Method for removing Pb2 + ions from body fluids using metal titanate ion exchangers

Abstract

A method for removing Pb2 + ions from a fluid, such as a gastrointestinal tract fluid, is described. The method comprises contacting the gastrointestinal tract fluid with a particulate metal titanate ion exchanger represented by the empirical formula: AmTixMyOz wherein A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrogen hydrate ions, and mixtures thereof, and M is optionally at least one framework metal selected from niobium (5 +), zirconium (4 +), tin (4 +), iron (3 +), iron (2 +), cobalt (2 +) and manganese (2 +). The particulate metal titanate ion exchangers of the present disclosure are synthesized in the presence of complexing agents including at least one polyhydroxy-containing complexing agent (MHCA) that promote metal transport and incorporation while conferring beneficial properties such as large aggregate sizes, exhibiting good particle size distribution, and large porosity.

Description

Technical Field

[0001] This disclosure relates to the removal of Pb from body fluids, particularly gastrointestinal fluids, using particulate metal titanate ion exchangers. 2+ An in vivo approach to ion exchange involves directly contacting a gastrointestinal fluid with a particulate metal titanate ion exchanger composition, which removes Pb present in the fluid. 2+ Toxins. This disclosure also relates to particulate metal titanate ion exchangers synthesized in the presence of complexing agents including at least one polyhydroxy complexing agent (MHCA), which promote metal incorporation and impart favorable properties, including large aggregate size, more uniform particle size distribution and high porosity. Background Technology

[0002] Lead has only been widely distributed in the biosphere in the last few millennia, entirely as a result of human activity. Once introduced into the environment, lead persists. Studies of human skeletal remains have shown that the lead burden on the bodies of today's population is 500 to 1000 times greater than that of pre-industrial populations (see *The New England Journal of Medicine*, Vol. 326, No. 19, pp. 1293–1294, 1992). To date, the largest contributor to global environmental lead pollution has been the use of lead in gasoline, primarily between 1965 and 1990 (see *Environment and Health Perspective*, Vol. 110, No. 7, pp. 721–728, 2002). As lead is now being removed from gasoline in developed countries, blood lead levels (BLL) in the United States and worldwide are projected to continue to decline slowly (see *American Journal of Medicine*, Vol. 129, pp. 1213–1218, 2016). However, hotspots from smelting, mining, old housing, water pipes, highways, and metal recycling operations (some of which are ongoing, while others are legacies from the past) remain significant issues.

[0003] Despite a century of accumulated evidence of the harmful effects of lead on children's health, lead continues to be commonly added to paints, pigments, toys, traditional medicines, cosmetics, and other consumer products, especially as manufacturing shifts to developing countries lacking environmental and product content controls and policies. Dust from lead-based paints remains a significant source of exposure (see *Journal of Pediatrics*, Vol. 140, No. 1, pp. 40–47, 2002). Soils in old urban areas are often heavily contaminated with lead due to past use of lead additives in gasoline and industrial sources.

[0004] Soil is not a passive source, and the periodic resuspension of fine lead-contaminated soil dust particles contributes to the seasonal variation in lead exposure among urban residents (see *Atmos. Environ.*, Vol. 49, pp. 302–310, 2012). Furthermore, there is a coupling between inhaled and ingested lead. Inhalation studies examining lead particles (approximately 1 μm) deposited at the back of the nose have demonstrated that they are typically swallowed over time. Additionally, particles deposited in the tracheobronchial region can be cleared from the lungs via the mucociliary escalator and reach the gastrointestinal system via the esophagus (see *Radiat. Prot. Dosim.*, Vol. 127, pp. 31–34, 2007).

[0005] Lead-contaminated water was brought to Flint, Michigan, through changes in water supply using old, contaminated infrastructure, where significant increases in blood lead (BLL) levels were observed in children (see *American Journal of Public Health*, Vol. 106, No. 2, pp. 283–290, 2016). A 2018 report by the Natural Resources Defense Council details how many other communities across the country are unable to adequately ensure their water supply remains lead-free (see E. Olson and KP Fedinick, *Natural Resources Defense Council*, New York, NY, 2016). Experts estimate that the United States is using 6 to 10 million lead-in-line pipes to serve 15 to 22 million Americans, most of which were installed at least 50 years ago (see J. Am. Water Works Assoc., Vol. 108, No. 4, pp. E182-E191, 2016).

[0006] Lead is highly toxic and can damage the brain, kidneys, bone marrow, and other bodily systems, especially in young children. The Third National Health and Nutrition Examination Survey (NHANES III, Phase 2, 1991–1994) found that 4.4% of children under the age of six in the United States had a BLL higher than 10 µg / dL, a level considered “poisonous.” (See “Eliminating Childhood Lead Poisoning: A Federal Strategy Targeting Lead Paint Hazards”; Presidential Working Group on Childhood Environmental Health and Safety Risks, February 2000). Exposure to lead paint was the primary culprit, with a greater impact on children living in older homes and low-income families, where 16% of these children were poisoned compared to the national average of 4.4% (see Morbidity and Mortality Weekly Report, U.S. Department of Health and Human Services / Public Health Service, Vol. 46, No. 7, February 21, 1997, pp. 141-146).

[0007] With increasing blood lead levels (BLL) in children, the adverse effects and morbidity associated with lead poisoning increase, including decreased IQ, hearing loss, and slowed growth. Furthermore, behavioral problems can be observed in children with BLL = 10 µg / dL, neurological impairment may occur at BLL = 20 µg / dL, reduced vitamin C metabolism may occur at BLL = 30 µg / dL, impaired hematopoietic function may occur at BLL = 40 µg / dL, severe gastric cramps may occur at BLL above 50 µg / dL, and severe brain and kidney damage and severe anemia may occur at BLL between 50 µg / dL and 100 µg / dL. Even low levels of elevated blood lead levels in children, such as below 5 μg / dL, can lead to a decline in cognitive function, as measured by IQ scores and academic performance (see Public Health Reports, Vol. 115, pp. 521–529, 2000; and Environment and Health Perspectives, Vol. 113, pp. 894–899, 2005).

[0008] For a given exposure level, lead-related IQ loss was proportionally greater at the lowest blood lead concentrations. While the mean IQ drop associated with an increase in blood lead concentration from <1 μg / dL to 30 μg / dL was 9.2 IQ points, the drop associated with an increase from <1 μg / dL to 10 μg / dL was 6.2 IQ points. The demographic impact of lead on intellectual ability is enormous, as lead toxicity results in an estimated total loss of 23 million IQ points in a cohort of U.S. children aged 6 years (see Environmental and Health Perspectives, Vol. 120, pp. 501–507, 2012). An inverse relationship was also found between early childhood lead exposure and performance on cognitive and behavioral tests at 10 and 20 years after blood lead levels were measured (see Pediatrics, Vol. 90, pp. 855–861, 1992). In addition, early exposure is associated with increased rates of ADHD, attention deficit, failure to graduate from high school, conduct disorder, juvenile delinquency, substance use, and incarceration (see PLoS Medicine, Vol. 5, p. e101, 2008).

[0009] In contrast to kidney damage, a study examining NHANES III (1988–1994) data reported that doubling of blood lead concentration led to a significant decrease in glomerular filtration rate in 769 adolescents with a median blood lead concentration of 1.5 μg / dL (15 ppb) (see Arch Intern Med., Vol. 170, pp. 75–82, 2010).

[0010] Numerous experimental and epidemiological studies have demonstrated that lead exposure is a risk factor for cardiovascular disease (CVD) and mortality. While a BLL level of 5 μg / dL in adults is considered elevated, recent studies have concluded that low levels of environmental lead exposure (i.e., <5 μg / dL) are a risk factor for CVD mortality (see *Lancet Public Health*, Vol. 3, pp. e177–184, 2018). The authors tracked NHANES III participants (1988–1994) until 2011 (approximately 14,000 adults) and examined the relationship between lower levels of lead in BLL as low as 1 μg / dL and CVD and ischemic heart disease mortality. Data analysis suggests that approximately 400,000 deaths annually in the United States are attributable to lead exposure in subjects with cardiovascular disease and / or diabetes, highlighting the potential risk factor of adult BLL concentrations in the 1–5 μg / dL range.

[0011] Chelation therapy has been used to remove lead from the blood. The best chelating agents should increase lead excretion, be easy to administer, affordable, and safe. However, lead chelates can persist in the tissues where binding occurs or redistribute to other tissues. Increased symptoms commonly reported with the positive initiation of chelation therapy are cited as contraindications to the use of any chelating agent. Chelating agents effectively remove lead from the blood and are suitable for patients with acute infections and BLL greater than 45 μg / dL, and should be administered after consultation with a specialist (see *Environmental Health Perspectives*, Vol. 115, No. 3, pp. 463-471, 2007). Chelating agents used to treat lead poisoning include intravenous (IV) calcium disodium edetate (CaNa2EDTA), intramuscular dimercaprol, and oral 2,3-dimercaptosuccinic acid (DMSA, also known as dimercaptosuccinic acid).

[0012] EDTA, ethylenediaminetetraacetic acid, in the form of CaNa2EDTA, is used to chelate lead to avoid hypocalcemia and possible death due to its ability to bind calcium. It can also bind other bioavailable cations such as zinc, copper, and iron (see *Int. J. Environ. Res. Public Health*, Vol. 7, pp. 2745–2788, 2010). It is commonly used to treat severe lead poisoning and is administered intravenously in hospital settings because extensive monitoring is required, including renal function, cardiac activity, and daily venipuncture to monitor serum electrolytes. Parenteral administration of CaNa2EDTA may cause pain and swelling, while other adverse reactions include fever, nausea, vomiting, and nephrotoxicity, such as microscopic hematuria and proteinuria. CaNa2EDTA has been reported to diffuse lead into other tissues and may increase lead concentrations in the central nervous system and potentially cause encephalopathy. Following a single dose of CaNa2EDTA, urinary lead levels increased, blood lead levels decreased, and brain lead levels increased significantly due to lead redistribution to the brain.

[0013] DMSA is indicated for the treatment of acute lead poisoning with blood lead levels greater than 45 µg / dL and does not require hospitalization. Oral DMSA is typically administered at 30 mg / kg / day for 5 days (see *Med. Toxicol. Adverse Drug Exp.*, Vol. 3, pp. 499-504, 1988), usually followed by a 14-day course of 20 mg / kg / day. This regimen increases urinary lead excretion and significantly reduces blood lead levels. Drug-induced neutropenia may occur; therefore, weekly blood cell counts are recommended, and treatment should be discontinued if the neutrophil count is too low. Adverse reactions to DMSA treatment include nausea, vomiting, diarrhea, loose stools, and a metallic taste; these adverse reactions were experienced alone or together in 12% of children and 21% of adults (see US 11,083,748). Back pain, abdominal cramps, chills, and flu-like symptoms have also been reported in 5% of children and 16% of adults.

[0014] Dimercaprol, also known as the British anti-Lewis gas (BAL), was originally developed as an experimental antidote for Lewis gas (an arsenic-based poison). To administer dimercaprol to patients, it was dissolved in peanut oil and injected intramuscularly—a procedure that children did not tolerate well. Dimercaprol (a small molecule) can cross the blood-brain barrier and can be used, often in combination with CaNa2EDTA, to treat encephalopathy. The most common side effects of treatment with dimercaprol are increases in systolic and diastolic blood pressure of 50 mmHg, among others. In the 1960s, dimercaprol was modified into DMSA, which has fewer side effects, and thus became less popular for treating lead poisoning.

[0015] Chelation therapy with CaNa2EDTA, DMSA, and dimercaprol is effective in reducing blood lead levels. However, rebound in BLL often occurs after treatment, likely due to the release of absorbed lead from bone and soft tissue. Given the considerable side effects associated with chelation therapy, addressing the health problems related to low-level lead poisoning discussed above is generally not implemented.

[0016] Zeolite, a microporous aluminosilicate ion exchanger based on a tetrahedral framework, has been proposed for the treatment of chronic lead poisoning and is administered in pill form (see US 11,038,748). However, zeolite exhibits limited stability in the acidic environments of blood and the gastrointestinal tract. In acidic solutions, Al naturally possesses octahedral coordination and can be extracted from the tetrahedral zeolite framework. In fact, treatment with acidic solutions is a strategy for modifying zeolite compositions via dealumination (see US 6,982,074). Furthermore, US 11,038,748 claims protection for 90% of the particulate sodium aluminosilicate with a particle size between 90 micrometers (µm) and 150 micrometers. A method for achieving this particle size distribution is disclosed, which appears to involve sieving using a sieve. Recently, examples of microporous ion exchangers that are substantially insoluble in fluids, such as bodily fluids (especially blood), have been developed, including zirconium-based and titanium-based silicates as provided in US 5,888,472, US 5,891,417, and US 6,579,460. The use of these zirconium-based or titanium-based silicate microporous ion exchangers for removing toxic ammonium cations from blood or dialysis fluid is described in US 6,814,871, US 6,099,737, and US 6,332,985. Furthermore, some of these compositions have been found to be selective in potassium ion exchange and capable of removing potassium ions from body fluids to treat hyperkalemia, as 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; US 2016 / 0271174 and US 10,695,365. The ex vivo applications of these materials, for example, in dialysis are described in US 9,943,637. Specifically, US 8,802,152 uses zirconium silicate compositions to treat hyperkalemia via the gastrointestinal tract and identifies particles smaller than 3 micrometers as undesirable because these particles may be absorbed into the patient's bloodstream, causing adverse reactions, including accumulation in the kidneys. Sieving techniques are used to reduce or virtually eliminate particles smaller than 3 micrometers from zirconium silicate products.

[0017] Numerous ion exchangers have been developed for the removal of "heavy metals" from various environments, often waste streams. Heavy metals removed by ion exchangers typically include lead, mercury, cadmium, zinc, iron, chromium, copper, cobalt, nickel, and even arsenic. While these metals are generally considered to have similar ion exchange properties, significant variations exist in reality. For example, the removal of Pb from solution... 2+Certain zeolites may not necessarily remove Hg from solution. 2+ In fact, in US 9,233,856 (“'856 Patent”), which is incorporated herein by reference in its entirety for all purposes, it is shown that zeolites have a high affinity for Hg. 2+ The uptake is highly dependent on the framework charge density or equally dependent on the Si / Al ratio. High charge density Si / Al = 1 zeolites such as X (FAU topology) and 4A (LTA topology) show up for Hg uptake under the test conditions. 2+ It has very low affinity and readily removes Ca. 2+ and Mg 2+ (See Example 10 of US '856 patent). In the same test using UZM-9, the zeolite with Si / Al=5.50 and zeolite 4A have the same LTA zeolite topology, which is reversed and affects Hg. 2+ It has high selectivity and is also effective against Ca. 2+ and Mg 2+ The selectivity is significantly reduced. In the case of zeolite 4A and UZM-9, this result decouples the structure from the framework charge density and demonstrates the importance of framework charge density in ion exchange selectivity (see Example 11 of the '856 patent). Meanwhile, zeolite X shows improved selectivity in removing Pb from aqueous solution. 2+ It excels in this aspect, and in removing Hg 2+ The performance in this aspect is poor (see Comparative Example 13 of '856 Patent). Therefore, in order to determine the cation selectivity of the ion exchanger, relevant data on each combination of removed metal cations / residual metal cations / ion exchanger must be collected.

[0018] A method for removing Sr from body fluids using Zr, Ti, Sn-based metal acid salt ion exchangers is disclosed. 2+ For methods involving ions, see US 11,577,014 (“'104 Patent”), the entire contents of which are incorporated herein by reference for all purposes. Most of the ion exchangers provided in the '104 Patent are crystalline and amorphous metal silicates, while a metal oxide, namely a commercially available sodium nonatitanate sample, is also disclosed. A method for removing Hg from body fluids using Ti metal salts is also disclosed. 2+ The method is described in US 11,484,875, which is incorporated herein by reference in its entirety for all purposes. Ti is required in compositions containing optional Nb and Si. Effective Hg 2+Removal requires very specific combinations of topologies / compositions, including the metal silicate Ti-Nb sitinakite and acid-treated zorite, as well as metal oxides (a commercial sodium nonatitanate from Allied-Signal). Furthermore, U.S. Patent Application US 11,964,266 (“'266 application”) discloses the use of Zr, Ti, Sn-based metal acid salt ion exchangers, metal silicates, and metal oxides for the removal of cobalt, lead, cadmium, and chromium ions from body fluids, the entire contents of which are incorporated herein by reference for all purposes. Most of the ion exchangers in '266 application are crystalline and amorphous metal silicates, while two metal oxides are disclosed: a commercial sample of sodium nonatitanate from Allied-Signal and a commercial potassium octatitanate product from Honeywell. Unlike sodium nonatitanate, potassium octatitanate is more effective for removing Hg. 2+ and Sr 2+ Removal is ineffective.

