Dialysate regenerator with reversible retainer

Abstract

One aspect of the present disclosure relates to a dialysate regenerator comprising a purification device; at least one reversible holder comprising an ion reservoir; a dialysate flow path comprising a dialysate inlet for receiving dialysate, a dialysate outlet for distributing dialysate, the reversible holder, and the purification device; and a pump connected to the dialysate flow path and configured to generate a dialysate flow from the dialysate inlet via the reversible holder and the purification device to the dialysate outlet, wherein the direction of the dialysate flow path through the reversible holder is reversible.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to Singapore Patent Application No. 10202003361W filed on April 13, 2020, Singapore Patent Application No. 10202003363P filed on April 13, 2020, and Singapore Patent Application No. 10202003365X filed on April 13, 2020, the contents of which are incorporated herein by reference in their entirety for all purposes. Technical Field

[0003] One aspect of the present disclosure relates to a dialysate regenerator. Another aspect of the present disclosure relates to a dialysis device including the dialysate regenerator. Another aspect of the present disclosure relates to medical uses of the dialysate regenerator. Background Art

[0004] Sorbent-based regenerative dialysis systems provide the same renal replacement therapy as conventional dialysis systems, while using an alternative method to generate dialysate. While conventional single-pass dialysis systems send used dialysate to a drain, sorbent-based regenerative dialysis systems allow dialysate to be regenerated and reused through the use of sorbent materials.

[0005] This allows sorbent-based regenerative dialysis systems to use significantly less water than single-pass systems. This can eliminate the need for specialized infrastructure for water supply and drainage, and reduce electricity consumption, allowing sorbent-based regenerative dialysis systems to be applied in a wider range of settings, including the home. Similarly, sorbent technology allows for the creation of smaller dialysis systems with greater portability and convenience.

[0006] All existing sorbent-based dialysate regeneration systems rely on direct or indirect contact with the spent dialysate through a series of sorbent materials (see Figure 1 ). These can be categorized as follows:

[0007] Activated carbon: This sorbent removes organic uremic metabolites such as creatinine, uric acid, and some intermediate molecules such as β2-microglobulin from the spent dialysate.

[0008] Anion exchangers: Most sorbent systems contain hydrous zirconium oxide (HZO) as an inorganic anion exchanger to adsorb negatively charged anions, such as phosphate and sulfide, by exchanging hydroxide. HZO also has some weak cation exchange properties, adsorbing divalent and polyvalent cations.

[0009] Urea adsorbent:Due to the low reactivity and specificity of urea, existing sorbent systems must employ a combination of enzyme-catalyzed urea hydrolysis and subsequent adsorption of the hydrolysis product, ammonia, on a non-selective cation exchanger, zirconium phosphate (ZP), which exchanges ammonium ions for sodium or hydrogen ions.

[0010] However, zirconium phosphate also adsorbs other cations, most notably calcium, magnesium, and potassium in exchange for sodium and hydrogen. This inadvertent electrolyte removal consumes cation exchange capacity (and thus urea adsorption capacity) and affects the sodium concentration and acidity of the dialysate. More importantly, additional elements are required for the dialysate reconstitution process, i.e., electrolyte reinfusion. Electrolyte reinfusion requires a controlled pumping system to add electrolytes to the regenerated dialysate to re-establish the electrolyte concentration that meets physiological requirements. To do this, solutions of calcium, magnesium, and / or potassium ions must usually be injected into the regenerated dialysate. The dispensed solutions must be prepared at the patient's side before treatment or provided in sterile, prepackaged form.

[0011] Figure 2 A cross-sectional view of a conventional device currently used for peritoneal dialysis using sorbent regeneration technology is shown. Figure 3 The basic elements of the sorbent regeneration process are schematically illustrated. As with other types of dialysis systems, fresh dialysate is provided for treating the patient. There, it absorbs the patient's uremic solutes, electrolytes, and fluid volume. The used dialysate, which contains uremic solutes and excess electrolytes expelled from the patient's body, is then purified as it passes through the sorbent. The uremic solutes are removed and the electrolytes are set to the target concentration. This typically requires an electrolyte infusion system (enrichment solution) to add the necessary electrolytes to produce regenerated dialysate, which is then returned to the patient to continue dialysis treatment.

[0012] To date, the most widely used sorbent-based regenerative hemodialysis device is the REDY system, introduced in 1973. The first-generation machine weighed 60 pounds, making it the first portable machine for home hemodialysis.

[0013] REDY sorbent cartridges regenerate dialysate by passing used dialysate through a train of regeneration materials to reprocess it into fresh dialysate. The cartridge effluent is then mixed with a proportional volume of infusate containing calcium, potassium, and magnesium to produce fresh dialysate as prescribed by the physician.

[0014] Most approaches to alternative sorbent-based dialysate regeneration focus on the core issue of urea removal. A key difficulty here is that urea is notoriously inert and unreactive, making it difficult to remove selectively. Consequently, some technologies still rely on chemical modification of urea followed by selective adsorption or removal of degradation products. For example, the use of "nanosorbents" has been proposed, which still use urease to selectively hydrolyze urea, followed by an ion exchange process on a clay-based ion exchanger. However, selectivity is limited, and electrolyte re-infusion systems may still be required.

[0015] In another approach, urea is electrochemically broken down into gaseous decomposition products. However, this "electrooxidation" is not very specific, and parallel degradation processes can form unwanted byproducts that are difficult to remove and raise serious concerns about biocompatibility and even toxicity. Furthermore, electrode lifetime and cost must be considered.

[0016] There are also methods for direct adsorption of urea using activated carbon. However, until now, this has required large sorbent cartridges and cumbersome regeneration processes.

[0017] In yet another approach, a method using direct adsorption of urea on a polyaldehyde sorbent has been proposed. This is also still in the early stages of development, and its feasibility for dialysate regeneration has not yet been determined.

[0018] The only viable method for dialysate regeneration currently available on the market is sorbent-based, which always results in the irreversible adsorption of essential electrolytes. Therefore, all current devices still rely on electrolyte re-infusion systems to function.

[0019] Therefore, there remains a need for improved dialysate regenerators with improved or enhanced ion control. Summary of the Invention

[0020] In a first aspect, a dialysate regenerator is provided. The dialysate regenerator may include a purification device. The dialysate regenerator may include at least one reversible retainer. The reversible retainer may include an ion reservoir. The dialysate regenerator may include a dialysate flow path. The dialysate flow path may include a dialysate inlet for receiving dialysate. The dialysate flow path may include a dialysate outlet for distributing dialysate. The dialysate regenerator may include a pump connected to the dialysate flow path. The pump may be configured to generate a dialysate flow from the dialysate inlet via the reversible retainer and the purification device to the dialysate outlet. The direction of the dialysate flow path through the reversible retainer may be reversible.

[0021] According to various embodiments, the ion reservoir may include an ion exchanger.

[0022] According to various embodiments, a dialysate regenerator may include a volume control device configured to direct a predetermined volume of dialysate from a dialysate inlet via a reversible holder and a purification device to a dialysate outlet.

[0023] According to various embodiments, the ion reservoir may be in the form of particles, granules, beads, fabrics, membranes, or combinations thereof.

[0024] According to various embodiments, the ion reservoir may be a reversible ion exchanger capable of retaining and releasing ions.

[0025] According to various embodiments, the ion reservoir may be a zwitterionic ion exchanger.

[0026] According to various embodiments, the ion exchanger can be changed from being primarily an anion exchanger at pH values ​​below 5 to being primarily a cation exchanger at pH values ​​above 8.

[0027] According to various embodiments, the ion reservoir may be hydrous zirconium oxide (HZO).

[0028] According to various embodiments, for each of the at least one reversible retainer, the amount of the ion reservoir may be less than about 50 grams (g) or less than about 20 g.

[0029] According to various embodiments, the average particle size of the ion reservoir may be in a range from about 25 microns to about 100 microns, or from about 50 microns to about 100 microns.

[0030] According to various embodiments, the ion reservoir in its original state may include an ionic salt.

[0031] According to various embodiments, the ion reservoir may be embedded in the filter mat and / or the additional sorbent bed.

[0032] According to various embodiments, at least one reversible retainer may be located upstream of the purification device in a first direction of the dialysate flow path and downstream of the purification device in a second direction of the dialysate flow path, wherein the second direction of the dialysate flow path is opposite to the first direction.

[0033] According to various embodiments, the reversible retainer can be configured to lower the pH of the dialysate upstream of the purification device by retaining ions from the dialysate.

[0034] According to various embodiments, the reversible retainer can be configured to increase the pH of the dialysate downstream of the purification device by releasing ions into the dialysate.

[0035] According to various embodiments, a dialysate regenerator may include a reversible retainer that is located upstream of a purification device in a first direction of a dialysate flow path through the reversible retainer and downstream of the purification device in a second direction of a dialysate flow path through the reversible retainer, wherein the second direction of the dialysate flow path through the reversible retainer is opposite to the first direction.

[0036] According to various embodiments, the dialysate regenerator may include one or more valves for alternating a dialysate flow path between a first flow phase in which the dialysate flow path runs from a dialysate inlet via a reversible holder to a temporary storage container, and a second flow phase in which the dialysate flow path runs from the temporary storage container via a purification device and the reversible holder to a dialysate outlet, wherein the direction of the dialysate flow path through the reversible holder in the second flow phase is opposite to the direction of the dialysate flow path through the reversible holder in the first flow phase.

[0037] According to various embodiments, a dialysate regenerator may include a first reversible holder located upstream of a purification device and a second reversible holder located downstream of the purification device.

[0038] According to various embodiments, the dialysate regenerator may include one or more valves for alternating the direction of the dialysate flow path through the reversible retainer between a first direction and a second direction, the second direction of the dialysate flow path through the reversible retainer being opposite to the first direction.

