Method and system for delivering high quality infusible peritoneal dialysis fluid online at high flow rates - Patents.com

Abstract

The system includes an apparatus configured to mix water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer to generate a supply dialysate, a supply chamber configured to store the supply dialysate, a first filter, a second filter, and one or more valves configured to receive the supply dialysate from the supply chamber and remove contaminants from the supply dialysate, where in a first configuration, the second filter receives used dialysate from the patient drain line and captures biological components from the used dialysate to allow the used dialysate to be dispensed via the system drain line, and in a second configuration, the second filter receives the supply dialysate and removes further contaminants from the supply dialysate to allow the supply dialysate and biological components to be dispensed via the patient fill line.

Description

[Technical field]

[0001]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 293,257, filed December 23, 2021, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] There are two main dialysis methods used to assist patients in need of renal replacement therapy: hemodialysis and peritoneal dialysis. Peritoneal dialysis utilizes the patient's own peritoneum as a semipermeable membrane. The peritoneum is a membranous lining of the body cavity that surrounds all of the organs between the diaphragm and the pelvis, which can act as a natural semipermeable membrane due to the large number of blood vessels and capillaries embedded within it.

[0003]

[0003] In peritoneal dialysis, sterile dialysate is infused into the peritoneal cavity via an indwelling catheter. This can be accomplished manually by gravity or using a machine known as a cycler. The dialysate is allowed to reside in the peritoneal cavity for a sufficient time (e.g., 4 hours) to result in a net removal of toxins and water, after which the dialysate is drained and replaced with fresh dialysate.

[0004] In hemodialysis, fluid removal is achieved by generating transmembrane pressure with a hemodialysis machine, which is not possible in peritoneal dialysis, necessitating a different strategy to remove excess fluid from the patient. In peritoneal dialysis, instead of creating a hydrostatic pressure gradient between the blood and the dialysate, an osmotic gradient is generated by including an osmotic agent in the peritoneal dialysis fluid. The osmotic agent used in the majority of peritoneal dialysis fluids is glucose. As will be described later, glucose presents significant problems in this application, but more than 40 years of research have not produced a suitable practical alternative for use during daily exchanges.

[0005] The main difficulty in including glucose in peritoneal dialysis fluid is encountered during terminal sterilization (e.g., by autoclaving). Any solution infused into a sensitive body cavity such as the peritoneum is ideally at physiological pH (e.g., 7.2-7.4), but it is not possible to terminally sterilize glucose-containing solutions at physiological pH. Peritoneal dialysis fluids (as well as other pharmaceutical solutions containing glucose, e.g., dextrose 5 water or total parenteral nutrition) are universally terminally heat sterilized (i.e., autoclaved) for about 2 hours, typically at 120°C, under pressure to ensure complete inactivation of bacteria and their spores, and to prevent boiling. Under autoclave conditions, when the pH of the solution is maintained in the physiological range, the glucose in the solution discolors (caramelizes) and also converts into several reaction products collectively known as glucose degradation products (GDP).

[0006] Some of these GDPs, such as 3-deoxyglucosone (3-DG), 3,4-dideoxyglucosone-3-ene (3,4-DGE), glyoxal, methylglyoxal, 5-hydroxymethylfurfural (5-HMF), 2-furaldehyde (2-FA), formaldehyde and acetaldehyde, have been identified in peritoneal dialysis fluid (PDF). GDP is the precursor of highly reactive advanced glycation end products (AGEs) in proteins. AGEs result from chemical reactions when reduced carbohydrates (such as glucose) react with amino acids or nucleotides. In 1912, Louis Maillard first described this nonenzymatic reaction, known as the "Maillard reaction." Among the above GDPs, 5-HMF and 2-FA are considered important indicators of degradation, which may appear in the glucose degradation process under sterile conditions.

[0007]

[0007] Although the exact toxicity threshold for GDPs and AGEs administered to patients with chronic diseases is not yet known, high levels of GDPs and AGEs have been shown to affect cell homeostasis, participate in oxidative stress, be associated with cell inhibition, induce apoptosis in human leukocytes and renal epithelial cells, cause degradation of mesothelial cells and peritoneal membrane properties, affect the cardiovascular system, be associated with increased cardiovascular morbidity and decreased renal function, or cause kidney damage. Other studies have shown that accumulation of AGEs in patients suffering from diabetes mellitus can lead to microvascular complications such as diabetic retinopathy or diabetic vascular complications. Very high levels of 5-HMF can lead to acute toxicity.

[0008] Therefore, manufacturers of PDFs must sterilize these solutions at sub-physiological pH to minimize caramelization and GDP formation. However, PDFs produced and infused at lower pH levels have also been shown to result in a temporary reduction in insufficient host defenses present in the peritoneal cavity, contributing to a reduced ability of the patient to respond to bacterial invasion, which in turn results in a higher incidence of peritonitis, one of the major complications of peritoneal dialysis. PDFs at low pH also cause pain upon infusion in many patients, contributing to patients choosing to perform hemodialysis instead, or dropping out of peritoneal dialysis after a period on the modality. All of which results in increased costs for clinical providers and suboptimal clinical outcomes for patients.

[0009]

[0009] Thus, manufacturers of PDFs have had to compromise between minimizing the formation of GDPs during sterilization and the complications caused by low pH. This compromise has resulted in the majority of PDFs being produced at a pH of 5.2 to 5.5, even though published studies have determined that GDP production is minimized only after the pH is lowered to the 2.0 to 2.6 range during sterilization (although solutions sterilized at 3.0 had only slightly higher GDP concentrations).

[0010] Within the past few years, several low GDP PDFs have been commercially available, featuring a dual-chamber bag system that allows sterilization and storage of glucose at low pH. The beneficial effects of neutral pH combined with low concentrations of GDP on cell viability and peritoneal host defense are abundantly documented in the literature. However, PDFs produced in this manner result in products that require incremental manipulation by the patient during each exchange, additional training for the patient, and increased costs to manufacture the product, all of which have led to poor adoption of these products by clinical providers of dialysis therapy.

[0011] Another major drawback of peritoneal dialysis, and the main reason patients fail to remain on this therapy, is inadequacy, which can manifest as either or both of the failure to remove adequate amounts of uremic toxins or adequate amounts of water (ultrafiltration) from the patient.

[0012]

[0012] There are two major forms of peritoneal dialysis (PD): continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD, also known as APD, automated peritoneal dialysis).

[0013] In CAPD, the patient infuses dialysate from a terminally sterilized plastic bag into the peritoneal cavity via a transfer set and an indwelling catheter. The volume infused is adjusted to the size of the patient, with 2 liters being the most typical. However, the larger the patient, the more toxins and water must be removed, so the volume infused must be increased, sometimes up to 3 liters.

[0014] Once the solution is infused, it is allowed to remain in the peritoneal cavity while toxins and water are transferred from the blood. A typical residence time is 4 hours. Removal of toxins and water is most rapid at the beginning of the residence, when the concentration gradient between the blood and the dialysate is greatest. As the blood and dialysate reach equilibrium, the removal rate approaches zero. At this point, a significant amount of glucose has been absorbed into the bloodstream.

[0015] After the dwell period, the patient transfers the peritoneal contents back into the empty bag used for infusion, disconnects and discards it, attaches a new bag, and begins another fill / dwell / drain cycle. CAPD patients perform this "exchange" four or five times a day, once in the morning, once at lunchtime, once at dinner, and once just before bedtime. This final nighttime exchange is left in place for about eight hours, during which time much of the water drawn into the peritoneum is reabsorbed along with the glucose used to attract it, unless a much higher concentration of glucose is used, e.g., 4.25% versus 1.5% for the daytime exchange. This dramatically increases the amount of glucose absorbed by the patient, leading to another major drawback of PD. About half of all dialysis patients suffer from end-stage renal failure secondary to diabetes, and accumulating sugar from the dialysate becomes a problem for diabetic patients.

[0016]

[0016] A real problem for any PD patient is the fact that the patient absorbs a significant number of calories through the uptake of sugar from the dialysate, which can reduce the appetite for protein and predispose to malnutrition, which is one of the reasons why patients die or drop out of this therapy.

[0017]

[0017] Compounding this under-intake of protein is the fact that amino acids and proteins also pass from the blood into the dialysate and are removed from the body with each effusion.

[0018]

[0018] The desired amino acid and protein bonds lost with each excretion are any components of the host defense / immune response (e.g., macrophages, chemotactic components) that may have migrated into the peritoneum to combat the bacterial invasion that causes any peritonitis. This, of course, results in an increase in the cases of peritonitis.

