Peritoneal dialysis apparatus

Abstract

The present application discloses a peritoneal dialysis device, by adding a preparation such as enzyme-loaded microspheres to a metabolic filtration module, the dialysis effluent from the effluent passage and the enzyme or enzyme preparation or enzyme-loaded microspheres are filtered out after the first toxin treatment, and the dialysis effluent metabolic treatment liquid is filtered out, at the same time, the enzyme or enzyme preparation or enzyme-loaded microspheres are intercepted in the metabolic filtration module, the treated liquid flows out of the metabolic filtration module through the metabolic filtration module, and then is treated by the adsorption device to generate dialysis regeneration liquid, after supplementing potassium, calcium and magnesium ions in the regeneration liquid pipeline, the dialysis regeneration liquid is used for dialysis again, so as to solve the problems of low exchange efficiency in the existing perfusion mode, increase of enzyme dosage, efficiency loss and safety risk of enzyme caused by enzyme shedding and the like.

Description

[0001] This application is a divisional application filed pursuant to Article 48 of the Implementing Regulations of the Patent Law. Its parent application is International Application No. PCT / CN2023 / 131926, with an international filing date of November 16, 2023, a priority date of December 9, 2022, priority number 202211584213.4, and entered the Chinese national phase on April 18, 2024. The national application number is 202380014058.9, and the invention is entitled "Dialysis Fluid Regeneration and Circulation System and Dialysis Equipment." The applicant is Shanghai Xinguang Biomedical Co., Ltd. The entire contents of the parent application are incorporated herein by reference. Technical Field

[0002] This application relates to the technical field of medical devices, and more particularly to a dialysate regeneration and circulation system and peritoneal dialysis equipment used in the field of dialysis. Background Technology

[0003] The Sorbent Dialysis system was originally developed by NASA for the recycling of astronauts' urine. The first commercially available model, the REDY Machine (Regeneration of Dialysate), achieved tremendous commercial success in 1973. Between 1973 and 1994, the REDY system successfully performed 6 million hemodialysis treatments, most of which were conducted at home, demonstrating its convenience, safety, and clinical value. However, the fatal flaw of adsorption dialysis (Achillesheel) was the extremely high cost of consumables, the extremely rigorous training required for its manufacture and maintenance, and the early systems containing biotoxic materials such as aluminum. This ultimately led to its gradual elimination from the market by the Single Pass type (the currently widely used traditional dialysis machine).

[0004] In traditional adsorption dialysis, urease is primarily used to process urea. Uremic patients have lost kidney function, so toxins accumulate in their bodies, including urea. Since all proteins in the body are metabolized into urea and excreted through the kidneys, urea levels in uremic patients are often very high, around 20 mM.

[0005] Urea molecules are highly polar and readily soluble in water, making them virtually unusable for traditional adsorbents, resulting in either extremely poor selectivity or prohibitively high costs. Early scientists used urease to decompose urea, producing carbon dioxide and ammonia, which were then adsorbed using zirconium phosphate. Traditionally, urease is loaded onto alumina microspheres and packed into an adsorption column. Liquid is then perfused in, and the urea is decomposed by the enzyme (though not necessarily completely). Due to the extremely high urea content, the required enzyme dosage is also extremely high. Furthermore, due to the unreliable adsorption, with continuous flushing, significant urease detachment occurs after each treatment, depositing in the downstream adsorption column material, resulting in substantial activity loss. This means that both the adsorption column and the urease can only be used once, greatly increasing the amount of urease used and the cost in adsorption dialysis.

[0006] In the fill perfusion mode, urease is relatively fixed while the liquid flows through, resulting in a much lower probability of collisions compared to homogeneous systems or solutions. This low exchange efficiency necessitates an increase in enzyme dosage to ensure therapeutic efficacy. Previous patents have used urease dosages between 20,000 U and 60,000 U, leading to increased consumable costs. Furthermore, enzyme shedding can result in efficiency loss and safety risks. Consumable costs are a significant limiting factor for the commercial application of regenerable dialysis machines and the promotion of home hemodialysis. Summary of the Invention

[0007] In view of the shortcomings of the above-mentioned related technologies, the purpose of this application is to provide a peritoneal dialysis device to solve the problems of low exchange efficiency in the existing filling perfusion mode, which leads to increased enzyme usage, and enzyme efficiency loss and safety risks due to enzyme shedding.

[0008] To achieve the above and other related objectives, this application provides a peritoneal dialysis device, comprising: a waste fluid passage with its input end connected to the human peritoneal cavity; a metabolic filtration module connected to the output end of the waste fluid passage, used to filter out a metabolically treated dialysis waste fluid after initial toxin treatment of a mixture of dialysis waste fluid from the waste fluid passage and added enzymes or enzyme preparations or enzyme-loaded microspheres; the metabolic filtration module includes a separation component to divide the metabolic filtration module into a first side for connecting the waste fluid passage and a second side for filtering out the metabolically treated dialysis waste fluid, wherein the enzymes or enzyme preparations or enzyme-loaded microspheres are retained on the first side; an adsorption device with its input end connected to the second side of the metabolic filtration module, used to perform a secondary toxin treatment on the metabolically treated dialysis waste fluid after initial toxin treatment to generate a regenerated fluid; a regenerated fluid pipeline with its inlet connected to the adsorption device for outputting the regenerated fluid and its outlet connected to the human peritoneal cavity; a driving device disposed on the peritoneal dialysis pipeline for driving fluid to flow periodically in the peritoneal dialysis pipeline; and a control device for executing a treatment mode to periodically exchange fluid within the human peritoneum.

[0009] In summary, this application provides a peritoneal dialysis device that, by adding a preparation such as enzyme-carrying microspheres to a metabolic filtration module, first-stage toxin treatment is performed on the mixture of dialysis waste liquid from the waste liquid pathway and enzymes, enzyme preparations, or enzyme-carrying microspheres, followed by filtration of the dialysis waste liquid metabolic treatment solution. Simultaneously, the enzymes, enzyme preparations, or enzyme-carrying microspheres are retained in the metabolic filtration module. The treated liquid flows out of the metabolic filtration module and is further treated by an adsorption device to generate dialysis regeneration solution. After supplementing potassium, calcium, and magnesium ions in the regeneration solution pipeline, it is reused in the dialysis process. This solves the problems of low exchange efficiency leading to increased enzyme usage in existing perfusion modes, as well as enzyme efficiency loss and safety risks due to enzyme shedding. Attached Figure Description

[0010] The specific features involved in this application are shown in the appended claims. A better understanding of the features and advantages of the invention can be achieved by referring to the exemplary embodiments and accompanying drawings described in detail below. A brief description of the drawings is as follows:

[0011] Figure 1 The diagram shown is a schematic representation of the dialysate regeneration and circulation system in one embodiment of this application.

[0012] Figure 2 The diagram shown is a schematic diagram of the dialysate regeneration and circulation system of this application in one embodiment.

[0013] Figure 3 The diagram shown is a schematic diagram of the dialysate regeneration and circulation system of this application in another embodiment.

[0014] Figure 4 The diagram shown is a schematic representation of the metabolic cycle device of this application in one embodiment.

[0015] Figure 5 The diagram shown is a schematic representation of the metabolic circulation device of this application in another embodiment.

[0016] Figure 6 The diagram shown is a schematic representation of the metabolic cycle device of this application in another embodiment.

[0017] Figure 7 The diagram shown is a schematic representation of the metabolic cycle device of this application in yet another embodiment.

[0018] Figure 8 The diagram shown is a schematic representation of the metabolic circulation device of this application in another embodiment.

[0019] Figure 9 The diagram shown is a schematic representation of the component architecture of the hemodialysis device of this application in one embodiment.

[0020] Figure 10 The diagram shown is a schematic representation of the composition architecture of the hemodialysis device of this application in another embodiment.

[0021] Figure 11 The diagram shows the structural composition of the hemodialysis device of this application in pre-dilution mode.

[0022] Figure 12 The diagram shows the structural composition of the hemodialysis device of this application in post-dilution mode.

[0023] Figure 13 The diagram shown is a structural schematic of the adsorption device of this application in one embodiment.

[0024] Figure 14 The diagram shown is a structural schematic of the adsorption device of this application in another embodiment.

[0025] Figure 15 The diagram shown is a structural schematic of the adsorption device of this application in another embodiment.

[0026] Figure 16 The diagram shown is a structural schematic of the adsorption device of this application in yet another embodiment.

[0027] Figure 17 The diagram shown is an embodiment of the adsorption device of this application in a regenerated liquid circulation system.

[0028] Figure 18 The diagram shows the location of the replacement fluid branch in the pre-dilution mode of the hemodialysis device of this application.

[0029] Figure 19 The diagram shows the location of the replacement fluid branch in the post-dilution mode of the hemodialysis device of this application.

[0030] Figure 20a and Figure 20b The diagrams show the first and second metabolic circulation pumps of this application connected in parallel upstream or downstream of the metabolic filtration module.

[0031] Figure 21 The diagram shown is a cross-sectional view of a pneumatic fluid pump according to one embodiment of this application.

[0032] Figure 22a and Figure 22b The diagram shown is a structural schematic of the metabolic circulation device of this application in one embodiment. Detailed Implementation

[0033] The following specific embodiments illustrate the implementation of this application. Those skilled in the art can easily understand other advantages and effects of this application from the content disclosed in this specification.

[0034] In the following description, reference is made to the accompanying drawings, which illustrate several embodiments of the present application. It should be understood that other embodiments may also be used, and changes in mechanical composition, structure, electrical, and operation may be made without departing from the spirit and scope of the present application. The following detailed description should not be considered limiting, and the scope of the embodiments of the present application is defined only by the claims of the published patent. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the present application. Spatially related terms, such as “upper,” “lower,” “left,” “right,” “below,” “below,” “lower part,” “above,” “upper part,” etc., may be used herein to illustrate the relationship between one element or feature shown in the figures and another element or feature.

[0035] While the terms first, second, etc., are used in some instances herein to describe various elements or parameters, these elements or parameters should not be limited by these terms. These terms are used only to distinguish one element or parameter from another. For example, a first interface may be referred to as a second interface, and similarly, a second interface may be referred to as a first interface, without departing from the scope of the various described embodiments. Both the first interface and the second interface describe an interface, but they are not the same interface unless the context explicitly indicates otherwise. Similar cases include a first connecting member and a second valve, or a first connecting member and a second valve.

[0036] Furthermore, as used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context indicates otherwise. It should be further understood that the terms “comprising,” “including,” indicate the presence of the stated feature, step, operation, element, component, item, kind, and / or group, but do not preclude the presence, occurrence, or addition of one or more other features, steps, operations, elements, components, items, kinds, and / or groups. The terms “or” and “and / or” as used herein are to be interpreted inclusively, or mean any one or any combination thereof. Thus, “A, B, or C” or “A, B, and / or C” means “any one of: A; B; C; A and B; A and C; B and C; A, B, and C.” Exceptions to this definition occur only when combinations of elements, functions, steps, or operations are inherently mutually exclusive in some way.

[0037] This application discloses a dialysis fluid regeneration and circulation system for use in medical devices, which is used to treat dialysis waste fluid generated during dialysis to generate regenerated fluid before it is introduced into dialysis equipment or the human body.

[0038] In this application, the medical devices include, but are not limited to, blood purification devices, extracorporeal circulation clearance systems, extracorporeal enrichment clearance devices, hemodialysis devices, plasma exchange devices, extracorporeal peritoneal dialysis devices, or extracorporeal membrane oxygenation devices. The blood purification devices include, but are not limited to, hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), hemoperfusion (HP), blood exchange (PE), immunoadsorption (IA), continuous renal replacement therapy (CRRT), and peritoneal dialysis (PD) devices.

[0039] In other embodiments, the medical device may be a module integrated into other extracorporeal circulation devices, such as artificial livers, artificial kidneys, hemodialysis equipment, peritoneal dialysis equipment, plasma exchange equipment, plasma purification equipment, lipid purification equipment, molecular adsorption recirculation systems, extracorporeal membrane oxygenation equipment, leukocyte removal equipment, and extracorporeal life support systems. In some embodiments, the medical device may function as a standalone medical device or treatment device, or it may be integrated into other medical devices or instruments involving the extracorporeal treatment of blood or other bodily fluids to form a new device.

[0040] In this application, "regenerated fluid" refers to dialysis waste fluid after the exchange of dialysate with blood or peritoneal fluid. This waste fluid is treated with adsorbent materials and enzymes (e.g., catalytic decomposition and adsorption treatment) to remove some or most of the toxins or toxic molecules from the dialysis waste fluid, and supplemented with beneficial or essential molecules such as potassium, calcium, and magnesium. The resulting regenerated fluid can be considered as fresh dialysate, and is exchanged with blood or peritoneal fluid again. This cycle is repeated to continuously remove toxins from the blood or peritoneal fluid, achieving the therapeutic goal. Dialysis equipment using this dialysate circulation and regeneration mode is called a dialysate regeneration dialysis machine. It includes dialysate regeneration hemodialysis machines and dialysate regeneration peritoneal dialysis machines. The biggest advantage of this type of dialysis machine is that it does not require a water source or water treatment system, making it very small and portable, suitable for home hemodialysis and wearable dialysis devices.

[0041] The dialysate regeneration and circulation system of this application includes a waste liquid passage, a metabolic circulation device, an adsorption device, and a regeneration liquid pipeline. Please refer to [link / reference]. Figure 1 The diagram shown is a schematic diagram of the composition of the dialysate regeneration circulation system in one embodiment of this application.

[0042] In the following embodiments, the application of a dialysate regeneration and circulation system to a blood purification device will be used as an example for illustration.

[0043] The waste liquid passage L2-1 of the dialysis fluid regeneration and circulation system of this application has an input end 620 connected to the outlet of the dialysis waste liquid; the output end of the waste liquid passage is connected to the metabolic circulation device 60, and the input end of the metabolic circulation device 60 is connected to the outlet of the waste liquid passage L2-1, for performing metabolic circulation of the input dialysis waste liquid for initial toxin treatment; the input end of the adsorption device 61 is connected to the output end of the metabolic circulation device 60, for performing secondary toxin treatment on the waste liquid after the initial toxin treatment by the metabolic circulation device 60 to generate regenerated liquid; the inlet of the regenerated liquid pipeline L2-7 is connected to the adsorption device 61 for outputting the regenerated liquid. In this embodiment, a formulation, such as enzyme-loaded microspheres, can be added to the metabolic circulation device 60. The formulation circulates in the circulation pipeline under the drive of a driving device. Specifically, the dialysis waste liquid containing a high concentration of target molecules is introduced into the metabolic circulation device 60 through the inlet. The target molecule formulation is decomposed into corresponding products. The metabolic filtration module in the metabolic circulation device 60 continuously separates the treated liquid and retains the formulation in the metabolic circulation device 60. The treated liquid flows out of the metabolic circulation device 60 through the metabolic filtration module and is then treated by an adsorption device to produce dialysis regeneration liquid. After potassium, calcium, and magnesium ions are added to the regeneration liquid pipeline L2-7, it is used again in the dialysis process.

[0044] Please see Figure 2 The diagram shown is a schematic diagram of the dialysate regeneration and circulation system of this application in one embodiment.