[0039] According to various embodiments, a dialysate regenerator may include a volume control device configured to direct a predetermined volume of dialysate from a dialysate inlet via a reversible retainer and a purification device to a dialysate outlet, wherein the volume control device includes a fluid portioning system to divide the dialysate flow into uniform portions for sequential regeneration.

[0040] According to various embodiments, the dialysate regenerator may include one or more valves for alternating a dialysate flow path between a dialysate inlet and a dialysate outlet between a first state and a second state, wherein in the first state the dialysate flow path passes through a reversible holder, a purification device, and a reversible holder, and in the second state the dialysate flow path passes through the reversible holder, the purification device, and the reversible holder, wherein in the second state the direction of the dialysate flow path through the reversible holder is opposite to the direction of the dialysate flow path through the reversible holder in the first state.

[0041] According to various embodiments, a dialysate regenerator may include a fluid portioning system to divide the dialysate flow into uniform portions for sequential regeneration.

[0042] According to various embodiments, the dialysate regenerator may include one or more valves for alternating the direction of the dialysate flow path through the reversible retainer between a first direction and a second direction, the second direction being opposite to the first direction.

[0043] According to various embodiments, a dialysate regenerator may include a pressure sensor.

[0044] According to various embodiments, one or more valves may be synchronized and redirect the dialysate flow path through the reversible retainer based on pressure changes detected by a pressure sensor.

[0045] According to various embodiments, the dialysate regenerator may include a temporary storage container.

[0046] According to various embodiments, a dialysate regenerator may include a flow regulator and optionally a pressure sensor.

[0047] In a second aspect, there is provided a use of an ion reservoir in the manufacture of a dialysate regenerator, the dialysate regenerator comprising the ion reservoir contained in at least one reversible retainer, for treating a patient suffering from renal insufficiency, hepatic failure or respiratory insufficiency with abnormally high levels of one or more toxins or metabolic wastes or inadequate removal of CO2, the treatment comprising passing the patient's dialysate through a dialysate flow path comprising a dialysate inlet for receiving dialysate by operation of a pump, a dialysate outlet for distributing the dialysate, and a purification device, wherein the dialysate flow generated is from the dialysate inlet via the reversible retainer and the purification device to the dialysate outlet, and the direction of the dialysate flow path through the reversible retainer is reversible.

[0048] In a third aspect, a dialysis device is provided, comprising the above-mentioned dialysate regenerator.

[0049] In a fourth aspect, there is provided a dialysate regenerator as described above for use in treatment.

[0050] In a fifth aspect, there is provided a method for treating a patient suffering from renal insufficiency, hepatic failure or respiratory insufficiency with abnormally high levels of one or more toxins or metabolic waste products or inadequate removal of CO2, the method comprising passing a dialysate from the patient through a dialysate flow path comprising a dialysate inlet for receiving dialysate by operation of a pump, a dialysate outlet for distributing the dialysate, and a purification device, wherein the dialysate flow is generated from the dialysate inlet via a reversible retainer comprising an ion reservoir and the purification device to the dialysate outlet, the direction of the dialysate flow path through the reversible retainer being reversible. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] The invention will be better understood with reference to the description of the detailed description taken in conjunction with the non-limiting examples and accompanying drawings, in which:

[0052] - Figure 1 shows a schematic diagram of a typical sorbent cartridge for hemodialysis fluid regeneration;

[0053] - Figure 2 The setup of a conventional sorbent-based peritoneal dialysis device is shown;

[0054] - Figure 3 is a schematic diagram illustrating the basic elements of a conventional sorbent regeneration process;

[0055] - Figure 4 is a schematic diagram illustrating the basic elements of the dialysate regenerator of the present disclosure;

[0056] - Figure 5A shows a schematic diagram of a dialysate regenerator according to some embodiments of the present disclosure in a first state ST1;

[0057] - Figure 5B shows a schematic diagram of a dialysate regenerator according to some embodiments of the present disclosure in a first state ST2;

[0058] - Figure 6A shows a schematic diagram of a dialysate regenerator according to some embodiments of the present disclosure in a first state ST1;

[0059] - Figure 6B shows a schematic diagram of a dialysate regenerator according to some embodiments of the present disclosure in a first state ST2;

[0060] - Figure 6C A schematic diagram of a fluid portioning system is shown;

[0061] - Figure 7 The diagram illustrates the valve control principle with an idealized pressure reading at PS1;

[0062] - Figure 8 a schematic diagram showing the flow of used dialysate through a reversible retainer;

[0063] - Figure 9 Schematic diagram showing the passage of regenerated dialysate through a reversible retainer;

[0064] - Figure 10 shows an integrated schematic diagram of the reversible retainer;

[0065] - Figure 11 shows the setup of the test;

[0066] - Figure 12 A cylindrical, full-scale reversible retainer prototype is shown;

[0067] - Figure 13 The setup for in vitro offline testing is shown;

[0068] - Figure 14 shows the integrated system test setup;

[0069] - Figure 15 is a graph of typical in vitro performance of reversible retainers without pretreatment;

[0070] - Figure 16 is the first preprocessed Figure 15 Similar diagrams for reversible retainers;

[0071] - Figure 17 A table of results showing performance of the reversible retainer with optimization is shown;

[0072] - Figure 18 A table of results showing performance of the reversible retainer with optimization is shown;

[0073] - Figure 19A is a graph of the sodium concentration in the dialysate in the HD model used for in vitro testing;

[0074] - Figure 19B is a graph of calcium and magnesium concentrations in the dialysate in the HD model used for in vitro testing;

[0075] - Figure 19C is a graph of dialysate bicarbonate concentration in an HD model used for in vitro testing, showing that the initial drop in bicarbonate is adjustable so that the bicarbonate curve can be flattened and / or shifted to a higher dialysate bicarbonate concentration if desired;

[0076] - Figure 20 Schematic model of an integrated prototype UDRS with a sorbent without infusate (top view) is shown;

[0077] - Figure 21 Schematic model of an integrated prototype UDRS with a sorbent without an infusate is shown (bottom view);

[0078] - Figure 22 Schematic model showing the removed cover of an integrated prototype UDRS with sorbent without infusate (bottom view);

[0079] - Figure 23 A single cylinder test setup is shown for determining the optimum air pressure setting in the cylinder; and

[0080] - Figure 24 Shown is a single cylinder test setup for determining the optimal air pressure setting in the cylinder. DETAILED DESCRIPTION

[0081] Specific embodiments are described below with reference to the accompanying drawings, which show the specific details and embodiments that can be put into practice of the present disclosure by way of illustration. These embodiments are described in sufficient detail to enable those skilled in the art to put into practice the present disclosure. Without departing from the scope of the present disclosure, other embodiments can be used and structural and logical changes can be made. Various embodiments are not necessarily mutually exclusive, because some embodiments can be combined with one or more other embodiments to form new embodiments.

[0082] In a first aspect, the present disclosure relates to a dialysate regenerator 100. The dialysate regenerator 100 may include a purification device 110. The dialysate regenerator 100 may include at least one reversible retainer 120. At least one reversible retainer 120 may include an ion reservoir. The dialysate regenerator 100 may include a dialysate flow path. The dialysate flow path may include a dialysate inlet 130 for receiving dialysate. The dialysate flow path may include a dialysate outlet 140 for distributing dialysate. The dialysate regenerator 100 may include a pump 150 connected to the dialysate flow path. The pump 150 may be configured to generate a dialysate flow from the dialysate inlet 130 via the reversible retainer 120 and the purification device 110 to the dialysate outlet 140. The direction of the dialysate flow path through the reversible retainer 120 may be reversible.

[0083] As used herein, and according to various embodiments, the term "dialysis" may refer to hemodialysis, hemofiltration, hemodiafiltration, plasmapheresis, peritoneal dialysis, hepatic dialysis, pulmonary dialysis, water purification, physiological fluid regeneration, or biological fluid regeneration. Similarly, the dialysate regenerator 100 may refer to a dialysate regenerator 100 for hemodialysis dialysate, a dialysate regenerator 100 for peritoneal dialysis dialysate, a dialysate regenerator 100 for hepatic dialysis dialysate, a dialysate regenerator 100 for pulmonary dialysis dialysate, a regenerator for water regeneration or purification, a dialysate regenerator for hemofiltrate regeneration, a dialysate regenerator for plasma regeneration, a dialysate regenerator for physiological fluid regeneration, or a dialysate regenerator for biological fluid regeneration.

[0084] The dialysate regenerator 100 according to the present disclosure may include a purification device 110, also referred to as a purification chamber. The purification device may include a toxin removal device. As used herein, and according to various embodiments, the term "purification device" may refer to a compartment that may contain one or more sorbent materials. The purification device may also include an electro-oxidation device, an electrodialysis device, or other purification devices that are not based on sorbent technology. The compartment can be connected to the dialysate flow path. The sorbent material in the purification device 110 is used to remove specific solutes, such as urea, from the solution. The purification device 110 may have a single compartment design, in which all sorbent materials necessary to perform dialysis are contained. Alternatively, the purification device 110 may have a modular design, in which the sorbent materials are dispersed in at least two different modules that can be connected to form a single body. The purification device 110 in the present disclosure may be a disposable purification device 110.

[0085] The dialysate regenerator 100 according to the present disclosure may include at least one reversible retainer 120, which includes or contains an ion reservoir. As used herein, and according to various embodiments, the term "reversible retainer" may refer to a component that retains ions in one direction of dialysate flow and releases the ions in the opposite direction of dialysate flow. The reversible retainer 120 may therefore include an ion reservoir. An ion reservoir may be any compound capable of retaining and releasing ions. Examples of such compounds include ion exchangers, ion exchange membranes, ion rejection membranes, and the like. Ion retention and release may be affected by dialysate parameters, such as pH, temperature, pressure, concentration, toxin or electrolyte concentration, density, and viscosity. According to one embodiment, the ion reservoir retains and releases ions based on pH. As used herein, and according to various embodiments, the term "ion," when used in conjunction with an ion reservoir, may refer to a charged atom or molecule. In particular, the ion may be a cation. The ion may be a cationic atom. The ion may be a physiologically essential ion. The ion may include a cation from Group II of the periodic table. Advantageously, because the essential ions are selected from Group II of the periodic table, their valence is higher than, for example, cations selected from Group I of the periodic table. This higher valence, in turn, influences the cations with higher valence, resulting in a greater affinity for the ion reservoir or ion exchanger contained in the reversible holder. The ions may include calcium. The ions may include magnesium. The ions may include potassium. Ions such as calcium, magnesium, and potassium may be referred to as essential ions due to their physiological relevance.

