Dialysis fluid regenerator and system comprising it

Abstract

One aspect of this disclosure relates to a dialysate regenerator for connection to a dialysis apparatus, the dialysate regenerator including a regenerator inlet for receiving dialysate; a regenerator outlet for dispensing regenerated dialysate; a hydraulic circuit connected between the regenerator inlet and the regenerator outlet; and a fluid dispensing system for dividing the dialysate flow into uniform portions for sequential regeneration. Another aspect of this disclosure relates to a dialysis system including a dialysis apparatus comprising: a fresh dialysate inlet; a used dialysate outlet; and a dialysate regenerator, wherein the regenerator inlet can be connected to the used dialysate outlet to receive used dialysate, and wherein the regenerator outlet can be connected to the fresh dialysate inlet to dispense regenerated dialysate.

Description

[0001] Cross-references to related applications

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

[0003] One aspect of this disclosure relates to a dialysate regenerator for connection to a dialysis apparatus. Another aspect of this disclosure relates to a dialysis system comprising a dialysis apparatus connected to the dialysate regenerator. Background Technology

[0004] Existing dialysis equipment utilizes fresh dialysate typically in bags and disposes of used dialysate in treated containers. Used dialysate is completely discarded, generating waste. Therefore, there is a need for an improved dialysis method and an improved dialysis system. Summary of the Invention

[0005] One aspect of this disclosure relates to a dialysate regenerator for connection to a dialysis apparatus. The dialysate regenerator may include a regenerator inlet for receiving dialysate and a regenerator outlet for dispensing regenerated dialysate. The dialysate regenerator may also include a hydraulic circuit connected between the regenerator inlet and the regenerator outlet. The dialysate regenerator may further include a fluid dispensing system to divide the dialysate flow into uniform portions for sequential regeneration. The dialysate regenerator may include a purification device configured to convert used dialysate into regenerated dialysate. For example, the purification device may include a compartment containing a toxin remover, such as an adsorbent.

[0006] According to several embodiments, sequential regeneration may include two alternating states, including a first state and a second state. The fluid dispensing system may include a chamber comprising a movable partition wall dividing the interior of the chamber into a first compartment and a second compartment. The fluid dispensing system may include a first opening for allowing exchange of dialysate into and from the first compartment. The fluid dispensing system may include a second opening for allowing exchange of dialysate into and from the second compartment. The fluid dispensing system may be configured to allow dialysate to flow from the regenerator inlet into one of the first and second compartments in a first state, and to flow into the other of the first and second compartments in a second state. Dialysate entering one compartment causes displacement of the movable partition wall and dialysate flows out from the other compartment.

[0007] According to several embodiments, the hydraulic circuit may also include a flow regulator configured to detect (individually) external flow or external pressure from one or each of the regenerator inlet and regenerator outlet, and regulate the internal flow or internal pressure such that the external flow or external pressure remains constant. Therefore, for one or each of the individual regenerator inlet and regenerator outlet, the external flow or external pressure remains substantially constant, for example, the pressure is maintained in a range close to zero, such as within + / - 7 kPa. The flow rates at the outlet and inlet may differ. It is normal for the dialysis unit to discharge fluid at a rate faster than it draws fresh fluid.

[0008] According to several embodiments, the flow regulator may include a damper for accommodating temporary changes in internal pressure. The damper may also be used to accommodate differences in external flow or pressure at the regenerator inlet and / or outlet.

[0009] According to several embodiments, the flow regulator may include a pressure sensor to detect external pressure at one or both of the regenerator inlet and regenerator outlet. The flow regulator may be configured to regulate internal flow or internal pressure based on the external pressure detected by the sensor.

[0010] According to some embodiments, the dialysate regenerator further includes a housing, wherein the housing may include a base and an opposing portion releasably attached to each other. The base may be a support. The chamber of the fluid dispensing system may include a base and a corresponding portion, the base being included within the base of the housing. When the opposing portion and the base are attached to each other, the base and corresponding portion of the chamber may be attached together. According to several embodiments, the corresponding portion of the chamber may be a replaceable cartridge. The cartridge may be disposable.

[0011] According to some embodiments, the movable partition wall may be attached to a corresponding portion of the chamber such that it remains within the opposing portion of the housing when the opposing portion is released from the base of the housing. According to some embodiments, the movable partition wall may be attached to a box such that it remains within the box when the box is removed from the base of the housing.

[0012] According to some embodiments, as an alternative to dividing the fluid distribution system into a base and an opposing portion of the housing, the fluid distribution system can be included in the opposing portion of the housing, so that when the opposing portion is replaced, the fluid distribution system is also replaced.

[0013] According to several embodiments, the partition wall may be a membrane. According to several embodiments, the membrane may be pre-formed, for example, having a convex side. The membrane may be switchable between a first membrane side convex in a first state and a second side convex in a second state.

[0014] According to some embodiments, the first compartment may include a first bag that is fluidly connected to the first opening. The partition wall may be a wall of the first bag.

[0015] According to some embodiments, the second compartment may include a second bag that is fluidly connected to the second opening. The partition wall may be the wall of the second bag.

[0016] According to some embodiments, the first compartment may include a first bag fluidly connected to a first opening, the second compartment may include a second bag fluidly connected to a second opening, and the walls of the first bag and the second bag are in contact with each other and form a partition wall.

[0017] According to several embodiments, the flow regulator may include a pump for increasing pressure. According to several embodiments, the pump may be a bellows pump, piston pump, gear pump, rotary vane pump, roller pump, or peristaltic pump. In a roller pump, the pump tubing and optionally the pump profile may be part of a housing, while the pump rollers and motor are part of a base. Disposable and non-disposable components may be engaged using suitable levers and locking mechanisms to ensure sufficient mechanical stability.

[0018] According to several embodiments, the pump may include two pump chambers configured to alternately allow dialysate to flow in and out through openings in the respective pump chambers. For example, the pump may be a bellows pump.

[0019] According to some embodiments, the pump can be controlled by the filling state of the filled pump chamber. For example, the pump may include one or more chamber filling sensors that detect when the pump chamber currently filled with dialysate has been filled to a predetermined volume (e.g., fully filled). When the predetermined volume is reached, the pump chamber switches to an emptying mode, for example, by a switching valve. The one or more chamber filling sensors may be pressure sensors. A flow regulator may be configured such that the emptied pump chamber is always empty before or simultaneously with the filled pump chamber being fully filled, which may be achieved, for example, by adjusting the pressure used to empty the chamber.

[0020] According to several embodiments, the pump can be pneumatic, i.e., pneumatically driven. Pumping out the dialysate may include applying pneumatic pressure to the side of the movable pump wall opposite the dialysate contact side on a corresponding pump chamber.

[0021] According to several embodiments, the pump can be connected to a housing. The housing may include a base and opposing portions that are releasably attached to each other.

[0022] According to several embodiments, one of the two pump chambers can be divided into two chambers connected in parallel to the pneumatic pressure receiving side. The two chambers can be arranged on opposite sides of the other pump chamber, such that the tension applied to the housing by one of the two pump chambers during pumping can be symmetrically distributed to the other pump chamber.

[0023] According to several embodiments, the pneumatic pressure receiving side of one of the two pump chambers and the other pneumatic pressure receiving side of the other of the two pump chambers are located on the base, for example, included in the base.

[0024] According to several embodiments, the base may be reusable and may include control elements, and the opposing portion may include disposable elements.

[0025] According to several embodiments, the base can be reusable. The opposing portion of the housing may include a replaceable case.

[0026] According to several embodiments, the base can be reusable. An opposing portion of the housing may include the replaceable cartridge.

[0027] According to several embodiments, the dialysate regenerator may also include a purification device.

[0028] According to several embodiments, the dialysate regenerator may also include a regeneration compartment containing a purification device.

[0029] According to several embodiments, the purification apparatus may include one or both of an adsorption filter or an adsorbent cartridge.

