Sorbent and chemical regeneration of dialysate

This application claims interests under Section 119 (e) of the U.S. Patent Act of earlier U.S. Provisional Patent Application No. 61 / 524,793 filed on August 18, 2011, the entire application of which is by reference. Incorporated herein.

Dialysis is a treatment that removes waste products, toxins (such as urea, creatinine and uric acid) and excess fluid that accumulate in the body's blood and tissues as a result of renal failure or impaired renal function. Dialysis treatment has significant implications for those suffering from renal failure or having impaired renal function because humans cannot survive without the filtering function provided by the kidneys.

Hemodialysis is a type of dialysis treatment that uses a hemodialysis machine to filter toxins from a patient's blood outside the body. A hemodialyzer generally includes a computer, a fluid pump, a blood line, a dialysate line, a dialyzer, and a drain line for discarding large amounts of dialysate used for each treatment. The patient's circulatory system is connected to the hemodialyzer via a catheter or fistula needle, and the patient's blood is continuously fed through the hemodialyzer. Blood passes through a dialyzer containing a semipermeable membrane in a hemodialyzer. The semipermeable membrane separates the blood on one side from the dialysis solution on the other side. The dialysis machine removes waste products, toxins, and excess water from the blood before returning the blood to the patient for reinjection. Waste products and toxins are transferred from the blood to the dialysis solution through the semipermeable membrane, and the dialysis solution is discarded. Most hemodialyzers use large amounts of dialysate, or about 90-120 liters of dialysate, during a single dialysis treatment. The used dialysate or used dialysate is then discarded. Hemodialysis treatment is generally performed 3-4 times a week in a service center under the supervision of a clinician. A single treatment takes about 4-6 hours and requires a large supply of dialysis solution or a continuous source of water. Used dialysate is generally discarded.

Peritoneal dialysis is another type of dialysis treatment in which toxins and excess water are removed by introducing a dialysis solution containing glucose or dextrose and other electrolytes into the peritoneal cavity and allowing the dialysis solution to stay for a period of time. It is filtered from the patient's blood and organs. The abdominal cavity has an exceptional blood supply through which urea and other toxins in the blood transfer to the dialysis solution. Patients use pre-prepared dialysis solution or prepare dialysis solution using home-purified water. Peritoneal dialysis treatment is generally performed daily at the patient's home and requires 10 to 15 liters of dialysate for each treatment. Used dialysate is generally discarded.

Continuous Ambulatory Peritoneal Dialysis (CAPD) and Continuous Cycling Peritoneal Dialysis (CCPD) are two types of peritoneal dialysis, in which the dialysis solution is applied to the peritoneal dialysis for a certain period of time. Allow it to stay. During CAPD and CCPD, the dialysis solution is introduced into the peritoneum, and after a period of time, the dialysis solution is drained and discarded. A new dialysis solution is then introduced into the peritoneum. During each treatment, the filling, draining and retention sequences are repeated, as described above. In CAPD, filling, retention and drainage are done manually. In CCPC, filling, retention and ejection are done mechanically.

Another type of peritoneal dialysis is continuous flow peritoneal dialysis (CFPD). During CFPD, the dialysis solution is introduced into the peritoneum through the inflow catheter with the outflow catheter tightened using two separate or double-tube catheters. When the desired filling amount is achieved, the outflow catheter is opened and the inflow and outflow are kept relatively constant so that the dialysis solution is continuously fed through the peritoneum. CFPD is typically performed at high flow rates and requires very large amounts of dialysis solution.

It has long been known to use specific devices to regenerate used dialysis solutions from hemodialysis and / or peritoneal dialysis. For example, the Redy (REcirculating DYalysis) Adsorbent System (Blumenkrantz et al., Artif Organs 3 (3): 230-236, 1978) is a multi-layered adsorbent that removes toxins and other waste products from the dialysis solution. Includes cartridge. Adsorbent cartridges require a significant amount of material and layers. Almost half of the material in the cartridge is zirconium phosphate, which binds and removes ammonia.