[0086] The dialysate regenerator 100 according to the present disclosure may include a pump 150. As used herein, and according to various embodiments, the term "pump" means any pumping device. In particular, it may include a volume control device 115 configured to guide a predetermined volume of dialysate from the dialysate inlet 130 via the reversible holder and the purification device 110 to the dialysate outlet 140. In addition or alternatively, it includes an actuator for moving the dialysate by suction or pressure, and a motor for mechanically moving the actuator. Suitable pump actuators may include impellers, pistons, diaphragms, cams of cam pumps, screws of screw pumps, rollers or linearly moving fingers of peristaltic pumps, or any other mechanical structure for moving dialysate. It may also include bellows pumps, gear pumps, and rotary vane pumps. The pump is connected to the dialysate flow path for pumping dialysate from the dialysate inlet 130 for receiving the dialysate to the dialysate outlet 140 for distributing the dialysate through the dialysate flow path. The pump 150 can be in a feedback loop or closed-loop control and can respond to pressure changes caused by changes in dialysate flow rate detected at the dialysate inlet or outlet, such as at a pressure sensor. In continuous dialysis, the pump 150 can actively adjust the dialysate regeneration flow rate in response to fluid supply or demand detected at the dialysate inlet or outlet. The pump 150 can also be configured to operate independently and generate a desired dialysate flow through the dialysate regenerator, for example, to provide the desired dialysate flow rate for a dialysis treatment.

[0087] The pump may include at least one volume control device 115, also referred to as a fluid control compartment. With reference to various embodiments further described below and in the case of a single reversible retainer, the volume control device 115 may be in the form of a temporary storage container 180. In the case of more than one reversible retainer, the volume control device 115 may be in the form of a fluid portioning system 160. In these embodiments, the volume control device 115 may ensure that the same concentration of essential ions is returned to the same volume of dialysate, thereby maintaining a constant concentration of essential ions in each aliquot of dialysate.

[0088] The dialysate that enters the dialysate flow path at the dialysate inlet 130 may be referred to as "spent dialysate" and may refer to dialysate containing one or more toxins, or waste types or waste substances, such as urea. It is generally understood that the purpose is to remove such one or more toxins, or waste types, or waste substances, such as urea, from the spent dialysate. The spent dialysate may also contain one or more electrolytes or ions. In accordance with the present disclosure, it may be desirable to retain these electrolytes or ions in the dialysate. In terms related to essential ions, "retention" may refer to retaining a larger amount of essential ions compared to the spent dialysate. For example, more than 80% of calcium and magnesium ions, or about 50% of potassium ions may be retained. The retention rate depends on the ion and / or its concentration. It is desirable to retain a fixed number of molecules of essential ions per volume of dialysate, and to allow any excess ions to pass through and be adsorbed in the purification device. It would also be advantageous to retain approximately 50% of the potassium ions on the reversible retainer compared to over 80% of the calcium and magnesium ions, as this would allow for a substantial net removal of potassium (which would otherwise be considered harmful) for the patient in the purification device.

[0089] The dialysate dispensed at dialysate outlet 140 may be referred to as "fresh dialysate" and may refer to dialysate that is substantially free of one or more toxins, or waste species or substances, such as urea. Fresh dialysate may also contain a desired concentration of one or more electrolytes or ions.

[0090] The purification device 110 and at least one reversible retainer 120 including an ion reservoir are connected via a dialysate flow path and are located between the dialysate inlet 130 and the dialysate outlet 140. The term "via" does not imply the order of the purification device 110 and the at least one reversible retainer 120 in the dialysate flow path. However, it should be understood that the dialysate may pass through the at least one reversible retainer 120 before passing through the purification device 110. Subsequently, after passing through the purification device 110, the dialysate may pass through the at least one reversible retainer 120 in the opposite direction, which may be the same reversible retainer 120 that the dialysate passed through before passing through the purification device 110, or may be a different reversible retainer. Accordingly, the dialysate flow generated by the pump 150 is from the dialysate inlet 130, through the reversible retainer 120 and the purification device 110, to the dialysate outlet 140. The flow is configured to pass through the reversible retainer 120, then through the purification device 110, and then through the same or another reversible retainer in the opposite direction. Thus, the dialysate can be configured to pass through the at least one reversible retainer 120 at least twice, but in opposite directions, and during these at least two times, the dialysate can pass through the purification device 110. Thus, the direction of dialysate flow through the reversible retainer can be reversible. The flow direction can be controlled by the volume control device 115. Specifically, the volume control device 115 can ensure that the volume of the dialysate is equal in both flow directions.

[0091] The dialysate flow can be an intermittent flow, optionally a tidal flow. Advantageously, when using tidal flow, the dialysate inlet 130 for receiving the dialysate and the dialysate outlet 140 for distributing the dialysate can be combined into a single access point. Having only one access point for the dialysate inlet 130 and the dialysate outlet 140 allows reliance on a single percutaneous access location, which minimizes the risk of infection in home and outdoor environments. In tidal flow, the pump 150 can provide a flow pattern within the dialysate flow path. A flow pattern can refer to each volume of dialysate that passes through the dialysate flow path at one time. In each flow pattern, the dialysate that can be moved through the dialysate flow path is about 100 milliliters (mL) to about 500 mL, or about 150 mL to about 400 mL, or about 200 mL to about 300 mL, optionally about 250 mL. Within these ranges, the total amount of essential divalent ions (e.g., calcium and magnesium) in the used dialysate retained by the reversible retainer 120 can be less than about 1 millimole (mmol), or less than 0.5 mmol, or less than 0.4 mmol. Thus, the concentration of the retained essential divalent ions is about 1 to 3 mmol / L, or about 2 mmol / L. Such a small amount of essential ions to be retained requires less ion storage (e.g., ion exchanger), thereby saving space and weight in the dialysate regenerator 100.

[0092] Alternatively, the dialysate flow can be a continuous flow. In a continuous flow, the dialysate typically flows through the dialysate flow path at a flow rate of about 100 mL / min to about 500 mL / min, or about 200 mL / min to about 400 mL / min, or about 250 mL / min to about 350 mL / min. Other higher and lower flow rates are also contemplated.

[0093] The present disclosure proposes to break away from the existing paradigm of inadvertent ion adsorption and reinjection requirements in sorbent-based dialysate regeneration systems by temporarily retaining essential ions (e.g., calcium and magnesium) in at least one reversible retainer 120 comprising an ion reservoir that is recovered simply by reversing the flow of regenerated dialysate (see Figure 4). Advantageously, such a dialysate flow path can improve or enhance the control of ions by the dialysate regenerator 100. The improved or enhanced control of essential ions can be attributed to at least one reversible retainer 120 comprising an ion reservoir, by which ions are retained in a first direction of the dialysate flow path and the same ions are released in the opposite direction of dialysate flow in the dialysate flow path. This system allows essential ions such as calcium and magnesium to be retained before the dialysate passes through the purification device 110 and released into the dialysate after passing through the purification device 110. Therefore, the dialysate regenerator 100 advantageously does not require the injection of electrolytes, as this simplifies the dialysate regenerator, making it easier to use, and saving space, cost, and materials. Further advantageously, retaining essential ions such as calcium and magnesium avoids wasting the capacity of the purification device for unnecessary adsorption of essential ions, allowing the size and cost of the purification device to be reduced. In a typical sorbent system, this can save more than 25% of sorbent capacity, for example, 30% to 50% of cartridge capacity, which can translate into a 30% to 50% reduction in equipment size. Even more advantageously, the retention of essential ions (such as calcium and magnesium) avoids the excessive release of other ions (such as sodium) in exchange for calcium and magnesium, thereby avoiding unwanted sodium fluctuations in the regenerated dialysate, a key challenge in conventional sorbent systems.

[0094] The dialysate flow path may include one or more valves (see Figure 4 ), for alternating the direction of the dialysate flow path through the reversible retainer 120 between a first direction and a second direction, the second direction being opposite to the first direction.

[0095] The ion reservoir can comprise ion exchange membrane, ion exchanger, reversible precipitation device, ion exclusion membrane or other reversible ion retention device. Advantageously, the dialysate stream flows directly through the ion reservoir, which means that the ion reservoir is located between the inlet and outlet of the reversible retainer. Therefore, the dialysate flow is in convection mode, and the ion exchange membrane or ion exclusion membrane of convection mode rather than diffusion mode will also be used. Advantageously, when using ion exchanger, the dialysate flow path does not have to pass through the membrane through selective diffusion. This allows to achieve sufficient purification efficiency under high exchange flow rate, low flow resistance and low cost. In addition, ion exchanger may be better than using ion exchange membrane or ion exclusion membrane, because ion exchange membrane may have high flow resistance and high material cost, thereby there is serious disadvantage when they are used together with disposable filter cartridge. When using the ion exchanger in particle form, convection mode is also especially advantageous.

[0096] As used herein, and according to various embodiments, the term "ion exchanger" can be a molecule consisting of a stable high molecular weight backbone structure and active ionic groups. The backbone provides stability, insolubility and structure, while the active groups provide ion exchange properties. The backbone can include any element or combination of elements that can be linked together to form a long chain, preferably with branches or a 3-dimensional network. Ion exchangers can include organic ion exchangers and inorganic ion exchangers. Ion exchangers can be crystalline or amorphous. The insolubility imparted by this backbone structure may be the reason why these reagents are non-toxic. Because ion exchangers are insoluble, they do not dissolve when used for dialysate regeneration.