[0019] Finally, dropout from CAPD has two other causes that are inherent to the procedure: one is "burn-out" due to the monotony of performing 4-5 exchanges daily for the rest of one's life, and the other is the relatively large amount of supply that must be received and stored in the patient's home each month.

[0020]

[0020] In CCPD, daytime exchanges are simply switched to 8 hours of sleep, with the inflow and outflow of dialysate controlled by the device (cycler). This is designed to reduce the patient's boredom of performing these exchanges during the patient's waking hours. Typically, the cycler leaves the patient with a final fill volume just before the patient wakes up, which is left in the peritoneum until around lunchtime, when the patient drains. The patient then has the option to remain "unhydrated" until the evening of the day, which has the advantage of allowing the peritoneum to recover from the constant onslaught of low pH / high osmolarity solutions, or another fill volume can be infused for the remainder of the day if more toxin and water removal is required.

[0021]

[0021] Although CCPD overcomes some of the drawbacks of CAPD, many remain. These drawbacks, which typically lead to dropout (to hemodialysis) or death, can be summarized as follows:

[0022] Inadequacy: This is a direct consequence of the limitations on how much dialysate can be delivered to the patient in a 24 hour period; that is, PD requires low dialysate flow rates (Q d With current technology, the Q d Attempts to increase dialysis time include increasing the number of exchanges and / or the volume of dialysate, which in turn increases burnout, increases storage space requirements, and increases costs, all of which are largely intolerable to both patients and providers.

[0023] Glucose uptake: This is highly undesirable for diabetic patients and leads to protein malnutrition. This is due to a) a lack of residence time (low Q) which allows the dialysate and blood to reach equilibrium. d ) due to the use of 4.25% glucose during the long residence time.

[0024]

[0024] Ultrafiltration failure and peritonitis: Low pH, high osmolality, and the presence of GDPs and AGEs contribute to scarring of the peritoneum, reducing its permeability to water penetration, inactivating components of the host defenses, and increasing inflammation.

[0025] Loss of amino acids, proteins, and white blood cells with each drainage: This is due to the used dialysate being sent directly to drainage, which contributes to protein malnutrition and a higher incidence of peritonitis.

[0026] Burnout: This results from the unavoidable and tedious daily CAPD exchange routine or set up / tear down of the cycler.

[0027]

[0027] Burden on the volume of supplies at home: This is primarily a result of performing PD with bags of terminally sterile solutions, their associated tubing sets and connectors, and the ancillary supplies required to perform sterile connections / disconnections.

[0028] Therefore, there is a need to overcome the aforementioned shortcomings of peritoneal dialysis. Summary of the Invention

[0029]

[0029] A first example is a system for peritoneal dialysis, comprising: a mixing device configured to mix water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer to generate a supply dialysate; a supply chamber configured to store the supply dialysate; a first filter including a first port and a second port, the first filter configured to receive the supply dialysate from the supply chamber at the first port and to remove contaminants from the supply dialysate; a second filter including a third port and a fourth port; a patient drain line connected to the third port; the second filter receives used dialysate from the patient drain line at the third port, a system drain line connected to the fourth port, and one or more valves, where in a first configuration, the second filter receives used dialysate from the patient drain line at the third port and captures biological components from the used dialysate to allow the used dialysate to be dispensed via the system drain line, and in a second configuration, the second filter receives supply dialysate from the second port at the fourth port and removes further contaminants from the supply dialysate to allow the supply dialysate and biological components to be dispensed via the patient fill line.

[0030]

[0030] A second example includes a method of operating the system of the first example, including moving used dialysate into a third port and then through a second filter to capture biological components from the used dialysate; mixing water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer via a mixing device to produce a supply dialysate; moving the supply dialysate into the first port to remove contaminants from the supply dialysate; moving the supply dialysate from the second port into a fourth port and then through a second filter to remove further contaminants from the supply dialysate; and dispensing the supply dialysate and biological components from the third port via a patient fill line.

[0031] A third example includes a computer readable medium storing instructions that, when executed by the system of the first example, cause the system to perform the method of the second example.

[0032]

[0032] A fourth example includes a system for peritoneal dialysis including a mixing device configured to mix water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer to produce a supply dialysate, a supply chamber configured to store the supply dialysate, a drain line, a filter, and one or more valves that, in a first configuration, allow the filter to receive used dialysate from the drain line at a first port of the filter to capture biological components within the used dialysate, and in a second configuration, allow the filter to receive supply dialysate from the supply chamber at a second port of the filter to remove contaminants from the supply dialysate.

[0033]

[0033] A fifth example includes a method for performing peritoneal dialysis comprising providing the system of the first example or the fourth example; mixing water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralizing buffer via a mixing device to produce a supply dialysate; moving the supply dialysate through a first filter into a first port to remove contaminants from the supply dialysate; moving the supply dialysate from a second port into a fourth port and then through a second filter to remove further contaminants from the supply dialysate; moving purified dialysate to the patient's peritoneal cavity for a predetermined time for peritoneal dialysis while producing used dialysate; moving the used dialysate into a third port and then through the second filter to capture biological components from the used dialysate and produce a depleted used dialysate and draining the depleted used dialysate; and repeating steps (ii)-(vi) to dispense the supply dialysate for further peritoneal dialysis while draining the captured biological components through the second filter for introduction back to the patient.

[0034]

[0034] When the term "substantially" or "about" is used herein, it means that the recited characteristic, parameter, or value need not be achieved exactly, but deviations or variations, including, for example, tolerances, measurement errors, measurement accuracy limits, and other factors known to those skilled in the art, may occur in an amount that does not eliminate the effect that the characteristic is intended to have. In some examples disclosed herein, "substantially" or "about" means within + / - 0 to 5% of the recited value.

[0035]

[0035] These and other aspects, advantages, and alternatives will become apparent to those skilled in the art from a reading of the following detailed description, with appropriate reference to the accompanying drawings. Moreover, it should be understood that this summary, as well as the other descriptions and figures provided herein, are intended to illustrate the invention by way of example only, and thus, numerous variations are possible. [Brief description of the drawings]

[0036] [Figure 1] FIG. 1 is a flow chart of a method according to an example. [Diagram 2] FIG. 2 is a block diagram of a computing device, according to an example. [Diagram 3] FIG. 3 is a schematic diagram of a system configured for capturing biological components from used dialysate, according to an example. [Figure 4] FIG. 4 is a schematic diagram of a system configured for removing contaminants from a dialysate supply as the dialysate supply and captured biological components are dispensed through a patient fill line, according to an example. [Diagram 5] FIG. 5 is a block diagram of a method according to an example. [Figure 6] FIG. 6 is a block diagram of a method according to an example. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037]

[0042] The present disclosure includes examples that may help alleviate some of the shortcomings of previous systems and methods used for peritoneal dialysis. Conventional methods for peritoneal dialysis may cause depleted levels of proteins and host defenses (e.g., leukocytes, macrophages and / or chemotactic components) in the patient's blood, as some proteins and host defenses may reach the used dialysis fluid drained from the patient along with metabolic waste products such as uremic toxins. Loss of host defenses may contribute to peritonitis, and loss of proteins may contribute to malnutrition. Thus, patients would benefit from retaining proteins and host defenses that are typically lost during peritoneal dialysis.

[0038]

[0043] This disclosure provides an example of a peritoneal dialysis solution preparation and processing system. The components included in the system and their functions are broadly delineated below in the order in which they are first contacted by the fluids flowing through the system:

[0039]

[0044] A three-way valve V1 at the inlet to the mixer allows water from a separate upstream water purification system to enter the mixer. This valve V1 is alternately used to recirculate fluid within the entire fluid path of the device through the disinfectant bypass fluid path between valves V1 and V16.

[0040]

[0045] A first conductivity cell C1 downstream of the inlet is used to ensure that the water being drawn into the mixer is below a safe conductivity upper limit set in a software lookup table in the system's memory.

[0041]

[0046] A pressure sensor P1 is installed downstream of the conductivity cell C1 to ensure that the water pressure presented to the inlet side of the water pump PU1 is high enough to prevent degassing and cavitation.

[0042]

[0047] The granular activated carbon cartridge (GAC) downstream of pressure sensor P1 is used to remove any chlorine or chloramines that may have been destroyed through a chlorine / chloramine removal device in a separate water purification system that supplies water to this device during treatment. This component may or may not be necessary depending on the method of chlorine / chloramine removal implemented in the upstream water purification system.

