Removing ions from a body fluid

Abstract

A method for removing Pb 2+ , Hg 2+ , K + , and NH4 + toxins from body fluids is disclosed. The method involves contacting the body fluid, which includes blood and gastrointestinal fluids, with an ion exchange composition to remove the metal toxins from the body fluid. Alternatively, the blood can be contacted with a dialysis solution and then with the ion exchange composition. The ion exchange composition is represented by the empirical formula: A r+ p M s+ 1‑ x M ’t+ x Si n O m . Compositions comprising the above ion exchange composition in combination with a body fluid or a dialysis solution are also disclosed. The ion exchange composition can be supported by a porous network of biocompatible polymers such as carbohydrates or proteins.

Description

[0001] CLAIM OF PRIORITY

[0002] This patent application claims priority to U.S. Provisional Application No. 63 / 085,804, filed September 30, 2020, which is incorporated herein in its entirety. TECHNICAL FIELD

[0003] The present invention relates to in vivo and in vitro methods for removing heavy metal toxins (e.g., lead and mercury ions) and metabolic toxins (e.g., potassium and ammonium ions) from body fluids. Blood or other body fluids are contacted with a rare earth silicate ion exchange composition that is capable of selectively removing the toxins. Alternatively, the blood can first be contacted with a dialysis solution and then with the rare earth silicate ion exchange composition. BACKGROUND

[0004] In mammals (e.g., humans), most other organs of the body will soon fail when the kidneys and / or liver are unable to remove metabolic waste products from the body. Therefore, extensive efforts have been made to find safe and effective methods for removing toxins from the blood of patients by extracorporeal treatment. A number of methods have been proposed for removing small molecule toxins, protein-bound molecules, or larger molecules believed to be responsible for coma and liver failure diseases. Some of these toxic compounds have been identified as urea, creatine, ammonia, phenols, thiols, short-chain fatty acids, aromatic amino acids, pseudoneurotransmitters (octopamine), neuroinhibitors (glutamate), and bile salts. The art exhibits a variety of ways of treating blood containing such toxins. The classical method is of course dialysis. Dialysis is defined as the removal of a substance from a liquid by diffusion into a second liquid across a semipermeable membrane. Dialysis of blood outside the body (hemodialysis) is the basis of the "artificial kidney". The treatment program commonly used today is similar to the program developed by Kolff in the early 1940s. Since the 1940s, there have been several disclosures relating to improvements of the artificial kidney or artificial liver. Thus, US 4,261,828 discloses an apparatus for detoxification of blood. The apparatus comprises a housing filled with adsorbents such as charcoal or resins and optionally an enzyme carrier. In order to prevent direct contact between the blood and the adsorbents, the adsorbents can be coated with a coating which allows penetration of the substances to be adsorbed, also preventing direct contact between the blood corpuscle blood components and the adsorbents. US 4,581,141 discloses a composition for dialysis containing surface adsorbing substances, water, a suspending agent, urease, calcium-loaded cation exchanger, aliphatic carboxylic acid resin, and a metabolizable organic acid buffer. The calcium-loaded cation exchanger can be a calcium-exchanged zeolite. EP 0046971A1 discloses that zeolite W can be used for hemodialysis to remove ammonia. Finally, US 5,536,412 discloses a blood filtration and plasma filtration device, wherein blood flows through the interior of hollow fiber membranes and during the flow of blood, an adsorbent suspension is circulated against the outer surface of the hollow fiber membranes. Another step involves alternatingly removing and reintroducing the plasma fraction of the blood into the interior of the membranes, thereby effecting removal of toxins. The adsorbents can be activated charcoal as well as ion exchangers such as zeolites or cation exchange resins.

[0005] There are problems associated with the adsorbents disclosed in the above patents. For example, charcoal does not remove any water, phosphates, sodium or other ions. A disadvantage of zeolites is that they can partially dissolve in the dialysis solution, thereby allowing aluminum and / or silicon to enter the blood. In addition, zeolites can adsorb sodium, calcium and potassium ions from the blood, thereby requiring addition of these ions back into the blood.

[0006] More recently, examples of microporous ion exchangers that are essentially insoluble in fluids such as body fluids (especially blood) have been developed, namely zirconium-based silicates and titanium-based silicates of US 5,888,472, US 5,891,417 and US 6,579,460. The use of these microporous ion exchangers of zirconium-based silicates or titanium-based silicates to remove toxic ammonium cations from blood or dialysate is described in US 6,814,871, US 6,099,737 and US 6,332,985. In addition, some of these compositions were found to be selective in potassium ion exchange as well and can remove potassium ions from body fluids to treat the disease hyperkalemia, which is discussed in patents US 8,802,152; US 8,808,750; US 8,877,255; US 9,457,050; US 9,662,352; US 9,707,255; US 9,844,567; US 9,861,658; US 10,413,569; US 10,398,730; US 2016 / 0038538 and US 10,695,365. The extracorporeal use of these materials, for example, in dialysis is described in US 9,943,637.

[0007] Blood compatible polymers have also been incorporated into devices for the treatment of body fluids. US 9033908 discloses a small benchtop and wearable device for removing toxins from blood. The device has an adsorptive filter that utilizes nanoparticles embedded in a porous blood compatible polymer matrix. The toxic materials targeted by this device and filter system are potassium, ammonia, phosphate, urea and uric acid. Similarly, a 3-D printed hydrogel matrix composed of cross-linked poly(ethylene glycol) diacrylate tethered with polydiacetylene-based nanoparticles has been demonstrated to be successful in removing the toxin melittin (Nat. Commun., 5, 3774, 2014).

[0008] In addition to toxins derived from metabolic waste, humans are susceptible to environmental toxins that can enter the body, for example, by ingestion, by absorption through the skin, or by inhalation. One well-known toxic metal is lead. For many years, lead was a key component of gasoline in the form of tetraethyl lead and was a key component of paints. Currently, lead is no longer used or is used sparingly in these industries, but environmental hazards still exist. Renovation activities in older homes painted with lead-containing paints generate dust that can be inhaled or end up in the soil nearby, where the lead is leached into groundwater or taken up by plants. Unreliable or unregulated water supplies represent a hazard of exposure to Pb 2+ toxicity, most notably the recent situation in Flint, Michigan, USA, where some residents were found to have dangerously high Pb in their blood after exposure to a new municipal water supply.2+ Lead contamination is associated with many adverse health conditions, including effects on the nervous system and urinary system and induction of learning and developmental disorders in exposed children. Removal of lead from the blood of afflicted patients will reduce further exposure and damage.

[0009] Another well-known toxic metal is mercury. Most human-produced mercury found in the environment comes from the combustion of fossil fuels, with the primary source being coal-fired power plants, although various industrial processes also release mercury into the environment. Environmental mercury is bioaccumulated in fish and shellfish in the form of methylmercury, which is a highly toxic form of the heavy metal, and consumption of contaminated seafood is the most common cause of human mercury poisoning. Once in the body, methylmercury is likely converted to divalent mercury, which enters the reduction-oxidation pathway in this case. Another common source of exposure is from amalgam dental fillings. Elevated blood levels of mercury can cause a variety of diseases, including neurological disorders and kidney failure, and these adverse effects are magnified in children.