[0097] Ion exchangers can contain active groups, optionally selected from negatively charged anionic groups or positively charged cationic groups. Negatively charged groups can include sulfonate groups, carboxyl groups, sulfates, sulfinates, phosphates, phosphonates, phosphinates, hydroxides, sulfides, (metal) oxygen anions. Positively charged groups can include amino groups (primary amino groups, secondary amino groups, tertiary amino groups, quaternary amino groups, imino groups, zeolites (aluminosilicates), metal oxides, hydrated metal oxides, acidic salts of polyvalent metals, insoluble salts of heteropolyacids. The active groups determine the main properties of the ion exchanger. When negatively charged anionic groups (such as sulfonate or carboxyl groups) are attached to the main chain structure, they impart a fixed negative charge, which is balanced by positively charged mobile cations. These cations can be exchanged, so that the compound constitutes a cation exchanger.

[0098] Positive groups attached to the main chain (such as quaternary amines) impart a positive charge which is balanced by negatively charged mobile anions. These anions can be exchanged and the compound accordingly represents an anion exchanger. Amphoteric ion exchangers have anionic and cationic active groups and can exchange cations and anions. Ion exchangers can exist as porous structures. Porosity, pore size and the number and type of active groups are the main determinants of the function of the sorbent. Ion exchangers can be considered as electrolyte sponges. For certain cations with a greater selectivity coefficient, more cations will be bound than for cations with a lower selectivity. Most cation exchangers show the following selectivity for physiologically important cations: Li <Na<K≈NH4<<Mg<Ca。

[0099] Therefore, in this sequence, Ca 2+The highest affinity is for typical cation exchangers. Generally speaking, the higher the valence of the cation, the greater its affinity. For ions of the same valence, affinity is generally directly related to molecular weight. This order of specificity means that if calcium is present in the biofluid, the dialysate exchange process will result in calcium adsorption. This can result in unnecessary depletion of adsorption capacity and depletion of ions whose removal is not part of the intended therapeutic goal. Because biofluids are polyelectrolyte solutions, the design of ion exchangers for specific clinical purposes is limited by the nonspecificity of the exchange process and the relative affinities of various ions for the exchanger.

[0100] Affinity can vary with different ion exchangers and can, within certain limits, be modified by the procedures used to synthesize or pretreat the ion exchanger prior to use.

[0101] The maximum capacity of an ion exchanger (i.e., its exchange potential or efficiency) is determined by the number of active groups and is usually expressed in milliequivalents per gram of exchanger. The capacity can be determined by titrating the ion exchanger, similar to determining the concentration of an acid or base. However, the capacity of the desired ion under the actual conditions of clinical use is of greater practical importance. This is usually determined empirically under actual conditions of use.

[0102] The capacity of an ion exchanger to adsorb ions may depend not only on its theoretical capacity but also on the selectivity coefficient and the concentration of the ion to be removed. Competitive binding of other ions may also limit the ability to achieve the full theoretical capacity. The action of some ion exchangers may also be pH-dependent, limiting their medical applications to those that are active at or near the pH of body fluids. This dependence can be exploited to achieve reversible ion adsorption.

[0103] Furthermore, the total exchange capacity of cations with relatively low selectivity coefficients is strongly dependent on the cation concentration. Thus, the cation may be adsorbed from a more concentrated solution and released into a more dilute solution.

[0104] The capacity of the ion exchanger according to the present disclosure can be selected so that essential ions are not quantitatively retained. Accordingly, the dialysate may still contain some essential ions after the first passage through the reversible retainer 120, which are then absorbed by the purification device 110. For example, the capacity can be selected so that an unwanted excess of essential ions is allowed to pass through the retainer, so that the excess ions will be adsorbed in the purification device 110. Advantageously, this can be used to correct an imbalance in a patient who suffers from an excessive concentration of essential ions.

[0105] The ion exchanger can be a cation exchanger or an anion exchanger. The ion reservoir can be in the form of particles, granules, beads, fabrics, membranes, or combinations thereof. The ion reservoir can be a reversible ion reservoir capable of retaining and releasing ions. Optionally, the ion reservoir can include an amphoteric ion exchanger. The ion exchanger can transition from being primarily an anion exchanger when the pH is below approximately 5, below approximately 6, or below approximately 7. The ion exchanger can transition from being primarily a cation exchanger when the pH is above approximately 8, above approximately 7, or above approximately 6. Advantageously, because the ion exchanger can be an amphoteric ion exchanger and changes its properties depending on the pH, the ion exchanger can retain ions at a specific dialysate pH and release ions at a different pH. Advantageously, the pH of the dialysate before passing through the at least one reversible retainer 120 and / or purification device 110 can be different from the pH of the dialysate after passing through the purification device 110 and the at least one reversible retainer 120 in the reverse direction. In addition or alternatively, depending on the pH of the dialysate, some essential ions may have a higher affinity for retention. For example, the affinity of calcium (Ca) versus protons depends on the pH. At high pH (or high calcium concentration), calcium is bound and protons are released. At low pH (or low Ca concentration), protons are bound and Ca is released.

[0106] Thus, in some embodiments, the present disclosure utilizes two features that result in a synergistic effect of retaining and releasing ions from the dialysate, avoiding the need for electrolyte re-infusion. On the one hand, the amphoteric nature of the ion exchanger causes the reversible retainer 120 to retain essential ions in one flow direction and release them in the opposite direction. On the other hand, the pH of the dialysate decreases after passing through the reversible retainer 120 and the purification device 110. This is because the pH of the dialysate returning from the purification device 110 (approximately 6.5-7.2) is typically slightly lower than the dialysate from the patient (approximately 7.4). The exchange of essential ions (e.g., Ca and Mg) with H and Na in the reversible retainer 120 has already lowered the pH of the used dialysate entering the purification device 110. The dialysate leaving the purification device 110 has a formally increased pCO2, resulting in a further slight decrease in the pH of the dialysate. When the dialysate passes through the reversible retainer 120 in the reverse direction, the lower pH facilitates the reverse exchange of H and Na with essential ions (e.g., Ca and Mg) previously retained in the reversible retainer 120. Thus, the interaction between the amphoteric ion reservoir and the purification device 110 that lowers the dialysate pH can result in a synergistic effect as described above. It should be understood that this interaction is a non-limiting embodiment of the present disclosure, and that omitting electrolyte re-infusion can also be achieved through other means described herein.

[0107] The ion exchanger can be hydrous zirconium oxide (HZO). HZO can generally be considered an anion exchanger. It is used in dialysate regeneration and water purification to adsorb phosphate, fluoride, and other potentially harmful anions. HZO has also been found to have amphoteric properties, exchanging anions at pH < 7 and cations at pH > 7. The ion exchange properties can be represented by the following scheme:

[0108] in acidic solution

[0109] In alkaline solution

[0110] Scheme 1: pH-dependent ion exchange properties of hydrous zirconium oxide

[0111] Advantageously, HZO appears to be unique in that it has a highly uniform distribution of reactive groups within its matrix, which advantageously allows the reversibility of the ion exchange process to be finely tuned depending on pH. This property may be a key factor in achieving very good results using this material.

[0112] The ion reservoir can be embedded in the filter pad. Additionally or alternatively, the ion reservoir can be embedded in an additional sorbent bed. An ideal arrangement of the reversible holder 120 including the ion reservoir would be in a small sorbent bed that is arranged in sequence with the purification unit 110 so that both the used dialysate delivered to the primary sorbent and the fresh dialysate returned from the purification unit 110 must pass through the sorbent bed, using direct filtration in two different flow modes. Compared to the previously described diffusion-controlled process, direct filtration has low flow resistance and high fluid exchange and purification rates. It is suitable for cost-effective miniaturization and paves the way for the development of the first sorbent dialysis system that does not rely on electrolyte reinfusion.

[0113] For each of the at least one reversible retainer 120, the amount of ion reservoir contained therein can be less than about 50 grams, or less than 20 grams (g), or less than about 15 grams, or less than about 10 grams, or less than about 5 grams. Advantageously, such a low amount of ion reservoir can help reduce the overall size of the dialysate regenerator 100.

[0114] The average particle size of the ion reservoir can be in the range of about 25 microns to about 100 microns, or about 50 microns to about 100 microns. Such a particle size range can be achieved by sieving the ion storage material before use. Advantageously, a particle size range of about 25 microns to about 100 microns, and more preferably about 50 microns to about 100 microns, achieves the lowest pressure drop and the fastest achievable dialysate flow rate.

[0115] An ion reservoir in its original state may refer to an ion reservoir before its first use. The ion reservoir in its original state may include essential ions. After pretreatment with an ion salt, the essential ions may be contained in the ion reservoir, and the ion reservoir may be pre-added with the essential ions accordingly. The ion salt may be a salt of the same ion that is retained and released in the ion reservoir. Advantageously, when the ion reservoir in its original state includes the essential ions, one of the key challenges of optimization, i.e., avoiding the tendency of the ion reservoir to gradually change during use, may be avoided. Therefore, if the ion reservoir in its original state does not include the essential ions, typically, the ion retention rate (e.g., Ca and Mg retention rate) is very low at the beginning of the experiment, and a satisfactory level can only be reached after a long period of stabilization.

[0116] Thus, in one aspect, the ion exchanger may contain preselected percentages of essential ions, such as Ca and Mg. The preselected percentages may be 0.1 to 10 wt% Ca and / or Mg.

[0117] At least one reversible retainer 120 may be located upstream of the purification device 110 in a first direction of dialysate flow through the reversible retainer and downstream of the purification device 110 in a second direction of dialysate flow through the reversible retainer, wherein the second direction of dialysate flow is opposite to the first direction. The reversible retainer 120 may lower the pH of the dialysate upstream of the purification device 110 by retaining ions from the dialysate. The reversible retainer 120 may increase the pH of the dialysate downstream of the purification device 110 by releasing ions into the dialysate.