[0043]

[0048] An in-line fluid heater with two associated temperature sensors is placed downstream of the GAC: one sensor upstream (T1) and one downstream (T2) of the heater, in conjunction with on-board circuitry and software, are used to control the temperature of the water passing through the heater.

[0044]

[0049] A water metering pump PU1 downstream of the heater precisely controls the flow of water to downstream components of the system.

[0045]

[0050] A metering pump PU2 downstream of the water metering pump PU1 precisely meters the amount of acid / electrolyte concentrate according to the dialysate recipe present in the software.

[0046]

[0051] A metering pump PU3 downstream of pump PU2 precisely meters the amount of neutralization buffer according to the dialysate recipe present in the software.

[0047]

[0052] A metering pump PU4 downstream of pump PU3 precisely meters the amount of osmotic concentrate according to the dialysate recipe present in the software.

[0048]

[0053] The flexible supply chamber is surrounded by a rigid enclosure that can be vented to atmosphere via valve V2. When vented via open valve V2, the supply chamber can expand to its maximum volume, as limited by the physical dimensions of the rigid enclosure, under positive pressure generated by pumps PU1, PU2, PU3, and PU4 that deliver components of the supply dialysate into the supply chamber, as long as downstream valves V3 and V4 are oriented to prevent any outflow from this chamber. This supply chamber can also be used to deliver its contents downstream by closing valve V2 and opening valve V15, allowing positive air pressure generated by an air compressor (AC) and stored in a rigid positive pressure reservoir (PPR) to be delivered into the rigid enclosure surrounding the supply chamber. The contents of the supply chamber are delivered downstream as long as the downstream valves, under the control of the system software, are correctly oriented to allow the outflow of the contents.

[0049]

[0054] Downstream of the supply chamber are included redundant conductivity cells C2 and C3, one a priming sensor and the other located in the safety system side of the software to verify priming. Their purpose is to ensure that the dialysate is made up in a safe range around the expected conductivity as set by the patient's physician and placed in the software lookup table for the dialysate prescription loaded into the software.

[0050]

[0055] As with the conductivity sensors, redundant temperature sensors T3 and T4 are included, one for priming and the other for safety, whose purpose is to ensure that the dialysate being delivered to the patient is within a physiologically safe range.

[0051]

[0056] Three-way valve V3 allows fluid to be directed either to valves V5 (PF2) and V6 (exhaust) or into a first pyrogen filter PF1. PF1 and / or PF2 can take the form of a Medica DiaPure® filter and / or a Nephros® DSU-D filter.

[0052]

[0057] The first pyrogen filter PF1, through which the supply dialysate must pass before it reaches the patient's peritoneal cavity, is designed to remove any pyrogens and microorganisms from the supply dialysate. While water is perfused through the fiber bundle, air is removed from the hollow fibers of PF1 by opening valve V7 (to atmosphere) with valve V4 closed (to drain and PF2). This forces the air through V7 and out through a 0.2 micron sterile filter to the atmosphere. After priming the fiber bundle by closing valve V7 and opening valve V4, the air in the space between the fiber bundle and the rigid case that encloses it is removed, allowing fluid to flow through the fibers, fill the case, and flow through the fluid path that connects the outlet port of PF1 to the drain line that runs through valves V6 and V16.

[0053]

[0058] A second (redundant) pyrogen filter PF2 must also be passed by the dialysate that first passed through PF1 before it can enter the patient's peritoneal cavity. PF2 is primed similarly to PF1 by opening valves V5 (to PF2) and V8 (to atmosphere) while valves V6 (to drain) and V9 (to patient fill) are closed, allowing air to exit through the 0.2 micron sterile filter. The case of PF2 is primed by closing V8 and V9 and opening valves V11 (to the patient drain and / or drain chamber) and V12 (to system drain), allowing fluid to fill the case and exit down the drain line through V16.

[0054]

[0059] Pressure sensor P2 is located immediately upstream of PF1, and pressure sensor P3 is located downstream of PF1 between valves V4 and V5. Their purpose is to calculate and monitor the transmembrane pressure (TMP) across the fibers of PF1 to ensure that the TMP never exceeds the maximum specified for that brand of pyrogen filter as shown in the product insert. Similarly, pressure sensor P4 is placed immediately downstream of PF2 and upstream of valves V9 and V11 so that the TMP of PF2 can be calculated from P3 and P4.

[0055]

[0060] The dialysate is conducted to and from the patient through a tubing fluid path that is external to the dialysate solution preparation and treatment system and is defined by a patient fill line and a patient drain line.

[0056]

[0061] In addition to being used to calculate the TMP of PF2, P4 is also used to ensure that the pressure of the dialysate flowing to the patient never exceeds the safe upper positive pressure limit set in the software.

[0057]

[0062] Sometimes an indwelling peritoneal dialysis catheter terminating in the patient's peritoneal cavity becomes mispositioned or kinked, restricting the flow of dialysate. To detect this, a flow sensor FM1 is placed upstream of the patient connection line (PCL). If the flow rate decreases below an alarm limit set in the software, or if the P4 detects a sudden increase in pressure, or both, an alarm alerts the patient to resolve the blockage.

[0058]

[0063] The patient drain line is connected to a mating receptacle on the face of the machine. This mating receptacle is, in turn, connected to a fluid path that flows through valve V10, flow sensor FM2, and into the drain chamber. Like the supply chamber, the drain chamber is a flexible container surrounded by a rigid enclosure. However, the drain chamber does not need to be vented to atmosphere, since its expansion and collapse is controlled by directing positive or negative air pressure from the positive pressure reservoir PPR and the negative pressure reservoir NPR through valves V13 and V14, respectively. The pressure present in these reservoirs is controlled by pressure sensors P5 and P6, whose readings are monitored by the software, which instructs when to turn the AC on or off to never exceed the safety limits of positive and negative pressure set in the software. This ensures that it is never possible to apply excessive pressure to the patient's peritoneum.

[0059]

[0064] Flow sensor FM2 is used to monitor for restriction of dialysate flow from the patient during the drain phase caused by a kinked or blocked catheter, PCL, or patient drain line (PDL). If such a restriction is detected, the dialysate flow is reversed first from the drain chamber back to the patient's peritoneum to attempt to resolve the blockage without waking the patient. If, after a series of reverse and forward flows, the restriction cannot be resolved, an alarm awakens the patient to change position.

[0060]

[0065] Two flow paths are provided for draining the drain chamber. One flow path is formed by closing V10 and V11 and opening V12 and V16, with V16 providing a direct path to drain. The other path is the path intended to be used during treatment. This flow path is formed by closing V10, V12 and opening V11, V6 and V16. By doing so, dialysate drained from the patient into the drain chamber is directed backwards through PF2 when positive pressure is applied to the drain chamber. Components of host defenses such as proteins, polypeptide chains of amino acids, and white blood cells are too large to pass through the pyrogen filter membrane, so they are captured on the patient-facing side of the membrane and can then be reinfused into the patient at the next fill cycle.

[0061]

[0066] A flow sensor FM3 is placed in the exhaust line between V6 and V16 to detect flow restrictions during various stages of operation.

[0062]

[0067] A conductivity sensor C4 is placed in the drain line upstream of V16 to detect air bubbles and help ensure the quality of the freshly made dialysate.

[0063]

[0068] Valve V16 is a three-way valve that either drains the flow directly or directs it through a disinfectant bypass flow path to allow recirculation of disinfectant through all flow paths.

[0064]

[0069] As shown in FIG. 1, a flow chart is provided illustrating the sequence of major operating modes through which the device goes when performing a single peritoneal dialysis treatment.

[0065]

[0070] The peritoneal dialysis solution preparation and treatment system is initially in a first operational stage where it is assumed that this is the first operation of the system and that it is filled with air and requires removal of the air. This is accomplished by perfusing highly purified water from a separate water purification system through a first flow path that includes V1, a mixing device, a supply chamber, V3, V6, and the system drain line.

[0066]

[0071] The fiber bundle of the first pyrogen filter PF1 is then primed by removing air through a 0.2 micron filter: water flows through V1, the mixer, the feed chamber, V3, PF1, and V7.

[0067]

[0072] The extracapillary space inside the case of PF1 is then primed via a fluid path that flows through valves V4, V6, and V16.

[0068]

[0073] The fiber bundle in the second pyrogen filter PF2 is then primed by removing air through a 0.2 micron filter: water flows through V1, the mixer, the feed chamber, V3, V5, PF2, and V8.

[0069]

[0074] The extracapillary space inside the case of PF2 is then primed via a fluid path that flows through valves V11 and V16.