[0045] In an embodiment where the dialysate regeneration and circulation system is applied to a blood purification device, the input end 620 of the waste fluid passage L2-1 is connected to the dialyzer to obtain dialysis waste fluid from the dialyzer. In this embodiment, the dialyzer is used to purify blood flowing in the blood circuit and forms a blood flow path for patient blood flow and a dialysate flow path for dialysate flow through a built-in purification membrane for blood purification. In this embodiment, the dialyzer includes a dialysate chamber, a blood chamber, and a semi-permeable membrane, which separates the dialysate chamber and the blood chamber from each other. In commonly used capillary dialyzers, the blood chamber is formed by the entire internal volume of a hollow fiber, and the dialysate chamber is formed by the inner cavity of the dialyzer housing surrounding the hollow fiber. In this embodiment, the top end of the dialyzer is connected to the arterial blood line, and the bottom end of the dialyzer is connected to the venous blood line. The type of dialyzer may include hemodialyzers, hemodialysis filters, blood filters, plasma separators, blood-plasma component separators, and other devices of various specifications or uses. Any device capable of separating toxins or molecular components from the blood is eligible for this application.

[0046] The dialysate circuit includes a regenerated liquid line L2-7 connecting the dialysate inlet of the dialyzer and a waste liquid passage L2-1 connecting the dialysate outlet, for inputting dialysate into the metabolic circulation device 60 and outputting it after processing. It should be understood that the dialysate circuit also includes necessary valves, sensors and other necessary components or assemblies.

[0047] In an embodiment where the dialysate regeneration and circulation system is applied to a peritoneal dialysis device, the input end of the waste fluid passage L2-1 is connected to the human peritoneal cavity to obtain dialysis waste fluid from the human peritoneal cavity.

[0048] In one embodiment, the waste fluid passage L2-1 may be a conduit connected by a catheter. It should be understood that the “catheter” or “conduit” disclosed in this application refers to components that can be fluidly connected to each other in order to provide a path for transferring fluids (i.e., saline, dialysate, etc.) between these components.

[0049] In another embodiment, compared with home-use dialysis equipment or portable dialysis equipment, based on the requirements of miniaturization of the overall volume and compactness of the dialysis equipment, the waste liquid passage L2-1 can be in the form of a flow channel, such as a flow channel formed by plates or closed guide grooves. In some necessary structural designs, the flow channel can adopt a multi-layer structure with intervals and stacking.

[0050] In one embodiment, the input end 620 of the waste liquid passage L2-1 is provided with a dialysate outlet valve 621. Specifically, the dialysate outlet valve 621 can be a solenoid valve, an electrically operated valve, or a clamp used to tighten the waste liquid passage L2-1 to close the flow of waste liquid.

[0051] In one embodiment, a leakage sensor 622 is provided in the waste fluid passage L2-1. In an embodiment where the dialysate regeneration circulation system is applied to a blood purification device, the leakage sensor 622 is, for example, a blood leakage sensor for detecting blood leakage; in an embodiment where the dialysate regeneration circulation system is applied to a peritoneal dialysis device, the leakage sensor 622 is, for example, a peritoneal fluid leakage sensor for detecting peritoneal fluid leakage.

[0052] In one embodiment, a pressure sensor 6231' for detecting the pressure of dialysis waste liquid is provided on the waste liquid passage L2-1. A hydrophobic filter 6230 is provided between the waste liquid passage L2-1 and the pressure sensor 6231', and the permeability of the hydrophobic filter 6230 allows the pressure sensor 6231' to detect the pressure of the waste liquid in the waste liquid passage L2-1.

[0053] In one embodiment, an ultrafiltration branch L2-2 is connected to the waste liquid passage L2-1. In this embodiment, the ultrafiltration branch L2-2 is equipped with an ultrafiltration container 6242 for storing ultrafiltrate, and an ultrafiltration pump 6241 for transporting the ultrafiltrate in the ultrafiltration container 6242 to the waste liquid passage L2-1. An ultrafiltration filter 6240 may be provided between the ultrafiltration pump 6241 and the waste liquid passage L2-1. In one example, the ultrafiltration container 6242 is, for example, an ultrafiltration bag, such as a liquid bag made of medical plastic; the ultrafiltration pump 6241 can be a plunger pump, a peristaltic pump, or a diaphragm pump, etc.

[0054] In embodiments where the dialysate regeneration and circulation system is applied to blood purification equipment, such as in hemodialysis treatment mode (HD), i.e., standard normal treatment mode, since the exchange between molecules is a free exchange driven by concentration difference, the purpose of exchange and removal of toxins is achieved. Since an ultrafiltration branch L2-2 is set on the waste liquid passage L2-1, ultrafiltration dehydration can be carried out simultaneously, which will bring an additional amount (e.g., 3-4L) of transmembrane flow.

[0055] In one embodiment, when the dialysate regeneration circulation system is applied to the blood purification equipment, the ultrafiltration pump 6241 continuously extracts water from the waste fluid passage L2-1, creating a transmembrane negative pressure. At this time, the dialyzer will filter more water to achieve pressure balance. Ultimately, the amount of water extracted by the ultrafiltration pump 6241 corresponds to the amount of water lost from the blood, thus helping the body remove excess water. In a practical embodiment, the ultrafiltration pump 6241 continuously pumps the dialysis waste fluid from the waste fluid passage L2-1 into a waste fluid bag. By accurately measuring the flow rate of the ultrafiltration pump 6241, excess water can be precisely extracted from the patient's body, thereby achieving dehydration.

[0056] In another embodiment, the ultrafiltration branch L2-2 can also be located on the regenerated liquid pipeline L2-7. That is, the ultrafiltration branch L2-2 includes a first ultrafiltration branch and a second ultrafiltration branch, wherein the first ultrafiltration branch is located on the waste liquid channel, and the second ultrafiltration branch is located on the regenerated liquid pipeline L2-7. In this embodiment, a weighing-type ultrafiltration control is adopted, that is, dual-pump control using an upstream pump and a downstream pump. The upstream pump is located on the first ultrafiltration branch, and the downstream pump is located on the second ultrafiltration branch in the regenerated liquid pipeline L2-7. The container connected to the filter branch, such as an ultrafiltration bag, contains the treated dialysis regeneration solution. Below the ultrafiltration bag is a weighing device. This device can determine the content of the regeneration solution inside the ultrafiltration bag by weighing it. The speed of the upstream and downstream pumps can be adjusted accordingly. For example, if the water content in the ultrafiltration bag exceeds a preset value (ultrafiltration curve), it indicates that too much water has been filtered out, so the speed of the upstream pump is reduced while the speed of the downstream pump is increased. Conversely, if the water content in the ultrafiltration bag is below the preset value (ultrafiltration curve), the speed of the upstream pump is increased while the speed of the downstream pump is decreased.

[0057] In one embodiment, a pre-prepared liquid bypass L2-3 is provided on the waste liquid passage L2-1 for pre-filling, emptying, or flushing the circulation passage of the dialysate regeneration circulation system. In this embodiment, a short-circuit valve 626 is provided on the waste liquid passage L2-1 in parallel with the pre-prepared liquid bypass L2-3.

[0058] In one embodiment, the pre-prepared liquid bypass L2-3 is a system for pre-filling and emptying a purification circuit, which is connected to a storage container in the circulation circuit (e.g., a...). Figure 2 The pre-filled liquid bag 625 shown (e.g., a liquid bag made of medical plastic) and, in conjunction with the working mode of the drive device, or the upright or inverted state of the liquid storage container, can realize two operations: pre-filling and emptying. That is, in the pre-filling mode, the outlet of the liquid in the liquid storage container is at a low position; while in the emptying mode, the outlet of the gas in the liquid storage container is at a high position. Compared with the conventional operation in the prior art, the system structure of this application is simple, easy to operate, and has a low learning cost. It does not require the operator to repeatedly invert the dialyzer for continuous pre-filling. Furthermore, the system of this application allows for more scientific treatment of tubing and waste liquid and other medical waste after emptying.

[0059] In this embodiment, the pre-filling and emptying purification circuit system includes a liquid storage container (i.e., Figure 2 The pre-formed liquid bag 625 shown), and the circulation loop (i.e. Figure 2 The circulation loop consisting of waste liquid passage L2-1 and regenerated liquid pipeline L2-7, and the drive device (i.e. Figure 2The dialysate pump 627). The storage container, used to store pre-filled liquid and recover emptied waste liquid, includes a container body and a first and a second interface on the container body for use as liquid and / or gas inlets / outlets; the first or second interface is both the inlet / outlet of fluid within the container body. For example, the first and second interfaces are... Figure 2 The first interface b1 and the second interface b2 of the pre-formed liquid bag 625 shown.

[0060] In this embodiment, the liquid storage container can switch between two states: upright and inverted. That is, the state of the liquid storage container being placed upright is upright, and the state of the liquid storage container being placed upside down is inverted. In order to switch between the two states more easily, a mechanism for uprighting or inverting the liquid storage container is also included. In one embodiment, the mechanism is, for example, a plate or frame for placing the liquid storage container. The plate or frame is provided with a structure for fixing the liquid storage container and a positioning structure for positioning the upright and inverted states, so that the liquid storage container can be stabilized when it is upright, or can be stabilized when it is inverted.

[0061] In this embodiment, the liquid storage container in the pre-filling and purging purification circuit system has two operating modes: in pre-filling mode, the liquid outlet of the liquid storage container is at a low position; in purging mode, the gas outlet of the liquid storage container is at a high position. For example, in pre-filling mode, the second interface is at a lower height, allowing the pre-filled liquid in the liquid storage container to preferentially enter the pipeline in the circulation loop from the second interface; while in purging mode, the first interface is at a higher height, allowing the gas / bubbles in the liquid storage container to preferentially enter the pipeline in the circulation loop from the first interface. In this application, the switching between the pre-filling mode and the purging mode can be achieved by adjusting the fluid flow direction and / or switching the liquid storage container to be upright or inverted.

[0062] In some embodiments, the pre-prepared liquid bypass is, for example, the pre-filling and purging purification circuit system described in patent document CN2022108507945; the full text of patent document CN2022108507945 is incorporated herein by reference.

[0063] In one embodiment, such as Figure 1 and Figure 2As shown, a dialysate pump 627 is installed on the waste liquid passage L2-1 to drive the fluid in the waste liquid passage L2-1 to flow forward or backward. In this embodiment, when the dialysate pump 627 rotates forward, it drives the dialysis waste liquid in the waste liquid passage L2-1 to flow downstream to the metabolic circulation device 60; when the dialysate pump 627 rotates backward, it drives the reverse flow in the waste liquid passage L2-1, such as in the working mode where the pre-prepared liquid bypass L2-3 needs to be flushed or emptied. The dialysate pump 627 includes a peristaltic pump, a diaphragm pump, a gear pump, or other drive pumps used to drive the liquid flow.

[0064] In one embodiment, a first dialysate pump is installed on the waste liquid passage, and a second dialysate pump is installed on the regenerated liquid pipeline, used to change the total liquid equilibrium volume of the dialysate regeneration circulation system by means of the differential speed of the first and second dialysate pumps; please refer to Figure 3 The diagram shown is a schematic of the dialysate regeneration circulation system of this application in another embodiment. A second dialysate pump 627” is simultaneously installed on the regeneration fluid pipeline L2-7. It drives the flow of the entire dialysate circulation in the same direction and flow rate as the first dialysate pump 627’ on the waste fluid passage L2-1. This design can significantly reduce the pressure on the adsorption device 61. In some embodiments, the speeds of the first dialysate pump 627’ and the second dialysate pump 627” are different to increase or decrease the metabolic circulation and / or the solution volume of the adsorption device 61, in order to achieve controllable and measurable ultrafiltration or filtration. When achieving ultrafiltration, additional weighing or volume detection methods are often required to determine the ultrafiltration volume. When achieving periodic blood filtration, the difference in the speeds of the two pumps is often periodic or dynamically adjusted according to the filtration volume or pressure.

[0065] In one embodiment, a temperature control device 628' is provided on the waste liquid passage L2-1 to control the temperature of the fluid in the waste liquid passage L2-1 to a preset range.

[0066] In another embodiment, a temperature control device 628” is provided on the regenerated liquid pipeline L2-7 to control the temperature of the fluid in the regenerated liquid pipeline L2-7 to a preset range.

[0067] exist Figure 3 In the illustrated embodiment, temperature control devices (628', 628") are respectively installed on the waste liquid passage L2-1 and the regenerated liquid pipeline L2-7. In the above embodiment, the temperature control device is a heating device or a constant temperature device.

[0068] In one embodiment, a sample dispensing device (not shown) is provided on the waste liquid passage L2-1 for adding an enzyme preparation (enzyme-carrying microspheres containing urease) to allow it to enter the metabolic circulation device 60. In this embodiment, the sample dispensing device may be, for example, an opening in the waste liquid passage L2-1, or an injection port, etc.

[0069] In another embodiment, the sampling device may also be disposed on the collection container 600 of the metabolic circulation device 60.

[0070] In this embodiment, the enzyme-loaded microspheres are microspheres immobilized with urease, with a size between 1-1000 μm, preferably 20-50 μm, and are not limited to the material or immobilization process of the microspheres. The enzyme-loaded microspheres are generally injected into a collection container as a solution before treatment and then enter circulation.

[0071] The metabolic circulation device 60 is a universal, platform-type device. When different enzyme preparations (enzyme-loaded microspheres) are added, different molecules can be cleared or have different catalytic decomposition or synthesis effects. For example, adding ethanol oxidase microspheres can oxidize ethanol, uric acid oxidase microspheres can oxidize uric acid, and phenylalanine ammonia-lyase microspheres can decompose phenylalanine. Therefore, theoretically, as long as there is an enzyme with corresponding decomposition or synthesis function, the concentration of dialysis waste liquid as any target molecule can be changed, thereby changing the concentration of blood as the target molecule to achieve the therapeutic purpose.

[0072] In one embodiment, the enzyme, enzyme preparation, or enzyme-carrying microspheres in the metabolic cycle are in a flowing state. Specifically, the enzyme, enzyme preparation, or enzyme-carrying microspheres added to the metabolic cycle device 60 flow along with the circulating liquid participating in the cycle within the metabolic cycle device 60. The circulating liquid refers to any liquid flowing within the metabolic cycle device 60, such as dialysis waste to be treated or dialysis waste that has undergone at least one treatment. In this way, the enzyme, enzyme preparation, or enzyme-carrying microspheres can be evenly distributed in the metabolic cycle pipeline through circulation, thereby solving the problem of decreased metabolic efficiency caused by the aggregation of the enzyme, enzyme preparation, or enzyme-carrying microspheres and improving the utilization rate of the enzyme, enzyme preparation, or enzyme-carrying microspheres. In one embodiment, the flow rate of the circulating liquid in the metabolic cycle is greater than the flow rate of the liquid in the waste liquid passage or regenerated liquid passage. In one example, the flow rate of the circulating liquid in the metabolic cycle is 4 to 7 times the flow rate of the liquid in the waste liquid passage or regenerated liquid passage. For example, the flow rate of the liquid in the waste liquid passage or regenerated liquid pipeline is 500 ml / min, and the flow rate of the circulating liquid in the metabolic cycle is 2000 ml / min. This allows the circulating liquid to circulate rapidly within the circulation device for multiple filtrations. It should be noted that although the example given is that the flow rate of the circulating liquid in the metabolic cycle is greater than that of the liquid in the waste liquid passage or regenerated liquid pipeline, this is not a limitation. In other embodiments, the flow rate of the circulating liquid in the metabolic cycle can also be equal to the flow rate of the liquid in the waste liquid passage or regenerated liquid pipeline.