[0118] In one embodiment, the dialysate regenerator 100 may include a reversible retainer 120. The at least one reversible retainer 120 may be located upstream of the purification device 110 in a first direction of dialysate flow through the reversible retainer, and the same reversible retainer may be located downstream of the purification device 110 in a second direction of dialysate flow through the reversible retainer, wherein the second direction of dialysate flow is opposite to the first direction. Figure 4 shown.

[0119] In another embodiment, the dialysate regenerator 100 may include a first reversible holder 120A upstream of the purification device 110 and a second reversible holder 120B downstream of the purification device 110. The dialysate regeneration may be performed sequentially and may include two alternating states, including a first state and a second state. Figure 5A and Figure 5B Shown in. Figure 5A and Figure 5B Two alternating states are shown respectively. Figure 5AA first state ST1 is shown, in which dialysate containing essential ions and toxins passes through a first reversible retainer 120A. The essential ions are retained in the ion reservoir within reversible retainer 120A. The dialysate then passes through purification device 110, where toxins are removed from the dialysate. The dialysate then passes through reversible retainer 120B, and the essential ions previously retained by reversible retainer 120B are released into the dialysate. Figure 5B A second state ST2 is shown with a reverse flow direction through the reversible retainer. Figure 5B In the embodiment of the present invention, the dialysate containing essential ions and toxins passes through the first reversible retainer 120B. The essential ions are retained in the ion reservoir in the reversible retainer 120B. The dialysate then passes through the purification device 110, and toxins are removed from the dialysate. The dialysate then passes through the reversible retainer 120A and the essential ions previously retained by the reversible retainer 120A are released into the dialysate. By alternating the flow direction between ST1 and ST2, the reversible retainers 120A and 120B play a role in retaining or releasing essential ions, wherein each reversible retainer 120A and 120B retains the essential ions upstream of the purification device 110 along the first direction, and releases the essential ions downstream of the purification device 110 along the second direction, i.e. the reverse direction. This arrangement allows for efficient regeneration in a continuous dialysate flow, which is divided (distributed) into two alternating states. This configuration is preferably combined with a fluid portioning system 160 that guides the switching between the two states so that the volume of dialysate processed is the same in both states.

[0120] As described above in conjunction with the pump and according to this embodiment, the dialysate regenerator 100 may additionally include a fluid portioning system 160 (see Figure 6C ), which may also serve as a pump to divide the dialysate flow into uniform portions for sequential regeneration. The fluid portioning system 160 may include dividing the dialysate flow into uniform portions for sequential regeneration.

[0121] exist Figure 6A and Figure 6B In the illustrated embodiment, the dialysate regenerator 100 may further include one or more valves. The valves may include two sets of reversing valve devices. Specifically, one or more valves or a set of valves can alternate the direction of the dialysate flow path through the reversible retainer 120 between a first direction and a second direction, the second direction being opposite to the first direction. In addition, one or more valves or a set of valves can alternate the direction of the dialysate flow path between the fluid portioning system 160 and the dialysate outlet 140 to distribute the dialysate.

[0122] According to some embodiments, the dialysate regenerator 100 may further include one or more pressure sensors. The one or more pressure sensors may detect the external pressure at the volume control device 115. For example, the pressure sensor may include Figure 6Aand Figure 6B The pressure sensor PS1 shown. One of the pressure sensors, such as PS2, can be located in the dialysis flow path upstream of the purification device 110. This sensor can be used to detect changes in the pressure or dialysate flow entering the dialysate inlet and adjust the pump accordingly. Another pressure sensor can be positioned in the dialysis flow path between the purification device and the fluid portioning system. The two sets of reversing valve devices can be synchronized and triggered by detecting a pressure increase at the pressure sensor. In another embodiment, a pressure sensor, such as pressure sensor PS2, can be positioned downstream of the fluid portioning system. This sensor can be used to detect changes in the pressure or dialysate flow drawn from the dialysate outlet and adjust the pump accordingly.

[0123] According to some embodiments, the purification device 110 may be connected to the dialysate flow path such that the purification device only receives dialysate that has passed through one of the reversible holders 120A or 120B while releasing dialysate to pass through the other reversible holder 120A or 120B. Figure 6A and Figure 6B An embodiment is shown in which the valve is connected to the pressure sensor 170 (PS1) and the fluid portioning system. With each pressure increase detected at the pressure sensor PS1 (see Figure 6B 、 Figure 7 ), the system reverses the flow direction via V1 / V2 and V3 / V4. The flow conduit system is thus arranged so that after the portioning system divides the dialysate into equal portions, the direction of flow of the dialysate through the purification device 110 never changes, while the direction of flow of the dialysate through the reversible holder 120A or 120B is regularly reversed.

[0124] refer to Figure 6A In the first state (ST1), the used dialysate from a connected dialysis machine, such as an HD machine, is directed via V4 to the reversible holder 120A, where the essential ions are temporarily bound. The pre-filtered toxin-laden dialysate is then detoxified in the purification device 110. The regenerated dialysate leaving the purification device 110 passes through the reversible holder 120B, thereby backwashing the reversible holder and releasing the previously bound essential ions into the regenerated dialysate. The thus reconstructed dialysate reaches the first compartment of the fluid portioning system via V3 and V2. At the same time, an equal volume of previously regenerated and reconstructed dialysate is released from the second compartment of the fluid portioning system 160 via V1 and delivered to the HD machine as fresh dialysate. Once PS1 detects that the first compartment of the fluid portioning system 160 is completely filled, all valves are switched synchronously and the system switches to Figure 6B ST2 shown.

[0125] exist Figure 6BIn the second state (ST2) in , the used dialysate discharged from the HD machine reaches the reversible retainer 120B through V4, which was previously backwashed in ST1. Before the purification device 110 removes toxins, the reversible retainer 120B adsorbs all essential ions from the used dialysate. The detoxified dialysate leaving the purification device 110 is directed to backwash the reversible retainer 120A and release all essential ions previously bound in ST1. Thus, the reconstructed dialysate flows through V3 and V1 into the second compartment of the fluid portioning system, releasing an equal volume of regenerated dialysate from the first compartment of the fluid portioning system 160 to the HD machine. Once PS1 detects that the second compartment of the fluid portioning system 160 is filled (see Figure 6A 、 Figure 7 ), all valves switch again and the system returns to ST1.

[0126] Repeated alternation between ST1 and ST2 at regular volume intervals determined by the fluid portioning system 160 allows for continuous regeneration and reconstitution of the dialysate (with Figure 5A and Figure 5B Compare).

[0127] As described above in conjunction with the pump and according to some embodiments, the dialysate regenerator 100 can include a temporary storage container 180. In one embodiment, the temporary storage container 180 is located upstream of the purification device 110. The temporary storage container is intended to accommodate tidal volume. In some embodiments, it can also serve as a portioning system and / or as a pump.

[0128] According to some embodiments, the dialysate regenerator 100 may include a sensing device or substance sensor. The sensing device may be configured to detect potentially harmful conditions in the regenerated dialysate. Such potentially harmful conditions may include excessive concentrations of ammonia or potassium in the regenerated dialysate. Due to the presence of the sensing device, the dialysate regenerator's electronic control can detect alarm conditions and initiate appropriate steps, such as stopping treatment and / or alerting the user.

[0129] According to some embodiments, the dialysate regenerator 100 may include control electronics. The control electronics may be configured to control the operation of the dialysate regenerator 100. An interface device may also be provided that can operably connect the control electronics and the dialysate regenerator 100 to enable toxin removal from the dialysate. The dialysate flow path may be fluidically sealed with the control electronics and the interface device.

[0130] The at least one reversible holder 120 including the ion reservoir can be part of a disposable system or can even be a non-disposable permanent component of the dialysate regenerator 100. Because it is continuously regenerated, it is not expected that the ion reservoir in the reversible holder 120 will be depleted. On the contrary, reusing the reversible holder 120 including the ion reservoir can be advantageous for continuous dialysis treatment because it will eliminate the stabilization period (as described above).

[0131] The embodiments describing the dialysate regenerator 100 are similarly applicable to dialysis devices. Similarly, the embodiments describing the dialysate regenerator 100 are similarly applicable to medical uses of the dialysate regenerator 100, and vice versa.

[0132] In a second aspect, there is provided a use of an ion reservoir in the manufacture of a dialysate regenerator 100, the dialysate regenerator 100 comprising the ion reservoir contained in at least one reversible retainer 120, for treating a patient suffering from renal insufficiency, liver failure, or respiratory insufficiency with abnormally high levels of one or more toxins or metabolic wastes or inadequate removal of CO2, the treatment comprising passing the patient's dialysate through a dialysate flow path comprising a dialysate inlet 130 for receiving dialysate by operation of a pump, a dialysate outlet for distributing the dialysate, and a purification device 110, wherein the dialysate flow generated is from the dialysate inlet via the reversible retainer 120 and the purification device 110 to the dialysate outlet 140, and the direction of the dialysate flow path through the reversible retainer 120 is reversible.

[0133] In a third aspect, a dialysis device 200 is provided, comprising the dialysate regenerator 100 described above.

[0134] In a fourth aspect, there is provided a dialysate regenerator 100 as described above for use in treatment.

[0135] In a fifth aspect, a method for treating a patient suffering from renal insufficiency, hepatic failure, or respiratory insufficiency with abnormally high levels of one or more toxins or metabolic waste products or inadequate removal of CO2 is provided, the method comprising passing a dialysate from the patient through a dialysate flow path comprising a dialysate inlet 130 for receiving dialysate by operation of a pump 150, a dialysate outlet 140 for distributing the dialysate, and a purification device 110, wherein the dialysate flow generated is from the dialysate inlet 130 via a reversible retainer 120 comprising an ion reservoir and the purification device to the dialysate outlet 140, the direction of the dialysate flow path through the reversible retainer 120 being reversible.

