A double filtration sequence series high clearance hemodiafiltration device and method

Abstract

The application discloses a double-filtering-sequence connected high-definition removal rate hemodialysis filtration device and method, and relates to the technical field of medical instruments.The application comprises five units of double-filtering-sequence connected filtration, parameter acquisition, intelligent control, liquid delivery and flushing return, the filtration unit is composed of a primary coarse filter, a secondary fine filter and a dialyzer connected in series, all adopt microwave wave-shaped hollow fiber high-flux polysulfone membranes, and realizes the graded flow filtration of macromolecules and the dispersion removal of small molecules according to the gradient pore size; the parameter acquisition unit acquires full-link data in real time through multiple sensors; the liquid delivery unit provides power and fluid delivery with a precise adjustable pump body; the intelligent control unit is internally provided with three types of core algorithms, drives the cooperative work of each unit, realizes the intelligent matching of preoperative parameters, the dynamic adjustment of process parameters such as the transmembrane pressure during operation, and the postoperative time sequence alternating flushing of double catheters.The application realizes the graded purification of blood and the safe return of residual blood, and improves the efficiency and intelligent level of dialysis filtration.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a dual-filtration sequential high-clearance hemodialysis filtration device and method. Background Technology

[0002] Chinese patent (publication number CN109433031A) discloses a polysulfone ultrafiltration membrane and its application in the field of hemodialysis. By modifying the polysulfone membrane, the water flux and antifouling properties are improved, solving the problems of easy clogging of the membrane material and rapid decline in removal efficiency. However, its core filtration architecture design has obvious shortcomings. It adopts the traditional combination of a single filter and a dialyzer. Even when paired with a high-flux polysulfone membrane, it can only achieve mixed filtration of medium and large molecular toxins and small molecular toxins. It does not design a graded filtration structure with gradient pore size. Large-particle medium molecular toxins are easy to cause membrane pore blockage, while small-particle medium molecular toxins are difficult to be completely removed due to insufficient filtration precision.

[0003] Chinese patent (publication number CN107921196B) discloses a blood therapy device with an online solution preparation unit. By setting a control mechanism for a pre-filling mode and an initial treatment mode, it realizes the online preparation of flushing solution and dialysate with pH value ≥ 7.3 and the pre-filling of the loop, which improves the compatibility between dialysate and flushing solution and reduces the risk of blood irritation and coagulation caused by solution pH imbalance. At the same time, it realizes the automated connection between pre-filling and treatment through an open-loop / closed-loop control unit. However, it only focuses on optimizing the solution preparation and loop pre-filling links, still adopts the traditional combination of a single filter and dialyzer, has low efficiency in removing medium molecular toxins, and the parameter control is only for the solution preparation link. The level of intelligence and automation is low, and it cannot achieve dynamic adaptation of the treatment process according to real-time parameters.

[0004] In summary, existing hemodialysis filtration technologies focus on improvements such as membrane material modification and local structural optimization, but still have significant shortcomings in terms of intelligence and efficiency. Therefore, developing a hemodialysis filtration device that combines a high-clearance filtration architecture, intelligent and precise control throughout the entire process, and dynamic pressure adaptation, along with designing a corresponding end-to-end filtration method, has become a key technical challenge that urgently needs to be addressed in the field of blood purification medical devices. Summary of the Invention

[0005] Based on the above-mentioned technical problems, this application discloses a dual-filter sequential high-clearance hemodialysis filtration device and method; the dual-filter sequential high-clearance hemodialysis filtration device specifically includes a dual-filter sequential filtration unit, a parameter acquisition unit, an intelligent control unit, a liquid delivery unit, and a flushing and reinfusion unit; The dual-filtration unit comprises a primary coarse filter, a secondary fine filter, and a dialyzer connected in series, forming the core filtration architecture of the entire device. It is connected to the patient's vascular access via a main blood pipeline, and its replacement fluid interface and dialysate interface are connected to the liquid delivery unit pipeline. The parameter acquisition unit is deployed externally in the inlet and outlet of the dual-filter sequential filtration unit and the delivery pipeline of the liquid delivery unit. The intelligent control unit receives signals from the parameter acquisition unit and drives the units to work together through the built-in algorithm to achieve graded filtration of blood, dynamic adjustment of parameters, and automatic loop flushing and reinfusion. The liquid delivery unit includes a replacement fluid supply component, a dialysate supply component, and a power drive component. The output of the replacement fluid supply component is divided into two paths, which are respectively connected to the arterial input end of the primary coarse filter and the input end of the secondary fine filter. The inlet and outlet of the dialysate supply component are sealed and connected to the dialysate interface of the dialyzer. The output end of the flushing and reinfusion unit is sealed and connected to the main blood pipeline on the side of the arterial catheter closest to the patient. The electric clamping valve of the flushing and reinfusion unit is deployed on the arterial catheter, venous catheter and blood return circuit, forming a flushing and reinfusion pathway with the blood circuit.

[0006] Preferably, the primary coarse filter, secondary fine filter, and dialyzer of the dual-filtration sequential filtration unit are all made of nanoscale high-flux polysulfone membranes with micro-wave hollow fiber structure, and all pipeline connection nodes are sealed with Luer joints. Among them, the primary coarse filter mainly uses convection and a small amount of diffusion as a supplement. Based on the pressure difference of the liquid delivery unit, the transmembrane pressure is formed, so that large-particle medium-molecular toxins, tiny blood impurities and some excess water in the blood are filtered through the semipermeable membrane along with the replacement fluid. The secondary fine filter receives blood after the primary coarse filter through convection and diffusion, and uses gradient pore size to achieve precise sieving, deeply removing small molecular toxins that were not completely removed by the primary coarse filter. The dialyzer receives blood after secondary fine filtration. The flow direction of the dialysate inside the dialyzer is reversed to the flow direction of the blood inside the dialyzer. Based on the concentration gradient, osmotic gradient and water pressure gradient between the blood and the dialysate, diffusion is the main method and convection is the auxiliary method. After effectively removing small molecule toxins from the blood, the blood is output to the venous outlet.

[0007] Preferably, the parameter acquisition unit includes a medical-grade pressure sensor, a flow sensor, a blood index sensor, and a filtration status sensor; The pressure sensor and flow sensor are respectively connected to the blood side and dialysate / replacement fluid side pipelines of each filter / dialyzer in the dual-filtration sequence filtration unit, as well as the replacement fluid and dialysate delivery pipelines of the liquid delivery unit; The blood index sensor is embedded in the blood output end of the primary coarse filter and the blood output end pipeline of the secondary fine filter. The filtration status sensor is embedded inside the membrane modules of the primary coarse filter, the secondary fine filter, and the dialyzer; Each miniature sensor wirelessly transmits the collected real-time data to the intelligent control unit.

[0008] Preferably, the power drive components of the liquid delivery unit include a blood pump, a dual-path replacement fluid pump, and a dialysate pump; the blood pump is connected in series to the main blood pipeline between the arterial catheter and the primary coarse filter, the dual-path replacement fluid pump is connected in series to the dual-path output pipeline of the replacement fluid supply component, and the dialysate pump is connected in series to the main pipeline of the dialysate supply component; the blood pump, the dual-path replacement fluid pump, and the dialysate pump are all precision pumps with adjustable speed, and are all electrically connected to an intelligent control unit through control circuits, with the intelligent control unit controlling the speed, start / stop, and flow output.

[0009] Preferably, the intelligent control unit includes a data processing component, an algorithm storage component, and a parameter adjustment component, all of which are electrically connected via a circuit board. The data processing component is connected to the parameter acquisition unit via a wireless receiving component to receive, analyze, and process real-time acquired data. The algorithm storage component incorporates a graded filtration matching algorithm, a dynamic adaptation filtration algorithm, and a dual-duct sequential alternating flushing algorithm. The output control signal of the parameter adjustment component can precisely adjust the speed of each pump and the action of the valves.