[0073] In one embodiment, the initial toxin treatment of the metabolic circulation device 60 is to remove urea from the dialysis waste by adding enzymes or enzyme preparations or enzyme-loaded microspheres. In this application scenario, it is mainly for patients with renal dysfunction or renal failure, or patients undergoing peritoneal dialysis or hemodialysis treatment.

[0074] When using the metabolic circulation device 60, the enzyme-carrying microspheres added to its metabolic circulation pipeline L2-4 contain urease. Urease decomposes urea to produce carbon dioxide and ammonia. Part of the produced carbon dioxide dissolves in the liquid, forming a buffer system, and part forms gas, causing the liquid level in the collection container 600 in the metabolic circulation pipeline L2-4 to drop. When the liquid level sensor 602 detects that the liquid level in the collection container 600 has reached a preset low level, the three-way valve, four-way valve, or flow channel switching device on the gas branch is activated to discharge excess carbon dioxide. In an embodiment, the urea content in the blood is detected by detecting the pH, urea concentration, or ammonia concentration of the metabolic circulation or metabolic circulation effluent, and the amount of urea removed, the usage of OCM or adsorbent is calculated, and displayed or prompted. By comparing with empirical or historical values, the enzyme activity is reflected or detected, and the operator is prompted to add or replace the enzyme preparation.

[0075] In use, enzyme-carrying microspheres can be added to the metabolic cycle. The enzyme-carrying microspheres circulate in the metabolic cycle pipeline L2-4 driven by the metabolic cycle pump. The treatment method is that the liquid to be treated containing a high concentration of target molecules enters the metabolic cycle pipeline L2-4 through the inlet. The target molecules are decomposed into corresponding products by the enzyme-carrying microspheres. The metabolic filtration module 605 continuously separates the treated liquid out, retaining the enzyme-carrying microspheres in the metabolic cycle pipeline L2-4. The treated liquid flows out of the metabolic cycle module through the metabolic filtration module 605.

[0076] In one embodiment, the metabolic circulation device 60 includes: a collection container 600, a metabolic circulation pipeline L2-4, a metabolic circulation pump 606, and a metabolic filtration module 605. In this embodiment, the metabolic circulation device 60 adds the dialysis waste liquid to be treated into the metabolic circulation pipeline L2-4 and drives the circulating liquid flow through the metabolic circulation pump 606. The circulating liquid flow is treated to selectively change the structure or concentration of molecules or molecular combinations in the liquid flow. During this process, the treated dialysis waste liquid in the circulation is allowed to leave the circulation as a metabolic treatment solution, while a residual amount of the mixed enzyme-carrying microspheres is retained in the circulation.

[0077] Please see Figure 4 The figure shows a schematic diagram of the metabolic circulation device of this application in one embodiment. As shown, in this embodiment, one end of the metabolic circulation pipeline L2-4 is connected to the second interface a2 of the collection container 600, and the other end is connected to the third interface a3 of the collection container 600, thereby forming a circulation loop. In this embodiment, the metabolic circulation pump 606 is disposed on the metabolic circulation pipeline L2-4 to drive the enzyme-carrying microspheres and dialysis waste liquid mixed in the collection container 600 to circulate in the metabolic circulation pipeline L2-4. The metabolic filtration module 605 is disposed on the metabolic circulation pipeline L2-4 to treat the mixture of enzyme-carrying microspheres and dialysis waste liquid circulating in the metabolic circulation pipeline L2-4 with toxins, retain the enzyme-carrying microspheres in the metabolic circulation pipeline L2-4, and filter out the metabolic treatment liquid of the dialysis waste liquid.

[0078] In one embodiment, the device further includes a means for controlling the metabolic circulation pump 606 to dynamically balance the total fluid volume in the metabolic circulation pipeline L2-4 under metabolic circulation mode. That is, by controlling the flow rate of the dialysis waste liquid introduced into the circulation and the metabolic treatment liquid of the dialysis waste liquid leaving the circulation in any circulation to maintain the dynamic balance of the total fluid volume in the circulation, the liquid to be treated containing a high concentration of target molecules enters the circulation through the inlet, the target molecules are decomposed into corresponding products by enzyme-loaded microspheres, the metabolic filtration module 605 in the metabolic circulation device 60 continuously separates the treated liquid out, retains the enzyme-loaded microspheres in the circulation, and the treated liquid flows out of the metabolic circulation module through the metabolic filtration module 605.

[0079] In one embodiment, the metabolic circulation pump disposed on the metabolic circulation pipeline includes a first metabolic circulation pump and a second metabolic circulation pump, wherein the first metabolic circulation pump is disposed upstream of the metabolic filtration module, and the second metabolic circulation pump is disposed downstream of the metabolic filtration module. Please refer to [link to relevant documentation]. Figure 5 The figure shows a schematic diagram of the metabolic circulation device of this application in another embodiment. As shown, the total liquid equilibrium volume of the metabolic circulation pipeline L2-4 is changed by the differential speed of the first metabolic circulation pump 606' and the second metabolic circulation pump 606". Figure 5 In the illustrated embodiment, the first metabolic circulation pump 606' and the second metabolic circulation pump 606" are, for example, peristaltic pumps.

[0080] In another embodiment, the metabolic circulation pump disposed on the metabolic circulation pipeline includes a first metabolic circulation pump disposed upstream or downstream of the metabolic filtration module and a second metabolic circulation pump connected in parallel with the first metabolic circulation pump. See also... Figure 20a and Figure 20b The figures show schematic diagrams of the first and second metabolic circulation pumps of this application connected in parallel upstream or downstream of the metabolic filtration module. As shown, the first metabolic circulation pump 607' and the second metabolic circulation pump 607" are connected in parallel on the metabolic circulation pipeline L2-4. Liquid in the collecting container 600 flows into the metabolic circulation pipeline L2-4 from the second interface a2. After passing through the metabolic filtration module and the first metabolic circulation pump 607', the liquid flows back into the collecting container 600 from the third interface a3. Furthermore, after passing through the metabolic filtration module and the second metabolic circulation pump 607", the liquid can also flow back into the collecting container 600 from the third interface a3.

[0081] The first metabolic circulation pump 607' and the second metabolic circulation pump 607" are pneumatic fluid pumps. Correspondingly, valves (not shown) are provided on both sides of the first metabolic circulation pump 607' and the second metabolic circulation pump 607" respectively. The valves can be pneumatic fluid valves or clamp valves, etc. The pneumatic fluid pump uses positive and negative pressure gas introduced through a pneumatic interface to control the forward or reverse flow of fluid in the fluid channel. In other words, the pneumatic fluid pump uses positive and negative pressure gas introduced through a pneumatic interface to control the forward or reverse flow of fluid in the metabolic circulation pipeline. The fluid channel is the part of the metabolic circulation pipeline that is connected to the pneumatic fluid pump and the pneumatic fluid valve. Figure 20a As shown, the inlet of the pneumatic fluid pump is connected to the second interface a2, and the outlet of the pneumatic fluid pump is connected to the metabolic filtration module. In this case, the pneumatic fluid pump can control the fluid to flow in the forward direction in the fluid channel. Conversely, if the inlet is connected to the metabolic filtration module and the outlet is connected to the second interface a2, the fluid can be controlled to flow in the reverse direction in the fluid channel.

[0082] In one embodiment, the pneumatic fluid pump is used to push fluid into its fluid channel using positive pressure gas introduced through the pneumatic interface, and to draw fluid into its fluid channel using negative pressure gas introduced through the first pneumatic interface. See also... Figure 21 The figure shows a cross-sectional view of a pneumatic fluid pump in one embodiment of this application. As shown, the pneumatic fluid pump includes a fluid chamber 6071, a pneumatic diaphragm 6070, and a gas chamber 6072. During fluid suction, the valve on the inlet 6080 side of the pneumatic fluid pump is open, and the valve on the outlet 6081 side is closed. The gas chamber 6072 is under negative pressure, causing the pneumatic diaphragm 6070 to deform upwards. Fluid is drawn from the inlet 6080 into the fluid chamber 6071 through the fluid channel 608. During fluid discharge, the valve on the inlet 6080 side is closed, and the valve on the outlet 6081 side is open. The gas chamber 6072 is under positive pressure, causing the pneumatic diaphragm 6070 to deform downwards. The fluid in the fluid chamber 6071 is discharged through the fluid channel 608 to the outlet 6081.

[0083] In one embodiment, the fluid cavity 6071 is formed on the flow channel plate 610, and further, the fluid channel 608 communicating with it can also be disposed on the flow channel plate 610. Specifically, multiple recesses, grooves, openings, and other structures reserved on the flow channel plate 610 form the fluid cavity 6071 and the fluid channel 608. In one embodiment, the flow channel plate 610 is injection molded from PMMA, PVC, or PC plastic.

[0084] In one embodiment, the fluid cavity 6071 is formed inside the flow channel plate 610. The inside of the flow channel plate 610 is the side of the flow channel plate 610 closest to the pneumatic diaphragm 6070. In one example, the fluid cavity 6071 is a cavity formed by a recess in the inside of the flow channel plate 610, directed away from the pneumatic diaphragm 6070. The recessed surface of the fluid cavity can be arc-shaped, curved, or similar.

[0085] In one embodiment, a first surface of the pneumatic diaphragm 6070 covers the fluid cavity 6071. The first surface is the surface facing the flow channel plate 610, and the second surface is the surface away from the flow channel plate 610. The first surface of the pneumatic diaphragm 6070 covering the fluid cavity 6071 is used to change the volume of the fluid cavity 6071 under pressure, so that the fluid cavity 6071 pushes fluid into the fluid channel 608 or draws fluid from the fluid channel 608.

[0086] In one embodiment, the pneumatic diaphragm is made of silicone rubber or PVC film. The pneumatic diaphragm deforms under force, and returns to its original state / shape after the force is removed. Specifically, when the pneumatic diaphragm deforms downwards under force, the cavity pressure within the fluid cavity is positive. Conversely, when the pneumatic diaphragm deforms upwards under force, the cavity pressure within the fluid cavity is negative.

[0087] The gas cavity 6072 is covered by the second surface of the pneumatic diaphragm 6070. In other words, the upper side of the pneumatic diaphragm 6070 is the gas cavity 6072, and the lower side of the pneumatic diaphragm 6070 is the corresponding fluid cavity 6071.

[0088] In one embodiment, the gas chamber 6072 is disposed on the air duct plate 611, which is combined with the flow channel plate 610 and the pneumatic diaphragm 6070 of the fluid pump 6071. In one embodiment, after the air duct plate 611 and the flow channel plate 610 are combined, they clamp the pneumatic diaphragm 6070 in the middle. In one embodiment, the air duct plate is injection molded from PMMA, PVC, or PC plastic. The air duct plate has multiple recesses, grooves, openings, and other structures.

[0089] In one embodiment, the gas chamber 6072 is formed inside the air duct plate 611. Multiple recesses, grooves, openings, and other structures pre-reserved on the air duct plate 611 form the gas chamber 6072. The fluid chamber 6071, the gas chamber 6072, and the pneumatic diaphragm 6070 between them constitute the pneumatic fluid pump described above.

[0090] The gas chamber 6072 has an opening 6074 for connecting to an external gas passage. The opening 6074 provides positive or negative pressure airflow into the gas chamber 6072 to drive the pneumatic diaphragm 6070 to change the volume of the fluid chamber 6071. When there is positive pressure airflow in the gas chamber 6072, the pneumatic diaphragm 6070 deforms downward under force; when there is negative pressure airflow in the gas chamber 6072, the pneumatic diaphragm 6070 deforms upward under force.

[0091] For this purpose, a pneumatic interface 609 communicating with the air vent 6074 is also provided on the outer side of the airway plate 611. The pneumatic interface 609 communicates with the pneumatic system of the dialysis device so that the pneumatic system can provide positive or negative pressure airflow to the gas chamber 6072 to control the forward or reverse flow of the fluid in the fluid channel 608.

[0092] In one embodiment, the flow channel plate and the air duct plate can be joined together by means of bonding, welding, snap-fitting, or screw fixing, and the pneumatic diaphragm is clamped between the flow channel plate and the air duct plate. Pre-fixing the flow channel plate, the pneumatic diaphragm, and the air duct plate together ensures the sealing between the pneumatic diaphragm and the flow channel plate and the air duct plate, thereby ensuring the airtightness of the air-driven system.

[0093] In one embodiment, a sealing ring 6073 is further provided on the pneumatic diaphragm to achieve a seal between the pneumatic diaphragm and the fluid cavity and / or the gas cavity. The sealing ring can be provided on the pneumatic diaphragm by means of adhesive or other methods, or it can be integrally formed with the pneumatic diaphragm.

[0094] Setting the first metabolic circulation pump 607' and the second metabolic circulation pump 607" as pneumatic fluid pumps can not only realize the function of traditional peristaltic pumps, but also reduce the number of electrical components in the dialysate regeneration circulation system and the dialysis equipment including the dialysate regeneration circulation system, thereby reducing the complexity of the equipment and improving the integration of the equipment.

[0095] Because the pneumatic fluid pump alternates between suction and discharge, it cannot suction fluid while discharging fluid, and vice versa. To ensure a continuous flow of fluid in the metabolic circulation pipeline and to prevent blockage by enzymes, enzyme preparations, or enzyme-carrying microspheres in the metabolic cycle, the first metabolic circulation pump 607' and the second metabolic circulation pump 607" operate alternately to drive the liquid flow in the metabolic cycle. For example, when the first metabolic circulation pump 607' suctions liquid, the second metabolic circulation pump 607" discharges fluid; conversely, when the first metabolic circulation pump 607' discharges liquid, the second metabolic circulation pump 607" suctions fluid. This ensures a continuous flow of fluid in the metabolic circulation pipeline.

[0096] In one embodiment, the valves disposed on both sides of the first metabolic circulation pump 607' and the second metabolic circulation pump 607" are pneumatic fluid valves. The structure of the pneumatic fluid valve is similar to that of the pneumatic fluid pump. The pneumatic fluid valve also includes a fluid chamber, a pneumatic diaphragm, and a gas chamber. When a positive pressure airflow is introduced into the gas chamber, the pneumatic diaphragm is deformed downward by force, and the pneumatic fluid valve closes. When a negative pressure airflow is introduced into the gas chamber, the pneumatic diaphragm is deformed upward by force, and the pneumatic fluid valve opens. In one embodiment, the fluid chamber and the gas chamber of the pneumatic fluid valve can also be integrated into the flow channel plate and the air channel plate respectively. The pneumatic diaphragm of the pneumatic fluid valve and the pneumatic diaphragm of the pneumatic fluid pump can be integral or independent.