[0136] Features described in one embodiment may be correspondingly applicable to the same or similar features in other embodiments. Features described in one embodiment may be correspondingly applicable to other embodiments, even if not explicitly described in these other embodiments. In addition, additions and / or combinations and / or substitutions described for features in one embodiment may be correspondingly applicable to the same or similar features in other embodiments.

[0137] In various embodiments, the articles “a,” “an,” and “the” used with respect to features or elements include reference to one or more of the features or elements.

[0138] "About" with respect to a given numerical value, such as weight percent (wt%), temperature, and time period, means that the value is included within 10% of the specified value.

[0139] As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0140] Examples

[0141] Some embodiments of the present disclosure relate to substantially quantitative adsorption and desorption of calcium and magnesium ions on a reversible retainer 120, which may be referred to in this section as a "pre-filter."

[0142] Advantageously, the ion exchanger used herein can produce a weak binding attraction for Ca and Mg ions. It can be, for example, a weakly acidic cation exchanger. The acid dissociation constant (pKa) of the cation exchanger can be in the range of 3 to 10, or alternatively in the pH range of the dialysate, i.e., close to the physiological range (pKa 5-8). The ion exchanger can be in the form of particles, granules, beads, fabrics or membranes. For example, hydrated zirconium oxide is a granular material that has a weak cation exchange property (in addition to its anion exchange property) in the desired range.

[0143] The prefilter can have sufficient binding capacity to adsorb the desired amount of Ca and Mg ions contained in the dialysate volume pumped during each flow mode. Its capacity can be selected so that excess Ca and Mg are deliberately "overflowed" from the prefilter into the primary sorbent, where they are adsorbed. The physical size of the filter can thus still be kept quite small. For example, a total of 250 ml of dialysate can be moved in each flow mode. This volume contains only about 0.35 mmol of Ca and Mg. This requires at most a few grams of typical ion exchange material, which can be achieved, for example, by a single layer of ion exchange fabric pads or ion exchange membranes.

[0144] The prefilter can release bound cations quantitatively (or substantially quantitatively) when backflushed with regenerated dialysate. This may be affected by variations in the concentrations of Ca and Mg ions in the regenerated dialysate. Sorbent regeneration of the dialysate also produces common pH fluctuations that can be used to aid the adsorption and desorption processes of Ca and Mg. The pH of the dialysate returning from the sorbent (approximately 6.5-7.2) is typically slightly lower than that of the dialysate from the patient (approximately 7.4). The exchange of Ca and Mg with H and Na in the prefilter has already lowered the pH of the used dialysate entering the sorbent system. The dialysate leaving the sorbent has a formally increased pCO2, resulting in a further slight decrease in pH. This lower pH facilitates the reverse exchange of H and Na with Ca and Mg in the prefilter. At the same time, the pH of the dialysate increases slightly, approaching the physiological target of 7.4.

[0145] Example 1

[0146] Figure 8 and Figure 9 Schematic diagram showing a possible arrangement of a prefilter, a temporary storage container and a purification device in the proposed dialysate regenerator for a tidal peritoneal dialysis machine.

[0147] In the first flow phase ("outflow", Figure 8 ), withdrawing the spent, toxin-laden dialysate from the patient. Appropriate pumping action and check valve configuration draw the dialysate through the prefilter into a temporary storage container. All calcium and magnesium are retained in the prefilter, resulting in calcium and magnesium saturation. The dialysate collected in the temporary storage container is free of calcium and magnesium but still contains sodium, chloride, hydrogen carbonate, potassium, and uremic toxins, most notably urea, creatinine, and phosphate.

[0148] In the second flow phase (“inflow”, Figure 9 ), the dialysate is squeezed out of a temporary storage container and passed through a sorbent system, where uremic toxins and K are adsorbed to >90%. The non-toxic dialysate leaving the sorbent system is essentially free of uremic toxins and contains almost exclusively Na, Cl, and HCO ions.

[0149] Figure 2 A conventional sorbent-based PD system is shown. Figure 10 The diagram shows the proposed modifications to the existing design to implement a prefilter. The main changes are an additional flow channel and two additional check valves to ensure the correct flow direction in both flow stages. With the infusion system eliminated, it can be removed and the sorbent system expanded accordingly.

[0150] If needed, a smaller version of the infusion system can be maintained to infuse concentrated solutions of osmotic agents, such as commercial glucose solutions. Crucially, unlike electrolyte reinfusion, osmotic agent infusion can be regulated independently of the primary dialysate pumping rate. This opens the possibility of future sensor-regulated control of dialysate osmotic pressure.

[0151] The requirement for electrolyte reinfusion is a major drawback of existing sorbent-based dialysate regeneration systems. It is inconvenient and complex to implement, presents potential safety risks, and increases the size and cost of disposables.

[0152] Unnecessary adsorption of Ca and Mg means wasted capacity for adsorbing urea, and at the same time increased Na concentration and / or acidification of the regenerated dialysate is undesirable. Electrolyte solutions used for peritoneal dialysis (PD) machine infusion must be sterile, and the machine design must ensure that sterility is maintained during connection and use.

[0153] Finally, considering PD, the infusion of hitherto unregistered electrolyte solutions into regenerative peritoneal dialysis fluid would lead to regulatory difficulties and classify PD sorbent systems as a combination of medical devices and unregistered drugs.

[0154] The goal of this disclosure is to find a way to reuse established and proven safe sorbent technology while eliminating the requirement for electrolyte reinfusion. The new approach should simplify existing designs, remove regulatory barriers, and provide a safe path to new, cost-effective, miniaturized devices.

[0155] The present disclosure is directed to a novel technique for selectively and efficiently regenerating sorbent dialysate without the need for electrolyte re-injection. This is achieved by reversibly binding the necessary electrolytes to a suitable pre-filter material (e.g., an ion exchanger). The calcium- and magnesium-free dialysate is then regenerated on a conventional sorbent system. The pre-filter is backwashed with the regenerated dialysate, dissolving any electrolytes retained in the process and effectively reconstituting the dialysate to its original electrolyte concentration.

[0156] The new approach has the potential to significantly simplify the design of disposable components for sorbent dialysis machines. It could allow for the development of miniature, self-care dialysis machines with high market potential, improving patient comfort, safety, and treatment outcomes at a lower cost than existing devices.

[0157] Material Screening. Several groups of materials were tested for their suitability as pre-filter materials. The powdered materials were loaded into custom plastic cartridges constructed from two connected 10 mL or 20 mL plastic syringes. The cartridge length can be customized based on the desired amount of ion exchanger it should contain. For example, a cartridge approximately 3 cm long constructed from 10 mL syringes can hold approximately 3 g of ZP or HZO, but only 1.5 g of resin-based ion exchanger.

[0158] Alternatively, a miniature glass column ("flexible column") is filled with the ion exchanger and the layer is tightly compressed with cotton. In yet another embodiment, a reusable cylindrical The prototype cartridges are filled with a 5-10 mm layer of ion exchanger. The membrane ion exchanger is held in a reusable 24 mm diameter disc membrane holder.

[0159] All test cylinders are suitable for both flow directions (see Figure 11 First, an ideal "dialysate outflow" solution is passed through the test cartridge in one direction, and the Ca and Mg in the fluid exiting the cartridge ("saline outflow") are quantified. The cartridge is then inverted, and the same volume of an ideal "saline inflow" solution (simulating toxin-free dialysate leaving the sorbent system) is passed through the cartridge in the opposite direction. The Ca and Mg in the fluid exiting the cartridge in this direction ("dialysate inflow") are again measured.

[0160] Such cycles were repeated at least 20 times to see whether the observed effects, if any, were reproducible. The ideal effluent solution is a bicarbonate-buffered dialysate at pH 7.5, free of toxins and glucose. The ideal influent solution is a solution containing only NaCl and NaHCO₃ at pH 6.3 to 6.5. Suitable prefilter materials are characterized by approximately quantitative adsorption of Ca and Mg from the "dialysate effluent" and approximately quantitative recovery of Ca and Mg in the "dialysate influent." Among other factors, binding capacity and flow resistance are also considered.

[0161] The volume of dialysate that can be regenerated and the mass of ion exchanger contained in such a microcartridge are used to deduce the mass required in a sorbent-based peritoneal dialysis device.

[0162] Offline testing. The following test steps involve a full-scale prototype containing the calculated amount of ion exchanger (see Figure 12 To this end, a cylindrical, one-off prototype was printed using a 3D printer. The prototype was designed so that its height could be easily increased or decreased as needed. If necessary, printed cylindrical spacers could be inserted to further reduce the internal volume.

[0163] like Figure 13As shown, the cylindrical prototype was used for in vitro testing with a simulated tidal volume of 275 mL for “dialysate outflow” and “saline inflow” for at least 20 cycles using a bidirectional peristaltic pump.

[0164] Online Testing. Once the prefilter size was optimized in offline testing, the filter was tested in conjunction with a conventional sorbent cartridge without electrolyte refill. Simulated patient dialysate containing toxins and glucose was used as the "dialysate outflow." Regenerated dialysate, after conventional purification procedures, was returned directly to the prefilter, replacing the "saline inflow" of the offline testing. Finally, the fluid exiting the prefilter was tested as the "dialysate inflow," and the recovery of Ca and Mg was evaluated.

[0165] Testing with integrated prototypes. Integrated system testing was performed using different versions of the integrated design. Some of these were tested at the local component level, while others were tested on complete prototypes using the new design (see Figure 14 ). These tests are primarily used for mechanical evaluation of design and in vitro assessment of performance.

[0166] Prototyping. Early prototypes were produced using stereolithography (SLA) or machining. Subsequent prototypes were produced using a Stratasys EDEN 260V 3D printer. This 3D printer enabled the development of waterproof prototypes with high precision and mechanical strength.