[0030] According to several embodiments, the hydraulic circuit may also include an infusion fluid inlet and be configured to add a predetermined volume of infusion fluid to the dialysate.

[0031] According to several embodiments, the hydraulic circuit may further include an adsorbent cartridge. The hydraulic circuit may also include at least one reversible retainer comprising an ion reservoir. The direction of dialysate flow through the reversible retainer may be reversible.

[0032] According to several embodiments, a dialysate regenerator may include an additive metering device (e.g., an infusion metering device) that allows the mixing of an additive (e.g., infusion solution) into the dialysate. The additive metering device may include its own dispensing system (additive dispensing system) that can be synchronized with a fluid dispensing system that dispenses the dialysate, such that the additive-to-dialysate ratio remains constant according to a predetermined ratio. In some embodiments, the dosage of the additive is sequential and provided by the additive dispensing system (or infusion solution dispensing system), which may include: an additive dispensing chamber including a movable partition wall dividing the interior of the additive dispensing chamber into a first additive dispensing compartment and a second additive dispensing compartment. The additive dispensing system may include a first opening for allowing the exchange of additive to and from the first additive dispensing compartment. The fluid dispensing system may include a second opening for allowing the exchange of additive to and from the second additive dispensing compartment. The additive dispensing system can be configured to allow additives to flow from an additive inlet or reservoir to one of the first and second additive dispensing compartments in a first state and to the other of the first and second additive dispensing compartments in a second state. Additive entering one additive dispensing compartment causes displacement of a movable partition wall and allows additive to flow out of the other additive dispensing compartment. A valve system can be employed to regulate the flow rate and mixing of the additive with the dialysate. Alternatively, the additive dispensing system may consist of only one pneumatically actuated additive dispensing compartment.

[0033] One aspect of this disclosure relates to a dialysis system including a dialysis apparatus and a dialysate regenerator according to various embodiments. The dialysis apparatus may include a fresh dialysate inlet and a used dialysate outlet. The regenerator inlet of the dialysate regenerator may be connected to the used dialysate outlet to receive used dialysate. The regenerator outlet of the dialysate regenerator may be connected to the fresh dialysate inlet for dispensing regenerated dialysate. Attached Figure Description

[0034] The invention will be better understood by referring to the description of specific embodiments in conjunction with the non-limiting examples and accompanying drawings, wherein:

[0035] Figure 1 A schematic diagram of the dialysate regenerator 100 is shown;

[0036] Figure 2 A schematic diagram of regeneration using an adsorbent and several optional adsorbent systems is shown;

[0037] Figure 3A A schematic diagram of the dialysate regenerator 100, including more details of the fluid dispensing system, is shown;

[0038] Figure 3BAn example of a flow regulator 130 is shown as a hydraulic circuit including a hydraulic component connected between the fluid distribution system 120 and one or both of the regenerator inlet 102 and the regenerator outlet 104.

[0039] Figures 4A to 4C A flow regulator 130 is shown, which includes hydraulic components for regulating pressure and / or flow rate.

[0040] Figure 5A and Figure 5B An example is shown in which the opposing portion 210 of the housing has the form of a box that can be attached to the base 220. Figure 5B In the middle, the opposing part 210 is attached to the base 220;

[0041] Figure 6A and Figure 6B An example is shown in which the opposing portion 210 of the housing includes a box that can be attached to the base 220. Figure 6B In the middle, the opposing part 210 is attached to the base 220 and the housing 200 is closed;

[0042] Figure 7A A fluid distribution system 120 is shown, as in a cross-sectional view A-A' at rest, comprising two compartments 124 and 126;

[0043] Figure 7B The end of the two states is shown Figure 7A Sectional view A-A' in the middle;

[0044] Figure 8 Details of the pump are shown;

[0045] Figure 9 A schematic diagram of a dialysis system 300 according to several embodiments is shown;

[0046] Figure 10A and Figure 10B The first state ST1 is shown. Figure 10A ) and the second state ST2 ( Figure 10B The following is an example schematic diagram according to Embodiment 1;

[0047] Figure 11 An exemplary valve control principle is illustrated by a pressure versus time graph, where the pressure can be the pressure at the filled compartment.

[0048] Figure 12A and Figure 12B An exemplary chamber 121 of the fluid dispensing system 120 is shown. Figure 12A The chamber 121 in its assembled state is shown. Figure 12B An exploded view of an exemplary chamber is shown;

[0049] Figure 13 and Figure 14 An example of an adsorbent compartment in a box that is the opposite part 210 of the housing 200 is shown;

[0050] Figure 15 The composition of the extracorporeal dialysate after re-infusion of Ca, Mg, and K is shown;

[0051] Figure 16 and Figure 17 The pneumatic components are shown, in which Figure 16 A portion is shown in the image. Figure 17 A schematic diagram is shown in the figure;

[0052] Figure 18 and Figure 19 The design of the hydraulic circuit valves (V1, V2, V3, and V4) is shown; and

[0053] Figure 20 The diagram shows a hydraulic flow chart where the distribution system and pumps are integrated into a dual-pump system. Detailed Implementation

[0054] Detailed embodiments are described below with reference to the accompanying drawings, which illustrate specific details and examples by way of illustration that may be used to practice this disclosure. These embodiments are described in sufficient detail to enable those skilled in the art to practice this disclosure. Other embodiments may be used and structural and logical changes may be made without departing from the scope of this disclosure. The various embodiments are not necessarily mutually exclusive, as some embodiments may be combined with one or more other embodiments to form new embodiments.

[0055] The system embodiments described in the context are similarly applicable to the regenerator, and vice versa.

[0056] Features described in the context of one embodiment may be correspondingly applied to the same or similar features in other embodiments. Features described in the context of one embodiment may be correspondingly applied to other embodiments, even if not explicitly described in those other embodiments. Furthermore, additions and / or combinations and / or substitutions described for features in the context of one embodiment may be correspondingly applied to the same or similar features in other embodiments.

[0057] In the context of various embodiments, the terms “a” and “the” used with respect to a feature or element include references to one or more of the features or elements.

[0058] In the context of various embodiments, the reference to "base" (or "base portion") can refer to a portion that cooperates to attach to an opposing portion (or corresponding portion) and is not necessarily limited to its position or orientation relative to a bottom surface. For example, in some embodiments, the base may be located below the opposing portion, while in other embodiments, the base may be located above or at the same level as the opposing portion. The base may be a support.

[0059] In this document, the term "and / or" includes any and all combinations of one or more of the related listed items.

[0060] The dialysate entering the regenerator input may be referred to as "used dialysate" and may refer to dialysate containing one or more toxins, waste types, or waste substances (e.g., urea). It is generally understood that the purpose of used dialysate is to remove one or more such toxins, waste types, or waste substances, such as urea. Used dialysate may also contain one or more electrolytes or ions. The dialysate dispensed at the regenerator outlet may be referred to as "fresh dialysate" (or regenerated dialysate) and may refer to dialysate that is substantially free of one or more toxins, waste types, or waste substances (e.g., urea). Fresh dialysate may also contain one or more electrolytes or ions at the desired concentration.

[0061] Dialysis fluid regeneration may include the removal of unwanted contaminants or patient waste from used dialysis fluid. Dialysis fluid regeneration requires accurate determination of the volume or volume ratio of the fluid used for regeneration. For example, this may involve accurately dispensing the infusion fluid into the purified dialysis fluid after adsorbent purification on an adsorbent system, or accurate aliquoting for regeneration in an electrolyte-retaining adsorbent. A relatively standalone system also needs to be able to passively control the regeneration flow rate in response to external flow requirements. Furthermore, a relatively standalone system needs to have specific safety features for the regeneration method implemented. For example, a sensing device for detecting potentially unsafe chemical components in the regenerated dialysis fluid. Compared to relatively standalone systems, dialysis fluid regenerators according to various embodiments may include one or more, such as all, of the following: fluid dispensing devices, infusion fluid dispensing devices, purification devices (e.g., toxin removal devices), flow regulating devices, sensing devices, and electronic control devices, which do not need to be integrated into existing dialysis equipment.