[0097] To reduce the manufacturing cost of the equipment, the pneumatic fluid pump and the pneumatic fluid valve in the metabolic circulation device are usually shared by a single pneumatic system. When the two share a single pneumatic system, when the pneumatic system supplies the pneumatic fluid pump and the pneumatic fluid valve with the same positive pressure airflow, the fluid in the fluid chamber of the pneumatic fluid pump will be rapidly pushed into the fluid channel, causing turbulence. This will further damage the microstructure of the enzyme, enzyme preparation, or enzyme-carrying microspheres.

[0098] To this end, the pneumatic interface of the pneumatic fluid pump is equipped with a gas damping element, which limits the instantaneous flow rate of airflow entering the gas chamber of the pneumatic fluid pump. Specifically, when the positive pressure airflow passes through the gas damping element, the instantaneous flow rate of the airflow is reduced, thereby causing the fluid in the fluid chamber of the pneumatic fluid pump to be smoothly pushed into the fluid channel, avoiding turbulence and preventing damage to the microstructure of the enzyme, enzyme preparation, or enzyme-carrying microspheres.

[0099] In one example, the gas damping element is disposed at the inlet end of the pneumatic interface. In other examples, the gas damping element may also be disposed at any position on the gas supply connection pipeline connecting the positive pressure gas source of the pneumatic system to the pneumatic fluid pump.

[0100] In some embodiments, the gas damping element is a small-diameter pipe. For example, the diameter of the gas damping element is 1 / 2 to 1 / 10 of the diameter of the pneumatic interface. Alternatively, the diameter of the gas damping element may be 1 / 2 to 1 / 10 of the diameter of the gas source connection pipe. The small-diameter pipe limits the instantaneous flow rate of air entering the gas chamber of the pneumatic fluid pump. In another embodiment, the gas damping element is, for example, an airflow regulating valve. This airflow regulating valve is a high-frequency valve, which, through high-frequency shut-off and opening, can limit the instantaneous flow rate of air entering the gas chamber of the pneumatic fluid pump.

[0101] Please see Figure 6 The figure shows a schematic diagram of the metabolic circulation device of this application in another embodiment. As shown, in this embodiment, the first interface a1 of the collecting container 600 is connected to the output end of the waste liquid passage L2-1. The collecting container 600 includes a liquid storage space 6001 located in the lower part of the cavity and a gas collection space 6000 located in the upper part of the cavity. That is, the collecting container 600 is functionally divided into two spaces: the upper gas collection space 6000 is used for gas collection, and the lower liquid storage space 6001 is used for collecting liquid passing through the collecting container 600. That is, the collecting container 600 has a gas-liquid separation layer. The liquid in the collecting container 600 flows into the metabolic circulation pipeline L2-4 through the second interface a2 and then flows back into the collecting container 600 through the third interface a3. Of course, when the metabolic circulation pump 606 reverses, the liquid in the collecting container 600 flows into the metabolic circulation pipeline L2-4 through the third interface a3 and then flows back into the collecting container 600 through the second interface a2. In this embodiment, a fourth interface a4 is provided on the top of the collecting container 600 for connecting to the gas branch L2-5.

[0102] In this embodiment, the liquid storage space 6001 includes a first extension 60010 and a second extension 60011 extending downwards respectively; wherein, the second interface a2 is located at the bottom end of the first extension 60010; the third interface a3 is located at the bottom end of the second extension 60011, and the isolation portion 60012 is higher than the second interface a2 and the third interface a3. In this embodiment, to ensure that the inlet and outlet of the liquid storage space 6001 are at the lowest position, the second interface a2 and the third interface a3 are respectively located at the bottom ends of the downwardly extending first extension 60010 and the second extension 60011, so that regardless of whether the fluid flows from the second interface a2 to the third interface a3 or from the third interface a3 to the second interface a2, the fluid flows from bottom to top within the collecting container 600. In this embodiment, both the first extension 60010 and the second extension 60011 of the liquid storage space 6001 extend downwards. It should be understood that "extending downwards" can mean extending vertically downwards or extending downwards at an angle.

[0103] In another embodiment, one of the first extension and the second extension of the liquid storage space extends horizontally and the other extends downward, so that the first extension and the second extension have an incident angle. In specific implementation, the angle of the incident angle can be designed according to parameters such as the actual fluid velocity, bubble content, or fluid flow rate.

[0104] In an embodiment, the length of the first extension with the second interface or the second extension with the third interface is related to the flow rate, bubble content, or flow rate of the fluid in the liquid storage space; or the length of the isolation portion located in the first extension and the second extension is related to the flow rate, bubble content, or flow rate of the fluid in the liquid storage space; or the shortest flow distance of the fluid from one of the second interface or the third interface to the other interface is related to the flow rate, bubble content, or flow rate of the fluid.

[0105] In an embodiment, for example, a liquid flows from a first extension with a second interface through the internal space of a collecting container to a second extension with a third interface. The shortest flow distance of the liquid is controlled by designing the internal structure of the collecting container and the relative positions of the second and third interfaces, so that bubbles in the liquid can float and escape, achieving the purpose of gas-liquid interface separation. The shortest flow distance of the liquid is related to the bubble content, flow rate, or flow rate of the liquid. For example, the higher the bubble content, the faster the flow rate, or the larger the flow rate, the longer the shortest flow distance of the liquid needs to be designed in practice. Corresponding to different embodiments, for example, in one example, the higher the bubble content in the liquid, or the faster the flow rate, the longer the length of the first extension or the second extension; in another example, the higher the bubble content in the liquid, or the faster the flow rate, or the larger the flow rate, the longer the length of the isolation portion located in the first extension and the second extension; in yet another example, the higher the bubble content in the liquid, or the faster the flow rate, or the larger the flow rate, the longer the shortest flow distance required for the fluid to flow from one of the second interface or the third interface to the other interface.

[0106] In this embodiment, in order to adjust the flow resistance of the fluid passing through the gas collecting cavity or to generate turbulence, or to adjust the flow rate of the fluid passing through the gas collecting cavity so that the gas / bubbles carried in the fluid are enriched above the liquid surface in the storage space, the length of the first extension and / or the second extension can be appropriately increased or decreased in practical applications; of course, the above purpose can also be achieved by changing the length of the isolation portion between the first extension and the second extension. In some embodiments, the isolation portion is a stepped structure relative to the first extension and / or the second extension; the isolation portion is an arched structure relative to the first extension and / or the second extension; or the isolation portion is a baffle structure extending upward from the bottom of the gas collecting cavity; for example, the gas collecting cavity is generally A-shaped, inverted V-shaped, inverted U-shaped, n-shaped, or "mountain"-shaped, etc., with a bottom extension.

[0107] It should be noted that, in order to better achieve gas-liquid separation, in one embodiment of this application, the cross-sectional area of ​​the fluid flowing from one of the second or third interfaces to the other is larger than the cross-sectional area of ​​the second or third interface. That is, by designing a redundant space in the internal space of the gas collecting chamber or the flow channel of the fluid, the cross-sectional area of ​​the liquid flow path is made much larger than the cross-sectional area of ​​the interface (second or third interface) to reduce the liquid flow rate and increase the gas escape time. For example, when the liquid flows horizontally, the cross-sectional area in the horizontal direction gradually increases, the flow rate gradually decreases, and the flow rate is consistent, so that the gas can escape easily.

[0108] In one embodiment, such as Figure 6 As shown, the first interface a1 of the collection container 600 is connected to the output end of the waste liquid passage L2-1, and has a function for mixing the added enzyme-carrying microspheres and dialysis waste liquid to ensure sufficient contact. In this embodiment, the collection container 600 is provided with a sample dispensing port (not shown) for adding enzyme preparations (enzyme-carrying microspheres containing urease). Specifically, the sample dispensing port includes a valve or clamp for opening and closing the port, and the shape of the port can be designed for easy connection with a syringe, while also having a certain degree of airtightness. The collection container 600 is, for example, a transparent liquid bag, such as a liquid bag made of medical plastic.

[0109] In some embodiments, the sampling port of the metabolic circulation device is further equipped with a sampling device for adding, supplementing, or replacing reaction substrates, catalytic units, drugs, and other cofactors or activators into the metabolic circulation pipeline L2-4. In this example, the sampling device can serve as a processing unit, allowing for manual or computational control of the addition, supplementation, or replacement of catalytic units, reaction substrates, activators, etc., into the metabolic circulation pipeline L2-4, thereby achieving fluid processing. In practical scenarios, the sampling device can also be used to control the concentration of catalytic units in the circulation. For example, when the concentration of the target substance in the fluid to be treated varies, the amount of catalytic unit added to the pipeline can be controlled to achieve a preset reaction effect.

[0110] The sample dispensing device can be an integral component with the tubing, or it can have two opposing inlets to connect the tubing and ensure fluid circulation. Through the sample dispensing device, the catalytic unit or reaction substrate can be immediately added to the metabolic circulation tubing L2-4; wherein, the reaction substrate can be any component in the fluid to be treated or a substance that can react with any component in the fluid to be treated, and the reaction includes, but is not limited to, biological, chemical, and physical reactions. The cofactor or activator can be used to assist the catalytic unit in reacting with the target substance; for example, when the catalytic unit is a metalloenzyme that requires metal ions as a cofactor.

[0111] In one example, the sampling port of the sampling device may also be equipped with a corresponding stopcock or sealing cap, which is used to open during sampling and close after sampling to ensure that the inside of the pipeline remains relatively sealed.

[0112] In another example, the sample application device may be equipped with a permeable component, such as a rubber stopper, which can be used to form a sample application port by injection or puncture during sample application. For example, the catalytic unit or reaction substrate to be added to the pipeline is stored in a syringe, and the catalytic unit or reaction substrate is added to the sample application device by puncturing the rubber stopper with the syringe.

[0113] In one embodiment, the collection container has a collection cavity for mixing the circulating catalytic unit, the fluid balance, and the liquid to be treated, so that the catalytic unit comes into contact with the target substance.

[0114] In one embodiment, the collection container can be used to expand the circulation volume. In examples where the fluid is a liquid, the collection container can help the circulating liquid mix better with the circulating catalytic unit, thereby enabling sufficient contact between the target substance and the catalytic unit.

[0115] In some embodiments, the collection container is also used to provide a sample inlet, an air outlet, or a liquid outlet. In this example, the collection container can also serve as an integrated platform for various liquid inlets / outlets or air outlets and a mixing and confluence site for various liquids.

[0116] In one embodiment, by determining the position of the collecting container in the pipeline, the fluid in the collecting container tends to flow in the direction of circulation due to gravity when naturally placed. This design can avoid or reduce the generation of air bubbles in the pipeline. In this example, the collecting device can also be provided with an exhaust port connected to the gas branch L2-5 to regulate the internal air pressure of the circulation.

[0117] like Figures 2 to 8 As shown, in one embodiment, a liquid level sensor 602 is provided on the collecting container 600 to detect the liquid level in the collecting container 600. The liquid level sensor 602 can transmit signals to decide whether to control the liquid level in the collecting container 600.

[0118] In one embodiment, a color sensor 601 is provided on the collection container 600 to detect the color of the liquid in the collection container 600 to detect information such as the content or concentration of enzyme-loaded microspheres, or as a detection signal to ensure that the operator has added enzyme-loaded microspheres, so as to ensure the correct operation procedures and programmed operation of the dialysis equipment.

[0119] In one embodiment, the metabolic circulation device 60 further includes a gas branch L2-5 for controlling the liquid volume in the collection container 600 by venting or inleting gas. In this embodiment, a gas pump 6030 is installed on the gas branch L2-5, and the gas pump 6030 is connected to a gas inlet and outlet. A vent valve 6031 or a flow channel switching device is installed on the vent branch L2-5 for connecting or closing the flowing gas on the vent branch. The vent valve 6031 is, for example, a three-way valve or a four-way valve. A hydrophobic filter 6230' is installed on the gas branch L2-5. A pressure sensor 6231' is installed on the vent branch L2-5 for detecting the pressure inside the collection container 600. The pressure sensor 6231' can reflect the fluid pressure of the metabolic circulation and / or downstream processes.

[0120] Please see Figure 7The figure shows a schematic diagram of the metabolic circulation device of this application in another embodiment. As shown, two air pumps (6030', 6030") are provided on the gas branch L2-5, namely a first air pump 6030' for degassing and a second air pump 6030" for adding gas. An exhaust valve 6031 or a flow channel switching device is provided between the first air pump 6030' and the second air pump 6030" to control the liquid level and liquid volume in the collection container 600 by selectively controlling the first air pump 6030' or the second air pump 6030".

[0121] In this embodiment, the pressure sensor 6231", air pump (6030', 6030"), and hydrophobic filter 6230' are all connected to the gas branch L2-5 via a three-way or four-way valve or flow channel switching device. This gas branch L2-5 is located on the collecting container 600. During use, the pressure sensor 6231" is connected; when rapid venting is required, the exhaust port is connected; when slow venting is required, the degassing pump (e.g., ...) is connected. Figure 7 The first air pump 6030' shown is connected when air needs to be pumped (e.g., ...). Figure 7 The second air pump 6030 shown is shown.

[0122] In this embodiment, the liquid level in the collection container 600 can be controlled by transmitting signals through the liquid level sensor 602, or the liquid level or gas content in the collection container 600 can be determined by the liquid level sensor 602 or the pressure sensor 6231”. Then, the air pump (6030', 6030”) or the exhaust valve 6031 on the gas branch L2-5 can be used to automatically control the closure of the exhaust port to discharge the gas generated in the metabolic cycle, or to control the total amount of liquid in the metabolic cycle, or to control the total amount of liquid in the dialysate regeneration cycle. In some embodiments, the total amount of dialysate regeneration cycle includes, in addition to, the above-mentioned… Figure 1 The contents shown include, for example, the external cavity of the dialyzer, similar to the water circuit of a traditional dialysis machine, such as the total amount of dialysis waste liquid and regenerated liquid.

[0123] Please see Figure 8 The figure shows a schematic diagram of the metabolic circulation device of this application in another embodiment. As shown, a weighing device 604 is provided at the bottom of the collection container 600 to detect the weight of the liquid in the collection container 600 to determine the volume of the liquid in the collection container 600, and then the liquid level and volume in the collection container 600 are controlled by the air pump (6030', 6030")

[0124] In this embodiment, when detecting the concentration of target molecules in the liquid to be treated within the collection container, the concentration or cumulative treatment amount of target molecules is detected by measuring the pH, substrate concentration, or product concentration of the effluent in the metabolic cycle, thereby reflecting the usage of the downstream adsorption device. Furthermore, the concentration of substances detected by the aforementioned sensors can be displayed or indicated using OCM (online clearance monitoring), or by comparing it with empirical, historical, or agreed-upon values ​​to reflect or detect enzyme activity. If the measured value is significantly lower than the historical or preset value, the operator is alerted to add or replace the enzyme preparation.

[0125] This application enables the design of a HDF treatment mode, namely, hemodialysis filtration with dynamic control of the total volume of circulating dialysate, by setting a gas branch L2-5 within the metabolic circulation device. By dynamically and periodically adjusting the volume or liquid level of any container within the dialysate circulation, the total volume of liquid in the dialysate circulation is controlled, thereby achieving periodic filtration and filtration, and increasing molecular convection exchange within the dialyzer.

