WO2024120144A1 - Système de circulation de régénération de dialysat et dispositif de dialyse - Google Patents

Système de circulation de régénération de dialysat et dispositif de dialyse Download PDF

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Publication number
WO2024120144A1
WO2024120144A1 PCT/CN2023/131926 CN2023131926W WO2024120144A1 WO 2024120144 A1 WO2024120144 A1 WO 2024120144A1 CN 2023131926 W CN2023131926 W CN 2023131926W WO 2024120144 A1 WO2024120144 A1 WO 2024120144A1
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Prior art keywords
metabolic
fluid
dialysate
regeneration
circulation system
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PCT/CN2023/131926
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English (en)
Chinese (zh)
Inventor
李祥海
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上海心光生物医药有限责任公司
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Priority to CN202380014058.9A priority Critical patent/CN118159312A/zh
Publication of WO2024120144A1 publication Critical patent/WO2024120144A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits

Definitions

  • the present application relates to the technical field of medical devices, and in particular to a dialysate regeneration circulation system and a dialysis device used in the dialysis field.
  • the Sorbent Dialysis system was first developed by NASA for the recycling of astronauts' urine. In 1973, the first commercial model, REDY Machine (Regeneration of dialysate), achieved great commercial success. Between 1973 and 1994, the REDY system successfully implemented 6 million hemodialysis treatments, most of which were performed at home, proving its good convenience, safety and clinical value.
  • the Achilles heel of adsorption dialysis is that the consumables are extremely expensive, the professional training for production and maintenance is extremely strict, and the early systems contain biotoxic materials such as aluminum, which eventually led to its gradual elimination from the market by the Single Pass type (the traditional dialysis machine currently widely used).
  • urease is mainly used to process urea.
  • Uremic patients have lost their kidney function, so toxins accumulate in the body, including urea. Since proteins in the human body are metabolized and converted into urea and excreted through the kidneys, the urea content in uremic patients is often very high, around 20mM.
  • Urea molecules are highly polar and easily soluble in water, so traditional adsorbents are basically unable to adsorb urea, or have extremely poor selectivity or extremely high costs.
  • Early scientists used urease to decompose urea to produce carbon dioxide and ammonia, and then adsorbed ammonia through zirconium phosphate.
  • Traditional urease is loaded on aluminum oxide microspheres and filled in the adsorption column. Liquid is infused into it, and urea is decomposed after enzyme treatment (not all decomposition is required).
  • the required enzyme dosage is also extremely high, and due to the unreliable adsorption, with the continuous flushing of the liquid, the urease falls off severely after one treatment and is deposited in the downstream adsorption column material, resulting in severe activity loss, resulting in the adsorption column and urease can only be used once, which greatly increases the dosage and cost of urease in adsorption dialysis.
  • urease In the filling perfusion mode, urease is relatively fixed and the liquid flows through, so the probability of mutual collision is much lower than that in a homogeneous system or solution.
  • the low exchange efficiency of the above mode increases the amount of enzyme to ensure the treatment effect.
  • the amount of urease used was between 20,000U and 60,000U, which in turn increased the cost of consumables.
  • the shedding of the enzyme will also lead to the loss of enzyme efficiency and safety risks.
  • the cost of consumables is an important limiting factor for the commercial application of dialysate regeneration dialysis machines and the promotion of home hemodialysis.
  • the purpose of the present application is to provide a dialysate regeneration circulation system and a dialysis device to solve the problems of low exchange efficiency in the existing filling perfusion mode, which increases the amount of enzyme used, and enzyme efficiency loss and safety risks caused by enzyme shedding.
  • the first aspect of the present application provides a dialysate regeneration circulation system, including a waste liquid passage, whose input end is connected to the outlet of the dialysate waste liquid; a metabolic circulation device, whose input end is connected to the outlet of the waste liquid passage, and is used to metabolically circulate the input dialysate waste liquid for primary toxin treatment; an adsorption device, whose input end is connected to the output end of the metabolic circulation device, and is used to perform secondary toxin treatment on the waste liquid after the primary toxin treatment by the metabolic circulation device to generate regeneration liquid; and a regeneration liquid pipeline, whose inlet is connected to the adsorption device for outputting the regeneration liquid.
  • the second aspect of the present application provides a hemodialysis device, comprising: a dialysate regeneration circulation system as described in the first aspect above; a purification circuit, comprising a first circuit whose input end is connected to a first part of a human body, and a second circuit whose output end is connected to a second part of a human body; a dialysis device, disposed on the purification circuit, for purifying a fluid flowing in the purification circuit, the dialysis device comprising: a dialysate output end connected to an input end of a waste fluid passage of the dialysate regeneration circulation system; and a dialysate input end connected to an output end of a regeneration fluid pipeline of the dialysate regeneration circulation system; a driving device, disposed on the first circuit and located in the purification circuit, for driving a fluid to flow in the purification circuit; and a control device, for executing a treatment mode to purify the fluid flowing in the purification circuit and then input it into the human body.
  • the third aspect of the present application provides a peritoneal dialysis device, comprising: a dialysate regeneration circulation system as described in the first aspect above; a peritoneal dialysis circuit, one end of which is connected to the human peritoneal cavity, and the other end of which is connected to the dialysate regeneration circulation system; a driving device, arranged on the peritoneal dialysis circuit, for driving the fluid to flow periodically in the peritoneal dialysis circuit; and a control device, for executing a treatment mode to periodically exchange the fluid in the human peritoneum.
  • the dialysate regeneration circulation system, hemodialysis equipment and peritoneal dialysis equipment provided by the present application, by adding a preparation such as enzyme-loaded microspheres into the metabolic circulation device, the preparation is circulated in the circulation pipeline by the drive of the driving device, specifically, the dialysis waste liquid to be treated containing a high concentration of target molecules enters the metabolic circulation device through the inlet, the target molecules are decomposed into corresponding products by the preparation, the metabolic filtration module provided in the metabolic circulation device continuously separates the treated liquid, retains the preparation in the metabolic circulation device, and maintains continuous circulation, the treated liquid flows out of the metabolic circulation device through the metabolic filtration module, and is then treated by the adsorption device to produce a dialysis regeneration liquid, and after potassium, calcium and magnesium ions are supplemented in the regeneration liquid pipeline, it is used again in the dialysis process, thereby solving the problems of low exchange efficiency in the existing perfusion mode, which increases the amount of enzyme used, and the loss of enzyme efficiency and safety risks caused by enzyme shedding.
  • FIG. 1 is a schematic diagram showing the composition of a dialysate regeneration circulation system in one embodiment of the present application.
  • FIG. 2 is a schematic diagram showing a dialysate regeneration circulation system according to an embodiment of the present application.
  • FIG. 3 is a schematic diagram showing another embodiment of the dialysate regeneration circulation system of the present application.
  • FIG. 4 is a schematic diagram showing a metabolic cycle device according to an embodiment of the present application.
  • FIG. 5 is a schematic diagram showing another embodiment of the metabolic cycle device of the present application.
  • FIG. 6 is a schematic diagram of a metabolic cycle device according to another embodiment of the present application.
  • FIG. 7 is a schematic diagram showing another embodiment of the metabolic cycle device of the present application.
  • FIG8 is a schematic diagram of another embodiment of the metabolic cycle device of the present application.
  • FIG. 9 is a schematic diagram showing the composition structure of a hemodialysis device in one embodiment of the present application.
  • FIG. 10 is a schematic diagram showing the composition structure of the hemodialysis device of the present application in another embodiment.
  • FIG. 11 is a schematic diagram showing the composition structure of the hemodialysis device of the present application in the pre-dilution mode.
  • FIG. 12 is a schematic diagram showing the composition structure of the hemodialysis device of the present application in the post-dilution mode.
  • FIG. 13 is a schematic diagram showing the structure of an adsorption device of the present application in one embodiment.
  • FIG. 14 is a schematic diagram showing the structure of the adsorption device of the present application in another embodiment.
  • FIG. 15 is a schematic structural diagram of another embodiment of the adsorption device of the present application.
  • FIG. 16 is a schematic diagram showing the structure of the adsorption device of the present application in yet another embodiment.
  • FIG. 17 is a structural diagram showing an implementation of the adsorption device of the present application in a regeneration liquid circulation system.
  • FIG. 18 is a schematic diagram showing the position of the replacement fluid branch of the hemodialysis device of the present application in the pre-dilution mode.
  • FIG. 19 is a schematic diagram showing the position of the replacement fluid branch of the hemodialysis device of the present application in the post-dilution mode.
  • FIG. 20 a and FIG. 20 b are schematic diagrams showing the structure of the first metabolic circulation pump and the second metabolic circulation pump of the present application being arranged in parallel upstream or downstream of the metabolic filtration module, respectively.
  • FIG. 21 is a schematic cross-sectional view of a pneumatic fluid pump according to an embodiment of the present application.
  • FIG. 22 a and FIG. 22 b are schematic diagrams showing the structure of the metabolic circulation device of the present application in one embodiment.
  • first, second, etc. are used to describe various elements or parameters in this article in some instances, these elements or parameters should not be limited by these terms. These terms are only used to distinguish an element or parameter from another element or parameter.
  • the first interface can be referred to as the second interface, and similarly, the second interface can be referred to as the first interface, without departing from the scope of the various described embodiments.
  • the first interface and the second interface are both describing an interface, but unless the context clearly indicates otherwise, they are not the same interface. Similar situations also include the first connecting member and the second valve part, or the first connecting member and the second valve part.
  • A, B or C or "A, B and/or C” means "any of the following: A; B; C; A and B; A and C; B and C; A, B and C". Only when the combination of elements, functions, steps or operations is inherently mutually exclusive in some way, will there be an exception to this definition.
  • the present application discloses a dialysate regeneration circulation system used in medical equipment, which is used to process dialysate waste generated during the dialysis process to generate regeneration fluid that is then input into the dialysis equipment or the human body.
  • the medical equipment includes, but is not limited to, blood purification equipment, extracorporeal circulation removal system, extracorporeal enrichment and removal equipment, hemodialysis equipment, plasma exchange equipment, extracorporeal peritoneal dialysis equipment, or extracorporeal membrane oxygenation equipment.
  • the blood purification equipment includes, but is not limited to, hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), hemoperfusion (HP), blood exchange (PE), immunoadsorption (IA) and continuous blood purification (CRRT), peritoneal dialysis (PD) and other equipment.
  • the medical device may also be a set of modules grafted onto other extracorporeal circulation devices.
  • Blocks such as artificial liver, artificial kidney, hemodialysis equipment, peritoneal dialysis equipment, plasma exchange equipment, plasma purification equipment, blood lipid purification equipment, molecular adsorption recirculation system, extracorporeal membrane oxygenation equipment, leukocyte removal equipment, extracorporeal circulation life support system, etc.
  • the medical device is used alone as a medical device or therapeutic device, and can also be integrated into other medical devices or instruments involving extracorporeal treatment of blood or other body fluids to form a new device.
  • the "regeneration fluid” refers to the dialysate waste liquid after the dialysate is exchanged with blood or peritoneal fluid, and 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 in the dialysate waste liquid, and supplemented with beneficial or necessary molecules such as potassium, calcium, and magnesium to form a dialysate waste liquid regeneration fluid, referred to as the regeneration fluid.
  • the regeneration fluid can be regarded as fresh dialysate, which is exchanged with blood or peritoneal fluid again, and the cycle is repeated to continuously remove toxins in the blood or peritoneal fluid to achieve the purpose of treatment.
  • the dialysis equipment using this dialysate circulation regeneration mode is called a dialysate regeneration type dialysis machine, which includes a dialysate regeneration type hemodialysis machine and a dialysate regeneration type peritoneal dialysis machine.
  • the biggest advantage of this type of dialysis machine is that it does not require a water source and a water treatment system, so it is very small and portable, suitable for home hemodialysis and wearable dialysis equipment.
  • the dialysate regeneration circulation system of the present application includes a waste liquid passage, a metabolic circulation device, an adsorption device, and a regeneration liquid pipeline. Please refer to Figure 1, which shows a schematic diagram of the dialysate regeneration circulation system in one embodiment of the present application.
  • the dialysate regeneration circulation system is mainly used as an example for explanation in a blood purification device.
  • the input end 620 of the waste liquid passage L2-1 of the dialysate regeneration circulation system of the present application is connected to the outlet of the dialysate 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, which is used to metabolically circulate the input dialysate waste liquid for the first toxin treatment; the input end of the adsorption device 61 is connected to the output end of the metabolic circulation device 60, which is used to perform a secondary toxin treatment on the waste liquid after the first toxin treatment by the metabolic circulation device 60 to generate regeneration liquid; the inlet of the regeneration liquid pipeline L2-7 is connected to the adsorption device 61 for outputting the regeneration liquid.
