Wearable portable device for recirculation flow dialysis

Abstract

Wearable portable device for recirculation flow dialysis. The invention relates to a dialysis device providing recirculation flow dialysis in a wearable and portable form. It uses interchangeable purification units containing volumes of dialysate and / or sorbent systems for in situ regeneration of the dialysate. The inventive dialysis device comprises a carrier mounted on a replaceable filter cartridge. The carrier contains electronics, user interface, actuators and sensors. It initiates, controls and monitors the dialysis operation. The filter cartridge is a replaceable piece connected to the patient via flexible tubes. It consists of a reusable housing with a memory chip and contains a disposable insert containing a purification unit with fluid lines, connectors, dialysate and / or sorbent combined with a nanofilter. The filter cartridge is intended for daytime use as a wearable system. The filter cartridge can be extended with an extension assembly to provide a larger capacity. The extended filter cartridge is intended for night use as a bedside device.

Description

Technical Field

[0001] This invention relates to a wearable and / or portable dialysis device for home use. Background Technology

[0002] Depending on the patient's characteristics and the hospital's resources, different dialysis methods can be used to treat renal failure. Peritoneal dialysis (PD) can be the preferred option in cases of hypotension, coagulation disorders, or difficulty accessing intravenous access. Existing peritoneal dialysis techniques include CAPD (Continuous Ambulatory Peritoneal Dialysis) and APD (Automated Peritoneal Dialysis). Both techniques use peritoneal dialysis fluid (usually 2L) entering the abdomen, which is drained after a period of time when the fluid is saturated with toxins. This is repeated 4 to 5 times daily (manual, CAPD) or overnight (automatic, APD). The main drawback of PD is its limited efficacy. This is due to the intermittent procedures of CAPD and APD and the rapid saturation of the peritoneal dialysis fluid. A second drawback is the high glucose concentration in the dialysis fluid added as an osmotic agent to remove excess fluid from the patient. Peak glucose concentrations can cause peritoneal reactions, leading to a decline in function over time, thus limiting the technology's lifespan (usually 5 years). Continuous Flow Peritoneal Dialysis (CFPD) is a more effective treatment than conventional peritoneal dialysis, in which fresh dialysis fluid is continuously recirculated. Continuous recirculation can improve the efficacy of peritoneal dialysis and prevent peak glucose concentrations. Currently, continuous flow peritoneal dialysis requires prolonged daily connection to a stationary dialysis machine, rendering patients immobile. This is impractical and hinders its application.

[0003] Several efforts have been made to develop a wearable and / or portable device for continuous flow peritoneal dialysis in more practical settings. The most notable system is described in patent application US 2011 / 0184340, which proposes a system for recirculating peritoneal dialysis fluid regenerated through an adsorbent filter cartridge. An adsorbent system is described in patent application US 2011 / 0171713. It comprises four components: activated carbon (binding organic toxins such as creatinine, uric acid, etc.), immobilized urease (an enzyme that converts urea into ammonia and carbon dioxide), zirconium phosphate (binding cations such as potassium, calcium, magnesium, and ammonia), and zirconium hydroxide (removing anions such as phosphates). This adsorbent system has proven effective in removing toxins, but commercialization has been hampered by several physiological drawbacks and the high cost of the system. The main reasons are: (1) Urease has a limited shelf life; (2) This enzyme converts urea into a large amount of (toxic) ammonia, which can only be removed by a large amount of zirconium phosphate; (3) In addition to ammonia, a large amount of carbon dioxide is also formed, which needs to be degassed from the dialysate; (4) Zirconium phosphate also binds magnesium and calcium ions, which need to be re-infused separately; (5) During ion exchange, both zirconium phosphate and zirconium oxide release sodium ions, which is detrimental to the patient's electrolyte balance. The release of sodium, the limited shelf life, the need for degassed and re-infused electrolytes, and the difficulty in controlling ammonium have all hindered the successful introduction of the system into the market. Similar systems have also appeared in other patent applications, such as US2010 / 0314314 and US2014 / 8777892, but with the same disadvantages.

[0004] Patent application US2015 / 0290384 discloses a different adsorbent system comprising activated carbon (binding most organic toxins), metal (Cu)-complexed chitosan (binding urea), and non-complexed chitosan (binding metal ions). In this system, the release of unwanted metal (Cu) ions is an excessively high risk factor.

[0005] Patent application WO 2016 / 190794 describes an adsorbent system containing a large amount of activated carbon (organic toxins and urea), a phosphate resin (polystyrene complexed with lanthanum or iron ions), and a cation exchange resin for potassium removal. This system requires a large amount of carbon due to its poor urea absorption capacity, which hinders wearable systems. Summary of the Invention

[0006] The purpose of this invention is to overcome the aforementioned problems of undesirable ion release and the need for large amounts of adsorbent (especially for urea) that hinder wearability and lead to high costs.

[0007] This problem is solved by the dialysis system according to the invention, which recirculates the dialysate in continuous or tidal mode and regenerates the dialysate in situ using a purification unit. The purification unit is held in a small filter cartridge (wearable, portable system) for daytime use. The purification unit contains a volume with dialysate and / or a volume containing an adsorbent system to enhance toxin removal. The adsorbent system comprises two components: activated carbon and an anionic binder. The adsorbent system is designed to bind and remove toxins such as phosphates, small and medium-sized molecules, and protein-bound toxins (creatinine, β2-microglobulin, p-cresol sulfate, indophenol sulfate, hippuric acid, CMPF). Optionally, a third adsorbent component can be added to remove specific contaminants from the dialysate, such as glucose degradation products. However, the system can also be used without an adsorbent system. In this case, the dialysate volume of the device is used to externally expand and dilute the peritoneal dialysate volume in the abdomen.