[0126] Assuming the volume of the collection container is approximately 20-30 mL, a four-way valve-like vent valve can be connected to an air pump or pressure sensor for degassing or regassing. Under standard conditions, the liquid level in the collection container is low, with approximately 25 mL of air. Due to the continuous injection of liquid into the dialysis waste passage L2-1, the air chamber within the collection container is under positive pressure.

[0127] In an embodiment, an HDF process can be broken down into many identical cycles, or gas pump (6030', 6030") gas filling or degassing cycles, such as those described above. Figure 7 The example provided.

[0128] During the degassing cycle (assuming 30s), the liquid level in the collection container rises slowly during the degassing process, and the amount of water filtered from the blood to the dialysate side increases. If the degassing speed of the air pump is 46ml / min, then the filtered water is 23mL.

[0129] During the gasification cycle (assuming 30 seconds), the gas pressurizes and the liquid level drops, allowing more dialysate to be filtered into the bloodstream at a rate of 46 ml / min. This means that the filtration rate increases by 23 mL per cycle (1 minute), resulting in a total filtration volume of 5.52 L over the entire 240-minute treatment cycle.

[0130] In another embodiment that increases filtration capacity, if the gas filling cycle is shorter than the degassing cycle, the gas filling speed is faster, for example, gas filling is completed in 5 seconds, and the flow rate is 276 ml / min; in this case, the time of one cycle is 35 seconds, and the treatment time of 240 minutes can work for 411.4 cycles, with a total filtration capacity of 9.45 L.

[0131] While exhaust can be achieved by setting up a gas branch L2-5 in the metabolic circulation device, it requires various devices such as an air pump and pressure sensor, which increases the complexity of the metabolic circulation device and thus increases the manufacturing cost.

[0132] Therefore, in another embodiment, please refer to Figure 22a and Figure 22b The diagram shown is a structural schematic of the metabolic circulation device of this application in one embodiment. Figure 22a As shown, the top of the collecting container 600 is provided with an exhaust port 6000, and a floating valve ball 6001 is suspended inside the collecting container 600 corresponding to the exhaust port 6000. The floating valve ball 6001 is used to seal the exhaust port as the liquid level in the collecting container 600 rises and to open the exhaust port as the liquid level in the collecting container 600 falls. Specifically, the gas in the collecting container 600 rises and accumulates at the top of the collecting container 600. As the gas gradually increases, the liquid level in the collecting container 600 gradually decreases. Simultaneously with the decrease in liquid level, the floating valve ball 6001 decreases with the liquid level, opening the exhaust port 6000, and the gas is discharged from the exhaust port 6000. When the liquid level rises, as... Figure 22b As shown, the floating valve ball 6001 rises with the liquid level. When the floating valve ball 6001 rises to the top of the collecting container 600, it seals the vent 6000 to prevent the liquid from being discharged from the vent 6000. In this way, gas in the collecting container 600 can be eliminated, and the complexity of the metabolic circulation device can be reduced, for example, by reducing the number of electrical components or parts.

[0133] In this embodiment, the enzyme preparation is reusable. Using the "pre-prepared solution bypass" method described above, an empty pre-prepared solution bag is connected to the metabolic circulation line. The liquid from the metabolic circulation line and the enzyme-carrying microspheres are flushed into the bag, and the enzyme preparation (a more diluted enzyme preparation) is stored at a low temperature. During the next treatment, the bag is connected to the metabolic circulation line and inverted with the outlet facing down. The enzyme preparation is then added to the metabolic circulation line, or a portion of the enzyme preparation is added based on empirical values, and the dialysis treatment continues.

[0134] In one embodiment, enzyme separation is achieved through a metabolic filtration module, which includes a separation component to divide the metabolic filtration module into a first side and a second side. The opposite ends of the first side of the metabolic filtration module are respectively connected to the inlet and outlet of the metabolic circulation pipeline L2-4, and the second side of the metabolic filtration module is connected to the input end of the adsorption device. In some embodiments, the metabolic filtration module may also be referred to as a separation module.

[0135] In this embodiment, the metabolic circulation pump drives the enzyme-loaded microspheres and dialysis waste liquid mixed in the collection container to circulate in the metabolic circulation pipeline L2-4 at a preset flow rate. The preset flow rate is related to at least one of the following: target substance, fluid composition, fluid temperature, separation component structure, separation component material, metabolic filtration module cavity structure, pipeline diameter, and fluid exchange efficiency. The metabolic circulation pump can be located upstream or downstream of the metabolic filtration module, and the direction of liquid flow driven by the metabolic circulation pump can be any single direction, or opposite directions, or the flow direction can be periodically adjusted, such as a combination of 1 minute forward drive, 1 minute reverse drive, or 10 minutes forward drive, 1 minute reverse drive, etc., to reduce the deposition of enzyme-loaded microspheres in the metabolic filtration module.

[0136] In this embodiment, the inlet and outlet of the pipeline in the metabolic circulation module are connected to the two ports corresponding to the metabolic filtration module, thereby the pipeline and the metabolic filtration module can jointly form a circulation path. The metabolic circulation pump controls the fluid flow rate in the pipeline. For example, by controlling the fluid rate introduced into the metabolic circulation module to be equal to the fluid rate leaving the circulation based on the metabolic filtration module, the total amount of fluid in the pipeline can be dynamically balanced.

[0137] The fluid in the pipeline contacted by the metabolic filtration module allows for selective permeation of components within the fluid, enabling components permeable to the metabolic filtration module to pass through the separation component from one side to the other, thus achieving a separation effect. In other words, the proxy filtration module can be considered a processing unit with selective processing capabilities for the fluid to be treated (e.g., the mixed enzyme-loaded microspheres and dialysis waste liquid in this application). In some examples, the fluid may also include a catalytic unit; correspondingly, the metabolic filtration module can be configured with a structure or material that is impermeable to the catalytic unit, thereby achieving the enzyme-loaded microsphere retention effect.

[0138] Here, the first side and the second side distinguish the positions of the fluid components that can pass through the metabolic filtration module from the retained fluid (liquid containing enzyme-loaded microspheres). The positional relationship between the first side and the second side is determined by the cavity structure of the metabolic filtration module and the structure of the separation component. For example, when the separation component is a planar structure and is arranged laterally in the proxy filtration module, the first side and the second side are the upper and lower sides, respectively; or when the separation component is a planar structure and is arranged vertically in the proxy filtration module, the first side and the second side are the left and right sides, respectively.

[0139] It should be understood that, in the embodiments provided in this application, the cavity in the metabolic filtration module that is connected to the pipeline is the first side, and the other cavities in the metabolic filtration module are the second side; in one example, when the metabolic filtration module includes multiple cavities, for example, the metabolic filtration module is divided into multiple cavities by multiple separation components in the form of plates and membranes, the cavity connected to the pipeline is the first side, and the remaining cavities are the second side.

[0140] In some embodiments, the separation component is a structure or material that has selective permeability to certain components in the fluid, such as a filter, a filter membrane, or a porous metal material.

[0141] In some embodiments, the separation component is a separation membrane, which can selectively remove molecules or combinations of molecules from the fluid to be treated (e.g., the mixed enzyme-carrying microspheres and dialysis waste liquid in this application) through selective permeability, for example, causing the enzyme-carrying microspheres to be retained in the cycle.

[0142] In some embodiments, the separation component is a porous membrane, including microfiltration, ultrafiltration, or nanofiltration membranes. Here, the average pore size or molecular weight cutoff (MWCO) of the porous membrane or reverse osmosis membrane is related to the target substance. In practical scenarios, based on the fluid composition and the identified target substance, a suitable porous membrane for retaining the target substance is selected. For example, when the target substance to be retained in the fluid has a particle size of 10 nm (i.e., 0.01 μm), a nanofiltration or reverse osmosis membrane can be used to achieve the retention of the target substance. Here, the specific type of separation membrane can be determined based on the differences in physicochemical properties between the fluid components and the target substance, and includes, for example: reverse osmosis membrane (average pore size 0.0001-0.001 μm), nanofiltration membrane (average pore size 0.001-0.01 μm), ultrafiltration membrane (average pore size 0.01-0.1 μm), microfiltration membrane (average pore size 0.1-10 μm), electrodialysis membrane, pervaporation membrane, liquid membrane, gas separation membrane, electrode membrane, etc.

[0143] In some embodiments, the separation membrane achieves the retention, filtration or exchange of components in the catalytic unit and fluid through steric hindrance, Donnan effect or electrostatic effect, adsorption, diffusion, charge repulsion effect, micropore effect or dissolution.

[0144] In some embodiments, particularly in the dialysis medical application of this application, the separation membrane is a high-purity polymer with inert chemical properties and good blood compatibility and tissue compatibility.

[0145] When the target substance is a substance that needs to be retained by the metabolic filtration module (such as the enzyme-carrying microspheres described in this application), the average pore size or molecular weight cut-off of the porous membrane or reverse osmosis membrane is related to the target substance. In practical scenarios, based on the fluid composition and the determined target substance, a membrane suitable for retaining the target substance or filtering the target substance is selected. For example, when the target substance to be retained in the fluid has a particle size of 10 nm (i.e., 0.01 μm), the corresponding separation membrane can be a nanofiltration membrane or a reverse osmosis membrane to achieve the retention of the target substance.

[0146] In some practical applications, the separation membrane pore size and type can be determined based on the separation component of the metabolic filtration module being able to retain more than 90% of the target substances. Alternatively, based on the requirement for higher separation effect, the retention rate of the separation component for the target substances can be set to more than 95% or even more than 99% to determine the corresponding separation membrane pore size and type.

[0147] In some embodiments, the average pore size or molecular weight cutoff of the separation component is related to at least one of the catalytic unit, the target substance, and the target product.

[0148] In one embodiment, the metabolic circulation device may further include a catalytic unit. To retain the catalytic unit within the pipeline, the average pore size or molecular weight cutoff of the separation component may be set to be smaller than the particle size or molecular weight of the catalytic unit. It should be noted that in the circulation module, the separation component may also achieve selective permeation of certain components in the fluid to be treated, while the retention component may be configured to retain only the catalytic unit. Furthermore, it should be understood that the target substance retained by the separation component and the target substance that can react under the action of the catalytic unit may refer to the same substance or different substances.

[0149] In embodiments, the separation component may also be configured as a separation membrane with different geometries to adapt to different fluids or achieve different filtration effects. In some embodiments, the separation component includes one or more of planar membranes, tubular membranes, spiral membranes, helical membranes, and hollow fiber membranes. In terms of microstructure, the separation membrane may include, for example, symmetrical membranes, asymmetrical membranes, composite membranes, multilayer composite membranes, etc.

[0150] It should be noted that, based on the different geometric shapes of the separation membranes provided by the separation components, the positional relationship between the first side and the second side of the corresponding proxy filter module may be different; for example, when the separation component is a planar membrane, the first side and the second side are opposite sides of a planar structure barrier; or, when the separation component is a hollow fiber membrane, the first side is the inner side of each fiber membrane tube wall, and the second side is the outer side of each fiber membrane tube wall.

[0151] The flow angle of the fluid relative to the separation membrane can be set to different angles, such as 0° to 90°. Here, when the flow angle of the fluid relative to the separation membrane is 0°, the fluid flows parallel to the surface of the separation membrane, such as in common tangential flow filtration; when the flow angle of the fluid relative to the separation membrane is 90°, the fluid flows perpendicular to the membrane surface, such as in conventional dead-end filtration (also known as vertical filtration).

[0152] In some embodiments, the flow channel in the proxy filter module can be configured as a folded reciprocating form, a spiral form, or a flow channel size gradient form. For example, by folding the planar membrane to increase the contact area between the fluid and the planar membrane, the flow channel is configured as a folded reciprocating form to match the structural shape of the separation membrane, so as to ensure that the separation membrane separates the proxy filter module into a first side and a second side.

[0153] In some embodiments, the metabolic circulation pump controls the fluid to flow in the pipeline at a preset flow rate, so that the catalytic unit flows from one end of the pipeline through the proxy filtration module to the other end. For example, when the metabolic filtration module is a TFFM (Total Fusion Filter), the fluid flow direction is parallel to the separation membrane in the TFFM. Here, when the fluid passes through the separation membrane in the TFFM, a transmembrane pressure difference perpendicular to the membrane surface is generated on both sides of the membrane, driving the low molecular weight components in the fluid to pass through the separation membrane and reach the other side. The low molecular weight components that pass through the separation membrane can leave the circulation, while the retained catalytic unit or other preset high molecular weight components to be retained are flushed off the membrane surface by the fluid momentum and continue to circulate in the pipeline. The pressure difference on both sides of the membrane in the TFFM is related to the preset flow rate. At the same time, the retained substances need a certain momentum to overcome the inhibition of polymerization between molecules or between molecules and the membrane to continue to circulate. The driving device controls the flow rate in the pipeline, which can be used to control the pressure difference on both sides of the separation membrane to achieve the retention and separation effect, and can also be used to prevent polymerization to ensure the sustainability of the circulation in the pipeline.

[0154] The fluid flow rate at the proxy filtration module is related to various parameters, such as fluid density and viscosity, the boundary layer shape of the fluid at the proxy filtration module (e.g., the surface shape of the separation membrane, i.e., the membrane structure) and the cavity structure of the proxy filtration module, the interaction force between the fluid and the separation membrane (e.g., the membrane surface roughness determined by the membrane material and the attraction between the membrane and the fluid), and the flow rate relationship between the proxy filtration module and the pipeline inlet determined by the cavity structure of the proxy filtration module and the pipeline diameter. Therefore, the fluid flow rate at the proxy filtration module may change. Here, the preset flow rate is used to determine the fluid flow rate at the pipeline inlet leading to the proxy filtration module. The preset threshold can be used as the initial flow rate at the proxy filtration module. Based on the initial flow rate and the influence parameters of the fluid flow rate at the aforementioned proxy filtration module, the pressure difference generated by controlling the preset flow rate in the proxy filtration module can be used to prevent trapped macromolecules, such as catalytic units, from agglomerating on the membrane surface. Thus, macromolecules can flow from the pipeline inlet through the proxy filtration module to the pipeline outlet.

[0155] In some implementations, the preset flow rate is related to the exchange efficiency of the target product. For example, in TFFM, the target product needs to reach a certain flow rate and then be driven by the pressure difference across the separation membrane to flow to the other side, thereby leaving the cycle. The pressure difference is related to the flow rate. When the flow rate is too low, the exchange efficiency of the target product flowing across the membrane may decrease. Therefore, the preset flow rate can also be determined based on the exchange efficiency.

[0156] In one embodiment, the metabolic filtration module includes N sub-filtration modules, which are connected in series and / or in parallel, where N is a positive integer greater than or equal to 2. In some embodiments, the N sub-filtration modules are connected in series according to a connection order, and the average pore size or molecular rejection of the separation components of the N sub-filtration modules decreases sequentially.

[0157] In some embodiments, the metabolic filtration process is implemented by N cycles, and the N sets of metabolic cycle modules corresponding to the N cycles process different molecules or combinations of molecules in the fluid, so that different components in the fluid are distributed and processed in the N cycles; wherein, N is a positive integer greater than 2.

[0158] Here, the N groups of processing units may perform different types of processing. For example, following the cyclic connection sequence, the fluid to be processed may be filtered in the first cycle, heated in the second cycle, and catalytically processed in the third cycle.