  • a preparation such as enzyme-loaded microspheres can be added to the metabolic circulation device 60, and the preparation is circulated in the circulation pipeline by the driving device.
  • the dialysis waste liquid to be treated containing a high concentration of target molecules enters the metabolic circulation device 60 through the inlet, and the target molecule preparation is decomposed into corresponding products.
  • the metabolic filtration module provided in the metabolic circulation device 60 continuously separates the treated liquid and retains the preparation 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 the adsorption device to produce a dialysis regeneration liquid, which is used again in the dialysis process after potassium, calcium and magnesium ions are supplemented in the regeneration liquid pipeline L2-7.
  • FIG. 2 is a schematic diagram of a dialysate regeneration circulation system according to an embodiment of the present application.
  • the input end 620 of the waste liquid passage L2-1 is connected to a dialyzer to obtain the dialysate waste from the dialyzer.
  • the blood flowing in the liquid circuit is purified, and a blood flow path for the patient's blood flow and a dialysate flow path for the dialysate flow are formed by a built-in purification membrane for blood purification;
  • the dialyzer includes a dialysate chamber, a blood chamber and a semi-permeable membrane, etc., and the membrane separates the dialysate chamber and the blood chamber from each other.
  • the blood chamber is formed by the entire internal volume of the hollow fiber
  • the dialysate chamber is formed by the inner cavity of the shell of the dialyzer surrounding the hollow fiber.
  • the top of the dialyzer is connected to the arterial blood line
  • the bottom of the dialyzer is connected to the venous blood line.
  • the type of the dialyzer can include various specifications or uses of hemodialyzers, hemodiafiltration devices, hemofilters, plasma separators, blood plasma component separators, etc., as long as the device can separate toxins or molecular components in the blood, the present application is used.
  • the dialysate circuit includes a regeneration liquid pipeline L2-7 connected to the dialysate inlet of the dialyzer and a waste liquid passage L2-1 at the dialysate outlet, which are used to input the dialysate into the metabolic circulation device 60 and output it after treatment. It should be understood that the dialysate circuit also includes necessary valves, sensors and other necessary elements or components.
  • the input end of the waste fluid passage L2 - 1 is connected to the human peritoneal cavity to obtain the dialysate waste from the human peritoneal cavity.
  • the waste fluid passage L2-1 can be a pipeline conducted by a catheter.
  • catheter or “pipeline” disclosed in the present application means that the components can be fluidically connected to each other so as to provide a path for transferring fluid (i.e., saline, dialysate, etc.) between these components.
  • the waste liquid passage L2-1 may adopt a flow channel, such as a flow channel formed by a plate or a closed guide groove.
  • the flow channel may adopt a multi-layer structure with intervals and stacking.
  • the input end 620 of the waste liquid passage L2-1 is provided with a dialysate outlet valve 621.
  • the dialysate outlet valve 621 may be a solenoid valve, an electrically switched valve, or a clamp for tightening the waste liquid passage L2-1 to close the waste liquid circulation.
  • a leakage sensor 622 is provided in the waste liquid passage L2-1.
  • the leakage sensor 622 is, for example, a blood leakage sensor for detecting blood leakage; in an embodiment in which the dialysate regeneration circulation system is applied to a peritoneal dialysis device, the leakage sensor 622 is, for example, a peritoneal fluid leakage sensor.
  • 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 enables the pressure sensor 6231' to detect the waste liquid pressure in the waste liquid passage L2-1.
  • the waste liquid passage L2-1 is connected to an ultrafiltration branch L2-2.
  • an ultrafiltration container 6242 for storing ultrafiltrate is provided on the ultrafiltration branch L2-2, 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.
  • the ultrafiltration container 6242 is, for example, an ultrafiltration bag, for example, a liquid bag made of medical plastic; the ultrafiltration pump 6241 may be a plunger roller pump, a peristaltic pump or a diaphragm pump, etc.
  • dialysate regeneration circulation system is applied to a blood purification device, for example, in a hemodialysis treatment mode (HD), that is, a standard normal treatment mode
  • hemodialysis treatment mode that is, a standard normal treatment mode
  • the exchange between molecules is a free exchange driven by concentration difference
  • the purpose of exchange and toxin removal is achieved.
  • an ultrafiltration branch L2-2 is provided on the waste liquid passage L2-1, simultaneous ultrafiltration and dehydration can bring about an additional amount (e.g., 3-4L) of transmembrane flow.
  • the ultrafiltration pump 6241 when the dialysate regeneration circulation system is applied to the circulation of a blood purification device, the ultrafiltration pump 6241 will continuously extract the water in the waste liquid passage L2-1 to form a transmembrane negative pressure. At this time, the dialyzer will ultrafilter more water to achieve pressure balance. Ultimately, the blood loses as much water as the ultrafiltration pump 6241 extracts, thereby achieving the purpose of helping the human body remove excess water. In an actual embodiment, the ultrafiltration pump 6241 continuously extracts the dialysate waste in the waste liquid passage L2-1 into a waste liquid bag. By accurately measuring the flow rate of the ultrafiltration pump 6241, the excess water in the patient's body can be accurately extracted from the body, thereby achieving the purpose of dehydration.
  • the ultrafiltration branch L2-2 can also be arranged on the regeneration 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 arranged on the waste liquid channel, and the second ultrafiltration branch is arranged on the regeneration liquid pipeline L2-7.
  • weighing ultrafiltration control is adopted, that is, dual pump control of an upstream pump and a downstream pump is adopted, wherein the upstream pump is arranged on the first ultrafiltration branch, and the downstream pump is arranged on the second ultrafiltration branch in the regeneration liquid pipeline L2-7, and the second ultrafiltration branch is connected to the second ultrafiltration branch.
  • the container connected to the filter branch such as an ultrafiltration bag, contains treated dialysis regeneration fluid.
  • the weighing device can obtain the content of the regeneration fluid in the ultrafiltration bag by weighing, and adjust the speed of the upstream pump and the downstream pump by controlling the speed. For example, if the water in the ultrafiltration bag exceeds the preset value (ultrafiltration curve), it means that more water has been ultrafiltrated, so the speed of the upstream pump is lowered and the speed of the downstream pump is increased. On the contrary, if the water in the ultrafiltration bag is lower than the preset value (ultrafiltration curve), the speed of the upstream pump can be increased and the speed of the downstream pump can be lowered.
  • the preset value ultrafiltration curve
  • a preformed liquid bypass L2-3 is provided on the waste liquid passage L2-1 for prefilling, emptying, or flushing the circulation passage of the dialysate regeneration circulation system.
  • a short-circuit valve 626 is provided on the waste liquid passage L2-1 in parallel with the preformed liquid bypass L2-3.
  • the preformed liquid bypass L2-3 is a system for prefilling and emptying the purification circuit, which is connected to a liquid storage container (for example, the preformed liquid bag 625 shown in FIG. 2, for example, a liquid made of medical plastic) in the circulation circuit.
  • a liquid storage container for example, the preformed liquid bag 625 shown in FIG. 2, for example, a liquid made of medical plastic
  • the two operations of pre-filling and emptying can be realized, that is, in the pre-filling mode, the outlet of the liquid in the liquid storage container is at a low position; and in the emptying mode, the outlet of the gas in the liquid storage container is at a high position;
  • the system of the present application has a simple structure, convenient operation, and low learning cost, and does not require the operator to repeatedly invert the dialyzer for continuous circulation pre-filling.
  • the application of the system of the present application enables more scientific treatment of medical waste such as pipelines and waste liquids after emptying.
  • the system of the pre-filling and emptying purification circuit includes a liquid storage container (i.e., the prefabricated liquid bag 625 shown in FIG. 2 ), a circulation circuit (i.e., the circulation circuit composed of the waste liquid passage L2-1 and the regeneration liquid pipeline L2-7 in FIG. 2 ), and a driving device (i.e., the dialysate pump 627 in FIG. 2 ).
  • the liquid storage container is used to store the pre-filled liquid and recover the emptied waste liquid, and includes a container body, and a first interface and a second interface provided on the container body for serving as the inlet and outlet of liquid and/or gas; the first interface or the second interface is the inlet and outlet of the fluid in the container body.
  • the first interface and the second interface are the first interface b1 and the second interface b2 of the prefabricated liquid bag 625 shown in FIG. 2 .
  • the liquid storage container can be switched between upright and inverted states, that is, the state of placing the liquid storage container upright is upright, and the state of placing the liquid storage container upside down is inverted.
  • a mechanism for placing the liquid storage container upright or inverted is also included.
  • the mechanism is, for example, a plate or a frame for placing the liquid storage container, and a structure for fixing the liquid storage container and a positioning structure for positioning the upright state and the inverted state are provided on the plate or the frame, so that the liquid storage container can be stabilized in the upright state when it is placed upright, or can be stabilized in the inverted state when it is inverted.
  • the system of the liquid storage container in the pre-filling and emptying purification circuit has two working modes, that is, in the pre-filling mode, the outlet of the liquid in the liquid storage container is at a low position; in the emptying mode, the outlet of the gas in the liquid storage container is at a high position; for example, in the pre-filling mode, the second interface is at a lower height so that the pre-filled liquid in the liquid storage container preferentially enters the pipeline in the circulation loop from the second interface, while in the emptying mode, the first interface is at a higher height so that the gas/bubble in the liquid storage container preferentially enters the pipeline in the circulation loop from the first interface.
  • the switching between the pre-filling mode and the emptying mode can be achieved by adjusting the flow direction of the fluid and/or switching the liquid storage container upright or inverted.
  • the pre-liquid bypass is, for example, a system for pre-filling and emptying a purification circuit as described in patent document CN2022108507945; in the present application, the full text of patent document CN2022108507945 is cited herein.
  • a dialysate pump 627 is provided on the waste liquid passage L2-1 to drive the fluid in the waste liquid passage L2-1 to flow forward or reverse.
  • the dialysate pump 627 rotates forward, it is used to drive the dialysis waste liquid in the waste liquid passage L2-1 to flow to the downstream metabolic circulation device 60; the dialysate pump 627 When reversed, it is used to drive the reverse flow in the waste liquid passage L2-1, such as in the working mode where the prefabricated liquid bypass L2-3 needs to be flushed or emptied.
  • the dialysate pump 627 includes a peristaltic pump, a diaphragm pump, a gear pump, etc., which are driving pumps for driving liquid flow.
  • a first dialysate pump is provided on the waste liquid passage
  • a second dialysate pump is provided on the regeneration liquid pipeline, for changing the total amount of liquid equilibrium state of the dialysate regeneration circulation system by the differential speed of the first dialysate pump and the second dialysate pump; please refer to FIG3, which is a schematic diagram of the dialysate regeneration circulation system of the present application in another embodiment, and a second dialysate pump 627' is also provided on the regeneration liquid pipeline L2-7, which drives the entire dialysate regeneration circulation system in the same direction and flow rate as the first dialysate pump 627' on the waste liquid passage L2-1.
  • the design of the dialysate circulation flow can significantly reduce the pressure of the adsorption device 61.
  • the speeds of the first dialysate pump 627' and the second dialysate pump 627" are different to increase or decrease the volume of the metabolic cycle and/or the adsorption device 61 to achieve controllable and measurable ultrafiltration or filtration, wherein the ultrafiltration is often achieved by additional weighing or volume detection methods to determine the ultrafiltration volume, wherein when periodic blood filtration is achieved, the difference in the speed of the two pumps is often periodic, or dynamically adjusted with the filtration volume or pressure.
  • 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.
  • a temperature control device 628" is provided on the regeneration liquid pipeline L2-7 for controlling the temperature of the fluid in the regeneration liquid pipeline L2-7 to a preset range.
  • the waste liquid passage L2 - 1 and the regeneration liquid pipeline L2 - 7 are respectively provided with temperature control devices ( 628 ′, 628 ′′).
  • the temperature control device is a heating device or a constant temperature device.
  • a sample adding device (not shown) is provided on the waste liquid passage L2-1 for adding enzyme preparation (enzyme-carrying microspheres containing urease) to allow it to enter the metabolic circulation device 60.
  • the sample adding device is, for example, an opening or an injection port provided on the waste liquid passage L2-1.
  • sample adding device may also be disposed on the collecting container 600 of the metabolic circulation device 60 .
  • the enzyme-loaded microspheres are microspheres immobilized with urease, with a size between 1-1000um, preferably 20-50um, and are not limited to the material or immobilization process of the microspheres.