<p num="0008"> There is a need to provide an improved dialysis system. This can be achieved by reducing the amount of water or dialysis solution required for a single treatment and by reducing the amount of adsorbent material required for a single treatment. .. A single dialysis treatment requires a large supply of dialysis solution or a continuous source of water. Patients undergoing hemodialysis three times a week require approximately 270-360 liters of dialysate per week. Patients undergoing peritoneal dialysis require about 70-105 liters per week.</p>

<p num="0009"> The present invention provides a system and method for regenerating a used dialysate solution, also known as dialysate. The dialysate regeneration system can be integrated into any dialysate system that requires the use of dialysate.</p><p num="0010"> In one aspect of the invention, the dialysis system comprises an adsorbent device configured to allow the dialysis solution to pass through, an extractor, and a fluid line communicating the device and the extractor. It is incorporated. The device is adapted to remove one or more substances from the dialysis solution as the dialysis solution passes through the device. The extractor is adapted to remove one or more substances from the dialysis solution as the dialysis solution passes through the extractor.</p><p num="0011"> The device can be one or more adsorbent cartridges. The adsorbent cartridge (s) can include at least one layer of water and / or a material capable of purifying the used dialysis solution (or otherwise present in the cartridge). The layer of the adsorbent cartridge can include jack bean meal, encapsulated sword bean powder, crosslinked sword bean powder or other stabilized urease or any combination thereof. One or more adsorbent cartridges may additionally comprise a layer of zirconium hydroxide, anion exchange resin, activated carbon or any combination thereof. One or more adsorbent cartridges can include one or more of this layer. One or more adsorbent cartridges can include two or more compartments.</p><p num="0012"> The playback system can further include a second device. The second device can be one or more adsorbent cartridges. The second adsorbent cartridge can include zirconium hydroxide or anion exchange resin or any combination thereof, for example in the form of one or more layers. The layer of the second adsorbent cartridge can contain activated carbon. The second adsorbent cartridge can include two or more compartments.</p><p num="0013"> The extraction system can include a liquid-liquid countercurrent extractor that complexes ammonia in the dialysate into an extracting molecule in the extraction fluid. The extraction molecule can be phosphinic acid, carboxylic acid or phosphoric acid, or any combination thereof. The extraction fluid can be noper 12, undecane, vegetable oil, modified vegetable oil or biodiesel. The extraction fluid can be a biodiesel containing dissolved di-2,4,4-trimethylpentylphosphinic acid.</p><p num="0014"> Other aspects, features and advantages of the present invention will be apparent by the claims.</p><p num="0015"> Additional features and advantages of the invention are described in part in the description below, and in part are manifested by the description below or learned by practicing the invention. The objects and other advantages of the present invention will be realized and achieved using the elements and combinations specifically noted in the claims below and attached.</p><p num="0016"> It should be understood that both the above overview and the detailed description below are for illustration and illustration purposes only and are intended to provide further description of the claimed invention.</p><p num="0017"> The accompanying drawings incorporated in the present application and forming a part thereof illustrate some of the features of the present invention and serve to explain the principles of the present invention together with the explanation.</p>

<figref num="1">It is a schematic diagram of the hemodialysis system according to an example of this application.</figref><figref num="2">It is a schematic diagram of the peritoneal dialysis system according to an example of this application.</figref>

The present invention relates to dialysis systems and methods, including modules for regenerating used dialysate. The module uses one or more adsorbent cartridges and a liquid-liquid countercurrent extractor to remove urea, phosphate and other organic uremic toxins from the used dialysate. Although details will be described later, the present invention is useful for regenerating dialysate used in hemodialysis and peritoneal dialysis. The present invention can be used to continuously regenerate dialysate during dialysis treatment or to regenerate post-dialysis dialysate for later use. For the purposes of the present disclosure, dialysate means a dialysis solution useful in hemodialysis or peritoneal dialysis systems.

The systems and methods described herein can advantageously reduce the costs associated with dialysis by reducing the amount of adsorbent and / or dialysate (or water) used in individual dialysis treatments. it can. Another advantage is that this system and method uses smaller cartridges and / or smaller amounts of dialysate (or water), thus reducing the amount of product and packaging waste produced by individual dialysis treatments. It is a point that can be done.