[0070]

[0075] Next, the tubing circuit that allows dialysate to flow to and from the patient is primed with water flowing from V1 through the mixing device and supply chamber, V3, V5, PF2, V9, FL, PCL, PDL, V10, the drain chamber, V12, and V16.

[0071]

[0076] The peritoneal dialysis fluid is then formulated and mixed in the supply chamber by having pumps PU1, PU2, PU3, and PU4 meter in water, acid / electrolyte concentrate, neutralizing buffer, and osmolality concentrate, respectively, in proportion to the concentrations of the final dialysis fluid formulation as recorded in the integrated software.

[0072]

[0077] The composition and temperature of the dialysate prescribed in the supply chamber is then ensured by allowing it to flow through temperature sensors T1 and T2 and conductivity sensors C2 and C3 via the flow path defined by V3, V6 and V16.

[0073]

[0078] The water previously used to prime the air from the fluid pathway is then replaced with dialysate. This is accomplished by delivering dialysate through a flow path from the supply chamber through both pyrogen filters, then through the FL, PCL, PDL, waste chamber, DCDL, V12, and finally through V16 and conductivity sensor C4. When the conductivity at C4 equals C2 / C3, dialysate priming of the fluid pathway is complete and the patient can be connected to the PCL to begin treatment.

[0074]

[0079] The patient connection line PCL is then disconnected from its mating receptacle on the face of the instrument and connected to the patient's transfer set in preparation for the initiation of treatment, the first step of which is the drainage of any residual dialysate present in the patient's peritoneum from the preceding treatment. This is accomplished by opening V10 while V9, V11, and V12 are closed and applying negative air pressure from the negative pressure reservoir NPR through valve V14 to the rigid enclosure surrounding the flexible drain chamber. This causes the drain chamber to expand to drain dialysate from the patient until the flow rate measured by FM2 is close to zero and the amount of dialysate removed as calculated by integration of FM2 flow rate over time falls within the expected range recorded in the software look-up table. At the same time that the initial drain is being performed, the amount of dialysate in the supply chamber can be replenished by having pumps PU1, PU2, PU3, and PU4 deliver their respective components into the supply chamber, as before, until the amount of dialysate in the supply chamber reaches a value set in the system software, replacing that used to prime the fluid pathways. The volume of dialysate delivered into the supply chamber is calculated by summing the volumes delivered by each of the precision volumetric pumps PU1, PU2, PU3, and PU4.

[0075]

[0080] The amount of dialysate prescribed in the system software is then drained from the patient during therapy using the same flow path and calculation methods as in the previous step, the only difference being that there is no need to generate more dialysate during the intra-therapy drain phase, as is typically achieved during the dwell phase.

[0076]

[0081] Then, during the drain phase, a flow restriction is detected by the flow rate measured by FM2 falling below an alarm limit set in the system software. This indicates that the patient has rolled over on the tubing or that the indwelling catheter has moved into an intraperitoneal position restricting the outflow of dialysate. Before sounding an audible alarm to awaken the patient, the device first attempts to resolve the blockage by pushing the previously drained dialysate from the drain chamber back into the patient. If there is no dialysate in the drain chamber when this condition occurs, fresh dialysate from the supply chamber is infused instead as shown in the following steps. Such catheter unblocking steps can be repeated multiple times over the course of several minutes as set in the system software preferences, but if the restriction persists, an audible alarm is sounded.

[0077]

[0082] Next is a predetermined amount of fresh dialysate infused into the patient's peritoneum. This is accomplished by applying positive air pressure to the rigid enclosure surrounding the supply chamber by opening valve V15 to the positive pressure reservoir PPR and closing valves V2, 6, 10, 11, and 12 while valves V3, 4, 5, and 9 are open. This ensures that dialysate is delivered to the patient only after first passing through pyrogen filters PF1 and PF2. The fill volume is guaranteed by calculating the totality of the flow rate at FM1 over time.

[0078]

[0083] The dialysate infused into the patient during the preceding fill phase is then allowed to dwell in the peritoneum for a defined number of minutes. During this dwell phase, the used dialysate present in the drain chamber from the previous drain phase is drained into the drain line by closing V10, opening V13 to the PPR and collapsing the drain chamber. The flow path used to drain the used dialysate is uniquely designed to allow this fluid, containing beneficial biomolecules of a molecular size too large to pass through the membrane of PF2 and desirably retained by the patient and components of the host defenses such as white blood cells whose preservation is highly desirable, to flow back through the capillary fibers of PF2 before heading to the drain through valves V5, 6, 16. The aforementioned beneficial organic materials present in the dialysate after the dwell period and too large to pass through the membrane are captured on the patient-facing side of the membrane and are reinfused into the patient during each subsequent fill phase. Also during the dwell phase, the next fill volume of fresh dialysate is mixed in the supply chamber as before, in preparation for the next fill phase.

[0079]

[0084] Then, when the patient is removed (and the PCL is reattached to its mating receptacle on the face of the instrument), any dialysate remaining in the system's flow paths after the end of treatment is completely flushed out by perfusing all flow paths with ultrapure water. This flushing is done in three stages. Water from the purification system is drawn into the instrument through V1 by PU1 and is flushed through V1, the mixer, the supply chamber, V3, V5, PF2, V11, V12, and V16. At this stage, the flow paths between V3, PF1, V4, and P3, the conduit flowing through V11, and the conduit flowing through V6 are not perfused. The V11 segment is then flushed, followed by the V3-V6 segment by appropriately orienting the valves.

[0080]

[0085] Next, the ultrapure water present in all flow paths from the previous flushing stage is recirculated by opening the disinfection bypass segment between the three-way valves V1 and V16. During this disinfection stage, the heater, under the control of the temperature sensors T1, T2 and the system software, heats the water such that the water entering the heater is maintained at 80 °C to 85 °C for at least one hour. This ensures that all flow paths receive a high level of disinfection, that the patient connection lines (FL, PCL, and PDL) can be used across multiple treatments, and that the internal flow paths are free of any bacterial colonization. As in the previous flushing stage, not all flow paths can be disinfected simultaneously, and the valves must be oriented alternately so that the flow paths connected to the concentrate container as well as the flow paths passing through valves V3, V6, and V11 also receive a high level of disinfection.

[0081]

[0086] The flow of infusible, high-quality peritoneal dialysis solution made by the peritoneal dialysis solution preparation and processing system to and from the patient is then controlled by any commercially available peritoneal cycler. All such cyclers have an associated tubing set in which one tube (the supply line) connects to a bag of fresh dialysate and directs the fresh dialysate into the patient's peritoneum. Another tube (the drain line) directs the used dialysate from the patient to a drain bag or directly to drain. In one current embodiment, the peritoneal dialysis solution preparation system replaces the supply and drain bags. Instead, the supply and drain lines of a conventional cycler are directly connected to mating receptacles (SLC and DLC) on the face of the solution preparation device.

[0082]

[0087] Because the cycler controls the flow of dialysate, there is no need for the flow meter FM2, drain chamber or negative pressure reservoir NPR of the previous embodiment. In a first use scenario, air present in the fluid paths and components of this embodiment is primed similarly to stages 1-6 of operation of the previous embodiment.

[0083]

[0088] A disinfection loop (DL) is then installed between the SLC and DLC at the end of the previous treatment, thereby creating a closed loop between all fluid paths of the peritoneal dialysis solution preparation and treatment system. This configuration allows the dialysis fluid remaining in the fluid paths from the previous treatment to be flushed out and replaced with ultrapure water, which is then disinfected with hot water, similar to the previous steps of the operation described above.

[0084]

[0089] A new batch of dialysate is then mixed in the supply chamber, its composition and temperature assured, and all fluid paths primed with dialysate are mixed in a manner similar to the operational phase described above.

[0085]

[0090] The cycler is then connected to the peritoneal dialysis solution preparation and processing system, and a volume of dialysate is loaded to the patient under the control of the cycler. When the cycler attempts to draw fluid from the peritoneal dialysis solution preparation and processing system, a negative pressure is created that is sensed by pressure sensor P6. When this negative pressure is identified by the system software, all valves are oriented accordingly to allow the dialysate present in the supply chamber to be drawn through both deoxygenation filters, into the cycler, and then to the patient.

[0086]

[0091] The previous fill volume is present in the patient at this point and can remain there according to the prescription present in the cycler. During this stage, when no pressure is applied to either P6 or P7, the peritoneal dialysis solution preparation and treatment system prepares the next fill volume by metering water and concentrate into the supply chamber and orienting all valves accordingly.