  • the enzyme-loaded microspheres are generally injected into the collection container in the form of a solution before treatment and then enter the circulation.
  • the metabolic circulation device 60 is a universal, platform-type device.
  • different enzyme preparations enzyme-loaded microspheres
  • different molecules can be removed, or different catalytic decomposition or synthesis effects can be played.
  • adding ethanol oxidase microspheres can oxidize ethanol
  • urate oxidase microspheres can oxidize uric acid
  • phenylalanine ammonia lyase microspheres can decompose phenylalanine. Therefore, in theory, as long as there are enzymes with corresponding decomposition or synthesis functions, the concentration of any target molecule in the dialysis waste liquid can be changed. This in turn changes the concentration of the target molecule in the blood to achieve the purpose of treatment.
  • the enzyme or enzyme preparation or enzyme-carrying microsphere in the metabolic cycle is in a flowing state.
  • the enzyme or enzyme preparation or enzyme-carrying microsphere added in the metabolic cycle device 60 flows with the circulating liquid participating in the circulation in the metabolic cycle device 60, wherein any liquid flowing in the metabolic cycle device 60 is the circulating liquid, and the circulating liquid is exemplified by the dialysis waste liquid to be treated, the dialysis waste liquid treated at least once, etc.
  • the enzyme or enzyme preparation or enzyme-carrying microsphere can be evenly distributed in the metabolic cycle pipeline through circulation, thereby solving the problem of decreased metabolic effect caused by aggregation of the enzyme or enzyme preparation or enzyme-carrying microsphere, and improving the utilization rate of the enzyme or enzyme preparation or enzyme-carrying microsphere.
  • 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 the regeneration liquid pipeline. 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 the regeneration liquid pipeline.
  • the flow rate of the liquid in the waste liquid passage or the regeneration liquid pipeline is 500 ml/min, and the flow rate of the circulating liquid in the metabolic cycle is 2000 ml/min.
  • the circulating liquid can be rapidly circulated in the circulation device for multiple filtrations.
  • the flow rate of the circulating liquid in the metabolic cycle may also be equal to the flow rate of the liquid in the waste liquid passage or the regeneration liquid pipeline.
  • the first toxin treatment of the metabolic circulation device 60 is to remove urea from the dialysis waste liquid by adding enzymes or enzyme preparations or enzyme-loaded microspheres.
  • it is mainly aimed at patients with renal dysfunction or renal failure, or patients undergoing peritoneal dialysis or hemodialysis treatment.
  • the enzyme-carrying microspheres added to the metabolic circulation pipeline L2-4 contain urease, and the urease decomposes urea to produce carbon dioxide and ammonia.
  • a part of the generated carbon dioxide dissolves in the liquid to form a buffer system, and a part forms gas, so that the liquid level of the collection container 600 in the metabolic circulation pipeline L2-4 drops.
  • the liquid level sensor 602 detects that the liquid level of the collection container 600 reaches a preset low level, the three-way valve or four-way valve or flow channel switching device on the gas branch is activated to discharge excess carbon dioxide.
  • 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 urea removal amount, OCM or adsorbent usage are calculated and displayed or prompted. By comparing with the empirical value or historical value, the enzyme activity is reacted or detected, and the operator is prompted to add or replace the enzyme preparation.
  • enzyme-loaded microspheres When in use, enzyme-loaded microspheres can be added to the metabolic cycle, and the enzyme-loaded microspheres are driven by the metabolic circulation pump to circulate in the metabolic circulation pipeline L2-4.
  • the treatment method is that the liquid to be treated containing a high concentration of target molecules enters the metabolic circulation pipeline L2-4 through the inlet, and the target molecules are decomposed into corresponding products by the enzyme-loaded microspheres.
  • the metabolic filtration module 605 continuously separates the treated liquid and retains the enzyme-loaded microspheres in the metabolic circulation pipeline L2-4. The treated liquid passes through the metabolic filtration module 605 flows out of the metabolic cycle module.
  • 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.
  • 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, and treats the liquid flow in the circulation to selectively change the structure or concentration of molecules or molecular combinations in the liquid flow.
  • the treated dialysis waste liquid metabolic treatment liquid in the circulation leaves the circulation, and the residual amount of the preparation of the mixed enzyme-loaded microspheres is retained in the circulation.
  • FIG 4 is a schematic diagram of the metabolic circulation device of the present application in one embodiment.
  • one end of the metabolic circulation pipeline L2-4 is connected to the second interface a2 of the collecting container 600, and the other end is connected to the third interface a3 of the collecting container 600, thereby forming a circulation loop;
  • the metabolic circulation pump 606 is arranged on the metabolic circulation pipeline L2-4, and is used to drive the enzyme-loaded microspheres and dialysis waste liquid mixed in the collecting container 600 to circulate in the metabolic circulation pipeline L2-4;
  • the metabolic filtration module 605 is arranged on the metabolic circulation pipeline L2-4, and is used to treat the mixed liquid of the enzyme-loaded microspheres and dialysis waste liquid circulating in the metabolic circulation pipeline L2-4 with toxins, retain the enzyme-loaded microspheres in the metabolic circulation pipeline L2-4, and filter out the dialysis waste liquid metabolic treatment liquid.
  • it also includes a device for controlling the metabolic circulation pump 606 to dynamically balance the total amount of fluid in the metabolic circulation pipeline L2-4 in the metabolic circulation mode, that is, by controlling the flow rate of the dialysate waste introduced into the circulation and the dialysate waste metabolic treatment liquid leaving the circulation in any cycle to maintain the dynamic balance of the total amount of fluid in the cycle, allowing the liquid to be treated containing a high concentration of target molecules to enter the circulation through the inlet, and the target molecules are decomposed into corresponding products by the enzyme-loaded microspheres, and the metabolic filtration module 605 in the metabolic circulation device 60 continuously separates the treated liquid and 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.
  • the metabolic circulation pump arranged on the metabolic circulation pipeline includes: a first metabolic circulation pump and a second metabolic circulation pump, wherein the first metabolic circulation pump is arranged upstream of the metabolic filtration module, and the second metabolic circulation pump is arranged downstream of the metabolic filtration module.
  • Figure 5 is a schematic diagram of the metabolic circulation device of the present application in another embodiment. As shown in the figure, the total amount of liquid equilibrium state in 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".
  • the first metabolic circulation pump 606' and the second metabolic circulation pump 606" are, for example, peristaltic pumps.
  • 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.
  • the liquid in the collecting container 600 flows into the metabolic circulation pipeline L2-4 from the second interface a2, and the liquid flows into the collecting container 600 from the third interface a3 after passing through the metabolic filtration module and the first metabolic circulation pump 607', and the liquid can also flow into the collecting container 600 from the third interface a3 after passing through the metabolic filtration module and the second metabolic circulation pump 607".
  • the first metabolic circulation pump 607' and the second metabolic circulation pump 607" are pneumatic fluid pumps, and correspondingly, valves (not shown) are arranged on both sides of the first metabolic circulation pump 607' and the second metabolic circulation pump 607" respectively.
  • the valve may be a pneumatic fluid valve or a pinch valve.
  • the pneumatic fluid pump controls the forward or reverse flow of the fluid in the fluid channel by using the positive pressure gas and the negative pressure gas introduced by a pneumatic interface.
  • the pneumatic fluid pump controls the forward or reverse flow of the fluid in the metabolic circulation pipeline by using the positive pressure gas and the negative pressure gas introduced by a pneumatic interface, wherein the fluid channel is a part of the metabolic circulation pipeline connected to the pneumatic fluid pump and the pneumatic fluid valve. As shown in FIG.
  • the inlet of the pneumatic fluid pump is connected to the second interface a2
  • the outlet of the pneumatic fluid pump is connected to the metabolic filtration module
  • the pneumatic fluid pump can control the forward flow of the fluid in the fluid channel, and vice versa, if the inlet is connected to the metabolic filtration module and the outlet is connected to the second interface a2, then the fluid can be controlled to flow in the reverse direction in the fluid channel.
  • the pneumatic fluid pump is used to push and discharge fluid into its fluid channel using the positive pressure gas introduced by the pneumatic interface, and to draw fluid into its fluid channel using the negative pressure gas introduced by the first pneumatic interface.
  • Figure 21 shows a cross-sectional structural schematic diagram of a pneumatic fluid pump in one embodiment of the present application.
  • the pneumatic fluid pump includes a fluid cavity 6071, a pneumatic diaphragm 6070, and a gas cavity 6072.
  • the valve on the side of the inlet 6080 of the pneumatic fluid pump is opened, and the valve on the side of the outlet 6081 of the pneumatic fluid pump is closed.
  • the fluid cavity 6071 is formed on the flow channel plate 610, and further, the fluid channel 608 communicating therewith may also be provided on the flow channel plate 610. Specifically, a plurality of recesses, grooves, openings and other structures reserved on the flow channel plate 610 form the fluid cavity 6071 and the fluid channel 608.
  • the flow channel plate 610 is injection molded by PMMA, PVC or PC plastic.
  • the fluid cavity 6071 is formed on the inner side of the flow channel plate 610.
  • the inner side of the flow channel plate 610 is a side of the flow channel plate 610 close to the pneumatic diaphragm 6070.
  • the inner side of the channel plate 610 is concave in a direction away from the pneumatic diaphragm 6070 to form a cavity.
  • the concave surface of the fluid cavity can be in an arc shape, a curve shape, or the like.
  • the 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 covers the fluid cavity 6071 and is used to change the volume of the fluid cavity 6071 when subjected to pressure so that the fluid cavity 6071 pushes the fluid into the fluid channel 608 or the fluid cavity 6071 draws the fluid from the fluid channel 608.
  • the pneumatic diaphragm is made of silicone rubber or PVC soft film.
  • the pneumatic diaphragm is deformed by force, and after the force is removed, the pneumatic diaphragm can return to its original state/shape.
  • the cavity pressure in the fluid cavity is positive pressure.
  • the cavity pressure in the fluid cavity is negative pressure.
  • the gas cavity 6072 is covered by the second surface of the pneumatic diaphragm 6070 .
  • the upper side of the pneumatic diaphragm 6070 is the gas cavity 6072
  • the lower side of the pneumatic diaphragm 6070 is the corresponding fluid cavity 6071 .
  • the gas cavity 6072 is disposed on the airway plate 611, and the airway plate 611 is combined with the flow plate 610 and the pneumatic diaphragm 6070 of the fluid pump 6071. In one embodiment, after the airway plate 611 is combined with the flow plate 610, the two clamp the pneumatic diaphragm 6070 in the middle.
  • the airway plate is injection molded by PMMA, PVC or PC plastic. A plurality of structures such as depressions, grooves, openings, etc. are reserved on the airway plate.
  • the gas cavity 6072 is formed inside the airway plate 611.
  • a plurality of recesses, grooves, openings and other structures reserved on the airway plate 611 form the gas cavity 6072.
  • the fluid cavity 6071, the gas cavity 6072 and the pneumatic diaphragm 6070 therebetween constitute the pneumatic fluid pump described above.
  • the gas cavity 6072 is provided with a gas hole 6074 for connecting to an external gas passage, and the gas hole 6074 provides a positive pressure airflow or a negative pressure airflow into the gas cavity 6072 to drive the pneumatic diaphragm 6070 to change the volume of the fluid cavity 6071.
  • the pneumatic diaphragm 6070 is forced to deform downward, and when there is a negative pressure airflow in the gas cavity 6072, the pneumatic diaphragm 6070 is forced to deform upward.
  • the outer side of the airway plate 611 is also provided with a pneumatic interface 609 connected to the air hole 6074.
  • the pneumatic interface 609 is connected to the pneumatic system of the dialysis device so that the pneumatic system provides positive pressure airflow or negative pressure airflow to the gas cavity 6072 to control the forward or reverse flow of the fluid in the fluid channel 608.
  • the flow channel plate and the air channel plate can be combined together by bonding, welding, snapping, or screwing, and the pneumatic diaphragm is clamped between the flow channel plate and the air channel plate.
  • the pneumatic diaphragm and the airway plate are pre-fixed together to ensure the sealing between the pneumatic diaphragm and the flow channel plate and the airway plate, so as to ensure the air tightness of the air drive.
  • the pneumatic diaphragm is further provided with a sealing ring 6073 to achieve sealing between the pneumatic diaphragm and the fluid cavity and/or the gas cavity.
  • the sealing ring can be provided on the pneumatic diaphragm by gluing or the like, or can be integrally formed with the pneumatic diaphragm.