[0008] For dialysis at night, the filter cartridge is expanded using an extension assembly (portable system). This extension assembly also removes the large amounts of urea and potassium toxins produced daily. These are small, rapidly diffusing ions that can be easily removed during an 8-hour overnight treatment. A second function, in the case of peritoneal dialysis, is to provide the possibility of releasing an osmotic agent (such as glucose) to extract fluid when needed.

[0009] Dialysis fluid recirculation can be continuous or tidal. Continuous recirculation requires a double-lumen catheter or two separate catheters. Since peritoneal patients typically have a single-lumen catheter, it is expected that most patients will use the system in tidal mode.

[0010] At a typical flow rate of 200 ml / min, the hourly circulation volume of dialysate is 6 liters (tidal mode) or 12 liters (continuous mode). For nighttime treatment, this translates to a dialysate circulation volume of 48 liters or 96 liters. In current CAPD and APD procedures, only 8-15 liters of dialysate are flushed in and out. The increased circulation volume enhances mass transfer within the peritoneal cavity. Therefore, the efficacy of dialysis treatment is improved. During the day, a similar volume of recirculation can be performed at a reduced flow rate of 100 ml / min.

[0011] This invention is also applicable to hemodialysis. In this case, the system is connected to the patient via a double-lumen central venous catheter or via a shunt or fistula. Blood, rather than dialysate, is circulated and purified through a purification unit and extension assembly. A dialyzer filter is used to separate the blood from the fluid in the purification unit and extension assembly. Attached Figure Description

[0012] The invention will now be further described with reference to the accompanying drawings. These drawings illustrate embodiments of the device according to the invention. In the drawings:

[0013] Figure 1 A wearable device with a day filter cartridge is shown;

[0014] Figure 2 Two parts are shown: (a) a replaceable day filter cartridge with adsorbent and liquid flow (left, dark) and (b) a carrier with electronics and sensors (right, white);

[0015] Figure 3 A device is shown that operates using a single patient line (and single-lumen catheter) in tidal mode;

[0016] Figure 4 A portable device with an extended night filter cartridge is shown;

[0017] Figure 5 A flowchart of a daytime device using a single patient line (and a single-lumen catheter) in tidal mode is shown;

[0018] Figure 6 A flowchart is shown of a nighttime device in tidal mode with an extended filter cartridge (extension assembly) and using a single patient tubing (and a single-lumen catheter);

[0019] Figure 7 An alternative flow chart for the daytime unit in tidal mode is shown, where the nanofilters are only present in the dialysate flow entering the patient;

[0020] Figure 8 A flowchart of a daytime device in continuous flow mode using two patient lines (and two catheters or a double-lumen catheter) is shown;

[0021] Figure 9 A flowchart is shown of a night device with an extension assembly in continuous flow mode using two patient lines (and two catheters or a double-lumen catheter);

[0022] Figure 10 A flowchart is shown of a daytime device in dialysis mode using a dialyzer filter and two pump units and using two patient lines (and two catheters or double-lumen catheters);

[0023] Figure 11 A flowchart is shown of a nighttime device in tidal mode with an extended filter cartridge (extension assembly) without adsorbents and nanofilters;

[0024] Figure 12 The dynamic light scattering of adsorbent-purified dialysate filtered through a 0.2 μm filter and a 3 nm high-throughput dialyzer filter is shown compared to ultrapure water;

[0025] Figure 13The relationship between the average dialysate flow rate (Qd, mL / min) and the mass transfer area coefficients (MTAC, mL / in) of urea, creatinine and phosphate is shown.

[0026] Figure 14 The diagram shows the device when used with two separate catheters;

[0027] Figure 15 A preferred single-port double-lumen catheter for use in tidal mode is shown, with one lumen delivering fluid at the top of the peritoneum and the other lumen retracting fluid at the bottom;

[0028] Figure 16 A dual-port, dual-lumen catheter is shown in continuous mode, with one lumen delivering fluid at the top of the peritoneum and the other lumen retracting fluid at the bottom; and Detailed Implementation

[0029] According to the present invention, through dialysis device 1 (see...) Figure 1 This solves the problem by recirculating the dialysate in either continuous or tidal mode, and regenerating the dialysate in situ using a purification unit. The purification unit is housed in a small filter cartridge 5, see... Figure 2 For daytime use (wearable, portable system), see [link / reference]. Figure 3 .

[0030] The purification unit is designed to bind and remove toxins with low diffusivity, such as phosphates, small and medium-sized molecules, and protein-bound toxins (creatinine, β2-microglobulin, p-cresol sulfate, indophenol sulfate, hippuric acid, CMPF).

[0031] For dialysis at night, filter cartridge 5 is enlarged via extension assembly 41, see Figure 4 (Extended filter cartridge, portable system). The extended component 41 also functions to remove the large amounts of urea and potassium toxins produced daily. These small ions diffuse rapidly across the peritoneum and are easily removed during an 8-hour overnight treatment. In the case of peritoneal dialysis, the extended component can also release an osmotic agent, such as glucose, if fluid extraction is required.

[0032] Dialysis fluid recirculation can be continuous or tidal. Continuous circulation requires a double-lumen catheter or two separate catheters. Since peritoneal patients typically have a single-lumen catheter, it is expected that most peritoneal patients will use the system in tidal mode. This is achieved by reversing the direction of the pump unit at regular intervals.