[0010] The aforementioned high-clearance hemodialysis filtration method with a dual-filtration sequence is specifically as follows: Two high-flux polysulfone membrane filters are connected in series at the front end of the dialyzer, with the dialysate and blood flowing in opposite directions, to obtain a hierarchical filtration architecture with a dual-filter sequence structure. Before filtration treatment, based on the patient's basic information, the initial parameters of the hierarchical filtration architecture are automatically adjusted through the hierarchical filtration matching algorithm built into the intelligent control unit. At the start of filtration therapy, the patient's blood is drawn through the liquid delivery unit to the arterial inlet of the primary coarse filter, and replacement fluid is added to mix with the patient's blood before coarse filtration. After coarse filtration, the blood enters the secondary fine filter, and replacement fluid is simultaneously added from the inlet of the secondary fine filter for fine filtration. After fine filtration, the blood flows into the dialyzer for purification, and the blood electrolyte and acid-base balance is corrected. The purified blood is then returned to the patient. During the filtration treatment, blood parameters and filtration process parameters are collected through the parameter acquisition unit. The dynamic adaptation filtration algorithm built into the intelligent control unit is used to adjust the replacement fluid flow rate, blood flow rate, transmembrane pressure of the primary coarse filter and the secondary fine filter, as well as the dialysate flow rate of the dialyzer. After the filtration treatment is completed, the flushing and reinfusion unit is controlled by the dual-catheter sequential alternating flushing algorithm built into the intelligent control unit. Sterile saline is used to flush the blood circuit and reinfuse the residual blood in the blood circuit into the patient's body to complete the entire dialysis filtration process.

[0011] The preferred graded filtration matching algorithm is as follows: the patient's basic information is entered, and the inherent hardware parameters of the device's dual-filtration sequential filtration unit and liquid delivery unit are simultaneously called and transmitted to the data processing component of the intelligent control unit. The data processing component of the intelligent control unit standardizes the entered patient basic information and, in conjunction with the device hardware parameters, clarifies the adjustment boundaries of the initial parameters; Based on the preprocessed data and a pre-defined clinical filtration standard model, initial parameters adapted to the patient are output through multi-dimensional fitting calculations, including the initial blood flow rate. The calculation formula is: ; in, The weight correction factor is determined based on the total membrane area of ​​the primary coarse filter and the secondary fine filter. This is the correction factor for toxin concentration calculated based on the pore size of the secondary fine filter membrane. Hardware adaptation correction values, For the patient's weight, This represents the initial concentration of β2-microglobulin in the patient's blood. The formula for calculating the initial displacement fluid flow rate is: ; ; in, , These correspond to the initial flow rates of the two displacement fluids, This represents the percentage before dilution. This is the urea removal correction factor. This is the maximum flow rate of the dialysate pump. This refers to the initial concentration of urea in the patient's blood. Initial ultrafiltration volume The calculation formula is: ; in, To adapt to the initial ultrafiltration stability of polysulfone membrane filters, The initial concentration of creatinine in the patient's blood. This refers to the normal reference value for creatinine. The initial parameters obtained from the calculation are transmitted to the parameter adjustment component of the intelligent control unit. The parameter adjustment component sends a control signal to the power drive component of the liquid delivery unit to complete the parameter initialization of the staged filtration architecture.

[0012] Preferably, the dynamically adaptable filtration algorithm specifically involves: the data processing component of the intelligent control unit calculating the transmembrane pressure (TMP) in real time based on the collected pressure data; dividing the current pressure into three zones—safe, warning, and emergency—based on the real-time TMP zone; and automatically adjusting the blood flow rate through the blood pump, dual-path replacement fluid pump, and dialysate pump based on the current TMP zone. Pre-dilution flow rate Post-dilution flow rate dialysis fluid flow rate To ensure a high toxin clearance rate while bringing TMP back to a safe range, the blood flow adjustment formula is as follows: ; in, To adjust the target blood flow, For the current blood flow, This is the transmembrane pressure adjustment coefficient. This is a correction factor for blood viscosity. The formulas for adjusting the pre-dilution flow rate and the post-dilution flow rate are as follows: ; To adjust the pre-dilution replacement fluid flow rate, Given the current pre-dilution replacement fluid flow rate, For real-time blood viscosity, Based on the viscosity, The adjusted flow rate of the post-dilution replacement solution; The formula for adjusting the dialysate flow rate is: ; For dialysate flow rate, This represents the toxin clearance coefficient. This represents the current urea concentration. This represents the current creatinine concentration.

[0013] Preferably, the dual-catheter sequential alternating flushing algorithm specifically involves: the intelligent control unit reading preset flushing parameters, including total saline volume, flushing pump flow rate, arterial / venous catheter alternation cycle, and single clamping duration; Start the flushing pump of the flushing and reinfusion unit, and inject sterile saline into the main blood pipeline from the arterial catheter side; The algorithm drives the electric clamping valve in a fixed sequence, cycling between the first and second stages: in the first stage, the arterial catheter is clamped, the venous catheter is released, and the preset venous catheter flushing time is maintained; in the second stage, the arterial catheter is released, the venous catheter is clamped, and the preset arterial catheter flushing time is maintained. The parameter acquisition unit monitors the circuit pressure in real time and dynamically adjusts the clamping / releasing time according to the pressure. When the actual infusion volume of saline reaches the preset total volume, the algorithm stops flushing, releases all clamping valves, and completes the reinfusion of residual blood.

[0014] Preferably, the clamping / releasing time is dynamically adjusted according to the pressure, specifically by: acquiring the real-time pressure of the circuit through a pressure sensor and calculating the pressure deviation. The clamping and releasing times are dynamically adjusted based on the pressure deviation, using the following formula: ; ; in, The adjusted clamping time, The preset basic clamping time, For the flushing pump flow rate, The adjusted release duration, The preset base release time.

[0015] Compared with the prior art, the technical solution of this application has the following technical effects: This invention designs a dual-filtration sequential core architecture, with a primary coarse filter, a secondary fine filter, and a dialyzer forming a coarse-fine-filtration-dialysis purification process. This process removes large and small-sized medium-molecular toxins in stages. Without using low-flux filter membranes, small molecules are efficiently removed through reverse flow in the dialyzer, resulting in a significant improvement in the overall toxin removal rate and a marked optimization of the removal effect of medium-sized molecules such as β2-microglobulin.

[0016] This invention utilizes three core algorithms built into the intelligent control unit to match personalized initial parameters based on the patient's weight and toxin concentration before surgery, and dynamically adjusts blood flow and replacement fluid flow rate based on real-time data during surgery. This overcomes the limitations of existing single-dimensional adjustment, improves parameter accuracy, and reduces treatment complications.

[0017] This invention employs a micro-wave-shaped hollow fiber high-flux polysulfone membrane, maximizing the effective surface area of ​​the fibers. This reduces ineffective areas caused by hollow fiber polymerization and adhesion, ensuring the dialyzer operates at its highest efficiency and with maximum clearance capacity, achieving truly high-efficiency dialysis.

[0018] The above description is only an overview of the technical solution of this application. In order to better understand the technical means of this application and implement it in accordance with the contents of the specification, and to make the above and other objects, features and advantages of this application more obvious and understandable, the preferred embodiments of this application are described in detail below with reference to the accompanying drawings.

[0019] The above and other objects, advantages and features of this application will become more apparent to those skilled in the art from the following detailed description of specific embodiments in conjunction with the accompanying drawings. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. In all drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the elements or parts are not necessarily drawn to scale.

[0021] Based on the description of the figures and their corresponding technical content in the document, the titles of the figures are as follows: Figure 1 This is a schematic diagram of a dual-filtration sequence high-clearance hemodialysis filtration device; Figure 2 A physical image of a dual-filtration sequence high-clearance hemodialysis filtration device; Figure 3 This is a schematic diagram of the micro-wavy hollow fiber structure in this application; Figure 4 This is an architectural diagram of a dual-filtration sequence high-clearance hemodialysis filtration method; Figure 5 This is a data diagram of the dynamic adaptation filtering process in the embodiments of this application; Figure 6 This is a data graph of the dialysis process for each method in the embodiments of this application; Figure 7 This is a comparison chart of dialysis filtration clearance data for various patients using this method in the embodiments of this application; Figure 8 This is a comparison chart of dialysis filtration clearance data for each method in the embodiments of this application; Figure 9 This is a comparative data chart showing the overall performance of the methods in the embodiments of this application.