[0159] Alternatively, the N sets of processing units may perform the same type of processing, but each may correspond to a different target substance; for example, the N sets of processing units corresponding to the N cycles may all be used to catalyze the fluid to be processed, so that different target substances are distributed in the N cycles and come into contact with different catalytic units respectively.

[0160] In some embodiments, fluid is introduced into N circulation modules for processing, the N circulation modules being connected in series and / or in parallel, wherein N is a positive integer greater than or equal to 2 (N≥2).

[0161] In one embodiment, the metabolic circulation device has a discharge port (not shown) for discharging enzyme-loaded microspheres from the device. The discharge port is connected to a storage container for storing the discharged enzyme-loaded microspheres. The enzyme-loaded microspheres are discharged from the discharge port by centrifugation or membrane filtration, for example, by slow gravity filtration or centrifugation, discharging the microspheres from the metabolic circulation device into a storage container, for example, a liquid bag made of medical-grade plastic.

[0162] In one embodiment, the metabolic circulation device is a reusable metabolic circulation device after sterilization. In this embodiment, the reusable circulating metabolic module contains non-liquid contact instantaneous sterilization devices in its upstream and downstream pipelines, such as non-contact sterilization devices such as ultraviolet light or gamma rays, or bacterial filtration membranes, typically 0.22µm or 0.45µm membranes.

[0163] In some embodiments, the metabolic reflux is, for example, a loop or loop system or loop in a cyclic processing system constituted by the “metabolic circulation module” described in patent document WO2022036739A1 or / and patent document WO2022036738A1; the full text of patent documents WO2022036739A1 and WO2022036738A1 is incorporated herein by reference.

[0164] Please see Figures 2 to 8 and combined Figure 1 The input end of the adsorption device 61 is connected to the output end of the metabolic circulation device 60, and is used to perform secondary toxin treatment on the waste liquid after the first toxin treatment by the metabolic circulation device 60 to generate regenerated liquid; the adsorption device 61 uses adsorption material to catalytically decompose and adsorb the dialysis waste liquid after blood exchange to generate dialysis regenerated liquid which enters the regenerated liquid pipeline L2-7.

[0165] In this embodiment, the adsorption device may not contain a urease layer. The adsorption device is an adsorption column comprising zirconium phosphate, hydrated zirconium oxide, and activated carbon. The activated carbon material is used to adsorb organic matter from the dialysis waste liquid. The zirconium phosphate layer material is used to adsorb various cations, including potassium, calcium, magnesium, and ammonia ions. Ammonia ions are a product of urease decomposition of urea; therefore, the zirconium phosphate layer must be downstream of the urease layer or the metabolic cycle. While adsorbing cations, zirconium phosphate releases hydrogen or sodium ions. Zirconium phosphate is a cation exchange material. The hydrated zirconium oxide layer material is used to adsorb various anions, such as phosphate and acetate ions. Hydrated zirconium oxide is an anion exchange material.

[0166] In one embodiment, the adsorption device is a single column containing multiple adsorbent materials. For example, the adsorption device comprises a multilayer material designed to remove contaminants and uremic solutes while retaining appropriate dialysate components. Waste dialysate flows from bottom to top through the filter cartridge. The layers in contact with the dialysate contain activated carbon. These layers absorb heavy metals, chloramines, and other contaminants that may be found in tap water. Additionally, the activated carbon absorbs many organic and medium-molecular-weight uremic solutes found in the waste dialysate, including creatinine and uric acid. The multilayer material contains a zirconium phosphate layer and is a cation exchange layer. Its primary function is to adsorb ammonium ions produced by the hydrolysis of urea. Additionally, this cation exchange material absorbs other positively charged substances, such as magnesium, calcium, and potassium, as well as heavy metal cations that may be found in tap water, such as copper and iron. For the adsorbed cations, zirconium phosphate releases or reacts with sodium to achieve exchange. The multilayer material also includes an anion exchange layer containing hydrated zirconium oxide. The material adsorbs phosphates, fluorides, and other anions, such as oxygen anions from heavy metals, and releases water or hydroxide anions through exchange. As in patent document US10603421B2, the packing material of a traditional adsorption column has a specific hierarchy and upstream / downstream relationship. Specifically, the zirconium phosphate layer needs to be downstream of the urease layer to adsorb amine ions produced by the decomposition of urea by urease; that is, the dialysis waste liquid to be treated first passes through the urease layer, then through the zirconium phosphate layer. It should be understood that the upstream / downstream relationship is determined by the liquid flow direction, with the first flow being upstream and the last flow downstream, rather than a physical spatial relationship. Generally, adsorption columns flow from bottom to top, therefore the downstream adsorbent material is often in the upper layer.

[0167] In some conventional adsorption column constructions, such as those described in patent document CN106111079A, zirconium phosphate is mixed with urease to increase pH buffering capacity and reduce pressure by increasing zirconium phosphate particle size.

[0168] Furthermore, in traditional Redy systems, the pressure on the adsorption column gradually increases during treatment, which can lead to excessive pressure and threaten the stability of the adsorption column, dialysis equipment, and dialysis system. Patent US9242036B2 addresses this by fully mixing zirconium phosphate, urease particles, and a hydrated zirconium oxide layer, and adjusting the pressure and pressure drop by regulating the size of the cation exchange particles. Another example is the packing structure of a traditional regeneration system adsorption column disclosed in patent document CN108025125A, where the packing material is mixed in layers within a column, with zirconium phosphate downstream of the urease layer.

[0169] The adsorption column described in this application, based on the aforementioned prior art, places a portion of zirconium phosphate upstream of the enzyme layer or metabolic cycle to specifically adsorb calcium and magnesium ions, thereby reducing the formation of calcium carbonate and magnesium carbonate. In one embodiment, the adsorption column contains a zirconium phosphate layer upstream of the urease layer for adsorbing calcium and magnesium ions.

[0170] Please see Figure 13 The figure shows a schematic diagram of the adsorption device of this application in one embodiment. As shown, in this embodiment, the adsorption device contains two zirconium phosphate layers, one of which is located upstream of the urease layer and the other downstream of the urease layer. In another embodiment, the adsorption device contains two zirconium phosphate columns, one of which is located upstream of the urease column and the other downstream of the urease column.

[0171] In some embodiments, the dialysate regeneration and recycling system includes a first adsorption device and a second adsorption device.

[0172] Please see Figure 14 The figure shows a schematic diagram of the adsorption device of this application in another embodiment. As shown in the figure, in this embodiment, the first adsorption device or the second adsorption device contains only zirconium phosphate.

[0173] Please see Figure 15 The figure shows a schematic diagram of the adsorption device of this application in another embodiment. As shown in the figure, in this embodiment, the first adsorption device or the second adsorption device is a mixed column containing zirconium phosphate, for example, a mixed column containing zirconium phosphate, hydrated zirconium oxide and activated carbon.

[0174] Please see Figure 16 The figure shows a schematic diagram of the adsorption device of this application in another embodiment. As shown in the figure, in this embodiment, the first adsorption device or the second adsorption device is a fully mixed column containing zirconium phosphate.

[0175] Please see Figure 17The figure shows an embodiment of the adsorption device of this application in a regeneration liquid circulation system. As shown in the figure, in this embodiment, the adsorption device contains at least two adsorption columns containing zirconium phosphate. The first adsorption device 61' is a column containing zirconium phosphate and is located upstream of the metabolic cycle. The other column containing zirconium phosphate is the second adsorption device 61" and is located downstream of the metabolic cycle. Alternatively, the first and second adsorption devices (61', 61") contain two fully mixed adsorption columns, both composed of zirconium phosphate, hydrated zirconium oxide, and activated carbon. One fully mixed adsorption column is located upstream of the metabolic cycle, and the other is located downstream. The adsorption materials of the two fully mixed adsorption columns have the same composition and proportion, but the packing amount or column size may be different.

[0176] In Redy systems and traditional regeneration systems, when a urea solution containing high concentrations of calcium and magnesium ions passes through a urease layer, the urea is decomposed into ammonium carbonate. At this point, the pH is between 8.5 and 9. Calcium and magnesium ions readily react with carbonate ions to form calcium carbonate and magnesium carbonate particles and precipitates, thereby increasing column pressure and reducing enzyme activity and local exchange efficiency. In the embodiments described above, the upstream zirconium phosphate column is primarily used to adsorb calcium and magnesium ions, which helps reduce the formation of calcium carbonate and magnesium carbonate particles in the urease layer or metabolic cycle, thus stabilizing the pressure. The downstream zirconium phosphate column is primarily used to adsorb amine ions from urea decomposition. In the embodiments described above, the weight of the upstream zirconium phosphate column is often less than that of the downstream zirconium phosphate column; in some embodiments, this ratio is 3:6 to 3:7. In some embodiments, the upstream zirconium phosphate column can be replaced with other cationic adsorbent materials, such as cationic adsorbent resins.

[0177] In some embodiments, the adsorption device further includes hollow fibers. The hollow fibers can repel positively charged ions and increase the capacity of the tube. The hollow fibers can be coated with an ion-repelling material that allows urea to pass through via a mechanism similar to water purification, but repels positively charged ions, such as calcium and magnesium. The material coating the hollow fibers can be any such material known to those skilled in the art (e.g., fatty acids or polymer chains such as polysulfones), which can effectively repel calcium and magnesium and thus retain the ions in the dialysis solution. Typically, to produce this effect, the material itself will be positively charged. In some embodiments, for example, the material used to coat the hollow fibers is cellulose acetate (e.g., cellulose triacetate). The hollow fibers to be coated are commercially available, for example, Fresenius Medical Care North America, and can be coated with any desired ion-repelling material available to those skilled in the art.

[0178] Alternatively, hollow fiber can comprise ion-selective nanofiltration membranes. These membranes are commercially available from numerous sources, including Amerida, Koch, GE, Hoechst, and Dow Chemical. The pore size of these membranes prevents the diffusion of ionic substances through the membrane. For example, there exist nanofiltration membranes that can repel ions with multiple negative charges (e.g., sulfate and phosphate) while allowing monovalent ions to pass through, and vice versa. In either case, hollow fiber devices can be available in a variety of sizes, requiring only a small enough fit into a replaceable tube sized for home systems.

[0179] In some embodiments, the adsorbent cartridge may further include a flat membrane covered with a positively charged material as described above. Alternatively, the membrane may be an ion exchange (e.g., anion exchange) membrane that restricts the passage of positively charged ions. Advantageously, the ion exchange membrane also has the ability to adsorb phosphates.

[0180] The cartridge and / or its components or layers can be replaced (e.g., membrane, urea-degrading enzyme), regenerated (e.g., resin, adsorbent), and / or sterilized as needed (e.g., saturation, damage, depletion) so that it can be reused. Additionally, the entire cartridge is replaceable and can be removed from the dialysis system, for example, when the cartridge's regeneration efficiency decreases (e.g., due to layer saturation) or when the cartridge becomes worn or damaged.

[0181] In another embodiment, the adsorption device comprises a plurality of columns connected in series, each column containing one or more adsorbent materials. For example, columns containing zirconia phosphate, hydrated zirconium oxide, and activated carbon are arranged in series. In this embodiment, one or more of a pressure sensor, a degassing device, and a pH sensor are provided between the plurality of columns connected in series.

[0182] In one embodiment, such as Figures 1 to 8 The dialysate regeneration and circulation system shown also includes an adsorption column bypass L2-6, one end of which is connected to the input end of the adsorption device 61 and the other end is connected to the output end of the adsorption device 61. A bypass valve 630 is provided on the bypass of the adsorption device 61.

[0183] In one embodiment, the zirconium phosphate and zirconium oxide in the adsorption device are separate and independent modules that can be disassembled individually to facilitate processing and regeneration outside the system (e.g., acid and alkali treatment), so that the zirconium phosphate and hydrated zirconium oxide materials can be reused.

[0184] In one embodiment, an ammonia sensor is installed between the adsorption device and the metabolic circulation module to detect the urea content of the liquid in the pipeline between the adsorption device and the metabolic circulation module. By combining the added urease dosage and the reaction time using the ammonia sensor, the urea content and the amount of urea removed can be calculated, forming a module for online real-time detection and display of urea content and decomposition amount.

[0185] In one embodiment, such as Figure 2 and Figure 3 As shown, a sensor for detecting the content of urea and ammonia in the regenerated liquid pipeline L2-7 is installed on the regenerated liquid pipeline L2-7. In this embodiment, a hydrophobic filter 6230” is installed between the ammonia sensor 6310 and the regenerated pipeline L2-7. In this embodiment, when the sensor for detecting the content of urea and ammonia in the regenerated liquid pipeline L2-7 detects that the ammonia content exceeds a preset value, an alarm device outputs an alarm signal, and the control device 4 opens the second short-circuit valve 626' installed between the input end of the waste liquid passage L2-1 and the output end of the regenerated liquid pipeline L2-7, allowing the liquid in the regenerated liquid pipeline L2-7 to flow into the waste liquid passage L2-1 and participate in the metabolic cycle again.

[0186] The output end of the regenerated fluid pipeline L2-7 is equipped with a regenerated fluid inlet valve 638, which is used to open or close the pathway for the regenerated fluid to flow into the dialyzer, the dialysis blood circuit, or directly into the body during peritoneal dialysis treatment. Specifically, the regenerated fluid inlet valve 638 can be a solenoid valve, an electrically operated valve, or a clamp used to tighten the regenerated fluid pipeline L2-7 to close the flow of regenerated fluid.

[0187] In one embodiment, a bypass valve (e.g., ...) is provided between the input end of the waste liquid passage L2-1 and the output end of the regenerated liquid pipeline L2-7. Figure 2 and Figure 3 The second short-circuit valve 626' shown is used to short-circuit the waste liquid passage L2-1 and the regenerated liquid pipeline L2-7 when the bypass valve is opened.

[0188] In one embodiment, such as Figure 2 and Figure 3As shown, the regenerated fluid pipeline L2-7 is equipped with a concentrate branch L2-8 for supplying concentrate to the regenerated fluid pipeline L2-7. After the urea is removed by the metabolic circulation device and other toxins are removed by the adsorption device, potassium-calcium-magnesium concentrate is replenished through the concentrate branch L2-8 to form dialysis waste fluid regenerated fluid, which is then used again for dialysis treatment. In this embodiment, the concentrate branch L2-8 is equipped with a container 6320 (e.g., a concentrate bag) for storing the concentrate, and a concentrate pump 6321 for transporting the concentrate in the container 6320 to the concentrate branch L2-8. The concentrate includes potassium-calcium-magnesium concentrate.

[0189] In one embodiment, a conductivity sensor 634 and / or a temperature sensor 635 are provided on the regenerated liquid pipeline L2-7 to detect the conductivity data and / or temperature data of the fluid in the regenerated liquid pipeline L2-7.