[0033] The dialysis device 1 of the present invention (see Figure 5 It includes the following components:

[0034] i. Carrier 3, housing electronics 11, user interface 13, actuator 15, and sensors 17, 18, and 19. It initiates, controls, and monitors the dialysis operation. It includes the following components:

[0035] • Outer shell, with

[0036] οMain button,

[0037] Alarm LEDs and buzzers,

[0038] Power connector (for battery and adapter),

[0039] Pump motor

[0040] Electronic devices, having

[0041] Temperature sensors 18 (3 units), pressure sensors 19 (3 ​​units), air / bubble detectors 17 (2 units)

[0042] Display screen

[0043] The main control board (MAB) is used for advanced control (operating system), user interface, and IT communications (portal).

[0044] Hardware Control Board (HCB): Operation of actuators and sensors, hardware safety control, data acquisition, and data storage.

[0045] ii. A replaceable filter cartridge 5, connected to the patient via a flexible tube 7. The filter cartridge 5 includes:

[0046] • Reusable housing 21, having

[0047] Pump 23

[0048] Leakage sensor 25

[0049] Memory chip 27 (CAB) is used for filter cartridge identification and data storage.

[0050] • Purification unit / disposable insert 31:

[0051] Compartment 32 has a storage volume 39 for dialysis fluid and a storage volume 37 for accommodating the adsorbent.

[0052] Pipe 33, connector 34, and check valve 35 (tidal mode)

[0053] ο Particulate filter 36

[0054] The filter cartridge 5 is designed for daytime use as a wearable system (day filter cartridge, wearable day device), and can also be used overnight under certain circumstances.

[0055] iii. Extended filter cartridge (see Figure 6 The filter cartridge 5, as described above, is enlarged using an extension assembly 41. The extension assembly includes the following components:

[0056] • The housing 42 includes a heating element 43, a temperature controller 44, and a power supply 45.

[0057] • One or more dialysate reservoirs 46, or alternatively, filled with potassium and urea.

[0058] The adsorbent has compartments or electroadsorption units. In the latter case, dialysate is not required.

[0059] The extended filter cartridge is intended for nighttime use as a portable bedside device (night filter cartridge, portable night device), but can also be used during the day when it is more suitable.

[0060] The prototype version of the device is as follows Figure 1 (Daytime installation) Figure 2 (Carrier and filter cartridge) Figure 3 (The daytime unit is connected in a tidal pattern) and Figure 4 (Night device with extended components) is shown.

[0061] Figure 1 A prototype version of device 1 is shown. It consists of two parts: a carrier mounted on interchangeable filter cartridges. These two parts are as follows... Figure 2 As shown. Carrier 3 contains electronics with actuators, sensors, and a user interface. This component initiates, controls, and monitors the dialysis operation. Filter cartridge 5 is a replaceable component that houses the fluid loop and the purification unit for dialysate regeneration.

[0062] The device is connected to the patient's catheter via fluid line 7. For patients using single-lumen catheters, the device operates in tidal mode using a single fluid line. This is as follows: Figure 3 As shown. Continuous mode is also possible, but requires a double-lumen catheter or two separate catheters. Due to its small size and weight (approximately 2 kg), the device can be easily carried by the patient.

[0063] For nighttime use, such as Figure 4 As shown, an extension assembly is used to enlarge the filter cartridge. This enlarged filter cartridge, known as a night device, can be used as a portable bedside device.

[0064] The enlarged filter cartridge can be made into two parts, with replaceable filter cartridge 5 via... Figure 4 The tube shown is connected to a separate expansion component 41, but it can also be made into an integrated component.

[0065] Patient Connection: The device connects to the patient's peritoneal catheter via a single patient line to a single-lumen or double-lumen catheter (tidal mode), or via two patient lines to a double-lumen catheter or two separate catheters (continuous mode). In a preferred embodiment, the catheter placement should ensure that the delivery of fresh / regenerated dialysate occurs at the top of the peritoneal cavity, and the return of dialysate occurs at the bottom of the peritoneal cavity. This ensures optimal contact between the dialysate and the peritoneum and promotes high mass transfer. Preferred catheter positions and layouts are as follows: Figure 14 As shown, there are two separate conduits that can operate in both continuous and tidal modes. Figure 15 There are single-port double-lumen catheters that can only be operated in tidal mode, and Figure 16 There are double-orifice, double-lumen catheters that can be operated in both continuous and tidal modes. Most peritoneal patients are equipped with standard single-lumen catheters. In tidal mode, this provides good performance. However, using such a single-lumen catheter to improve mass transfer through continuous or semi-continuous tidal flow is suboptimal because the inflow and outflow of this catheter occur within the limited volume of the peritoneal cavity. Figures 14-16 As shown, using two separate catheters or a dedicated double-lumen catheter can achieve a larger volume and peritoneal area for mass transfer.

[0066] exist Figure 14 The diagram shows two separate catheters, with a preferred configuration where one catheter delivers regenerative dialysis fluid at the top of the peritoneum (liver, stomach) and the second catheter retrieves the fluid at the bottom of the peritoneal cavity. The catheters are positioned such that one catheter delivers regenerative dialysis at the top of the peritoneum (liver, stomach) and the second catheter retrieves the fluid at the bottom of the peritoneal cavity. This configuration can be used in both continuous and tidal modes.

[0067] Figure 15 The design of a single-port double-lumen catheter 51 is shown, with one lumen delivering fluid at the top of the peritoneum and the other lumen recovering fluid at the bottom. In the figure, a: Luer-lock connector, b: shunt with internal check valve, c: subcutaneous cannula, d: outlet port for delivering regenerated dialysate at the top of the peritoneum (liver, stomach), e: inlet port for recovering fluid from the peritoneal cavity at the bottom. The double-lumen catheter has a built-in check valve and shunt.