[0167] Example 2: Results and Discussion

[0168] Selection of Preferred Prefilter Materials. Table 1 shows a summary of the screening results obtained by selecting different ion exchange materials. It should be noted that only a limited number of materials were used, and it may be found that other materials within the tested class may have different performance. Therefore, the suitability assessment should be understood only for the specific material sample tested, rather than for the entire material class.

[0169]

[0170] Table 1: Material screening results

[0171] Zirconium phosphate. Zirconium phosphate was an obvious candidate to be tested in this study; it is a cation exchanger currently used in conventional sorbent systems. Its cation exchange properties are based on interactions with phosphate groups over a wide pH range of pH 2–pH 8. However, its performance as a prefiltration material was unsatisfactory. This is believed to be due to its significantly higher affinity for Ca and Mg than for Na and H, possibly due to complex formation. In other words, H is unable to displace any significant amount of Ca and Mg from its binding sites. The resulting retention of Ca and Mg is too low to be used in prefiltration applications.

[0172] Carboxylic acid-based ion exchangers. Most weakly acidic cation exchangers rely on carboxylic acid functional groups that bind to H or other cations. Their pKa range of 3–5 means that typical pH fluctuations during dialysate regeneration can lead to significant changes in the material's protonation degree, an essential requirement for reversible ion exchange in this study.

[0173] The resin-based cation exchangers tested in this study, as well as oxidized activated carbon and oxidized cellulose, belong to this group. All of these materials exhibited similarly unsatisfactory Ca and Mg retention. This is likely due to complex formation with divalent cations, resulting in a significantly higher affinity for Ca and Mg than for Na and H.

[0174] Ion exchange membranes. The ion exchange membranes tested had relatively high binding capacity and recovery efficiency. However, their high flow resistance and high material cost were significant drawbacks for their use in disposable cartridges.

[0175] Hydrated zirconium oxide. Hydrated zirconium oxide is generally considered an anion exchanger, exchanging hydroxide or acetate for other anions (e.g., phosphate or fluoride). However, it also exhibits cation exchange properties, which became apparent during material testing, where not only the actual target phosphate was removed, but also Ca and Mg, which were unexpectedly removed. The hypothesized mechanisms for anion and cation exchange are shown in Scheme 1. Thus, anion exchange involves the dissociation of the Zr-O bond, and cation exchange involves the dissociation of the ZrO-H bond.

[0176] Materials screening experiments demonstrated that HZO possesses properties suitable for the objectives of this study. A difference of one pH unit is sufficient to achieve complete adsorption of Ca and Mg at high pH and complete desorption at low pH. The material has the added advantage of being well-established for biocompatibility as part of a conventional sorbent system. Using the same material for the primary sorbent and prefilter is also expected to facilitate regulatory processes. This makes HZO the material of choice.

[0177] However, three issues need to be addressed:

[0178] Quantitative recovery of Ca and Mg can only be achieved after multiple adsorption and desorption cycles;

[0179] Imperfect Na loading and cation exchange capacity;

[0180] ·Slightly higher flow resistance.

[0181] Efforts have been made to overcome these shortcomings by appropriately modifying HZO.

[0182] Optimization of material properties. Two types of HZO ("Type 1" and "Type 2") are available through two different production methods. One type has a greater capacity for Ca and Mg with better retention and is therefore preferred.

[0183] Pretreatment and drying. One of the key challenges in optimization is that prefilter materials have a tendency to change gradually during use, which often means that the retention of Ca and Mg is low at the beginning of the experiment and only reaches satisfactory levels after a long period of stabilization (see Figure 15 This problem was eventually overcome by an appropriate process of pre-treating HZO with Ca and Mg salt solutions (see Figure 16 Optimal pretreatment conditions were found empirically by repeatedly modifying the concentration, duration, number of repetitions, and number of washing steps. The result was a prefilter that provided stable Ca and Mg retention from the start of the experiment – ​​see Table 2. A suitable procedure is, for example, to place 400 g of HZO in a solution of 2.28 g NaCl, 1.18 g NaHCO₃, 6.98 g CaCl₂, and 0.44 g MgCl₂ at room temperature, followed by filtration and air drying at 40°C.

[0184]

[0185] Table 2: is a table showing the performance of the reversible retainer after optimizing the pretreatment conditions, 5g pretreated type I, 250mL

[0186] Sieving. The material's resistance to flow is affected by washing, pretreatment, and drying. However, the best results are achieved by sieving the material after drying. Therefore, sieving and selecting the desired particle size range (e.g., 50–100 μm) provides the lowest pressure drop and the fastest achievable dialysate flow rate.

[0187] HZO filter pad. HZO filter pad has been studied, and attempts have been made to transform from a fixed particle bed to a pre-filter comprising HZO fixed on a 3-dimensional support (filter pad). The flow resistance of this filter pad is mainly determined by the structure of the cellulose carrier. The filter pad also has the obvious advantage of being easy to assemble. For example, a suitable filter pad manufacturing procedure is to mix 5.6g filter paper (small pieces) and 37.56g HZO in a solution of 2.87g NaCl, 1.49g NaHCO3, 14.37g CaCl2 and 1.06g MgCl2. The mixture is mechanically stirred until a uniform paste is obtained. Then, 1.40g dextrin, 0.06g starch, 0.37g sodium carboxymethyl cellulose and 0.01g sodium benzoate are added. Casting and drying give 4 HZO filter pads.

[0188] Optimization of Prefilter Size. The next step in development involved optimizing the capacity and size of the prefilter. This was accomplished using component-level prototypes that were run either offline using idealized dialysate solutions or online with conventional sorbent cartridges. In the initial stages, attempts were made to fully retain the desired target concentrations of Ca and Mg while removing any excess. During the course of these attempts, it became apparent that the prefilter also had a tendency to partially adsorb K and phosphate during the outflow, which then desorbed equally during the inflow, resulting in partial retention of these unwanted components. Larger prefilter sizes resulted in higher Ca and Mg retention but also reduced K and phosphate removal (e.g., 80 g, see Table 3).

[0189]

[0190] Table 3: is a table showing IV performance of large size reversible retainer, 80g pre-treated type I, 250mL

[0191] Smaller filters improved K and phosphate removal, sometimes to undesirably high levels. Adjustments to pretreatment conditions and reductions in prefilter size further improved performance (see Tables 4 and 5).

[0192]

[0193]

[0194] Table 4: Table showing IV performance of small size reversible retainer, 10 g pre-treated Type I, 250 mL

[0195]

[0196] Table 5: Table showing the performance of the optimized reversible retainer size IV, 10 g type I, 250 mL

[0197] Attempts to reduce the retention of K and phosphate (i.e., increase removal) by presaturating the filter with K and phosphate solutions were unsuccessful. The final optimization result was a compromise between these two factors, in which the prefilter retained approximately 90% of the target Ca and Mg, while allowing approximately 60-70% of K and 30-40% of phosphate to pass through the primary sorbent and be removed (see Table 5). A prefilter suitable for a 250 mL dialysate volume has, for example, a diameter of 70 mm and contains approximately 12 g of HZO.

[0198] Example 3: In vitro test

[0199] Offline experiments. Offline experiments use idealized settings to simulate expected conditions. The predictive value of these experiments is limited by the absence of toxins and proteins in the effluent solution and the choice of pH and Na concentration in the influent solution. Furthermore, the composition of the effluent and influent solutions is assumed to be constant, ignoring the possibility of gradual concentration changes over the expected treatment time span. However, these experiments have proven very useful for advanced material screening and initial material optimization steps.

[0200] In vitro testing. Most of the optimization work was done in component level testing using a modular setup of full-size pre-filter prototypes and conventional sorbent cartridge prototypes. For an outflow / inflow volume of 250 mL, the best results were obtained using a cylindrical prototype pre-filter with a diameter of 70 mm. When used in combination with a conventional sorbent cartridge, this pre-filter had an average retention rate of 97% and 87% for Ca and Mg, respectively, while allowing the removal of 66% of K and 37% of phosphate (see Table 5). The filter also performed well under simulated extreme conditions of high Ca, high Mg and high K. Similar results were obtained with HZO type II, such as Figure 17 and Figure 18 As expected, excess Ca in the effluent was readily removed, bringing the influent Ca concentration to the target standard. Thus, the prefilter was able to correct the effects of the simulated hypercalcemia. The situation with excess Mg was slightly different, with some Mg being retained and Ca slightly reduced. The absolute effect was relatively low, as the Mg concentration was only approximately one-fifth of the Ca concentration. The total amount of potassium retained appeared to be constant, even with varying effluent potassium concentrations. Therefore, higher K concentrations resulted in higher K removal rates. A similar situation occurred with phosphate. Phosphate was also retained only to a certain level; any additional amount was removed. Incomplete removal of K and phosphate is considered advantageous, as high-volume dialysis with dialysate depleted of K and phosphate may result in hypokalemia and hypophosphatemia. Therefore, partial retention of both components may be desirable.

[0201] Example 4: Embodiment with at least two reversible retainers

[0202] All test cylinders are suitable for both flow directions (see Figure 11 First, an idealized "dialysate outflow" solution is passed through the test cartridge in one direction, and Ca and Mg are detected in the fluid exiting the cartridge ("saline outflow"). The cartridge is then inverted, and the same volume of idealized "saline inflow" solution is passed through in the opposite direction. Ca and Mg are again measured in the fluid exiting the cartridge in this direction ("dialysate inflow").

[0203] The ideal effluent solution is a bicarbonate-buffered dialysate at a pH of 7.3 to 7.5, free of toxins and glucose. The ideal influent solution is a solution containing only NaCl and NaHCO₃ at a pH of 6.3 to 6.5. The desired material properties are approximately quantitative adsorption of Ca and Mg from the "dialysate effluent" and approximately quantitative recovery of Ca and Mg from the "dialysate influent." Other factors, such as flow resistance, are also considered.