[0010] Chelation therapy is generally the preferred treatment for heavy metal poisoning. The chelator CaNa2EDTA (ethylenediaminetetraacetic acid) has been used to remove Pb 2+ from the blood, but this complex is difficult to absorb from the gastrointestinal tract and must usually be administered intravenously. This chelate has been observed to mobilize Pb 2+ , transferring it to other tissues, including the brain (Int. J. Environ. Res. Public Health, 2010, 7, 2745-2788). Dimercaptosuccinic acid (DMSA) is considered a chelating agent for heavy metal poisoning and has been used to treat Pb 2+ and Hg 2+ poisoning (see US 5,519,058). Supported chelators, i.e., chelators bound to resins, have been used for heavy metal removal in a dialysis mode, where blood is on one side of a semi-permeable membrane and resin-supported chelates are on the other side (see US 4612122).

[0011] Zeolites have been proposed for use in treating chronic lead poisoning, taken in pill form in US 20180369279A1, but zeolites have limited stability, especially in the gastrointestinal tract.

[0012] The Applicant has identified microporous compositions, identified as rare earth silicate ion exchange compositions, which are capable of selectively removing Pb 2+ , Hg 2+ , K + and NH4 +ions. Some microporous compositions are described in US 6,379,641, incorporated by reference. These ion exchangers are further defined by their empirical formula on an anhydrous basis:

[0013] A r+ p M s+ 1-x M ’t+ x Si n O m

[0014] wherein A is an exchangeable cation such as sodium, M is at least one element selected from the group consisting of rare earth elements, and M' is a framework metal having a valence of +2, +3, +4, or +5. Since the compositions are substantially insoluble in body fluids (at neutral and slightly acidic or basic pH), they can be ingested orally for the removal of heavy metals and metabolic toxins from the gastrointestinal system and for the removal of toxins, particularly Pb 2+ , Hg 2+ , K + , and NH4 + from dialysis fluid solutions. SUMMARY

[0015] As stated, the present invention relates to a method for removing heavy metals and metabolic toxins (such as Pb 2+ , Hg 2+ , K + , NH4 + or combinations thereof) from a fluid selected from the group consisting of body fluids, dialysis fluid solutions, and mixtures thereof, the method comprising contacting the toxin-containing fluid with a rare earth silicate ion exchanger under ion exchange conditions, thereby removing the toxin from the fluid, the rare earth silicate ion exchanger having an empirical formula on an anhydrous basis of:

[0016] A r+ p M s+ 1-x M ’t+ x Si n O m

[0017] In this formula, "A" is a structure directing cation, which also serves as a counter cation, and is selected from the group consisting of: alkali metals, alkaline earth metals, hydronium ions, ammonium ions, quaternary ammonium ions, and mixtures thereof. Specific examples of alkali metals include, but are not limited to, sodium, potassium, and mixtures thereof. Examples of alkaline earth metals include, but are not limited to, magnesium and calcium. "r" is the weighted average valence of A and varies between 1 and 2. The value of "p", which is the mole ratio of "A" to total metal elements (total metal elements = M + M'), varies between 1 and 5. The framework structure consists of silicon, at least one rare earth element (M), and optionally M' metal. The total metal elements are defined as M + M', where the mole fraction of the total metal elements that are rare earth metals M is given by "1 - x", and the mole fraction of the total metal elements that are M' metal is given by "x". The rare earth elements, represented by M, have a valence of +3 or +4, and include scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium. Depending on these options for M, "s" (the weighted average valence of M) varies between 3 and 4. Similarly, more than one M' metal can be present, and each M' metal can have a different valence. The M' metals that can be substituted into the framework have a valence of +2, +3, +4, or +5. Examples of these metals include, but are not limited to, zinc (+2), iron (+3), titanium (+4), zirconium (+4), and niobium (+5). Thus, "t" (the weighted average valence of M') varies between 2 and 5. Finally, "n" is the mole ratio of Si to total metal elements and has a value of 3 to 10, and "m" is the ratio of O to total metal elements and is given by the formula

[0018]

[0019] This and other objects and embodiments will become clear in the detailed description of the application. DETAILED DESCRIPTION

[0020] As stated, Applicants have developed a novel method for removing toxins from a fluid selected from the group consisting of a body fluid and a dialysate solution. An essential element of the method of the present invention is an ion exchanger having a large capacity and a strong affinity (i.e., selectivity for at least one or more heavy metals or metabolic toxins, especially Pb 2+ , Hg 2+ , K + , or NH4 + ). The composition is identified as a rare earth silicate having the following complex empirical formula (on an anhydrous basis):

[0021] A r+ p M s+ 1-x M ’t+ x Sin O m

[0022] In this formula, "A" is a structure directing cation, which also serves as a counter cation, and is selected from the group consisting of: alkali metals, alkaline earth metals, hydronium ions, ammonium ions, quaternary ammonium ions, and mixtures thereof. Specific examples of alkali metals include, but are not limited to, sodium, potassium, and mixtures thereof. Examples of alkaline earth metals include, but are not limited to, magnesium and calcium. "r" is the weighted average valence of A and varies between 1 and 2. The value of "p", which is the mole ratio of "A" to total metal elements (total metal elements = M + M'), varies between 1 and 5. The framework structure consists of silicon, at least one rare earth element (M), and optionally M' metal. The total metal elements are defined as M + M', where the mole fraction of the total metal elements that are rare earth metals M is given by "1 - x", and the mole fraction of the total metal elements that are M' metals is given by "x". The rare earth elements, represented by M, have a valence of +3 or +4, and include scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium. Depending on these options for M, "s" (the weighted average valence of M) varies between 3 and 4. Similarly, more than one M' metal can be present, and each M' metal can have a different valence. The M' metals that can be substituted into the framework have a valence of +2, +3, +4, or +5. Examples of these metals include, but are not limited to, zinc (+2), iron (+3), titanium (+4), zirconium (+4), and niobium (+5). Thus, "t" (the weighted average valence of M') varies between 2 and 5. Finally, "n" is the mole ratio of Si to total metal elements and has a value of 3 to 10, and "m" is the ratio of O to total metal elements and is given by the formula

[0023]

[0024] The composition has a framework structure consisting of SiO2tetrahedral oxide units, at least one rare earth metal oxide unit, and optionally M' metal oxide units. In addition, the rare earth metal is 6, 7, or 8 coordinated, and the M' metal is 4, 5, or 6 coordinated.