[0062] As described herein, and according to various embodiments, the term "dialysis" may refer to hemodialysis (HD), hemofiltration, hemodiafiltration, plasma exchange, peritoneal dialysis (PD), liver dialysis, lung dialysis, water purification, physiological fluid regeneration, or biological fluid regeneration. Dialysis can be regenerative dialysis based on an adsorbent. Similarly, a dialysate regenerator may refer to a dialysate regenerator for hemodialysis dialysate, a dialysate regenerator for peritoneal dialysis dialysate, a dialysate regenerator for liver dialysis dialysate, a dialysate regenerator for lung dialysis dialysate, a regenerator for water purification hydrolysate, a dialysate regenerator for hemofiltrate, a dialysate regenerator for plasma regeneration, a dialysate regenerator for physiological fluid regeneration, or a dialysate regenerator for biological fluid regeneration.

[0063] Several embodiments disclose a dialysate regenerator 100 for connection to a dialysis apparatus. This is for illustrative purposes and not for limitation. Figure 1 A schematic diagram of a dialysate regenerator 100 is disclosed. The dialysate regenerator 100 may include a regenerator inlet 102 for receiving dialysate, and may further include a regenerator outlet 104 for dispensing regenerated dialysate. The dialysate regenerator 100 may include a hydraulic circuit 110 connected between the regenerator inlet 102 and the regenerator outlet 104. The dialysate regenerator 100 may also include a fluid distribution system 120 to divide the dialysate flow into uniform portions for sequential regeneration.

[0064] According to several embodiments, the dialysate regenerator 100 may include a purification device 123 configured to convert used dialysate into regenerated dialysate. For example, the purification device may include a compartment containing a toxin remover, such as an adsorbent.

[0065] Adsorbent systems rely on direct contact between a series of adsorbent materials and the used dialysate (see [link to relevant documentation]). Figure 2 These can be categorized as follows:

[0066] Activated carbon: This adsorbent can remove organic uremic metabolites, such as creatinine, uric acid, and some intermediate molecules, such as β2-microglobulin, from used dialysis fluid.

[0067] Anion exchanger: Our adsorbent system contains hydrated zirconium oxide (HZO) as an inorganic anion exchanger to adsorb negatively charged anions, such as phosphates and sulfides, by exchanging hydroxide ions.

[0068] Urea adsorbent:Due to the low reactivity and specificity of urea, adsorbent systems must employ a combination of enzymatic (urease) hydrolysis of urea followed by adsorption of the hydrolysis product, ammonia, onto a non-selective cation exchanger. This cation exchanger is zirconium phosphate (ZP), which primarily exchanges ammonium ions for hydrogen ions. However, zirconium phosphate also adsorbs other cations, most notably calcium, magnesium, and potassium, primarily exchanging sodium. This unintentional electrolyte removal depletes cation exchange capacity (and thus urea adsorption capacity) and affects the sodium concentration and acidity of the dialysate. An additional element may be required for the dialysate remodeling process, namely electrolyte re-infusion. Electrolyte re-infusion requires a controlled pumping system to add electrolytes to the regenerated dialysate to re-establish physiologically appropriate electrolyte concentrations. For this purpose, a solution of calcium, magnesium, and / or potassium ions must typically be injected into the regenerated dialysate. The dispensed solution must be prepared at the patient's side prior to treatment or provided in a sterile pre-packaged form.

[0069] According to several embodiments, the dialysate regenerator 100 may include a sensor for detecting whether the regenerated dialysate is within predetermined parameters. For example, the dialysate regenerator 100 may include an electronic ammonia sensor configured to detect the ammonia level in the regenerated dialysate. If the regenerator controller detects an error, such as the presence of excessive ammonia in the regenerated dialysate, it may stop the regenerator from operating, for example, by simply stopping the pump, thereby triggering a pressure alarm in the connected dialysis machine.

[0070] According to several embodiments, the dialysate regenerator 100 may include a hydrophobic vent to discharge larger gas contents (if any). This vent may also serve as an interface for connection to a sensor (e.g., an electronic ammonia sensor), which may be located in a base.

[0071] According to several embodiments, sequential regeneration may include two alternating states ST1 and ST2, including a first state ST1 and a second state ST2. Figure 3AA schematic diagram of a dialysate regenerator 100 is disclosed, including further details of the fluid dispensing system, which is for illustrative purposes and not for limitation. The fluid dispensing system 120 may include a chamber 121. Chamber 121 may include a movable partition wall 122 for dividing the interior of chamber 121 into a first compartment 124 and a second compartment 126. Chamber 121 may also include a first opening 128 to allow dialysate exchange into and from the first compartment 124. Chamber 121 may also include a second opening 129 for allowing dialysate exchange into and from the second compartment 126. The fluid dispensing system 120 may be configured in a first state ST1 to allow dialysate to flow from the regenerator inlet 102 into one of the first and second compartments 124, 126, and in a second state ST2 to flow into the other of the first and second compartments 126, 124. The entry of dialysate into one compartment 124, 126 causes displacement of the movable partition wall 122 and dialysate flows out from the other compartment 126, 124. For example, valves V1 and V2 can be controlled such that during a first state ST1, valve V2 allows dialysate to flow into the first compartment 124, and valve V1 allows dialysate to flow out of the second compartment 126. In this example, valves V1 and V2 can be controlled such that during a second state ST2, valve V1 allows dialysate to flow into the second compartment 126, and valve V2 allows dialysate to flow out of the first compartment 124. Figure 3A In the first state ST1, valve V2 connects the regenerator inlet 102 to the first compartment 124 and disconnects the regenerator outlet 104 from the first compartment 124. Further, in the second state ST2, valve V1 connects the regenerator inlet 102 to the second compartment 126 and disconnects the regenerator outlet 104 from the second compartment 124. However, Figure 3A It is not restrictive and other elements may be incorporated in further developments as described herein.

[0072] According to several embodiments, the hydraulic circuit 110 may further include a flow regulator 130 configured to detect external flow or external pressure from one or both of the regenerator inlet 102 and the regenerator outlet 104, and to regulate the internal flow or internal pressure such that the external flow remains constant. For example, the external pressure is maintained in a near-zero range, such as within + / - 7 kPa. The external pressure from the regenerator inlet 102 refers to the pressure measured near the regenerator inlet 102. The external pressure from the regenerator outlet 104 refers to the pressure measured near the regenerator outlet 104. Figure 3BAn example of a flow regulator 130 as a hydraulic circuit is shown, which includes hydraulic components connected between the fluid distribution system 120 and one or both of the regenerator inlet 102 and the regenerator outlet 104. A damper 134' may include a pressure sensor for measuring external pressure PS1 from the regenerator inlet 102. A damper 134" may include a pressure sensor for measuring external pressure PS2 from the regenerator outlet 104.

[0073] As used herein, and according to various embodiments, the term "external" can refer to the regenerator inlet or outlet and adjacent piping. For example, external pressure from the regenerator inlet can be measured at the end forming an inlet port or at a piping connected to the inlet port. For example, external pressure from the regenerator outlet can be measured at the end forming an outlet port or at a piping connected to the outlet port.

[0074] According to several embodiments, the purification device 123 may be connected in series with a flow regulator.

[0075] According to several embodiments, the flow regulator 130 may include dampers 134' and / or 134" to accommodate temporary changes in internal pressure, temporary changes in external pressure, temporary differences in external flow at the regenerator inlet, temporary differences in external flow at the regenerator outlet, or combinations thereof.

[0076] According to several embodiments, the flow regulator 130 may also include electronic control devices to regulate the flow rate in response to the supply or demand of the connected dialysis equipment, for example by adjusting the pump speed. Such regulation may be achieved, for example, through closed-loop control of a pressure sensor at the regenerator inlet or outlet of the dialysate regeneration device, or a level detector in a reservoir at the regenerator inlet or outlet.