[0019] This disclosure provides and includes a method for removing Pb from bodily fluids. 2+ The ion exchange method utilizes polycrystalline aggregates of metal titanate ion exchangers that are substantially insoluble in bodily fluids, particularly gastrointestinal fluids. Metal titanate ion exchangers, on an anhydrous basis, possess the following empirical formula:

[0020] A m Ti x M y O z

[0021] Wherein A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is at least one skeletal metal selected from the group consisting of niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to total metal and has a value of 1.55 to about 2.85; and the composition is synthesized in the presence of at least one polyhydroxy complexing agent (MHCA). These compositions are substantially insoluble in body fluids (at neutral and weakly acidic or alkaline pH), and therefore can be used for the removal of Pb from the gastrointestinal fluid system. 2+ Toxins can be ingested into the body. Summary of the Invention

[0022] This disclosure provides and includes a particulate metal titanate ion exchanger having the following empirical formula on an anhydrous basis:

[0023] A m Ti x M y O z

[0024] in

[0025] A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.85.

[0026] The particulate metal titanate ion exchanger was synthesized in the presence of at least one polyhydroxy complexing agent (MHCA), and the particulate metal titanate ion exchanger has a median particle size of greater than 3 micrometers (μm).

[0027] This disclosure also provides and includes a macroporous granular titanate ion exchanger having the following empirical formula on an anhydrous basis:

[0028] A m TiO z

[0029] in

[0030] A is an exchangeable cation selected from the group consisting of potassium ions, hydrated hydrogen ions, and mixtures thereof; "m" is the molar ratio of A to Ti and has a value of 0.10 to 0.60; and "z" is the molar ratio of O to Ti and has a value of 2.05 to 2.60.

[0031] The macroporous titanate ion exchanger was synthesized in the presence of a polyhydroxy complexing agent (MHCA), namely d-sorbitol. The macroporous particulate titanate ion exchanger has a median particle size between 25 micrometers (μm) and 125 micrometers, with less than 3.0% of the particles having a particle size of less than 3 micrometers (μm). Furthermore, the macroporous particulate titanate ion exchanger has a particle size of at least 150 m² / g. 2Bruno-Emet-Teller (BET) surface area ( / g).

[0032] This disclosure also provides and includes a macroporous granular titanate ion exchanger having the following empirical formula on an anhydrous basis:

[0033] A m TiO z

[0034] in

[0035] A is an exchangeable cation selected from the group consisting of potassium ions, hydrated hydrogen ions, and mixtures thereof; "m" is the molar ratio of A to Ti and has a value of 0.10 to 0.60; and "z" is the molar ratio of O to Ti and has a value of 2.05 to 2.60.

[0036] The macroporous titanate ion exchanger was synthesized in the presence of a polyhydroxy complexing agent (MHCA), namely d-sorbitol. The macroporous particulate titanate ion exchanger has a median particle size between 25 micrometers (μm) and 125 micrometers, with less than 0.5% of the particles having a particle size of less than 3 micrometers (μm). Furthermore, the macroporous particulate titanate ion exchanger has a particle size of at least 150 m² / g. 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0037] This disclosure also provides and includes a method for manufacturing tablets or capsules or for oral administration, the tablets or capsules comprising a granular metal titanate ion exchanger having the following empirical formula on an anhydrous basis:

[0038] A m Ti x M y O z

[0039] in

[0040] A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to total metal and has a value of 1.55 to 2.85, wherein the particulate metal titanate ion exchanger has a median particle size greater than 3 micrometers (μm).

[0041] The method includes the following steps:

[0042] (a) Forming a reaction mixture comprising a reactive A source, a Ti source, at least one polyhydroxy complexing agent (MHCA) source, optionally an M source, optionally a hydrogen peroxide source, optionally a complexing agent (C) source, and water.

[0043] (b) Heating the reaction mixture for a certain period of time to form a metal titanate ion exchanger.

[0044] (c) Treating the synthesized metal titanate ion exchanger by acid extraction and / or ion exchange with alkali metals, alkaline earth metals, or mixtures thereof to form a particulate metal titanate ion exchanger with the desired composition.

[0045] (d) Optionally, a metal titanate ion exchanger is mixed with one or more pharmaceutically acceptable adjuvants, diluents, or carriers to form a metal titanate ion exchanger drug, and

[0046] (e) Forming capsules or tablets containing particulate metal titanate ion exchangers.

[0047] The reaction mixture has a composition expressed in the molar ratio of the following oxides:

[0048] p A2O : a TiO2 : b MO q / 2 : c H2O2 : d MHCA : e C : f H2O

[0049] Where “p” has a value of approximately 4 to 40; “a” has a value of approximately 0.5 to 1; “b” has a value of 0 to 0.5, a+b=1; “q” is the charge on M and has a value of 2 to 5; “c” has a value of 0 to 6; “d” has a value of 0.2 to 4; “e” has a value of 0 to 4; and “f” has a value of 20 to 1000.

[0050] This disclosure also provides and includes a method for selectively removing Pb from gastrointestinal fluids. 2+ A method for removing Pb from a toxin involves contacting a fluid containing the toxin with a particulate metal titanate ion exchanger to produce an ion-exchanged ion exchanger, thereby removing Pb from the fluid. 2+ Toxins, granular metal titanate ion exchangers, on an anhydrous basis, possess the following empirical formula:

[0051] A m Ti x M y O z

[0052] in

[0053] A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.85.

[0054] The metal titanate ion exchanger was synthesized in the presence of at least one polyhydroxy complexing agent (MHCA). The particulate metal titanate ion exchanger has a median particle size greater than 3 micrometers (μm), and the particulate metal titanate ion exchanger is minimally interfered with by means of Na. + Mg 2+ K + and Ca 2+ The level of any one or more ions.

[0055] This disclosure also provides and includes a method for removing Pb from gastrointestinal fluids. 2+ An in vivo method for removing toxins, comprising contacting a fluid containing the toxin with a particulate aggregate of metal titanate ion exchanger to generate an ion-exchanged ion exchanger, thereby removing the toxin from the fluid. The particulate metal titanate ion exchanger has the following empirical formula on an anhydrous basis:

[0056] A m Ti x M y O z

[0057] Wherein A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof, M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+), "m" is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60, "x" is the molar fraction of total metal Ti and has a value of 0.5 to 1, "y" is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1, and "z" is the molar ratio of O to total metal and has a value of 1.55 to 2.85, wherein the metal titanate ion exchanger has been synthesized in the presence of at least one polyhydroxy complexing agent (MHCA).

[0058] This disclosure also provides and includes a method for preparing particulate metal titanate ion exchangers, the particulate metal titanate ion exchangers having the following empirical formula on an anhydrous basis:

[0059] A m Ti x M y O z

[0060] in

[0061] A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.85.

[0062] The method includes the following steps:

[0063] (a) Forming a reaction mixture comprising a reactive A source, a Ti source, at least one polyhydroxy complexing agent (MHCA) source, optionally an M source, optionally a hydrogen peroxide source, optionally a complexing agent (C) source, and water, and

[0064] (b) The reaction mixture is heated at a temperature of about 85°C to about 225°C for a period of 0.5 to 30 days to form a particulate metal titanate ion exchanger.

[0065] The reaction mixture has a composition expressed in the molar ratio of the following oxides:

[0066] p A2O : a TiO2 : b MO q / 2 : c H2O2 : d MHCA : e C : f H2O

[0067] Where “p” has a value of approximately 4 to 40; “a” has a value of approximately 0.5 to 1; “b” has a value of 0 to 0.5, a+b=1; “q” is the charge on M and has a value of 2 to 5; “c” has a value of 0 to 6; “d” has a value of 0.2 to 4; “e” has a value of 0 to 4; and “f” has a value of 20 to 1000.

[0068] This disclosure also provides and includes the synthesis of metal titanate ion exchanger compositions from a highly alkaline aqueous solution phase reaction mixture, the solution properties of which are promoted by a complexing agent comprising at least one MHCA, hydrogen peroxide, and a carboxylic acid (such as citric acid). The solution properties of the reaction mixture enhance the reactivity of the system, allowing the metal to be incorporated into the lattice under conditions where any metal (Ti, Sn, Zr, Nb, Co, Fe, Mn) would precipitate during synthesis and is otherwise difficult to transport. In one aspect, the hydrothermal synthesis of ion exchange compositions from highly alkaline aqueous solutions in the presence of MHCA (especially d-sorbitol) and other complexing agents promotes the formation of polycrystalline aggregates, including spheres, interpenetrating spheres, blocks, and other morphologies that are generally large enough (>3 µm) not to be absorbed in the gastrointestinal tract.

[0069] This disclosure also provides and includes the synthesis of metal titanate ion exchanger compositions from TiO2 powder in a highly alkaline reaction mixture containing complexing agents, at least one of which is MHCA, which imparts unique properties to the resulting metal titanate ion exchanger. In one aspect, synthesis in the presence of at least one MHCA can provide the transformation of TiO2 powder into macroporous polycrystalline aggregate particles, which are large enough to avoid absorption in the gastrointestinal tract. In another aspect, synthesis in the presence of multiple complexing agents including at least one MHCA and, for example, carboxylic acids (such as citric acid) and optionally hydrogen peroxide, dissolves a metal substituent M source in a highly alkaline solution, making it usable for reaction with and incorporation into TiO2 powder, and enabling the formation of large, generally large, macroporous polycrystalline aggregates of metal titanate to avoid absorption in the gastrointestinal tract.

[0070] This disclosure also provides and includes the synthesis of metal titanate ion exchanger compositions from pre-formed TiO2, such as spray-dried TiO2 spheres, in an alkaline reaction mixture containing a complexing agent, at least one of which is MHCA, which imparts unique properties to the resulting metal titanate ion exchanger. In one aspect of the titanate ion exchange composition, synthesis in the presence of at least one MHCA enables the conversion of pre-formed TiO2 spheres into macroporous alkaline metal titanate spheres large enough to avoid absorption into the gastrointestinal tract. In the case of the metal titanate composition, synthesis in the presence of multiple complexing agents including at least one MHCA and, for example, carboxylic acids (such as citric acid) and optionally hydrogen peroxide, dissolves a metal substituent M source in a highly alkaline solution, making it available for reaction with and incorporation into the formed TiO2 spheres, providing conversion into macroporous metal titanate spheres large enough to avoid absorption into the gastrointestinal tract.

[0071] This disclosure also provides and includes forming the metal titanates of this disclosure (including mixtures of different metal titanates) into shaped products, such as spray-dried spheres, wherein each of the metal titanates synthesized in the presence of at least one MHCA and the resulting shaped product being a macroporous sphere has a sufficient size to avoid absorption into the gastrointestinal tract.

[0072] This disclosure also provides and includes a method for removing Pb-containing substances from fluids. 2+ A method for removing toxins, comprising contacting a fluid containing the toxin with a metal titanate ion exchanger to generate an ion-exchanged ion exchanger, thereby removing the toxin from the fluid, the metal titanate ion exchanger having the following empirical formula on an anhydrous basis:

[0073] A m Ti x M y O z

[0074] Wherein A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof, M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+), "m" is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60, "x" is the molar fraction of total metal Ti and has a value of 0.5 to 1, "y" is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1, "z" is the molar ratio of O to total metal and has a value of 1.55 to 2.85, wherein the metal titanate ion exchanger has been synthesized in the presence of at least one complexing agent, the complexing agent being a polyhydroxy complexing agent (MHCA). Attached Figure Description

[0075] Figure 1, including Figure 1A- Figure 1F The image shows a scanning electron microscope (SEM) image of the metal titanate product synthesized in aqueous solution in the presence of MHCA d-sorbitol, showing the separation of large polycrystalline aggregates of the metal titanate ion exchanger from the synthesis carried out in a homogeneous solution.

[0076] Figure 1A shows Na with a polycrystalline spherical morphology from Example 5B. 0.25 Fe 0.20 Ti 0.80 Scanning electron microscope (SEM) image.

[0077] Figure 1B shows Na 0.25 Fe 0.20 Ti 0.80 SEM image of (Example 5B). Polycrystalline morphology.

[0078] Figure 1C shows Na 0.33 Fe 0.38 Ti 0.62 SEM image of (Example 7B). Polycrystalline interpenetrating spheres.

[0079] Figure 1D shows Na 0.33 Fe 0.38 Ti 0.62 SEM image of (Example 7B). Polycrystalline interpenetrating spheres.

[0080] Figure 1E shows Na 0.39 Zr 0.03 Ti 0.97 SEM image of (Example 9). Polycrystalline interpenetrating spheres.

[0081] Figure 1F SEM images of K-Nb-Ti-O (Example 11) are shown. A block of polycrystalline interpenetrating spheres.

[0082] Figure 2, including Figure 2A- Figure 2L This paper demonstrates that a metal titanate ion exchanger consisting of large polycrystalline aggregates is synthesized in a strongly alkaline medium in the presence of a polyhydroxy complexing agent from TiO2 powder and pre-formed spray-dried TiO2 spheres.

[0083] Figure 2A shows K 0.26 SEM image of Ti (Example 17). Polycrystalline sponge-like morphology obtained from TiO2 powder in the presence of KOH / catechol solution.

[0084] Figure 2B shows a SEM image of Na-Ti-O (Example 20A). It is a complex aggregate of very large polycrystalline interpenetrating spheres obtained from pre-formed TiO2 spheres through hydrothermal treatment in the presence of a NaOH / d-sorbitol solution.

[0085] Figure 2C shows a SEM image of Na-Fe-Ti-O (Example 21A). The Na-Fe-Ti-O polycrystalline spheres were obtained from pre-formed TiO2 spheres that underwent hydrothermal treatment with a Fe(NO3)3 / citric acid / d-sorbitol / NaOH solution.

[0086] Figure 2D shows a SEM image of Na-Fe-Ti-O (Example 21A). The Na-Fe-Ti-O polycrystalline spheres were obtained from pre-formed TiO2 spheres that underwent hydrothermal treatment with a Fe(NO3)3 / citric acid / d-sorbitol / NaOH solution.

[0087] Figure 2E shows K 0.40 SEM image of Ti (Example 24A). Sponge-like macroporous polycrystalline aggregates obtained by hydrothermal treatment of TiO2 powder in the presence of d-sorbitol / KOH solution.

[0088] Figure 2F K is shown 0.40 SEM image of Ti (Example 24A). Close-up of the sponge-like macroporous polycrystalline network in the aggregates. Obtained by hydrothermal treatment of TiO2 powder in the presence of d-sorbitol / KOH solution.

[0089] Figure 2G shows the composite sample K. 0.30 SEM image of Ti (Example 24E). Sponge-like macroporous polycrystalline aggregates obtained by hydrothermal treatment of TiO2 powder in the presence of d-sorbitol / KOH solution.

[0090] Figure 2H shows the composite sample K. 0.30 SEM image of Ti (Example 24E). Close-up view of the sponge-like macroporous polycrystalline network in the aggregates. Obtained by hydrothermal treatment of TiO2 powder in the presence of d-sorbitol / KOH solution.

[0091] Figure 2I shows the composite sample K 0.28 SEM image of Ti (Example 25D). K2 obtained by hydrothermal treatment of pre-formed spray-dried TiO2 spheres in the presence of d-sorbitol / KOH solution. 0.28 A view of a Ti sphere.

[0092] Figure 2J shows the composite sample K. 0.28SEM image of Ti (Example 25D). K2 obtained by hydrothermal treatment of pre-formed spray-dried TiO2 spheres in the presence of d-sorbitol / KOH solution. 0.28 A close-up of a Ti sphere.

[0093] Figure 2K shows the acid-treated composite sample K. 0.16 SEM image of Ti (Example 25E). Field view of the acid-treated composite sample from Example 25D. The spheres maintained structural integrity during acid treatment.

[0094] Figure 2L Acid-treated composite sample K is shown. 0.16 SEM image of Ti (Example 25E). Close-up view of the acid-treated composite sample from Example 25D. The spheres maintained structural integrity during acid treatment.