[0068] Figure 16 The design of a dual-port, dual-lumen catheter 53 is shown, with one lumen delivering fluid at the top of the peritoneum and the other lumen retrieving fluid at the bottom. In the figure, a: two separate Luer-locking connectors, b: header, c: subcutaneous cannula, d: outlet port for delivering regenerated dialysate at the top of the peritoneum (liver, stomach), and e: inlet port for retrieving fluid from the peritoneal cavity at the bottom.

[0069] Fluid flow: Dialysis fluid is extracted using a pump unit and returned to the patient. In a preferred embodiment, this is a peristaltic pump with silicone or similar biocompatible tubing. Before being returned to the patient, the dialysate is regenerated through a purification unit, which includes a volume of dialysate and / or an adsorbent system combined with a nanofilter.

[0070] Figure 5 A fluid loop is described for a daytime unit using a single patient tubing (connected to a single-lumen catheter) in tidal mode. Peritoneal dialysis fluid is drawn from the abdomen via a nanofilter by a peristaltic pump and stored in a reservoir. Here, the peritoneal dialysis fluid is diluted according to the dialysis volume and purified by an optional adsorbent system that absorbs toxins. When the reservoir is full (reaching the tidal volume), the pump unit reverses, and the purified dialysis fluid is returned to the patient via the same nanofilter. The process is monitored by sensors for temperature, pressure, fluid leakage, and air / gas entrainment.

[0071] exist Figure 6 The diagram shows the fluid circuit of the nighttime device, also in tidal mode, but now including an extension assembly. In a preferred embodiment, the dialysate extracted from the patient is sent to the extension assembly, then to the purification unit, and finally back to the patient. Alternatively, the extracted dialysate can be sent first to the adsorbent / tidal reservoir before being sent to the extension assembly. In this case, Figure 6 The two check valves in the system should be reversed.

[0072] exist Figure 5 and Figure 6 In this system, a nanofilter is located on the patient's tubing. The dialysate flow is then filtered in two directions: the dialysate flow to the peritoneal cavity is filtered to remove potential particles and microparticles released from the adsorbent, while the dialysate flow extracted from the peritoneal cavity is filtered to block large molecules. Large proteins such as albumin and other large molecules such as high molecular weight glucose (macro-cyclodextrins, highly branched cyclodextrins, and cluster dextrins) cannot pass through the nanofilter and are not removed by the device. Generally, removal of these large molecules is not necessary. However, if the patient's need for this is less significant, it is recommended. Figure 7 The alternative method described in [the document]. Figure 7 An alternative fluid loop is shown, in which the nanofilter is used only to filter the reflux of purified dialysate, and not to filter the dialysate extracted from the patient's abdomen. Here, the nanofilter is placed directly downstream of the purification unit and functions solely as a particulate filter. In this case, the dead volume of the nanofilter does not affect the performance of the device.

[0073] In continuous mode, the device has two patient lines: one for extracting fluid and the other for returning regenerated dialysate. Figure 8 (Daytime device) and Figure 9(Nighttime device) provides relevant charts for the continuous mode. Figure 8 The fluid circuit for the daytime unit in continuous mode is shown, using two separate fluid lines for dialysate extraction and return (requiring two tubing or one double-lumen tubing). In continuous mode, the internal reservoir contains only adsorbent. The fluid circuit for the nighttime version is shown below. Figure 9 As shown. The patient tubing is connected to either two separate peritoneal catheters or a double-lumen catheter. Figure 8 and Figure 9 The system uses a peristaltic pump, with the nanofilter placed directly downstream of the adsorbent unit. If it is preferable not to remove larger molecules (albumin, high molecular weight glucose) from the peritoneal cavity, a different approach can be adopted. Figure 10 The setup shown depicts a dialyzer used to exchange toxins from the peritoneal cavity into the device. The fluid contents of the abdomen are then dialyzed, similar to the procedure in a hemodialysis machine. The dialysate in the peritoneum is continuously circulated through the dialyzer filter. Toxins are exchanged from this dialysate into the fluid in the purification unit and extension assembly. This fluid is recirculated and purified using ultrafiltration in continuous or tidal modes via an adsorbent and the extension assembly. The circulation rate of the peritoneal dialysate is independent of the circulation rate of the fluid in the purification unit. Such a setup requires two pump units and a dual-port access system to the peritoneum, such as a double-lumen catheter or two separate catheters.

[0074] Figure 10 This approach also applies to hemodialysis. For hemodialysis, the patient tubing is connected to the hemodialysis blood inlet (shunt / fistula or CVC catheter). Blood is recirculated through the dialyzer filter. The dialyzer filter separates the blood from the fluid in the purification unit and extension assembly. Toxins are exchanged from the blood into this fluid through the membrane of the dialyzer filter. The fluid in the purification unit is recirculated and purified using ultrafiltration in continuous or tidal mode through the adsorbent and extension assembly in the device. The fluid in the purification unit and extension assembly can be dialysate, such as the dialysate used in conventional hemodialysis.

[0075] Figure 11 The fluid circuit of the nighttime device in tidal mode is shown, including the extension assembly, but without adsorbent. In this case, the storage capacity of adsorbent 37 is omitted or filled with dialysate. In this case, the peritoneal dialysate in the peritoneal cavity is circulated and diluted together with the dialysate in the filter cartridge and extension assembly. Without adsorbent, there is no need to install a nanofilter.