[0025] The rare earth silicates described herein are prepared by hydrothermal crystallization of a reaction mixture prepared by mixing silicon, a rare earth metal (M), optionally an M' metal, at least one reactive source of a cation (A), and water. Sources of silicon include, but are not limited to, colloidal silica, fumed silica, tetraorthosilicate, and sodium silicate. Sources of the rare earth metal (M) include, but are not limited to, metal halides, metal nitrates, metal acetates, metal sulfates, metal oxides, metal hydroxyl oxides, and mixtures thereof. Specific examples of rare earth metal (M) precursors include, but are not limited to, cerium (III) sulfate, cerium (IV) sulfate, yttrium chloride, ytterbium oxide, ytterbium nitrate, ytterbium sulfate octahydrate, ytterbium carbonate, and ytterbium oxalate. Sources of M' metal include, but are not limited to, metal halides, metal nitrates, metal acetates, metal oxides, metal hydroxyl oxides, metal alkoxides, and mixtures thereof. Specific examples include, but are not limited to, zinc chloride, zirconium butoxide, titanium (IV) chloride, titanium (III) chloride solution, niobium (V) chloride, and niobium (V) oxide. Sources of base include, but are not limited to, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, rubidium carbonate, cesium carbonate, sodium halide, potassium halide, rubidium halide, and cesium halide.

[0026] Generally, the hydrothermal process for preparing the rare earth silicate ion exchange compositions used in the present application involves forming a reaction mixture comprising reactive sources of the desired components in molar ratios of oxides expressed by the following formula:

[0027] aA 2 / m O:1-bMO h / 2 :bM'O g / 2 :cSiO2:dH2O

[0028] where "a" has a value of 1 to 100, "M" is the valence of the A component and has a value of +1 or +2, "b" has a value of 0 to less than 1.0, "h" is the valence of the M component and has a value of +3 or +4, "g" is the valence of the M component and has a value of +2, +3, +4, or +5, "c" has a value of 0.5 to 150, and "d" has a value of 30 to 10,000.

[0029] The reaction mixture is prepared by mixing the appropriate sources of the rare earth metals, silicon, the templating cations, and the optional M' element in any order to obtain the desired mixture. The basicity of the mixture is controlled by the addition of an excess of alkali hydroxide, quaternary ammonium hydroxide, and / or basic compound of the other components of the mixture. The reaction mixture is then reacted under autogenous pressure in a sealed reaction vessel at a temperature of 100°C to 300°C for a period of 1 hour to 30 days. After the reaction is complete, the resulting mixture is filtered or centrifuged to isolate the solid product, which is washed with deionized water and dried in air or at 100°C. As noted, the compositions of the present application have a framework structure composed of tetrahedral SiO2units, at least one rare earth metal oxide unit, and optionally M' metal oxide units. This framework generally results in a microporous structure having an intracrystalline pore system with uniform pore diameters (varying greatly between about 4 A and 10 A) and a surface area of 300 to 1000 m2 / g. The compositions of the present application can also be amorphous.

[0030] Upon initial synthesis, the compositions of the present application will contain some alkali or alkaline earth metal template in the pores, between the layers, or at other charge balancing locations. These metals are described as exchangeable cations, which means that they can be exchanged for other (secondary) A' cations. Typically, the A exchangeable cations can be exchanged for A' cations selected from other alkali metal cations (K + , Na + , Rb + , Cs + ), alkaline earth metal cations (Mg 2+ , Ca 2+ , Sr 2+ , Ba 2+ ), hydronium, or mixtures thereof. It is understood that the A' cations are different from the A cations. Methods for exchanging one cation for another are well known in the art and involve contacting the composition under exchange conditions with a solution containing the desired cation in molar excess. Exchange conditions include temperatures of 25°C to 100°C and times of 20 minutes to 2 hours. The particular cation (or mixture thereof) present in the final product will depend on the particular use of the composition and the particular composition used. One particular composition is an ion exchanger in which the A' cations are a mixture of Na + , Ca 2+ , and H + ions.

[0031] ​As noted above, the materials of the present application are prepared at high pH, and thus can increase the pH of any liquid to which they are exposed. Body fluids such as gastrointestinal fluids are acidic throughout the digestive tract, reaching a pH as low as 1.0 in the lower stomach. Blood has a pH of 7.4. Both of these types of body fluids would experience a pH increase if exposed directly to the as-synthesized materials of the present application. It is therefore preferred to ion exchange the materials of the present application. In one preferred embodiment, the as-synthesized rare earth silicate ion exchanger is treated with an acid to form the proton / hydrated proton ion exchanger form of the ion exchanger, which avoids the pH increase upon contact with body fluids. In another embodiment, the as-synthesized rare earth silicate ion exchanger can be ion exchanged with Na + or Ca 2+ cations, or both. In a third embodiment, the as-synthesized rare earth silicate ion exchanger can be first ion exchanged with an acid, and subsequently ion exchanged with Na + or Ca 2+ or both. If the patient being treated for Pb 2+ poisoning is hypocalcemic, it would be advantageous to use the Ca 2+ exchanged form of the rare earth silicate ion exchanger to avoid lowering the Ca 2+ level in the patient.

[0032] In some cases, when a quaternary ammonium cation is used as the hydroxide source in the synthesis, the quaternary ammonium cation can be incorporated into the product. Typically, this is not the case, as the quaternary ammonium cation will typically be displaced by an alkali metal cation, which has a higher affinity for incorporation into the product. However, the quaternary ammonium ion must be removed from the product. This can typically be accomplished by the ion exchange methods mentioned in the previous paragraph. At times, the quaternary ammonium ion can be trapped in the pores, and the quaternary ammonium cation can not be removed by ion exchange, in which case calcination is required. Typically, calcination consists of heating the sample to a temperature of 500-600 °C in flowing air or flowing nitrogen followed by flowing air for 2-24 hours. In this process, the quaternary ammonium cation is decomposed and replaced by a residual proton. Once calcination is complete, the sample can be ion exchanged into the desired A' cation composition as described above.