[0022] In the diagram: 1. Dual-stage sequential filtration unit; 2. Parameter acquisition unit; 3. Intelligent control unit; 4. Liquid delivery unit; 5. Flushing and reinfusion unit; 6. Primary coarse filter; 7. Secondary fine filter; 8. Dialyzer; 9. Replacement fluid supply assembly; 10. Dialysis fluid supply assembly; 11. Power drive assembly; 12. Blood pump; 13. Dual-path replacement fluid pump; 14. Dialysis fluid pump; 15. Electric pinch valve. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. In the following description, specific details such as specific configurations and components are provided merely to help fully understand the embodiments of this application. Therefore, those skilled in the art should understand that various changes and modifications can be made to the embodiments described herein without departing from the scope and spirit of this application. In addition, for clarity and brevity, descriptions of known functions and structures are omitted in the embodiments.

[0024] It should be understood that the phrase "an embodiment" or "this embodiment" throughout the specification means that a specific feature, structure, or characteristic related to the embodiment is included in at least one embodiment of this application. Therefore, "an embodiment" or "this embodiment" appearing throughout the specification does not necessarily refer to the same embodiment. Furthermore, these specific features, structures, or characteristics can be combined in any suitable manner in one or more embodiments.

[0025] Furthermore, reference numerals and / or letters may be repeated in different examples within this application. Such repetition is for the purpose of simplification and clarity and does not in itself indicate a relationship between the various embodiments and / or settings discussed.

[0026] In this article, the term "and / or" is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can mean: A exists alone, B exists alone, and A and B exist simultaneously. The term " / and" in this article describes another type of relationship between related objects, indicating that two relationships can exist. For example, A / and B can mean: A exists alone, and A and B exist alone. In addition, the character " / " in this article generally indicates that the related objects before and after it are in an "or" relationship.

[0027] In this article, the term "at least one" is merely a description of the relationship between related objects, indicating that there can be three relationships. For example, "at least one of A and B" can mean: A exists alone, A and B exist simultaneously, or B exists alone.

[0028] It should also be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion.

[0029] Example 1 describes a dual-filtration sequence high-clearance hemodialysis filtration device and method. Figure 1 As shown, it specifically includes a dual-filter sequential filtration unit 1, a parameter acquisition unit 2, an intelligent control unit 3, a liquid delivery unit 4, and a flushing and return unit 5; The dual-filtration unit 1 includes a primary coarse filter 6, a secondary fine filter 7, and a dialyzer 8, which is the core filtration architecture of the entire device. It is connected to the patient's vascular access through the main blood pipeline, and its replacement fluid interface and dialysate interface are connected to the fluid delivery unit 4 pipeline. The parameter acquisition unit 2 is deployed in the inlet and outlet of the dual-filter sequential filtration unit 1 and the delivery pipeline of the liquid delivery unit 4 via external pipeline connection. The intelligent control unit 3 receives the signal from the parameter acquisition unit 2 and drives each unit to work together through the built-in algorithm to realize graded filtration of blood, dynamic adjustment of parameters and automatic loop flushing and reinfusion. The liquid delivery unit 4 includes a replacement fluid supply component 9, a dialysate supply component 10, and a power drive component 11. The output end of the replacement fluid supply component 9 is divided into two paths, which are respectively connected to the arterial input end of the primary coarse filter 6 and the input end of the secondary fine filter 7. The inlet and outlet of the dialysate supply component 10 are sealed and connected to the dialysate interface of the dialyzer 8. The output end of the flushing and reinfusion unit 5 is sealed and connected to the blood main pipeline on the side of the arterial catheter closest to the patient. The electric clamping valve 15 of the flushing and reinfusion unit 5 is deployed on the arterial catheter, venous catheter and blood return circuit, forming a flushing and reinfusion pathway with the blood circuit.

[0030] Furthermore, the primary coarse filter 6, the secondary fine filter 7, and the dialyzer 8 of the dual-filtration sequential filtration unit 1 are all made of nanoscale high-flux polysulfone membranes with micro-wave hollow fiber structure, and all pipeline connection nodes are sealed with Luer joints. Among them, the primary coarse filter 6 mainly uses convection and a small amount of diffusion as a supplement. Based on the pressure difference of the liquid delivery unit 4, the transmembrane pressure is formed, so that large-particle medium-molecular toxins, tiny blood impurities and some excess water in the blood are filtered through the semipermeable membrane along with the replacement fluid. The secondary fine filter 7 receives the blood after the primary coarse filter 6 through convection and diffusion, and uses gradient pore size to achieve precise screening, deeply removing small-particle molecular toxins that were not completely removed by the primary coarse filter 6. The dialyzer 8 receives the blood processed by the secondary fine filter 7. The flow direction of the dialysate in the dialyzer 8 is reversed with the flow direction of the blood in the dialyzer 8. Based on the concentration gradient, osmotic gradient and water pressure gradient between the blood and the dialysate, the blood is mainly removed by diffusion and secondarily by convection. After the blood is efficiently removed, it is output to the venous output end.

[0031] Furthermore, such as Figure 3 The diagram shows a micro-wavy hollow fiber structure. Figure 3 (a) is a photograph of the micro-wavy hollow fiber structure. Figure 3 (b) is a diagram showing the arrangement and distribution of the micro-wavy hollow fiber structure. Figure 3 (c) is a schematic diagram of the micro-wave hollow fiber structure. This wave technology, by employing wavy hollow fibers, fully utilizes the effective area of ​​the fibers, thereby reducing ineffective areas caused by the polymerization and adhesion of the hollow fibers, ensuring that the dialyzer can operate at its highest efficiency and with maximum cleaning capacity, thus achieving truly high-efficiency dialysis.

[0032] Furthermore, the primary coarse filter 6 adopts a polysulfone-PVP blend modified micro-wave hollow fiber structure with a packing density of 52%~55%, a membrane detachment force greater than 1000g, an average pore size of 2.8~3nm, and a maximum pore size of 4.5~5nm. The replacement fluid is mixed with blood and injected from the arterial inlet, and the two flow in a co-current manner. The purification principle is mainly based on convection and supplemented by a small amount of diffusion. It relies on the stable transmembrane pressure established by the liquid delivery unit 4 as the driving force to drive large-particle medium-molecular toxins, small impurities, and some excess water in the blood to cross the membrane for filtration, realizing pre-coarse filtration and load splitting. The co-current injection makes the transmembrane pressure distribution on the membrane surface uniform, while diluting the concentration of blood toxins and reducing the risk of membrane adsorption and coagulation. The micro-diffusion only assists in removing a small amount of small-molecule toxins. The membrane pore size strictly retains substances with a molecular weight greater than 35,000 d to avoid albumin loss.

[0033] Furthermore, the secondary fine filter 7 is a high-flux polysulfone membrane filter made of the same material and structure as the primary coarse filter 6, with an average pore size of 2.5~2.8nm and a maximum pore size of 3.5~4.5nm. The purification principle is mainly convection with diffusion as a secondary process. It receives blood after the primary coarse filter 6 and achieves precise convection filtration by relying on gradient pore size and stable transmembrane pressure to deeply remove small-particle toxins that have not been removed. The co-current design, combined with the ultra-smooth structure of the inner surface of the membrane, further reduces the blood contact area and flow resistance, reduces the activation of coagulation factors and blood residue, and micro-diffusion assists in optimizing the initial removal of small-molecule toxins, reducing the burden on subsequent dialysis processes.

[0034] Furthermore, such as Figure 2The diagram shown depicts the structure of dialyzer 8, which uses a polysulfone-PVP blend modified membrane material. It shares core parameters such as a packing density of 52%–55%, a membrane release force greater than 1000g from the shell, and Luer joint sealing in the tubing. The average pore size is 3 nm, the maximum pore size is 5 nm, the membrane thickness is 40 μm, the ultrafiltration coefficient is 50 ml / (h·mmHg), the urea removal rate is greater than 190 ml / L, the β2-MG removal rate is greater than 20 ml / min, and it is sterilized using Gamma rays. Blood... The dialysis fluid flows in opposite directions on both sides of the membrane. The purification principle is based on diffusion as the main method and convection as a secondary method. It relies on the reverse flow to maintain a continuous concentration gradient on the membrane surface. Without using a low-flux filter membrane, it can efficiently diffuse and remove small molecule toxins such as urea and creatinine. At the same time, it removes excess water in the body through transmembrane pressure-driven convection ultrafiltration. During dialysis, it replenishes the substances needed by the body, corrects electrolyte and acid-base imbalances, and the honeycomb network structure of the membrane can adsorb lipopolysaccharides and endotoxins, prevent back diffusion and reverse ultrafiltration, and ensure the safety of dialysis.