[0076] Particulate filter: The purified dialysate is filtered before being returned to the patient. Figure 12The results of dynamic light scattering (DLS) analysis of adsorbent-purified dialysate after filtration through a 0.2 μm filter and a 3 nm filter (high-flux dialyzer) are shown. The results indicate that the 0.2 μm filter is insufficient to block submicron particles in the adsorbent, and a nanofilter is required to obtain ultrapure quality. Therefore, a nanofilter (nanofilter membrane) with a pore size of 1 nm-10 nm is used. In a preferred embodiment, the nanofilter comprises a filter with a pore size less than 4 nm, particularly a dialyzer filter with a pore size in the range of 2 nm-3 nm. This dialyzer filter can be a low-flux, medium-flux, or high-flux dialyzer filter. The nanofilter can also be used to filter the dialysate stream drawn from the patient. This configuration is as follows... Figure 5 and Figure 6 As shown. Here, the nanofilter blocks the passage of large molecules (>10kDa for low-flux filters, >30kDa for high-flux filters) and prevents their removal by the filter cartridge. Therefore, the loss of useful components such as albumin and high molecular weight glucose is minimized. If the extension assembly is equipped with an electro-oxidation unit, it is recommended to block glucose polymers. This is to prevent the degradation of glucose polymers that are undesirable due to electro-oxidation. Glucose polymer blocking is achieved by using a high molecular weight glucose polymer as a permeabilizer, for example, combining a glucose polymer with a molecular weight >10kDa with a low-flux filter with a cutoff value <10kDa. In other configurations, a preferred embodiment will include a high-flux filter to allow the removal of intermediate molecules, such as β2-microglobulin. Combining the nanofilter with a dialysate packing material containing a high molecular weight glucose polymer (preferably >30kDa, maltodextrin, highly branched cyclodextrin) as a permeabilizer will allow for very low glucose additions for ultrafiltration, as these molecules cannot pass through the filter and are retained in the peritoneal cavity, while the lymphatic system has a low capacity to absorb these large molecules.

[0077] Purification Unit: The disposable insert of the filter cartridge houses the storage volume for the dialysate and the storage volume for the adsorbent system. These two volumes can be in two separate compartments or combined into a single integrated compartment. The design of the compartments and the inlet / outlet should ensure minimal risk of shortcut flows. In a preferred embodiment, the disposable insert is made of a flexible bag, given its low manufacturing cost and ease of sterilization.

[0078] Adsorbent: The adsorbent system is designed to bind toxins with low diffusivity, such as phosphates, small and medium-sized molecules, and protein-bound toxins (creatinine, β2-microglobulin, p-cresol sulfate, indophenol sulfate, hippuric acid, CMPF). It consists of two components: (1) activated carbon for removing organic toxins and (2) a phosphate binder, such as ferric hydroxide or lanthanum carbonate or a carrier material containing iron or lanthanum metal complexes (polystyrene, starch). In a preferred embodiment, the phosphate binder is polystyrene modified with ferric hydroxide. The volume of the adsorbent may be between 100 ml and 2000 ml, but is typically between 400 ml and 600 ml. In addition to toxin binding, the adsorbent also serves as a buffer system for glucose (added-function activated carbon) and bicarbonate or lactic acid (added-function phosphate binder), as described below.

[0079] Optionally, the adsorbent system may include a third component for removing unwanted contaminants that may be present in the dialysate. Typical examples are glucose degradation products (primarily aldehydes) that may be present in peritoneal dialysis fluid. These contaminants can be removed using dedicated activated carbon (after oxidation or chemical pretreatment) or a third adsorbent. For glucose degradation products, the third component could be an aldehyde remover, such as Lewatit VP OC 1065 or DIAIONcr20.

[0080] Pre-loaded: The adsorbent is pre-loaded with specific compounds to achieve neutral behavior (no adsorption or release of electrolytes) or specific adsorption or release (bicarbonate, lactic acid, glucose). Here, the adsorbent contains electrolytes (Na+). + Mg 2+ Ca 2+ Cl -The dialysate is balanced with a neutral pH (6-7.4) conditioning solution containing bicarbonate, lactate, and / or glucose ions. Bicarbonate and lactate ions are captured by a phosphate binder. During treatment, the trapped bicarbonate and lactate ions are released after ion exchange with phosphate in the patient's dialysate. The release of bicarbonate and lactate helps the patient maintain a healthy acid-base balance. The pre-loaded concentration is typically similar to that in the peritoneal dialysis fluid of the expansion unit, but can be lower or higher if absorption or additional release is required. Preloading magnesium and calcium ions is generally not required; omitting these ions eliminates the possibility of calcium and magnesium carbonate precipitation during storage. If glucose degradation products may form during sterilization (e.g., during heat sterilization), it is recommended to omit glucose during the pre-loading of the adsorbent. Activated carbon initially adsorbs glucose from the dialysate, but as glucose levels decrease, the adsorbed glucose is subsequently (partially) released. Activated carbon acts as a glucose buffer, providing peak regulation and stabilization of glucose levels. In very special cases, adsorbents may also be pre-loaded with other ingredients, such as vitamins and antioxidants such as ascorbic acid, glutathione, or cysteine ​​compounds, to protect patients from oxidative stress.