[0033] It is also within the scope of the present invention that these ion exchange compositions can be used in powder form or can be formed into various shapes by means well known in the art. Examples of these various shapes include pellets, extrudates, spheres, spheroids and irregularly shaped particles. This has been demonstrated previously in US 6,579,460 B1 and US 6,814,871 B1. The ion exchange compositions of the present invention can also desirably be supported in a porous network, including insertion into or incorporation into a blood compatible porous network, such as the porous network in the sorbent filter disclosed in US 9,033,908 B2. The porous network can consist of natural or synthetic polymers and biopolymers as well as mesoporous metal oxides and silicates. Suitable natural polymers (biopolymers) can include cross-linked carbohydrates or proteins made from oligomeric and polymeric carbohydrates or proteins. The biopolymers are preferably polysaccharides. Examples of polysaccharides include alpha-glucans with 1,3-, 1,4- and / or 1,6-bonds. Among these polysaccharides, the "starch family" (including amylose, amylopectin and dextrin) is particularly preferred, but pullulan, elsinan, reuteran and other alpha-glucans are also suitable, although the proportion of 1,6-bonds is preferably lower than 70%, more preferably lower than 60%. Other suitable polysaccharides include beta-1,4-glucans (cellulose), beta-1,3-glucans, xyloglucans, glucomannans, galactans and galactomannans (guar gum and locust bean gum), other gums, including heterogamous gums, such as xanthan gum, ghatti, carrageenan, alginate, pectin, beta-2,1 - and beta-2,6-fructans (inulin and Ievan) and the like. A preferred cellulose is carboxymethyl cellulose (CMC, e.g. AKUCELL from AKZO Nobel). Carbohydrates that can thus be used are carbohydrates consisting only of C, H and O atoms, such as for example glucose, fructose, sucrose, maltose, arabinose, mannose, galactose, lactose as well as oligomers and polymers of these sugars, cellulose, dextrin (such as maltodextrin), agarose, amylose, amylopectin and gums (e.g. guar gum). Preferably, oligomeric carbohydrates with a degree of polymerization (DP) higher than DP2 or polymeric carbohydrates higher than DP50 are used. These carbohydrates can be naturally occurring polymers, such as starches (amylose, amylopectin), cellulose and gums or derivatives thereof, which can be formed by phosphorylation or oxidation. The starches can be cationically or anionically modified starches. Examples of suitable (modified) starches that can be modified are corn starch, potato starch, rice starch, tapioca starch, banana starch and manioc starch. Other polymers (e.g. caprolactone) can also be used.In certain embodiments, the biopolymer is preferably a cationic starch, most preferably an oxidized starch (e.g., C6 oxidized with hypochlorite). The level of oxidation can be freely chosen to suit the application of the sorbent material. Very suitably, the level of oxidation is between 5% and 55%, most preferably between 25% and 35%, still more preferably between 28% and 32%. Most preferably, the oxidized starch is cross-linked. A preferred cross-linking agent is a diepoxide. The level of cross-linking can be freely chosen to suit the application of the sorbent material. Very suitably, the level of cross-linking is between 0.1% and 25%, more preferably between 1% and 5%, and most preferably between 2.5% and 3.5%. Proteins that can be used include albumin, ovalbumin, casein, myosin, actin, globulin, hemoglobin, myoglobin, gelatin, and small peptides. In the case of proteins, proteins obtained from hydrolysates of plant or animal material can also be used. A particularly preferred protein polymer is gelatin or a gelatin derivative.

[0034] As stated, these compositions have a particular utility in adsorbing metals and metabolic toxins (Pb 2+ , Hg 2+ , K + , and NH4 + ) from fluids selected from the group consisting of body fluids, dialysate solutions, and mixtures thereof. As used herein and in the claims, body fluids will include, but are not limited to, blood, plasma, and gastrointestinal fluids. Likewise, the compositions mean that they can be used to treat the body fluids of any mammal, including, but not limited to, humans, cows, pigs, sheep, monkeys, gorillas, horses, dogs, etc. The present method is particularly suited for removing toxins from the human body. There are a number of ways in which fluids can be brought into direct or indirect contact with the desired ion exchanger and thus have the toxins removed. One technique is hemoperfusion, which involves packing the ion exchange compositions described above into a column through which blood is flowed. One such system is described in U.S. Patent No. 4,261,828. As described in the '828 patent, the ion exchange compositions are preferably formed into a desired shape, such as a sphere. Additionally, the ion exchange composition particles can be coated with a compound, such as a cellulose derivative, which is compatible with blood but impermeable to the blood cell components. In one particular case, the spheres of the desired ion exchange compositions described above can be packed into hollow fibers, thus providing a semipermeable membrane. It should also be noted that more than one type of ion exchange composition can be mixed and used in the method to enhance the efficiency of the method.

[0035] Another way to perform the method is by preparing a suspension or slurry of the molecular sieve adsorbent by means known in the art, such as described in U.S. Patent No. 5,536,412. The apparatus described in the '412 patent can also be used to perform the method. The method essentially involves passing a fluid containing metal toxins (e.g., blood) through the interior of a hollow fiber and circulating an adsorbent suspension through the outer surface of the hollow fiber membrane during said passing. Simultaneously, intermittent pulses of positive pressure are applied to the adsorbent solution such that the fluid alternately exits and re-enters the interior of the hollow fiber membrane, thereby removing toxins from the fluid.

[0036] Another type of dialysis is peritoneal dialysis. In peritoneal dialysis, the peritoneal cavity or abdomen (belly) is filled via a catheter inserted into the peritoneal cavity with a dialysis fluid or solution that contacts the peritoneum. Toxins and excess water flow from the blood through the peritoneum into the dialysis fluid, which is a membrane that surrounds the organs outside the belly. The dialysis fluid is kept in the body for a time sufficient to remove toxins (dwell time). After the desired dwell time, the dialysis fluid is removed from the peritoneal cavity through the catheter. There are two types of peritoneal dialysis. In continuous ambulatory peritoneal dialysis (CAPD), dialysis is performed throughout the day. This method involves keeping a dialysis solution in the peritoneal cavity and periodically removing spent dialysis fluid (containing toxins) and refilling the cavity with fresh dialysis solution. This is done several times during the day. The second type is automated peritoneal dialysis or APD. In APD, the dialysis solution is exchanged through a device at night while the patient is sleeping. In both types of dialysis, a fresh dialysis solution must be used for each exchange.

[0037] The rare earth silicate ion exchanger of the present invention can be used to regenerate the dialysis fluid solution used in peritoneal dialysis, thereby further reducing the amount of dialysis fluid required to clean the blood and / or the amount of time required to perform the exchange. This regeneration is performed by any of the above-described means for conventional dialysis. For example, in the indirect contact method, the dialysis fluid from the peritoneal cavity (i.e., the first dialysis fluid that has absorbed the metal toxins transferred across the peritoneum) is now contacted with the membrane and a second dialysis solution and metal toxins are transferred across the membrane, thereby purifying the first dialysis solution, i.e., the purified dialysis solution. The second dialysis solution containing the metal toxins is flowed through at least one adsorbent bed containing at least one of the ion exchangers described above, thereby removing the metal toxins and producing a purified second dialysis solution. It is generally preferred that the second dialysis solution be continuously circulated through the adsorbent bed until the toxic metal ions (i.e., Pb 2+ , Hg 2+ , K + , or NH4 + ) have been removed. It is also preferred that the first dialysis solution be circulated through the peritoneal cavity, thereby increasing the toxic metal removal efficiency and reducing the overall dwell time.

[0038] A direct contact method can also be performed in which a first dialysate solution is introduced into the peritoneal cavity and then flowed through at least one bed containing at least one ion exchanger. As noted above, this can be performed as CAPD or APD. The composition of the dialysate solution can be varied in order to ensure proper electrolyte balance in the body. This, along with the various apparatuses used to perform dialysis, are well known in the art.

[0039] Rare earth silicate ion exchangers can also be formed into pills or other shapes that can be ingested orally and absorb toxins in the gastrointestinal fluids as the ion exchanger passes through the intestines and is eventually excreted. In order to protect the ion exchanger from the high acid content of the stomach, the shaped article can be coated with various coatings that will not dissolve in the stomach but will dissolve in the intestines.