[0077] Figure 4A A flow regulator 130 is shown, including hydraulic components for regulating pressure and / or flow rate. The flow regulator 130 may include more or fewer components than shown; for example, according to several embodiments, the flow regulator 130 may have only one pump 132' or 132'", or two pumps. Figure 14 As shown, the flow regulator 130 connected to the regenerator inlet 102 may include a damper 134' and a first pressure sensor PS1, as well as a first pump 132' connected in series with the damper. Figure 4AFurther shown, the flow regulator 130 connected to the regenerator outlet 104 may include a damper 134” and a second pressure sensor PS2, as well as a second pump 132” connected in series with the damper. The first pump 132” can be activated when the pressure measured by the first pressure sensor PS1 is below a first threshold, and stopped when the pressure exceeds the threshold. Control of the first pump can be electronic, electric, pneumatic, or a combination thereof. Alternatively or additionally, a second pump 132” can be activated when the pressure measured by the second pressure sensor PS2 is below a second threshold, and stopped when the pressure exceeds the threshold. Control of the second pump can be electronic, electric, pneumatic, or a combination thereof. In another variation, only one pump (e.g., 132' or 132”) is used, and the pump is controlled based on the pressure measured by the first pressure sensor PS1, the pressure measured by the second pressure sensor PS2, the fill level of damper 134', the fill level of damper 134”, a state dependent on the first and second pressures, and a state dependent on the fill levels of dampers 134' and 134”. The flow regulator 130 may include a reservoir connected to the regenerator inlet 102. Figure 4A (Not shown in the image).

[0078] Figure 4B Another flow regulator 130 is shown, which includes hydraulic components for regulating pressure and / or flow rate. Flow regulator 130 may include more or fewer components than shown. Flow regulator 130 may include a reservoir 135 connected to regenerator inlet 102. The reservoir ensures that the pressure at regenerator inlet 102 is substantially zero, allowing inlet 102 to be connected to the discharge port of the dialysis apparatus without any further modification. Reservoir 135 may also hold excess dialysate and may have a capacity of up to 5 L (by volume). Flow regulator 130 may include a pump 132. Figure 4B As shown, the flow regulator 130 connected to the regenerator outlet 104 may include a damper 134 and a pressure sensor PS2. The pump 132 can be activated when the pressure measured by the pressure sensor PS2 is below a first threshold (e.g., below 7 kPa) and stopped when the pressure exceeds the threshold. The control of the first pump can be electronic, electric, pneumatic, or a combination thereof.

[0079] Alternatively, the flow regulator 130 may include a reservoir 134 connected to the regenerator outlet 104. The reservoir ensures that the pressure at the regenerator outlet 104 is substantially zero, allowing the outlet 104 to be connected to the inlet of the dialysis apparatus without any further modification. The reservoir 134 may also hold excess dialysate and may have a capacity of up to 5 L (by volume). The flow regulator 130 may include a pump 132. Figure 4CAs shown, the flow regulator 130 connected to the regenerator inlet 102 may include a damper 135 and a pressure sensor PS1. The pump 132 can be activated when the pressure measured by the pressure sensor PS1 is higher than a first threshold (e.g., higher than 7 kPa) and stopped when the pressure is lower than the threshold. The control of the first pump can be electronic, electric, pneumatic, or a combination thereof.

[0080] According to several embodiments, the flow regulator 130 may include a pressure sensor 136 to detect external pressure at one or both of the regenerator inlet 102 and the regenerator outlet 104, such as Figure 3B As shown, pressure sensor 136 may include pressure sensor PS1 and / or pressure sensor PS2. Flow regulator 130 can be configured to regulate internal flow or internal pressure based on external pressure detected by sensor 136. Thus, the dialysis apparatus connected to regenerator inlet 102 and regenerator outlet 104 has the same flow resistance as the comparative example, and therefore operates within the normal operating parameters of the dialysis apparatus, where the dialysis apparatus in the comparative example uses a dialysate damper and dialysate discharge line.

[0081] Figure 5A , Figure 5B , Figure 6A and Figure 6B Different exemplary embodiments of the housing 200 according to various embodiments are shown.

[0082] According to several embodiments, the dialysate regenerator 100 may also include a housing 200. The housing 200 may include a base 220 and an opposing portion 210 detachably attached to each other. The opposing portion 210 may include a housing that can be attached to the base. Alternatively or additionally, the housing 200 may include a cover 221, such as a hinged cover, with its hinged side attached to the base and its side opposite the hinged side removably locked to the base 220. For example, the opposing portion 210 may include a housing that remains in place when the cover 221 is closed.

[0083] According to some embodiments, the chamber 121 of the fluid dispensing system 120 may include a reusable portion as part of a base 220 and a replaceable portion as part of an opposing portion 210 (e.g., part of a cartridge). The reusable portion may be a pneumatic portion that does not contact the dialysate. The replaceable portion may be a hydraulic portion that contacts a liquid such as dialysate and may be replaced, for example, after one use, after a predetermined number of uses, after a predetermined time before the first use, after reaching a certain criterion, after the filter is full, after the infusion reservoir is emptied, or a combination thereof. According to some embodiments, as an alternative to dispensing the fluid dispensing system in the base and opposing portion of the housing, the fluid dispensing system may be included in the opposing portion of the housing, so that the fluid dispensing system is replaced when the opposing portion is replaced.

[0084] Figure 5A and Figure 5B An example is shown in which the opposing portion 210 of the housing has the form of a box that can be attached to the base 220. See also Figure 5B The opposing portion 210 is connected to the base 220. For example... Figure 5A and Figure 5B As shown, the chamber 121 of the fluid distribution system 120 may include a corresponding portion 212 contained in the opposing portion 210, and a base 222 contained in the base 220 of the housing 200. Figure 5B As shown, when the opposing portion 210 and the base 220 are attached to each other, the corresponding portion 212 and the base 222 of the chamber 121 can be attached together. Figure 5A As shown, the partition wall 122 or a layer thereof can be arranged, for example, attached to the corresponding portion 212 of the chamber, so that it can be replaced together with the opposing portion 210. Figure 5B The partition wall 122 is shown in two positions under the alternating first state ST1 and second state ST2.

[0085] Figure 6A and Figure 6B An example is shown where the opposing portion 210 of the housing includes a box that can be attached to the base 220. The box can be secured to the base when the cover 221 is locked to the base, for example, when the cover is closed. Figure 6B In this configuration, the opposing portion 210 is attached to the base 220 and the housing 200 is closed. The cover 221 can be a lid, one side of which is hinged to the base, and the opposite side is lockable to the base. For example... Figure 6A and Figure 6B As shown, the chamber 121 of the fluid dispensing system 120 may be composed of a corresponding portion 212 of the housing. The chamber 121 of the fluid dispensing system 120 may also include a base 222, which is composed of the base 220 of the housing 200. (As shown...) Figure 6B As shown, when the housing is closed, the corresponding portion 212 and the base 222 of the chamber 121 can be attached and fixed together. Figure 6A In this case, the partition wall 122 or one of its layers can be arranged, for example, attached to the corresponding part 212 of the chamber, so that it can be replaced together with the box.

[0086] As previously described, and according to some embodiments, as an alternative to dividing the fluid distribution system into a base and an opposing portion of the housing, the fluid distribution system may be included in the opposing portion of the housing, so that when the opposing portion is replaced, the fluid distribution system is also replaced.

[0087] According to several embodiments, the partition wall 122 may be a membrane. According to several embodiments, the membrane may be preformed and may alternate between a first membrane side bulging in a first state ST1 and a second side bulging in a second state ST2. Since the partition wall is a membrane, the side that is not bulging in one state is recessed.

[0088] According to several embodiments, the corresponding portion 212 of the chamber 121 may be composed of a replaceable box, and the base 220 may be reusable.

[0089] According to several embodiments, the movable partition wall 122 or one of its layers may be attached to the corresponding portion 212 of the chamber 121 such that when the opposing portion 210 or the box is released from the base 220 of the housing 200, it can be retained in the opposing portion 210 or the box of the housing 200.

