can be maximized or minimized and the ratio of AAm and MBAAm can be varied to obtain hydrogels with varying cross-linking and water absorption volume.

[0101] b. To the above flask, 20 mL of deionized water was added and the reaction flask was gently rotated using a magnetic stir bar on a magnetic stir plate until both the reactants were completely dissolved.

[0102] c. The resulting solution was deoxygenated for 15 minutes to prevent reaction between oxygen and initiator.

[0103] d. Now 50 μL of ammonium persulfate (APS) solution 10% w / v and 10 μL of TEMED was added to the reaction flask to initiate the polymerization reaction. The amount of initiator can be varied to modify the gelation time.

[0104] e. The reactor flask was rotated by hand for 5-6 times and the resulting mixed solution was poured into a suitable petri dish under nitrogen.

[0105] f. The poured solution was left at room temperature for 2 hours to polymerize and form a hydrogel.

[0106] g. Now the resulting hydrogel was immersed in deionized water for up to 2 days with water change 3 times a day to remove any unreacted monomers.

[0107] h. After the cleaning process, the resulting hydrogel was transferred to a suitable container for further processing. This process can yield a simple hydrogel without any functionalization.

[0108] Synthesis of functionalized polyacrylamide (PAAm-PEG) hydrogel:

[0109] a. To synthesize PEG-functionalized PAAm hydrogel, APS (0.056 M) and TEMED (0.32 M) were used as a redox initiator system.

[0110] b. AAm (1.0 g), APS (1 ml) and MBAAm (0.05 g) were added to a 50 ml reaction flask and 5 ml distilled water was added to it.

[0111] c. PEG (concentration 4.8-20 wt%) was then dissolved in the monomer solution, which was purged with nitrogen for 10 minutes to remove any oxygen that can react with the initiator.

[0112] d. To the above solution, 0.2 ml of TEMED is added and the solution is transferred to a polypropylene petri dish under a nitrogen environment.

[0113] e. The PEG wt.% and PEG molecular weight are varied based on the target pore size to be formed on the hydrogel. PEG comes in various sizes ranging from 100,000 Da to 1 million Da. The PEG size typically used in the hydrogels generated according to the present disclosure is less than 100,000 Da. Other pore forming agents can be used in place of PEG, including polyvinyl alcohol (PVA) in various molecular weights. In this example, when PEG 4000 is used, the PEG can include 4.8 wt% (PEGs generally do not react with any of the other ingredients of this reaction).

[0114] f. The petri dish is left for 24 hours to continue the polymerization reaction by maintaining the temperature at 20-27 °C.

[0115] g. After the reaction is complete, the hydrogel is cut into the specific shape and size desired and placed in a large excess of water for at least 72 hours, with at least periodic changes of water each day to wash away any excess unreacted reagents and pore forming agents.

[0116] h. The sample is then dried at room temperature to the desired constant weight or swelled according to each need using water / buffer solutions.

[0117] Preparation of hydrogel containing dialysis fluid buffer:

[0118] a. Preparation of acidifying agent:

[0119] The acidifying agent is prepared according to the preparation provided below

[0120] Sodium chloride (NaCl)………………………………… 21.48 g

[0121] Potassium chloride (KCl)………………………………… 0.65 g

[0122] Calcium chloride (CaCl2·2H2O)……………………… 0.772 g

[0123] Magnesium chloride (MgCl2·6H2O)…………………… 0.53 g

[0124] Pure water…………………………………………… 100 mL+

[0125] The required concentration of citric acid is added to the above solution to induce the anticoagulation effect. The concentration of citric acid should be 0.1-2.5 mEq / L to induce the anticoagulation effect. The addition of citric acid significantly increases the pH. Therefore, the pH can be adjusted after the addition of the basifying agent.

[0126] b. Preparation of the basifying agent:

[0127] Sodium bicarbonate (NaHCO3) 7 g

[0128] Pure water 100 ml

[0129] The above amount of NaHCO3 is added to 100 ml of pure water, which is added to the above prepared acidifying agent in a weight ratio of 1 : 1.26:32.74.