[0095] Figures 3-8 Particle size distribution data for selected embodiments and comparative examples of the prior art are shown. Definitions of terms: D3 (µm): The minimum 3% by volume of particles in the sample that are smaller than the particle size D3 (µm) measured in micrometers. Similarly, D10 (µm) is the particle size of the sample where the minimum 10% by volume occurs. D50 (µm) is equivalent to the median particle size, i.e., the particle size of the sample where the minimum 50% by volume occurs. D90 (µm) is the particle size of the sample where the minimum 90% by volume occurs. The parameter <3µm (volume%) indicates the volume percentage of samples with a size smaller than 3µm. The average value is the average particle size in the sample.

[0096] Figure 3 The particle size distribution of prior art sodium nonatitanium material from Comparative Example C1 is shown.

[0097] Figure 4 The particle size distribution of the prior art potassium octatitanate material from Comparative Example C2 is shown.

[0098] Figure 5 The particle size distribution of the product of Example 24F, prepared from TiO2 powder that has undergone hydrothermal treatment followed by acid treatment in the presence of d-sorbitol / KOH solution, is shown.

[0099] Figure 6 The particle size distribution of the product of Example 25D, prepared from pre-formed spray-dried TiO2 spheres that have undergone hydrothermal treatment in the presence of a KOH / d-sorbitol solution, is shown.

[0100] Figure 7 The particle size distribution of the product of Example 25E, prepared from pre-formed spray-dried TiO2 spheres that have undergone hydrothermal treatment followed by acid treatment in the presence of KOH / d-sorbitol solution, is shown.

[0101] Figure 8 The particle size distribution of the product of Example 26, synthesized from nano-titanium dioxide powder that has been hydrothermally treated in the presence of KOH / d-sorbitol solution, is shown. Detailed Implementation

[0102] A. Metal titanate ion exchangers

[0103] This disclosure provides and includes methods for removing Pb-containing substances from gastrointestinal fluids. 2+ A novel approach to toxins. Unrestricted by theory, one aspect of the method disclosed herein is its high capacity and strong affinity (i.e., for both free and complexed Pb). 2+ Ion exchangers (selective ion exchange). Similarly, without being limited by a particular theory, another aspect of the method disclosed herein is the synthesis of metal titanate ion exchangers in the presence of at least one polyhydroxy complexing agent (MHCA), which provides readily available chemical properties of titanium and M elements in highly alkaline aqueous solutions and imparts properties such as a favorable particle size that helps avoid undesirable absorption during gastrointestinal treatment. The metal titanate compositions of this disclosure are identified as synthesized alkali metal titanate compositions, which, in addition to Ti… 4+ In addition, it may also contain Mn 2+ Co 2+ Fe 2+ Fe 3+ Sn 4+ Zr 4+ and Nb 5+ Or mixtures thereof, and can be further modified by ion exchange. They are further identified by their composite empirical formula (on an anhydrous basis), which is:

[0104] A m Ti x M y O z

[0105] The composition has a composition of at least TiO₂ 6 / n A framework structure composed of octahedral units, where n can be 2, 3, or both, or optionally include MO. 6 / nOctahedral unit, where n can be 2, 3, or both, but other coordination environments may exist for Ti and M. A is an exchangeable cation selected from the group consisting of potassium, sodium, lithium, calcium, magnesium, hydrated hydrogen, or mixtures thereof; M is an optional framework metal selected from the group consisting of cobalt (2+), manganese (2+), iron (2+), iron (3+), tin (4+), zirconium (4+), or niobium (5+), or mixtures thereof; "m" is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.6; "x" is the molar fraction of total metal Ti and has a value of 0.5 to 1.0; "y" is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to total metal and has a value of 1.55 to 2.85.

[0106] In one aspect, the synthesis of the metal titanate ion exchangers of this disclosure utilizes novel chemistry to facilitate the incorporation of M and Ti into the same network. In another aspect, the metal titanate is a cation exchange composition requiring a negative charge on the metal oxide component. To obtain a negatively charged metal oxide framework that can function as an ion exchanger, the synthesis must be carried out at a pH higher than the pH associated with the zero charge point of the metal oxide, a pH relevant to neutral metal oxides. In another aspect, the metal titanate ion exchangers of this disclosure are synthesized in alkaline solutions, typically highly alkaline solutions. Ti and M metals are insoluble in highly alkaline solutions, which can be detrimental to the successful incorporation of the metals into the same phase. Metals are typically obtained in the form of salts and form acidic solutions when dissolved in water. The same is true for M metals Sn, Zr, Co, Mn, and Fe. The solubility of these metals can be extended to alkaline pH, possibly up to pH 10-12, using complexing agents such as citric acid, amines, or EDTA; however, when the higher pH required for the synthesis of the metal titanates of this disclosure is reached, these metals will precipitate. Dissolving Ti and Nb reagents in aqueous solutions can also be problematic, as salts such as TiCl4 or NbCl5 and alkoxides such as titanium isopropoxide Ti(OiPr)4 and niobium ethoxide Nb(OEt)5 can hydrolyze and precipitate immediately. However, aqueous solutions of such Ti and Nb reagents can be formed in acidic solutions in the presence of sufficient H2O2. The solubility of these Ti and Nb solutions can be extended to higher pH levels by adding complexing agents such as citric acid; the formation of Nb-peroxy-citric acid solution from sparingly soluble niobium oxalate at pH 7.5 is documented (see *Chem. Mater.*, Vol. 9, pp. 580-587, 1997). Peroxy-citric acid solutions of Nb and Ti also precipitate upon further treatment with hydroxides, and solubility at higher pH levels is not achieved. However, the addition of a high pK group to these metal citrate solutions or metal peroxy-citric acid solutions... aIn the case of polyhydroxy complexing agents (MHCA) such as d-sorbitol or catechol, the solution can retain its solution properties because the addition of hydroxides increases the pH, thereby producing stable solutions of Ti and M metals at very high pH (greater than pH = 14 if desired). Not bound by theory, at high pH, ​​the hydroxyl groups of sugar alcohols (such as d-sorbitol) or aromatic diols (such as catechol) can be deprotonated, thus becoming strong complexing agents that can stabilize metals in highly alkaline aqueous solutions. The availability of Ti and M metals in these highly alkaline solutions promotes their mutual incorporation into the metal titanate ion exchanger compositions of this disclosure during their synthesis. The hydrothermal digestion of these reaction mixtures forms products consisting of large polycrystalline aggregates, typically spheres, interpenetrating spheres, blocks, and other morphologies; the particles are typically large enough (e.g., greater than 3 µm) to avoid absorption into the gastrointestinal tract.

[0107] In one respect, MHCA can be used to enhance the metal titanate ion exchanger compositions disclosed herein synthesized from TiO2 powder. In the presence of MHCA, hydrothermal treatment of TiO2 powder in an alkaline solution favors the formation of macroporous polycrystalline aggregates larger than those observed in solution synthesis, and, in one respect, large enough to avoid absorption into the gastrointestinal tract. The metal M is incorporated into TiO2 powder by preparing a highly alkaline solution containing the metal M using a suitable complexing agent such as H2O2, citric acid, and MHCA to retain the metal M in solution and aid in the transport of Ti; mixing the TiO2 powder with the solution; and hydrothermally treating the resulting mixture to form a product composed of large macroporous polycrystalline aggregates conferred by the presence of MHCA.

[0108] In one approach, MHCA can be applied to pre-formed TiO2 powder starting materials, particularly spray-dried spheres. Hydrothermal treatment of the TiO2 spheres with an alkaline solution containing MHCA produces macroporous spheres. The metal M is incorporated into the TiO2 spheres in a similar manner to the TiO2 powder, for example, by preparing a highly alkaline solution containing M using a suitable complexing agent such as H2O2, citric acid, and MHCA. The TiO2 spheres are then mixed with the M-containing alkaline solution, and the resulting mixture is hydrothermally treated to form macroporous spheres. The resulting spheres are large enough to avoid absorption by the gastrointestinal tract.

[0109] The metal titanate ion exchanger compositions disclosed herein can be prepared by hydrothermal crystallization of a reaction mixture, which is prepared by mixing a reactive titanium source with, optionally, one or more M metals, at least one alkali metal, at least one complexing agent including at least one MHCA, optionally hydrogen peroxide, and water. Without being theoretically limited, alkali metals can act as framework charge balancing agents and template agents. Examples of titanium metal sources include, but are not limited to, titanium alkoxides, titanium tetrachloride, titanium trichloride, amorphous titanium hydroxyaoxide, titanium dioxide, rutile titanium dioxide, anatase titanium dioxide, nanoscale titanium dioxide (crystal size of about 200 nm, preferably 100 nm or smaller), and pre-formed spray-dried TiO2 spheres. Examples of metal sources M include, but are not limited to, cobalt acetate, cobalt nitrate, cobalt chloride, manganese acetate, manganese nitrate, manganese chloride, manganese sulfate, ferric nitrate (3+), ferric chloride (3+), ferric chloride (2+), ferric chloride (2+), ferric sulfate (2+), ferric acetate (2+), tin chloride (4+), zirconium oxychloride, zirconium oxynitrate, zirconium alkoxide, zirconium acetate, zirconium chloride, niobium oxalate, niobium oxalate ammonium, niobium chloride, and niobium alkoxide. Examples of base sources A include, but are not limited to, potassium hydroxide, sodium hydroxide, lithium hydroxide, sodium halide, potassium halide, lithium halide, sodium acetate, potassium acetate, and lithium acetate. Hydrogen peroxide is an optional complexing agent, preferably a 30% by weight aqueous solution. Examples of polyhydroxy complexing agents (MHCA) include, but are not limited to, sugar alcohols such as d-sorbitol, mannitol, and xylitol; sugars such as glucose and fructose; and polyhydroxy aromatic compounds such as catechol. MHCA is understood to contain at least two hydroxyl groups. One or more complexing agents (C) may be used in any reaction. Complexing agent sources include, but are not limited to, carboxylic acids, such as citric acid and tartaric acid; nitrogen-containing complexing agents such as EDTA; and bipyridine; and mixtures thereof. In one aspect, a hydrothermal method for preparing the titanium metal salt ion-exchange compositions of this disclosure includes forming a reaction mixture, which is expressed according to the molar ratio of the oxides by the following formula:

[0110] p A2O : a TiO2 : b MO q / 2 : c H2O2 : d MHCA : e C : f H2O

[0111] Wherein, "p" has a value of about 4 to 40, "a" has a value of about 0.5 to 1, "b" has a value of 0 to 0.5, a+b=1, "c" has a value of 0 to 6, "MHCA" is at least one polyhydroxy complexing agent, "d" has a value of 0.2 to 4, "C" is at least one complexing agent, "e" has a value of 0 to 4, and "f" has a value of 20 to 1000. The reaction mixture can be prepared by mixing the desired alkali metal source, titanium source, polyhydroxy complexing agent MHCA source, optional hydrogen peroxide source, optional complexing agent C source, optional M metal source, and water to obtain the desired mixture. Furthermore, the final reaction mixture has an alkaline pH, and preferably at least 12.5. The alkalinity of the mixture is controlled by adding alkali metal hydroxide. After the reaction mixture is formed, it is then subjected to autogenous pressure in a sealed reaction vessel at a temperature of about 85°C to about 225°C for a period of about 0.5 days to about 30 days. After the allotted time, the mixture is filtered or centrifuged to separate the solid product, which is then washed with deionized water and dried in air. As provided above, the compositions of this disclosure can have a composition primarily composed of octahedral TiO₂. 6 / n Units and optional octahedral MO 6 / n The framework structure consists of units (n=2 or 3), but other coordination environments may exist. The metal titanate ion exchangers disclosed herein can exhibit various levels of crystallinity or can be amorphous.

[0112] During initial synthesis, in one aspect, the metal titanate ion exchanger compositions of this disclosure may contain alkali metal templates within the pores, between layers and chains, or at other charge-balanced locations. These metals are described as exchangeable cations, meaning they can exchange with other (secondary) A' cations. Typically, A exchangeable cations can exchange with A' cations selected from: other alkali metal cations (K... + Na + Li + ), alkaline earth metal cations (Mg 2+ Ca 2+ A' cation is a hydrated hydrogen ion or a mixture thereof. As used herein, A' cation is different from A cation. Methods for exchanging one cation for another are well known in the art and include contacting the metal titanate ion exchanger composition of this disclosure with a solution containing the desired cation (molar excess) under exchange conditions. Exchange conditions include temperatures from about 25°C to about 100°C and times from about 20 minutes to about 2 hours. The specific cation (or mixture thereof) present in the final product will depend on the specific use of the composition and the specific composition used. For example, for treating calcium deficiency... 2+ For patients with low blood calcium levels, a specific composition is one containing calcium. 2+An ion exchanger in which the A' cation is Na - Ca 2+ and H + A mixture of ions.

[0113] In one aspect, the metal titanate ion exchangers of this disclosure are typically synthesized in powder form as particles with a size greater than 3 micrometers, which is desirable. However, it may be desirable for a subset of these particles to be smaller than 3 micrometers, with an upper limit of 3% by volume for particles smaller than 3 micrometers. In one aspect, the metal titanate ion exchangers of this disclosure have a median particle size greater than 3 micrometers. In another aspect, the metal titanate ion exchangers of this disclosure have a median particle size in the range of 25 micrometers to 125 micrometers.

[0114] The following are also within the scope of this disclosure: ion exchange compositions can be used in the methods provided herein in the form of a pre-synthesized powder, or can be formed into various shapes by means well known in the art. Examples of these various shapes include pellets, extrusions, spheres, pellets, and irregularly shaped particles. See, for example, US 6579460B1 and US6814871B1. In one aspect, the formation process may include the addition of a binder, such as zirconium oxide, which may require annealing. Annealing can be performed by calcining in air at a temperature of up to 350°C for 2 to 6 hours. In another aspect, formation can also occur at several scales, for example at one scale for the synthesis of metal titanate ion exchangers and at another scale for the delivery of metal titanate ion exchangers to the body. For example, in Examples 20-23 and 25 provided herein, pre-formed spray-dried TiO2 spheres are used as starting materials for the synthesis of metal titanate ion exchangers with diameters of tens of micrometers, which can then be formed into larger pellets for delivery to the body. Conversely, in one aspect, the metal titanate ion exchangers of this disclosure can be first synthesized from solution, and then one or more of these metal titanates can be spray-dried to form a product consisting of larger aggregates (such as spherical aggregates), which can then be formed into pellets. In one aspect, pellets or other shapes of the metal titanate ion exchangers of this disclosure can be ingested orally and toxins are isolated in the gastrointestinal fluid as the ion exchangers pass through the intestines and are eventually excreted. In one aspect, the ion exchangers of this disclosure can be protected from high acid content (such as that found in the stomach) by coating the formed articles with various coatings that will not dissolve in the stomach but will dissolve in the intestines.

[0115] As provided herein, in one aspect, the metal titanate ion exchanger compositions of this disclosure can adsorb various Pb-containing compounds from gastrointestinal fluids. 2+ Toxins, including free Pb 2+ Ions and Pb from complex2+ Pb ions 2+ This has particular practical applications. The metal titanate ion exchangers disclosed herein are not limited to the treatment of gastrointestinal fluids; they can also be used to remove Pb from other bodily fluids, such as blood, plasma, urine, and dialysate solutions. 2+ As used herein and in the claims, while the present focus is on gastrointestinal fluids, body fluids will include, but are not limited to, blood, plasma, and gastrointestinal fluids. Furthermore, in one aspect, the metal titanate ion exchanger compositions disclosed herein can be used to remove Pb from body fluids of any mammalian body. 2+ The mammals in question include, but are not limited to, humans, cattle, pigs, sheep, monkeys, gorillas, horses, and dogs. The method of this invention is particularly suitable for removing toxins from human bodily fluids.

[0116] As provided herein, in one aspect, while the metal titanate ion exchanger compositions of this disclosure can be synthesized using a variety of exchangeable cations (“A”), it is preferable to exchange cations with secondary cations (A’) that are more compatible with blood or do not adversely affect blood. Without being theoretically limited, the compositional requirements of the ion exchanger will vary depending on the patient’s needs. For this reason, preferred cations are potassium, sodium, lithium, calcium, hydrated hydrogen ions, and magnesium. In one aspect, preferred compositions include those containing potassium ions. In another aspect, preferred compositions include those containing hydrated hydrogen ions. In yet another aspect, preferred compositions include those containing a combination of potassium and hydrated hydrogen ions. The relative amounts of any two cations within the metal titanate ion exchanger can vary significantly and can depend on the composition itself and the concentrations of the two ions in the blood.