[0087]

[0092] After the dwell time has elapsed, the cycler begins the drain phase by pumping fluid from the patient through drain line DL, which registers a positive pressure at pressure sensor P7 and causes the software to orient the valve to allow the used dialysate to pass through deoxygenating filter PF2 on its way out.

[0088]

[0093] Once the final drain and fill are accomplished, the patient disconnects the cycler tube from the peritoneal dialysis solution preparation and processing system and replaces it with the disinfection loop DL. The patient then instructs the peritoneal dialysis solution preparation and processing system to enter the rinse and disinfect mode by pressing a button on the usage interface, or the disinfection loop is designed to be automatically sensed by the peritoneal dialysis solution preparation and processing system and then triggers it to enter the rinse and disinfect mode in a manner similar to the previous embodiment.

[0089]

[0094] Disclosed embodiments

[0090]

[0095] Embodiment 1: A peritoneal dialysis system produces good quality injectable dialysis fluid by proportioning near-zero conductivity water from a separate source with concentrates containing essential ingredients as per the doctor's prescription, perfusing the thoroughly mixed and final constituted dialysis fluid through two deoxygenation filters in series before injecting into the patient, and recirculating all fluid paths, including those carrying the dialysis fluid to the patient, in ultrapure water with a temperature above 80° C. for more than one hour after every patient treatment, thereby achieving a high level of disinfection and reducing the possibility of bacterial colonization therein, and allowing the patient connection flow path to be reused across multiple treatments.

[0091]

[0096] Embodiment 2: A system as described in embodiment 1, wherein the used dialysate drained from the patient is directed backwards through a second deoxygenation filter on its way thereto, thereby trapping any organic matter too large to pass through the membrane of the filter, from which it can be reinfused back into the patient on a subsequent fill cycle.

[0092]

[0097] Embodiment 3: A system of embodiment 1 in which a concentrate containing the necessary electrolytes and acids is provided in one container, a neutralizing buffer such as sodium bicarbonate is provided in a second container, concentrated glucose that is not autoclaved but rather aseptically filled is provided in a third container, the contents of each container are metered into a stream of ultrapure water, the flow rate of each stream is precisely controlled so that the composition of the final composed dialysis solution can be customized by adjusting the individual ratios of the separate components by precisely controlling the flow rate of each metering pump, if the glucose component is not autoclaved, its pH can be near neutral rather than in the range of a minimum value of 5.2 or less, if it is not zero, glucose degradation products are formed, and the dialysis solution is composed immediately prior to infusion into the patient, so that for example sodium bicarbonate can be used as a buffering agent without any concern about the formation of calcium and magnesium carbonate precipitates, and a physiological range pH (7.1 to 7.5) of the infused dialysis solution can be achieved,

[0093]

[0098] Embodiment 4: A peritoneal dialysis system in which the chemical components of the peritoneal dialysis solution are metered into a flexible mixing chamber housed within a breathable rigid outer housing sealed around an inner flexible portion. This chamber serves a dual purpose; 1.) it provides a volume in which the chemical components of the peritoneal dialysis solution can be mixed together uniformly, and 2.) it acts as a pump to deliver its contents to the patient's peritoneal cavity. The flexible portion is allowed to expand under the positive pressure of a metering pump that delivers the chemical components therein, while the vent to the atmosphere of the rigid outer portion is open and the outlet conduit is blocked by a valve, thereby allowing the water and chemicals to mix together. The contents of this flexible chamber are then delivered to the patient by opening a valve at the outlet of the chamber and closing the vent and the inlet to the flexible chamber while exposing the space between the rigid outer portion and the flexible chamber to positive air pressure generated by an air compressor. This positive air pressure causes the flexible portion to collapse and deliver the dialysis solution downstream.

[0094]

[0099] Thus, a system for peritoneal dialysis includes a mixing device configured to mix water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer to generate a supply dialysate. The system also includes a supply chamber configured to store the supply dialysate. The system also includes a first filter including a first port and a second port. The first filter is configured to receive the supply dialysate from the supply chamber at the first port and remove contaminants (e.g., endotoxins and / or peptidoglycans) from the supply dialysate. The system also includes a second filter including a third port and a fourth port, a patient drain line connected to the third port, a patient fill line connected to the third port, and a system drain line connected to the fourth port. The system also includes one or more valves such that, in a first configuration, the second filter receives used dialysate from the patient drain line at a third port and allows for the capture of biological components (e.g., polypeptides, proteins, glycoproteins, leukocytes, macrophages and / or chemotactic components that tend to have a higher molecular weight than that of uremic toxins) from the used dialysate and allows the used dialysate to be distributed via the system drain line, and in a second configuration, the second filter receives supply dialysate from the second port at a fourth port and allows for the removal of further contaminants (e.g., endotoxins and / or peptidoglycans) from the supply dialysate and allows the supply dialysate and biological components to be distributed via the patient fill line (e.g., into the patient's peritoneum).

[0095]

[0100] 2 is a block diagram of a computing device 100. Computing device 100 includes one or more processors 102, a non-transitory computer-readable medium 104, a communication interface 106, and a user interface 108. The components of computing device 100 are linked together by a system bus, network, or other connection mechanism 112.

[0096]

[0101] The one or more processors 102 may be any type of processor, such as a microprocessor, a field programmable gate array, a digital signal processor, a multi-core processor, etc., coupled to a non-transitory computer-readable medium 104 .

[0097]

[0102] The non-transitory computer-readable medium 104 can be any type of memory, such as volatile memory, like random access memory (RAM), dynamic random access memory (DRAM), static random access memory (SRAM), or non-volatile memory, like read-only memory (ROM), flash memory, magnetic or optical disk, or compact disk read-only memory (CD-ROM), among other devices used to temporarily or permanently store data or programs.

[0098]

[0103] Additionally, the non-transitory computer-readable medium 104 may store instructions 111. The instructions 111 are executable by the one or more processors 102 to cause the computing device 100 to perform any of the functions or methods described herein.

[0099]

[0104] The communication interface 106 may include hardware that enables communication within the computing device 100 and / or between the computing device 100 and one or more other devices. The hardware may include, for example, any type of input and / or output interface, Universal Serial Bus (USB), PCI Express, transmitters, receivers, and antennas. The communication interface 106 may be configured to facilitate communication with one or more other devices according to one or more wired or wireless communication protocols. For example, the communication interface 106 may be configured to facilitate wireless data communication for the computing device 100 according to one or more wireless communication standards, such as one or more of the Institute of Electrical and Electronics Engineers (IEEE) 801.11 standard, the ZigBee standard, the Bluetooth standard, and the like. As another example, the communication interface 106 may be configured to facilitate wired data communication with one or more other devices. The communication interface 106 may also include an analog-to-digital converter (ADC) or a digital-to-analog converter (DAC) that the computing device 100 may use to control various components of the computing device 100 or an external device.

[0100]

[0105] The user interface 108 may include any type of display component configured to display data. As an example, the user interface 108 may include a touch screen display. As another example, the user interface 108 may include a flat panel display, such as a liquid crystal display (LCD) or a light emitting diode (LED) display. The user interface 108 may include one or more pieces of hardware used to provide data and control signals to the computing device 100. For example, the user interface 108 may include a mouse or pointing device, a keyboard or keypad, a microphone, a touchpad, or a touch screen, among other possible types of user input devices. In general, the user interface 108 may enable an operator to interact with a graphical user interface (GUI) provided by the computing device 100 (e.g., displayed by the user interface 108).

[0101]

[0106] 3 is a schematic diagram of a system 200 for peritoneal dialysis. The system 200 includes a mixing device 202 configured to mix water 204, an acid / electrolyte concentrate 206, an osmotic concentrate 208, and a neutralization buffer 210 to generate a supply dialysate 212. The system 200 also includes a supply chamber 214 configured to store the supply dialysate 212. The system 200 also includes a filter 216 including a port 218 and a port 220. The filter 216 is configured to receive the supply dialysate 212 from the supply chamber 214 at the port 218 and remove contaminants 222 from the supply dialysate 212. The system 200 also includes a filter 224 including a port 226 and a port 228, a patient drain line 230 connected to the port 226, a patient fill line 232 connected to the port 226, and a system drain line 234 connected to the port 228. 3, filter 224 receives used dialysate 238 from patient drain line 230 at port 226 and captures biological components 240 (e.g., proteins and host defenses, such as leukocytes, macrophages, and / or chemotactic components) from used dialysate 238 so that the used dialysate 238 can be dispensed via system drain line 234. The various components of system 200 can be in fluid communication with one another via flexible tubing or other known means for transporting fluids.