  • first metabolic circulation pump 607' and the second metabolic circulation pump 607" as pneumatic fluid pumps can not only realize the functions of traditional peristaltic pumps, but also reduce the number of electrical components in the dialysate regeneration circulation system and the dialysis device including the dialysate regeneration circulation system, reduce the complexity of the device and improve the integration of the device.
  • the pneumatic fluid pump Since the pneumatic fluid pump alternately sucks fluid and pushes and discharges fluid, the pneumatic fluid pump cannot suck fluid when pushing and discharging fluid, and the pneumatic fluid pump cannot push and discharge fluid when sucking fluid.
  • the first metabolic circulation pump 607' and the second metabolic circulation pump 607" work alternately to drive the flow of liquid in the metabolic cycle.
  • the second metabolic circulation pump 607 when the first metabolic circulation pump 607' is sucking liquid, the second metabolic circulation pump 607" is pushing and discharging fluid, and correspondingly, when the first metabolic circulation pump 607' is pushing and discharging liquid, the second metabolic circulation pump 607" is sucking fluid. In this way, it can be ensured that the metabolic circulation pipeline always has fluid flowing continuously.
  • the valves arranged 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 cavity, a pneumatic diaphragm, and a gas cavity. When a positive pressure airflow is introduced into the gas cavity, the pneumatic diaphragm is forced to deform downward, and the pneumatic fluid valve is closed; when a negative pressure airflow is introduced into the gas cavity, the pneumatic diaphragm is forced to deform upward, and the pneumatic fluid valve is opened.
  • the fluid cavity and the gas cavity of the pneumatic fluid valve can also be correspondingly integrated into the flow channel plate and the air channel plate, and the pneumatic diaphragm of the pneumatic fluid valve and the pneumatic diaphragm of the pneumatic fluid pump can be integrated or independent.
  • the pneumatic fluid pump and the pneumatic fluid valve in the metabolic circulation device usually share a pneumatic system.
  • the pneumatic system passes positive pressure airflow of equal pressure to the pneumatic fluid pump and the pneumatic fluid valve, the fluid in the fluid cavity of the pneumatic fluid pump will be quickly pushed into the fluid channel, causing turbulence, and further destroying the microstructure of the enzyme or enzyme preparation or enzyme-loaded microspheres.
  • the pneumatic interface of the pneumatic fluid pump is provided with a gas damping element, which is used to limit the instantaneous flow rate of the airflow entering the gas cavity 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 cavity of the pneumatic fluid pump to be smoothly pushed into the fluid channel, avoiding turbulence and avoiding damage to the microstructure of the enzyme or enzyme preparation or enzyme-loaded microspheres.
  • the gas damping element is disposed at the inlet end of the pneumatic interface. In other examples, the gas damping element can also be disposed at any position on the gas source connecting pipeline connecting the positive pressure gas source of the pneumatic system and the pneumatic fluid pump.
  • the gas damping element is a small-diameter pipeline.
  • the diameter of the gas damping element is 1/2-1/10 of the diameter of the pneumatic interface.
  • the diameter of the gas damping element is 1/2-1/10 of the diameter of the gas source connecting pipeline, and the instantaneous flow rate of the airflow entering the gas cavity of the pneumatic fluid pump is limited through the small-diameter pipeline.
  • the gas damping element is exemplified by an airflow regulating valve, and the airflow regulating valve is a high-frequency valve, which can limit the instantaneous flow rate of the airflow entering the gas cavity of the pneumatic fluid pump through high-frequency shutoff and opening.
  • FIG. 6 is a schematic diagram of a metabolic circulation device of the present application in another embodiment.
  • the first interface a1 of the collection container 600 is connected to the output end of the waste liquid passage L2-1, and the collection 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.
  • the collection container 600 is divided into two spaces according to function, the upper gas collection space 6000 is used for gas collection, and the lower liquid storage space 6001 is used to collect liquid passing through the collection container 600, that is, there is a gas-liquid separation layer in the collection container 600, and the liquid in the collection container 600 flows from the second interface a2 into the metabolic circulation pipeline L2-4, and then flows into the collection container 600 from the third interface a3.
  • the liquid in the collection container 600 flows from the third interface a3 into the metabolic circulation pipeline L2-4, and then flows into the collection container 600 from the second interface a2.
  • a fourth interface a4 is provided on the top of the collecting container 600 for connecting with the gas branch L2 - 5 .
  • the liquid storage space 6001 includes a first extension part 60010 and a second extension part 60011 extending downwards respectively; wherein the second interface a2 is provided at the bottom end of the first extension part 60010; the third interface a3 is provided at the bottom end of the second extension part 60011, and the isolation part 60012 is higher than the second interface a2 and the third interface a3.
  • the second interface a2 and the third interface a3 are respectively provided at the bottom ends of the first extension part 60010 and the second extension part 60011 extending downwards, so that no matter 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, in the collecting container 600, the fluid flows from the bottom to the top.
  • the first extension part 60010 and the second extension part 60011 of the liquid storage space 6001 both extend downwards, and it should be understood that the “extending downwards” refers to extending vertically downwards, and may also include extending obliquely downwards.
  • 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.
  • the angle of the incident angle can be adjusted according to the actual parameters such as the flow rate, bubble content, or fluid flow rate of the fluid. Should be designed.
  • the length of the first extension portion with the second interface or the second extension portion with the third interface is related to the flow rate, bubble content, or fluid flow rate of the fluid in the liquid storage space; or the length of the isolation portion located between the first extension portion and the second extension portion is related to the flow rate, bubble content, or fluid flow rate of the fluid in the liquid storage space; or the shortest flow distance of the fluid flowing from one interface of the second interface or the third interface to the other interface is related to the flow rate, bubble content, or fluid flow rate of the fluid.
  • a fluid such as a liquid flows from a first extension portion having a second interface through an internal space of a collecting container to a second extension portion having a third interface.
  • the shortest flow distance of the liquid flowing through is controlled by designing the internal structure of the collecting container and the relative positions of the second interface and the third interface, so that the bubbles in the liquid can float and escape and achieve 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, when the bubble content in the liquid is higher, or the flow rate is faster, or the flow rate is larger, in practice, the shortest flow distance of the liquid that needs to be designed is longer.
  • the length of the first extension portion or the second extension portion is longer; in another example, when the bubble content in the liquid is higher, or the flow rate is faster, or the flow rate is larger, the length of the isolation portion located at the first extension portion and the second extension portion is longer; in another example, when the bubble content in the liquid is higher, or the flow rate is faster, or the flow rate is larger, the shortest flow distance of the fluid flowing from one of the second interface or the third interface to the other interface needs to be longer.
  • the length of the first extension part and/or the second extension part can be appropriately increased or shortened in actual applications; of course, the above purpose can also be achieved by changing the length of the isolation part between the first extension part and the second extension part.
  • the isolation part is a step structure relative to the first extension part and/or the second extension part; the isolation part is an arched structure relative to the first extension part and/or the second extension part; or the isolation part is a baffle structure extending upward from the bottom of the gas collecting chamber; for example, the gas collecting chamber is roughly A-shaped, inverted V-shaped, inverted U-shaped, n-shaped, or "mountain"-shaped, etc., with a bottom extension shape or structure.
  • the path cross-section of the fluid flowing from one of the second interface or the third interface to the other interface is larger than the cross-section of the second interface or the third interface, that is, by designing a redundant space structure for the internal space of the gas collecting cavity or the flow channel of the fluid, so that the cross-section of the liquid flow path is much larger than the cross-sectional area of the interface (the second interface or the third interface), so as to reduce the liquid flow rate and increase the gas escape time.
  • the horizontal cross-sectional area gradually increases, the flow velocity gradually decreases, and the flow rate is consistent, so that the gas can easily escape.
  • the first interface a1 of the collection container 600 is connected to the output end of the waste liquid passage L2-1, and is used to mix the added enzyme-loaded microspheres and the dialysis waste liquid to fully contact.
  • the collection container 600 is provided with a sample addition port (not shown) for adding an enzyme preparation (enzyme-loaded microspheres containing urease).
  • the sample addition port contains a valve or a clamp for switching and closing the sample addition port, and the shape of the sample addition port can be designed to be easy for syringe connection and has a certain air tightness.
  • the collection container 600 is, for example, a transparent liquid bag, for example, a liquid bag made of medical plastic.
  • the sample addition port in the metabolic circulation device is also equipped with a sample addition device for adding, supplementing or replacing reaction substrates, catalytic units, drugs, and other auxiliary factors or activators to the metabolic circulation pipeline L2-4.
  • the sample addition device can be used as a processing unit, and the sample addition device can be manually controlled or controlled by a computing device to add, supplement or replace catalytic units and reaction substrates, activators, etc. to the metabolic circulation pipeline L2-4, thereby achieving the processing of the fluid.
  • the sample addition device can also be used to control the concentration of the catalytic unit in the cycle. For example, when the concentration of the target substance in the fluid to be treated is different, the corresponding amount of the catalytic unit added to the pipeline can be controlled to achieve a preset reaction effect.
  • the sample adding device can be configured as a component integrated with the pipeline, or as a component having two opposite access ports to connect the pipeline and ensure that the fluid forms a circulation.
  • the catalytic unit or reaction substrate can be immediately added to the metabolic circulation pipeline 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 reaction, chemical reaction, and physical reaction.
  • the auxiliary factor or activator can be used to assist the catalytic unit to react with the target substance, for example, when the catalytic unit is a metal enzyme that requires metal ions as auxiliary factors.
  • the sample adding port of the sample adding device may also be configured with a corresponding stopper or sealing cover, which is used to be opened during sample adding and closed after sample adding is completed, so as to ensure that the interior of the pipeline remains relatively airtight.
  • the sample adding device may be configured with a permeable component such as a rubber stopper, and a sample adding port may be formed by injection or puncture when adding samples.
  • a permeable component such as a rubber stopper
  • a sample adding port may be formed by injection or puncture when adding samples.
  • the catalytic unit or reaction substrate to be added to the pipeline is stored in a syringe, and the rubber stopper is pierced by the syringe to add the catalytic unit or reaction substrate to the sample adding device.
  • the collecting container has a collecting chamber for mixing the circulating catalytic unit, the fluid surplus and the liquid to be treated so as to make the catalytic unit contact with the target substance.
  • the collection container can be used to expand the volume of the cycle.
  • the collecting container can help the circulating liquid and the circulating catalytic unit to be better mixed, thereby achieving full contact between the target substance and the catalytic unit.
  • the collection container is also used to set a sample addition port, an air discharge port, or a liquid discharge port.
  • the collection container can also serve as an integration platform for various liquid inlets and outlets or air inlets and outlets and a place for the intersection and mixing of various liquids.
  • the fluid in the collecting container tends to flow in the circulation direction due to gravity when placed naturally. This design can avoid or reduce the generation of bubbles in the pipeline.
  • the collecting device can also be provided with an exhaust port connected to the gas branch L2-5 to adjust the internal air pressure of the circulation.
  • a liquid level sensor 602 is provided on the collecting container 600 for detecting the liquid level in the collecting container 600 .
  • the liquid level sensor 602 can transmit a signal to decide whether to control the liquid level in the collecting container 600 .
  • a color sensor 601 is provided on the collection container 600 for detecting 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 indicate whether the operator has added enzyme-loaded microspheres, so as to ensure the correct operating procedures and programmed operation of the dialysis equipment.
  • the metabolic circulation device 60 also includes a gas branch L2-5, which is used to control the amount of liquid in the collecting container 600 by exhausting or intake.
  • an air pump 6030 is provided on the gas branch L2-5, and the air pump 6030 is connected to a gas inlet and outlet.
  • An exhaust valve 6031 or a flow channel switching device is provided on the exhaust branch L2-5, which is used to connect or close the circulating gas on the exhaust branch.
  • the exhaust valve 6031 is, for example, a three-way valve or a four-way valve.
  • a hydrophobic filter 6230' is provided on the gas branch L2-5.
  • the exhaust branch L2-5 is provided with a pressure sensor 6231'' for detecting the pressure in the cavity of the collecting container 600.
  • the pressure sensor 6231'' can reflect the metabolic circulation or/and the fluid pressure conditions downstream.
  • FIG 7 is a schematic diagram of the metabolic circulation device of the present application in another embodiment.
  • two air pumps 6030', 6030" are arranged 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 arranged between the first air pump 6030' and the second air pump 6030", and the liquid level and liquid amount in the collecting container 600 are controlled by selectively controlling the first air pump 6030' or the second air pump 6030".
  • the pressure sensor 6231", the air pump (6030', 6030"), and the hydrophobic filter 6230' are connected to the gas branch L2-5 through a three-way or four-way valve or a flow channel switching device.