[0117] In one aspect, the particulate metal titanate ion exchanger according to this disclosure is in a solid dosage form. Solid dosage forms for oral administration may include capsules, tablets, pills, powders, extrusions, spheres, pellets, granules, and irregularly shaped particles. In these solid dosage forms, the active particulate metal titanate ion exchanger is mixed with at least one conventional inert excipient (or medium) (such as sodium citrate or dicalcium phosphate) or with any or more of the following components: (a) fillers or compatibilizers, such as starch, lactose, sucrose, glucose, mannitol, and silica; (b) binders, such as hydroxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, and gum arabic; (c) humectants, such as glycerin; (d) disintegrants, such as agar, calcium carbonate, potato starch or cassava starch, alginate, some complex silicates, and sodium carbonate; (e) slow solvents, such as paraffin; (f) absorption promoters, such as quaternary ammonium compounds; (g) wetting agents, such as cetyl alcohol and glyceryl monostearate; (h) adsorbents, such as kaolin; and (i) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium dodecyl sulfate, or mixtures thereof. Capsules, tablets, and pills may also contain buffers.

[0118] In one aspect, solid dosage forms such as tablets, sugar pills, capsules, pellets, and granules can be prepared using coatings and shells (such as enteric coatings and other materials known in the art). The solid dosage forms may contain light-blocking agents, and furthermore, the active particulate metal titanate ion exchanger or the particulate metal titanate ion exchanger in such compositions can be released in a delayed manner into a portion of the digestive tract. Non-limiting examples of encapsulating components that can be employed are polymeric materials and waxy materials. The active particulate metal titanate ion exchanger can also be formed into microcapsules together with one or more of the excipients described above.

[0119] In one aspect, the particulate metal titanate ion exchanger according to the present disclosure is in tablet form. In another aspect, the particulate metal titanate ion exchanger according to the present disclosure is in capsule form. In one aspect, the particulate metal titanate ion exchanger in tablet form further comprises a tablet coating. In one aspect, the particulate metal titanate ion exchanger in capsule form further comprises a capsule coating.

[0120] In one aspect, the particulate metal titanate ion exchanger according to this disclosure can be mixed with one or more pharmaceutically acceptable adjuvants, diluents, or carriers, such as lactose, sucrose, sorbitol, mannitol; starch, such as potato starch, corn starch, or amylopectin; cellulose derivatives; binders, such as gelatin or polyvinylpyrrolidone; disintegrants, such as cellulose derivatives; and / or lubricants, such as magnesium stearate, calcium stearate, polyethylene glycol, waxes, paraffin, etc., and then compressed into tablets. If coated tablets are required, the tablet core prepared as described above can be coated with a suitable polymer dissolved or dispersed in water or a volatile organic solvent. Alternatively, the tablets can be coated with a concentrated sugar solution, which may contain, for example, gum arabic, gelatin, talc, and titanium dioxide.

[0121] In one aspect, a sustained-release formulation of the particulate metal titanate ion exchanger of the present disclosure is provided. Examples of sustained-release formulations include a semi-permeable matrix of a solid hydrophobic polymer containing the particulate metal titanate ion exchanger, wherein the matrix is ​​in the form of a molded article such as a membrane or microcapsule. Examples of sustained-release matrices include polyesters, hydrogels, and polylactide.

[0122] In one aspect, the particulate metal titanate ion exchanger disclosed herein is macroporous. In one aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 50 nanometers (nm) and about 500 nm. In one aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 50 nm and about 400 nm. In one aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 50 nm and about 300 nm. In one aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 50 nm and about 200 nm. In one aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 50 nm and about 100 nm. In one aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 50 nm and about 75 nm. In one aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 100 nm and about 500 nm. In one aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 200 nm and about 500 nm. In another aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 300 nm and about 500 nm. In another aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 400 nm and about 500 nm. In another aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 100 nm and about 350 nm. In another aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 200 nm and about 300 nm. In another aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 225 nm and about 275 nm. In another aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 240 nm and about 260 nm. In another aspect, the macroporous particulate metal titanate ion exchanger has a pore size between about 350 nm and about 450 nm.

[0123] In one aspect, the granular metal titanate ion exchanger of this disclosure has a median particle size in the range of 25 µm to 125 µm. In another aspect, the granular metal titanate ion exchanger has a median particle size in the range of 25 µm to 100 µm. In another aspect, the granular metal titanate ion exchanger has a median particle size in the range of 25 µm to 75 µm. In another aspect, the granular metal titanate ion exchanger has a median particle size in the range of 25 µm to 50 µm. In another aspect, the granular metal titanate ion exchanger has a median particle size in the range of 25 µm to 35 µm. In another aspect, the granular metal titanate ion exchanger has a median particle size in the range of 35 µm to 100 µm. In another aspect, the granular metal titanate ion exchanger has a median particle size in the range of 50 µm to 75 µm. In another aspect, the granular metal titanate ion exchanger has a median particle size in the range of 35 µm to 125 µm. In one aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 50 µm to 125 µm. In another aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 75 µm to 125 µm. In yet another aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 100 µm to 125 µm.

[0124] In one aspect, the particulate metal titanate ion exchanger disclosed herein has a particle size distribution between about 5 micrometers (µm) and about 70 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 5 µm and about 60 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 5 µm and about 50 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 5 µm and about 40 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 5 µm and about 30 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 5 µm and about 20 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 20 µm and about 70 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 30 µm and about 70 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 40 µm and about 70 µm. 10Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 50 µm and about 70 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 10 µm and about 35 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 10 µm and about 25 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 15 µm and about 45 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 25 µm and about 45 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 35 µm and about 45 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 10 µm and about 20 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 12 µm and about 18 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution of approximately 15 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 40 µm and about 50 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 42 µm and about 48 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution of approximately 45 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 50 µm and about 60 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 51 µm and about 57 µm. 10 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution of approximately 54 µm. 10 value.

[0125] In one aspect, the particulate metal titanate ion exchanger disclosed herein has a particle size distribution between about 25 micrometers (µm) and about 125 µm. 50 Value. In one respect, particulate metal titanate ion exchangers have a particle size distribution between about 25 µm and about 90 µm. 50Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 25 µm and about 80 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 25 µm and about 70 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 25 µm and about 60 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 60 µm and about 125 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 70 µm and about 125 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 80 µm and about 125 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 90 µm and about 125 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 60 µm and about 90 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 60 µm and about 80 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 50 µm and about 80 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 50 µm and about 70 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 45 µm and about 55 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 48 µm and about 54 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution of approximately 51 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 70 µm and about 80 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 71 µm and about 77 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution of approximately 74 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 85 µm and about 95 µm. 50Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 89 µm and about 95 µm. 50 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution of approximately 92 µm. 50 value.

[0126] In one aspect, the particulate metal titanate ion exchanger disclosed herein has a particle size distribution between about 55 micrometers (µm) and about 185 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 55 µm and about 165 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 55 µm and about 145 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 55 µm and about 135 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 55 µm and about 125 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 55 µm and about 115 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 55 µm and about 105 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 55 µm and about 95 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 55 µm and about 85 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 85 µm and about 185 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 105 µm and about 185 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 125 µm and about 185 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 145 µm and about 185 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 165 µm and about 185 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 75 µm and about 145 µm. 90Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 85 µm and about 145 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 95 µm and about 145 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 105 µm and about 145 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 115 µm and about 145 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 125 µm and about 145 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 95 µm and about 105 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 99 µm and about 105 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution of approximately 102 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 135 µm and about 145 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 137 µm and about 143 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution of approximately 140 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 155 µm and about 165 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution between about 156 µm and about 162 µm. 90 Value. In one respect, the particulate metal titanate ion exchanger has a particle size distribution of approximately 159 µm. 90 value.

[0127] In one aspect, less than 5% of the particles of the granular metal titanate ion exchanger of the present disclosure have a particle size of less than 3 µm. In one aspect, less than 4% of the particles of the granular metal titanate ion exchanger have a particle size of less than 3 µm. In one aspect, less than 3% of the particles of the granular metal titanate ion exchanger have a particle size of less than 3 µm. In one aspect, less than 2% of the particles of the granular metal titanate ion exchanger have a particle size of less than 3 µm. In one aspect, less than 1% of the particles of the granular metal titanate ion exchanger have a particle size of less than 3 µm. In one aspect, less than 0.5% of the particles of the granular metal titanate ion exchanger have a particle size of less than 3 µm. In one aspect, less than 0.1% of the particles of the granular metal titanate ion exchanger have a particle size of less than 3 µm. In one aspect, between about 5% and about 0.1% of the particles of the granular metal titanate ion exchanger have a particle size of less than 3 µm. In one aspect, the particles of the granular metal titanate ion exchanger, ranging from about 5% to about 0.5%, have a particle size of less than 3 µm. In another aspect, the particles of the granular metal titanate ion exchanger, ranging from about 5% to about 1%, have a particle size of less than 3 µm. In another aspect, the particles of the granular metal titanate ion exchanger, ranging from about 5% to about 3%, have a particle size of less than 3 µm. In another aspect, the particles of the granular metal titanate ion exchanger, ranging from about 3% to about 0.1%, have a particle size of less than 3 µm. In another aspect, the particles of the granular metal titanate ion exchanger, ranging from about 1% to about 0.1%, have a particle size of less than 3 µm. In another aspect, the particles of the granular metal titanate ion exchanger, ranging from about 0.5% to about 0.1%, have a particle size of less than 3 µm.

[0128] In one aspect, the metal titanate ion exchanger compositions used in the methods provided herein can be directly synthesized and / or sieved to achieve a particle size distribution (PSD) that meets FDA standards for non-systematic solid particles (more than 97% of the material by volume has a particle size greater than 3 micrometers). This avoids the infusion of particles into the bloodstream from the small intestine, which could lead to material accumulation in the liver and kidneys. In another aspect, the non-systematic metal titanate ion exchanger compositions of this disclosure can be designed to achieve minimal side effects compared to placebo. As described in U.S. Patents 8,802,152, 8,808,750, 9,844,567, and 10,335,432, and without being limited by any theory, there is a theory that small particles of insoluble powder with a diameter less than 3 μm may be absorbed into the patient's bloodstream through the small intestine, resulting in undesirable effects such as particle accumulation in the patient's urinary tract, and particularly in the patient's kidneys. Indeed, the FDA-approved drug LOKELMA ®The label for (sodium zirconium cyclosilicate) describes it as a non-absorbable powder containing no more than 3% particles smaller than 3 μm in diameter. In vivo pharmacokinetic studies in rats showed no significant signs of systemic absorption when a dose of sodium zirconium cyclosilicate powder conforming to this particle size distribution was recovered in feces.

[0129] In one aspect, the particulate metal titanate ion exchanger disclosed herein has a concentration greater than 150 m² / g (m²). 2 The Bruno-Emmett-Teller (BET) surface area ( / g) is significant. In one respect, the particulate metal titanate ion exchanger has a surface area greater than 160 m². 2 / g BET surface area. In one aspect, particulate metal titanate ion exchangers have a BET surface area greater than 170m. 2 / g BET surface area. In one aspect, particulate metal titanate ion exchangers have a BET surface area greater than 180m. 2 / g BET surface area. In one aspect, particulate metal titanate ion exchangers have a BET surface area greater than 190m. 2 / g BET surface area. In one respect, particulate metal titanate ion exchangers have a BET surface area greater than 200m. 2 / g BET surface area. In one aspect, particulate metal titanate ion exchangers have a BET surface area greater than 210m. 2 / g BET surface area. In one aspect, particulate metal titanate ion exchangers have a BET surface area greater than 220m. 2 / g BET surface area. In one aspect, particulate metal titanate ion exchangers have a BET surface area greater than 230m. 2 / g BET surface area. In one aspect, particulate metal titanate ion exchangers have a BET surface area greater than 240m. 2 The BET surface area is approximately 190 m² / g. In one aspect, particulate metal titanate ion exchangers have a BET surface area of ​​approximately 190 m² / g. 2 / g and approximately 240m 2 The BET surface area is between / g. In one aspect, particulate metal titanate ion exchangers have a BET surface area of ​​approximately 190m². 2 / g and approximately 225m 2 The BET surface area is between / g. In one aspect, particulate metal titanate ion exchangers have a BET surface area of ​​approximately 190m². 2 / g and approximately 210m 2 The BET surface area is between / g. In one aspect, particulate metal titanate ion exchangers have a BET surface area of ​​approximately 190m². 2 / g and approximately 200m 2 The BET surface area is between / g. In one aspect, particulate metal titanate ion exchangers have a BET surface area of ​​200m. 2 / g and 240m 2The BET surface area is between / g. In one aspect, particulate metal titanate ion exchangers have a BET surface area of ​​approximately 210 m² / g. 2 / g and approximately 240m 2 The BET surface area is between 225 m² / g. In one aspect, particulate metal titanate ion exchangers have a BET surface area of ​​approximately 225 m² / g. 2 / g and approximately 240m 2 The BET surface area is between / g. In one aspect, particulate metal titanate ion exchangers have a BET surface area of ​​approximately 236m². 2 / g BET surface area. In one aspect, particulate metal titanate ion exchangers have approximately 203m². 2 / g BET surface area. In one aspect, particulate metal titanate ion exchangers have approximately 197m². 2 / g of BET surface area.

[0130] In one aspect, the particulate metal titanate ion exchanger of this disclosure has a Pb-resistance ratio between about 100,000 mL / g and about 2,500,000 mL / g. 2+ The allocation coefficient (K) d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 200,000 mL / g and approximately 2,000,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-resistance ratio between approximately 395,000 mL / g and approximately 1,600,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-resistance ratio between approximately 320,000 mL / g and approximately 1,100,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 320,000 mL / g and approximately 1,000,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 320,000 mL / g and approximately 900,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 320,000 mL / g and approximately 800,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 320,000 mL / g and approximately 700,000 mL / g. 2+ Kd In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 320,000 mL / g and approximately 600,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 320,000 mL / g and approximately 500,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 320,000 mL / g and approximately 400,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-resistance ratio between approximately 400,000 mL / g and approximately 1,100,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-resistance ratio between approximately 500,000 mL / g and approximately 1,100,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 600,000 mL / g and approximately 1,100,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 700,000 mL / g and approximately 1,100,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-resistance ratio between approximately 800,000 mL / g and approximately 1,100,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-resistance ratio between approximately 900,000 mL / g and approximately 1,100,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-resistance ratio between approximately 1,000,000 mL / g and approximately 1,100,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 400,000 mL / g and approximately 1,000,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 500,000 mL / g and approximately 900,000 mL / g. 2+ Kd In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 600,000 mL / g and approximately 800,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 800,000 mL / g and approximately 850,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio between approximately 950,000 mL / g and approximately 1,000,000 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio of approximately 321,900 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio of approximately 495,800 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio of approximately 809,500 mL / g. 2+ K d In one respect, particulate metal titanate ion exchangers have a Pb-to-Pb ratio of approximately 967,800 mL / g. 2+ K d .

[0131] In one aspect of the method presented herein, minimal interference with Na-selected substances is achieved in eligible subjects after administration. + Mg 2+ K + and Ca 2+ The normal physiological levels of one or more ions. In one aspect of the method provided herein, the physiological levels of one or more ions are measured in the blood of a subject in need. In one aspect of the method provided herein, the normal physiological levels of the cation Na+ are measured. + K + Mg 2+ and Ca 2+ These ions have unique concentrations in the body (in the blood) and a unique range of concentrations considered normal in the body. The normal ranges for these ions are given in the table below. In one aspect of the methods presented herein, the minimum disturbance to the concentration of these ions will be considered to be a change less than half the magnitude of the variation seen within the normal range. For example, normal Na+... + The concentration varied by 23 mg / dL within the range of approximately 310 mg / dL to 333 mg / dL; Na +The minimum interference at concentration in this case will be less than ±12 mg / dL. The minimum interference values ​​are given in the table below.

[0132]

[0133] In one aspect, the granular metal titanate ion exchanger disclosed herein is an acid-treated granular metal titanate ion exchanger. In another aspect, the granular metal titanate ion exchanger disclosed herein is a macroporous, acid-treated granular metal titanate ion exchanger. In another aspect, the granular metal titanate ion exchanger disclosed herein is a polycrystalline aggregate metal titanate ion exchanger. In another aspect, the granular metal titanate ion exchanger disclosed herein is a macroporous polycrystalline aggregate metal titanate ion exchanger. In another aspect, the granular metal titanate ion exchanger disclosed herein is a granular metal titanate ion exchanger having a spherical or amorphous morphology. In another aspect, the granular metal titanate ion exchanger disclosed herein is a granular metal titanate ion exchanger having a spherical morphology. In another aspect, the granular metal titanate ion exchanger disclosed herein is a granular metal titanate ion exchanger having an amorphous morphology.