[0130] Citric acid is then added to adjust the pH to 7.25-7.45 (physiological pH), anything below 7.25 will cause acidosis and anything above 7.45 will cause alkalosis.

[0131] After 2 hours, the hydrogel obtained is swollen using dialysis fluid buffer (instead of water). The hydrogel is cut into the desired shape and then placed in a beaker containing dialysis fluid and swelled for up to 72 hours. The dialysis fluid buffer is changed at least twice a day to replenish the dialysis fluid buffer and remove any unreacted components remaining after the synthesis of the hydrogel.

[0132] The above buffer can also be used directly in the synthesis of the hydrogel instead of deionized water, which will allow the hydrogel to form from the beginning at the required pH of the dialysis fluid. Once the hydrogel is fully swelled, it can be cut into the desired shape to fit the diffusion chamber and monitor the diffusion of the toxin molecules.

[0133] The properties of the hydrogel, such as its large water absorption volume and the porosity formed on the hydrogel, allow it to have a high level of saturation with water-soluble compounds. This porosity allows the compounds diffused into the hydrogel through the semi-permeable filter to slowly diffuse into the deeper layers of the hydrogel, thus forming a lower concentration layer inside and around the semi-permeable membrane, resulting in a continuous influx of toxin molecules.

[0134] The diffusion of uremic toxins from a high temperature zone to a low temperature zone (Soret effect) can improve the ability of the hydrogel to absorb toxins. As uremic toxins diffuse through the hydrogel, using the principle of the Soret effect, an unsaturated region is created around the semi-permeable membrane and at the top layer of the hydrogel. The temperature difference in the hydrogel compartment keeps one part of the hydrogel at a specific temperature while the other part is at a different temperature. This temperature difference arrangement creates thermophoretic migration in the molecular compounds in the solution / hydrogel, resulting in their diffusion / movement from the higher temperature zone to the lower temperature zone. The thermophoretic response of the solute is quantified by the Soret coefficient, ST, which is proportional to the concentration gradient established in response to the thermal gradient. A positive Soret coefficient indicates that the solute accumulates at the cold side (thermophobic), while a negative sign indicates a drift towards the warm side (thermophilic). As described in D. Niether, S. Di Lecce, F. Bresme and S Wiegand, Phys. Chem. Chem. Phys., 2017, DOI: 10.1039 / C7CP05843H (incorporated herein by reference in its entirety), urea solution concentrations of 0.1 M and 0.05 M are thermophobic (equivalent to 2 g / L and 1 g / L urea solution, respectively, related to dialysis physiology).

[0135] As disclosed herein, it was found that the Soret effect can improve the ability of the hydrogel to absorb uremic toxins. In one embodiment, using a Peltier cooling device to maintain a temperature gradient of ~20°C across a small thickness (3 mm) of the hydrogel, it was demonstrated that it improved the ability to remove urea from a urea solution. If the temperature gradient is maintained, the Soret effect drives the diffusion of urea from the fibers to the cooler part of the gel, and the use of the Soret effect increases the removal volume of the gel fiber device compared to the control experiment. Figure 7 The setup of the experimental device to test the hydrogel embedded with hollow fibers is shown, as illustrated in Figures 8A and 8B; however, in the control experiment, the Peltier cooling device was excluded. The experimental procedure was:

[0136] 1. Maintain the temperature of the urea solution at ~37°C, the Peltier device at 17°C (20°C temperature gradient);

[0137] 2. Pump the urea solution at a low flow rate to ensure that the pressure does not cause leakage to occur (in this case, 17 ml / min was used, resulting in a pressure of approximately 6 PSI);

[0138] 3. Sample at the following times (in minutes): 0, 5, 10, 15, 20, 25, 30;

[0139] 4. Record the final volume of the urea solution at the end of the experiment; and

[0140] 5. The urea concentration of each sample was analyzed and the total removal per time interval was determined.