[0040] As has also been stated, although the compositions of the present invention are synthesized with a variety of exchangeable cations ("A"), it is preferred that the exchangeable cations be secondary cations (A') that are more compatible with blood or do not adversely affect blood. For this reason, the preferred cations are sodium, calcium, hydronium, and magnesium. The preferred compositions are those containing sodium and calcium or sodium, calcium, and hydronium ions. The relative amounts of sodium and calcium can vary significantly and depend on the concentrations of these ions in the composition and blood.

[0041] The x-ray patterns presented in the following examples were obtained using standard x-ray powder diffraction techniques. The irradiation source was a high intensity x-ray tube operating at 45 kV and 35 mA. The diffraction pattern from the copper K-alpha irradiation was obtained by suitable computer-based techniques. Flat, compressed powder samples were scanned continuously from 2° to 70° (2 theta). The interplanar spacing (d) was obtained from the position of the diffraction peaks expressed as theta, where theta is the Bragg angle as observed from the digitized data. Intensity was determined from the integrated area of the diffraction peak after background subtraction, "I" is the intensity of the strongest line or peak, and "I" is the intensity of each of the other peaks. o

[0042] As will be appreciated by those skilled in the art, the determination of the parameter 2 theta is subject to both human and mechanical error, the combination of which can impart an uncertainty of ±0.4° to each reported value of 2 theta. This uncertainty is of course also embodied in the reported d-spacing values, which are calculated from the 2 theta values. This imprecision is ubiquitous in the art and is insufficient to eliminate the differentiation of the crystalline materials of the present invention from one another and from the compositions of the prior art. In the reported x-ray patterns, the relative intensities of the d-spacings are indicated by the symbols vs, s, m, and w, which stand for very strong, strong, medium, and weak, respectively. According to 100 x I / I o The above nomenclature is defined as:

[0043] ​w > 0 - 15, m > 15 - 60: s > 60 - 80 and vs > 80 - 100.

[0044] In certain instances, the purity of a synthetic product can be assessed with reference to its x-ray powder diffraction pattern. Thus, for example, if a sample is described as pure, it is intended only to mean that the x-ray pattern of the sample contains no lines attributable to crystalline impurities, not that there is no amorphous material present.

[0045] In order to more fully illustrate the application, the following examples are set forth. It is to be understood that these examples are merely illustrative of the application and are not intended to limit the broad scope of the application as set forth in the appended claims.

[0046] Example

[0047] Example 1 : Sodium Ytterbium Silicate

[0048] In a 250 mL beaker equipped with a high speed overhead stirrer, 9.71 g of NaOH pellets (98%) were dissolved in 25.00 g of deionized water. To this solution was added 20.25 g of colloidal silica (Ludox AS-40, 40% Si02) and stirred vigorously for 60 minutes. Separately, 5.25 g of YbCl3-6H2O (99.9%) was dissolved in 125.00 g of deionized water containing 3.75 g of concentrated H2SO4, resulting in a clear solution. The solution containing the digested Si02 was then added dropwise to the YbCl3-6H2O solution while using the overhead stirrer to stir vigorously at 400 RPM, resulting in a uniform white reaction mixture. After stirring for 30 minutes, the reaction mixture was then transferred to a 45 cc autoclave and digested at 200 °C under static conditions for 4 days. After cooling to room temperature, the product was isolated by centrifugation. The sample was then re-dispersed in deionized water and then centrifuged again, and this process was repeated twice. The final product was then dried at 100 °C overnight.

[0049] Chemical analysis of the product gave an empirical formula of Na 3.72 YbSi 7.78 O 18.93 and its powder x-ray diffraction pattern was characterized by the representative diffraction lines listed in Table 1.

[0050] Table 1

[0051]

[0052]

[0053] Example 2: Sodium Yttrium Silicate

[0054] In a 250 mL beaker equipped with a high speed overhead stirrer, 4.85 g of NaOH pellets (98%) were dissolved in 12.50 g of deionized water. To this solution was added 10.13 g of colloidal silica (Ludox AS-40, 40% Si02) and stirred vigorously for 60 minutes. Separately, 2.59 g of Y(N03)3-6H20 (99.9%) was dissolved in 62.50 g of deionized water containing 1.88 g of concentrated H2S04, resulting in a clear solution. The solution containing the digested Si02 was then added dropwise to the Y(N03)3-6H20 solution while stirring vigorously using the overhead stirrer at 400 RPM, resulting in a uniform white reaction mixture. After stirring for 30 minutes, the reaction mixture was then transferred to a 45 cc autoclave and digested at 200 °C under static conditions for 4 days. After cooling to room temperature, the product was isolated by centrifugation. The sample was then re-dispersed in deionized water and then centrifuged again, and this process was repeated twice. The final product was then dried at 100 °C overnight.

[0055] Chemical analysis of the product gave an empirical formula of Na 3.66 YSi 7.83 O 18.99 and its powder X-ray diffraction pattern was characterized by the representative diffraction lines listed in Table 2.

[0056] Table 2

[0057]

[0058] Example 3: Sodium Erbium Silicate

[0059] In a 250 mL beaker equipped with a high speed overhead stirrer, 5.80 g of NaOH pellets (98%) were dissolved in 18.07 g of deionized water. To this solution was added 12.16 g of colloidal silica (Ludox AS-40, 40% Si02) and stirred vigorously for 60 minutes. Separately, 3.10 g of ErCl3-6H20 (99.9%) was dissolved in 78.02 g of deionized water containing 2.25 g of concentrated H2S04, resulting in a clear solution with a faint red tint. The solution containing the digested Si02 was then added dropwise to the ErCl3-6H20 solution while stirring vigorously using the overhead stirrer at 400 RPM, resulting in a uniform reaction mixture with a faint red tint. After stirring for 30 minutes, the reaction mixture was then transferred to a 45 cc autoclave and digested at 200 °C under static conditions for 4 days. After cooling to room temperature, the product was isolated by centrifugation. The sample was then re-dispersed in deionized water and then centrifuged again, and this process was repeated twice. The final product was then dried at 100 °C overnight.

[0060] Chemical analysis of the product gave the empirical formula Na 3.71 ErSi 8.02 O 21.90 and its powder X-ray diffraction pattern was characterized by the representative diffraction lines listed in Table 3.

[0061] Table 3

[0062]

[0063] Example 4: K + Exchanged ytterbium silicate

[0064] The product described in this example was synthesized by ion exchange to produce the potassium form of the product described in Example 1. 2 g of the product described in Example 1 was dispersed in 100 mL of deionized water followed by the addition of 200 mL of a 2 M KCl solution. The mixture was stirred at 50 °C for 2 hours followed by cooling. The resulting solid was collected by centrifugation and the process was repeated twice. The final product was washed three times and dried at 100 °C overnight.