[0134] In one aspect, the granular metal titanate ion exchanger of this disclosure is a powdered granular metal titanate ion exchanger. In another aspect, the granular metal titanate ion exchanger of this disclosure is a powder. In another aspect, the granular metal titanate ion exchanger of this disclosure is in tablet form. In another aspect, the granular metal titanate ion exchanger of this disclosure in capsule form. In another aspect, the tablet form of the granular metal titanate ion exchanger of this disclosure further comprises a tablet coating.

[0135] In one aspect, the granular metal titanate ion exchanger of this disclosure is stable in a liquid environment with a pH of 1-2. In one aspect, the granular metal titanate ion exchanger of this disclosure is substantially insoluble in a pH range of 1-7. In one aspect, the granular metal titanate ion exchanger of this disclosure is substantially insoluble in a pH range of 7-13. In one aspect, the granular metal titanate ion exchanger of this disclosure is substantially insoluble in a pH range of 1-13. In one aspect, the granular metal titanate ion exchanger of this disclosure is insoluble at physiological pH. In one aspect, the granular metal titanate ion exchanger of this disclosure is substantially insoluble at physiological pH. As used herein, "physiological pH" refers to a pH range of 7.35-7.45. In one aspect, the granular metal titanate ion exchanger of this disclosure is insoluble at gastric pH. In one aspect, the granular metal titanate ion exchanger of this disclosure is substantially insoluble at gastric pH. As used herein, "gastric pH" refers to a pH range of 1-5.0. As used herein, “substantially insoluble” means a solubility in a fluid of <1%. According to the 2015 CRC manual, a material is considered soluble in a solvent if a saturated solution contains more than 1% (m / v); any material that dissolves 1% or less is considered substantially insoluble. The solubility of a compound in body fluids will be quite different from its solubility in pure water due to the influence of proteins, pH, and other solutes in the body. When determining the solubility of a material in gastrointestinal fluids and bloodstream, the pH of the biological fluid must be considered. The pH of gastrointestinal fluids varies considerably (see *J. Pharm. Sci.*, Vol. 104, No. 9, pp. 2855–2863, 2015 and *J. Indian Soc. Periodontol.*, Vol. 17, No. 4, pp. 461–465, 2013). For example, saliva has a pH of approximately neutral (average in the range of 6.2–7.6), gastric acid has an acidic pH (average in the range of 1.7–4.7), and the pH in the small intestine and colon is approximately neutral (average in the range of 5–8). Blood is approximately neutral, with an average pH of approximately 7.4 (see Crit. Care, Vol. 4, pp. 6–14, 2000). Therefore, if 1% or less of the material dissolves in a simulated biological fluid with a pH in the range of 1.5–8, the material is essentially insoluble in gastrointestinal fluids. (CRC Handbook of Chemistry and Physics, 95th edition, CRC Press: Boca Raton, FL, 2015, Editor: W.M. Haynes).In one aspect, the particulate metal titanate ion exchanger of this disclosure is insoluble in one or more bodily fluids selected from the group consisting of blood, urine, and gastrointestinal fluids. In one aspect, the particulate metal titanate ion exchanger of this disclosure is insoluble in blood. In one aspect, the particulate metal titanate ion exchanger of this disclosure is insoluble in urine. In one aspect, the particulate metal titanate ion exchanger of this disclosure is insoluble in gastrointestinal fluids. In one aspect, the particulate metal titanate ion exchanger of this disclosure is insoluble in both blood and urine. In one aspect, the particulate metal titanate ion exchanger of this disclosure is insoluble in both blood and gastrointestinal fluids. In one aspect, the particulate metal titanate ion exchanger of this disclosure is insoluble in both urine and gastrointestinal fluids. In one aspect, the particulate metal titanate ion exchanger of this disclosure is insoluble in each of blood, urine, and gastrointestinal fluids.

[0136] In one respect, “A” m Ti x M y O z In this context, "A" is an exchangeable cation. In one aspect, "A" is optionally selected from the group consisting of potassium ions, sodium ions, calcium ions, and hydrated hydrogen ions. In another aspect, "A" is selected from two or more of the group consisting of potassium ions, sodium ions, calcium ions, and hydrated hydrogen ions. In another aspect, "A" is selected from three or more of the group consisting of potassium ions, sodium ions, calcium ions, and hydrated hydrogen ions. In one aspect, "A" is a potassium ion. In another aspect, "A" is a sodium ion. In another aspect, "A" is a calcium ion. In another aspect, "A" is a hydrated hydrogen ion.

[0137] In one respect, “A” m Ti x M y O z The “M” in the designation stands for the framework metal. In one respect, the framework metal “M” is optionally chosen from Nb. 5+ Zr 4+ Sn 4+ Fe 3+ Fe 2+ Co 2+ Mn 2+ The group consists of [a specific component]. In one aspect, the skeleton metal "M" is optionally selected from Nb. 5 + Zr 4+ Sn 4+ Fe 3+ Fe 2+ Co 2+ Mn 2+ Two or more of the components in the group. In one aspect, the skeleton metal "M" is optionally selected from Nb.5+ Zr 4+ Sn 4+ Fe 3+ Fe 2+ Co 2+ Mn 2+ Three or more members in a group. In one respect, "M" is Nb 5+ In one respect, "M" is Zr 4+ In one respect, “M” is Sn 4+ In one respect, "M" is Fe. 3+ In one respect, "M" is Fe. 2+ In one respect, "M" is Co. 2+ In one respect, "M" is Mn 2+ .

[0138] In one respect, “A” m Ti x M y O z The “m” in the figure is the molar ratio of A to total metal (total metal = Ti + M). In one aspect, “m” has a value between about 0.10 and about 0.60. In another aspect, “m” has a value between about 0.10 and about 0.50. In another aspect, “m” has a value between about 0.10 and about 0.40. In another aspect, “m” has a value between about 0.10 and about 0.30. In another aspect, “m” has a value between about 0.10 and about 0.20. In another aspect, “m” has a value between about 0.20 and about 0.50. In another aspect, “m” has a value between about 0.30 and about 0.50. In another aspect, “m” has a value between about 0.40 and about 0.50. In one aspect, “m” has a value of about 0.28. In another aspect, “m” has a value of about 0.30. In another aspect, “m” has a value of about 0.40.

[0139] In one respect, “A” m Ti x M y O zThe “x” in the figure represents the mole fraction of total metallic titanium (Ti). In one aspect, “x” has a value between 0.50 and 1. In another aspect, “x” has a value between 0.60 and 1. In another aspect, “x” has a value between 0.70 and 1. In another aspect, “x” has a value between 0.80 and 1. In another aspect, “x” has a value between 0.90 and 1. In another aspect, “x” has a value between 0.50 and 0.90. In one aspect, “x” has a value between 0.50 and 0.60. In one aspect, “x” has a value between 0.50 and 0.70. In one aspect, “x” has a value of 0.50. In one aspect, “x” has a value of 0.60. In one aspect, “x” has a value of 0.70. In one aspect, “x” has a value of 0.80. In one aspect, “x” has a value of 0.90. In one aspect, “x” has a value of 1.

[0140] In one respect, “A” m Ti x M y O z The "y" in "x + y = 1" represents the mole fraction of the total metal "M". In one aspect, according to the stoichiometric equation "x + y = 1", "y" corresponds to "x". In one aspect, "y" has a value between 0 and 0.50. In one aspect, "y" has a value between 0 and 0.40. In one aspect, "y" has a value between 0 and 0.30. In one aspect, "y" has a value between 0 and 0.20. In one aspect, "y" has a value between 0 and 0.10. In one aspect, "y" has a value between 0.10 and 0.50. The values ​​of "y" are between 0.20 and 0.50. In one aspect, "y" has a value between 0.30 and 0.50. In one aspect, "y" has a value between 0.40 and 0.50. In one aspect, "y" has a value of zero. In one aspect, "y" has a value of 0.10. In one aspect, "y" has a value of 0.20. In one aspect, "y" has a value of 0.30. In one aspect, "y" has a value of 0.40. In one aspect, "y" has a value of 0.50.

[0141] In one respect, "x" is 1 and "y" is 0.

[0142] In one respect, “A” m Ti x M y O zThe “z” in the figure represents the molar ratio of oxygen (O) to total metal (total metal = Ti + M). In one aspect, “z” has a value between about 1.55 and about 2.85. In another aspect, “z” has a value between about 1.55 and about 2.70. In another aspect, “z” has a value between about 1.55 and about 2.55. In another aspect, “z” has a value between about 1.55 and about 2.40. In another aspect, “z” has a value between about 1.55 and about 2.25. In one aspect… In one aspect, "z" has a value between about 1.55 and about 2.10. In another aspect, "z" has a value between about 1.55 and about 1.95. In another aspect, "z" has a value between about 1.55 and about 1.80. In another aspect, "z" has a value between about 1.55 and about 1.65. In another aspect, "z" has a value between about 1.65 and about 2.85. In another aspect, "z" has a value between about 1.80 and about 2.85. In another aspect, "z" has... There are values ​​between about 1.95 and about 2.85. In one aspect, "z" has a value between about 2.10 and about 2.85. In one aspect, "z" has a value between about 2.25 and about 2.85. In one aspect, "z" has a value between about 2.40 and about 2.85. In one aspect, "z" has a value between about 2.55 and about 2.85. In one aspect, "z" has a value between about 2.70 and about 2.85. In one aspect, "z" has a value between about 1.55. The value of "z". In one aspect, "z" has a value of approximately 1.65. In one aspect, "z" has a value of approximately 1.80. In one aspect, "z" has a value of approximately 1.95. In one aspect, "z" has a value of approximately 2.10. In one aspect, "z" has a value of approximately 2.25. In one aspect, "z" has a value of approximately 2.40. In one aspect, "z" has a value of approximately 2.55. In one aspect, "z" has a value of approximately 2.70. In one aspect, "z" has a value of approximately 2.85.

[0143] In one respect, “A” m Ti x M y O z The Ti in “” includes Ti derived from one or more Ti-containing compounds, including but not limited to Ti(OiPr)4, TiCl4 and TiO2.

[0144] In one aspect, a multihydroxyl-containing complexing agent (MHCA) is a reactive complexing agent containing at least two hydroxyl groups. In one aspect, MHCA includes, but is not limited to, sugar alcohols such as d-sorbitol, mannitol, and xylitol; sugars such as glucose and fructose; and multihydroxyl-containing aromatic compounds such as catechol. In one aspect, MHCA is d-sorbitol. In one aspect, MHCA is mannitol. In one aspect, MHCA is xylitol. In one aspect, MHCA is catechol. In one aspect, MHCA is glucose. In one aspect, MHCA is fructose. In one aspect, MHCA is a mixture of one or more of d-sorbitol, mannitol, xylitol, catechol, fructose, and glucose. In one aspect, MHCA is a mixture of two or more of d-sorbitol, mannitol, xylitol, catechol, fructose, and glucose. In one aspect, this disclosure provides a pharmaceutical composition comprising a particulate metal titanate ion exchanger containing 0.01% by weight (w / w) to 4.0% by weight of at least one MHCA. In another aspect, this disclosure provides a pharmaceutical composition comprising a particulate metal titanate ion exchanger containing 0.01% by weight (w / w) to 2.0% by weight of at least one MHCA. In another aspect, this disclosure provides a pharmaceutical composition comprising a particulate metal titanate ion exchanger containing 0.01% by weight (w / w) to 1.0% by weight of at least one MHCA. In yet another aspect, this disclosure provides a pharmaceutical composition comprising a particulate metal titanate ion exchanger containing 0.01% by weight (w / w) to 0.6% by weight of at least one MHCA.

[0145] In one aspect, this disclosure provides a particulate metal titanate ion exchanger that, on an anhydrous basis, has the following empirical formula: A m Ti x M y O zA is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to total metal and has a value of 1.55 to 2.85, wherein the particulate metal titanate ion exchanger has been synthesized in the presence of at least one polyhydroxy complexing agent (MHCA), and wherein the particulate metal titanate ion exchanger has a median particle size greater than 3 micrometers (µm).

[0146] In one aspect, this disclosure provides a macroporous particulate titanate ion exchanger having the following empirical formula on an anhydrous basis: A m TiO z Where A is an exchangeable cation, i.e., potassium ion; "m" is the molar ratio of A to Ti and has a value of 0.10 to 0.60; and "z" is the molar ratio of O to Ti and has a value of 2.05 to 2.60. The macroporous titanate ion exchanger has been synthesized in the presence of a polyhydroxy complexing agent (MHCA), i.e., d-sorbitol. The macroporous particulate titanate ion exchanger has a median particle size between 25 micrometers (µm) and 125 micrometers. Less than 3.0% of the particles in the macroporous particulate titanate ion exchanger have a particle size of less than 3 micrometers (µm), and the macroporous particulate titanate ion exchanger has a particle size of at least 150 m² / g (m³). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0147] In one aspect, this disclosure provides a macroporous particulate titanate ion exchanger having the following empirical formula on an anhydrous basis: A m TiO zWhere A is an exchangeable cation, i.e., potassium ion; "m" is the molar ratio of A to Ti and has a value of 0.10 to 0.60; and "z" is the molar ratio of O to Ti and has a value of 2.05 to 2.60. The macroporous titanate ion exchanger has been synthesized in the presence of a polyhydroxy complexing agent (MHCA), i.e., d-sorbitol. The macroporous particulate titanate ion exchanger has a median particle size between 25 micrometers (µm) and 125 micrometers. Less than 0.5% of the particles in the macroporous particulate titanate ion exchanger have a particle size of less than 3 micrometers (µm), and the macroporous particulate titanate ion exchanger has a particle size of at least 150 m² / g (m³). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0148] B. Method

[0149] In one aspect, this disclosure provides and includes a method for manufacturing a tablet or capsule for oral administration, the tablet or capsule comprising a particulate metal titanate ion exchanger having the following empirical formula on an anhydrous basis: A m Ti x M y O z Wherein A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); “m” is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; “x” is the molar fraction of total metal Ti and has a value of 0.5 to 1; “y” is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1; and “z” is the molar ratio of O to total metal and has a value of 1.55 to 2.85. The granular metal titanate ion exchanger has a median particle size greater than 3 micrometers (μm). The method includes the following steps: (a) forming a reaction mixture comprising a reactive A source, a Ti source, at least one polyhydroxy complexing agent (MHCA) source, optionally an M source, optionally a hydrogen peroxide source, optionally a complexing agent (C) source, and water; (b) heating the reaction mixture for a certain period of time to form the metal titanate ion exchanger; (c) treating the metal titanate ion exchanger with an alkali metal base to form the granular metal titanate ion exchanger; and (d) forming capsules or tablets containing the granular metal titanate ion exchanger, wherein the reaction mixture has a composition expressed as the molar ratio of the following oxides: pA₂O : aTiO₂ : bMO q / 2: c H2O2 : d MHCA : e C : f H2O, wherein “p” has a value of about 4 to 40; “a” has a value of about 0.5 to 1; “b” has a value of 0 to 0.5, a+b=1; “q” is the charge on M and has a value of 2 to 5; “c” has a value of 0 to 6; “d” has a value of 0.2 to 4; “e” has a value of 0 to 4; and “f” has a value of 20 to 1000. In one aspect, at least one MHCA is selected from the group consisting of sugar alcohols, sugars, and aromatic compounds. In one aspect, at least one MHCA is d-sorbitol, mannitol, xylitol, catechol, fructose, or glucose. In one aspect, at least one MHCA is d-sorbitol. In one aspect, at least one MHCA is mannitol. In one aspect, at least one MHCA is xylitol. In one aspect, at least one MHCA is catechol. In one aspect, at least one MHCA is fructose. In one aspect, at least one MHCA is glucose. In one aspect, the Ti source is TiO2 powder or spray-dried TiO2 spheres. In one aspect, the Ti source is TiO2 powder. In one aspect, the Ti source is pre-formed spray-dried TiO2 spheres. In one aspect, the Ti source further includes Ti(OiPr)4. In one aspect, C is selected from the group consisting of citric acid, tartaric acid, EDTA, bipyridine, and any combination thereof. In one aspect, C is citric acid. In one aspect, C is tartaric acid. In one aspect, C is EDTA. In one aspect, C is bipyridine. In one aspect, C is a combination of two or more of citric acid, tartaric acid, EDTA, and bipyridine. In one aspect, hydrogen peroxide is a 30 wt% aqueous solution of hydrogen peroxide. In one aspect, the alkali metal base is potassium hydroxide. In one aspect, heating is carried out at about 85°C to about 225°C. In one aspect, the time period is between 0.5 days and 30 days. In one aspect, the method for manufacturing tablets or capsules for oral administration further includes the step of treating the particulate metal titanate ion exchanger with acid after step (c). In one aspect, the acid is selected from the group consisting of nitric acid, hydrochloric acid, perchloric acid, and sulfuric acid. In one aspect, the acid is nitric acid. In one aspect, the acid is hydrochloric acid. In one aspect, the acid is perchloric acid. In one aspect, the acid is sulfuric acid. In one aspect, the step of treating the particulate metal titanate ion exchanger with acid after step (c) is carried out at a pH between 1 and 3 for at least 15 minutes. In one aspect, the method for manufacturing tablets or capsules for oral administration further includes the step of sterilizing the particulate metal titanate ion exchanger. In one aspect, sterilization is carried out by an autoclave. In one aspect, the step (d) of forming capsules or tablets further includes adding a binder. In one aspect, the binder is zirconium oxide. In one aspect, the step (d) of forming capsules or tablets further includes annealing the particulate metal titanate ion exchanger.In one aspect, the method for manufacturing tablets or capsules for oral administration further includes the step of spray drying the particulate metal titanate ion exchanger to form expanded aggregates of the particulate metal titanate ion exchanger prior to forming the capsule or tablet.