  • the gas branch L2-5 is located on the collection container 600.
  • the pressure sensor 6231" is connected.
  • the exhaust port is connected.
  • the exhaust port is connected.
  • the degassing pump (the first air pump 6030' as shown in FIG7) is connected, and when air needs to be inflated, the air pump (the second air pump 6030" as shown in FIG7) is connected.
  • the liquid level in the collecting container 600 can be controlled by transmitting a signal through the liquid level sensor 602, or the liquid level or gas content in the collecting container 600 can be determined by the liquid level sensor 602 or the pressure sensor 6231", and then the air pump (6030', 6030") or the exhaust valve 6031 on the gas branch L2-5 can be used to automatically control the closing of the exhaust port to discharge the gas produced by the reaction 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.
  • the total amount of the dialysate regeneration cycle in addition to the contents shown in FIG. 1 above, also includes, for example, the outer cavity of the dialyzer and other water channels similar to those of a traditional dialysis machine, such as being equal to the total amount of dialysis waste liquid and regeneration liquid.
  • FIG 8 is a schematic diagram of the metabolic circulation device of the present application in another embodiment.
  • a weighing device 604 is set at the bottom of the collection container 600, which is used to detect the weight of the liquid in the collection container 600 to determine the capacity of the liquid in the collection container 600, and then control the liquid level and liquid volume in the collection container 600 through an air pump (6030', 6030").
  • the concentration of the target molecules or the cumulative treatment volume is detected by measuring the pH, substrate concentration, or product concentration of the active effluent in the metabolic cycle, so as to reflect the use of the downstream adsorption device.
  • the concentration of the substance detected by the above-mentioned sensor can be used to display or prompt the concentration of the initial, treated, or remaining target molecules and product molecules OCM (on-line clearance monitoring, online urea clearance monitoring, abbreviated as OCM), or by comparing with the empirical value or historical value or agreed value to reflect or detect the activity of the enzyme. If the measured value is much lower than the historical value or the preset value, the operator will be prompted to add or replace the enzyme preparation.
  • OCM on-line clearance monitoring, online urea clearance monitoring
  • the present application can realize the design of HDF treatment mode by setting gas branch L2-5 in the metabolic circulation device, that is, hemodiafiltration with dynamic control of the total amount of (circulating dialysate).
  • gas branch L2-5 in the metabolic circulation device
  • dynamic control of the total amount of (circulating dialysate) By dynamically and periodically regulating the volume or liquid level of any container in the dialysate circulation, the total amount of liquid in the dialysate circulation is regulated, thereby achieving periodic filtration and filtration, and increasing the molecular convection exchange of the dialyzer.
  • the exhaust valve such as a four-way valve, can be connected to an air pump or a pressure sensor for degassing or aerating.
  • the liquid level in the collection container is at a low level, and the air is about 25 mL. Since the dialysis waste liquid passage L2-1 is continuously injected with liquid, the air chamber in the collection container is at a positive pressure.
  • one HDF process can be divided into a plurality of identical cycles, or gas pump (6030', 6030") gas filling or degassing cycles, such as that illustrated in FIG. 7 above.
  • the liquid level in the collection container rises slowly during the degassing process, and the amount of water in the blood filtered to the dialysate side increases. If the degassing speed of the air pump is 46 ml/min, the filtered water is 23 mL.
  • the gas pressurized liquid level drops, and more dialysate is filtered into the blood at the same rate of 46 ml/min. That is, the increased filtration rate in one cycle (1 minute) is 23 mL, so the filtration volume in the entire treatment cycle of 240 minutes is 5.52 L.
  • the gas filling speed is faster, for example, the gas filling is completed in 5 seconds, and the flow rate is 276ml/min; in this case, the time of one cycle is 35s, and the treatment time of 240min can work 411.4 cycles, and the total filtration volume is 9.45L.
  • exhaust can be performed by setting up a gas branch L2-5 in the metabolic circulation device
  • various devices such as an air pump and a pressure sensor need to be set up, which increases the complexity of the metabolic circulation device and further increases the manufacturing cost.
  • FIG. 22a and FIG. 22b are schematic diagrams of the structure of the metabolic circulation device of the present application in one embodiment.
  • a vent 6000 is provided at the top of the collection container 600, and a floating valve ball 6001 is suspended in the collection container 600 corresponding to the vent 6000.
  • the floating valve ball 6001 is used to seal the vent as the liquid level in the collection container 600 rises and to open the vent as the liquid level in the collection container 600 drops.
  • the gas in the collection container 600 will rise and gather at the top of the collection container 600. As the gas gradually increases, the liquid level in the collection container 600 gradually decreases.
  • the floating valve ball 6001 decreases with the liquid level, opens the exhaust port 6000, and the gas is discharged from the exhaust port 6000.
  • the floating valve ball 6001 rises with the liquid level.
  • the exhaust port 6000 is sealed to prevent the liquid from being discharged from the exhaust port 6000. In this way, the gas in the collection container 600 can be eliminated and the complexity of the metabolic cycle device can be reduced, such as reducing the setting of electrical components or elements.
  • the enzyme preparation is reusable, and through the above-mentioned "prefabricated liquid bypass” method, an empty prefabricated liquid bag is connected to the metabolic circulation, the liquid and enzyme-carrying microspheres in the metabolic circulation are flushed into the bag, and the enzyme preparation (more diluted enzyme preparation) is stored at low temperature.
  • the bag is connected to the metabolic circulation pipeline, inverted, with the outlet at the bottom, and the enzyme preparation is supplemented to the metabolic circulation, or a part of the enzyme preparation is supplemented according to the empirical value, and then it is continued for dialysis treatment.
  • the enzyme preparation separation is achieved by a metabolic filtration module, wherein the metabolic filtration module includes a separation component to separate the metabolic filtration module into a first side and a second side, wherein 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
  • the metabolic filtration module is connected to the input end of the adsorption device.
  • the metabolic filtration module can also be called a separation module.
  • 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; during the period, the preset flow rate is related to at least one of the 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 upstream or downstream of the metabolic filtration module, and the direction of the metabolic circulation pump driving the liquid flow can be any single direction, or it can be the opposite direction, or it can periodically adjust the flow direction, such as 1min forward drive, 1min reverse drive, or 10min forward drive, 1min reverse drive, etc., to reduce the deposition of enzyme-loaded microspheres in the metabolic filtration module.
  • the inlet and outlet of the pipeline in the metabolic circulation module are connected to the two ports corresponding to the metabolic filtration module, so that the pipeline and the metabolic filtration module can jointly form a circulation passage, and the metabolic circulation pump controls the flow rate of the fluid 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.
  • the fluid in the pipeline contacted by the metabolic filtration module can thus achieve selective permeation of components in the fluid based on the metabolic filtration module, and make the components that can penetrate the metabolic filtration module pass through the separation component from one side to the other side, so as to achieve the separation effect.
  • the proxy filtration module can be regarded as a processing unit with a selective treatment function for the treated fluid (such as the mixed enzyme-loaded microspheres and dialysis waste liquid in the present application).
  • the fluid may also include a catalytic unit, and correspondingly, the metabolic filtration module can be set to a structure or material that is not permeable to the catalytic unit, so as to achieve the enzyme-loaded microsphere retention effect.
  • the first side and the second side are used to distinguish the position of the fluid component that can pass through the metabolic filtration module and the trapped fluid (liquid containing enzyme-loaded microspheres), and 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.
  • the separation component is a planar structure and is laterally arranged in the proxy filtration module
  • the first side and the second side are respectively the upper side and the lower side
  • the separation component is a planar structure and is vertically arranged in the proxy filtration module
  • the first side and the second side are respectively the left side and the right side.
  • 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 plate membranes, the cavity among the multiple cavities that is connected to the pipeline is the first side, and the remaining cavities are the second side.
  • the separation component is a structure or material that has selective permeability to some components in the fluid, such as a filter, a filter membrane, or a porous metal material.
  • the separation component is a separation membrane
  • the selective permeability of the separation membrane can be used to selectively remove molecules or combinations of molecules from the treated fluid (e.g., the mixed enzyme-loaded microspheres and dialysis waste in the present application), for example, so that the enzyme-loaded microspheres are retained in the circulation.
  • the separation component is a porous membrane, wherein the porous membrane includes a microfiltration membrane, an ultrafiltration membrane, or a nanofiltration membrane.
  • the average pore size or molecular weight cutoff (MWCO) of the porous membrane or reverse osmosis membrane is related to the target substance.
  • MWCO molecular weight cutoff
  • a porous membrane suitable for intercepting the target substance is selected. For example, when the target substance to be intercepted in the fluid has a particle size of 10 nm (i.e., 0.01 ⁇ m), the corresponding separation membrane can use a nanofiltration membrane or a reverse osmosis membrane to achieve the interception of the target substance.
  • the specific type of the separation membrane can be determined based on the differences in the physicochemical properties between the components of the fluid and the target substance, and includes, for example: reverse osmosis membrane (average pore size 0.0001-0.001 ⁇ m), nanofiltration membrane (average pore size 0.001-0.01 ⁇ m) ultrafiltration membrane (average pore size 0.01-0.1 ⁇ m) microfiltration membrane (average pore size 0.1-10 ⁇ m), electrodialysis membrane, permeation vaporization membrane, liquid membrane, gas separation membrane, electrode membrane, etc.
  • the separation membrane achieves the interception, filtration or exchange of the components in the catalytic unit and the fluid through steric effect, Donan effect or electrostatic effect, adsorption, diffusion, charge repulsion effect, pore effect, or dissolution.
  • the separation membrane is a high-purity polymer with inactive chemical properties and good blood compatibility and tissue compatibility.
  • the target substance is a substance that needs to be retained by the metabolic filtration module (such as the enzyme-loaded microspheres described in the present application)
  • the average pore size or molecular weight cutoff of the porous membrane or reverse osmosis membrane is related to the target substance.
  • a membrane that is suitable for retaining the target substance or filtering the target substance is selected.
  • the corresponding separation membrane can use a nanofiltration membrane or a reverse osmosis membrane to achieve retention of the target substance.
  • the separation component of the metabolic filtration module can be used to determine the corresponding separation membrane pore size and type based on its ability to retain more than 90% of the target substance.
  • the separation component can be set to have a retention rate of more than 95% or even more than 99% to determine the corresponding separation membrane pore size and type.
  • 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.
  • the metabolic circulation device may also be provided with a catalytic unit.
  • the average pore size or molecular weight cutoff of the separation component may be correspondingly set to be smaller than the particle size or molecular weight of the catalytic unit.
  • the separation component may also achieve the retention of the middle part of the fluid to be treated.
  • the selective permeation of the components, and the retention component can be set to only retain the catalytic unit; at the same time, 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, the target substance here refers to the same substance or different substances.
  • the separation component can also be configured as a separation membrane of different geometric shapes to adapt to different fluids or achieve different filtering effects.
  • the separation component includes one or more of a flat membrane, a tubular membrane, a rolled membrane, a spiral membrane, and a hollow fiber membrane.
  • the separation membrane can include, for example, a symmetric membrane, an asymmetric membrane, a composite membrane, a multilayer composite membrane, and the like.
  • the positional relationship between the first side and the second side of the corresponding proxy filtration 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; for another example, 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.
  • the flow angle of the fluid relative to the separation membrane can be set to different angles, such as 0° to 90°.
  • the fluid flows parallel to the surface of the separation membrane, such as common tangential flow filtration;
  • the flow angle of the fluid relative to the separation membrane is 90°, the fluid flows in a direction perpendicular to the membrane surface, such as conventional dead-end filtration (also called vertical filtration).
  • the flow channel in the proxy filtration module may be configured in a folded reciprocating form, a spiral form, or a form in which the size of the flow channel changes gradually.
  • the flow channel is correspondingly configured in a folded reciprocating form to match the structural form of the separation membrane, thereby ensuring that the separation membrane separates the proxy filtration module into a first side and a second side.
  • 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 of the pipeline; for example, when the metabolic filtration module is a TFFM, the flow direction of the fluid is parallel to the separation membrane in the TFFM.
  • 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 to drive the small molecular weight components in the fluid to pass through the separation membrane and reach the other side.
  • the small molecular weight components that pass through the separation membrane can leave the circulation, and the trapped catalytic unit or other preset macromolecular components to be trapped are washed away from the membrane surface under the momentum of the fluid 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.
  • the trapped substances need a certain momentum to overcome the inhibition between molecules or between molecules and membranes 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 interception and separation effect, and can be used to prevent inhibition to ensure the sustainability of the circulation in the pipeline.