[0081] Adsorbent-free purification unit: This system can also operate as an adsorbent-free system. In this case, the adsorbent storage volume is omitted or filled with dialysate. In this configuration, the peritoneal dialysate in the peritoneal cavity is continuously circulated and diluted along with the dialysate in the device. In fact, the dialysate volume in the peritoneal cavity expands with the external dialysate in the filter cartridge and extension assembly. Compared to CAPD and APD, this adsorbent-free system remains highly efficient because continuous circulation allows for multiple reuses of the dialysate, which is more effective and provides better mixing and mass transfer in the peritoneum. The adsorbent-free setup is particularly useful when used in conjunction with an expanded filter cartridge filled with dialysate, as the larger dialysate volume prevents saturation. However, replaceable filter cartridges can also be considered for daytime use. In this case, the filter cartridge typically contains 1000-2000 ml of dialysate. Without an adsorbent, there is no risk of particle release, so the nanofilter can also be omitted. Omitting the adsorbent and filter helps reduce the cost of dialysis treatment. The system setup is as follows: Figure 11 As shown, for example, two dialysate chambers 39 are connected in series in the filter cartridge, and two dialysate chambers 46 are connected in series in the extension assembly. Using more than one dialysate chamber helps reduce dialysate short-circuiting during circulation and provides the opportunity to use combinations of dialysate, such as two or three dialysates with different glucose concentrations, to establish a uniform glucose load during treatment.

[0082] Tidal pattern: The dialysate volume may be between 50 ml and 500 ml, but is usually 200 ml to 300 ml. In tidal pattern, this volume is circulated in and out of the peritoneal cavity at a flow rate of 50 ml / min to 300 ml / min. In tidal pattern, with a flow rate typically 200 ml / min, the hourly circulation volume of dialysate is 6 liters. For nighttime treatment, this means a dialysate circulation volume of 48 liters. In current CAPD and APD procedures, only 8 to 15 liters of dialysate are flushed in and out. The high circulation volume increases mass transfer along the peritoneum. Therefore, the efficacy of dialysis treatment is enhanced. During the day, a similar circulation can be performed at a flow rate of 100 ml / min.

[0083] Fluid Management: For continuous circulation (two catheters / double-lumen catheter), the patient can select an appropriate flow rate, typically in the range of 50 ml / min–300 ml / min. The pump rate is set according to this flow rate. For tidal mode (single-lumen catheter), the fluid flow is defined by two adjustable parameters: the tidal volume and flow rate in and out of the peritoneal cavity. The tidal volume can be controlled, for example, by a timer, during the circulation of dialysate into the abdomen. The circulation time is equal to the tidal volume divided by the flow rate. At the end of this circulation, the pump reverses direction, and dialysate is pumped out of the cavity into the device's tidal reservoir. During this circulation, a sensor monitors the infusion status of the reservoir. This can be any type of sensor. In a preferred embodiment, the tidal reservoir is made of a flexible bag, and the sensor can be a simple pressure sensor or force sensor.

[0084] Air / bubble detection: Dialysis fluid entering and leaving the peritoneal cavity is monitored by an air / bubble detector, typically an ultrasound detector clipped onto the patient tubing at the device outlet. Detection of bubbles triggers an alarm and causes the device to automatically stop. A second air / bubble detector is located between the particulate filter and the adsorbent chamber. During the circulation of dialysate into the peritoneal cavity, when air or bubbles are detected in tidal mode, the pump reverses direction, and the air or bubbles are pumped back to the adsorbent chamber, where they are captured (internal air / bubble removal system).

[0085] Preventing underfilling / overfilling: To limit the risk of accidental underfilling or overfilling of the peritoneal cavity, the system is equipped with sensors that monitor filling pressure (pressure sensors), fluid loss sensors (leakage sensors), and air leakage sensors (air / bubble detectors).

[0086] Leak detection: Poor pipe or fluid system connections or mechanical failures can cause leaks. Fluid loss is detected by leak sensors (e.g., conductivity sensors). Leaking air is detected by one of the air / bubble detectors.

[0087] Detection of fluid line blockage: Blockage of fluid lines is detected by pressure / force sensors in or on the patient's tubing.

[0088] Extension Component: The filter cartridge extension component 41 includes a housing 42 having a heating element 43, a temperature control unit 44, and a power supply 45. It can accommodate a compartment 46 for holding 5L-15L (typically 7L-10L) of dialysate. In a preferred embodiment, the compartment 46 has a capacity of 9L-10L and is made of a flexible bag system (one or more bags) that can be placed within the housing 42. The compartment 46 is filled with a conventional peritoneal dialysis fluid formulation containing NaCl, MgCl2, CaCl2, sodium bicarbonate and / or sodium lactate, glucose and / or dextran. The physician fine-tunes the actual composition according to the patient's needs. The dialysate in the compartment is composed of… Figure 6 and Figure 9 The apparatus shown circulates. The function of the dialysate compartment is to increase the storage capacity for toxins such as urea and potassium, and to release glucose required for ultrafiltration (fluid extraction).

[0089] Uniform glucose release: Activated carbon in the filter cartridge acts as a glucose buffer: it begins to adsorb glucose when the glucose concentration is relatively high, and releases glucose as the concentration decreases due to dilution (ultrafiltration) and patient reabsorption. Therefore, glucose levels are stable, and the peak concentration can be maintained at a much lower level than in conventional peritoneal dialysis. Without the use of an adsorbent system, the dialysate compartments in the extension assembly can contain two dialysate components, separated into two tandem compartments: a low-concentration glucose dialysate (e.g., 1%–2% glucose) that enters the patient first in one compartment and a high-concentration glucose dialysate (e.g., 2%–4% glucose) dialysate in the second compartment. When the low-concentration glucose dialysate compartment enters the patient, the glucose in the high-concentration glucose dialysate compartment is diluted by the dialysate effluent returning from the patient. This setup can be improved by using three or more dialysate components in a multi-bag system. If the filter cartridge does not contain any adsorbent and is used in combination with an extension assembly filled with a high concentration of glucose dialysate, the same applies to the dialysate composition in replaceable filter cartridges filled with a combination of glucose-free dialysate and adsorbent, or dialysate with a glucose content from zero to (e.g., 1%-2%).