[0190] In hemodialysis filtration (HDF) mode, the dialysate regeneration circulation system of this application also includes a replacement fluid branch L2-9 on the regeneration fluid line L2-7. Please refer to [link to relevant documentation]. Figure 18 and Figure 19 , Figure 18 This diagram shows the location of the replacement fluid branch in the pre-dilution mode of the hemodialysis device of this application. Figure 19 The diagram shows the location of the replacement fluid branch in the post-dilution mode of the hemodialysis device of this application. As shown, one end of the replacement fluid branch L2-9 is connected to the regeneration fluid line L2-7, and the other end is used to connect to the dialysis circuit. In an embodiment where the dialysate regeneration circulation system is applied to a blood purification device, the output end of the replacement fluid branch L2-9 is used to connect to the blood circuit of hemodialysis. In an embodiment where the dialysate regeneration circulation system is applied to a peritoneal dialysis device, the output end of the replacement fluid branch L2-9 is used to connect to the peritoneal fluid circuit.

[0191] In one embodiment, a first bacterial filter 633' for filtering bacteria in the regenerated fluid is provided on the regenerated fluid line L2-7. The first output end of the first bacterial filter 633' is connected to the output end of the regenerated fluid line L2-7, and the second output end is connected to the replacement fluid branch L2-9. In this embodiment, the first bacterial filter 633' is a tangential flow filter or a dead-end filtration filter. A replacement fluid pump 650 is provided on the replacement fluid branch L2-9 for delivering the regenerated fluid to the dialysis circuit.

[0192] In another embodiment, a second bacterial filter 633” is provided on the replacement fluid branch L2-9 for filtering the dialysis regeneration fluid in the replacement fluid branch L2-9 again and then delivering it to the dialysis circuit.

[0193] In this embodiment, the replacement fluid branch L2-9 is used to divert the flow rate in the regenerated fluid pipeline L2-7 to balance the real-time dynamic balance in the dialysate regeneration circulation system.

[0194] This application also provides a hemodialysis device for dialysis treatment, wherein the dialysis treatment includes treatment suitable for home dialysis treatment scenarios and treatment in hospital dialysis scenarios.

[0195] Please see Figure 9 The figure shows a schematic diagram of the composition architecture of the hemodialysis device of this application in one embodiment. As shown in the figure, the hemodialysis device includes: a purification circuit (not shown), a dialysis device 64, a drive device 3, and a control device 4.

[0196] The connection method and working principle of the dialysate regeneration circulation system are as described above. Figures 1 to 8 The methods described in each embodiment will not be repeated here. Specifically, when using the metabolic circulation device 60 of the dialysate regeneration circulation system, the enzyme-carrying microspheres added to its metabolic circulation pipeline L2-4 contain urease. Urease decomposes urea to produce carbon dioxide and ammonia. Part of the produced carbon dioxide dissolves in the liquid, forming a buffer system, while part may form gas, causing the liquid level in the collection container 600 in the metabolic circulation pipeline L2-4 to drop. When the liquid level sensor 602 detects that the liquid level in the collection container 600 has reached a preset low level, the three-way or four-way valve or flow channel switching device on the gas branch L2-5 is activated to discharge excess carbon dioxide. In this embodiment, the urea content in the blood is detected by monitoring the pH, urea concentration, or ammonia concentration of the metabolic circulation or metabolic circulation effluent, and the amount of urea removed, the usage of OCM or adsorbent, and the results are displayed or indicated. By comparing with empirical or historical values, enzyme activity is reflected or detected, and the operator is prompted to add or replace enzyme preparations.

[0197] In use, enzyme-carrying microspheres can be added to the metabolic cycle. The enzyme-carrying microspheres circulate in the metabolic cycle pipeline L2-4 driven by the metabolic cycle pump. The treatment method is that the liquid to be treated containing a high concentration of target molecules enters the metabolic cycle pipeline L2-4 through the inlet. The target molecules are decomposed into corresponding products by the enzyme-carrying microspheres. The metabolic filtration module continuously separates the treated liquid out, retaining the enzyme-carrying microspheres in the metabolic cycle pipeline L2-4. The treated liquid flows out of the metabolic cycle module through the metabolic filtration module.

[0198] The purification circuit includes a first line with an input end connected to the first part of the human body, namely the arterial blood line L1, and a second line with an output end connected to the second part of the human body, namely the venous blood line L3; the dialysate output end 641 is connected to the input end of the waste liquid passage L2-1 of the dialysate regeneration circulation system; the dialysate input end 640 is connected to the output end of the regenerated liquid pipeline L2-7 of the dialysate regeneration circulation system.

[0199] The driving device 3 is located on the first line and in the purification circuit, and is used to drive the fluid to flow in the purification circuit. In embodiments, the driving device 3 includes, but is not limited to, a peristaltic pump, a pneumatic diaphragm pump, or a pressure pump, for providing power to the fluid in the pipeline, causing the fluid to circulate in a preset flow direction. In medical applications, the driving device 3 should not directly contact the fluid, but only apply pressure to the pipeline and drive the fluid flow. A preferred embodiment of the driving device 3 is a non-contact pump such as a peristaltic pump or a pneumatic diaphragm pump; more specifically, the peristaltic pump is, for example, a dialysis pump or a blood pump. The forward and reverse rotation (reverse rotation) of the peristaltic pump will cause the fluid in the circulation circuit to flow in different directions. In applications where the circulation circuit is a water circuit, the driving device 3 can be a contact-type driving pump or the like to drive the fluid to flow forward or backward in the circulation circuit.

[0200] It should be understood that the driving device 3 can drive the fluid in the pipeline at different positions in the pipeline. The flow rate may change due to factors such as pipeline resistance, temperature, and pressure. However, in the embodiment of the application of hemodialysis provided in this application, the driving device 3 is located on the circulation loop, especially on the arterial blood line L1 of the purification loop.

[0201] The control device 4 is used to execute the treatment mode to purify the fluid flowing in the purification circuit before introducing it into the human body. In an embodiment, the control device 4 is, for example, a controller or system processor of a hemodialysis device, which outputs corresponding control commands by writing a program into the system processor; or it accepts trigger commands input by the operator to execute related control commands.

[0202] The hemodialysis device of this application utilizes the dialysate regeneration and circulation system. A preparation containing, for example, enzyme-carrying microspheres is added to the metabolic circulation device. This preparation circulates in the circulation pipeline under the drive of a driving device. Specifically, dialysis waste liquid containing a high concentration of target molecules enters the metabolic circulation device 60 through the inlet. The target molecule preparation decomposes into corresponding products. The metabolic filtration module 605 in the metabolic circulation device 60 continuously separates the treated liquid, retaining the preparation within the metabolic circulation device. The treated liquid flows out of the metabolic circulation device 60 through the metabolic filtration module 605 and undergoes catalytic decomposition and adsorption to generate dialysis regeneration liquid. After supplementing the regeneration liquid pipeline L2-7 with beneficial ions such as potassium, calcium, and magnesium, it is reused in the dialysis process.

[0203] The hemodialysis device is a hemodialysis apparatus that includes a hemodialyzer or a hemodiafiltration filter. In embodiments, the hemodialysis apparatus includes one or a combination of multiple treatments selected from hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), hemoperfusion (HP), blood exchange (PE), immunoadsorption (IA), or continuous renal replacement therapy (CRRT).

[0204] Please see Figure 10 The figure shows a schematic diagram of the composition of the hemodialysis device according to another embodiment of this application. As shown, the hemodialysis device further includes a dialysis unit 64 for purifying the fluid flowing in the purification circuit. The dialysis unit 64 includes a dialysate output end and a dialysate input end. In this embodiment, the dialysis unit 64 includes a dialyzer, which includes a dialysate chamber, a blood chamber, and a semi-permeable membrane, etc. The membrane separates the dialysis chamber and the blood chamber from each other. In commonly used capillary dialyzers, the blood chamber is formed by the entire internal volume of a hollow fiber, and the dialysate chamber is formed by the inner cavity surrounding the hollow fiber in the dialyzer housing. In this embodiment, the top end of the dialyzer is connected to the arterial blood line L1, and the bottom end of the dialyzer is connected to the venous blood line L3.

[0205] The purification circuit of the hemodialysis device includes a first line, a second line, and a dialysate regeneration circulation system disposed between the first and second lines for connecting the dialysis device. In embodiments where the dialysis device is a hemodialysis device, the first line is an arterial blood line and the second line is a venous blood line. Specifically, the purification circuit includes an arterial blood line L1 and a venous blood line L3 connected to the arterial blood line L1. The purification circuit includes an arterial blood line L1 for accessing a first part of the human body (e.g., a human artery), a dialysis pathway connected to the arterial blood line L1, and a venous blood line L3 connected to the dialysis pathway. The venous blood line L3 is used for accessing a second part of the human body (e.g., a human vein). In some embodiments, such as when some patients have poor vascular conditions, for example, when using single-needle dialysis or a PICC central venous catheter, the first and second parts of the human body may be the same location. The venous blood line L3 is provided with a gas collection chamber; the gas collection chamber is used to enrich the gas in the purification circuit when the fluid in the purification circuit flows from the venous blood line to the arterial blood line; in an embodiment, the purification circuit includes an arterial blood line L1, a dialysis passage (the passage including the dialysis device in the figure), and a venous blood line L3. The arterial end 50 of the arterial blood line L1 and the venous end 90 of the venous blood line L3 are interconnected, so that the arterial blood line L1, the dialysis passage, and the venous blood line L3 constitute a circulation loop, i.e., a purification loop. In this application, the circulation loop can serve as a pre-charge loop in the pre-charge procedure; it also serves as a flushing loop in the flushing procedure; and it also serves as an emptying loop in the emptying procedure.

[0206] In the treatment mode of the dialysis device, an arterial puncture needle is connected to the front end of the arterial blood line L1 via a connector, and a driving device for a peristaltic blood pump is provided midway through the line. Conversely, a venous puncture needle is connected to the front end of the venous blood line L3 via a connector, and a drip chamber / venous reservoir or a gas collection chamber that functions as a venous reservoir is connected midway through the line. During dialysis treatment, the arterial and venous puncture needles are inserted into the target artery and vein of the patient, respectively. If the blood pump is activated, the patient's blood reaches the dialysis device through the arterial blood line L1, where it is purified. Defoaming is performed in the drip chamber / venous reservoir, and the blood is returned to the patient through the venous blood line L3. In other words, the patient's blood is circulated externally from the front end of the arterial blood line L1 to the front end of the venous blood line L3 while being purified by the dialysis device.

[0207] In some embodiments, the hemodialysis device includes one or more detection devices for detecting the concentration of target molecules in the dialysis waste liquid, detecting the content of enzyme-carrying microspheres in the waste liquid passage L2-1 (e.g., detecting the amount of enzyme-carrying microspheres added or whether they have been removed), or detecting the content of enzyme-carrying microspheres in the regeneration fluid line L2-7.

[0208] In some embodiments, the hemodialysis device further includes a mode selection device for receiving an input mode selection signal and sending determined operating mode information to the control device to execute operations corresponding to the operating mode. In this embodiment, the operating mode includes one or more treatment modes selected from HF treatment mode, HD treatment mode, HDF treatment mode, and / or ultrafiltration mode.

[0209] In one embodiment of the HF treatment mode, please refer to Figure 11 The figure shows a schematic diagram of the composition architecture of the hemodialysis device of this application in the pre-dilution mode. As shown in the figure, the control device 4 controls the regenerated fluid output from the dialysate regeneration circulation system to be directly input into the first line L1, such as the arterial chamber 53. This mode of directly inputting the regenerated fluid into the arterial chamber 53 can be called the pre-dilution mode.

[0210] In another embodiment of the HF treatment mode, please refer to Figure 12 The figure shows a schematic diagram of the composition architecture of the hemodialysis device of this application in the post-dilution mode. As shown in the figure, the control device 4 controls the regenerated fluid output from the dialysate regeneration circulation system to be directly input into the second line L3, such as the venous reservoir 93. This mode of directly inputting the regenerated fluid into the venous reservoir 93 can be called the post-dilution mode.

[0211] In an embodiment of the HD treatment mode, the control device 4 controls the input of the regenerated fluid output from the dialysate regeneration circulation system to the dialysate input terminal 640 of the dialysis device 64. (As shown...) Figure 9 and Figure 10 The example shown.

[0212] In this application, the hemodialysis device can also be designed to implement HDF treatment modes, namely, hemodialysis filtration with dynamic control of the total volume of circulating dialysate. In the embodiments, the total volume of liquid in the dialysate circulation is controlled by dynamically and periodically adjusting the volume or liquid level of any container in the dialysate circulation, thereby achieving periodic filtration and filtration, and increasing molecular convection exchange in the dialyzer.

[0213] like Figure 18As shown, in one embodiment of the HDF treatment mode, the control device 4 controls the regenerated fluid output from the dialysate regeneration circulation system to be input into the first line, such as the arterial chamber 53, via the replacement fluid branch L2-9. This mode, in which the regenerated fluid is directly input into the arterial chamber 53, can be called the pre-dilution mode.

[0214] like Figure 19 As shown, in another embodiment of the HDF treatment mode, the control device 4 controls the regenerated fluid output from the dialysate regeneration circulation system to be input into the second line, such as the venous reservoir 93, via the replacement fluid branch L2-9. This mode, in which the regenerated fluid is directly input into the venous reservoir 93, can be called the post-dilution mode.

[0215] exist Figure 18 or Figure 19 In one embodiment of the HDF treatment mode described herein, the control device 4 regulates the output of the replacement fluid branch L2-9 by periodically and dynamically adjusting the fluid volume in the waste fluid pathway L2-1, the metabolic circulation device 60, or the regeneration fluid pipeline L2-7, thereby controlling the molecular convection exchange rate of the dialysis device 64. In another embodiment, the control device 4 regulates the output of the replacement fluid branch L2-9 by dynamically adjusting the working cycle or power of the air pump in the metabolic circulation device 60 to regulate the fluid volume in the collection container 600, thereby controlling the molecular convection exchange rate of the dialysis device 64.

[0216] In one embodiment, the control device periodically changes the total equilibrium volume of the dialysis fluid circulation to periodically achieve the filtration and extraction of fluid inside and outside the dialyzer. In this embodiment, changing the total equilibrium volume of the dialysis fluid circulation is achieved by the control device periodically injecting or removing air into any container in the flow path, thereby changing the liquid volume of any container.

[0217] In one embodiment, in the HDF treatment mode, changing the total volume of the dialysate circulation fluid balance is achieved by the control device periodically changing the volume of any container in the flow path. For example, this could be a collection container in the metabolic cycle, or the control device periodically expanding or shrinking the volume of any channel, pipe, or container in the flow path.

[0218] In one embodiment, it is presented as follows Figure 3 As shown, in the HDF treatment mode, the total amount of fluid in the dialysis fluid circulation is changed by adjusting the differential speed of the two dialysis fluid pumps, namely the first dialysis pump 627' in the waste fluid passage L2-1 and the second dialysis fluid pump 627" in the regenerated fluid line L2-7.

[0219] This application enables the design of a HDF treatment mode, namely, hemodialysis filtration with dynamic control of the total volume of circulating dialysate, by setting a gas branch L2-5 within the metabolic circulation device. By dynamically and periodically adjusting the volume or liquid level of any container within the dialysate circulation, the total volume of liquid in the dialysate circulation is controlled, thereby achieving periodic filtration and filtration, and increasing molecular convection exchange within the dialyzer.