The used dialysate can be delivered through a cartridge containing a urease source. As an option, the used dialysate is sword bean flour (jack bean). Can be sent through a cartridge containing meal), encapsulated sword bean flour, crosslinked sword bean flour or other stabilized urease, or any combination thereof, and in the cartridge in one or more layers or other forms. Present in, hydrolyzes urea to ammonia and carbon dioxide, or to ammonium carbonate, or performs other hydrolytic conversion of urea to ammonia. The dialysate containing ammonia is then treated by a liquid-liquid countercurrent extractor to remove the ammonia. The extractor contains an extract (s) that are immiscible with ammonia, including dialysate. The extract combines ammonia to remove ammonia from the used dialysate (eg, completely, almost completely, substantially, or 95-100% by weight, 96-100% by weight, 97 of the total ammonia present. It contains an extractant such as di-2,4,4-trimethylpentylphosphinic acid that removes at least a portion (such as removing ~ 100% by weight or 97-99.9% by weight). The used dialysate can then be delivered through a second cartridge containing, for example, zirconium hydroxide (HZO) and / or anion exchange resin to remove phosphate. HZO is the chemical formula ZrO_２. NH_２O (eg zirconium oxide hydrate), or ZrO in anionic form_２. NOH H^＋An⁻(An can have an anion attached to HZO, such as acetate or chloride). In the absence of anions, various degrees of O bound to Zr^２−, OH⁻And H_２Partially oxolated zirconium hydride, including O, i.e. Zr (OH)_xO_y(H_２O)_ZCan be thought of. The second cartridge may instead contain activated charcoal for removing organic uremic toxins, or the activated charcoal may be contained in a third cartridge. After passing through the final cartridge, the regenerated dialysate is ready for reuse. The second cartridge can contain both the HZO or anion exchange resin and the activated activated carbon in separate layers or multiple layers.

As used herein, "ammonia" is ammonium hydroxide (NH)._４^＋OH⁻), Or ammonium carbonate ((NH)_４^＋)_２CO_３^−２), Ammonium bicarbonate (NH_４^＋HCO_３⁻) And Ammonium Chloride (NH_４^＋Cl⁻Nonionic ammonia (NH), which is any form containing ammonium salts such as)_３) And ammonium ion (NH_４^＋) Refers to at least one.

FIG. 1 shows an exemplary hemodialysis system 100 including an example of the present invention. Fresenius Hemodialyzers such as the 2008T (not shown) control blood and dialysate flow rates and monitor the dialysis process. Patient 114 is coupled to hemodialyzer 111 via blood lines 112, 113. Blood flows from the patient 114 through the blood inlet 112 to the dialyzer 111 and exits through the blood outlet 113 using a catheter or any other suitable blood access device. Clean blood is returned to the patient. Clean dialysate flows into the dialyzer 111 through the dialysate inlet 115 and exits through the dialysate outlet 116. Blood flows in the direction opposite to the dialysate, as indicated by the directional arrows. The blood flow and dialysate flow in the dialyzer can be exchanged so that the blood flow flows from top to bottom and the dialysate flows from bottom to top. The used dialysate 101 is delivered through a cartridge 102 containing a substance that hydrolyzes urea into ammonia or ammonium carbonate. The used dialysate 101 is then processed by the extraction system 110 to remove ammonia. The extraction system 110 includes a liquid-liquid countercurrent extractor 103 and a heat exchanger or heat circulator (heat). cycler) 105. The extractor 103 uses a solvent containing dissolved extract molecules to remove ammonia from the used dialysate. The extracted molecule binds or complexes with ammonia. The thermal circulator 105 heats a solvent containing an extract molecule complexed with ammonia to break the complex and release the extract molecule and ammonia. The temperature provided by the thermal circulator is 100 ° C. or higher, for example 125 ° C. or higher (eg, 100 ° C. to 170 ° C., 100 ° C. to 150 ° C., 110 ° C. to 150 ° C. or 115 ° C. to 150 ° C.). In essence, the heat provided is such that the extraction molecules release ammonia. The recovered extract molecules and solvent can be returned to the extractor 103 for reuse. The used dialysate 101 can exit the extraction system 110 and be sent through a cartridge 108 containing a substance that removes phosphate and / or other organic uremic toxins. The regenerated dialysate 109 can be returned to the dialyzer 111 to continue dialysis treatment.

The cartridge 102 includes a housing that contains any suitable amount and any type of substance that effectively hydrolyzes urea in the dialysate into ammonia as the dialysate flows along the fluid pathway. This material is disposable and can be removed from the housing after use and replaced with new material, for example. This material is renewable and can be processed for reuse after use, for example. The substance is sword bean flour, encapsulated sword bean flour, crosslinked sword bean flour, alumina (aluminum oxide) containing sword bean flour or other stabilized urease, or any combination thereof.

Cartridge 108 contains any suitable amount and any type of substance that effectively removes phosphate and other organic uremic toxins in the dialysate as the dialysate flows along the fluid pathway. Includes housing. This material is disposable and can be removed from the housing after use and replaced with new material, for example. This material is one or more materials selected from activated carbon, zirconium oxide, and / or zirconium hydroxide. This material may be zirconium hydroxide or activated carbon. The substance that removes the phosphate may be an anion exchange resin. The anion exchange resin is renewable and can be processed for reuse, for example after use.