[0150] In one aspect, this disclosure provides and includes a method for selectively removing Pb from gastrointestinal fluids. 2+ A method for removing Pb from a toxin involves contacting a fluid containing the toxin with a particulate metal titanate ion exchanger to produce an ion-exchanged ion exchanger, thereby removing Pb from the fluid. 2+ The toxin, this granular metal titanate ion exchanger, has the following empirical formula on an anhydrous basis: A m Ti x M y O z Wherein A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); “m” is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; “x” is the molar fraction of total metal Ti and has a value of 0.5 to 1; “y” is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1; and “z” is the molar ratio of O to total metal and has a value of 1.55 to 2.85, wherein the metal titanate ion exchanger has been synthesized in the presence of at least one polyhydroxy complexing agent (MHCA), wherein the particulate metal titanate ion exchanger has a median particle size greater than 3 micrometers (μm), and wherein the particulate metal titanate ion exchanger allows Na2+ from the fluid to react with Na2+. + Mg 2+ K + and Ca 2+ The level of any one or more ions is reduced by 3% or less. In one respect, particulate metal titanate ion exchangers reduce the level of ions selected from Na+. + Mg 2+ K + and Ca 2+ The level of any one or more ions is reduced by 2% or less. In one respect, particulate metal titanate ion exchangers reduce the level of ions selected from Na+. + Mg 2+ K + and Ca 2+ The level of any one or more ions is reduced by 1% or less. In one respect, particulate metal titanate ion exchangers reduce the level of ions selected from Na+. + Mg 2+K + and Ca 2+ The level of any one or more ions is reduced by 0.5% or less. In one aspect, particulate metal titanate ion exchangers allow the levels of ions selected from Na+ to decrease. + Mg 2+ K + and Ca 2+ The level of any one or more ions is reduced by 1% to 3%. In one aspect, particulate metal titanate ion exchangers reduce the level of ions selected from Na+. + Mg 2+ K + and Ca 2+ The level of any one or more ions is reduced by 0.5% to 3%. In one aspect, particulate metal titanate ion exchangers allow the levels of ions selected from Na+ to decrease. + Mg 2+ K + and Ca 2+ The level of any one or more ions is reduced by 1% to 2%. In one aspect, particulate metal titanate ion exchangers reduce the level of ions selected from Na+. + Mg 2+ K + and Ca 2+ The level of any one or more ions decreases by 0.5% to 1%. In one aspect, one or more ions are Na+. + Mg 2+ K + and Ca 2+ In one respect, particulate metal titanate ion exchangers do not substantially reduce the concentration of Na+ selected from Na+. + Mg 2+ K + and Ca 2+ The level of any one or more ions. In one respect, particulate metal titanate ion exchangers do not substantially reduce the level of Na+. + The level. On one hand, particulate metal titanate ion exchangers do not substantially reduce Mg. 2+ The level. In one respect, particulate metal titanate ion exchangers do not substantially reduce K. + The level. On one hand, particulate metal titanate ion exchangers do not substantially reduce Ca. 2+ The level. On one hand, particulate metal titanate ion exchangers do not substantially reduce Na+ levels. + Mg 2+ K + and Ca 2+ The levels of each of them. In one aspect, the elements selected from Na are measured by inductively coupled plasma (ICP) elemental analysis of the fluid. + Mg 2+ K+ and Ca 2+ The level of any one or more ions. In one respect, as measured by inductively coupled plasma (ICP) elemental analysis of the fluid, unbound Pb was not detected in the fluid after contact. 2+ Toxins. In one respect, Pb 2+ The toxin is isolated within an ion-exchange resin after contact. In one aspect, it is used for the selective removal of Pb from gastrointestinal fluids. 2+ Selective removal of toxins is an in vivo method.

[0151] In one aspect, this disclosure provides and includes a method for removing Pb from gastrointestinal fluids. 2+ An in vivo method for removing toxins, comprising contacting a fluid containing the toxin with a particulate metal titanate ion exchanger to generate an ion-exchanged ion exchanger, thereby removing the toxin from the fluid, the particulate metal titanate ion exchanger having the following empirical formula on an anhydrous basis: A m Ti x M y O z In this process, A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to total metal and has a value of 1.55 to 2.85, wherein the particulate metal titanate ion exchanger has been synthesized in the presence of at least one polyhydroxy complexing agent (MHCA). In one aspect, the particulate metal titanate ion exchanger product has been annealed at a temperature of 350°C for 2 to 6 hours. In one aspect, granular metal titanate ion exchangers have been formulated into molded articles for oral ingestion. In another aspect, the molded articles are selected from the group consisting of pellets, extrudates, spheres, pellets, and irregularly shaped particles. In one aspect, the molded article is a pellet. In another aspect, the molded article is an extrudate. In another aspect, the molded article is a sphere. In another aspect, the molded article is a pellet. In another aspect, the molded article is an irregularly shaped particle.

[0152] In one aspect, this disclosure provides and includes a method for preparing particulate metal titanate ion exchangers, which, on an anhydrous basis, have the following empirical formula: Am Ti x M y O z Where A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); “m” is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; “x” is the molar fraction of total metal Ti and has a value of 0.5 to 1; “y” is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y =1; and “z” is the molar ratio of O to total metal and has a value of 1.55 to 2.85. The method comprises the following steps: (a) forming a reaction mixture comprising a reactive A source, a Ti source, at least one polyhydroxy complexing agent (MHCA) source, optionally an M source, optionally a hydrogen peroxide source, optionally a complexing agent (C) source, and water; and (b) heating the reaction mixture at a temperature of about 85°C to about 225°C for a period of time from 0.5 days to 30 days to form a particulate metal titanate ion exchanger, wherein the reaction mixture has a composition expressed in the molar ratio of the following oxides:

[0153] p A2O : a TiO2 : b MO q / 2 : c H2O2 : d MHCA : e C : f H2O

[0154] Wherein “p” has a value of about 4 to 40; “a” has a value of about 0.5 to 1; “b” has a value of 0 to 0.5, a+b=1; “q” is the charge on M and has a value of 2 to 5; “c” has a value of 0 to 6; “d” has a value of 0.2 to 4; “e” has a value of 0 to 4; and “f” has a value of 20 to 1000. In one aspect, at least one MHCA is d-sorbitol, mannitol, xylitol, catechol, fructose, or glucose. In one aspect, at least one MHCA is d-sorbitol. In one aspect, at least one MHCA is mannitol. In one aspect, at least one MHCA is xylitol. In one aspect, at least one MHCA is catechol. In one aspect, at least one MHCA is fructose. In one aspect, at least one MHCA is glucose. In one aspect, C is selected from the group consisting of citric acid, tartaric acid, EDTA, bipyridine, and any combination thereof. In one aspect, C is citric acid. In one aspect, C is tartaric acid. In one aspect, C is EDTA. In one aspect, C is bipyridine. In another aspect, C is a combination of two or more of citric acid, tartaric acid, EDTA, and bipyridine. In one aspect, the reaction mixture of step (b) comprises hydrogen peroxide, a complexing agent (C), an MHCA, a Ti source namely Ti(OiPr)4, and optionally M. In one aspect, the reaction mixture of step (b) is a homogeneous solution. In one aspect, the Ti source is TiO2 powder. In one aspect, the Ti source is spray-dried TiO2 spheres. In one aspect, the Ti source is TiO2 powder, at least one MHCA is d-sorbitol, M is selected from the group consisting of Fe, Mn, Co, Sn, Zr, and mixtures thereof, and C is citric acid. In one aspect, the Ti source is TiO2 powder, optionally comprising another Ti source namely Ti(OiPr)4, at least one MHCA is d-sorbitol, the hydrogen peroxide is 30 wt% hydrogen peroxide, M is selected from the group consisting of Fe, Mn, Co, Sn, Zr, Nb, and mixtures thereof, and C is citric acid. In one aspect, the Ti source is spray-dried TiO2 spheres, at least one MHCA is d-sorbitol, M is Fe, Mn, Co, Sn, Zr or a mixture thereof, and C is citric acid. In another aspect, the Ti source is spray-dried TiO2 spheres, optionally including another Ti source namely Ti(OiPr)4, at least one MHCA is d-sorbitol, hydrogen peroxide is 30 wt% hydrogen peroxide, M is Fe, Mn, Co, Sn, Zr, Nb or a mixture thereof, and C is citric acid.

[0155] C. Definition

[0156] When used in a list of two or more items, the term "and / or" means that any one of the listed items can be used alone or in combination with any one or more of the listed items. For example, the expression "A and / or B" is intended to mean either or both of A and B, i.e., A alone, B alone, or a combination of A and B. The expression "A, B and / or C" is intended to mean A alone, B alone, C alone, a combination of A and B, a combination of A and C, a combination of B and C, or a combination of A, B and C.

[0157] As used herein, unless the context clearly states otherwise, the singular and singular forms of the terms “a,” “an,” and “the” include, for example, multiple referents.

[0158] When a range of values ​​is provided, it should be understood that every intermediate value between the upper and lower limits of the range, as well as any other specified value or intermediate value within the specified range, is covered within this disclosure. The upper and lower limits of these smaller ranges may be independently included in the smaller range and are also covered within this disclosure, subject to any specific exclusion of the specified range. Where a specified range includes one or two limits, the range excluding any one or both of those included limits is also included in this disclosure. Whenever the phrase “comprising” is used, variations such as “substantially consisting of” and “composed of” are also contemplated.

[0159] Unless otherwise defined herein, terms should be understood according to their conventional usage by one of ordinary skill in the art. Where a term is provided in the singular, the inventors also contemplate aspects of this disclosure described by the plural of that term. Where there are discrepancies between the terms and definitions used in references incorporated herein by reference, the terms used herein shall have the definitions given herein. Other technical terms used have their common meaning in the field in which they are used, as exemplified by various domain-specific dictionaries, such as "The American Heritage Dictionary of Science". ® "Science Dictionary" (Houghton Mifflin Harcourt, Boston and New York, 2011) or "McGraw-Hill Dictionary of Scientific and Technical Terms" (6th edition, 2002, McGraw-Hill, New York).

[0160] As used in this article, the term “about” refers to a range extending to + / - 10% of the specified value.

[0161] As used herein, "metalate" refers to a complex anionic compound comprising one or more metal atoms bonded to one or more nonmetal atoms. Metalates may also comprise one or more cations. In one aspect, the one or more metal atoms of a metalate are selected from titanium (Ti), niobium (Nb), zirconium (Zr), tin (Sn), cobalt (Co), and manganese (Mn). In one aspect, the one or more nonmetal atoms are selected from oxygen (O) and sulfur (S). In one aspect, the one or more cations of a metalate are selected from potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, and hydrated hydrogen ions. In one aspect, the metalate is inorganic. In one aspect, the metalate comprises titanium, oxygen, and potassium.

[0162] As used herein, "nano-sized titanium dioxide" or "nano-sized TiO2" refers to titanium dioxide reagents with a crystallite size or particle size spanning less than 200 nm, preferably about 100 nm or smaller. Any form of titanium dioxide can be nano-sized, including nano-sized anatase, nano-sized rutile, nano-sized brookite, nano-sized amorphous titanium dioxide, and nano-sized titanium hydroxyl oxide. Nano-sized titanium dioxide sources can be used to prepare pre-formed, spray-dried spherical reagents.

[0163] As used herein, "ion exchanger" refers to a complex in which one or more charged substances can exchange with one or more charged substances in the surrounding environment. In one respect, ion exchangers are cation exchangers.

[0164] As used in this article, “morphology” refers to the form or shape of a particle. The morphology of a particle can include, but is not limited to, spheres, interpenetrating spheres, fibers, masses, entangled plates, and amorphous forms.

[0165] As used in this article, "spherical morphology" refers to the morphology of particles that are essentially and distinguishably spherical.

[0166] As used in this article, “amorphous morphology” refers to a particle morphology that is substantially and identifiable as not having an ordered or repetitive form.

[0167] As used in this article, "macropore" refers to the porosity of particles with a pore size greater than approximately 50 nanometers (nm).

[0168] As used in this article, "polycrystalline" refers to the crystallinity of a material containing multiple microcrystals of different orientations and sizes.

[0169] As used in this article, "polycrystalline aggregate" refers to the crystallinity of an aggregate material containing several microcrystals of different orientations and sizes.

[0170] As used in this paper, “Bruno-Emmett-Teller (BET)” surface area refers to the specific surface area of ​​a solid porous material characterized by BET analysis based on gas adsorption measurements. See Brunauer et al., “Adsorption of Gas in Multimolecular Layers”, Journal of the American Chemical Society (J. Am. Chem. Soc.) 60(2):309-319. Unbound by theory, in BET analysis, the true or specific surface area (including surface roughness and pore walls) of porous solid particles is determined at the atomic level by adsorption of nonreactive gases. The BET equation calculates the surface coverage θ, where (p / p o ) is the relative pressure, and c is the BET C constant related to the heat of adsorption:

[0171] .

[0172] As used in this article, "in vivo" refers to a process that occurs within a subject or patient. For example, a process used to remove Pb. 2- The in vivo process of toxins refers to the removal of Pb from fluids such as gastrointestinal fluids in a subject or patient. 2+ The process.

[0173] As used herein, “annealing” refers to the process of heat-treating a material at one or more elevated temperatures for one or more predetermined time periods, wherein annealing can alter one or more physical or chemical properties of the material, including but not limited to crystallinity, particle morphology, particle size distribution, and porosity. Annealing parameters / conditions can selectively alter one or more physical or chemical properties of the material and may include, but are not limited to, heating rate, peak temperature, holding time, cooling rate, and gas environment. The gas environment used in the annealing process can be selected from, but is not limited to, the atmosphere and inert gases such as nitrogen (N2) or argon (Ar).

[0174] As used herein, “spray drying” refers to a technique that dries a sprayed liquid mixture or slurry into a substantially uniform dry powder by means of a heated gas. The heated gas can be a heated atmospheric gas or a heated inert gas, such as nitrogen (N2) or argon (Ar).

[0175] All publications, patents and patent applications mentioned in this disclosure are incorporated herein by reference to the extent that each individual publication, patent or patent application is specifically and individually indicated to be incorporated by reference.

[0176] Now that the disclosure has been described in its entirety, it will be more readily understood by referring to the following embodiments and examples, which are provided by way of illustration and are not intended to limit the disclosure, unless otherwise stated.

[0177] Implementation Plan

[0178] Implementation Scheme 1. A method for removing Pb from gastrointestinal fluids 2+ An in vivo method for removing a toxin, the method comprising contacting a fluid containing the toxin with a particulate metal titanate ion exchanger to generate an ion-exchanged ion exchanger, thereby removing the toxin from the fluid, the particulate metal titanate ion exchanger having the following empirical formula on an anhydrous basis:

[0179] A m Ti x M y O z

[0180] in

[0181] A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.85.

[0182] The particulate metal titanate ion exchanger described therein has been synthesized in the presence of at least one polyhydroxy complexing agent (MHCA).

[0183] Implementation Scheme 2. The method according to Implementation Scheme 1, wherein the polyhydroxy complexing agent (MHCA) is selected from the group consisting of d-sorbitol, mannitol, xylitol, catechol, fructose, glucose, and mixtures thereof.

[0184] Implementation Scheme 3. The method according to Implementation Scheme 1 or Implementation Scheme 2, wherein the particulate metal titanate ion exchanger has a median particle size greater than 3 micrometers (μm).