[0102]

[0107] In the configuration shown in FIG. 4 and discussed further below, the valves 236A-E are in a configuration such that the filter 224 receives the supply dialysate 212 from port 220 at port 228, removes further contaminants 223 from the supply dialysate 212, and allows the supply dialysate 212 and biological components 240 to be dispensed via the patient fill line 232.

[0103]

[0108] 3, the mixer 202 is configured to receive water 204, typically from a source external to the system 200, such as a reverse osmosis purification system. The mixer 202 includes a positive displacement metering pump configured to deliver a controlled amount of the water 204 to the delivery chamber 214.

[0104]

[0109] The mixing device 202 also includes a metering pump configured to deliver a controlled amount of the acid / electrolyte concentrate 206 to the supply chamber 214. The acid / electrolyte concentrate 206 includes one or more of water, anhydrous glucose, sodium, calcium, magnesium, chloride, bicarbonate, and / or lactate. The electrolyte components of the acid / electrolyte concentrate 206 will generally be, for example, about 140 (mmol / L) sodium, 2.5 mmol / L calcium, or 0.75 mmol / L magnesium.

[0105]

[0110] The mixing device 202 also includes a metering pump configured to deliver a controlled amount of the osmotic concentrate 208 to the delivery chamber 214. The osmotic concentrate 208 includes water, glucose (e.g., sterile packed glucose and / or dextroglucose), and / or icodextrin.

[0106]

[0111] The mixing device 202 also includes a metering pump configured to deliver a controlled amount of neutralization buffer 210 to the delivery chamber 214. The neutralization buffer 210 includes water and a neutralizing base, such as sodium bicarbonate, sodium lactate, and / or sodium carbonate.

[0107]

[0112] The supply chamber 214 includes a rigid housing and a flexible container (e.g., a plastic bag) disposed within the rigid housing. The flexible container is configured to store the supply dialysate 212, and the rigid housing is configured to apply pressure to compress or expand the flexible container, thereby expelling the supply dialysate 212 from the flexible container into the filter 216 or drawing the supply dialysate 212 from the mixing device 202 into the flexible container, respectively.

[0108]

[0113] Filters 216 and 224 generally take the form of oxygen-removing filters configured to retain contaminants 222 and further contaminants 223 in the form of endotoxins and peptidoglycans. In some examples, filters 216 and 224 have a molecular weight cut-off (MWCO) defined by a 90% retention within the range of 50 Daltons to 80,000 Daltons.

[0109]

[0114] The patient drain line 230, the patient fill line 232, and the system drain line 234 may take the form of flexible tubing, although other examples are possible.

[0110]

[0115] 3 shows the system 200 after removal of at least a portion of the used dialysate 238 from the patient's peritoneal cavity 252. The used dialysate 238 was previously the supply dialysate 212, but after possibly dwelling in the peritoneal cavity 252 for several hours, this supply dialysate 212 has absorbed toxins and water that has crossed the patient's peritoneal membrane and into the peritoneal cavity 252, becoming the used dialysate 238.

[0111]

[0116] 3, valve 236A can be opened and valves 236B and 236C can be closed such that drain chamber 215 can receive used dialysate 238 from peritoneal cavity 252 (e.g., via a catheter). The used dialysate 238 can move into drain chamber 215 by gravity and / or drain chamber 215 can operate to apply a negative pressure that draws the used dialysate 238 into drain chamber 215.

[0112]

[0117] In some examples, the drain chamber 215 is not included as part of the system 200, and instead a peritoneal dialysis cycler is used. For example, the system 200 receives used dialysate 238 directly from a peritoneal dialysis cycler, where the used dialysate 238 travels through the valve 236C and the filter 224 as described above.

[0113]

[0118] As shown in FIG. 3, valve 236A is then closed, valve 236C is opened, and system 200 moves used dialysate 238 from drain chamber 215 (or from the peritoneal dialysis cycler) through valve 236C into port 226 and then through filter 224 to capture biological components 240 from the used dialysate 238. System 200 then dispenses (e.g., disposes of) the used dialysate 238 (e.g., along with uremic toxins that passed through filter 224) through valve 236D and through system drain line 234. The used dialysate 238 can be moved by positive pressure applied to drain chamber 215 or by operation of the peritoneal dialysis cycler. This process produces depleted used dialysate 238 with biological components 240 removed, which is disposed of via system drain line 234.

[0114]

[0119] FIG. 4 is a schematic diagram of a system 200 configured for removing contaminants 222 and further contaminants 223 from the dialysate supply 212 such that the dialysate supply 212 and captured biological components 240 are dispensed into the peritoneal cavity 252 via a patient fill line 232.

[0115]

[0120] Before, simultaneously with, or after the filter 224 captures the biological components 240, the system 200 mixes the water 204, the acid / electrolyte concentrate 206, the osmotic concentrate 208, and the neutralizing buffer 210 via the mixer 202 to generate the feed dialysate 212. For example, controlled amounts of the water 204, the acid / electrolyte concentrate 206, the osmotic concentrate 208, and the neutralizing buffer 210 are introduced into the feed chamber 214 such that the feed dialysate 212 is substantially homogenous within the feed chamber 214. The mixing can be performed at room temperature, at a temperature, for example, less than 100° F., and at a hydrogen potential (pH) that is greater than 7.1 and less than 7.5.

[0116]

[0121] After the biological components 240 are captured by the filter 224 (as described above with reference to FIG. 3), the system 200 moves the supply dialysate 212 into the port 218 via positive pressure applied to the supply chamber 214, which causes the filter 216 to remove contaminants 222 from the supply dialysate 212. By opening the valve 236E and closing the valve 236D, the supply dialysate 212 moves from the port 220 into the port 228 of the filter 224. The filter 224 removes further contaminants 223 from the supply dialysate 212. The system 200 then uses the positive pressure applied to the supply chamber 214 to dispense the supply dialysate 212 and the biological components 240 from the port 226 into the peritoneal cavity 252 via the patient fill line 232. The purified supply dialysate 212 can remain in the peritoneal cavity 252 for several hours to facilitate the removal of toxins from the patient's blood via the peritoneal membrane. This process results in the production of used dialysate 238 containing toxins. This cycle of removing spent dialysate 238 from the peritoneal cavity 252, capturing biological components 240 within the spent dialysate 238 using the filter 224, and reintroducing the supply dialysate 212 and biological components 240 into the peritoneal cavity 252 can be repeated several times.

[0117]

[0122] In some examples, the system 200 has various interlock mechanisms. For example, the system 200 can make a determination that the water 204 received by the mixing device 202 has a conductivity below a threshold (e.g., 0.055 μS / cm + / - 10%) and mix the water 204, the acid / electrolyte concentrate 206, the osmotic concentrate 208, and the neutralization buffer 210 in response to the determination. The conductivity can be detected using a sensor configured to sample the water 204 as it enters the mixing device 202. The water 204 should have a low conductivity corresponding to high purity for the benefit of the patient.

[0118]

[0123] Similarly, the system 200 can make a determination that the supply dialysate 212 has a conductivity greater than a first threshold and less than a second threshold (e.g., within a desired range, such as 12.2±0.2 ms / cm). In response to making the determination, the system 200 can move the supply dialysate 212 into the port 218. The supply dialysate 212 should have a conductivity corresponding to the desired range for the benefit of the patient.

[0119]

[0124] 5 and 6 are block diagrams of methods 300 and 400, which in some examples are performed by system 200 and / or manually. As shown in FIGS. 5 and 6, methods 300 and 400 include one or more operations, functions, or acts, as illustrated by blocks 302, 304, 306, 308, 310, 402, 404, 406, 408, 410, 412, and 414. Although the blocks are illustrated in sequential order, the blocks may also be performed in parallel and / or in a different order than that described herein. Additionally, various blocks may be combined into fewer blocks, split into additional blocks, and / or removed based on the desired implementation.

[0120]

[0125] In block 302, the method 300 includes moving the used dialysate 238 into the port 226 and then through the filter 224 to capture biological components 240 from the used dialysate 238. The functionality associated with block 302 is described above with reference to FIG.

[0121]

[0126] At block 304, the method 300 includes mixing water 204, acid / electrolyte concentrate 206, osmotic concentrate 208, and neutralization buffer 210 via mixer 202 to produce dialysate supply 212. The functionality associated with block 304 is described above with reference to FIG.