The cartridges 102 and 108 can be arranged in series or combined into a single cartridge. The cartridge and / or the material contained in the cartridge can be placed in any form such that the urea in the dialysis solution is hydrolyzed to ammonia prior to the extraction system.

The extraction system 110 includes a liquid-liquid countercurrent extractor 103 and a heat circulator 105. Liquid-liquid extraction, also known as solvent extraction, is the extraction of a substance from one liquid phase of two different immiscible liquids into another. The liquid is usually water and an organic solvent. The extraction system can include one, two or more extraction compartments. The used dialysate can pass through multiple compartments (if used) in a continuous manner. When multiple compartments are used, the solvent and / or extracted molecules may be the same or different. The solvent and extract molecules are separated from the used dialysate by immiscibility so that one can be removed from the top or bottom of the compartment, for example by the specific gravity of the liquid.

In the present invention, the liquid-liquid countercurrent extractor 103 contains two immiscible liquids and one extract molecule for the continuous removal of ammonia from the used dialysate 101. One of the liquids in the extractor 103 is the used dialysate 101, and the other liquid is a solvent containing the extract molecules. The used dialysate 101 is purified water containing a dissolved water-soluble salt. The used dialysate 101 may additionally contain a penetrant such as sucrose or glucose.

The extraction molecule can be one or more cation exchange molecules dissolved in a solvent. The extracted molecules combine with ammonia to form a complex, which removes ammonia from the used dialysate 101. The solvent containing the complexed ammonia 104 is heated by the heat circulator 105 to destroy the complex, discharge the ammonia, and regenerate the extracted molecules in the solvent. The solvent containing the extraction molecules 106 is returned to the liquid-liquid countercurrent extractor 103 in order to continue removing ammonia from the used dialysate 101. The discharged ammonia 107 is captured for disposal or used for other purposes such as commercial use.

The extracted molecule has the property of forming an ion pair with ammonium ion and thermally decomposing to release ammonia. The extracted molecules may be thermally stable at the temperatures required to carry out the removal of ammonia and the regeneration of the extracted molecules. The extracted molecule can be soluble in a solvent, more easily bound to ammonia than other cations, easily recovered after thermal release of ammonia, and / or have a pKa value of about 3-7. The extract molecule is, or contains, phosphinic acid, carboxylic acid or phosphoric acid, or any combination thereof.

The extracted molecule is or contains dialkylphosphinic acid, such as di-2,4,4-trimethylpentylphosphinic acid. The use of di-2,4,4-trimethylpentylphosphinic acid as a liquid cation exchanger to remove ammonia from wastewater in a combined back-stripping / extraction process is http: // escholarship. Search from org / uc / item / 2rc4q0b2, Poole, LJ (2008), "Novel Regenerated Solvent Extraction Processes for the Recovery of Carboxylic Acids or Ammonia from Aqueous Solutions Part II. Recovery of Ammonia from Sour Waters", Lawrence Berkley National Laboratory, LBNL Paper LBL-28615, which is incorporated herein by reference in its entirety.

The extracted molecule is, or contains, an α, α-di-substituted medium chain length carboxylic acid. The di-substituted portion of the carboxylic acid is strongly electron attracting and is substituted with an element such as chlorine or fluorine. α-carbon refers to the first carbon attached to the carboxyl group. α, α-di substitution refers to the carbon closest to the α carbon or carboxyl group having two substitution atoms so that two fluorine atoms or two chlorine atoms are bonded to α carbon. These substitutions make the carboxylic acid more acidic.

The extracted molecule is or contains a dialkyl phosphate having the following chemical structure:

<chemistry id="" num="1"><img id="000003" he="35" wi="23" file="2014530643.tif" img-format="tif" img-content="drawing" /></chemistry>

The R group is any sufficiently large water repellant group that makes phosphoric acid oil soluble. The R group can have 8 to 20 carbon atoms. The R group can be a linear, aromatic or alkyl ring including, but not limited to, naphthyl, cyclohexyl, benzyl or phenyl groups. The R groups may be the same or different from each other in the chemical structure described above.