[0090] Figure 7A A fluid dispensing system 120 is shown, comprising two compartments, a first compartment 124 and a second compartment 126, as shown in cross-sectional view A-A' in a resting position. The two compartments may be formed by two bags, each bag connected to one of the first and second openings 128, 129. Each of the two bags may be flexible, allowing its volume to change while the total volume of the two compartments remains constant. The fluid dispensing system 120 may include a housing 121, which may be rigid to limit the total volume of the two compartments. One compartment has the largest volume when the other compartments are at their minimum volume (i.e., completely empty). According to some embodiments, the two bags may be separate and independent bags, which may or may not be connected, for example, by welding. Alternatively, the two bags may be formed by welding three sheets together, such that the first bag is formed between the first and second sheets (intermediate sheet), and the second bag is formed between the second and third sheets. Thus, a partition wall 122 is formed from the second sheet.

[0091] Figure 7B The cross-section A-A' at the end of the two states is shown. In the second state ST2, the second compartment 126 is full and substantially occupies the entire volume of the fluid distribution system 120, while the first compartment 124 is empty and substantially has zero volume.

[0092] According to several embodiments, the first compartment may include a first bag fluidly connected to the first opening 128, and the partition wall 122 may be a wall of the first bag. At least a portion of the partition wall, such as only the first bag, may be included in the opposing portion 210 or box of the housing 200.

[0093] According to several embodiments, the second compartment may include a second bag fluidly connected to the second opening 129, and the partition wall 122 may be the wall of the second bag, or a combination thereof, wherein the walls of the first bag and the second bag are in contact with each other and form the partition wall 122. At least a portion of the partition wall, such as the second bag, may be included in the opposing portion 210 or box of the housing 200.

[0094] According to several embodiments, the first compartment may include a first bag fluidly connected to a first opening 128, and the second compartment may include a second bag fluidly connected to a second opening 129, with the walls of the first bag and the walls of the second bag contacting each other to form a partition wall 122. At least a portion of the partition wall, such as the first bag, may be included in an opposing portion 210 or box of the housing 200.

[0095] Combination Figure 8 Details of the pump according to several embodiments are described below. Figure 8 This is a schematic diagram for illustrative purposes; however, the pumps according to different embodiments are not limited thereto.

[0096] According to several embodiments, the flow regulator 130 may include a pump 132 (e.g., pump 132' or 132" as illustrated in conjunction with FIG4) to increase pressure.

[0097] According to several embodiments, pump 132 may include two pump chambers C1, C2, which may be configured, for example, to alternately allow dialysate to flow in and out through the respective pump chamber openings via a one-way valve and a pneumatic control system.

[0098] According to several embodiments, pump 132 may be pneumatic, and for each of the two pump chambers C1, C2, pumping dialysate may include applying pneumatic pressure to the side of the movable pump wall opposite the dialysate contact side.

[0099] According to several embodiments, pump 132 may be connected to housing 200. Housing 200 may include opposing portions 210 and base 220 that are releasably attached to each other.

[0100] According to several embodiments, one of the two pump chambers, C2, can be divided into two chambers connected in parallel 131 to the pneumatic pressure receiving side. Alternatively or additionally, the hydraulic sides of the two chambers can be connected in parallel 136 and thus operate as a single pump chamber C2. The two chambers can be positioned on opposite sides of another pump chamber C1, such that the tension applied to the housing 200 during pumping in one of the two pump chambers C1, C2 can be at least partially symmetrically distributed to the other of the two pump chambers C2, C1. Therefore, shear stress on the housing and / or the pump can be reduced, and the life of the base can be increased.

[0101] According to several embodiments, a pneumatic pressure receiving side of one of the two pump chambers and another pneumatic pressure receiving side of the other of the two pump chambers can be disposed on the base 220. For example, line 137 can represent the separation at the junction of the two parts of the pump chamber.

[0102] According to several embodiments, base 220 may be reusable and may include control elements, such as pneumatic and / or electronic control elements. Opposite portion 210 may include disposable hydraulic circuit elements, such as all components in surface contact with the dialysate.

[0103] According to several embodiments, the base 220 may be reusable. The opposing portion 210 of the housing 200 may include a replaceable, for example, disposable box. The housing 200 may also include a cover 221, such as a lid. The lid may be hinged to the base and may secure the box to the base.

[0104] The dialysate regenerator according to this disclosure may include a purification device, which may be, for example, a toxin removal device, exemplified by a purification compartment. As used herein, and according to various embodiments, the term "purification device" may refer to a compartment containing one or more adsorbent materials. Purification methods may also include electro-oxidation methods, electrodialysis methods, or other purification methods not based on adsorbent technology. The compartment may be connected to the dialysate flow path. The adsorbent material in the purification device is used to remove a specific solute, such as urea, from the solution. The purification device may have a single-compartment design, wherein all the adsorbent material necessary for dialysis is contained in a single compartment. Alternatively, the purification device may have a modular design, wherein the adsorbent material is dispersed in at least two different modules that can be connected to form a single unit. The purification device of the present invention may be a disposable purification device.

[0105] According to several embodiments, the hydraulic circuit 110 may further include an adsorbent cartridge. According to several embodiments, the hydraulic circuit 110 may also include at least one reversible retainer containing an ion reservoir. The direction of dialysate flow through the reversible retainer may be reversible.

[0106] According to different embodiments, the dialysate regenerator may include one or more valves for alternating dialysate flow paths between a first flow stage and a second flow stage, wherein in the first flow stage, the dialysate flows from the dialysate inlet through a reversible retainer to a temporary storage container; and in the second flow stage, the dialysate flows from the temporary storage container through a purification device and the reversible retainer to the dialysate outlet, wherein the direction of the dialysate flow path through the reversible retainer in the second flow stage is opposite to the direction of the dialysate flow path through the reversible retainer in the first flow stage.

[0107] According to several embodiments, the dialysate regenerator may include a first reversible retainer upstream of the purification apparatus and a second reversible retainer downstream of the purification apparatus. According to several 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, wherein the second direction of the dialysate flow path through the reversible retainer is opposite to the first direction.

[0108] An ion reservoir can be any compound capable of retaining and releasing ions. Examples of such compounds include ion exchangers, ion exchange membranes, ion repulsion membranes, etc. 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 cation atom. The ion may be a physiologically essential ion. The ion may include cations from Group II of the periodic table. Advantageously, because essential ions are selected from Group II of the periodic table, they have a higher valence than, for example, cations from Group I of the periodic table. The higher valence, in turn, allows cations with higher valences to have a greater affinity for the ion reservoir or ion exchanger contained in the reversible reservoir. The ion may include calcium. The ion may include magnesium. The ion may include potassium. These ions, such as calcium, magnesium, and potassium, can be called essential ions due to their physiological relevance.

[0109] Figure 9 A schematic diagram of a dialysis system 300 according to several embodiments is shown. According to several embodiments, the dialysis system 300 may include a dialysis apparatus 310 and a dialysate regenerator 100 according to several embodiments. According to several embodiments, the dialysis apparatus 310 may include a fresh dialysate inlet 314 and a used dialysate outlet 312. A regenerator inlet 102 may be connected to the used dialysate outlet 312 to receive used dialysate, and a regenerator outlet 104 may be connected to the fresh dialysate inlet 314 for dispensing regenerated dialysate. Therefore, dialysate regeneration can be provided without any modifications to existing dialysis equipment.

[0110] The dialysate regenerator includes a fluid dispensing system that works by dispensing a dialysate of unknown flow rate into aliquots of known volume (“dialysate dose volume”), and optionally mixing each aliquot with a defined volume of infusion fluid (“infusion dose volume”).