[0141] Tables 1 and 2 provide the results of the experiments.

[0142] Table 1. Results of the control experiment

[0143]

[0144] Initial volume: 150 mL

[0145] Final volume: 120 mL

[0146] Filtration rate: 1 mL / min

[0147] Table 2. Results of the experiment using the Soret effect

[0148]

[0149] Initial volume: 100 mL

[0150] Final volume: 70 mL

[0151] Filtration rate: 1 mL / min

[0152] Continuing with the above example, the efficiency of the experiment using the Soret effect was 1.5 times greater than the control experiment over the course of the experiment, with the exception of the initial volume, which was greater in the control experiment and would normally favor diffusion in the control experiment. The results indicate that the efficiency of using the Soret effect is at least 1.5 times greater, and even slightly more.

[0153] FIG. 8A depicts a perspective view of a particular embodiment of a sorbent cartridge according to the present disclosure, and FIGS. 8B and 8C depict cross-sectional views along line A-A of FIG. 8A, respectively, where FIG. 8B depicts an embodiment sorbent cartridge including a hollow fiber membrane, and FIG. 8C depicts an embodiment sorbent cartridge including a flat sheet membrane. Figure 8CEmbodiment sorbent cartridges comprising substantially flat or substantially corrugated membranes are described. As shown in FIG. 8B, sorbent cartridge 800 can comprise housing 801, hydrogels 806a, 806b, and membrane 802h. Housing 801 can be a flexible or ridged material, such as acrylic glass. In non-limiting embodiments, hydrogels 806a and 806b are hydrogel materials formed from polyacrylamide (PAAm). Membrane 802h, described in FIG. 8B as a hollow fiber membrane, is defined by hydrogel 806. Optional support member(s) 804, such as wire mesh, can provide rigidity to hydrogel 806a and membrane 802h to be positioned within sorbent cartridge 800. Support member 804 is configured to provide fluid communication between hydrogels 806a and 806b, allowing solutes in the hydrogels, such as uremic toxins, to move between hydrogels 806a and 806b. Electrically conductive member 803 can be positioned a distance (e.g., 3 mm) away from membrane 802h and configured to couple with cooling element 805. Electrically conductive member 803 can be configured to uniformly transfer heat across the surface interface between hydrogel 806 and electrically conductive member 803. Electrically conductive member 803 can be made of a metallic material or other suitable thermally conductive material. Cooling element 805 can be a component of sorbent cartridge 800 or a component of a renal therapy system coupled with the sorbent cartridge. When sorbent cartridge 800 is used, process fluid enters membrane 802h, as shown by flow direction F, which describes the flow direction of process fluid through hydrogel 801. Process fluid can be about 37°C (plus or minus 1°C). A heating element (not shown) can be positioned near membrane 802h, such as along a surface of housing 801 opposite cooling element 805 and / or electrically conductive member 803, to maintain process fluid at a desired temperature, such as 37°C. Cooling element 805 can create a temperature gradient across the distance of hydrogels 806a and 806b between conductive member 803 and membrane 802h. Uremic toxins and other solutes in the process fluid will move into hydrogels 806a and 806b. The Soret effect described above can improve diffusion of uremic toxins from the process fluid into the hydrogels when a temperature gradient exists in the hydrogels.

[0154] Figure 8C Embodiment sorbent cartridges having the same functionality and elements as the sorbent cartridge described in FIG. 8B are described; however, the hollow fiber membrane is replaced with substantially flat or substantially corrugated membrane 802. Substantially flat or substantially corrugated membrane 802 can be positioned directly on hydrogel 806 and optionally held in place by support member 804. Flow path 809 can be defined by the membrane and housing 801. When process fluid moves through flow path 809, uremic toxins and other solutes in the process fluid will move into hydrogel 806, as described above with reference to FIG. 8B.