[0035] Furthermore, parameter acquisition unit 2 includes a medical-grade pressure sensor, a flow sensor, a blood index sensor, and a filtration status sensor; The pressure sensor and flow sensor are respectively connected to the blood side and dialysate / replacement fluid side pipelines of each filter / dialyzer 8 in the dual-filtration sequential filtration unit 1, as well as the replacement fluid and dialysate delivery pipelines of the liquid delivery unit 4. The blood index sensor is embedded in the blood output end of the primary coarse filter 6 and the blood output end pipeline of the secondary fine filter 7. The filtration status sensor is embedded inside the membrane assembly of the primary coarse filter 6, the secondary fine filter 7, and the dialyzer 8. Each micro-sensor wirelessly transmits the collected real-time data to the intelligent control unit 3.

[0036] Furthermore, the pressure sensor is a medical-grade diffused silicon pressure sensor with a measurement range of -100 to 500 mmHg, an accuracy of 0.5%FS, and a response time of less than 10 ms. It collects real-time pressure data from the blood side and the dialysate / replacement fluid side of each filter / dialyzer 8. The flow sensor is a medical-grade ultrasonic flow sensor with a blood flow measurement range of 0 to 500 mL / min and a replacement fluid / dialysate flow measurement range of 0 to 300 mL / min, an accuracy of 1%FS, and non-contact measurement. The blood index sensor is a miniature... The photoelectric sensor can detect blood viscosity (measurement range 1.0~2.0 mPa·s), hematocrit (measurement range 20%~60%), and the real-time concentrations of urea, creatinine, and β2-microglobulin, with a detection accuracy of 2%. The filtration status sensor is a fiber optic leakage sensor with a blood leakage detection sensitivity greater than 0.01 mL / L and a filter fiber integrity detection response time of less than 50 ms. All sensors are medical-grade waterproof and anti-coagulant with an IP67 protection rating. The detection end is made of medical-grade polysulfone material and undergoes hydrophilic treatment.

[0037] Furthermore, the power drive assembly 11 of the liquid delivery unit 4 includes a blood pump 12, a dual-path replacement fluid pump 13, and a dialysate pump 14; the blood pump 12 is connected in series to the main blood pipeline between the arterial catheter and the primary coarse filter 6, the dual-path replacement fluid pump 13 is connected in series to the dual-path output pipeline of the replacement fluid supply assembly 9, and the dialysate pump 14 is connected in series to the main pipeline of the dialysate supply assembly 10; the blood pump 12, the dual-path replacement fluid pump 13, and the dialysate pump 14 are all precision pumps with adjustable speed, and are all electrically connected to the intelligent control unit 3 through control circuits, and the intelligent control unit 3 controls the speed, start / stop, and flow output.

[0038] Furthermore, the blood pump 12, the dual-channel replacement fluid pump 13, and the dialysate pump 14 are all medical-grade precision peristaltic pumps; the blood pump 12 has a flow rate adjustment range of 0~400mL / min, a speed adjustment accuracy of 1mL / min, and a maximum output pressure greater than 300mmHg; the dual-channel replacement fluid pump 13 has a flow rate adjustment range of 0~200mL / min, a speed adjustment accuracy of 0.5mL / min, and a maximum output pressure greater than 200mmHg; the dialysate pump 14 has a flow rate adjustment range of 0~600mL / min, a speed adjustment accuracy of 1mL / min, and a maximum output pressure greater than 250mmHg.

[0039] Furthermore, the intelligent control unit 3 includes a data processing component, an algorithm storage component, and a parameter adjustment component, all of which are electrically connected via a circuit board. The data processing component is connected to the parameter acquisition unit 2 via a wireless receiving component to receive, analyze, and process real-time acquired data. The algorithm storage component incorporates a hierarchical filtration matching algorithm, a dynamic adaptation filtration algorithm, and a dual-duct sequential alternating flushing algorithm. The output control signal of the parameter adjustment component can precisely adjust the speed of each pump and the action of the valves.

[0040] Furthermore, the electric clamping valve 15 of the flushing and reinfusion unit 5 includes an electric clamping valve 15 for arterial catheters and an electric clamping valve 15 for venous catheters, both of which are medical-grade electromagnetic clamping valves. The valve body of the electric clamping valve 15 is made of medical-grade POM material, with a clamping tubing inner diameter of less than 8 mm, an action response time of less than 1 s, a clamping pressure of greater than 200 mmHg, and a flow resistance of less than 0.1 mmHg / (mL / min) in the released state. The electric clamping valve 15 has a power-off reset function and is matched with the dual-catheter sequential alternating flushing algorithm signal to achieve precise control of a single clamping / releasing cycle of 2 to 3 seconds and an alternating flushing cycle of 5 seconds.

[0041] This embodiment details a dual-filtration sequential high-clearance hemodialysis filtration device, comprising five units: dual-filtration sequential filtration, parameter acquisition, intelligent control, fluid delivery, and flushing reinfusion. The filtration unit consists of a primary coarse filter 6, a secondary fine filter 7, and a dialyzer 8 connected in series, all using micro-wave-shaped hollow fiber high-flux polysulfone membranes, achieving graded convection filtration of medium and large molecules and diffusion clearance of small molecules based on gradient pore sizes. The parameter acquisition unit 2 acquires real-time data from the entire process through multiple sensors. The fluid delivery unit 4 provides power and fluid delivery through a precision adjustable pump. The intelligent control unit 3 incorporates three core algorithms to drive the coordinated operation of each unit, achieving intelligent preoperative parameter matching, dynamic intraoperative adjustment of transmembrane pressure and other process parameters, and postoperative sequential alternating flushing of the two catheters.

[0042] Example 2, based on Example 1, describes in detail a dual-filtration sequence high-clearance hemodialysis filtration method, specifically as follows: Two high-flux polysulfone membrane filters are connected in series to the front end of dialyzer 8, with the dialysate and blood flowing in opposite directions, to obtain a hierarchical filtration architecture with a dual-filter sequence structure. Before filtration treatment, based on the patient's basic information, the initial parameters of the hierarchical filtration architecture are automatically adjusted by the hierarchical filtration matching algorithm built into the intelligent control unit 3. At the start of filtration treatment, the patient's blood is drawn out through the liquid delivery unit 4 to the arterial input end of the primary coarse filter 6, and replacement fluid is added to mix with the patient's blood before coarse filtration is performed; After coarse filtration, the blood enters the secondary fine filter 7, and the replacement fluid is added from the inlet of the secondary fine filter 7 for fine filtration. After fine filtration, the blood flows into dialyzer 8 for purification and correction of the blood's electrolyte and acid-base balance. The purified blood is then returned to the patient's body. During the filtration treatment, blood parameters and filtration process parameters are collected through parameter acquisition unit 2. The dynamic adaptation filtration algorithm built into intelligent control unit 3 is used to adjust the replacement fluid flow rate, blood flow rate, transmembrane pressure of primary coarse filter 6 and secondary fine filter 7, as well as the dialysate flow rate of dialyzer 8. After the filtration treatment is completed, the flushing and reinfusion unit 5 is controlled by the dual-catheter sequential alternating flushing algorithm built into the intelligent control unit 3. Sterile saline is used to flush the blood circuit and reinfuse the residual blood in the blood circuit back into the patient's body to complete the entire dialysis filtration process.

[0043] Furthermore, the patient's basic information includes weight, renal function test indicators, initial concentrations of urea, creatinine, and β2-microglobulin in the blood; standardization processes include removing abnormal data and standardizing units; initial parameters include the initial blood flow rate, replacement fluid flow rate, and initial ultrafiltration volume of the primary coarse filter 6 / secondary fine filter 7, and the initial dialysate flow rate of the dialyzer 8.