The solvent in the extractor 103 is undecane, Norpar. 12), vegetable oils, modified vegetable oils, biodiesel, or any combination thereof. The solvent can be, for example, modified vegetable oil or biodiesel. Modified vegetable oils and biodiesel are well-known products and are readily commercially available. Vegetable oils contain triglycerides, which are three fatty acids esterified with glycerin. To convert vegetable oils to biodiesel, the material can be transesterified to produce a low viscosity liquid. The modified vegetable oil can be a transesterified diglyceride and triglyceride. Transesterification occurs when diglycerides and triglycerides react with ethanol and methanol. The modified vegetable oil can reduce the viscosity of the original vegetable oil and can improve its function as a solvent and as a phase separator from the dialysate. Biodiesel can be a substance made from vegetable oils or animal fats. All biodiesels are triglycerides (three fatty acids bound by glycerin). The production of biodiesel with improved properties is well known. For example, US Pat. No. 6,583,302, which is incorporated herein by reference in its entirety, describes the preparation of triglyceride oils with unsaturated fatty acid substituents from vegetable oils. The resulting triglyceride oil can have improved thermal and / or oxidative stability and / or low temperature performance properties and / or be environmentally friendly. .. Further examples of biodiesel are described in US Pat. Nos. 6,015,440, 6,235,104, 7,918,905 and 7,101,519, all of which are incorporated herein by reference in their entirety.

The solvent of the present invention can have one or more properties or properties such as water insolubility, thermal stability, oxidative stability, low viscosity and / or low density. The solvent can have at least two, at least three, or at least four of the above properties. The solvent can have all of the above properties. The solvent can have a water solubility range of about 100 ppm water or less. The solvent can have a density of about 0.70 to 0.95 Kg / L, such as about 0.7 to 0.8 Kg / L. The solvent can have a viscosity of about 2-30 cSt, such as about 2-20 cSt. The solvent can have a melting point of about 20 ° C. or lower and / or a boiling point of about 130 ° C. or higher and / or a flash point of about 130 ° C. or higher. The solvent can be non-toxic and / or biocompatible. The solvent can have the ability to easily dissolve the extracted molecules and / or can be fairly immiscible or completely immiscible with water.

FIG. 2 shows an explanatory peritoneal dialysis system 200 including an example of the present invention. An extraordinary peritoneal dialysis machine, such as the Fresenius Liberty (Mal c) Cycler, controls the time of dialysate filling, retention and drainage and monitors the dialysis process. Patient 210 receives clean dialysate from a container 212 connected to the peritoneal cavity via a catheter or any other suitable access device 211. The used dialysate 201 is drained from the patient 210 into the container 212 via a catheter or any other suitable access device 211, either continuously or after a certain retention period. Container 212 can be one or more containers. The used dialysate 201 is delivered through a cartridge 202 containing a substance that hydrolyzes urea to remove phosphate and other organic uremic toxins. The used dialysate 201 is then processed by the extraction system 209 to remove ammonia. As mentioned above, the extraction system 209 includes a liquid-liquid countercurrent extractor 203 and a heat circulator 205. The regenerated dialysate 208 exits the extraction system 209. The regenerated dialysate 208 is returned to container 212 to continue dialysis treatment.

The cartridge 202 contains a housing that contains any suitable amount and any type of substance that effectively hydrolyzes urea in the dialysate as the dialysate flows along the fluid pathway and removes other toxins from the dialysate. Can include. This material is disposable and can be removed from the housing after use, for example and replaced with a new material. This material can be layered. The layer of this substance may include a urea removing layer containing a urea degrading enzyme, an organic uremic toxin removing layer containing activated carbon, and / or an ion exchange layer containing a phosphate binder or an ion exchange adsorbent. ..

The cartridge can include the following layers and materials: That is, sodium zirconium carbonate or other alkali metal-Group IV metal carbonates, alumina or other similar substances, alumina-bearing ureases or other immobilization enzyme layers, or other substances that convert urea to ammonia, and charcoal or Granular activated charcoal such as other absorbent substances can be included. Zirconium sodium carbonate can function as a phosphate adsorbent. Zirconium oxide or zirconium hydroxide can function as a counterion or ion exchanger that removes phosphate. Zirconium oxide and sodium zirconium oxide can be in separate layers or may be blended together in the same layer. The hydrous zirconium can function as an anion exchange resin for removing phosphate.

Some examples of urea converting enzymes include natural enzymes, enzymes produced by recombinant techniques, or synthetically produced enzymes. This enzyme can be urease. The enzyme source can be cross-linked sword bean powder.

Further examples of suitable amounts for adsorbent cartridges and cartridge components are described in U.S. Pat. Nos. 6,627,164, 6,878,283, 7,033,498, and 7,101,519, all of which are herein by reference. Incorporate.