[0155] As disclosed herein, vibrations can increase the rate of solute (e.g., uremic toxins) sorption into the hydrogel. The transfer of uremic toxins (e.g., urea) from the process fluid can initially be fast because urea adsorbs onto the surface of the hydrogel and then can slow because it must permeate into the pores to be adsorbed by the internal surface. In one embodiment, vibrations were shown to increase the rate of sorption or urea into the hydrogel. Equal amounts of urea solution (equivalent to 2.5 grams of urea per 1 liter of water) were placed on two hydrogel trays, each with the same formulation, with a surface area of 124 mm x 55 mm (0.007 m 2 Table 3: Percent reduction of urea in urea solution

[0156] Table 3: Percent reduction of urea in urea solution

[0157]

[0158] In one specific embodiment, a vibrating element 807 can be provided to vibrate the sorption cartridge according to the disclosure herein. As shown in FIG. 8B, the sorption cartridge 800 can include a vibrating element 807 configured to vibrate the hydrogels 806a and 806b. The vibrating element can be external to the sorption cartridge and as a component of a kidney treatment system coupled to the sorption cartridge. In use, the vibrating element 807 can vibrate the sorption cartridge and the hydrogels therein to increase the rate of solute (e.g., uremic toxins) sorption from the process fluid into the hydrogels.

[0159] Figures 2-5 Embodiment kidney treatment fluid systems are described in which a sorption cartridge according to the disclosure herein is incorporated into a hemoperfusion, hemofiltration, hemodialysis, or peritoneal dialysis system. The embodiment systems are not limiting on how a sorption cartridge according to the disclosure herein can be used.

[0160] As Figures 2-5As shown, the sorption cartridge according to the present disclosure can be placed in the dialysis fluid system of a hemodialysis or peritoneal dialysis system, thereby enabling removal of toxins consisting of small size molecules, medium size molecules and ionic solutes from the dialysis fluid. The sorption cartridge can continuously purify the dialysate fluid, keeping the concentration of toxins in the dialysate fluid, which can improve the efficiency of hemodialysis and peritoneal dialysis, and can reduce the consumption of dialysate. An additional and optional function of the sorption cartridge is to release supplementary materials to the blood, such as calcium, magnesium, anticoagulants, antibacterial agents, other minerals and specific medicaments, etc. The transported supplementary materials can be contained in an aqueous gel solution, and after gelation, they are dispersed in the gel matrix of the formed hydrogel. Due to the concentration gradient of the transported supplementary materials, the supplementary materials diffuse from the hydrogel to the process fluid, such as blood or dialysate fluid. This optional transport of supplementary materials can simplify the operation of existing hemodialysis systems and can reduce the probability of peritoneal infection in peritoneal dialysis systems.

[0161] The sorption cartridge according to the present disclosure can also be formed as a component of a wearable peritoneal dialysis system, wherein the sorption cartridge package is placed in the flow path of the wearable peritoneal dialysis system. Due to the continuous removal of toxins by the sorption cartridge, the volume of dialysate can be reduced. As shown in the system, Figure 5 The wearable peritoneal dialysis system can include a tubular channel system leading to the abdominal cavity, and a system including a fluid pump, a power source, sensors, an electronic control unit, a device for placing and replacing the sorption cartridge package (usually daily), and a system for handling the removed fluid. An additional and optional function of the sorption filter is to release supplementary ingredients to the blood, such as calcium, anticoagulants, antibacterial agents, minerals and specific medicaments, etc. This option will enhance the operation of the peritoneal dialysis system and reduce the probability of infection.

[0162] The sorption cartridge according to the present disclosure can also be formed as a component of a wearable hemodialysis system, wherein the sorption cartridge package is placed in the wearable hemodialysis system. The continuous filtration of the sorption cartridge can reduce the volume of dialysate to typically 1-2 litres. Referring to Figure 4 As described, the wearable hemodialysis system can include a vascular channel tube system and a unit including a small blood filter system, a fluid pump, a power source, sensors, an electronic control unit, a device for placing and replacing the sorption cartridge package (usually daily or more frequently as needed), and a system for removing excess water. An additional and optional function of the sorption cartridge is to release electrolyte and / or buffer solutions to the blood.