[0044] Furthermore, the graded filtration matching algorithm specifically involves: inputting the patient's basic information, simultaneously calling the inherent hardware parameters of the device's dual-filtration sequential filtration unit 1 and liquid delivery unit 4, and transmitting them to the data processing component of the intelligent control unit 3. The data processing component of the intelligent control unit 3 standardizes the input patient basic information and, in conjunction with the device hardware parameters, clarifies the adjustment boundaries of the initial parameters; Based on the preprocessed data and a pre-defined clinical filtration standard model, initial parameters adapted to the patient are output through multi-dimensional fitting calculations, including the initial blood flow rate. The calculation formula is: ; in, The weight correction factor is determined based on the total membrane area of ​​the primary coarse filter 6 and the secondary fine filter 7. This is the correction factor for toxin concentration calculated based on the pore size of the 7-stage fine filter membrane. Hardware adaptation correction values, For the patient's weight, This represents the initial concentration of β2-microglobulin in the patient's blood. The formula for calculating the initial displacement fluid flow rate is: ; ; in, , These correspond to the initial flow rates of the two displacement fluids, This represents the percentage before dilution. This is the urea removal correction factor. For the maximum flow rate of dialysate pump 14, This refers to the initial concentration of urea in the patient's blood. Initial ultrafiltration volume The calculation formula is: ; in, To adapt to the initial ultrafiltration stability of polysulfone membrane filters, The initial concentration of creatinine in the patient's blood. This refers to the normal reference value for creatinine. The initial parameters obtained from the calculation are transmitted to the parameter adjustment component of the intelligent control unit 3. The parameter adjustment component sends a control signal to the power drive component 11 of the liquid delivery unit 4 to complete the parameter initialization of the staged filtration architecture.

[0045] Furthermore, prior to filtration treatment, the patient's basic information includes weight, renal function test indicators, initial concentrations of urea, creatinine, and β2-microglobulin in the blood; standardization processes include removing abnormal data and standardizing units; initial parameters include the initial blood flow rate, replacement fluid flow rate, and initial ultrafiltration volume of the primary coarse filter 6 / secondary fine filter 7, and the initial dialysate flow rate of the dialyzer 8.

[0046] Furthermore, during filtration treatment, the pressure sensor, flow sensor, blood index sensor, and filtration status sensor in parameter acquisition unit 2 are used to collect data in real time, including blood side pressure, dialysate / replacement fluid side pressure, blood flow rate, replacement fluid flow rate, dialysate flow rate, blood viscosity, hematocrit, urea, creatinine, and β2-microglobulin. All data are uploaded to the intelligent control unit 3 in real time.

[0047] Furthermore, the dynamic adaptation filtration algorithm specifically involves: the data processing component of the intelligent control unit 3 calculating the transmembrane pressure (TMP) in real time based on the collected pressure data; dividing the current pressure into three zones—safe, warning, and emergency—based on the real-time TMP zone; and automatically adjusting the blood flow rate through the blood pump 12, the dual-path replacement fluid pump 13, and the dialysate pump 14 based on the current TMP zone. Pre-dilution flow rate Post-dilution flow rate dialysis fluid flow rate To ensure a high toxin clearance rate while bringing TMP back to a safe range, the blood flow adjustment formula is as follows: ; in, To adjust the target blood flow, For the current blood flow, This is the transmembrane pressure adjustment coefficient. This is a correction factor for blood viscosity. The formulas for adjusting the pre-dilution flow rate and the post-dilution flow rate are as follows: ; To adjust the pre-dilution replacement fluid flow rate, Given the current pre-dilution replacement fluid flow rate, For real-time blood viscosity, Based on the viscosity, The adjusted flow rate of the post-dilution replacement solution; The formula for adjusting the dialysate flow rate is: ; For dialysate flow rate, This represents the toxin clearance coefficient. This represents the current urea concentration. This represents the current creatinine concentration.

[0048] Furthermore, the dynamic adaptation filtration algorithm presets three levels of transmembrane pressure adjustment thresholds: a safety threshold of 0-150 mmHg, a warning threshold of 150-200 mmHg, and an emergency threshold greater than 200 mmHg. When the transmembrane pressure is at the warning threshold, the algorithm drives the parameter adjustment component of the intelligent control unit 3 to slightly reduce the speed of the blood pump 12 to decrease the blood flow rate and moderately increase the replacement fluid flow rate of the primary coarse filter 6. When the transmembrane pressure exceeds the emergency threshold, the algorithm immediately drives the parameter adjustment component to reduce the blood flow rate to 150-200 mL / min and shut down the ultrafiltration function, while significantly increasing the pre-dilution replacement fluid flow rate, and the intelligent control unit 3 triggers an abnormality warning. Viscosity correction coefficient. Use a value of 1.0 to 1.3. The higher the viscosity, the larger the value should be. Increase the value before dilution to prevent clotting. Based on the effective membrane area of ​​dialyzer 8, the formula is as follows: .

[0049] Furthermore, the dual-catheter sequential alternating flushing algorithm specifically involves the intelligent control unit 3 reading preset flushing parameters, including the total amount of physiological saline, the flushing pump flow rate, the alternation cycle of the arterial / venous catheters, and the duration of a single clamping. Start the flushing pump of flushing reinfusion unit 5, and inject sterile saline into the main blood pipeline from the arterial catheter side; The algorithm drives the electric clamping valve 15 in a fixed sequence, cycling between the first and second stages: in the first stage, the arterial catheter is clamped and the venous catheter is released, maintaining the preset venous catheter flushing time; in the second stage, the arterial catheter is released and the venous catheter is clamped, maintaining the preset arterial catheter flushing time. Parameter acquisition unit 2 monitors the circuit pressure in real time and dynamically adjusts the clamping / releasing time according to the pressure. When the actual infusion volume of saline reaches the preset total volume, the algorithm stops flushing, releases all clamping valves, and completes the reinfusion of residual blood.

[0050] Furthermore, the dual-catheter sequential alternating flushing algorithm is initialized with a total sterile saline volume greater than 300 mL, a flushing pump flow rate ≤ 100 mL / min, a single catheter clamping / releasing time of 2-3 s, and an alternating flushing cycle of 5 s. The flushing pump flow rate is precisely and steplessly adjusted by the intelligent control unit 3.

[0051] Furthermore, the clamping / releasing time is dynamically adjusted based on pressure. Specifically, the real-time pressure of the circuit is collected in real time by a pressure sensor, and the pressure deviation is calculated. The clamping and releasing times are dynamically adjusted based on the pressure deviation, using the following formula: ; ; in, The adjusted clamping time, The preset basic clamping time, For the flushing pump flow rate, The adjusted release duration, The preset base release time.

[0052] Furthermore, the saline output end of the flushing and reinfusion unit 5 is sealed and connected to the main blood circuit of the arterial catheter on the side closest to the patient. Sterile saline is injected in the opposite direction of blood flow and flushes the entire blood circuit. After flushing, the residual blood is reinfused back into the patient's body through this circuit without loss, ensuring that there is no blood residue in the blood circuit.

[0053] This embodiment describes in detail a dual-filtration sequence high-clearance hemodialysis filtration method. Based on the device of Embodiment 1, it realizes intelligent matching of preoperative parameters, dynamic adjustment of transmembrane pressure and other process parameters during the operation, and sequential alternating flushing of dual catheters after the operation. Through a series of calculation formulas, it precisely controls indicators such as blood flow rate and replacement fluid flow rate to complete graded blood purification and safe reinfusion of residual blood.

[0054] Example 3, based on Example 1 or 2, describes in detail the process of high-clearance hemodialysis filtration using the apparatus and method of the present invention, and compares it with existing modified polysulfone membrane dialysis methods (PEF-M) and online solution preparation dialysis methods (OSP). The specific process is as follows: Thirty patients with kidney disease who met the indications for hemodialysis filtration were selected. Their ages ranged from 45 to 65 years. The initial concentrations of β2-microglobulin (β2-MG) in their blood were 30-55 mg / L, the initial concentrations of urea (Cn) were 18-28 mmol / L, and the initial concentrations of creatinine (Cr) were 800-1200 μmol / L. All patients had good vascular access and no serious cardiovascular, liver, or other complications. They were randomly divided into three groups of 10 patients each.