The present invention may further include a pump that moves the fluid through the system. The pump can be placed in front of the adsorbent cartridges 102, 202. For example, the pump (not shown) can be located in the fluid flow path between the used dialysate outlet 116 and the adsorbent cartridge 102, or between the dialysate bag 212 and the adsorbent cartridge 202. Through a fluid circuit that includes an adsorbent cartridge 102 (202), a liquid-liquid countercurrent separator 103 (203), an optional supplemental adsorbent cartridge 108, and a dialyzer 111 (dialysate bag 212). Can be moved. The pumps may be located elsewhere in the fluid circuit, or may use multiple pumps located in multiple locations along the fluid circuit. The present invention may include a pump placed after the heat circulators 105, 205 to return the fluid to the extractors 103, 203. For example, in order to return the regenerated fluid from the heat circulator to the separator after discharging ammonia, a pump (not shown) is placed between the heat circulators 105 and 205 and the liquid-liquid countercurrent separators 103 and 203. Can be placed in the fluid flow path of.

The present invention is a chiller (not shown) such as a chilled water coil or constant temperature bath that cools the solvent exiting the heat circulators 105, 205 before returning it to the extractor, the heat circulators 105, 205. A chiller may be further provided after and in front of the liquid-liquid countercurrent extractors 103, 203.

The present invention is an ion exchange resin or other placed in front of the liquid-liquid countercurrent extractors 103, 203 to raise the pH of the dialysis solution before it enters the liquid-liquid countercurrent extractors 103, 203. You may also have a suitable device. The present invention is placed after the liquid-liquid countercurrent extractors 103, 203 to lower the pH of the solution before returning to the hemodialyzer 111 or to the dialysate bag 212 connected to the patient 210. It may further have a second ion exchange resin or other suitable device.

As an option, neither adsorbent cartridge contains zirconium phosphate. In other words, as an option, the invention can be practiced without the presence or need of zirconium phosphate as one of the substances used in one or more cartridges. Zirconium phosphate has the chemical formula Zr (HPO)._４)_２・nH_２Can have O. This can have the significant advantage that zirconium phosphate can make up the majority of the material used in the cartridge in conventional cartridge systems. Having the option and ability to avoid the use of zirconium phosphate or to minimize the amount of zirconium phosphate can provide many advantages in terms of cost, cartridge size, and other benefits.

The invention further comprises (a) at least one adsorbent cartridge or other device capable of converting urea to ammonia and carbon dioxide or ammonium carbonate, and (b) a liquid-liquid countercurrent extractor and heater device. The present invention comprises a liquid-liquid countercurrent extractor and a heater device, wherein the heater device has the ability to heat a solvent containing one or more extract molecules and ammonia so as to remove ammonia by heating. It relates to a method of performing either hemodialysis or peritoneal dialysis using the system. This method transfers the dialysate to one or more subsequent cartridges after removing ammonia, eg, to one or more cartridges capable of removing phosphate and / or organic uremic toxins and / or other impurities. Passing can be further included.