[0185] Implementation Scheme 4. The method according to any one of Implementation Schemes 1 to 3, wherein the particulate metal titanate ion exchanger has a median particle size in the range of 25 micrometers (μm) to 125 micrometers.

[0186] Implementation Scheme 5. The method according to any one of Implementation Schemes 1 to 4, wherein less than 3% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (μm).

[0187] Implementation Scheme 6. The method according to Implementation Scheme 5, wherein less than 0.5% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (μm).

[0188] Implementation Scheme 7. The method according to any one of Implementation Schemes 1 to 6, wherein the particulate metal titanate ion exchanger has a concentration greater than 150 m² / g (m²). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0189] Implementation Scheme 8. The method according to any one of Implementation Schemes 1 to 7, wherein the particulate metal titanate ion exchanger product has been annealed at a temperature of 350°C for 2 to 6 hours.

[0190] Implementation Scheme 9. The method according to any one of Implementation Schemes 1 to 8, wherein the particulate metal titanate ion exchanger has been formed into a molded article for oral ingestion.

[0191] Implementation Scheme 10. The method according to Implementation Scheme 9, wherein the molded article is selected from the group consisting of pellets, extrudates, spheres, granules and irregularly shaped particles.

[0192] Implementation Scheme 11. A method for preparing particulate metal titanate ion exchangers, wherein the particulate metal titanate ion exchangers have the following empirical formula on an anhydrous basis:

[0193] A m Ti x M y O z

[0194] in

[0195] A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.85.

[0196] The method includes the following steps:

[0197] (a) Forming a reaction mixture comprising a reactive A source, a Ti source, at least one polyhydroxy complexing agent (MHCA) source, optionally an M source, optionally a hydrogen peroxide source, optionally a complexing agent (C) source, and water, and

[0198] (b) The reaction mixture is heated at a temperature of about 85°C to about 225°C for a period of 0.5 days to 30 days to form the particulate metal titanate ion exchanger.

[0199] The reaction mixture has a composition expressed in the molar ratio of the following oxides:

[0200] p A2O : a TiO2 : b MO q / 2 : c H2O2 : d MHCA : e C : f H2O

[0201] Where “p” has a value of approximately 4 to 40; “a” has a value of approximately 0.5 to 1; “b” has a value of 0 to 0.5, a+b=1; “q” is the charge on M and has a value of 2 to 5; “c” has a value of 0 to 6; “d” has a value of 0.2 to 4; “e” has a value of 0 to 4; and “f” has a value of 20 to 1000.

[0202] Implementation Scheme 12. The method according to Implementation Scheme 11, wherein the at least one polyhydroxy complexing agent (MHCA) is selected from the group consisting of d-sorbitol, mannitol, xylitol, catechol, fructose, glucose, and mixtures thereof.

[0203] Implementation Scheme 13. The method according to Implementation Scheme 11 or Implementation Scheme 12, wherein C is citric acid, tartaric acid, EDTA, bipyridine, or a mixture thereof.

[0204] Implementation Scheme 14. The method according to any one of Implementation Schemes 11 to 13, wherein the reaction mixture comprises hydrogen peroxide, C, a polyhydroxy complexing agent (MHCA), a Ti source of Ti(OiPr)4, and optionally M.

[0205] Implementation Scheme 15. The method according to any one of Implementation Schemes 11 to 14, wherein the reaction mixture is a homogeneous solution.

[0206] Implementation Scheme 16. The method according to any one of Implementation Schemes 11 to 13, wherein the Ti source is TiO2 powder, including nano-sized titanium dioxide.

[0207] Implementation Scheme 17. The method according to any one of Implementation Schemes 11 to 13, wherein the Ti source is TiO2 powder, the at least one polyhydroxy complexing agent (MHCA) is d-sorbitol, M is selected from the group consisting of Fe, Mn, Co, Sn, Zr and mixtures thereof, and C is citric acid.

[0208] Implementation Scheme 18. The method according to any one of Implementation Schemes 11 to 13, wherein the Ti source is TiO2 powder, optionally including an additional Ti source namely Ti(OiPr)4, the at least one polyhydroxy complexing agent (MHCA) is d-sorbitol, the hydrogen peroxide is 30 wt% hydrogen peroxide, M is selected from the group consisting of Fe, Mn, Co, Sn, Zr, Nb and mixtures thereof, and C is citric acid.

[0209] Implementation Scheme 19. The method according to any one of Implementation Schemes 11 to 13, wherein the Ti source is a pre-formed spray-dried TiO2 sphere.

[0210] Implementation Scheme 20. The method according to any one of Implementation Schemes 11 to 13, wherein the Ti source is a pre-formed spray-dried TiO2 sphere, the at least one polyhydroxy complexing agent (MHCA) is d-sorbitol, M is Fe, Mn, Co, Sn, Zr or a mixture thereof, and C is citric acid.

[0211] Implementation Scheme 21. The method according to any one of Implementation Schemes 11 to 13, wherein the Ti source is spray-dried TiO2 spheres, optionally including an additional Ti source namely Ti(OiPr)4, the at least one polyhydroxy complexing agent (MHCA) is d-sorbitol, the hydrogen peroxide is 30 wt% hydrogen peroxide, M is Fe, Mn, Co, Sn, Zr, Nb or a mixture thereof, and C is citric acid.

[0212] Implementation Scheme 22. A particulate metal titanate ion exchanger, wherein the particulate metal titanate ion exchanger has the following empirical formula on an anhydrous basis:

[0213] A m Ti x M y O z

[0214] in

[0215] A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.85.

[0216] The particulate metal titanate ion exchanger has been synthesized in the presence of at least one multi-hydroxy complexing agent (MHCA), and the particulate metal titanate ion exchanger has a median particle size greater than 3 micrometers (μm).

[0217] Implementation Scheme 23. The ion exchanger according to Implementation Scheme 22, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0218] Implementation Scheme 24. The ion exchanger according to Implementation Scheme 22 or Implementation Scheme 23, wherein A is potassium ion, hydrated hydrogen ion or a mixture thereof.

[0219] Implementation Scheme 25. An ion exchanger according to any one of Implementation Schemes 22 to 24, wherein A is a potassium ion.

[0220] Implementation Scheme 26. The ion exchanger according to Implementation Scheme 22 or Implementation Scheme 23, wherein A is a sodium ion.

[0221] Implementation Scheme 27. The ion exchanger according to any one of Implementation Schemes 22 to 24, wherein A is a mixture of potassium and hydrated hydrogen ions.

[0222] Implementation Scheme 28. The ion exchanger according to any one of Implementation Schemes 22 to 27, wherein the particulate metal titanate ion exchanger is a polycrystalline aggregate metal titanate ion exchanger.

[0223] Implementation Scheme 29. The ion exchanger according to any one of Implementation Schemes 22 to 28, wherein the particulate metal titanate ion exchanger is macroporous.

[0224] Implementation Scheme 30. The ion exchanger according to any one of Implementation Schemes 22 to 29, wherein the particulate metal titanate ion exchanger has a spherical morphology.

[0225] Implementation Scheme 31. The ion exchanger according to any one of Implementation Schemes 22 to 29, wherein the particulate metal titanate ion exchanger has an amorphous morphology.

[0226] Implementation Scheme 32. The ion exchanger according to any one of Implementation Schemes 22 to 31, wherein the particulate metal titanate ion exchanger is a powder.

[0227] Implementation Scheme 33. The ion exchanger according to any one of Implementation Schemes 22 to 32, wherein the median particle size is between 25 micrometers (μm) and 125 micrometers.

[0228] Implementation Scheme 34. The ion exchanger according to any one of Implementation Schemes 22 to 33, wherein less than 3% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (μm).

[0229] Implementation Scheme 35. The ion exchanger according to Implementation Scheme 34, wherein less than 0.5% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (μm).

[0230] Implementation Scheme 36. The ion exchanger according to any one of Implementation Schemes 22 to 35, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 5 micrometers (μm) and about 70 μm. 10 value.

[0231] Implementation Scheme 37. The ion exchanger according to Implementation Scheme 36, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 12 μm and about 18 μm. 10 value.

[0232] Implementation Scheme 38. The ion exchanger according to Implementation Scheme 37, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 15 μm. 10 value.

[0233] Implementation Scheme 39. The ion exchanger according to Implementation Scheme 36, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 42 μm and about 48 μm. 10 value.

[0234] Implementation Scheme 40. The ion exchanger according to Implementation Scheme 39, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 45 μm. 10 value.

[0235] Implementation Scheme 41. The ion exchanger according to Implementation Scheme 36, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 51 μm and about 57 μm. 10 value.

[0236] Implementation Scheme 42. The ion exchanger according to Implementation Scheme 41, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 54 μm. 10 value.

[0237] Implementation Scheme 43. The ion exchanger according to any one of Implementation Schemes 22 to 42, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 25 micrometers (μm) and about 125 μm. 50 value.

[0238] Implementation Scheme 44. The ion exchanger according to Implementation Scheme 43, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 48 μm and about 54 μm. 50 value.

[0239] Implementation Scheme 45. The ion exchanger according to Implementation Scheme 44, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 51 μm. 50 value.

[0240] Implementation Scheme 46. The ion exchanger according to Implementation Scheme 43, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 71 μm and about 77 μm. 50 value.

[0241] Implementation Scheme 47. The ion exchanger according to Implementation Scheme 46, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 74 μm. 50 value.

[0242] Implementation Scheme 48. The ion exchanger according to Implementation Scheme 43, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 89 μm and about 95 μm. 50 value.

[0243] Implementation Scheme 49. The ion exchanger according to Implementation Scheme 48, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 92 μm. 50value.

[0244] Implementation Scheme 50. An ion exchanger according to any one of Implementation Schemes 22 to 49, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 55 micrometers (μm) and about 185 μm. 90 value.

[0245] Implementation Scheme 51. The ion exchanger according to Implementation Scheme 50, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 99 μm and about 105 μm. 90 value.

[0246] Implementation Scheme 52. The ion exchanger according to Implementation Scheme 51, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 102 μm. 90 value.

[0247] Implementation Scheme 53. The ion exchanger according to Implementation Scheme 50, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 137 μm and about 143 μm. 90 value.

[0248] Implementation Scheme 54. The ion exchanger according to Implementation Scheme 53, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 140 μm. 90 value.

[0249] Implementation Scheme 55. The ion exchanger according to Implementation Scheme 50, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 156 μm and about 162 μm. 90 value.

[0250] Implementation Scheme 56. The ion exchanger according to Implementation Scheme 55, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 159 μm. 90 value.

[0251] Implementation Scheme 57. The ion exchanger according to any one of Implementation Schemes 22 to 56, wherein the particulate metal titanate ion exchanger is stable in a liquid environment with a pH of 1-2.

[0252] Implementation Scheme 58. The ion exchanger according to any one of Implementation Schemes 22 to 57, wherein the particulate metal titanate ion exchanger has a concentration greater than 150 m² / g (m²). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0253] Implementation Scheme 59. The ion exchanger according to Implementation Scheme 58, wherein the particulate metal titanate ion exchanger has a density of approximately 197 m 2 / g of BET surface area.

[0254] Implementation Scheme 60. The ion exchanger according to any one of Implementation Schemes 22 to 57, wherein the particulate metal titanate ion exchanger has a concentration greater than 200 m² / g (m³). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0255] Implementation Scheme 61. The ion exchanger according to Implementation Scheme 60, wherein the particulate metal titanate ion exchanger has a particle size of approximately 203 μm. 2 / g of BET surface area.

[0256] Implementation Scheme 62. The ion exchanger according to any one of Implementation Schemes 22 to 57, wherein the particulate metal titanate ion exchanger has a concentration greater than 230 m² / g (m³). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0257] Implementation Scheme 63. The ion exchanger according to Implementation Scheme 62, wherein the particulate metal titanate ion exchanger has a particle size of approximately 236 μm. 2 / g of BET surface area.

[0258] Implementation Scheme 64. The ion exchanger according to any one of Implementation Schemes 22 to 63, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-7.

[0259] Implementation Scheme 65. The ion exchanger according to any one of Implementation Schemes 22 to 63, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 7-13.

[0260] Implementation Scheme 66. The ion exchanger according to any one of Implementation Schemes 22 to 63, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-13.

[0261] Implementation Scheme 67. The ion exchanger according to any one of Implementation Schemes 22 to 63, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0262] Implementation Scheme 68. The ion exchanger according to any one of Implementation Schemes 22 to 63 and 67, wherein the particulate metal titanate ion exchanger is substantially insoluble at gastric pH.

[0263] Implementation Scheme 69. The ion exchanger according to any one of Implementation Schemes 22 to 68, wherein the particulate metal titanate ion exchanger is substantially insoluble in one or more body fluids.

[0264] Implementation Scheme 70. The ion exchanger according to Implementation Scheme 69, wherein the one or more bodily fluids are selected from the group consisting of blood, urine and gastrointestinal fluids.

[0265] Implementation Scheme 71. An ion exchanger according to any one of Implementation Schemes 22 to 70, wherein the particulate metal titanate ion exchanger has a Pb-peptide ratio in solution between about 50,000 mL / g and about 5,500,000 mL / g. 2+ The allocation coefficient (K) d ).

[0266] Implementation Scheme 72. The ion exchanger according to Implementation Scheme 71, wherein the particulate metal titanate ion exchanger has a Pb-to-g ratio between about 100,000 mL / g and about 2,500,000 mL / g. 2+ K d .

[0267] Implementation Scheme 73. The ion exchanger according to Implementation Scheme 72, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 967,800. 2+ K d .

[0268] Implementation Scheme 74. The ion exchanger according to Implementation Scheme 72, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 809,500. 2+ K d .

[0269] Implementation Scheme 75. The ion exchanger according to Implementation Scheme 72, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 495,800. 2+ K d .

[0270] Implementation Scheme 76. The ion exchanger according to Implementation Scheme 72, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 321,900. 2+ K d .

[0271] Implementation Scheme 77. The ion exchanger according to any one of Implementation Schemes 22 to 76, wherein the at least one MHCA is selected from the group consisting of sugar alcohols, sugars, aromatic compounds, and any combination thereof.

[0272] Implementation Scheme 78. The ion exchanger according to Implementation Scheme 77, wherein at least one MHCA is a sugar alcohol.

[0273] Implementation Scheme 79. The ion exchanger according to Implementation Scheme 78, wherein the sugar alcohol is selected from the group consisting of d-sorbitol, mannitol and xylitol.

[0274] Implementation Scheme 80. The ion exchanger according to any one of Implementation Schemes 77 to 79, wherein the at least one MHCA is d-sorbitol.

[0275] Implementation Scheme 81. The ion exchanger according to Implementation Scheme 77, wherein at least one MHCA is a sugar.

[0276] Implementation Scheme 82. The ion exchanger according to Implementation Scheme 81, wherein the sugar is glucose or fructose.

[0277] Implementation Scheme 83. The ion exchanger according to Implementation Scheme 77, wherein at least one MHCA is an aromatic compound.

[0278] Implementation Scheme 84. The ion exchanger according to Implementation Scheme 83, wherein the aromatic compound is catechol.

[0279] Implementation Scheme 85. The ion exchanger according to any one of Implementation Schemes 22 to 84, wherein the particulate metal titanate ion exchanger comprises 0.01% by weight (w / w) to 4.0% by weight of the at least one MHCA.

[0280] Implementation Scheme 86. The ion exchanger according to Implementation Scheme 85, wherein the particulate metal titanate ion exchanger comprises 0.01% w / w to 0.6% w / w of the at least one MHCA.

[0281] Implementation Scheme 87. An ion exchanger according to any one of Implementation Schemes 22 to 86, wherein x is 1 and y is 0.

[0282] Implementation Scheme 88. An ion exchanger according to any one of Implementation Schemes 22 to 87, wherein m is between 0.10 and 0.50.

[0283] Implementation Scheme 89. The ion exchanger according to Implementation Scheme 88, wherein m is about 0.40.

[0284] Implementation Scheme 90. The ion exchanger according to Implementation Scheme 88, wherein m is about 0.30.

[0285] Implementation Scheme 91. The ion exchanger according to Implementation Scheme 88, wherein m is about 0.28.

[0286] Implementation Scheme 92. The ion exchanger according to any one of Implementation Schemes 22 to 91, wherein the particulate metal titanate ion exchanger has characteristic diffraction lines with a d-spacing of 3.00 Å to 3.11 Å in its X-ray diffraction (XRD) pattern.