[0163] The sorption cartridge according to the present disclosure can also be formed as a component of existing continuous renal replacement therapy (CRRT) equipment, such that the solution from a bag containing ultrafiltrate or used dialysis solution can be recycled using the technology through the purification cartridge, such that the solution can be continuously reused.

[0164] The sorption cartridge according to the present disclosure can also be formed as a component of an existing portable dialysis machine, such that solution from a bag containing ultrafiltrate or used dialysis solution can be circulated through the purification cartridge using this technology, such that the solution can be continuously reused, such that much less solution is required to complete a treatment. Using this system can further reduce the limitations on fluid usage in portable systems, such that dialysate flow rates can be made higher to improve clearance and reduce the required dialysis time or reduce the need for higher flow rates of blood.

[0165] The sorption cartridge according to the present disclosure can also be formed as a component of an existing hemodialysis machine, such that used dialysis solution can be circulated through the purification cartridge and returned to the dialyzer using this technology, such that the solution can be continuously reused, such that much less solution is required to complete a treatment. In this way, there is no need for a continuous supply of pure water. Some of the existing fluid management mechanisms of a dialysis machine, such as pressure sensors, blood leak detectors, ultrafiltration pumps and metering systems, can continue to be used in this mode. This can allow for flexible use of regular dialysis machines in situations where it is difficult or expensive to provide a reliable supply of pure water in a hospital or home treatment. This capability can also allow dialysis clinics to continue to provide treatment in the event of a disruption in the safe supply of water, such as in the event of a flood, earthquake or other natural disaster. Using existing machines in this way can enable the staff working at the clinic to continue to provide treatment with only minimal additional training.

[0166] In any of the embodiments, the sorption cartridge according to the present disclosure can further comprise means for replenishing the (purified) plasma or dialysate fluid with at least one of minerals (such as calcium, sodium and potassium), anticoagulants, antibacterial agents and other pharmaceutical agents.

[0167] In any of the embodiments, the sorption cartridge according to the present disclosure can further comprise means for selective sorption of middle molecules, vitamins and minerals (such as calcium, sodium and potassium). Thus, the hydrogel can be loaded with a certain amount of minerals, vitamins or electrolytes and can only absorb a specified amount.

[0168] Optionally, the sorption cartridge according to the present disclosure can incorporate other ion exchange systems.

[0169] In another aspect, according to the present disclosure, the invention provides a method for removing toxic substances from blood using a sorption cartridge.

[0170] The sorption cartridge of the present disclosure can be in the form of a commercially available hollow fiber dialyzer, wherein the dialysate compartment is filled with the sorption material described herein.

[0171] In one particular embodiment, other suitable sorbent materials as small particles can be dispersed throughout the entire or partial hydrogel to enhance sorption or electrolyte control of the cartridge. Examples of other suitable sorbent materials can be, but are not limited to, activated carbon particles, nano-clay particles, graphene-based nanostructured particles, zirconium phosphate particles, and hydrated zirconium oxide particles. Additional sorbent elements can be incorporated into the device at any stage, but are preferably incorporated into the sorbent cartridge system.