  • the fluid flow rate at the proxy filter module is related to different parameters, for example, based on different fluid properties such as fluid density and viscosity, the boundary layer shape of the fluid at the proxy filter module such as the surface shape of the separation membrane (i.e., membrane structure) and the cavity structure of the proxy filter module, the interaction force between the fluid and the separation membrane such as the membrane surface roughness determined by the membrane material and the attraction between the fluid and the separation membrane, the flow rate relationship between the proxy filter module and the pipeline inlet determined by the cavity structure of the proxy filter module and the pipeline diameter, the fluid flow rate at the proxy filter module may change;
  • the preset flow rate is used to determine the fluid flow rate at the pipeline inlet flowing to the proxy filter module, and the preset threshold value can be used as the initial flow rate at the proxy filter module.
  • the fluid flow rate in the proxy filter module can be determined based on controlling the preset flow rate to generate a pressure difference for achieving separation and prevent the trapped macromolecules such as the catalytic unit from being blocked on the membrane surface, thereby, the macromolecules can flow from the pipeline inlet through the proxy filter module to the pipeline outlet.
  • the preset flow rate is related to the exchange efficiency of the target product.
  • the target product needs to be driven by the pressure difference on both sides of the separation membrane to flow to the other side after reaching a certain flow rate, thereby leaving the cycle; the pressure difference is related to the flow rate.
  • the preset flow rate can also be determined by the exchange efficiency.
  • the metabolic filtration module includes N sub-filtration modules, and the N sub-filtration modules are connected in series or/and in parallel, wherein N is a positive integer greater than 2.
  • the N sub-filtration modules are connected in series according to a connection order, and the average pore size or molecular retention corresponding to the separation components of the N sub-filtration modules decreases in sequence.
  • the metabolic filtration process is implemented by N cycles, and N groups of metabolic cycle modules corresponding to the N cycles respectively process different molecules or molecular combinations 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.
  • the processing types performed by the N groups of processing units may be different.
  • the treated fluid is filtered in the first cycle, heated in the second cycle, and catalytically treated in the third cycle.
  • the processing categories performed by the N groups of processing units may be the same, but correspond to different target substances respectively; for example, the N groups of processing units corresponding to the N cycles are all used to perform catalytic treatment on the fluid to be treated, so that different target substances are distributed in the N cycles and contact different catalytic units respectively.
  • the fluid is introduced into N circulation modules for treatment, and the N circulation modules are connected in series and/or in parallel, wherein N is a positive integer greater than 2 (N ⁇ 2).
  • the metabolic circulation device has a discharge port (not shown) for discharging the metabolic circulation device.
  • the discharge port is connected to a storage device for storing the discharged enzyme-loaded microspheres.
  • the enzyme-loaded microspheres are discharged from the discharge port by centrifugation or membrane filtration, such as slowly filtering by gravity or centrifuging to discharge the enzyme-loaded microspheres from the metabolic circulation device into a storage device such as a liquid bag made of medical plastic.
  • the metabolic circulation device is a metabolic circulation device that can be reused after sterilization.
  • the upstream and downstream pipelines of the reusable circulating metabolic module contain non-liquid contact instant sterilization devices, such as non-contact sterilization devices such as ultraviolet rays, gamma rays, or bacterial filtration membranes, usually 0.22um or 0.45um membranes.
  • the metabolic cycle reflux is, for example, a loop or a loop system or a loop in a circulation treatment system constituted by the "metabolic cycle module" described in patent document WO2022036739A1 or/and patent document WO2022036738A1; in the present application, the full text of patent documents WO2022036739A1 and WO2022036738A1 is cited herein.
  • 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 a secondary toxin treatment on the waste liquid after the first toxin treatment by the metabolic circulation device 60 to generate a regeneration liquid; the adsorption device 61 uses an adsorption material to catalytically decompose and adsorb the dialysis waste liquid after exchange with blood to produce a dialysis regeneration liquid that enters the regeneration liquid pipeline L2-7.
  • the adsorption device may not contain a urease layer, and the adsorption device is an adsorption column comprising zinc phosphate, hydrated zirconium oxide, and activated carbon.
  • the activated carbon material is used to adsorb organic substances from the dialysis waste liquid
  • the zirconium phosphate layer material is used to adsorb various cationic substances, including potassium, calcium, magnesium and ammonium ions, wherein the ammonium ions are the products of urease decomposition of urea, so the zirconium phosphate layer must be downstream of the urease layer or the metabolic cycle, while adsorbing cations, zirconium phosphate will release hydrogen ions or sodium ions
  • zirconium phosphate is a cation exchange material
  • the hydrated zirconium oxide layer material is used to adsorb various anionic substances, such as phosphate, acetate, etc., and the hydrated zirconium oxide is an
  • the adsorption device is a single column containing multiple adsorption materials.
  • the adsorption device includes multiple layers of material designed to remove contaminants and uremic solutes while retaining appropriate dialysate composition.
  • the spent dialysate flows through the filter cartridge from bottom to top.
  • 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.
  • activated carbon absorbs many organic and middle molecular uremic solutes found in spent dialysate, including creatinine and uric acid.
  • the multilayer material includes a zirconium phosphate layer and is a cation exchange layer.
  • 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 of heavy metals, and releases water or hydroxide in exchange. Anions.
  • the filler of the traditional adsorption column in patent document US10603421B2 has a certain hierarchy and upstream and downstream relationship.
  • the zirconium phosphate layer needs to be downstream of the urease layer to adsorb the 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 and then passes through the zirconium phosphate layer.
  • the upstream and downstream relationship is determined according to the flow direction of the liquid, the first flow is the upstream, and the later flow is the downstream, rather than the upper and lower relationship in physical space.
  • the adsorption column flows from bottom to top, so the downstream adsorption material is often in the upper layer.
  • zirconium phosphate is mixed with urease to increase the pH buffering capacity through zirconium phosphate and reduce pressure by increasing the particle size of zirconium phosphate.
  • Patent US9242036B2 fully mixes zirconium phosphate, urease particles and hydrated zirconium oxide layers, and adjusts the pressure and pressure drop by adjusting the size of the cation exchange particles.
  • the filling structure of the adsorption column of the traditional regeneration system disclosed in patent document CN108025125A the filling materials are mixed in a column in a layered manner, and the zirconium phosphate is downstream of the urease layer.
  • the adsorption column described in the present application is based on the above-mentioned prior art, and a portion of zirconium phosphate is placed upstream of the enzyme layer or metabolic cycle to specifically adsorb calcium and magnesium ions and reduce the formation of calcium carbonate and magnesium carbonate.
  • the adsorption column contains a zirconium phosphate layer upstream of the urease layer for adsorbing calcium and magnesium ions.
  • Figure 13 is a schematic diagram of the structure of the adsorption device of the present application in one embodiment.
  • the adsorption device contains two zirconium phosphate layers, one of which is located upstream of the urease layer, and the other is located downstream of the urease layer.
  • the adsorption device contains two zirconium phosphate columns, one of which is located upstream of the urease column, and the other is located downstream of the urease column.
  • the dialysate regeneration circulation system includes a first adsorption device and a second adsorption device.
  • FIG. 14 is a schematic diagram of the structure of the adsorption device of the present application in another embodiment.
  • the first adsorption device or the second adsorption device only includes zirconium phosphate.
  • Figure 15 is a schematic diagram of the structure of the adsorption device of the present application in another 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.
  • FIG. 16 is a schematic diagram of the structure of the adsorption device of the present application in another embodiment.
  • the first adsorption device or the second adsorption device is a fully mixed column containing zirconium phosphate.
  • FIG. 17 shows a structural diagram of an implementation of the adsorption device of the present application in a regeneration liquid circulation system.
  • the adsorption device contains at least two adsorption columns containing zirconium phosphate, wherein the first adsorption device 61' is a column containing zirconium phosphate, the first adsorption device 61' is located upstream of the metabolic cycle, and the other column containing zirconium phosphate is the second adsorption device 61", which is located downstream of the metabolic cycle.
  • the first and second adsorption devices contain two fully mixed adsorption columns, both of which are fully mixed columns of zirconium phosphate, hydrated zirconium oxide and activated carbon, wherein one fully mixed adsorption column is located upstream of the metabolic cycle, and the other is located downstream of the metabolic cycle, wherein the composition of the adsorption materials of the two fully mixed adsorption columns is the same in proportion, and the filler amount or column size may be different.
  • the zirconium phosphate column located upstream is mainly used to adsorb calcium and magnesium ions, which helps to reduce the formation of calcium carbonate and magnesium carbonate particles in the urease layer or metabolic cycle, thereby stabilizing the pressure.
  • the zirconium phosphate located downstream is mainly used to adsorb amine ions after urea decomposition.
  • the weight of the zirconium phosphate upstream is often less than the weight of the zirconium phosphate downstream. In some embodiments, this ratio is 3:6-3:7.
  • the zirconium phosphate upstream can be replaced with other cationic adsorption materials, such as cationic adsorption resins.
  • the adsorption device further comprises a hollow fiber.
  • the hollow fiber can repel positively charged ions and increase the capacity of the cartridge.
  • the hollow fiber can be coated with an ion-repelling material that allows urea to pass through a mechanism similar to water purification, but repels positively charged ions, such as calcium and magnesium.
  • the material coating the hollow fiber can be any such material known to those skilled in the art (e.g., a fatty acid or a polymer chain such as polysulfone) that can effectively repel calcium and magnesium and thus retain the ions in the dialysis solution. Typically, in order to produce this effect, the material itself will be positively charged.
  • the material used to coat the hollow fiber is cellulose acetate (e.g., cellulose triacetate).
  • the hollow fiber to be coated is commercially available, for example, from Fresenius Medical Care North America, and can be coated with any desired ion-repelling material available to those skilled in the art.
  • the hollow fibers may include ion-selective nanofiltration membranes.
  • ion-selective nanofiltration membranes are commercially available from a number of sources (e.g., Amerida, Koch, GE, Hoechst, and Dow Chemical).
  • the pore size of these membranes prevents diffusion of ionic species through the membrane.
  • nanofiltration membranes that are capable of rejecting ions with multiple negative charges (e.g., sulfates and phosphates) while allowing singly charged ions to pass, and vice versa.
  • the hollow fiber devices are available in a variety of sizes, only small enough to fit into a replaceable cartridge that can be sized to be used in a home system.
  • the sorbent cartridge may also include a flat membrane covered with a positively charged material as described above.
  • the membrane may be an ion exchange (e.g., anion) membrane that restricts the passage of positively charged ions.
  • the Ion exchange membranes also have the ability to adsorb phosphates.
  • the tube and/or its parts or layers can be replaced (e.g., membrane, urea degrading enzyme), regenerated (e.g., resin, adsorbent) and/or sterilized when needed (e.g., saturated, damaged, exhausted) to enable reuse.
  • regenerated e.g., resin, adsorbent
  • sterilized when needed (e.g., saturated, damaged, exhausted) to enable reuse.
  • the regeneration efficiency of the tube decreases (e.g., due to layer saturation) or the tube becomes worn or damaged, the entire tube is replaceable and therefore can be removed from the dialysis system.
  • the adsorption device includes a plurality of columns connected in series, wherein each column contains one or more adsorption materials.
  • each column contains one or more adsorption materials.
  • columns containing potassium phosphate, hydrated zirconium oxide, and activated carbon materials are respectively connected in series.
  • one or more of a pressure sensor, a degassing device, and a pH sensor are provided between the plurality of columns connected in series.
  • the dialysate regeneration circulation system 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.
  • the zirconium phosphate and zirconium oxide in the adsorption device are separate modules and can be disassembled individually to facilitate treatment and regeneration (such as acid-base treatment) outside the system so that the zirconium phosphate and hydrated zirconium oxide materials can be reused.
  • an ammonia sensor is provided 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.
  • the ammonia sensor can calculate the urea content and the urea content treated by combining the added urease dosage and the action time, so as to form a module for online real-time detection and display of urea content and decomposition amount.
  • the regeneration liquid pipeline L2-7 is provided with a sensor for detecting the content of urea and ammonia in the regeneration liquid pipeline L2-7.
  • a hydrophobic filter 6230 is provided between the ammonia sensor 6310 and the regeneration pipeline L2-7.
  • an alarm device when the sensor for detecting the content of urea and ammonia in the regeneration liquid pipeline L2-7 detects that the ammonia content exceeds a preset value, an alarm device is made to output an alarm signal, and the control device 4 is made to conduct a second short-circuit valve 626' provided between the input end adjacent to the waste liquid passage L2-1 and the output end adjacent to the regeneration liquid pipeline L2-7, so that the liquid in the regeneration liquid pipeline L2-7 flows into the waste liquid passage L2-1 and participates in the metabolic cycle again.