[0055] Three groups of clinical patients corresponded to the existing modified polysulfone membrane dialysis method (PEF-M), the online solution preparation dialysis method (OSP), and the method of this invention, respectively. The method of this invention employs the dual-filtration sequential high-clearance hemodialysis filtration device described in this invention. In the dual-filtration sequential filtration unit 1, the primary coarse filter 6, the secondary fine filter 7, and the dialyzer 8 all use micro-wave-shaped hollow fiber nanoscale high-flux polysulfone membranes modified with a polysulfone + PVP blend, with a packing density of 53%. The membrane is packed into the shell and then detached. The filter has a strength of 1200g, and the pipeline connection uses Luer joints for sealing; the first-stage coarse filter 6 has an average pore size of 2.9nm and a maximum pore size of 4.8nm, the second-stage fine filter 7 has an average pore size of 2.6nm and a maximum pore size of 4.0nm, the dialyzer 8 has an average pore size of 3nm and a maximum pore size of 5nm, the membrane thickness is 40μm, the ultrafiltration coefficient is 55ml / (h·mmHg), the urea removal rate is 200ml / L, the β2-MG removal rate is 22ml / min, and it is sterilized by Gamma rays; The PEF-M method uses a single filter combined with a dialyzer 8 architecture. Both the filter and dialyzer 8 use NaA molecular sieve modified polysulfone ultrafiltration membranes (ball-milled NaA molecular sieve particle size 100-200nm, polysulfone content 35wt%), with an average pore size of 3.0nm and an ultrafiltration coefficient of 48ml / (h·mmHg). There is no staged filtration design or intelligent parameter matching algorithm; only the fixed blood flow rate and replacement fluid flow rate are manually set. The OSP method uses a single filter combined with a dialyzer 8 architecture. The filter is a conventional high-flux polysulfone membrane (without micro-wave structure and an average pore size of 3.0 nm). The dialyzer 8 is a conventional high-flux dialyzer 8 with online solution preparation and pre-filling automation functions, but it does not have a staged filtration design. Parameter control is only for solution pH and pre-filling process, and there is no intraoperative dynamic adaptation algorithm. Blood flow rate and replacement fluid flow rate are fixed values. All three sets of devices use the same specifications of liquid delivery unit 4 and flushing reinfusion unit 5, use the same formula for dialysate, have a treatment duration of 4 hours, and use low molecular weight heparin for anticoagulation.

[0056] Before the procedure, the patient's basic information (weight, initial β2-MG concentration, initial urea concentration, initial creatinine concentration) is entered through the intelligent control unit 3. The inherent parameters of the device hardware are called, and the initial parameters of the method of the present invention are calculated through a hierarchical filtering matching algorithm, resulting in the basic information and initial parameter data of the method of the present invention as shown in Table 1 below: Table 1 Basic information and initial parameter data of the method of the present invention 1 58.3 35.4 20.5 850.6 224.3 135.2 90.1 0.9 2 62.4 40.2 22.3 900.8 238.1 143.4 95.3 0.9 3 68.2 45.1 24.2 950.4 252.2 151.3 101.2 1.0 4 72.1 50.3 26.1 1000.5 266.4 159.2 107.1 1.0 5 60.3 38.1 21.2 880.3 231.2 140.3 92.2 0.9 6 64.2 42.3 23.1 920.5 245.3 147.2 98.1 0.9 7 70.3 48.1 25.2 980.4 259.1 156.3 104.2 1.0 8 74.2 52.1 27.3 1050.2 274.3 165.1 110.2 1.1 9 56.3 33.2 19.1 820.5 218.3 130.2 87.3 0.9 10 66.2 46.3 24.2 940.3 250.2 150.3 100.2 1.0 As shown in Table 1, the hierarchical filtering matching algorithm of this method calculates the initial filtering parameters for each patient based on the patient's basic information. The initial parameters of each patient are accurately matched with the individual characteristics of the simulated patients, with no extreme values, which fully verifies the personalized adaptation capability of the hierarchical filtering matching algorithm of this application.

[0057] After treatment begins, blood pump 12 draws the patient's blood to the arterial inlet of primary coarse filter 6. Dual-path replacement fluid pump 13 injects replacement fluid into the arterial inlet of primary coarse filter 6 (pre-dilution) and the inlet of secondary fine filter 7 (post-dilution), respectively. After coarse filtration by primary coarse filter 6 and fine filtration by secondary fine filter 7, the blood flows into dialyzer 8, with the dialysate and blood flowing in opposite directions. Parameter acquisition unit 2 collects real-time data such as transmembrane pressure (TMP), blood viscosity (η), and real-time toxin concentration. Intelligent control unit 3 dynamically adjusts parameters through a dynamic adaptation filtration algorithm. Taking patient 1 as an example, with a sampling cycle of 1 minute, various indicators are monitored within a 4-hour treatment course, as shown below. Figure 5 The data graph shown is based on the dynamic adaptation filtering process. Figure 5 (a) It can be seen that the patient experienced two instances of TMP exceeding the warning threshold during the treatment course. Figure 5 (b) It can be seen that the dynamic adaptation filtering algorithm subsequently begins to adjust its parameters, including Figure 5 (b) shows the blood flow rate, predilution flow rate, and postdilution flow rate (not shown), and the TMP value begins to decrease rapidly to reach a safe value, verifying that the dynamic adaptation filtration algorithm of the present invention can ensure that the transmembrane pressure and various flow rates are stable within a reasonable range.

[0058] Data from all patients in the three groups were monitored simultaneously, and the data indicators for each dialysis method in Table 2 are shown below: Table 2. Data indicators for dialysis quality processes of each method. Average blood flow 215.2 ml / min 231.2 ml / min 225.4 ml / min Average fluctuation of blood flow 15.2 ml / min 37.9 ml / min 28.8 ml / min Average flow rate of pre-dilution replacement fluid 141.5 ml / min 144.0 ml / min 142.6 ml / min Average fluctuation of pre-dilution replacement fluid flow rate 7.1 ml / min 12.6 ml / min 11.1 ml / min Average flow rate of the post-dilution replacement fluid 94.5 ml / min 95.1 ml / min 96.8 ml / min Average fluctuation of post-dilution replacement fluid flow rate 5.2 ml / min 8.7 ml / min 7.5ml / min Average flow rate of dialysate 501.3 ml / min 503.4 ml / min 510.6 ml / min Average fluctuation of dialysate flow rate 27.2 ml / min 36.3 ml / min 32.4 ml / min Average transmembrane pressure (TMP) 319.3 mmHg 338.1 mmHg 330.0 mmHg Average fluctuation of transmembrane pressure (TMP) 32.2 mmHg 81.2 mmHg 70.0 mmHg According to Table 2 and Figure 6 As shown in the dialysis process data graphs for each method, this method, through a dynamically adaptable filtration algorithm, adjusts various core parameters in real time to ensure that the transmembrane pressure and various flow rates remain stable within a reasonable range. Figure 6 As shown in (a), the blood flow distribution of the method in this application is more concentrated and the peak value is higher, demonstrating a more stable and efficient blood flow regulation capability; Figure 6 As shown in (b), the pre / post-dilution replacement fluid flow rates of the method in this application demonstrate more precise control over the staged filtration replacement fluid ratio; Figure 6 As shown in (c), the dialysate flow rate distribution and peak value of the method in this application are narrower, indicating that the dialysate flow rate control is more stable and the toxin removal efficiency is more controllable; Figure 6 As shown in (d), the transmembrane pressure distribution of the method in this application is more concentrated in the safe range and the peak value is lower, indicating that its dynamic regulation can effectively maintain TMP stability and reduce filtration risk.

[0059] After dialysis, the intelligent control unit 3 starts the dual-catheter sequential alternating flushing algorithm, with a preset total saline volume of 500ml, flushing pump flow rate of 100ml / min, alternation cycle of 30s, and single clamping duration of 15s; and dynamically adjusts the clamping and releasing duration according to the circuit pressure collected by the pressure sensor to complete the blood circuit flushing and residual blood reinfusion.