[0220] Please refer to the following: Figure 7 As shown in the figure, assuming the volume of the collecting container 600 is approximately 20-30 mL, for example, a four-way valve vent valve 6031 can be connected to an air pump (6030', 6030") or a pressure sensor 6231" for degassing or adding gas. Under standard conditions, the liquid level in the collecting container 600 is low, with approximately 25 mL of air. Due to the continuous injection of liquid into the dialysis waste liquid passage L2-1, the air chamber in the collecting container 600 is under positive pressure.

[0221] In an embodiment, an HDF process can be broken down into many identical cycles, or air pump filling or degassing cycles, by utilizing... Figure 7 In the illustrated embodiment, the liquid level and volume within the collection container 600 are controlled by selectively controlling either the first air pump 6030' or the second air pump 6030". During the degassing cycle (assuming 30 seconds), the liquid level in the collection container 600 rises slowly, increasing the amount of water filtered from the blood to the dialysate side. If the degassing rate of the air pump is 46 ml / min, then 23 mL of water is filtered. During the gas-pressurization cycle (assuming 30 seconds), the gas pressurizes, causing the liquid level to drop, and more dialysate is filtered into the blood, also at a rate of 46 ml / min. That is, the filtration rate increases by 23 mL per cycle (1 minute), resulting in a total filtration volume of 5.52 L over the entire 240-minute treatment cycle.

[0222] In another embodiment that increases filtration capacity, if the gas filling cycle is shorter than the degassing cycle, the gas filling speed is faster, for example, gas filling is completed in 5 seconds, and the flow rate is 276 ml / min; in this case, the time of one cycle is 35 seconds, and the treatment time of 240 minutes can work for 411.4 cycles, with a total filtration capacity of 9.45 L.

[0223] In the embodiment of the ultrafiltration mode, the ultrafiltration branch L2-2 in the dialysate regeneration circulation system diverts the dialysis waste liquid in the waste liquid passage L2-1 to increase the transmembrane pressure or negative pressure, so that an equal amount of liquid filtered from the blood or peritoneal fluid flowing through the dialysis device enters the dialysis waste liquid, thereby achieving dehydration treatment.

[0224] In an embodiment of the ultrafiltration mode, the control device controls the rotational speed or empirical value of the ultrafiltration pump to measure the flow rate of dialysis waste liquid diverted from the waste liquid passage L2-1 by the ultrafiltration branch L2-2. For example, in one embodiment, the control device controls the rotational speed of the ultrafiltration pump by obtaining the volume or weight of the regenerated liquid in the regenerated liquid line L2-7 to measure the flow rate of dialysis waste liquid diverted from the waste liquid passage L2-1 by the ultrafiltration branch L2-2. For example, in another embodiment, the volume or weight of the regenerated liquid is obtained by weighing or liquid level measurement.

[0225] In embodiments where the dialysate regeneration and circulation system is applied to blood purification equipment, such as in hemodialysis treatment mode (HD), i.e., standard normal treatment mode, since the exchange between molecules is a free exchange driven by concentration difference, the purpose of exchange and removal of toxins is achieved. Since an ultrafiltration branch L2-2 is set on the waste liquid passage L2-1, ultrafiltration dehydration can be carried out simultaneously, which will bring an additional amount (e.g., 3-4L) of transmembrane flow.

[0226] In one embodiment, when the dialysate regeneration circulation system is applied to the blood purification equipment, the ultrafiltration pump continuously extracts water from the waste fluid passage L2-1, creating a transmembrane negative pressure. At this time, the dialyzer will filter out more water to achieve pressure balance. Ultimately, the amount of water extracted by the ultrafiltration pump corresponds to the amount of water lost from the blood, thus achieving dehydration. In a practical embodiment, the ultrafiltration pump continuously draws dialysis waste fluid from the waste fluid passage L2-1 into a waste fluid bag. By accurately measuring the flow rate of the ultrafiltration pump, excess water can be precisely extracted from the patient's body, thereby achieving dehydration.

[0227] In another embodiment, the ultrafiltration branch L2-2 can also be located on the regenerated liquid pipeline L2-7. That is, the ultrafiltration branch L2-2 includes a first ultrafiltration branch and a second ultrafiltration branch, wherein the first ultrafiltration branch is located on the waste liquid channel, and the second ultrafiltration branch is located on the regenerated liquid pipeline L2-7. In this embodiment, a weighing-type ultrafiltration control is adopted, that is, dual-pump control using an upstream pump and a downstream pump. The upstream pump is located on the first ultrafiltration branch, and the downstream pump is located on the second ultrafiltration branch in the regenerated liquid pipeline L2-7. The container connected to the filter branch, such as an ultrafiltration bag, contains the treated dialysis regeneration solution. Below the ultrafiltration bag is a weighing device. This device can determine the content of the regeneration solution inside the ultrafiltration bag by weighing it. The speed of the upstream and downstream pumps can be adjusted accordingly. For example, if the water content in the ultrafiltration bag exceeds a preset value (ultrafiltration curve), it indicates that too much water has been filtered out, so the speed of the upstream pump is reduced while the speed of the downstream pump is increased. Conversely, if the water content in the ultrafiltration bag is below the preset value (ultrafiltration curve), the speed of the upstream pump is increased while the speed of the downstream pump is decreased.

[0228] This application also provides a peritoneal dialysis device for dialysis treatment, wherein the dialysis treatment includes treatment using the dialysis device in home dialysis treatment scenarios and treatment in hospital dialysis scenarios. The peritoneal dialysis device includes a dialysate regeneration and circulation system, peritoneal dialysis tubing, a drive device, and a control device.

[0229] The peritoneal dialysis tubing has one end connected to the human peritoneal cavity and the other end connected to the dialysate regeneration and circulation system. The peritoneal dialysis tubing uses a single-ended catheter to periodically drain the fluid from the human peritoneal cavity and periodically introduce the dialysate regeneration system.

[0230] The driving device is located on the peritoneal dialysis tubing and is used to drive the fluid to flow periodically in the peritoneal dialysis tubing.

[0231] The control device is used to execute treatment modes to periodically exchange fluid within the human peritoneum.

[0232] The connection method and working principle of the dialysate regeneration circulation system are as described above. Figures 1 to 8 The methods described in each embodiment will not be repeated here. Specifically, when using the metabolic circulation device of the dialysate regeneration circulation system, the enzyme-carrying microspheres added to its metabolic circulation line L2-4 contain urease. Urease decomposes urea to produce carbon dioxide and ammonia. Part of the carbon dioxide dissolves in the liquid, forming a buffer system, while some may form gas, causing the liquid level in the collection container of the metabolic circulation line L2-4 to drop. When the liquid level in the collection container reaches a preset low level detected by the liquid level sensor, the three-way or four-way valve or flow channel switching device on the gas branch L2-5 is activated to discharge excess carbon dioxide. In this embodiment, the urea content in the blood is detected by monitoring the pH, urea concentration, or ammonia concentration of the metabolic circulation or effluent, and the amount of urea removed, the usage of OCM or adsorbent, and the results are displayed or indicated. By comparing with empirical or historical values, enzyme activity is reflected or detected, and the operator is prompted to add or replace enzyme preparations.

[0233] In use, enzyme-carrying microspheres can be added to the metabolic cycle. The enzyme-carrying microspheres circulate in the metabolic cycle pipeline L2-4 driven by the metabolic cycle pump. The treatment method is that the liquid to be treated containing a high concentration of target molecules enters the metabolic cycle pipeline L2-4 through the inlet. The target molecules are decomposed into corresponding products by the enzyme-carrying microspheres. The metabolic filtration module continuously separates the treated liquid out, retaining the enzyme-carrying microspheres in the metabolic cycle pipeline L2-4. The treated liquid flows out of the metabolic cycle module through the metabolic filtration module.

[0234] The dialysis device of this application adds a preparation, such as enzyme-carrying microspheres, to a metabolic circulation device. The preparation circulates in the circulation pipeline driven by a drive device. The processed liquid is continuously separated out by a metabolic filtration module in the metabolic circulation device, while the preparation is retained in the metabolic circulation device. The processed liquid flows out of the metabolic circulation device through the metabolic filtration module and is then catalytically decomposed and adsorbed to produce dialysis regeneration solution. After potassium, calcium, and magnesium ions are added to the regeneration solution pipeline, it is reused in the dialysis process. This solves the problems of low exchange efficiency in existing perfusion modes, which leads to increased enzyme usage, and enzyme efficiency loss and safety risks due to enzyme shedding.

[0235] The above embodiments are merely illustrative of the principles and effects of this application and are not intended to limit this application. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of this application. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in this application should still be covered by the claims of this application.

Claims

1. A peritoneal dialysis device, characterized in that, include: The waste liquid passage connects to the human abdominal cavity at its inlet. A metabolic circulation device, the input end of which is connected to the output end of the waste liquid passage, is used to perform metabolic circulation of the input dialysis waste liquid for initial toxin treatment; The metabolic cycle device includes: A collection container, the first interface of which is connected to the output end of the waste liquid passage, is used to mix the added enzyme or enzyme preparation or enzyme-loaded microspheres with the dialysis waste liquid to ensure full contact. A metabolic circulation tubing, one end of which is connected to the second interface of the collection container, and the other end of which is connected to the third interface of the collection container; A metabolic circulation pump is installed on the metabolic circulation pipeline to drive the mixed enzymes or enzyme preparations or enzyme-loaded microspheres and dialysis waste liquid in the collection container to circulate in the metabolic circulation pipeline. A metabolic filtration module, disposed on the metabolic circulation pipeline, is used to filter out the metabolic waste fluid metabolic treatment liquid after initial toxin treatment of the mixture of enzymes or enzyme preparations or enzyme-loaded microspheres and dialysis waste fluid circulating in the metabolic circulation pipeline; the metabolic filtration module includes a separation component to divide the metabolic filtration module into a first side and a second side for filtering out the dialysis waste fluid metabolic treatment liquid, the opposite ends of the first side are respectively connected to the inlet and outlet of the metabolic circulation pipeline, and the enzymes or enzyme preparations or enzyme-loaded microspheres are retained on the first side; An adsorption device, whose input end is connected to the second side of the metabolic filtration module, is used to perform secondary toxin treatment on the dialysis waste fluid metabolic treatment liquid after the first toxin treatment to generate regenerated liquid. The regenerated liquid pipeline has its inlet connected to the adsorption device for outputting the regenerated liquid, and its outlet connected to the human abdominal cavity. Peritoneal dialysis tubing, one end of which is connected to the human peritoneal cavity, is used to periodically drain the accumulated fluid from the human peritoneal cavity and periodically introduce the regenerated fluid into the human peritoneal cavity. A driving device, located on the peritoneal dialysis tubing, is used to drive the fluid to flow periodically within the peritoneal dialysis tubing. A control device used to execute treatment modes to periodically exchange fluid within the human peritoneum.

2. The peritoneal dialysis device according to claim 1, characterized in that, The waste liquid passage is connected to an ultrafiltration branch; the ultrafiltration branch is equipped with an ultrafiltration container for storing ultrafiltrate and an ultrafiltration pump for transporting the ultrafiltrate in the ultrafiltration container to the waste liquid passage.

3. The peritoneal dialysis device according to claim 2, characterized in that, An ultrafiltration filter is installed between the ultrafiltration pump and the waste liquid passage.

4. The peritoneal dialysis device according to claim 1, characterized in that, A pre-prepared liquid bypass is provided on the waste liquid passage for pre-filling, emptying, or flushing the circulation passage. The circulation passage consists of the waste liquid passage and the regenerated liquid pipeline.

5. The peritoneal dialysis device according to claim 4, characterized in that, A short-circuit valve connected in parallel with the pre-prepared liquid bypass is installed on the waste liquid passage.

6. The peritoneal dialysis device according to claim 1, characterized in that, A dialysis fluid pump is installed in the waste liquid passage to drive the fluid in the waste liquid passage to flow in either the forward or reverse direction.

7. The peritoneal dialysis device according to claim 1, characterized in that, A first dialysate pump is installed on the waste liquid passage, and a second dialysate pump is installed on the regenerated liquid pipeline. The difference in speed between the first and second dialysate pumps is used to change the total amount of liquid in the dialysate circulation in equilibrium.

8. The peritoneal dialysis device according to claim 1, characterized in that, The separation component is a porous membrane or a reverse osmosis membrane, wherein the porous membrane includes a microfiltration membrane, an ultrafiltration membrane, or a nanofiltration membrane; or, the separation component includes one or more of a planar membrane, a tubular membrane, a spiral membrane, a spiral membrane, and a hollow fiber membrane.

9. The peritoneal dialysis device according to claim 1, characterized in that, The metabolic filtration module includes N sub-filtration modules, which are connected in series and / or in parallel, where N is a positive integer greater than or equal to 2.

10. The peritoneal dialysis device according to claim 9, characterized in that, The N sub-filtration modules are connected in series according to the connection order, and the average pore size or molecular rejection of the separation components of the N sub-filtration modules decreases sequentially.

11. The peritoneal dialysis device according to claim 1, characterized in that, The adsorption device comprises zirconium phosphate, hydrated zirconium oxide, and activated carbon.

12. The peritoneal dialysis device according to claim 1, characterized in that, The adsorption device is a single mixed column containing multiple adsorbent materials; or multiple columns connected in series, wherein each column contains one or more adsorbent materials.

13. The peritoneal dialysis device according to claim 1, characterized in that, Upstream of the metabolic circulation device, there is also an activated carbon column; or a mixed column of activated carbon and hydrated zirconium oxide; or a mixed column of activated carbon and zirconium phosphate; or a mixed column of activated carbon, hydrated zirconium oxide, and zirconium phosphate.

14. The peritoneal dialysis device according to claim 1, characterized in that, The adsorption device located upstream of the metabolic cycle device contains a cation adsorption material.

15. The peritoneal dialysis device according to claim 1, characterized in that, Downstream of the metabolic circulation device, there is also a column containing zirconium phosphate; or a column consisting of a mixture of activated carbon, hydrated zirconium oxide, and zirconium phosphate.

16. The peritoneal dialysis device according to claim 1, characterized in that, The adsorption device includes multiple columns connected in series, each column containing one or more adsorbent materials, and one or more of the following are provided between the multiple columns connected in series: a pressure sensor, a degassing device, and a pH sensor.

17. The peritoneal dialysis device according to claim 1, characterized in that, The adsorption device is a dialysis fluid regeneration adsorption column, which contains zirconium phosphate, hydrated zirconium oxide, enzyme-carrying microspheres, and activated carbon.

18. The peritoneal dialysis device according to claim 1, characterized in that, The adsorption device is a dialysis fluid regeneration adsorption column, which contains a cation exchanger layer, a urease layer, and a zirconium phosphate layer. Dialysis waste liquid passes through the cation exchanger layer, the urease layer, and the zirconium phosphate layer in sequence.

19. The peritoneal dialysis device according to claim 1, characterized in that, The adsorption device is a dialysate regeneration adsorption column, which is a fully mixed layer of cation exchanger, hydrated zirconium oxide, enzyme-carrying microspheres, and activated carbon, and contains a zirconium phosphate layer or a column containing zirconium phosphate downstream.

20. The peritoneal dialysis device according to claim 18 or 19, characterized in that, The cation exchanger is used to effectively adsorb calcium and magnesium ions, and the cation exchanger is zirconium phosphate or a cation adsorption resin.

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