[0090] Alternative Extension Components: Extension components can accommodate alternatives to dialysate compartments, including electro-oxidation units or electrocatalytic adsorption units, as described in WO 2012060700 and WO 2015060716. The contents of these two patent applications are incorporated herein by reference. When the electro-oxidation unit contains a potassium binder (cation exchanger), it provides the ability to remove urea and potassium simultaneously without dialysate. The volume of such extension components is typically 1L-1.5L. In this case, a high molecular weight glucose polymer as an osmotic agent is used for dialysate filling for the patient along with a low-flux filter. The low-flux filter prevents the glucose polymer from entering the electro-oxidation unit, thereby preventing glucose degradation. As a safety measure, a release system for antioxidants (such as ascorbic acid, glutathione, cysteine ​​compounds) can be implemented. Such a system can be an active system with a small pump and antioxidant reservoir, or a passive system that releases antioxidants via pre-loaded adsorbent.

[0091] Alternative expansion components: Expansion components can accommodate alternatives to dialysate compartments, including compartments containing adsorbents for urea and potassium. This may reduce the volume of the expansion component to 2-3 L. This option requires a separate glucose or similar osmotic fluid infusion or release system.

[0092] Example

[0093] like Figures 1-6 and Figure 11 The prototype device shown has been tested in vitro and in vivo (animal models) to verify the biocompatibility and efficacy of the new system. The prototype is equipped with a filter cartridge containing 325 ml of activated carbon and 135 ml of phosphate binder (ferrous oxide), and operates in tidal mode with a tidal volume of 200-300 ml and a flow rate of 150-200 ml / min. Furthermore, filter cartridges containing only dialysate and no adsorbent have been tested and evaluated. Experiments were conducted during the day and night using extended units containing 9 L and 10 L of dialysate. The typical continuous duration for each experiment was 8 hours, with some cases up to 16 hours. Compared to static (standard peritoneal permeability analysis, SPA), the mass transfer area coefficients (MTAC) for potassium (175%), urea (200%), creatinine, and phosphate (250%) increased. This increase is attributed to the continuous recirculation of the dialysate. The system's absorbability depends on the amount of dialysate and adsorbent used. The absorption capacity has been proven to be very sufficient by utilizing the capacity of the adsorbent and dialysis fluid described above, thereby significantly improving the removal rate.

[0094] Based on these findings, scenarios of daily patient use were assessed. These involved scenarios such as: using the night system for 8 hours at night, followed by 16 hours of dialysis fluid resting during the day (Scenario A), or two subsequent 8-hour resting periods (Scenario B), or 16-hour dialysis fluid resting periods combined with 4 hours of daytime system use (Scenario C) or 8 hours of daytime use (Scenario D).

[0095] The assessment was conducted using a physiological model that predicted daily removal based on 24-hour in vivo toxin formation, mass transfer through the peritoneum to the dialysate, absorption of toxins by the dialysate, and adsorption of toxins by the adsorbent in the purification device.

[0096] Example 1: 10L of dialysate from the nighttime system

[0097] A patient weighing 72 kg and with 42 liters of body fluid received an 8-hour nighttime systemic treatment. The system was equipped with a filter cartridge and a dialysate expansion assembly containing only dialysate and no adsorbent. The total dialysate volume was 10 L. Following this treatment, the patient received a new indwelling of 2 L of fresh dialysate (dextran) in the morning for the remainder of the day, either 16 hours (Scenario 1a), or a single indwelling of 2 L of dextran for 8 hours followed by a second 8-hour rest (Scenario 2b), or a single indwelling of 2 L of dextran for 16 hours, combined with a 4-hour treatment using a daytime filter cartridge starting 6 hours later (Scenario 1c), or an 8-hour daytime systemic treatment starting 4 hours after a 4-hour rest. The daytime filter cartridge was filled with adsorbent (325 ml activated carbon, 135 ml phosphate binder) and some dialysate. The total volume was 1 L. The patient's daily toxin production was set at 240 mmol urea, 40 mmol potassium, 15 mmol phosphate, and 10 mmol creatinine. During system operation using either the night filter cartridge or the day filter cartridge, the dialysate is circulated, increasing mass transfer by 2 times.

[0098]

[0099]

[0100] For each scenario, the daily removal rate was predicted by the model and compared with the removal rates, CAPD and APD, in current peritoneal dialysis treatment practice. The values ​​predicted by the same model were in good agreement with the values ​​in practice.

[0101] The removal results are listed in the "Scenario 1 Nighttime Filter Cartridge 10L Dialysate" table. The simplest scenario, with only one daytime retention, shows a 30% higher removal rate than the current practice (Scenario 1a). Two daytime retentions increase the removal rate by 60% (Scenario 1b). In Scenario 1c, with only a single daytime retention and a 4-hour daytime system usage period, the removal rate increases to 85%. The longer the daytime system usage, the higher the removal rate will be, reaching 120% (Scenario 1d).

[0102] With the help of a daytime system, patients can increase potassium removal rates by approximately two times. Without a daytime system, the improvement rate is limited to 30%–60%. However, it is still an important advancement. The listed increase in potassium removal is actually excessive and can lead to hypokalemia. This can be offset by pre-adding some potassium to the dialysate.