[0111] Aliquots of the sample can be determined with the aid of a fluid fractionation system, which is, for example, a chamber (e.g., a rigid chamber) containing two distinct compartments (a first compartment and a second compartment) separated by a movable partition wall (e.g., a flexible membrane). Each compartment can be connected to a separate opening within the chamber, allowing fluid to flow in or out of the compartment. The partition wall can be moved to either side of the rigid chamber, allowing the volume of each compartment to vary between zero and the total volume of the chamber. The sum of the volumes of the two compartments is always equal to the volume of the chamber (“dialysis fluid dose volume”). In use, the system can exist in two alternating states, a first state ST1 and a second state ST2. In the first state ST1, fluid flow is directed through a first opening into the first compartment, displacing the fluid contained in the second compartment and forcing it out of the chamber through the second opening. Once the first compartment is full (i.e., the second compartment is empty), there is no more volume for the first compartment to expand, resulting in an increase in fluid pressure within the first compartment. The first chamber now contains precisely a fraction of the fluid volume equal to the volume of the rigid chamber. The increase in pressure can be detected by a pressure sensor and can be further used to switch a reversing valve assembly, which consists, for example, a three-way valve or two two-way valves connected to either opening of the rigid chamber. The valves can be pneumatically or electromechanically controlled (e.g., using solenoid valves or a servo system). Switching the valve assembly places the system in a second state ST2: the fluid flow direction is reversed, causing fluid to be directed through the second opening of the chamber to the second compartment, while the fluid contained in the first compartment (corresponding to a fraction of the sample volume equal to the volume of the rigid chamber) is discharged through the first opening. The system then remains in this state until the fluid pressure increases again, indicating that the first compartment is completely emptied and the second compartment now contains precisely a fraction of the sample volume equal to the volume of the chamber. Switching the reversing valve assembly again, the process continues again in the first state ST1. This operation allows for the division of a flowing fluid at an unknown velocity into uniform fractional volumes, each fraction equal to the volume of the chamber.

[0112] A fraction of purified dialysate can then be precisely mixed with a fixed volume of infusion solution (“infusion dose volume”). The process of determining this fixed infusion volume is similar to the process of determining the volume of the dialysate fraction. A chamber (e.g., a rigid chamber) can be divided into two compartments by a movable partition wall, each compartment connected to a separate opening in the chamber to allow infusion solution to flow into or out of the compartment. A reversing valve assembly, for example, comprising a three-way valve or two two-way valves at either opening of the rigid chamber, can again be positioned in two alternating positions and switched corresponding to the two possible states described above. Each switching of the valve assembly allows for the precise dispensing of a dose of infusion solution equal to the chamber volume of the dispensing device (“infusion dose volume”). To provide the driving force to fill the compartment with the infusion dose volume, the pressure of the infusion solution must be higher than the pressure in the fluid line dispensing the contents of the other compartment. This can be readily achieved, for example, by supplying the infusion solution from a closed storage container pressurized with air pressure.

[0113] In an alternative embodiment, the infusion volume can also be used to dispense a volume of infusion solution while simultaneously draining an equal volume of excess dialysate. In this arrangement, the first state of the system would involve filling the first compartment with dialysate taken from a point immediately upstream of the adsorbent compartment when the fluid pressure in the adsorbent compartment is high. The second compartment contains the infusion solution, which is dispensed into the purified dialysate using the high pressure in the first compartment as the driving force. When the system is in the second state, the contents of the first compartment can be drained into the drain container, and the second compartment is filled with the infusion solution. This filling can be driven by gravity (the hydrostatic pressure between the infusion container and the drain container) or by pressurizing the closed infusion solution storage container.

[0114] Figure 10A and Figure 10B The first state ST1 according to embodiment 1 is shown. Figure 10A ) and the second state ST2 ( Figure 10BAn exemplary schematic diagram is shown. The regenerator inlet 102 allows the reception of used dialysate, for example, dialysate from a dialysis apparatus, which can be stored in a dialysate reservoir 135. The external pressure at the regenerator inlet 102 can be in the range of 0 to P1, for example, P1 can be 7 kPa. Downstream of inlet 102, the dialysate can pass through, for example, adsorbent in adsorbent cartridge 123. Pump 132 can increase the pressure of the dialysate after the reservoir. The pump can be controlled according to the external pressure PS2 of the regenerator outlet 104, for example, such that the external pressure PS2 of the regenerator outlet 104 is in the range of 0 and P1. Another damper can be located downstream of adsorbent cartridge 123 and can measure the pressure PS1 at a selected input of chamber 121 of the fluid dispensing system, in a first state ST1, where the selected input can be a compartment ① being filled while another compartment ② is being emptied. The selection of chambers can be performed by valves, for example, by the three-way valves V1 and V2 shown. Once compartment ① is filled, pressure sensor PS1 records an increase in pressure, which can trigger a reversing valve assembly (e.g., three-way valves V1 and V2) to switch to... Figure 10B The second state ST2 is shown, in which compartment ① is being emptied while another compartment ② is being filled. In both states, dialysate flows from chamber 121 to regenerator outlet 104 (from different compartments of chamber 121). A damper with pressure sensor PS2 can be arranged downstream of chamber 121 and the reversing valve assembly.

[0115] According to several embodiments, the dialysate regenerator may include an infusion metering device that allows additives (e.g., infusion fluid) to be mixed into the dialysate. Figure 10A and Figure 10B As shown, the infusion dispensing device 400 may include a reservoir 435 and an infusion dispensing system, which includes, for example, additional directional valve devices (e.g., three-way valves V3 and V4) and a dual-compartment dispensing chamber 421. The dual-compartment dispensing chamber 421 and the additional directional valve devices can be configured and controlled similarly to chamber 121 and the directional valve devices, except that the infusion fluid aliquot is smaller than the dialysate aliquot. The mixing ratio is determined by the volume ratio of the dialysate aliquot to the infusion fluid aliquot.

[0116] Figure 11 An exemplary valve control principle is illustrated by a pressure versus time graph, where the pressure can be the pressure at the filled compartment, such as PS1 in Figure 10. It can be seen that as the compartment is filled, the pressure increases (in example, from 100 to 200), at which point (marked by the vertical dashed line) a state transition occurs.

[0117] In several embodiments, an exemplary chamber 121 or additional chamber (for additive metering) of the fluid dispensing system 120 may include two rigid half-shells (e.g., composed of two rigid half-shells) with a flexible diaphragm sandwiched between them. Alternatively, the two chambers may include two fluid bags (e.g., composed of two fluid bags) contained within the rigid chamber (e.g., two parallel fluid bags sharing a common bag wall). The latter arrangement further inspires the possibility of constructing the rigid chamber from the wall of a disposable cassette, which is locked at a profile located on the surface of a base (e.g., a non-disposable support).

[0118] Figure 12A and Figure 12B An exemplary chamber 121 of the fluid dispensing system 120 is shown. Figure 12A The chamber 121 is shown in its assembled state, while Figure 12B An exploded view of chamber 121 is shown. Chamber 121 may include a movable partition wall 122 that divides the interior of chamber 121 into a first compartment 124 and a second compartment 126. Chamber 121 may also include a first opening 128 for allowing dialysate to be exchanged into and from the first compartment 124. Chamber 121 may also include a second opening 129 for allowing dialysate to be exchanged into and from the second compartment 126. Additional chambers for the additive metering device can be constructed in the same or similar manner by adjusting the volume as needed.

[0119] The reversing valve device can be constructed from a commercially available disposable three-way faucet, which is mechanically coupled to a servo motor on a non-disposable bracket. Alternatively, a diaphragm valve system with a pneumatic piston can be used to construct the reversing flow device via a two-way diaphragm valve.

[0120] Figure 13 and Figure 14 An example of an adsorbent compartment in a cartridge, which is the corresponding part 210 of the housing 200, is shown. Dialysis fluid regeneration occurs in the adsorbent compartment. The cartridge may include a body, a top cover, a check valve, and a filter. Figure 14 An example of a base is shown, such as a bracket, which has a receiving box and may include the lower part of the pump.