[0204] 3D printed prototypes are Figure 13 In vitro testing as shown. A bidirectional peristaltic pump was used to simulate a dispense volume of 300 mL of "dialysate outflow" and "saline inflow" for at least 20 cycles.

[0205] Initial attempts focused on screening different types of HZO adsorbent materials (see Table 6). A preferred material was identified that demonstrated greater than 70% electrolyte recovery and good potassium and phosphate removal under standardized testing conditions. Compared to the initial concentrations of the dialysate solution, 81.7% of Ca and 72.9% of Mg were recovered, while 52.6% of K and 76.1% of PO4 were removed.

[0206]

[0207] Table 6: Different types of HZO sorbent materials and their removal effects

[0208] Full System Integration / Integrated Cartridge Design: Incorporates optimized pre-filter size into a fully integrated disposable cartridge design.

[0209] Hydraulic circuit valve design (V1, V2, V3 and V4). Each directional control valve (V1, V2, V3 and V4) in the integrated cartridge consists of a rigid flow chamber, one side of which is sealed by a flexible PVC membrane (see Figure 23 and Figure 24 The flow chamber has a fluid inlet channel and a fluid outlet channel. The inlet channel is located close to the flexible PVC membrane so that the membrane can be pressed against the opening of the inlet channel to seal the channel. This pressing is accomplished with the help of a pneumatic cylinder (one per valve) equipped with a silicone plunger. The valve is thus a naturally open 2 / 2 valve that can be closed by actuating the pneumatic plunger. The optimal pressure setting for the pneumatic cylinder has been determined for different fluid pressures and silicone plunger diameters.

[0210] The preferred cylinder is the CJ2B6 from SMC Corporation because the size is considered suitable for the overall integrated design. The diameter of the valve inlet channel is 3mm (inner diameter) and 6mm (outer diameter). The test results are shown in Table 7 below:

[0211]

[0212] Table 7: Full System Test / Verification

[0213] For system testing and validation, components equivalent to the integrated prototype were used. Simulated dialysate concentrations included normal, low, and high set concentrations of Ca, Mg, K, and phosphate. Calcium recovery rates of >80% were found for various concentrations. Magnesium recovery rates of >70% were observed. Potassium and phosphate removal rates were found to be 48-63% (K) and 28-50% (PO4), respectively. It was also noted that at low calcium concentrations, recovery rates of >100% were achieved, indicating that a small amount of Ca was released from the (pre-treatment) prefilter.

[0214]

[0215] Table 8: Summary of performance of the sorbent system without infusion fluid at different concentration ranges

[0216] Another full-system test was performed at the component level, simulating slow, low-flow hemodialysis conditions with a dialysate flow rate of 170 mL / min for a total duration of 7 hours. Throughout the 7-hour experiment, the sodium, calcium, magnesium, and bicarbonate concentrations of the regenerated dialysate remained stable within the desired target concentration range (see Figure 19A 、 Figure 19B 、 Figure 19C ).

[0217] Although the present disclosure has been particularly shown and described with reference to specific embodiments, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the appended claims. The scope of the present invention is therefore defined by the appended claims and is intended to encompass all changes that come within the meaning and range of equivalents of the claims.

Claims

1. A dialysate regenerator (100), comprising a purification device (110); at least one reversible holder (120) comprising an ion reservoir; a dialysate flow circuit comprising a dialysate inlet (130) for receiving the dialysate, and a dialysate outlet (140) for distributing the dialysate; a pump (150) connected to the dialysate flow path and configured to generate a dialysate flow from the dialysate inlet (130) via the reversible holder and the purification device to the dialysate outlet (140), wherein the direction of the dialysate flow path through the reversible retainer (120) is reversible; wherein the at least one reversible retainer (120) is located upstream of the purification device (110) in a first direction of the dialysate flow path and downstream of the purification device (110) in a second direction of the dialysate flow path, wherein the second direction of the dialysate flow path through the reversible retainer (120) is opposite to the first direction of the dialysate flow path through the reversible retainer (120); or The dialysate regenerator (100) comprises a first reversible holder (120A) located upstream of the purification device (110) and a second reversible holder (120B) located downstream of the purification device (110).

2. The dialysate regenerator (100) according to claim 1, characterized in that The ion reservoir comprises an ion exchanger.

3. The dialysate regenerator (100) according to claim 2, characterized in that: The dialysate regenerator (100) comprises a volume control device (115) configured to direct a predetermined volume of the dialysate from the dialysate inlet (130) via the reversible holder and the purification device (110) to the dialysate outlet (140).

4. The dialysate regenerator (100) according to claim 2, characterized in that: The ion exchanger is in the form of particles, fabrics, membranes or a combination thereof.

5. The dialysate regenerator (100) according to claim 4, characterized in that: The ion exchanger is in the form of particles, and the average particle size of the ion exchanger is in the range of 25 microns to 100 microns, or in the range of 50 microns to 100 microns.

6. The dialysate regenerator (100) according to claim 2, characterized in that: The ion exchanger is a reversible ion exchanger capable of retaining and releasing ions.

7. The dialysate regenerator (100) according to claim 2, characterized in that: The ion exchanger is an amphoteric ion exchanger.

8. The dialysate regenerator (100) according to claim 2, characterized in that: The ion exchanger changes from being primarily an anion exchanger at pH values ​​below 5 to being primarily a cation exchanger at pH values ​​above 8.

9. The dialysate regenerator (100) according to claim 2, characterized in that: The ion exchanger is hydrous zirconium oxide (HZO).

10. The dialysate regenerator (100) according to claim 2, characterized in that: For each of the at least one reversible retainer, the amount of the ion exchanger is less than 50 grams.

11. The dialysate regenerator (100) according to claim 2, characterized in that: The ion exchanger in its original state comprises the essential ions.

12. The dialysate regenerator (100) according to claim 2, characterized in that: The ion exchanger is embedded in the filter mat and / or in an additional sorbent bed.

13. The dialysate regenerator (100) according to claim 1, characterized in that: The dialysate regenerator (100) includes one or more valves for alternating the direction of the dialysate flow path through the reversible retainer (120) between a first direction and a second direction, the second direction being opposite to the first direction.

14. The dialysate regenerator (100) according to claim 1, characterized in that: The reversible retainer (120) is configured to lower the pH of the dialysate upstream of the purification device (110) by retaining ions from the dialysate.

15. The dialysate regenerator (100) according to claim 1, characterized in that: The reversible retainer (120) is configured to increase the pH of the dialysate downstream of the purification device (110) by releasing ions into the dialysate.

16. The dialysate regenerator (100) according to claim 1, characterized in that: The dialysate regenerator (100) comprises a first pressure sensor (PS1).

17. The dialysate regenerator (100) according to claim 1, characterized in that: The dialysate regenerator (100) comprises a reversible retainer, wherein the reversible retainer (120) is located upstream of the purification device (110) in a first direction of the dialysate flow path through the reversible retainer (120), and the same reversible retainer (120) is located downstream of the purification device (110) in a second direction of the dialysate flow path, wherein the second direction of the dialysate flow path through the reversible retainer (120) is opposite to the first direction of the dialysate flow path through the reversible retainer (120).

18. The dialysate regenerator (100) according to claim 1, characterized in that: The dialysate regenerator (100) comprises a temporary storage container (180).

19. The dialysate regenerator (100) according to claim 18, characterized in that: The dialysate regenerator (100) comprises one or more valves for alternating the dialysate flow path between the following phases: a first flow phase in which the dialysate flow path is from the dialysate inlet (130) via the reversible holder (120) to the temporary storage container (180); and a second flow phase, wherein the dialysate flow path flows from the temporary storage container (180) via the purification device (110) and the reversible holder (120) to the dialysate outlet (140), wherein the direction of the dialysate flow path through the reversible holder (120) in the second flow phase is opposite to the direction of the dialysate flow path through the reversible holder in the first flow phase.

20. The dialysate regenerator (100) according to claim 1, characterized in that: When the dialysate regenerator (100) includes a first reversible retainer (120A) located upstream of the purification device (110) and a second reversible retainer (120B) located downstream of the purification device (110), the dialysate regenerator (100) includes a volume control device (115), which is configured to guide a predetermined volume of the dialysate from the dialysate inlet (130) via the first and second reversible retainers (120A, 120B) and the purification device (110) to the dialysate outlet (140), wherein the volume control device (115) includes a fluid portioning system (160) to divide the dialysate flow into uniform parts for sequential regeneration.

21. The dialysate regenerator (100) according to claim 16, characterized in that: When the dialysate regenerator (100) comprises a first reversible retainer (120A) located upstream of the purification device (110) and a second reversible retainer (120B) located downstream of the purification device (110), the dialysate regenerator (100) comprises one or more valves for alternating the dialysate flow path between the dialysate inlet (130) and the dialysate outlet (140) between a first state and a second state, wherein in the first state the dialysate flow path passes through the first reversible retainer (120A) and the second reversible retainer (120B) located downstream of the purification device (110). A), the purification device (110), the second reversible holder (120B), in the second state the dialysate flow path passes through the second reversible holder (120B), the purification device (110), and the first reversible holder (120A), wherein the direction of the dialysate flow path through the first and second reversible holders (120A, 120B) in the second state is opposite to the direction of the dialysate flow path through the first and second reversible holders (120A, 120B) in the first state.

22. The dialysate regenerator (100) according to claim 21, characterized in that The one or more valves are synchronized and cause the dialysate flow path to alternate between the first and second states based on pressure changes detected by the first pressure sensor (PS1).

23. The dialysate regenerator (100) according to claim 1, characterized in that The dialysate regenerator (100) comprises a flow regulator (165).

24. The dialysate regenerator (100) according to claim 1, characterized in that The dialysate regenerator (100) comprises a second pressure sensor (PS2).

25. A dialysis device (200), comprising the dialysate regenerator (100) according to any one of claims 1 to 24.

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