[0065] The powder X-ray diffraction pattern of the product was characterized by the representative diffraction lines shown in Table 4.

[0066] Table 4

[0067]

[0068] Example 5: K + Exchanged yttrium silicate

[0069] The product described in this example was synthesized by ion exchange to produce the potassium form of the product described in Example 2. 2 g of the product described in Example 2 was dispersed in 100 mL of deionized water followed by the addition of 200 mL of a 2 M KCl solution. The mixture was stirred at 50 °C for 2 hours followed by cooling. The resulting solid was collected by centrifugation and the process was repeated twice. The final product was washed three times and dried at 100 °C overnight.

[0070] Chemical analysis of the product gave the empirical formula K 2.65 YSi 5.72 O 14.27 and its powder X-ray diffraction pattern was characterized by the representative diffraction lines listed in Table 5.

[0071] Table 5

[0072]

[0073]

[0074] Example 6: Tin-doped Sodium Ytterbium Silicate

[0075] The tin-doped version of Example 1 was prepared as follows. In a 250 mL beaker equipped with a high speed overhead stirrer, 6.45 g of NaOH pellets (98%) were dissolved in 20.13 g of deionized water. To this solution was added 13.49 g of colloidal silica (Ludox AS-40, 40% Si02) and stirred vigorously for 60 minutes. Separately, 3.19 g of YbCl3-6H2O (99.9%) was dissolved in 80.10 g of deionized water containing 2.43 g of concentrated H2SO4, resulting in a clear solution. The solution containing digested Si02 was then added dropwise to the YbCl3-6H2O solution while using the overhead stirrer to stir vigorously at 400 RPM, resulting in a uniform white reaction mixture. After stirring for 1 hour, 0.18 g of SnCl4-5H2O was added and the reaction solution was stirred for an additional hour. The resulting reaction mixture was then transferred to a 45 cc autoclave and digested at 200 °C for 4 days under static conditions. After cooling to room temperature, the product was isolated by centrifugation. The sample was then re-dispersed in deionized water and then centrifuged again, and this process was repeated twice. The final product was then dried at 100 °C overnight.

[0076] Analysis of the product using a scanning electron microscope equipped with energy dispersive X-ray spectroscopy showed a uniform distribution of Sn in the material. Chemical analysis of the product gave an empirical formula of Na 5.00 Yb 0.73 Sn 0.27 Si 7.68 O 19.50 and its powder X-ray diffraction pattern was characterized by the representative diffraction lines listed in Table 6.

[0077] Table 6

[0078]

[0079]

[0080] Example 7: Potassium Ytterbium Silicate

[0081] In a 250 mL beaker equipped with a high speed overhead stirrer, 16.07 g of KOH pellets (86%) were dissolved in 26.37 g of deionized water. To this solution was added 42.93 g of colloidal silica (Ludox AS-30, 30% Si02) and stirred vigorously for 30 minutes. Separately, a second solution was prepared by dissolving 5.29 g of YbCl3-6H20 (99%) in 8.33 g of deionized water, which was then added dropwise while stirring. The reaction mixture was stirred vigorously for 2.5 hours, and then transferred to a high speed mixer where it was homogenized for 1 minute. The mixture was then transferred to a 45 cc autoclave and digested at 200 °C under static conditions for 5 days. After cooling to room temperature, the product was isolated by centrifugation, washed with deionized water, and then dried at 100 °C overnight.

[0082] Chemical analysis of the product gave an empirical formula of K 3.67 YbSi 7.89 O 19.11 and its powder X-ray diffraction pattern was characterized by the data given in Table 7.

[0083] Table 7

[0084]

[0085]

[0086] Example 8: Sodium Cerium Silicate

[0087] In a 250 mL beaker equipped with a high speed overhead stirrer, 19.41 g of NaOH pellets (98%) were dissolved in 50.50 g of deionized water. To this solution was added 40.51 g of colloidal silica (Ludox AS-40, 40% Si02) and stirred vigorously for 60 minutes. Separately, 8.98 g of Ce(S04)2(99.9%) was dissolved in 250.40 g of deionized water containing 7.50 g of concentrated H2S04, resulting in a bright orange solution. The solution containing the digested Si02 was then added dropwise to the Ce(S04)2solution while stirring vigorously using an overhead stirrer at 400 RPM, resulting in a uniform white reaction mixture. After stirring for 60 minutes, the reaction mixture was then transferred to a 45 cc autoclave and digested at 200 °C under static conditions for 4 days. After cooling to room temperature, the product was isolated by centrifugation, washed with deionized water, and then dried at 100 °C overnight.

[0088] The oxidation state of Ce in the resulting product was analyzed using X-ray absorption near-edge spectroscopy (XANES), which indicated that essentially all of the cerium atoms were in the +4 oxidation state (Ce 4+). Chemical analysis of the product gave an empirical formula of Na 1.24 CeSi 3.68 O 9.98 and its powder X-ray diffraction pattern is characterized by the data given in Table 8.

[0089] Table 8

[0090]

[0091]

[0092] Example 9: NH4 + - exchanged cerium silicate

[0093] The product described in the following examples was synthesized by ion exchange of the product of Example 9 to produce the ammonium form. 3 g of the product described in Example 9 was dispersed in 250 mL of a 2 M NH4C1 exchange solution. Three ion exchanges were performed at 50 °C, 2 hours for each exchange step. The exchanged solid was separated by centrifugation, washed with deionized water and then dried at 100 °C overnight. The powder X-ray diffraction pattern of the product is characterized by the representative diffraction lines shown in Table 9.

[0094] Table 9

[0095]

[0096] Example 10: Removal of Pb from solution 2+ and Hg 2+ ions

[0097] The samples disclosed in Examples 1-9 were tested to determine their ability to selectively adsorb Pb 2+ and Hg 2+ ions from a solution that also contained essential electrolytes found in vivo, including Na, K, Mg and Ca. The test solution was prepared by dissolving sodium nitrate, potassium nitrate, magnesium nitrate, calcium nitrate and lead nitrate (or mercury nitrate) in a sodium acetate buffered solution. The buffered solution was used to maintain a constant pH of 4.7 and 1 L of the buffered solution was prepared by dissolving 4.18 g of sodium acetate and 2.49 g of acetic acid in 1 L of deionized water. The test solution was first analyzed by ICP and it contained 3000 ppm Na + , 300 ppm K + , 25 ppm Mg 2 + , 25 ppm Ca 2+ and 200 ppb Pb 2+ (or 200 ppb Hg 2+concentration of the cation of interest. For this test, 100 mg of rare earth silicate ion exchanger was placed in a 125 mL plastic bottle with 100 mL of test solution. The capped bottle was rolled at room temperature for 2 hours. Once the ion exchanger was in contact with the test solution for the desired amount of time, the solid / solution suspension was passed through a 0.2 μιη syringe filter to remove solids and then the solution was analyzed using ICP. The K d value for the distribution of a metal between the solution and the solid was calculated using the following equation:

[0098]

[0099] Where: V = volume of waste mimic (mL)

[0100] Ac = concentration of cations adsorbed on the ion exchanger (g / mL)

[0101] W = mass of ion exchanger being evaluated (g)

[0102] Sc = concentration of cations in the supernatant after reaction (g / mL)

[0103] The results of the Pb 2+ and Hg 2+ uptake studies are summarized in Tables 10 and 11, respectively. Data left blank in the tables indicate that there was no statistically significant change or increase in the electrolyte concentration due to the release of cations from the rare earth ion exchanger. The criteria for inclusion of an ion exchanger in this patent application is that it must remove at least 75% of the heavy metal (Pb 2+ , Hg 2+ ) while not removing more than 10% of the other electrolytes in the test solution.