[0121] In some embodiments, to integrate the absorbent compartment with other disposable components, its top cover may be designed such that the top cover also forms the lower portion (or multiple portions) of chamber 121 and additional chamber 421. The bottom side of the absorbent compartment may form the upper portion (or upper part) of a pump, such as the upper portion of a bellows pump chamber. Thus, the disposable components, together with the membrane and / or bag, can be combined into a single module as a disposable cartridge assembly.

[0122] Figure 15 The composition of the extracorporeal dialysate after re-infusion of Ca, Mg, and K is shown.

[0123] Figure 16 and Figure 17 The pneumatic components are shown, in which Figure 16 A portion is shown in the image. Figure 17 A schematic diagram is shown.

[0124] According to several embodiments, the pump may include a force sensor that senses internal pressure, which can be used to detect whether the chamber (or filled compartment) is full. For example, the pressure sensor may be integrated into the wall of the pump chamber.

[0125] According to several embodiments, the dispensing system may include a force sensor that senses internal pressure, which can be used to detect whether a chamber (or a filled compartment) is full. For example, the pressure sensor may be integrated into the wall of a chamber used for dispensing.

[0126] Hydraulic circuit valve designs (V1, V2, V3, and V4) are illustrated according to various embodiments. Each directional control valve (V1, V2, V3, and V4) in the integrated housing includes a rigid flow chamber, one side of which is sealed by a flexible PVC membrane (see [link to documentation]). Figure 18 and Figure 19 The flow chamber has a fluid inlet channel and a fluid outlet channel. The inlet channel is located immediately adjacent to the flexible PVC membrane, so pressing the flexible membrane against the opening of the inlet channel seals the channel. Pressing is accomplished using a cylinder (one for each valve) equipped with a silicone plunger. Therefore, the valve is a naturally opening 2 / 2 valve, which can be closed by actuating the pneumatic plunger. The optimal pressure setting of the cylinder is determined for different fluid pressures and silicone plunger diameters.

[0127] In the experiment, the preferred cylinder was the SMC CJ2B6, as its dimensions were considered suitable for the overall integrated design. The valve inlet channel diameter was 3 mm (inner diameter) and 6 mm (outer diameter). The test results are shown in Table 4 below:

[0128]

[0129] Figure 20 A hydraulic flow diagram showing the integration of the distribution system and pump into a dual-pump system is presented.

[0130] A simplified model study was conducted to determine the achievable accuracy of the simplified component-level prototype. The following modifications were made: A variant of the dialysate volumetric component was designed, comprising three liquid bags: two identically sized compartments used to produce equal volumes of dialysate; and a third bag filled with water. The available volume was empirically optimized to the required aliquot volumes. Tap water was used instead of the dialysate, an off-the-shelf laboratory peristaltic pump replaced the dialysate pump, a flow resistor replaced the adsorbent system, and a concentrated solution of blue dye replaced the infusion fluid. The system's quantitative accuracy was then verified by measuring the concentration (i.e., absorption intensity) of the blue dye in each aliquot of "fresh" dialysate leaving the system. This test was repeated at different flow rates.

[0131] In another test, simulated purified dialysate (simulated dialysate after adsorbent purification) was pumped through a damper representing the flow resistance of the adsorbent system and subsequently recombined with actual infusion solution. In this experiment, the accuracy of quantification was assessed by periodically performing chemical analysis on the collected "fresh" dialysate. Figure 15 The composition of the extracorporeal dialysate after reinfusion of Ca, Mg, and K is shown. The experiments demonstrate the accuracy and consistency achievable with the fractionation system. The average fractionation ratio is very close to the target value, with only minor variations in individual fractions.

[0132] A complete prototype was constructed according to the various implementation schemes, and good results were shown in animal models using dialysis fluid.

[0133] The dialysate regeneration compartment is used to purify used dialysate, for example, by removing uremic toxins and other unwanted solutes. The regenerator is configured to regenerate dialysate collected from a connected dialysis unit. The regenerator itself is not configured to perform dialysis. Used dialysate is collected from the connected dialysis unit, and fresh (regenerated) dialysate is supplied to the connected dialysis unit at a predetermined rate, according to the flow rate set by the connected dialysis unit. The dialysate regeneration device performs this task entirely autonomously, and no electronic communication or control is required between the dialysate regenerator and the connected dialysis unit. This dialysate regenerator is designed as an accessory to conventional dialysis units, extending their application to adsorbent-based regeneration dialysis without requiring modifications to the conventional dialysis unit. This significantly reduces the development and regulatory work typically required for adsorbent-based regeneration dialysis units.

[0134] The regenerator may optionally include any combination of the following:

[0135] - A fluid dispensing system, which may include a valve system to divide the dialysate flow into uniform portions for sequential regeneration;

[0136] - A dispensing system for adding concentrated solutions of additives, such as infusion solutions, in the required proportions;

[0137] - A valve system used to guide fluid flow in alternating fluid channels or to reverse the flow direction in a portion of the fluid channel;

[0138] - Additional filter or adsorber compartment;

[0139] - Pumping device to deliver used dialysate from the regenerator inlet through the regeneration compartment to the regenerator outlet;

[0140] - A control device for adjusting the dialysate regeneration rate. This control device may include a level detector or pressure sensor at the inlet or outlet, and an electronic control unit to adjust the pump speed in response to the fluid demand or supply of the connected dialysis unit;

[0141] - Sensing devices used to detect harmful conditions in the regenerated dialysate, such as ammonia sensors or electrolyte sensors;

[0142] - A storage container (“inlet reservoir”) for receiving used dialysate from a conventional dialysis machine (e.g., an HD or PD machine);

[0143] - A storage container (“outlet storage”) for receiving regenerated dialysate for use by a conventional dialysis machine;

[0144] In some embodiments, the volume of the regeneration device is from 10 dL to 50 dL, for example from 20 dL to 30 dL, and the net weight is from 1 kg to 10 kg, for example from 2 kg to 6 kg.

[0145] Fluid dispensing systems may include one or more of the following:

[0146] - A chamber, which may be rigid, is divided into two compartments by a movable partition wall (e.g., a flexible membrane), wherein each compartment is connected to a separate opening in the chamber to allow fluid to flow into or out of the compartment;

[0147] - A reversing valve assembly connected to two openings of a rigid chamber;

[0148] -A device that switches the directional valve according to fluid pressure;

[0149] - Additive dispensing device;

[0150] - A discharge device for draining excess liquid;

[0151] The partition walls can move back and forth on either side of the chamber, allowing the volume of each compartment to vary between zero and the total volume of the chamber. The sum of the volumes of the two compartments is always equal to the volume of the chamber, thus allowing the fluid to be divided into uniform portions equal to the volume of the rigid chamber.

[0152] Next, these volumes can be accurately mixed with a fixed volume of additive (e.g., infusion solution) dispensed from the additive dispensing device. The additive dispensing device can be mechanically controlled by the force of increased fluid pressure (e.g., using a piston pump), or electronically controlled using pressure sensors, valves, and electronic control devices. For example, the additive dispensing device can consist of: an auxiliary chamber divided into two compartments by a movable partition wall, each compartment being connected to a separate opening in the auxiliary chamber to allow additive to flow into or out of the compartment; valves connected to the two openings of the auxiliary chamber; and a device for switching the valves based on the fluid pressure in the main fluid line.

[0153] Alternatively, the uniform fractionation of the fluid can be regenerated by passing them through separate adsorbent compartments, additional filters, or absorbent compartments.

[0154] Additional filters and adsorbent compartments can be configured to allow fluid regeneration without requiring concentrate formulation or additive dispensing devices.

[0155] Compared to developing entirely new dialysis devices, this disclosure allows existing dialysis equipment to be converted into adsorbent-based regeneration devices, overcoming a major hurdle of conventional dialysis equipment (such as HD) that requires large quantities of high-purity water or dialysate. This conversion does not require significant or any alterations to the physical and electronic structure of existing dialysis equipment.