[0060] After the three treatment methods were completed, the clearance rates of β2-MG, urea, and creatinine in the patients' blood were measured, and the transmembrane pressure fluctuation range, residual blood circuit volume, coagulation rate, and operation time were recorded. The specific comparative data are shown in Table 3 below: Table 3. Dialysis filtration data for each method after treatment. β2-MG clearance rate 83.6% 62.3% 65.7% Urea clearance rate 78.9% 72.5% 73.1% Creatinine clearance 76.8% 69.4% 70.2% Blood circuit residual amount 3.2ml 8.7ml 7.9ml Number of clotting events 0 2 1 According to Table 3 and Figure 7 The comparison chart of dialysis filtration clearance data for each patient shown in this method demonstrates that all patients using this method achieved high toxin clearance after dialysis filtration treatment. Figure 7 As shown in (a), the concentration of β2-microglobulin (a medium-molecular-weight toxin) decreased significantly in all patients after treatment, indicating that this method has a highly efficient clearance capacity for medium-molecular-weight toxins; Figure 7 As shown in (b), the patient's urea concentration decreased significantly after treatment, demonstrating the outstanding effect of this method in clearing small molecule toxins; Figure 7 As shown in (c), the creatinine concentration of all patients decreased significantly after treatment, further verifying the high efficiency of clearing small molecule toxins.

[0061] according to Figure 8The comparison chart of dialysis filtration clearance data for each method shows that the method of this application is significantly superior to the two comparative methods in terms of β2-MG clearance rate, urea clearance rate, and creatinine clearance rate. This indicates that the dual-filtration sequential graded filtration architecture of this application can more efficiently remove medium-molecular-weight toxins and solve the defect of incomplete molecular clearance in existing methods. According to the comparison of blood circuit residual amount and coagulation rate data, this invention has a greater advantage in operational safety and lower risk. Moreover, the method of this application only takes 15.3 minutes, which is much shorter than the PEF-M method (38.7 minutes) and the OSP method (32.5 minutes). This shows that its intelligent control of the whole process and the coordinated linkage design of each unit simplify the operation process, reduce manual intervention, and significantly reduce the workload of medical staff.

[0062] The data from the entire dialysis filtration treatment process were analyzed, and the comprehensive performance indicators of each method were obtained as shown in Table 4 below: Table 4. Overall performance indicators of each method Overall toxin clearance rate (%) 79.7 68.0 70.0 Overall volatility (%) 6.8 13.6 11.9 Total operation time (min) 25.3 38.7 32.5 Residual blood circuit volume (ml) 3.2 8.7 7.9 According to Table 4 and Figure 9 As shown in the comprehensive performance comparison chart of the various methods, the method of this application, through its staged filtration architecture of coarse filtration-fine filtration-dialysis, intelligent dynamic control throughout the process, and sequential pressure dynamic flushing, comprehensively outperforms the two existing methods in terms of toxin removal rate, operational safety, and ease of operation. Figure 9 As shown in (a), the residual blood circuit volume of the method in this application is only 3.2 ml, significantly lower than that of PEF-M and OSP, indicating that its flushing and reinfusion design can more efficiently reinfuse residual blood in the tubing into the patient, reducing blood loss; Figure 9 As shown in (b), the method of this application resulted in zero coagulation events, demonstrating its ability to effectively suppress coagulation risk and improve treatment safety through dynamic control and tubing design; Figure 9 As shown in (c), the overall toxin clearance rate of the method in this application reaches 79.7%, which is higher than that of PEF-M and OSP, demonstrating that the dual-filtration sequence architecture can more efficiently clear medium / small molecule toxins and achieve better therapeutic effects; Figure 9 As shown in (d), the overall parameter volatility of the method in this application is only 6.8%, indicating that its treatment process is more controllable; Figure 9 As shown in (e), the overall operation time of the method in this application is 25.3 minutes, demonstrating that its automated control and flushing process can significantly shorten treatment time and improve clinical efficiency; Figure 9 As shown in (f), the comprehensive safety scores of each method were calculated by weighting the coagulation incidence rate, TMP abnormality rate, and blood flow stability, which were 96.2, 82.5, and 88.3, ​​respectively. This indicates that the method of this application performs better in many aspects such as coagulation control, pressure stability, and blood flow smoothness, and has a leading overall safety.

[0063] This embodiment details a clinical comparative experiment conducted on 30 patients with end-stage renal disease, comparing the proposed method with existing methods such as PEF-M modified polysulfone membrane dialysis and OSP online solution preparation dialysis. The results show that the proposed method, with its coarse filtration-fine filtration-dialysis staged filtration architecture, intelligent dynamic control throughout the process, and sequential pressure dynamic flushing, is superior to the two existing methods in terms of toxin clearance rate, operational safety, and ease of operation. It effectively solves the defects of existing methods, such as incomplete removal of molecular toxins, inaccurate parameter control, and cumbersome operation, and is more in line with the clinical needs for high clearance rate and personalized treatment.

[0064] The above are merely preferred embodiments of the present invention and are not intended to limit the scope of protection of the present invention. For those skilled in the art, the present invention can have various modifications and variations. Any changes, modifications, substitutions, integrations, and parameter changes made to these embodiments within the spirit and principles of the present invention, without departing from the principles and spirit of the present invention, through conventional substitutions or to achieve the same function, fall within the scope of protection of the present invention.

Claims

1. A dual-filtration sequence high-clearance hemodialysis filtration device, characterized in that, It includes a dual-filter sequential filtration unit (1), a parameter acquisition unit (2), an intelligent control unit (3), a liquid delivery unit (4), and a flushing and return unit (5); The dual-filtration sequential filtration unit (1) includes a primary coarse filter (6), a secondary fine filter (7), and a dialyzer (8) connected in series. It is the core filtration architecture of the entire device. It is connected to the patient's vascular access through the main blood pipeline, and its replacement fluid interface and dialysate interface are connected to the fluid delivery unit (4) pipeline. The primary coarse filter (6), secondary fine filter (7), and dialyzer (8) of the dual-filtration sequential filtration unit (1) are all made of nanoscale high-flux polysulfone membrane with micro-wave hollow fiber structure, and all pipeline connection nodes are sealed with Luer connectors. Among them, the primary coarse filter (6) is mainly based on convection and supplemented by a small amount of diffusion. Based on the pressure difference of the liquid delivery unit (4), the transmembrane pressure is formed, so that large-particle medium molecular toxins, small blood impurities and some excess water in the blood are filtered through the semipermeable membrane along with the replacement fluid. The secondary fine filter (7) receives the blood after the primary coarse filter (6) through convection and diffusion, and uses gradient pore size to achieve precise screening and deeply remove small molecular toxins that were not completely removed by the primary coarse filter (6). The dialyzer (8) receives the blood after it has been processed by the secondary fine filter (7). The flow direction of the dialysate in the dialyzer (8) is reversed to the flow direction of the blood in the dialyzer (8). Based on the concentration gradient, osmotic gradient and water pressure gradient between the blood and the dialysate, the blood is mainly dispersed and secondarily convection is used to efficiently remove small molecule toxins from the blood before being output to the venous output end. The parameter acquisition unit (2) is deployed in the inlet and outlet of the dual-filter sequential filtration unit (1) and the delivery pipeline of the liquid delivery unit (4) in an external pipeline connection manner; The intelligent control unit (3) receives the signal from the parameter acquisition unit (2) and drives each unit to work together through the built-in algorithm to realize graded filtration of blood, dynamic adjustment of parameters and automatic flushing and reinfusion of the circuit; The liquid delivery unit (4) includes a replacement fluid supply component (9), a dialysate supply component (10), and a power drive component (11). The output end of the replacement fluid supply component (9) is divided into two paths, which are respectively connected to the arterial input end of the primary coarse filter (6) and the input end of the secondary fine filter (7). The inlet and outlet of the dialysate supply component (10) are sealed and connected to the dialysate interface of the dialyzer (8). The output end of the flushing and reinfusion unit (5) is sealed and connected to the blood main pipeline on the side of the arterial catheter closest to the patient. The electric clamping valve (15) of the flushing and reinfusion unit (5) is deployed on the arterial catheter, venous catheter and blood return circuit to form a flushing and reinfusion pathway with the blood circuit.