  • the output end of the regeneration liquid pipeline L2-7 is provided with a regeneration liquid inlet valve 638, which is used to open or close the passage of the regeneration liquid to the dialyzer, or to the dialysis blood circuit, or directly input into the human body during peritoneal dialysis treatment.
  • the regeneration liquid inlet valve 638 can be a solenoid valve, a valve of an electric switch, or a clamp used to tighten the regeneration liquid pipeline L2-7 to close the circulation of the regeneration liquid.
  • a bypass valve (such as the second short-circuit valve 626' shown in Figures 2 and 3) is provided between the input end of the waste liquid passage L2-1 and the output end of the regeneration liquid pipeline L2-7, which is used to short-circuit the waste liquid passage L2-1 and the regeneration liquid pipeline L2-7 when the bypass valve is opened.
  • the regeneration liquid pipeline L2-7 is provided with a concentrated liquid branch L2-8 for conveying concentrated liquid to the regeneration liquid pipeline L2-7, and after the urea is removed by the metabolic circulation device and other toxins are removed by the adsorption device, the potassium, calcium and magnesium concentrated liquid is replenished through the concentrated liquid branch L2-8 to form a dialysis waste liquid regeneration liquid, which is used again for dialysis treatment.
  • the concentrated liquid branch L2-8 is provided with a container 6320 (for example, a concentrated liquid bag) for storing the concentrated liquid, and a concentrated liquid pump 6321 for conveying the concentrated liquid in the container 6320 to the concentrated liquid branch L2-8.
  • the concentrated liquid includes potassium, calcium and magnesium concentrated liquid.
  • a conductivity sensor 634 and/or a temperature sensor 635 is provided on the regeneration liquid pipeline L2-7 to detect the conductivity data and/or temperature data of the fluid in the regeneration liquid pipeline L2-7.
  • the regeneration fluid pipeline L2-7 of the dialysate regeneration circulation system of the present application is also provided with a replacement fluid branch L2-9, please refer to Figures 18 and 19,
  • Figure 18 shows a schematic diagram of the position of the replacement fluid branch of the hemodialysis device of the present application in the pre-dilution mode
  • Figure 19 shows a schematic diagram of the position of the replacement fluid branch of the hemodialysis device of the present application in the post-dilution mode.
  • one end of the replacement fluid branch L2-9 is connected to the regeneration fluid pipeline L2-7, and the other end is used to connect the dialysis circuit.
  • the output end of the replacement fluid branch L2-9 is used to connect the blood circuit of hemodialysis
  • the output end of the replacement fluid branch L2-9 is used to connect the peritoneal fluid circuit.
  • the regeneration liquid pipeline L2-7 is provided with a first bacterial filter 633' for filtering bacteria in the regeneration liquid, and the first output end of the first bacterial filter 633' is connected to the output end of the regeneration liquid pipeline L2-7, and the second output end is connected to the replacement liquid branch L2-9.
  • the first bacterial filter 633' is a tangential flow filter or a filter in a dead-end filtration mode.
  • the replacement liquid branch L2-9 is provided with a replacement liquid pump 650 for transporting the regeneration liquid to the dialysis circuit.
  • 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.
  • the replacement fluid branch L2-9 is used to divert the flow in the regeneration fluid pipeline L2-7 to balance the real-time dynamic balance in the dialysate regeneration circulation system.
  • the present application also provides a hemodialysis device for dialysis treatment, wherein the dialysis treatment includes the treatment of home dialysis treatment scenarios and hospital dialysis treatment scenarios.
  • FIG. 9 is a schematic diagram of the composition structure of the hemodialysis device of the present application in one embodiment.
  • the hemodialysis device includes: a purification circuit (not shown), a dialysis device 64 , a driving device 3 , and a control device 4 .
  • connection mode and working principle of the dialysate regeneration circulation system are as described in the above embodiments of Figures 1 to 8, and will not be repeated here.
  • the enzyme-carrying microspheres added to the metabolic circulation pipeline L2-4 contain urease, and the urease decomposes urea to produce carbon dioxide and ammonia.
  • a part of the generated carbon dioxide is dissolved in the liquid to form a buffer system, and a part may form gas, so that the liquid level of the collection container 600 in the metabolic circulation pipeline L2-4 drops.
  • the three-way four-way valve or the flow channel switching device on the gas branch L2-5 is started to discharge the excess carbon dioxide.
  • 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 urea removal amount, the use of OCM or adsorbent are calculated, and displayed or prompted, and the enzyme activity is reacted or detected by comparing with the experience value or historical value, and the operator is prompted to add or replace the enzyme preparation.
  • enzyme-loaded microspheres When in use, enzyme-loaded microspheres can be added to the metabolic cycle, and the enzyme-loaded microspheres are circulated in the metabolic circulation pipeline L2-4 driven by the metabolic circulation pump.
  • the treatment method is that the liquid to be treated containing a high concentration of target molecules enters the metabolic circulation pipeline L2-4 through the inlet, and the target molecules are decomposed into corresponding products by the enzyme-loaded microspheres.
  • the metabolic filtration module continuously separates the treated liquid and retains the enzyme-loaded microspheres in the metabolic circulation pipeline L2-4. The treated liquid flows out of the metabolic circulation module through the metabolic filtration module.
  • the purification circuit includes a first circuit whose input end is connected to the first part of the human body, namely, the arterial blood circuit L1, and a second circuit whose output end is connected to the second part of the human body, namely, the venous blood circuit 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 regeneration liquid pipeline L2-7 of the dialysate regeneration circulation system;
  • the driving device 3 is arranged on the first line and located in the purification circuit, and is used to drive the fluid to flow in the purification circuit; in an embodiment, the driving device 3 includes but is not limited to a peristaltic pump, a pneumatic diaphragm pump, or a pressure pump, which is used to provide power to the fluid in the pipeline so that the fluid circulates in a preset flow direction.
  • the driving device 3 should not directly contact the fluid, but only apply pressure to the pipeline and drive the fluid to flow.
  • the preferred embodiment of the driving device 3 is a non-contact pump device such as a peristaltic pump or a pneumatic diaphragm pump.
  • the peristaltic pump is, for example, a dialysis pump or a blood pump.
  • the forward and reverse (reversal) rotation of the peristaltic pump will cause the flow direction of the fluid in the circulation loop to be different.
  • the driving device 3 can be a contact driving pump or the like to drive the fluid to flow forward or reverse in the circulation loop.
  • the driving device 3 can be a contact driving pump or the like to drive the fluid to flow forward or reverse in the circulation loop.
  • the device 3 may be a contact-type driving pump or the like to drive the fluid to flow in a forward or reverse direction in the circulation loop.
  • the driving device 3 can drive the fluid in the pipeline at different positions in the pipeline, and its flow rate may change due to factors such as pipeline resistance, temperature, pressure, etc. in the direction of fluid flow.
  • the driving device 3 is arranged on the circulation loop, especially on the arterial blood line L1 of the purification loop.
  • the control device 4 is used to execute the treatment mode to purify the fluid flowing in the purification circuit and then input it into the human body.
  • the control device 4 is, for example, a controller or a system processor of a hemodialysis device, which outputs corresponding control instructions through a program written into the system processor; or receives a trigger instruction input by an operator to execute the relevant control instructions.
  • the hemodialysis equipment of the present application utilizes the dialysate regeneration circulation system.
  • a preparation containing enzyme-loaded microspheres can be added to the metabolic circulation device.
  • the preparation is driven by a driving device to circulate in the circulation pipeline.
  • the dialysis waste liquid to be treated containing a high concentration of target molecules enters the metabolic circulation device 60 through an inlet, and the target molecule preparation is decomposed into corresponding products.
  • the metabolic filtration module 605 provided in the metabolic circulation device 60 continuously separates the treated liquid and retains the preparation in the metabolic circulation device.
  • the treated liquid flows out of the metabolic circulation device 60 through the metabolic filtration module 605, and is then catalytically decomposed and adsorbed to produce a dialysis regeneration liquid. After supplementing beneficial ions such as potassium, calcium, and magnesium in the regeneration liquid pipeline L2-7, it is used again in the dialysis process.
  • the hemodialysis equipment is a hemodialysis device including a hemodialyzer or a hemodiafiltration device.
  • the hemodialysis device includes a combination of one or more treatments of hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), hemoperfusion (HP), hemoexchange (PE), immunoadsorption (IA), or continuous blood purification (CRRT).
  • HD hemodialysis
  • HF hemofiltration
  • HDF hemoperfusion
  • HP hemoexchange
  • IA immunoadsorption
  • CRRT continuous blood purification
  • the hemodialysis device also includes a dialysis device 64 for purifying the fluid flowing in the purification circuit, and the dialysis device 64 includes a dialysate output end and a dialysate input end.
  • the dialysis device 64 includes a dialyzer, and the dialyzer includes a dialysate chamber, a blood chamber and a semi-permeable membrane, etc., and the membrane separates the dialysate chamber and the blood chamber from each other.
  • the blood chamber is formed by the entire internal volume of the hollow fiber, and the dialysate chamber is formed by the inner cavity of the shell of the dialyzer surrounding the hollow fiber.
  • the top of the dialyzer is connected to the arterial blood line L1
  • the bottom of the dialyzer is connected to the venous blood line L3.
  • the purification circuit of the hemodialysis device includes a first circuit, a second circuit, and a dialysate regeneration circulation system disposed between the first circuit and the second circuit for connecting the dialysis device.
  • the first line is an arterial blood line
  • the second line is a venous blood line.
  • 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 a human body (for example, a human arterial blood vessel), 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 to access a second part of a human body (for example, a human venous blood vessel); in some embodiments, for example, when some patients have poor vascular conditions, such as single-needle dialysis or a PICC central venous catheter, the first part and the second part of the human body can be the same part.
  • a gas collecting chamber is provided on the venous blood line L3; the gas collecting 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;
  • the purification circuit includes an arterial blood line L1, a dialysis pathway (a pathway including a 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 connected to each other, so that the arterial blood line L1, the dialysis access, and the venous blood line L3 form a circulation loop, i.e., a purification loop.
  • the circulation loop can be used as a priming loop in the priming procedure; in the flushing procedure, the circulation loop is also a flushing loop; in the emptying procedure, the circulation loop is also an emptying loop.
  • an arterial puncture needle is connected to the front end of the arterial blood line L1 through a connector, and a driving device such as a peristaltic blood pump is provided in the middle.
  • a venous puncture needle is connected to the front end of the venous blood line L3 through a connector, and a drip chamber/venous pot or a gas collecting chamber having the function of a venous pot in the present application is connected in the middle.
  • the arterial puncture needle and the venous puncture needle are respectively punctured into the target arterial blood vessel and the target venous blood vessel of the patient's body.
  • the patient's blood reaches the dialysis device through the arterial blood line L1, and then the blood is purified through the dialysis device, while debubbling is performed in the drip chamber/venous pot, and the blood is returned to the patient's body through the venous blood line L3. That is, the patient's blood is circulated from the front end of the arterial blood line L1 of the circulation loop to the front end of the venous blood line L3 in vitro, while the blood is purified through the dialysis device.
  • the hemodialysis equipment includes one or more detection devices for detecting the concentration of target molecules in the dialysis waste fluid, detecting the content of enzyme-loaded microspheres in the waste fluid passage L2-1 (such as detecting the amount of enzyme-loaded microspheres added or whether they have been cleared), or detecting the content of enzyme-loaded microspheres in the regeneration fluid pipeline L2-7.
  • the hemodialysis device further comprises a mode selection device, which is used to receive an input mode selection signal and send the determined working mode information to the control device to perform the operation corresponding to the working mode.
  • the working mode includes a combination of one or more treatment modes of HF treatment mode, HD treatment mode, HDF treatment mode, or/and ultrafiltration mode.
  • FIG. 11 shows the hemodialysis device of the present application in the front
  • FIG. 11 shows the hemodialysis device of the present application in the front
  • the control device 4 controls the regeneration fluid output by the dialysate regeneration circulation system to be directly input into the first line L1, such as the arterial pot 53.
  • This mode of directly inputting the regeneration fluid into the arterial pot 53 can be called the pre-dilution mode.
  • FIG. 12 is a schematic diagram of the composition architecture of the hemodialysis equipment of the present application in the post-dilution mode.
  • the control device 4 controls the regeneration fluid output by the dialysate regeneration circulation system to be directly input into the second line L3, such as the venous pot 93.