The present invention includes the following viewpoints / embodiments / features in any order and / or in any combination. 1. 1. The present invention comprises at least one adsorbent device and at least one liquid-liquid countercurrent extractor that communicates with the at least one adsorbent device in a fluid manner. It relates to a dialysis system comprising at least one liquid that is immiscible with the dialysis solution and (b) at least one extract molecule capable of removing ammonia from the dialysis solution. 2. The dialysis system of any preceding or subsequent embodiment / feature / aspect further comprises at least one heater associated with said at least one liquid-liquid extractor, which releases ammonia from the complex for extraction. In order to regenerate the molecules, after the at least one liquid and the extracted molecules have flowed countercurrently through the used dialysate containing ammonia in the at least one liquid-liquid extractor, with the at least one liquid. , The extracted molecule complexed with ammonia can be heated. 3. 3. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the at least adsorbent device is in fluid communication with a hemodialysis machine or peritoneal dialysis machine to receive used dialysate from it and said liquid-liquid. A countercurrent extractor is in fluid communication with the hemodialyzer or peritoneal dialysis machine and is regenerated dialysate with one or more additional adsorbent devices fluid-connected between them, or without fluid connection. Return. 4. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the extracted molecule is a cation exchange molecule. 5. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the extracted molecule is phosphinic acid, carboxylic acid, phosphoric acid, or any combination thereof. 6. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the at least one liquid is undecane, noper 12, vegetable oil, modified vegetable oil, biodiesel, or any combination thereof. 7. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the adsorbent device comprises a urease source capable of converting urea to ammonia. 8. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the urease source is sword bean powder, encapsulated sword bean powder, crosslinked sword bean powder or other stabilized urease or any combination thereof. Is. 9. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the urease source is in the form of one or more layers within the cartridge. 10. The present invention involves passing a used dialysate containing urea through at least one adsorbent device capable of converting at least a portion of the urea to ammonia, followed by the liquid-liquid passage of the used dialysate. Further covered is a method of regenerating a used dialysate, comprising the step of removing at least a portion of the ammonia from the used dialysate through a countercurrent extractant. 11. The method of any preceding or subsequent embodiment / feature / viewpoint is to remove at least a portion of the ammonia and then pass the used dialysate through one or more subsequent adsorbent devices to the spent dialysate. Further comprises the step of further purifying. 12. In any of the preceding or subsequent embodiments / features / viewpoint methods, the one or more adsorbent devices can remove the phosphate or a portion thereof and / or remove the organic uremic toxin or a portion thereof. It comprises at least one cartridge that can be. 13. In any of the preceding or subsequent embodiments / features / viewpoint methods, the step of passing the used dialysate through the solution-liquid countercurrent extractant is a method of passing the used dialysate containing ammonia and the extracted molecules. The extraction molecule is complexed with ammonia removed from the used dialysate, comprising the step of countercurrently passing at least one liquid immiscible with the contained dialysis solution through the liquid-liquid countercurrent extractor. To form a complex. 14. The method of any preceding or subsequent embodiment / feature / viewpoint heats the at least one liquid and the complex after the step of countercurrently passing the used dialysate and the at least one liquid. Further comprises the step of breaking the complex and releasing ammonia from it to regenerate the extracted molecule. 15. The method of any preceding or subsequent embodiment / feature / viewpoint is the step of discharging the ammonia from the liquid-liquid countercurrent extractor after breaking the complex and regenerating the at least one liquid. It further comprises the step of returning the extracted molecules to the liquid-liquid countercurrent extractor. 16. In any of the preceding or subsequent embodiments / features / viewpoint methods, the extracted molecule is a cation exchange molecule. 17. In any of the preceding or subsequent embodiments / features / viewpoint methods, the extracted molecule is phosphinic acid, carboxylic acid, phosphoric acid, or any combination thereof. 18. In any of the preceding or subsequent embodiments / features / viewpoint methods, the at least one liquid is undecane, noper 12, vegetable oil, modified vegetable oil, biodiesel or any combination thereof. 19. In any of the preceding or subsequent embodiments / features / viewpoint methods, the extracted molecule removes 95-100% by weight of the total ammonia from the used dialysate. 20. The present invention relates to a method of performing dialysis on a patient, further comprising using any preceding or subsequent embodiment / feature / viewpoint dialysis system with a hemodialysis machine or a peritoneal dialysis machine.

The present invention can include any combination of these various features or embodiments described above and / or described below in the text and / or paragraph. Any combination of features disclosed herein is considered part of the invention and there are no restrictions on the features that can be combined.

Applicants expressly incorporate the entire content of all cited references in this disclosure. Further, when an amount, concentration, or other value or parameter is given as either a range, a preferred range, or a list of preferred upper and lower bounds, this is whether the range is disclosed individually. Regardless, it should be understood as specifically disclosing all ranges formed from any pair of any range upper limit or preferred upper limit value and any range lower limit or preferred lower limit value. Where a range of numbers is listed herein, the range shall include its endpoints and all integers and fractions within the range, unless otherwise specified. The scope of the present invention is not limited to the specific values listed in defining the scope.

Other embodiments of the invention will become apparent to those skilled in the art by reviewing the specification and implementing the invention disclosed herein. The present specification and examples are merely examples, and the true scope and gist of the present invention is shown by the following claims and their equivalents.

100 An example of the reproduction system of the present invention 101 Used dialysate 102 Adsorbent cartridge that hydrolyzes urea 103 Liquid-liquid countercurrent separator 104 Ammonia complexed in the extraction fluid 105 heat circulator 106 Regenerated extract fluid 107 Discharged ammonia 108 Phosphorus-containing and organic uremic toxin adsorbent cartridge 109 Regenerated dialysate 110 extraction system 111 dialyzer 112 Blood inlet 113 Blood outlet 114 patients 115 Regenerated dialysate inlet 116 Used dialysate outlet 200 An example of the reproduction system of the present invention 201 Used dialysate 202 Adsorbent cartridge that hydrolyzes urea and removes phosphates and organic uremic toxins 203 Liquid-liquid countercurrent separator 204 Ammonia complexed in the extraction fluid 205 Thermal circulator 206 Regenerated extract fluid 207 Discharged ammonia 208 Regenerated dialysate 209 extraction system 210 patients 211 Patient catheter 212 dialysate bag