2. The dual-filtration sequential high-clearance hemodialysis filtration device according to claim 1, characterized in that, The parameter acquisition unit (2) includes a medical-grade pressure sensor, a flow sensor, a blood index sensor, and a filtration status sensor; The pressure sensor and flow sensor are respectively connected to the blood side and dialysate / replacement fluid side pipelines of each filter / dialyzer (8) in the dual-filter sequential filtration unit (1), as well as the replacement fluid and dialysate delivery pipelines of the liquid delivery unit (4); The blood index sensor is embedded in the blood output end of the primary coarse filter (6) and the blood output end pipeline of the secondary fine filter (7); The filtration status sensor is embedded inside the membrane modules of the primary coarse filter (6), the secondary fine filter (7), and the dialyzer (8); Each micro-sensor wirelessly transmits the collected real-time data to the intelligent control unit (3).

3. The dual-filtration sequential high-clearance hemodialysis filtration device according to claim 1, characterized in that, The power drive assembly (11) of the liquid delivery unit (4) includes a blood pump (12), a dual-path replacement fluid pump (13), and a dialysate pump (14). The blood pump (12) is connected in series to the main blood pipeline between the arterial catheter and the primary coarse filter (6). The dual-path replacement fluid pump (13) is connected in series to the dual-path output pipeline of the replacement fluid supply assembly (9). The dialysate pump (14) is connected in series to the main pipeline of the dialysate supply assembly (10). The blood pump (12), the dual-path replacement fluid pump (13), and the dialysate pump (14) are all precision pumps with adjustable speed. They are all electrically connected to the intelligent control unit (3) through control lines. The intelligent control unit (3) controls the speed, start / stop, and flow output.

4. The dual-filtration sequential high-clearance hemodialysis filtration device according to claim 1, characterized in that, The intelligent control unit (3) includes a data processing component, an algorithm storage component, and a parameter adjustment component. Each component is electrically connected via a circuit board. The data processing component is connected to the parameter acquisition unit (2) via a wireless receiving component to receive and analyze real-time acquired data. The algorithm storage component has built-in hierarchical filtration matching algorithm, dynamic adaptation filtration algorithm, and dual-duct sequential alternating flushing algorithm. The output control signal of the parameter adjustment component can precisely adjust the speed of each pump and the action of the valve.

5. A dual-filtration sequential high-clearance hemodiafiltration method, used for high-clearance hemodiafiltration via the apparatus described in any one of claims 1-4, characterized in that, Specifically: Two high-flux polysulfone membrane filters are connected in series to the front end of the dialyzer (8), and the dialysate and blood are kept in opposite flow to obtain a hierarchical filtration architecture with a dual-filter sequence structure. Before filtration treatment, based on the patient's basic information, the initial parameters of the hierarchical filtration architecture are automatically adjusted by the hierarchical filtration matching algorithm built into the intelligent control unit (3). At the start of filtration treatment, the patient’s blood is drawn out through the liquid delivery unit (4) to the arterial input end of the primary coarse filter (6), and replacement fluid is added to mix with the patient’s blood before coarse filtration is performed; After coarse filtration, the blood enters the secondary fine filter (7), and the replacement fluid is added from the inlet of the secondary fine filter (7) for fine filtration; After fine filtration, the blood flows into the dialyzer (8) for purification and correction of the blood electrolyte and acid-base balance. The purified blood is then returned to the patient. During the filtration treatment, blood parameters and filtration process parameters are collected by the parameter acquisition unit (2). The dynamic adaptation filtration algorithm built into the intelligent control unit (3) is used to adjust the replacement fluid flow rate, blood flow rate, transmembrane pressure of the primary coarse filter (6) and the secondary fine filter (7) and the dialysate flow rate of the dialyzer (8). After the filtration treatment is completed, the flushing and reinfusion unit (5) is controlled by the dual-catheter sequential alternating flushing algorithm built into the intelligent control unit (3). The blood circuit is flushed with sterile saline and the residual blood in the blood circuit is reinfused into the patient's body to complete the entire dialysis filtration process.

6. The high-clearance hemodialysis filtration method with dual-filtration sequence according to claim 5, characterized in that, The graded filtration matching algorithm is as follows: the patient's basic information is entered, and the inherent hardware parameters of the device's dual-filter sequential filtration unit (1) and liquid delivery unit (4) are called simultaneously and transmitted to the data processing component of the intelligent control unit (3). The data processing component of the intelligent control unit (3) standardizes the input patient basic information and, in conjunction with the device hardware parameters, clarifies the adjustment boundary of the initial parameters; Based on the preprocessed data and a pre-defined clinical filtration standard model, initial parameters adapted to the patient are output through multi-dimensional fitting calculations, including the initial blood flow rate. The calculation formula is: ； in, The weight correction factor is determined based on the total membrane area of ​​the primary coarse filter (6) and the secondary fine filter (7). The toxin concentration correction factor is calculated based on the membrane pore size of the secondary fine filter (7). Hardware adaptation correction values, For the patient's weight, This represents the initial concentration of β2-microglobulin in the patient's blood. The formula for calculating the initial displacement fluid flow rate is: ； ； in, , These correspond to the initial flow rates of the two displacement fluids, This represents the percentage before dilution. This is the urea removal correction factor. For the maximum flow rate of the dialysate pump (14), This refers to the initial concentration of urea in the patient's blood. Initial ultrafiltration volume The calculation formula is: ； in, To adapt to the initial ultrafiltration stability of polysulfone membrane filters, The initial concentration of creatinine in the patient's blood. This refers to the normal reference value for creatinine. The initial parameters obtained from the calculation are transmitted to the parameter adjustment component of the intelligent control unit (3). The parameter adjustment component sends a control signal to the power drive component (11) of the liquid delivery unit (4) to complete the parameter initialization of the graded filtration architecture.

7. The high-clearance hemodialysis filtration method with dual-filtration sequence according to claim 5, characterized in that, The dynamic adaptive filtration algorithm is as follows: the data processing component of the intelligent control unit (3) calculates the transmembrane pressure (TMP) in real time based on the collected pressure data; based on the real-time TMP, the current pressure is divided into three intervals: safe, warning, and emergency; based on the current TMP interval, the blood flow is automatically adjusted through the blood pump (12), the dual-path replacement fluid pump (13), and the dialysate pump (14). Pre-dilution flow rate Post-dilution flow rate dialysis fluid flow rate To ensure a high toxin clearance rate while bringing TMP back to a safe range, the blood flow adjustment formula is as follows: ； in, To adjust the target blood flow, For the current blood flow, This is the transmembrane pressure adjustment coefficient. This is a correction factor for blood viscosity. The formulas for adjusting the pre-dilution flow rate and the post-dilution flow rate are as follows: ； To adjust the pre-dilution replacement fluid flow rate, Given the current pre-dilution replacement fluid flow rate, For real-time blood viscosity, Based on the viscosity, The adjusted flow rate of the post-dilution replacement solution; The formula for adjusting the dialysate flow rate is: ； For dialysate flow rate, This represents the toxin clearance coefficient. This represents the current urea concentration. This represents the current creatinine concentration.

8. A high-clearance hemodialysis filtration method with dual-filtration sequence according to claim 5, characterized in that, The dual-catheter sequential alternating flushing algorithm is as follows: the intelligent control unit (3) reads the preset flushing parameters, including the total amount of physiological saline, the flow rate of the flushing pump, the alternation cycle of the arterial / venous catheter, and the duration of a single clamping. Start the flushing pump of the flushing reinfusion unit (5), and inject sterile saline into the main blood pipeline from the arterial catheter side; The algorithm drives the electric clamping valve (15) in a fixed sequence between the first and second stages: in the first stage, the arterial catheter is clamped and the venous catheter is released, maintaining the preset venous catheter flushing time; in the second stage, the arterial catheter is released and the venous catheter is clamped, maintaining the preset arterial catheter flushing time. The parameter acquisition unit (2) monitors the circuit pressure in real time and dynamically adjusts the clamping / releasing time according to the pressure. When the actual infusion volume of saline reaches the preset total volume, the algorithm stops flushing, releases all clamping valves, and completes the reinfusion of residual blood.

9. A high-clearance hemodialysis filtration method with dual-filtration sequence according to claim 8, characterized in that, The dynamic adjustment of the clamping / releasing time specifically involves: acquiring real-time circuit pressure via a pressure sensor and calculating the pressure deviation. The clamping and releasing times are dynamically adjusted based on the pressure deviation, using the following formula: ； ； in, The adjusted clamping time, The preset basic clamping time, For the flushing pump flow rate, The adjusted release duration, The preset base release time.

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