  • This mode of directly inputting the regeneration fluid into the venous pot 93 can be called the post-dilution mode.
  • control device 4 controls the regeneration fluid output by the dialysate regeneration circulation system to be input into the dialysate input end 640 of the dialysis device 64. This is an embodiment as shown in FIG9 and FIG10.
  • the hemodialysis equipment can also realize the design of HDF treatment mode, that is, hemodiafiltration with dynamic control of the total amount of (circulating dialysate).
  • the total amount of liquid in the dialysate circulation is regulated by dynamically and periodically regulating the volume or liquid level of any container in the dialysate circulation, thereby achieving periodic filtration and filtration, and increasing the molecular convection exchange of the dialyzer.
  • the control device 4 controls the regeneration fluid output by the dialysate regeneration circulation system to be input into the first circuit, such as the arterial pot 53, through the substitution fluid branch L2-9.
  • This mode of directly inputting the regeneration fluid into the arterial pot 53 can be called a pre-dilution mode.
  • the control device 4 controls the regeneration fluid output by the dialysate regeneration circulation system to be input into the second line, such as the venous pot 93, via the substitution fluid branch L2-9.
  • This mode of directly inputting the regeneration fluid into the venous pot 93 can be called a post-dilution mode.
  • the control device 4 dynamically adjusts the liquid volume in the waste liquid passage L2-1, the metabolic circulation device 60, or the regeneration liquid pipeline L2-7 periodically to adjust the output of the replacement liquid branch L2-9 to control the molecular convection exchange volume of the dialysis device 64.
  • the control device 4 dynamically adjusts the working cycle or power of the air pump in the metabolic circulation device 60 to adjust the liquid volume in the collection container 600 to adjust the output of the replacement liquid branch L2-9, thereby controlling the molecular convection exchange volume of the dialysis device 64.
  • control device periodically changes the total amount of liquid equilibrium state of the dialysate circulation to periodically filter and filter out the liquid inside and outside the dialyzer.
  • changing the total amount of liquid equilibrium state of the dialysate circulation is achieved by the control device periodically injecting or sucking air into or out of any container in the flow path to change the liquid volume of any container.
  • changing the total amount of fluid equilibrium in the dialysate circulation is accomplished by
  • the control device periodically changes the volume of any container in the flow path, such as a collection container in a metabolic cycle, or the control device periodically expands or reduces the volume of any flow channel, pipeline or container in the flow path.
  • the total amount of liquid equilibrium state in the dialysate circulation is changed by adjusting the differential speed of two dialysate pumps, a first dialysate pump 627' in the waste liquid passage L2-1 and a second dialysate pump 627" in the regeneration liquid line L2-7.
  • the present application can realize the design of HDF treatment mode by setting gas branch L2-5 in the metabolic circulation device, that is, hemodiafiltration with dynamic control of the total amount of (circulating dialysate).
  • gas branch L2-5 in the metabolic circulation device
  • dynamic control of the total amount of (circulating dialysate) By dynamically and periodically regulating the volume or liquid level of any container in the dialysate circulation, the total amount of liquid in the dialysate circulation is regulated, thereby achieving periodic filtration and filtration, and increasing the molecular convection exchange of the dialyzer.
  • the exhaust valve 6031 for example, a four-way valve, can be connected to an air pump (6030', 6030") or a pressure sensor 6231" for degassing or aerating.
  • the liquid level in the collection container 600 is at a low level, and the air is about 25mL. Since liquid is continuously injected into the dialysis waste liquid passage L2-1, the air chamber in the collection container 600 is at positive pressure.
  • an HDF process can be divided into many identical cycles, or air pump gasification or degassing cycles.
  • the liquid level and liquid volume in the collection container 600 are controlled by selectively controlling the first air pump 6030' or the second air pump 6030".
  • the degassing cycle (assuming 30 seconds)
  • the liquid level in the collection container 600 rises slowly, and the amount of water in the blood filtered to the dialysate side increases. If the degassing speed of the air pump is 46 ml/min, then the filtered water is 23 mL.
  • the gas pressurized liquid level drops, and more dialysate is filtered into the blood at the same speed of 46 ml/min. That is, the increased filtration rate in one cycle (1 minute) is 23 mL, so the filtration volume in the entire treatment cycle of 240 minutes is 5.52 L.
  • the gas filling speed is faster, for example, the gas filling is completed in 5 seconds, and the flow rate is 276ml/min; in this case, the time of one cycle is 35s, and the treatment time of 240min can work 411.4 cycles, and the total filtration volume is 9.45L.
  • the ultrafiltration branch L2-2 in the dialysate regeneration circulation system diverts the dialysate waste in the waste fluid passage L2-1 to increase the transmembrane pressure or negative pressure, so that the dialysis device filters an equal amount of liquid from the blood or peritoneal fluid flowing through it into the dialysate waste, thereby achieving dehydration treatment.
  • the control device controls the speed of the ultrafiltration pump or the empirical value to measure the flow rate of the dialysis waste liquid in the waste liquid passage L2-1 diverted by the ultrafiltration branch L2-2.
  • the control device controls the speed of the ultrafiltration pump by obtaining the volume or weight of the regeneration liquid in the regeneration liquid pipeline L2-7 to measure the ultrafiltration branch L2-2.
  • the flow of the dialysis waste liquid in the waste liquid passage L2-1 is diverted by the passage L2-2.
  • the volume or weight of the regeneration liquid is obtained by weighing or liquid level measurement.
  • dialysate regeneration circulation system is applied to a blood purification device, for example in a hemodialysis treatment mode (HD), that is, a standard normal treatment mode
  • hemodialysis treatment mode that is, a standard normal treatment mode
  • the exchange between molecules is a free exchange driven by concentration difference
  • the purpose of exchange and toxin removal is achieved.
  • an ultrafiltration branch L2-2 is provided on the waste liquid passage L2-1, simultaneous ultrafiltration and dehydration can bring about an additional amount (e.g., 3-4L) of transmembrane flow.
  • the ultrafiltration pump when the dialysate regeneration circulation system is applied to the circulation of a blood purification device, the ultrafiltration pump will continuously extract the water in the waste liquid passage L2-1 to form a transmembrane negative pressure. At this time, the dialyzer will ultrafilter more water to achieve pressure balance. Ultimately, the blood loses as much water as the ultrafiltration pump extracts, thereby achieving the purpose of dehydration.
  • the ultrafiltration pump continuously draws the dialysate waste in the waste liquid passage L2-1 into a waste liquid bag. By accurately measuring the flow rate of the ultrafiltration pump, the excess water in the patient's body can be accurately extracted from the body, thereby achieving the purpose of dehydration.
  • the ultrafiltration branch L2-2 can also be arranged on the regeneration 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 arranged on the waste liquid channel, and the second ultrafiltration branch is arranged on the regeneration liquid pipeline L2-7.
  • weighing ultrafiltration control is adopted, that is, dual pump control of an upstream pump and a downstream pump is adopted, wherein the upstream pump is arranged on the first ultrafiltration branch, and the downstream pump is arranged on the second ultrafiltration branch in the regeneration liquid pipeline L2-7, and the second ultrafiltration branch is connected to the second ultrafiltration branch.
  • the container connected to the filter branch such as an ultrafiltration bag, contains treated dialysis regeneration fluid.
  • the weighing device can obtain the content of the regeneration fluid in the ultrafiltration bag by weighing, and adjust the speed of the upstream pump and the downstream pump by controlling the speed. For example, if the water in the ultrafiltration bag exceeds the preset value (ultrafiltration curve), it means that more water has been ultrafiltrated, so the speed of the upstream pump is lowered and the speed of the downstream pump is increased. On the contrary, if the water in the ultrafiltration bag is lower than the preset value (ultrafiltration curve), the speed of the upstream pump can be increased and the speed of the downstream pump can be lowered.
  • the preset value ultrafiltration curve
  • the present application also provides a peritoneal dialysis device for dialysis treatment, wherein the dialysis treatment includes the treatment of home dialysis treatment scenarios and hospital dialysis treatment scenarios.
  • the peritoneal dialysis device includes a dialysate regeneration circulation system, a peritoneal dialysis pipeline, a driving device and a control device.
  • One end of the peritoneal dialysis pipeline is connected to the human peritoneal cavity, and the other end is connected to the dialysate regeneration circulation system; the peritoneal dialysis pipeline uses a single-pass catheter to periodically drain the accumulated fluid in the human peritoneal cavity and periodically introduce the dialysate regeneration fluid.
  • the driving device is disposed on the peritoneal dialysis pipeline and is used to drive the fluid to flow periodically in the peritoneal dialysis pipeline;
  • the control device is used to execute a treatment mode to periodically exchange fluid in the peritoneum of a human body.
  • connection mode and working principle of the dialysate regeneration circulation system are as described above for each embodiment of FIG. 1 to FIG. 8. The method is not described here.
  • the enzyme-loaded microspheres added to the metabolic circulation pipeline L2-4 contain urease, and the urease decomposes urea to produce carbon dioxide and ammonia.
  • a part of the generated carbon dioxide is dissolved in the liquid to form a buffer system, and a part may form gas, so that the liquid level of the collection container in the metabolic circulation pipeline L2-4 drops.
  • the three-way four-way valve or the flow channel switching device on the gas branch L2-5 is started to discharge excess carbon dioxide.
  • 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 urea removal amount, OCM or adsorbent usage are calculated, and displayed or prompted. By comparing with the empirical value or historical value, the activity of the enzyme is reacted or detected, and the operator is prompted to add or replace the enzyme preparation.
  • enzyme-loaded microspheres When in use, enzyme-loaded microspheres can be added to the metabolic cycle, and the enzyme-loaded microspheres are circulated in the metabolic circulation pipeline L2-4 driven by the metabolic circulation pump.
  • the treatment method is that the liquid to be treated containing a high concentration of target molecules enters the metabolic circulation pipeline L2-4 through the inlet, and the target molecules are decomposed into corresponding products by the enzyme-loaded microspheres.
  • the metabolic filtration module continuously separates the treated liquid and retains the enzyme-loaded microspheres in the metabolic circulation pipeline L2-4. The treated liquid flows out of the metabolic circulation module through the metabolic filtration module.
  • the dialysis device of the present application adds a preparation such as enzyme-loaded microspheres to a metabolic circulation device, and the preparation circulates in a circulation pipeline through the drive of a driving device.
  • the treated liquid is continuously separated out by a metabolic filtration module provided in the metabolic circulation device, and the preparation is retained in the metabolic circulation device.
  • the treated liquid flows out of the metabolic circulation device through the metabolic filtration module, and is then catalytically decomposed and adsorbed to produce a dialysis regeneration liquid.
  • the dialysis liquid is used again in the dialysis process, thereby solving the problems of low exchange efficiency in the existing perfusion mode, which increases the amount of enzyme used, and the loss of enzyme efficiency and safety risks due to enzyme shedding.

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Abstract

La présente invention concerne un système de circulation de régénération de dialysat et un dispositif de dialyse. Une formulation, telle que des microsphères chargées d'enzyme, est ajoutée à un appareil de circulation métabolique (60). La formulation circule dans une conduite de circulation au moyen de l'entraînement d'un appareil d'entraînement. Un liquide traité est séparé en continu au moyen d'un module de filtre métabolique disposé dans l'appareil de circulation métabolique (60), la formulation est retenue dans l'appareil de circulation métabolique (60), et le liquide traité s'écoule hors de l'appareil de circulation métabolique (60) au moyen du module de filtre métabolique et est ensuite soumis à une décomposition catalytique et à une adsorption pour produire un liquide de régénération de dialyse. Après l'ajout d'ions potassium, calcium et magnésium dans une conduite de liquide de régénération (L2-7), le liquide de régénération de dialyse est réutilisé dans le processus de dialyse, de façon à résoudre les problèmes de faible efficacité d'échange dans les modes de perfusion existants, qui conduisent à une utilisation d'enzyme accrue, la perte d'efficacité d'enzyme et les risques de sécurité provoqués par une libération d'enzyme, et analogues.
PCT/CN2023/131926 2022-12-09 2023-11-16 Système de circulation de régénération de dialysat et dispositif de dialyse WO2024120144A1 (fr)

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JPH1071201A (ja) * 1996-01-19 1998-03-17 Terumo Corp 血液浄化排液再生装置、血液浄化液回路および血液浄化装置
CN101374558A (zh) * 2006-01-30 2009-02-25 加利福尼亚大学董事会 腹膜透析方法和装置
US20120273354A1 (en) * 2011-04-29 2012-11-01 Medtronic, Inc. Multimodal dialysis system
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