[0172] Figure 2 A sorbent cartridge in a hemoperfusion system 200 as described herein is shown. Blood enters the arterial line, the inlet (19a), and its pressure is sensed by a pressure sensor (1). A blood pump (3) pumps blood through the blood vessel (25). An anticoagulant pump (7) can infuse anticoagulant from an anticoagulant solution container (15) into the blood vessel (25) at a desired rate. A fluid removal pump (6) pumps a desired amount of ultrafiltrate from the cartridge's hemofilter (8) section into an ultrafiltrate bag (16). A hydrogel cartridge (9), i.e., a sorbent cartridge comprising a hydrogel sorbent, is provided according to herein. The sorbent adsorbs uremic toxins and modifies electrolytes in the blood comprising the hydrogel cartridge (9) section. A heating and / or cooling element (20), which can be located within the hydrogel cartridge (9) or as a component of the system 200 outside the hydrogel cartridge (9), maintains the temperature at an optimal level using readings from one or more temperature sensors (18) within the cartridge to facilitate efficient toxin adsorption. The optimal temperature level of the blood can be 37°C to prevent damage to the blood re-entering the body. The heating element and / or cooling element 20 can be located within the hydrogel cartridge (9) or proximate to the hydrogel cartridge (9). A second temperature sensor (18) measures the temperature of the blood exiting the hydrogel cartridge (9) to ensure that the temperature of the blood is within a safe physiological range. A primary solution bag (17) and a manual clamp (2) are used to prime the circuit with fluid before treatment, return blood at the end of treatment, and if needed, allow for infusion of fluid during treatment. An air removal filter (11) traps any air that accumulates in the blood and allows it to be removed using an attached syringe (14). An ultrasonic air detector (13) detects the presence of air bubbles in the blood vessel (25) and then returns them to the patient via the outlet (19b). When air is detected in the blood vessel (25), an alarm sounds and the blood pump (3) will stop so that corrective action can be taken. The blood returned to the patient is monitored by another pressure sensor (1).

[0173] Figure 3The adsorption cartridge in the blood filtration system 300 is described. Blood enters the arterial line via inlet 19a, and its pressure is sensed by a pressure sensor (1). A blood pump (3) pumps blood through the blood vessel (25). An anticoagulant pump (7) injects an anticoagulant, such as heparin and / or citrate, which enters the blood vessel (25) from the anticoagulant solution container (15) at the desired rate. An ultrafiltrate pump (4) pumps the required amount of ultrafiltrate from the blood filter (8) through a hydrogel cartridge (9) and then back into the blood vessel (25) via a re-infusion fluid filter (10). The re-infusion fluid filter (10) prevents bacteria, endotoxins, and particles from entering the blood. The hydrogel cartridge (9) adsorbs uremic toxins and modulates electrolytes in the blood. A fluid removal pump (6) pumps the required amount of ultrafiltrate from the outlet of the ultrafiltrate pump (4) into an ultrafiltrate bag (16). A main solution bag (17) and a manual clamp (2) are used to fill the circuit with fluid before treatment, return blood at the end of treatment, and allow fluid infusion during treatment if necessary. An air removal filter (11) blocks any accumulated air in the blood and allows it to be removed using an attached syringe (14). An ultrasonic air detector (13) detects the presence of air bubbles in the blood vessel (25) and then returns it to the patient via outlet 19b. When air is detected in the blood vessel (25), an alarm sounds and the blood pump (3) stops for corrective action. The blood returned to the patient is monitored by another pressure sensor (1).

[0174] Figure 4 A suction cartridge is shown in the hemodialysis system described herein. Blood enters the arterial line via inlet 19a, and its pressure is sensed by a pressure sensor (1). A blood pump (3) pumps blood through the blood vessel (25). An anticoagulant pump (7) injects anticoagulant, which enters the blood vessel (25) at the desired rate from the anticoagulant solution container (15). A dialysate pump (5) pumps the required amount of fluid from the filter (8) into the hydrogel cartridge (9), and then back to the filter (8) through the dialysate detector (12). The hydrogel cartridge (9) adsorbs uremic toxins and modifies the electrolytes in the fluid. A fluid removal pump (6) pumps the required amount of ultrafiltrate from the outlet of the hydrogel cartridge (9) into the ultrafiltrate bag (16). A main solution bag (17) and a manual clamp (2) are used to fill the circuit with fluid before treatment, return blood at the end of treatment, and allow fluid infusion during treatment if necessary. An air removal filter (11) blocks any accumulated air in the blood and allows it to be removed using an attached syringe (14). An ultrasonic air detector (13) detects the presence of air bubbles in the blood vessel and then returns the information to the patient. When air is detected in the blood vessel (25), an alarm sounds and the blood pump (3) stops to allow for corrective action. The blood returned to the patient via outlet 19b is monitored by another pressure sensor (1).