[0104] Table 10

[0105] Pb 2+ , Na + , K + , Mg 2+ , Ca 2+ uptake is expressed as a K d value (mL / g).

[0106]

[0107]

[0108] Table 11 Hg 2+ , Na + , K + , Mg 2+ , Ca 2+ uptake is expressed as a K d value (mL / g).

[0109]

[0110] Example 12: Removal of K from solution + and NH4 + ions

[0111] The samples disclosed in Examples 1-9 were tested to determine their ability to selectively adsorb K + and NH4 + ions from a simulated dialysate solution containing essential electrolytes found in vivo, including Mg and Ca. The test solution was prepared by dissolving sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, and ammonium chloride in 1 L of a 40 mM (mM = millimolar) sodium bicarbonate solution. The test solution was first analyzed by aqueous cation liquid chromatography and contained concentrations of 507 ppm NH4 + , 109 ppm K + , 3053 ppm Na + , 37 ppm Ca 2+ , and 9.5 ppm Mg 2+ . For the test, 100 mg of rare earth silicate ion exchanger was placed in a 20 mL plastic vial with 20 mL of the dialysate solution. The vial was then tumbled at room temperature for 2 hours. Once the ion exchanger was in contact with the test solution for the desired amount of time, the solid / solution suspension was passed through a 0.2 pm syringe filter to remove the solids, and then the solution was analyzed using aqueous liquid chromatography.

[0112] Table 11 and Table 12 summarize the results of the uptake studies, showing the change in cation concentration (in ppm) and the amount of cations taken up by each material (in mmol / g basis), respectively.

[0113] Table 11 NH4 + , K + , Mg 2+ , Ca 2+ uptake summary

[0114]

[0115] Table 12

[0116] NH4 + , K + , Mg 2+ , Ca 2+ uptake in mmol cation / g material

[0117]

[0118] Specific Embodiments

[0119] While the following is described in conjunction with the specific embodiments, it will be understood that it is intended to cover not only this description but also the preceding description and the accompanying claims.

[0120] A first embodiment of the present invention is a method for removing Pb 2+ , Hg 2+ , K + , and NH4 + toxins or mixtures thereof from a body fluid, the method comprising contacting a fluid containing the toxins with an ion exchanger to remove the toxins from the fluid by ion exchange between the ion exchanger and the body fluid, the ion exchanger being a rare earth silicate composition having an empirical formula on an anhydrous basis of A r+ p M s+ 1-x M ’t+ x Si n O m wherein A is an exchangeable cation selected from the group consisting of alkali metals, alkaline earth metals, hydronium ions, ammonium ions, quaternary ammonium ions, and mixtures thereof, "r" is a weighted average valence of A and varies from 1 to 2, "p" is a mole ratio of A to total metal elements (total metal elements = M + M') and varies from 1 to 5, "M" is a framework rare earth metal selected from the group consisting of scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium, and mixtures thereof, "s" is a weighted average valence of M and varies from 3 to 4, "1 - x" is a mole fraction of total metal elements that are M, M' is a framework metal having a valence of +2, +3, +4, or +5, "t" is a weighted average valence of M' and varies from 2 to 5, "x" is a mole fraction of total metal elements that are M' and varies from 0 to 0.99, "n" is a mole ratio of Si to total metal elements and has a value of 3 to 10, and "m" is a mole ratio of O to total metal elements and is given by the formula One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein the body fluid is selected from the group consisting of: whole blood, plasma or other components of blood, gastrointestinal fluid, and dialysate solutions containing blood, plasma, other components of blood, or gastrointestinal fluid. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein x = 0. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein A is a mixture of calcium and one alkali metal. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein A is not potassium. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein A is not ammonium. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein the ion exchanger is packed into hollow fibers incorporated into a membrane. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein the ion exchanger is contained on particles coated with a coating comprising a cellulose derivative composition. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein the method is a hemoperfusion method in which the body fluid is passed through a column containing the ion exchanger. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein the dialysate solution is introduced into a peritoneal cavity and then flowed through at least one adsorbent bed containing at least one of the ion exchangers. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein the ion exchanger is formed into a shaped article for oral ingestion, then ion exchanges between the ion exchanger and Pb 2+ , Hg 2+ , K + , and NH4 + toxins contained in the gastrointestinal fluid contained in the mammal's intestines, and then excreted. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the first embodiment in this paragraph, wherein the shaped article is coated with a coating that is insoluble under gastric conditions.

[0121] A second embodiment of the application is a composition comprising a combination of a body fluid, a dialysate solution, or a mixture of a body fluid and a dialysate solution, the combination further comprising an ion exchanger having an empirical formula on an anhydrous basis of A r+p M s+ 1-x M ’t+ x Si n O m A rare earth silicate ion exchanger, wherein A is an exchangeable cation selected from alkali metals, alkaline earth metals, hydrated hydrogen ions, ammonium ions, quaternary ammonium ions, and mixtures thereof; "r" is the weighted average valence of A, varying between 1 and 2; "p" is the molar ratio of A to total metal elements (total metal elements = M + M'), varying between 1 and 5; "M" is a framework rare earth metal selected from scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium, and mixtures thereof; and "s" is a cation exchanger for rare earth silicates. "t" is the weighted average valence of M, varying between 3 and 4; "1-x" is the mole fraction of total metallic elements in M; M' is a framework metal with valences of +2, +3, +4, or +5; "t" is the weighted average valence of M', varying between 2 and 5; "x" is the mole fraction of total metallic elements in M', varying between 0 and 0.99; "n" is the mole ratio of Si to total metallic elements, ranging from 3 to 10; and "m" is the mole ratio of O to total metallic elements, given by the following formula. One embodiment of the invention is one, any or all of the embodiments described in the preceding embodiments of this paragraph up to the second embodiment of this paragraph, wherein the body fluid is whole blood, plasma, other blood components or gastrointestinal fluid.