[0156] A dialysate regenerator serves as an accessory to existing dialysis equipment, collecting used dialysate from the drain line, regenerating it into a fresh device, and then returning the fresh dialysate to the dialysis unit. Development efforts for regenerators can focus on optimizing the mechanisms of adsorbent regeneration and / or electrolyte re-infusion. This provides a shorter pathway to meeting patients' needs for HD (e.g., home HD) compared to developing entirely new dialysis equipment. As an added benefit, physicians, nurses, and patients already familiar with and proficient in existing equipment can readily use dialysate regenerators as an adjunct device to operate these devices in adsorbent regeneration mode.

[0157] Dialysis fluid regenerators can be universally connected to a variety of dialysis devices, including HD and PD machines. Dialysis fluid regenerators can be based on existing adsorbent technology and provide an accelerated pathway to bring this technology to patients, combining it with the established safety profiles of existing dialysis devices.

[0158] While this disclosure has been specifically shown and described with reference to particular embodiments, those skilled in the art will understand that various changes in form and detail may be made without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the scope of the invention is defined by the appended claims and is thus intended to include all modifications falling within the meaning and scope of the claims' equivalents.

Claims

1. A dialysate regenerator (100) for connection to a dialysis apparatus, the dialysate regenerator (100) comprising: The regenerator inlet (102) is used to receive dialysate; The regenerator outlet (104) is used to dispense the regenerated dialysate; A hydraulic circuit (110) connected between the regenerator inlet (102) and the regenerator outlet (104) also includes a fluid distribution system (120) to divide the dialysate flow into uniform portions for sequential regeneration; The sequential regeneration includes two alternating states (ST1, ST2), comprising a first state (ST1) and a second state (ST2), and the fluid distribution system (120) comprises: Chamber (121), which includes Movable partition walls (122) divide the interior of the chamber (121) into a first compartment (124) and a second compartment (126). A first opening (128) is used to allow dialysate to be directed into and from the first compartment (124). The first compartment (124) was used for the exchange; A second opening (129) is provided for allowing the exchange of dialysate into and from the second compartment (126); and The fluid distribution system (120) is configured to allow dialysate to flow from the regenerator inlet (102) to one of the first and second compartments (124, 126) in the first state (ST1), and to flow to the other of the first and second compartments (124, 126) in the second state (ST2), wherein dialysate entering one compartment (124, 126) causes displacement of the movable partition wall (122) and dialysate flows out from the other compartment (124, 126).

2. The dialysate regenerator (100) according to claim 1, characterized in that, The hydraulic circuit (110) also includes a flow regulator (130) configured to detect external flow or external pressure from one or both of the regenerator inlet (102) and the regenerator outlet (104) and regulate the internal flow or internal pressure such that the external flow remains constant.

3. The dialysate regenerator (100) according to claim 2, characterized in that, The flow regulator (130) includes dampers (134, 135) for adapting to temporary changes in internal pressure.

4. The dialysate regenerator (100) according to claim 2 or 3, characterized in that, The flow regulator (130) includes a pressure sensor (136) to detect the external pressure at one or both of the regenerator inlet (102) and the regenerator outlet (104), and wherein the flow regulator (130) is configured to regulate the internal flow or internal pressure based on the external pressure detected by the sensor (136).

5. The dialysate regenerator (100) according to claim 2 further comprises a housing (200), The housing (200) includes a base (220) and opposing portions (210) that are releasably attached to each other. The chamber (121) comprises a base (222) and a corresponding portion (212), the base being formed by the base (220) of the housing (200). When the opposing portion (210) and the base (220) are attached to each other, the corresponding portion (212) of the chamber (121) and the base (222) are attached together.

6. The dialysate regenerator (100) according to claim 5, characterized in that, The corresponding part (212) of the chamber (121) is composed of a replaceable box and the base (220) is reusable.

7. The dialysate regenerator (100) according to claim 5, characterized in that, The movable partition wall (122), or one of the multiple partition walls in the case of multiple partition walls, may be attached to the corresponding part (212) of the chamber (121).

8. The dialysate regenerator (100) according to claim 1, characterized in that, The partition wall (122) is a membrane.

9. The dialysate regenerator (100) according to claim 8, characterized in that, The membrane is preformed and variable, such that it protrudes from a first membrane side in the first state (ST1) and from a second membrane side in the second state (ST2).

10. The dialysate regenerator (100) according to claim 8, characterized in that, The first compartment contains a first bag fluidly connected to the first opening (128), and the partition wall (122) is the wall of the first bag, or The second compartment contains a second bag that is fluidly connected to the second opening (129), and the partition wall (122) is the wall of the second bag. Alternatively, the first compartment may contain a first bag fluidly connected to the first opening (128), the partition wall (122) being the wall of the first bag, and the second compartment may contain a second bag fluidly connected to the second opening (129), the partition wall (122) being the wall of the second bag, wherein the wall of the first bag and the wall of the second bag are in contact with each other and form the partition wall (122).

11. The dialysate regenerator (100) according to claim 2, characterized in that, The flow regulator (130) includes a pump (132) for increasing pressure or increasing internal flow.

12. The dialysate regenerator (100) according to claim 11, characterized in that, The pump (132) includes two pump chambers (C1, C2) configured to alternately allow dialysate to flow in and out through openings in the corresponding pump chambers.

13. The dialysate regenerator (100) according to claim 12, characterized in that, The pump (132) is pneumatic, and pumping out the dialysate involves applying pneumatic pressure to the side of the movable pump wall opposite to the dialysate contact side in the corresponding pump chambers (C1, C2).

14. The dialysate regenerator (100) according to claim 12 or 13, further comprising a housing (200), wherein, The pump (132) is connected to the housing (200), and the housing (200) includes opposing portions (210) and a base (220) that are releasably attached to each other.

15. The dialysate regenerator (100) according to claim 14, characterized in that, One of the two pump chambers (C2) is divided into two chambers connected in parallel (131) to the pneumatic pressure receiving side, the two chambers being located on opposite sides of the other of the two pump chambers (C1), such that the tension applied to the housing (200) by one of the two pump chambers (C1, C2) during pumping is symmetrically distributed to the other of the two pump chambers (C1, C2).

16. The dialysate regenerator (100) according to claim 15, characterized in that, The pneumatic pressure receiving side of one of the two pump chambers and the other pneumatic pressure receiving side of the other of the two pump chambers are located on the base (220).

17. The dialysate regenerator (100) according to claim 5, characterized in that, The base (220) is reusable and contains control elements, while the opposing part (210) contains disposable elements.

18. The dialysate regenerator (100) according to claim 5, characterized in that, The base (220) is reusable, and the opposing portion (210) of the housing (200) contains a replaceable box.

19. The dialysate regenerator (100) according to claim 1 further comprises a purification device.

20. The dialysate regenerator (100) according to claim 19 further comprises a regeneration compartment, the regeneration compartment including the purification device.

21. The dialysate regenerator (100) according to claim 19, characterized in that, The purification device includes one or both of an adsorption filter or an adsorbent cartridge.

22. The dialysate regenerator (100) according to claim 19, characterized in that, The hydraulic circuit (110) also includes an infusion fluid inlet and is configured to add a predetermined volume of infusion fluid to the dialysate.

23. The dialysate regenerator (100) according to claim 1 further comprises an additive metering device (400) configured to mix an additive into the dialysate, the additive metering device (400) comprising an additive dispensing system synchronized with the fluid dispensing system dispensing the dialysate.

24. The dialysate regenerator (100) according to claim 19, characterized in that, The hydraulic circuit (110) further includes: The purification device; and At least one reversible retainer, comprising an ion reservoir, The direction in which the dialysate flows through the reversible retainer is reversible.

25. A dialysis system (300), comprising Dialysis equipment (310), comprising: Fresh dialysate inlet (314) Used dialysis fluid output end (312); and The dialysate regenerator (100) according to any one of claims 1 to 24, The regenerator inlet (102) is connected to the used dialysate outlet (312) to receive used dialysate, and the regenerator outlet (104) is connected to the fresh dialysate inlet (314) to dispense regenerated dialysate.

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