[0175] Figure 5 A sorption cartridge in a peritoneal system as described herein is shown. Dialysate fluid enters from the patient and its pressure is sensed by pressure sensor (1) to alert to a blocked peritoneal catheter (not shown) or an empty abdominal cavity issue. In the outflow cycle, dialysate pump (5) pumps dialysate from pressure sensor (1) through hydrogel cartridge (9) to dialysate reservoir (24). Dialysate return pump (26) stops dialysate from circulating from reservoir (24). Hydrogel cartridge (9) adsorbs uremic toxins and improves electrolytes in the fluid. Heating and / or cooling element (20) maintains temperature at optimal levels using readings from temperature sensor (18) inside the cartridge for efficient toxin adsorption. Second temperature sensor (18) measures the temperature of dialysate fluid exiting hydrogel cartridge (9) to ensure the temperature of the dialysate fluid is within a safe physiological range. Infusion pump (21) pumps fluid from an infusion solution container (23) to dialysate line (27) to restore electrolyte levels and glucose levels as needed. In the inflow cycle, dialysate return pump (26) pumps dialysate fluid from dialysate reservoir (24) through dialysate filter (22) to pressure sensor (1) to return to the patient. Dialysate pump (5) stops dialysate from circulating back to hydrogel cartridge (9). Pressure is sensed by pressure sensor (1) to alert to a catheter blockage. The total amount of fluid pumped by dialysate return pump (26) in the return cycle can be less than the total amount of fluid pumped by dialysate pump (5) and infusion pump (21) so that the patient is net fluid removed from the dialysate. Excess fluid removed from the patient is stored in reservoir (9).

[0176] The above description is merely exemplary in nature and variations will be obvious to those skilled in the art, the pertinence of which are to be considered within the scope of the application disclosed herein. The present disclosure can be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The disclosures are to be considered in all respects as illustrative only; and not restrictive. The scope of the application is indicated by the appended claims, and all changes that come within the meaning and range of equivalents are intended to be embraced therein. Furthermore, no action taking activity hereunder is indicative of a patentable subject matter realization or working.

[0177] References

[0178] D. Niether, S. Di Lecce, F. Bresme and S. Wiegand, Phys. Chem. Chem. Phys., 2017, DOI: 10.1039 / C7CP05843H

[0179] Mueller BA, Jasiak KD, Thiel SR, et al. Vibration enhances clearance of solutes with varying molecular weights during in vitro hemodialysis. ASAIO Journal (American Society for Artificial Internal Organs: 1992). 2013 Mar-Apr;59(2): 140-144. DOI: 10.1097 / mat.0b013e3182837ff0.

[0180] Kim J, C, Kim J, C, Garzotto F, Cruz D, N, Goh C, Y, Nalesso F, KimJ, H, Kang E, Kim H, C, Ronco C: Enhancement of Solute Removal in a Hollow-Fiber Hemodialyzer by Mechanical Vibration. Blood Purif 2011;31:227-234. doi: 10.1159 / 000321073

[0181] Hornik, B.; Dufawa, J.; Marcisz, C.; Korchut, W.; Durmala, J. The Effect of Mechanically-Generated Vibrations on the Efficacy of Hemodialysis; Assessment of Patients’ Safety: Preliminary Reports. Int. J. Environ. Res. Public Health 2019, 16, 594.

[0182] M. J. Story, J. C. R. Turner: Thermal diffusion of diphenyl in benzene and of urea in water. Trans. Faraday Soc., 1969, 65, 1810-1811. DOI: 10.1039 / TF9696501810.

[0183] B. D. Butler, J. C. R. Turner, Flow-cell studies of thermal diffusion in liquids. Part 1.— Cell construction and calibration. Trans. Faraday Soc., 1966, 62, 3114-3120. doi / 10.1039 / TF9666203114

[0184] The disclosures of the above-referenced documents are hereby incorporated by reference in their entirety.