The present invention includes the following viewpoints / embodiments / features in any order and / or in any combination. 1. 1. The present invention comprises at least one adsorbent device and at least one liquid-liquid countercurrent extractor that communicates with the at least one adsorbent device in a fluid manner. It relates to a dialysis system comprising at least one liquid that is immiscible with the dialysis solution and (b) at least one extract molecule capable of removing ammonia from the dialysis solution. 2. The dialysis system of any preceding or subsequent embodiment / feature / aspect further comprises at least one heater associated with said at least one liquid-liquid countercurrent extractor, which releases ammonia from the complex. After the at least one liquid and the extracted molecules have flowed countercurrently through the used dialysate containing ammonia in the at least one liquid-liquid extractor to regenerate the extracted molecules. The liquid and the extract molecules complexed with ammonia can be heated. 3. 3. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the at least adsorbent device is in fluid communication with a hemodialysis machine or peritoneal dialysis machine to receive used dialysate from it and said liquid-liquid. A countercurrent extractor is in fluid communication with the hemodialyzer or peritoneal dialysis machine and is regenerated dialysate with one or more additional adsorbent devices fluid-connected between them, or without fluid connection. Return. 4. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the extracted molecule is a cation exchange molecule. 5. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the extracted molecule is phosphinic acid, carboxylic acid, phosphoric acid, or any combination thereof. 6. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the at least one liquid is undecane, noper 12, vegetable oil, modified vegetable oil, biodiesel, or any combination thereof. 7. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the adsorbent device comprises a urease source capable of converting urea to ammonia. 8. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the urease source is sword bean powder, encapsulated sword bean powder, crosslinked sword bean powder or other stabilized urease or any combination thereof. Is. 9. In any preceding or subsequent embodiment / feature / viewpoint dialysis system, the urease source is in the form of one or more layers within the cartridge. 10. The present invention involves passing a used dialysate containing urea through at least one adsorbent device capable of converting at least a portion of the urea to ammonia, followed by the liquid-liquid passage of the used dialysate. Further covered is a method of regenerating a used dialysate, comprising the step of removing at least a portion of the ammonia from the used dialysate through a countercurrent extractor. 11. The method of any preceding or subsequent embodiment / feature / viewpoint is to remove at least a portion of the ammonia and then pass the used dialysate through one or more subsequent adsorbent devices to the spent dialysate. Further comprises the step of further purifying. 12. In any of the preceding or subsequent embodiments / features / viewpoint methods, the one or more adsorbent devices can remove the phosphate or a portion thereof and / or remove the organic uremic toxin or a portion thereof. It comprises at least one cartridge that can be. 13. In any of the preceding or subsequent embodiments / features / viewpoint methods, the step of passing the used dialysate through the liquid-liquid countercurrent extractor is a method of passing the used dialysate containing ammonia and the extracted molecules. The extraction molecule is complexed with ammonia removed from the used dialysate, comprising the step of countercurrently passing at least one liquid immiscible with the contained dialysis solution through the liquid-liquid countercurrent extractor. To form a complex. 14. The method of any preceding or subsequent embodiment / feature / viewpoint heats the at least one liquid and the complex after the step of countercurrently passing the used dialysate and the at least one liquid. Further comprises the step of breaking the complex and releasing ammonia from it to regenerate the extracted molecule. 15. The method of any preceding or subsequent embodiment / feature / viewpoint is the step of discharging the ammonia from the liquid-liquid countercurrent extractor after breaking the complex and regenerating the at least one liquid. It further comprises the step of returning the extracted molecules to the liquid-liquid countercurrent extractor. 16. In any of the preceding or subsequent embodiments / features / viewpoint methods, the extracted molecule is a cation exchange molecule. 17. In any of the preceding or subsequent embodiments / features / viewpoint methods, the extracted molecule is phosphinic acid, carboxylic acid, phosphoric acid, or any combination thereof. 18. In any of the preceding or subsequent embodiments / features / viewpoint methods, the at least one liquid is undecane, noper 12, vegetable oil, modified vegetable oil, biodiesel or any combination thereof. 19. In any of the preceding or subsequent embodiments / features / viewpoint methods, the extracted molecule removes 95-100% by weight of the total ammonia from the used dialysate. 20. The present invention relates to a method of performing dialysis on a patient, further comprising using any preceding or subsequent embodiment / feature / viewpoint dialysis system with a hemodialysis machine or a peritoneal dialysis machine.