[0122]

[0127] At block 306, the method 300 includes moving the dialysate supply 212 into the port 218 to remove contaminants 222 from the dialysate supply 212. The functionality associated with block 306 is described above with reference to FIG.

[0123]

[0128] In block 308, the method 300 includes moving the dialysate supply 212 from the port 220 into the port 228 and then through a filter 224 to remove further contaminants 223 from the dialysate supply 212. The functionality associated with block 308 is described above with reference to FIG.

[0124]

[0129] In block 310, the method 300 includes dispensing the dialysate supply 212 and the biological components 240 from the port 226 via the patient fill line 232. The functionality associated with block 310 is described above with reference to FIG.

[0125]

[0130] At block 402, the method 400 includes providing the system 200. The functionality associated with block 402 is described above with reference to FIGS.

[0126]

[0131] At block 404, the method 400 includes mixing water 204, acid / electrolyte concentrate 206, osmotic concentrate 208, and neutralization buffer 210 via mixer 202 to produce dialysate supply 212. The functionality associated with block 404 is described above with reference to FIG.

[0127]

[0132] At block 406, the method 400 includes moving the dialysate supply 212 into the port 218 and through the filter 216 to remove contaminants 222 from the dialysate supply 212. The functionality associated with block 406 is described above with reference to FIG.

[0128]

[0133] In block 408, the method 400 includes moving the dialysate supply 212 from the port 220 into the port 228 and then through the filter 224 to remove further contaminants 223 from the dialysate supply 212. The functionality associated with block 408 is described above with reference to FIG.

[0129]

[0134] At block 410, the method 400 includes transferring the purified dialysate 212 to the patient's peritoneal cavity 252 for a predetermined period of time for peritoneal dialysis while producing used dialysate 238. The functionality associated with block 410 is described above with reference to FIG.

[0130]

[0135] In block 412, the method 400 includes moving the used dialysate 238 into the port 226 and then through the filter 224 to capture biological components 240 from the used dialysate 238, generating a depleted used dialysate 238, and draining the depleted used dialysate 238. The functions associated with block 410 are described above with reference to FIG.

[0131]

[0136] In block 414, the method 400 includes repeating blocks 404-412 to dispense the dialysate supply 212 for further peritoneal dialysis while draining the captured biological components 240 from the filter 224 for introduction back to the patient. The functionality associated with block 410 is described above with reference to Figures 3 and 4.

[0132]

[0137] Further exemplary embodiments

[0133]

[0138] Example 1 is a system for peritoneal dialysis, comprising: a mixing device configured to mix water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer to generate a supply dialysate; a supply chamber configured to store the supply dialysate; a first filter including a first port and a second port, the first filter configured to receive the supply dialysate from the supply chamber at the first port and to remove contaminants from the supply dialysate; a second filter including a third port and a fourth port; a patient drain line connected to the third port; a patient fill line connected to the third port; a system drain line connected to a port of the second filter, and one or more valves, where in a first configuration, the second filter receives used dialysate from the patient drain line at a third port and captures biological components from the used dialysate to allow the used dialysate to be dispensed via the system drain line, and in a second configuration, the second filter receives supply dialysate from the second port at a fourth port and removes further contaminants from the supply dialysate to allow the supply dialysate and biological components to be dispensed via the patient fill line.

[0134]

[0139] Example 2 is the system of Example 1, where the mixer is configured to receive water from a source external to the system.

[0135]

[0140] Example 3 is the system of any one of Examples 1-2, wherein the mixing device includes a positive displacement metering pump configured to deliver a controlled amount of water to the supply chamber.

[0136]

[0141] Example 4 is the system of any one of Examples 1-3, wherein the mixing device comprises a metering pump configured to deliver a controlled amount of the acid / electrolyte concentrate to the delivery chamber.

[0137]

[0142] Example 5 is the system of any one of Examples 1-4, wherein the mixing device comprises a metering pump configured to deliver a controlled amount of the osmotic concentrate to the delivery chamber.

[0138]

[0143] Example 6 is the system of any one of Examples 1-5, wherein the mixing device comprises a metering pump configured to deliver a controlled amount of the neutralization buffer to the delivery chamber.

[0139]

[0144] Example 7 is the system of any one of Examples 1-6, wherein the supply chamber comprises a rigid housing and a flexible container disposed within the rigid housing, the flexible container configured to store a supply dialysate, and the rigid housing configured to apply pressure to compress or expand the flexible container, thereby expelling the supply dialysate from the flexible container or drawing the supply dialysate into the flexible container.

[0140]

[0145] Example 8 is the system of any one of Examples 1-7, wherein the first filter and / or the second filter comprises an oxygen scavenging filter.

[0141]

[0146] Example 9 is the system of any one of Examples 1 to 8, wherein the first filter and / or the second filter have a 90% retention rate within the range of 50 Daltons to 80,000 Daltons and a 10 5 The pyrogen removal coefficient (MWCO) is equal to or greater than 1.

[0142]

[0147] Example 10 is the system of any one of Examples 1-9, wherein the first filter and the second filter are configured to retain endotoxins and peptidoglycan.

[0143]

[0148] Example 11 is a method of operating the system of any one of Examples 1-10, including moving used dialysate into a third port and then through a second filter to capture biological components from the used dialysate; mixing water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer via a mixing device to generate a supply dialysate; moving the supply dialysate into the first port to remove contaminants from the supply dialysate; moving the supply dialysate from the second port into a fourth port and then through a second filter to remove further contaminants from the supply dialysate; and dispensing the supply dialysate and biological components from the third port via a patient fill line.

[0144]

[0149] Example 12 is the method of example 11, further comprising dispensing spent dialysate through the system drain line.

[0145]

[0150] Example 13 is the method of any one of Examples 11-12, further comprising receiving used dialysate from the patient's peritoneum prior to moving the used dialysate into the third port.

[0146]

[0151] Example 14 is the method of example 13, wherein dispensing the supply of dialysate and the biological component includes dispensing the supply of dialysate and the biological component into the peritoneum.

[0147]

[0152] Example 15 is the method of any one of Examples 11-14, further comprising receiving used dialysate from the peritoneal dialysis cycler prior to moving the used dialysate into the third port.

[0148]

[0153] Example 16 is the method of example 15, where dispensing the supply dialysate and the biological component includes dispensing the supply dialysate and the biological component into a peritoneal dialysis cycler.

[0149]

[0154] Example 17 is the method of any one of Examples 11-16, wherein the neutralization buffer comprises sodium bicarbonate, sodium lactate, and / or sodium carbonate.

[0150]

[0155] Example 18 is the method of any one of Examples 11-17, wherein the osmotic concentrate comprises glucose and / or icodextrin.

[0151]

[0156] Example 19 is the method of any one of Examples 11-18, wherein the contaminant comprises endotoxin and / or peptidoglycan.

[0152]

[0157] Example 20 is the method of any one of Examples 11-19, wherein the acid / electrolyte concentrate comprises anhydrous glucose, sodium, calcium, magnesium, chloride, bicarbonate, and / or lactate.

[0153]

[0158] Example 21 is the method of any one of Examples 11-20, further including determining that the conductivity of the water is below a threshold value, and wherein the mixing occurs in response to making the determination.

[0154]

[0159] Example 22 is the method of any one of Examples 11-21, further including determining that the supply dialysate has a conductivity greater than a first threshold and less than a second threshold, and moving the supply dialysate into the first port is performed in response to the determination being made.

[0155]

[0160] Example 23 is the method of any one of Examples 11-22, wherein the mixing includes mixing the supply dialysate such that the supply dialysate is substantially homogenous within the supply chamber.

[0156]

[0161] Example 24 is the method of any one of Examples 11-23, wherein the mixing includes mixing the water, the acid / electrolyte concentrate, the osmotic concentrate, and the neutralization buffer while at a temperature less than 100° F.

[0157]

[0162] Example 25 is the method of any one of Examples 11-24, wherein the osmotic concentrate comprises dextroglucose.

[0158]

[0163] Example 26 is the method of any one of Examples 11-25, wherein the osmotic concentrate comprises sterilely packed glucose.

[0159]

[0164] Example 27 is the method of any one of Examples 11-26, wherein the mixing includes mixing at a potential of hydrogen (pH) greater than 7.1 and less than 7.5.

[0160]

[0165] Example 28 is the system of any one of Examples 1-10, further including one or more processors and a computer-readable medium storing instructions that, when executed by the one or more processors, cause the system to perform the method of any one of Examples 11-25.

[0161]

[0166] Example 29 is a computer-readable medium storing instructions that, when executed by the system of Example 28, cause the system to perform the method of any one of Examples 11-27.