Claims

1. A sorbent cartridge for a portable wearable renal therapy system, the sorbent cartridge comprising: an inlet configured to receive process fluid from a renal therapy system and an outlet configured to discharge treated process fluid; a hydrogel configured to absorb and adsorb toxins from the process fluid without using dialysate to purify the process fluid; a membrane separating the hydrogel and the process fluid; The hydrogel is separated from the process fluid by a membrane having an internal surface area of 0.1 to 1.0 m 2 / m 3 ; a temperature sensor, a heating element, and a cooling element configured to receive an output signal from a controller; the heating element disposed proximate to the membrane to maintain the process fluid at a desired temperature; a conductive member configured to couple with the cooling element and distal to the membrane, the conductive member and the cooling element disposed opposite the heating element to create a temperature gradient along a length distance of the hydrogel between the conductive member and the membrane; wherein the inlet and the outlet are each configured to releasably couple to the renal therapy system to remove the sorbent cartridge; the hydrogel configured to release at least one of a buffer, a mineral, a vitamin, or an anticoagulant to the process fluid.

2. A sorbent cartridge for a renal therapy system, the cartridge comprising: a hydrogel configured to absorb or adsorb toxins from a process fluid, and the sorbent cartridge configured to releasably couple to the renal therapy system for easy removal; a membrane separating the hydrogel and the process fluid; The hydrogel is separated from the process fluid by a membrane having an internal surface area of 0.1 to 1.0 m 2 / m 3 ; a temperature sensor, a heating element, and a cooling element configured to receive an output signal from a controller; the heating element disposed proximate to the membrane to maintain the process fluid at a desired temperature; a conductive member configured to couple with the cooling element and distal to the membrane, the conductive member and the cooling element disposed opposite the heating element to create a temperature gradient along a length distance of the hydrogel between the conductive member and the membrane; the hydrogel configured to release at least one of a buffer, a mineral, a vitamin, or an anticoagulant to the process fluid.

3. The sorbent cartridge of claim 2, wherein, the buffer is sodium bicarbonate.

4. The sorbent cartridge of claim 2, wherein, the anticoagulant is at least one of heparin and citrate.

5. The sorbent cartridge of claim 2, wherein, the hydrogel configured to absorb 1-100 grams of urea from the process fluid in 24 hours without adjusting electrolyte levels outside of a range that would cause physiological harm to a user of the renal therapy system.

6. The sorbent cartridge of claim 2, wherein, the hydrogel configured to absorb electrolytes into the hydrogel to reduce a specific electrolyte level of the process fluid.

7. The sorbent cartridge of claim 2, wherein, the renal therapy system is a portable wearable system.

8. The sorbent cartridge of claim 2, wherein, the sorbent cartridge includes a first compartment including a membrane configured to remove water from the process fluid and a second compartment including a membrane configured to remove toxins.

9. The sorbent cartridge of claim 2, wherein, the hydrogel is attached to the membrane in the sorbent cartridge, wherein the membrane is a hollow fiber membrane.

10. The sorbent cartridge of claim 2, including a vibrating element configured to vibrate the hydrogel.

11. The sorbent cartridge of claim 2, wherein, the hydrogel forms a hydrogel layer having a thickness greater than or equal to about 1 mm.

12. The sorbent cartridge of claim 11, wherein, The thickness is 1-3 mm.

13. The sorbent cartridge of claim 11, wherein, The thickness is greater than or equal to 3 mm.

14. A renal therapy system comprising the sorbent cartridge of any one of claims 2 to 13, characterized by, The renal therapy system is at least one of a hemodialysis system, a peritoneal dialysis system, a hemoperfusion system, a hemofiltration system, or a hemodiafiltration system.

15. The renal therapy system of claim 14, wherein, The system is a portable wearable system.

16. The renal therapy system of claim 14, comprising a vibrating element configured to vibrate the hydrogel.

Images