[0103] Scene 1: 10L dialysis fluid filter cartridge overnight

[0104]

[0105] Example 2: 2L Nighttime System with EO Unit and Adsorbent

[0106] The conditions, scenario, and procedure are the same as in Example 1. However, in this scenario, the extended assembly includes an electro-oxidation unit (EO unit) for removing urea and other organic toxins. The total volume of the night filter cartridge, including this extended assembly, is only 2L. Next to the EO unit are 300ml of phosphate adsorbent, 150ml of potassium adsorbent, and 400ml of activated carbon. The resulting volume is filled with dialysate. The day filter cartridge is similar to that in Example 1, filled with 325ml of activated carbon and 135ml of phosphate binder, for a total volume of 2L. The EO unit is operated at 6A, removing urea at a rate of 20mmol / h.

[0107] The removal results are listed in the table "Scenario 2: Nighttime Filter Cartridge 2L with EO Unit and Adsorbent". In the simplest scenario with only one daytime retention, the removal rates of creatinine and phosphate were improved by 40%-60% compared to the current practice (Scenario 2a). With two daytime retentions, this increased to 80% (Scenario 2b). In Scenario 1c, with a single daytime retention combined with 4 hours of use of the daytime system, the removal rates of creatinine and phosphate reached 100% (Scenario 2c), and according to Scenario 2d, even 130%-150% was achieved with 8 hours of use. In this case, the increase in potassium removal rate was limited to prevent hypokalemia. The increase in urea removal rate was limited to 50% (sufficient), but could be increased by applying greater power to the EO unit.

[0108] Scenario 2: 2L night filter cartridge with EO unit and adsorbent.

[0109]

Claims

1. An apparatus (1) for removing toxins from a patient via dialysis, characterized in that, The device includes: i) A carrier (3) including electronic devices (11) including control software, a user interface (13), an actuator (15) and sensors (17, 18, 19), the carrier (3) initiating, controlling and monitoring dialysis operations; ii) A replaceable filter cartridge (5), connected to the patient via a flexible tube (7), the filter cartridge (5) being connected to the carrier (3) and comprising: The reusable housing (21) includes a pump (23), a leak sensor (25), and a memory chip (27) for cartridge identification and data storage. A purification unit (31) for daytime use includes an adsorbent system for removing toxins with low diffusivity, including phosphate, small molecule and protein-bound toxins. The purification unit (31) also includes a compartment (32) having a tube (33), a connector (34), a check valve (35) and a compartment having a volume for dialysate (39) and an adsorbent system (37) having a particulate filter (36). iii) An extension assembly (41) for nighttime use, configured to remove daily urea and potassium toxins, wherein the extension assembly (41) is connected to the replaceable filter cartridge (5), the extension assembly (41) including one or more compartments for containing dialysate and / or additional adsorbent, and / or an electro-oxidation unit mounted in a housing (42) having a heating element (43), a temperature controller (44) for the heating element (43), and a power supply (45).

2. The apparatus according to claim 1, characterized in that, The purification unit (31) includes a compartment filled with dialysis fluid (39) and a compartment filled with an adsorbent, the adsorbent comprising: i) Activated carbon, used to bind organic toxins and to buffer glucose or glucose polymers in peritoneal dialysis, thereby preventing the peritoneum from being exposed to high glucose spikes, and ii) Anionic binders for removing phosphates and buffering bicarbonate and / or lactate, stabilizing the release of sodium bicarbonate and / or lactate. iii) Adsorbents used to remove contaminants that may be present in the dialysate, including glucose degradation products.

3. The apparatus according to claim 1, characterized in that, The extension assembly (41) includes one or more compartments (46) for containing dialysate, the compartments (46) being filled with fresh dialysate including NaCl, MgCl2, CaCl2, sodium bicarbonate and / or sodium lactate, and in the case of peritoneal dialysis, including glucose, glucose polymers or other permeabilizing agents required for ultrafiltration.

4. The apparatus according to claim 1, characterized in that, The extension assembly (41) includes two or more compartments (46) connected in series for containing dialysate, each compartment being filled with dialysate of different composition to achieve uniform glucose release during treatment, with a low concentration of osmotic agent, comprising glucose or a glucose polymer, applied in the compartment that first circulates to the patient, and a higher concentration of osmotic agent applied in the upstream compartment.

5. The apparatus according to claim 1, characterized in that, The extended component (41) includes a dialysate and is supplemented with an adsorbent for removing potassium and urea, wherein the dialysate includes NaCl, MgCl2, CaCl2, sodium bicarbonate and / or sodium lactate, and in the case of peritoneal dialysis, includes glucose, glucose polymers or other permeabilizers required for ultrafiltration.

6. The apparatus according to claim 5, characterized in that, When using high molecular weight glucose polymers as dialysate for peritoneal dialysis, the extension assembly (41) also includes a low-flux filter that prevents the high molecular weight glucose polymers from entering the electro-oxidation unit.

7. The apparatus according to claim 1 or 2, characterized in that, The adsorbents in the purification unit (31) and the extension assembly (41) are pre-loaded with electrolytes, bicarbonates, lactates, and, if applicable, glucose or glucose polymers or other permeabilizers and antioxidants suitable for ultrafiltration, including ascorbic acid, glutathione or cysteine ​​compounds.

8. The apparatus according to any one of claims 1-6, characterized in that, The device is configured to connect to a single-lumen catheter or a double-lumen catheter via a single patient line, or to connect to a double-lumen catheter or two separate catheters via two patient lines.

9. The apparatus according to claim 7, characterized in that, The device is configured to connect to a single-lumen catheter or a double-lumen catheter via a single patient line, or to connect to a double-lumen catheter or two separate catheters via two patient lines.

10. The apparatus according to claim 8, characterized in that, The device is connected to a single-port double-lumen catheter (51) that operates in tidal mode.

11. The apparatus according to claim 8, characterized in that, The device is configured to connect to a dual-port dual-lumen catheter (53) capable of operating in both continuous and tidal modes.

Images