[0162]

[0167] Example 30 is a system for peritoneal dialysis including a mixing device configured to mix water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer to produce a supply dialysate, a supply chamber configured to store the supply dialysate, a drain line, a filter, and one or more valves that, in a first configuration, allow the filter to receive used dialysate from the drain line at a first port of the filter to capture biological components within the used dialysate, and in a second configuration, allow the filter to receive supply dialysate from the supply chamber at a second port of the filter to remove contaminants from the supply dialysate.

[0163]

[0168] Example 31 is a method for performing peritoneal dialysis, the method including providing the system of any one of Examples 1-10; mixing water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer via a mixing device to generate a supply dialysate; moving the supply dialysate through a first filter into a first port to remove contaminants from the supply dialysate; moving the supply dialysate from a second port into a fourth port and then through a second filter to remove further contaminants from the supply dialysate; moving purified dialysate to a patient's peritoneal cavity for a predetermined time for peritoneal dialysis while generating a used dialysate; moving the used dialysate into a third port and then through a second filter to capture biological components from the used dialysate and generate a depleted used dialysate, draining the depleted used dialysate; and repeating steps (ii)-(vi) to dispense the supply dialysate for further peritoneal dialysis while draining the captured biological components through the second filter for introduction back to the patient.

[0164]

[0169] While various exemplary aspects and exemplary embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various exemplary aspects and exemplary embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.

Claims

1. 1. A system for peritoneal dialysis comprising: a mixing device configured to mix water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer to generate a feed dialysate; a supply chamber configured to store the supply dialysate; a first filter including a first port and a second port, the first filter configured to receive the supply dialysate from the supply chamber at the first port and to remove contaminants from the supply dialysate; a second filter including a third port and a fourth port; a patient exhaust line connected to the third port; a patient fill line connected to the third port; a system exhaust line connected to the fourth port; and One or more valves, In a first configuration, the second filter receives used dialysate from the patient drain line at the third port and captures biological components from the used dialysate to allow the used dialysate to be dispensed via the system drain line; one or more valves, in a second configuration, for allowing the second filter to receive the supply dialysate from the second port at the fourth port and remove further contaminants from the supply dialysate to allow the supply dialysate and the biological component to be dispensed via the patient fill line; Including, the system.

2. The system of claim 1 , wherein the mixing device is configured to receive the water from a source external to the system.

3. The system of any one of claims 1 to 2, wherein the mixing device comprises a positive displacement metering pump configured to deliver a controlled amount of the water to the supply chamber.

4. The system of any one of claims 1 to 3, wherein the mixing device comprises a metering pump configured to deliver a controlled amount of the acid / electrolyte concentrate to the supply chamber.

5. The system of any one of claims 1 to 4, wherein the mixing device comprises a metering pump configured to deliver a controlled amount of the osmotic concentrate to the supply chamber.

6. The system of any one of claims 1 to 5, wherein the mixing device comprises a metering pump configured to deliver a controlled amount of the neutralization buffer to the supply chamber.

7. The supply chamber comprises: A rigid housing, and a flexible container disposed within the rigid housing, the flexible container configured to store the supply dialysate, the rigid housing configured to apply pressure to compress or expand the flexible container, thereby expelling the supply dialysate from the flexible container or drawing the supply dialysate into the flexible container; The system according to any one of claims 1 to 6, comprising:

8. The system of any one of claims 1 to 7, wherein the first filter and / or the second filter comprises an oxygen removing filter.

9. The first filter and / or the second filter have a 90% retention rate in the range of 50 Daltons to 80,000 Daltons and a 10 ５ 9. The system of claim 1, having a molecular weight cut off (MWCO) defined by a pyrogen removal factor of at least 100%.

10. The system of any one of claims 1 to 9, wherein the first filter and the second filter are configured to retain endotoxins and peptidoglycan.

11. moving the used dialysate into the third port and then through the second filter to capture the biological components from the used dialysate; mixing the water, the acid / electrolyte concentrate, the osmolality concentrate, and the neutralization buffer via the mixing device to produce the supply dialysate; moving the dialysate supply into the first port to remove the contaminants from the dialysate supply; moving the supply dialysate from the second port into the fourth port and then through the second filter to remove the additional contaminants from the supply dialysate; and dispensing the supply dialysate and the biological component from the third port via the patient fill line; A method of operating a system according to any one of claims 1 to 10, comprising:

12. 12. The method of claim 11, further comprising dispensing the used dialysate through the system drain line.

13. 13. The method of any one of claims 11-12, further comprising receiving the used dialysate from a patient's peritoneum prior to moving the used dialysate into the third port.

14. 14. The method of claim 13, wherein dispensing the supply of dialysate and the biological components comprises dispensing the supply of dialysate and the biological components into the peritoneum.

15. 15. The method of any one of claims 11-14, further comprising receiving the used dialysate from a peritoneal dialysis cycler prior to moving the used dialysate into the third port.

16. 16. The method of claim 15, wherein dispensing the supply of dialysate and the biological components comprises dispensing the supply of dialysate and the biological components into the peritoneal dialysis cycler.

17. The method of any one of claims 11 to 16, wherein the neutralization buffer comprises sodium bicarbonate, sodium lactate and / or sodium carbonate.

18. The method according to any one of claims 11 to 17, wherein the osmotic concentrate comprises glucose and / or icodextrin.

19. The method of any one of claims 11 to 18, wherein the contaminants include endotoxins and / or peptidoglycan.

20. 20. The method of any one of claims 11 to 19, wherein the acid / electrolyte concentrate comprises anhydrous glucose, sodium, calcium, magnesium, chloride, bicarbonate, and / or lactate.

21. determining that the conductivity of the water is below a threshold; The method of any one of claims 11 to 20, wherein said mixing is performed in response to making said determination.

22. determining that the dialysate supply has a conductivity greater than a first threshold and less than a second threshold; The method of any one of claims 11 to 21, wherein the moving of the supply dialysate into the first port occurs in response to the determination being made.

23. The method of any one of claims 11 to 22, wherein the mixing comprises mixing the supply dialysate so that it is substantially homogenous within the supply chamber.

24. 24. The method of any one of claims 11-23, wherein said mixing comprises mixing while the water, the acid / electrolyte concentrate, the osmotic concentrate, and the neutralization buffer are at a temperature of less than 100°F.

25. 25. The method of any one of claims 11 to 24, wherein the osmotic concentrate comprises dextroglucose.

26. 26. The method of any one of claims 11 to 25, wherein the osmotic concentrate comprises sterilely packed glucose.

27. 27. The method of any one of claims 11 to 26, wherein said mixing comprises mixing at a potential of hydrogen (pH) greater than 7.1 and less than 7.

5.

28. one or more processors; and A computer readable medium storing instructions which, when executed by said one or more processors, cause said system to perform the method of any one of claims 11 to 25. The system of any one of claims 1 to 10, further comprising:

29. A computer readable medium storing instructions which, when executed by a system according to claim 28, cause said system to carry out the method according to any one of claims 11 to 27.

30. 1. A system for peritoneal dialysis comprising: a mixing device configured to mix water, an acid / electrolyte concentrate, an osmolality concentrate, and a neutralization buffer to generate a feed dialysate; a supply chamber configured to store the supply dialysate; Discharge line, Filters, and one or more valves that, in a first configuration, allow the filter to receive the used dialysate from the drain line at a first port of the filter for capturing biological components within the used dialysate, and, in a second configuration, allow the filter to receive the supply dialysate from the supply chamber at a second port of the filter for removing contaminants from the supply dialysate. Including, the system.

31. 1. A method for performing peritoneal dialysis, comprising: (i) providing a system according to any one of claims 1 to 10; (ii) mixing the water, the acid / electrolyte concentrate, the osmolality concentrate, and the neutralization buffer via the mixing device to produce the supply dialysate; (iii) moving the supply dialysate through the first filter into the first port to remove the contaminants from the supply dialysate; (iv) moving the supply dialysate from the second port into the fourth port and then through the second filter to remove the additional contaminants from the supply dialysate; (v) transferring the purified dialysate to a patient's peritoneal cavity for peritoneal dialysis for a predetermined period of time while producing used dialysate; (vi) moving the used dialysate into the third port and then through the second filter to capture the biological components from the used dialysate and generate a depleted used dialysate, and draining the depleted used dialysate; and (vii) repeating steps (ii)-(vi) to dispense the supply dialysate for further peritoneal dialysis while draining the captured biological components from the second filter for introduction back into the patient. A method comprising:

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