[0122] A third embodiment of the invention is a device comprising a matrix containing a support material for a rare earth silicate ion exchanger having an anhydrous empirical formula A. r+ p M s+ 1-x M ’t+ x Si n O mwherein A is an exchangeable cation selected from the group consisting of alkali metals, alkaline earth metals, hydronium ions, ammonium ions, quaternary ammonium ions, and mixtures thereof, "r" is the weighted average valence of A and varies between 1 and 2, "p" is the molar ratio of A to the total metal elements (total metal elements = M + M') and varies between 1 and 5, "M" is a framework rare earth metal selected from the group consisting of scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium, and mixtures thereof, "s" is the weighted average valence of M and varies between 3 and 4, "1 - x" is the mole fraction of the total metal elements that are M, M' is a framework metal having a valence of +2, +3, +4, or +5, "t" is the weighted average valence of M' and varies between 2 and 5, "x" is the mole fraction of the total metal elements that are M' and varies between 0 and 0.99, "n" is the molar ratio of Si to the total metal elements and has a value of 3 to 10, and "m" is the molar ratio of O to the total metal elements and is given by the formula One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the third embodiment in this paragraph, wherein the matrix comprises a porous network comprising a biocompatible polymer and a metal oxide and a silicate. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the third embodiment in this paragraph, wherein the biocompatible polymer comprises a cross-linked carbohydrate or a protein. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the third embodiment in this paragraph, wherein the biocompatible polymer is a polysaccharide selected from alpha-glucans having 1,3-, 1,4- or 1,6- linkages. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the third embodiment in this paragraph, wherein the biocompatible polymer is a carbohydrate selected from the group consisting of glucose, fructose, sucrose, maltose, arabinose, mannose, galactose, lactose, and oligomers and polymers comprising one or more of the carbohydrates. One embodiment of the application is one, any or all of the preceding embodiments in this paragraph up to the third embodiment in this paragraph, wherein the biocompatible polymer comprises a protein selected from the group consisting of albumin, ovalbumin, casein, myosin, actin, globulin, hemoglobin, myoglobin, gelatin, and small peptides.

[0123] Although no further detailed description has been provided, it is believed that those skilled in the art will be able to make full use of the invention by employing the foregoing description and will be able to readily identify the essential features of the invention without departing from its spirit and scope, and to make various changes and modifications to adapt it to various uses and situations. Therefore, the foregoing preferred embodiments should be understood as illustrative only and not as limiting the remainder of this disclosure in any way, and are intended to cover various modifications and equivalent arrangements included within the scope of the appended claims.

[0124] In the foregoing, all temperatures are expressed in degrees Celsius, and all portions and percentages are by weight unless otherwise specified.

Claims

1. A method for removing Pb from body fluids 2+ Hg 2+ K + and NH4 + A method for removing toxins or mixtures thereof, the method comprising contacting a fluid containing the toxin with an ion exchanger to remove the toxin from the fluid by ion exchange between the ion exchanger and the body fluid, the ion exchanger being a rare earth silicate composition having an anhydrous empirical formula: And r+ p M s+ 1-x M' t+ x You n About m Where A is an exchangeable cation selected from alkali metals, alkaline earth metals, hydrated hydrogen ions, ammonium ions, quaternary ammonium ions, and mixtures thereof; "r" is the weighted average valence of A, varying between 1 and 2; "p" is the molar ratio of A to the total metallic elements (total metallic elements = M + M'), varying between 1 and 5; "M" is a framework rare earth metal selected from scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium, and mixtures thereof; and "s" is... The weighted average valence of M varies between 3 and 4, "1-x" is the mole fraction of total metallic elements in M, M' is a framework metal with valences of +2, +3, +4, or +5, "t" is the weighted average valence of M' varies between 2 and 5, "x" is the mole fraction of total metallic elements in M' and is 0, "n" is the mole ratio of Si to total metallic elements and has a value between 3 and 10, and "m" is the mole ratio of O to total metallic elements and is given by the following formula.

2. The method according to claim 1, wherein A is a mixture of calcium and an alkali metal.

3. The method according to claim 1, wherein A is not potassium or ammonium.

4. The method of claim 1, wherein the ion exchanger is filled into hollow fibers, the hollow fibers being incorporated into a membrane or contained on particles coated with a coating comprising a cellulose derivative composition.

5. The method of claim 1, wherein the method is a hemoperfusion method, wherein the body fluid passes through a column containing the ion exchanger.

6. The method of claim 1, wherein the dialysate solution is introduced into the peritoneal cavity and then flows through at least one adsorbent bed containing at least one of the ion exchangers.

7. The method of claim 1, wherein the ion exchanger is formed into a shaped article for oral ingestion, and then the Pb in the ion exchanger is reacted with gastrointestinal fluid contained in the mammalian intestine. 2+ Hg 2+ K + and NH4 + The toxins exchange ions with each other and then excrete the ion exchanger containing the toxins.

8. A composition comprising a combination of a body fluid, a dialysate solution, or a mixture of the body fluid and the dialysate solution, the combination further comprising a rare earth silicate ion exchanger having an empirical formula on an anhydrous basis: And r+ p M s+ 1-x M' t+ x You n About m Where A is an exchangeable cation selected from alkali metals, alkaline earth metals, hydrated hydrogen ions, ammonium ions, quaternary ammonium ions, and mixtures thereof; "r" is the weighted average valence of A, varying between 1 and 2; "p" is the molar ratio of A to the total metallic elements (total metallic elements = M + M'), varying between 1 and 5; "M" is a framework rare earth metal selected from scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium, and mixtures thereof; and "s" is... The weighted average valence of M varies between 3 and 4, "1-x" is the mole fraction of total metallic elements in M, M' is a framework metal with valences of +2, +3, +4, or +5, "t" is the weighted average valence of M' varies between 2 and 5, "x" is the mole fraction of total metallic elements in M' and is 0, "n" is the mole ratio of Si to total metallic elements and has a value between 3 and 10, and "m" is the mole ratio of O to total metallic elements and is given by the following formula.

9. An apparatus comprising a matrix containing a support material for a rare earth silicate ion exchanger, the rare earth silicate ion exchanger having an anhydrous empirical formula: And r+ p M s+ 1-x M' t+ x You n About m Where A is an exchangeable cation selected from alkali metals, alkaline earth metals, hydrated hydrogen ions, ammonium ions, quaternary ammonium ions, and mixtures thereof; "r" is the weighted average valence of A, varying between 1 and 2; "p" is the molar ratio of A to the total metallic elements (total metallic elements = M + M'), varying between 1 and 5; "M" is a framework rare earth metal selected from scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium, and mixtures thereof; and "s" is... The weighted average valence of M varies between 3 and 4, "1-x" is the mole fraction of total metallic elements in M, M' is a framework metal with valences of +2, +3, +4, or +5, "t" is the weighted average valence of M' varies between 2 and 5, "x" is the mole fraction of total metallic elements in M' and is 0, "n" is the mole ratio of Si to total metallic elements and has a value between 3 and 10, and "m" is the mole ratio of O to total metallic elements and is given by the following formula.

10. The device of claim 9, wherein the matrix comprises a porous network containing a biocompatible polymer and metal oxides and silicates, wherein the biocompatible polymer comprises cross-linked carbohydrates or proteins.

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