[0287] Implementation Scheme 93. An ion exchanger according to any one of Implementation Schemes 22 to 92, wherein the particulate metal titanate ion exchanger has an X-ray diffraction (XRD) pattern having characteristic diffraction lines within the range provided in Table A or Table B below:

[0288] .

[0289] Implementation Scheme 94. The ion exchanger according to any one of Implementation Schemes 22 to 91, wherein the particulate metal titanate ion exchanger has characteristic diffraction lines with a d-spacing of 3.00 Å to 3.10 Å in its X-ray diffraction (XRD) pattern.

[0290] Implementation Scheme 95. An ion exchanger according to any one of Implementation Schemes 22 to 91 and 94, wherein the particulate metal titanate ion exchanger has an X-ray diffraction (XRD) pattern having characteristic diffraction lines within the range provided in Table C or Table D below:

[0291] .

[0292] Implementation Scheme 96. A macroporous granular titanate ion exchanger, wherein the macroporous granular titanate ion exchanger has the following empirical formula on an anhydrous basis:

[0293] A m TiO z

[0294] in

[0295] A is an exchangeable cation selected from the group consisting of potassium ions, hydrated hydrogen ions, and mixtures thereof; "m" is the molar ratio of A to Ti and has a value of 0.10 to 0.60; and "z" is the molar ratio of O to Ti and has a value of 2.05 to 2.60.

[0296] The macroporous titanate ion exchanger was synthesized in the presence of a polyhydroxy complexing agent (MHCA), namely d-sorbitol. The macroporous particulate titanate ion exchanger has a median particle size between 25 micrometers (μm) and 125 micrometers, with less than 3.0% of the particles having a particle size of less than 3 micrometers (μm), and the macroporous particulate titanate ion exchanger having a particle size of at least 150 m² / g.2 Bruno-Emet-Teller (BET) surface area ( / g).

[0297] Implementation Scheme 97. The ion exchanger according to Implementation Scheme 96, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0298] Implementation Scheme 98. The ion exchanger according to Implementation Scheme 96 or Implementation Scheme 97, wherein A is a potassium ion.

[0299] Implementation Scheme 99. The ion exchanger according to Implementation Scheme 96 or Implementation Scheme 97, wherein A is a hydrated hydrogen ion.

[0300] Implementation Scheme 100. The ion exchanger according to Implementation Scheme 96 or Implementation Scheme 97, wherein A is a mixture of potassium and hydrated hydrogen ions.

[0301] Implementation Scheme 101. The ion exchanger according to any one of Implementation Schemes 96 to 100, wherein the macroporous particulate titanate ion exchanger is a polycrystalline aggregate titanate ion exchanger.

[0302] Implementation Scheme 102. The ion exchanger according to any one of Implementation Schemes 96 to 101, wherein the macroporous particulate titanate ion exchanger has an amorphous morphology.

[0303] Implementation Scheme 103. The ion exchanger according to any one of Implementation Schemes 96 to 102, wherein the macroporous particulate titanate ion exchanger is a powder.

[0304] Implementation Scheme 104. The ion exchanger according to any one of Implementation Schemes 96 to 103, wherein about 2.1% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (μm).

[0305] Implementation Scheme 105. An ion exchanger according to any one of Implementation Schemes 96 to 104, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 5 micrometers (μm) and about 45 μm. 10 value.

[0306] Implementation Scheme 106. The ion exchanger according to Implementation Scheme 105, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 12 μm and about 18 μm. 10 value.

[0307] Implementation Scheme 107. The ion exchanger according to Implementation Scheme 106, wherein the macroporous particulate titanate ion exchanger has a particle size distribution of about 15 μm. 10 value.

[0308] Implementation Scheme 108. An ion exchanger according to any one of Implementation Schemes 96 to 107, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 25 micrometers (μm) and about 75 μm. 50 value.

[0309] Implementation Scheme 109. The ion exchanger according to Implementation Scheme 108, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 48 μm and about 54 μm. 50 value.

[0310] Implementation Scheme 110. The ion exchanger according to Implementation Scheme 109, wherein the macroporous particulate titanate ion exchanger has a particle size distribution of approximately 51 μm. 50 value.

[0311] Implementation Scheme 111. An ion exchanger according to any one of Implementation Schemes 96 to 110, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 55 micrometers (μm) and about 140 μm. 90 value.

[0312] Implementation Scheme 112. The ion exchanger according to Implementation Scheme 111, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 99 μm and about 105 μm. 90 value.

[0313] Implementation Scheme 113. The ion exchanger according to Implementation Scheme 112, wherein the macroporous particulate titanate ion exchanger has a particle size distribution of approximately 102 μm. 90 value.

[0314] Implementation Scheme 114. The ion exchanger according to any one of Implementation Schemes 96 to 113, wherein the macroporous particulate titanate ion exchanger is stable in a liquid environment with a pH of 1-2.

[0315] Implementation Scheme 115. The ion exchanger according to any one of Implementation Schemes 96 to 114, wherein the macroporous particulate titanate ion exchanger has a porosity of about 197 μm. 2 / g of BET surface area.

[0316] Implementation Scheme 116. An ion exchanger according to any one of Implementation Schemes 96 to 114, wherein the macroporous particulate titanate ion exchanger has a porosity of about 236 μm. 2 / g of BET surface area.

[0317] Implementation Scheme 117. The ion exchanger according to any one of Implementation Schemes 96 to 116, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-7.

[0318] Implementation Scheme 118. The ion exchanger according to any one of Implementation Schemes 96 to 116, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 7-13.

[0319] Implementation Scheme 119. The ion exchanger according to any one of Implementation Schemes 96 to 116, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-13.

[0320] Implementation Scheme 120. The ion exchanger according to any one of Implementation Schemes 96 to 116, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0321] Implementation Scheme 121. The ion exchanger according to any one of Implementation Schemes 96 to 116 and 120, wherein the particulate metal titanate ion exchanger is substantially insoluble at gastric pH.

[0322] Implementation Scheme 122. The ion exchanger according to any one of Implementation Schemes 96 to 121, wherein the macroporous particulate titanate ion exchanger is substantially insoluble in one or more body fluids.

[0323] Implementation Scheme 123. The ion exchanger according to Implementation Scheme 122, wherein the one or more bodily fluids are selected from the group consisting of blood, urine and gastrointestinal fluids.

[0324] Implementation Scheme 124. An ion exchanger according to any one of Implementation Schemes 96 to 123, wherein the macroporous particulate titanate ion exchanger has a Pb-to-g ratio between about 100,000 mL / g and about 2,500,000 mL / g. 2+ The allocation coefficient (K) d ).

[0325] Implementation Scheme 125. The ion exchanger according to Implementation Scheme 124, wherein the macroporous particulate titanate ion exchanger has a Pb-to-Pb ratio of approximately 809,500. 2+ K d .

[0326] Implementation Scheme 126. The ion exchanger according to Implementation Scheme 124, wherein the macroporous particulate titanate ion exchanger has a Pb-to-Pb ratio of approximately 495,800. 2+ K d .

[0327] Implementation Scheme 127. An ion exchanger according to any one of Implementation Schemes 96 to 126, wherein the macroporous particulate titanate ion exchanger comprises 0.01% by weight (w / w) to 4.0% by weight of the MHCA.

[0328] Implementation Scheme 128. The ion exchanger according to Implementation Scheme 127, wherein the particulate metal titanate ion exchanger comprises 0.01% w / w to 0.6% w / w of the MHCA.

[0329] Implementation Scheme 129. The ion exchanger according to any one of Implementation Schemes 96 to 128, wherein m is about 0.40.

[0330] Implementation Scheme 130. The ion exchanger according to any one of Implementation Schemes 96 to 128, wherein m is about 0.30.

[0331] Implementation Scheme 131. A macroporous granular titanate ion exchanger, wherein the macroporous granular titanate ion exchanger has the following empirical formula on an anhydrous basis:

[0332] A m TiO z

[0333] in

[0334] A is an exchangeable cation selected from the group consisting of potassium ions, hydrated hydrogen ions, and mixtures thereof; "m" is the molar ratio of A to Ti and has a value of 0.10 to 0.60; and "z" is the molar ratio of O to Ti and has a value of 2.05 to 2.60.

[0335] The macroporous particulate titanate ion exchanger described herein has been synthesized in the presence of a polyhydroxy complexing agent (MHCA), namely d-sorbitol. The macroporous particulate titanate ion exchanger has a median particle size between 25 micrometers (μm) and 125 micrometers, with less than 0.5% of the particles having a particle size of less than 3 micrometers (μm), and the macroporous particulate titanate ion exchanger having a particle size of at least 150 m² / g. 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0336] Implementation Scheme 132. The ion exchanger according to Implementation Scheme 131, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0337] Implementation Scheme 133. The ion exchanger according to Implementation Scheme 131 or Implementation Scheme 132, wherein A is a potassium ion.

[0338] Implementation Scheme 134. The ion exchanger according to Implementation Scheme 131 or Implementation Scheme 132, wherein A is a hydrated hydrogen ion.

[0339] Implementation Scheme 135. The ion exchanger according to Implementation Scheme 131 or Implementation Scheme 132, wherein A is a mixture of potassium and hydrated hydrogen ions.

[0340] Implementation Scheme 136. The ion exchanger according to any one of Implementation Schemes 131 to 135, wherein the macroporous particulate titanate ion exchanger is a polycrystalline aggregate titanate ion exchanger.

[0341] Implementation Scheme 137. The ion exchanger according to any one of Implementation Schemes 131 to 136, wherein the macroporous particulate titanate ion exchanger has a spherical morphology.

[0342] Implementation Scheme 138. The ion exchanger according to any one of Implementation Schemes 131 to 137, wherein the macroporous particulate titanate ion exchanger is a powder.

[0343] Implementation Scheme 139. An ion exchanger according to any one of Implementation Schemes 131 to 138, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 30 micrometers (μm) and about 70 μm. 10 value.

[0344] Implementation Scheme 140. The ion exchanger according to Implementation Scheme 139, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 42 μm and about 48 μm. 10 value.

[0345] Implementation Scheme 141. The ion exchanger according to Implementation Scheme 140, wherein the macroporous particulate titanate ion exchanger has a particle size distribution of approximately 45 μm. 10 value.

[0346] Implementation Scheme 142. The ion exchanger according to Implementation Scheme 139, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 51 μm and about 57 μm. 10 value.

[0347] Implementation Scheme 143. The ion exchanger according to Implementation Scheme 142, wherein the macroporous particulate titanate ion exchanger has a particle size distribution of approximately 54 μm. 10 value.

[0348] Implementation Scheme 144. An ion exchanger according to any one of Implementation Schemes 131 to 143, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 55 micrometers (μm) and about 125 μm. 50 value.

[0349] Implementation Scheme 145. The ion exchanger according to Implementation Scheme 144, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 71 μm and about 77 μm. 50 value.

[0350] Implementation Scheme 146. The ion exchanger according to Implementation Scheme 145, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 74 μm. 50 value.

[0351] Implementation Scheme 147. The ion exchanger according to Implementation Scheme 144, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 89 μm and about 95 μm. 50 value.

[0352] Implementation Scheme 148. The ion exchanger according to Implementation Scheme 147, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 92 μm. 50 value.

[0353] Implementation Scheme 149. An ion exchanger according to any one of Implementation Schemes 131 to 148, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 120 micrometers (μm) and about 180 μm. 90 value.

[0354] Implementation Scheme 150. The ion exchanger according to Implementation Scheme 149, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d between about 137 μm and about 143 μm. 90 value.

[0355] Implementation Scheme 151. The ion exchanger according to Implementation Scheme 150, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 140 μm. 90 value.

[0356] Implementation Scheme 152. The ion exchanger according to Implementation Scheme 149, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 156 μm and about 162 μm. 90 value.

[0357] Implementation Scheme 153. The ion exchanger according to Implementation Scheme 152, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 159 μm. 90 value.

[0358] Implementation Scheme 154. The ion exchanger according to any one of Implementation Schemes 131 to 153, wherein the macroporous particulate titanate ion exchanger is stable in a liquid environment with a pH of 1-2.

[0359] Implementation Scheme 155. An ion exchanger according to any one of Implementation Schemes 131 to 154, wherein the macroporous particulate titanate ion exchanger has a porosity of about 203 μm. 2 / g of BET surface area.

[0360] Implementation Scheme 156. The ion exchanger according to any one of Implementation Schemes 131 to 155, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-7.

[0361] Implementation Scheme 157. The ion exchanger according to any one of Implementation Schemes 131 to 155, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 7-13.

[0362] Implementation Scheme 158. The ion exchanger according to any one of Implementation Schemes 131 to 155, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-13.

[0363] Implementation Scheme 159. The ion exchanger according to any one of Implementation Schemes 131 to 155, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0364] Implementation Scheme 160. The ion exchanger according to any one of Implementation Schemes 131 to 155 and 159, wherein the particulate metal titanate ion exchanger is substantially insoluble at gastric pH.

[0365] Implementation Scheme 161. An ion exchanger according to any one of Implementation Schemes 131 to 160, wherein the macroporous particulate titanate ion exchanger is substantially insoluble in one or more body fluids.

[0366] Implementation Scheme 162. The ion exchanger according to Implementation Scheme 161, wherein the one or more bodily fluids are selected from the group consisting of blood, urine and gastrointestinal fluids.

[0367] Implementation Scheme 163. An ion exchanger according to any one of Implementation Schemes 131 to 162, wherein the macroporous particulate titanate ion exchanger has a Pb-to-g ratio between about 100,000 mL / g and about 2,500,000 mL / g. 2+ The allocation coefficient (K) d ).

[0368] Implementation Scheme 164. The ion exchanger according to Implementation Scheme 163, wherein the macroporous particulate titanate ion exchanger has a Pb-to-Pb ratio of approximately 967,800. 2+ K d .

[0369] Implementation Scheme 165. The ion exchanger according to Implementation Scheme 163, wherein the macroporous particulate titanate ion exchanger has a Pb-to-Pb ratio of approximately 321,900. 2+ K d .

[0370] Implementation Scheme 166. An ion exchanger according to any one of Implementation Schemes 131 to 165, wherein the macroporous particulate titanate ion exchanger comprises 0.01% by weight (w / w) to 4.0% by weight of the MHCA.

[0371] Implementation Scheme 167. An ion exchanger according to any one of Implementation Schemes 131 to 166, wherein m is about 0.28.

[0372] Implementation Scheme 168. A method for manufacturing tablets or capsules for oral administration, said tablets or capsules comprising a particulate metal titanate ion exchanger having the following empirical formula on an anhydrous basis:

[0373] A m Ti x M y O z

[0374] in

[0375] A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to total metal and has a value of 1.55 to 2.85, wherein the particulate metal titanate ion exchanger has a median particle size greater than 3 micrometers (μm), and the method includes the following steps:

[0376] (a) Forming a reaction mixture comprising a reactive A source, a Ti source, at least one polyhydroxy complexing agent (MHCA) source, optionally an M source, optionally a hydrogen peroxide source, optionally a complexing agent (C) source, and water.

[0377] (b) Heating the reaction mixture for a sufficient period of time is sufficient to form particulate metal titanate ion exchangers.

[0378] (c) Optionally, the metal titanate ion exchanger is treated by acid extraction and / or ion exchange with an alkali metal, alkaline earth metal, or a mixture thereof to form the particulate metal titanate ion exchanger having the desired composition, and

[0379] (d) Forming capsules or tablets containing the granular metal titanate ion exchanger.

[0380] The reaction mixture has a composition expressed in the molar ratio of the following oxides:

[0381] p A2O : a TiO2 : b MO q / 2 : c H2O2 : d MHCA : e C : f H2O

[0382] Where “p” has a value of approximately 4 to 40; “a” has a value of approximately 0.5 to 1; “b” has a value of 0 to 0.5, a+b=1; “q” is the charge on M and has a value of 2 to 5; “c” has a value of 0 to 6; “d” has a value of 0.2 to 4; “e” has a value of 0 to 4; and “f” has a value of 20 to 1000.

[0383] Implementation Scheme 169. The method according to Implementation Scheme 168, wherein the at least one MHCA is selected from the group consisting of sugar alcohols, sugars and aromatic compounds.

[0384] Implementation Scheme 170. The method according to Implementation Scheme 168 or Implementation Scheme 169, wherein the at least one MHCA is d-sorbitol, mannitol, xylitol, catechol, fructose or glucose.

[0385] Implementation Scheme 171. The method according to Implementation Schemes 168 to 170, wherein the Ti source is Ti(OiPr)4 and the reaction mixture is a solution.

[0386] Implementation Scheme 172. The method according to any one of Implementation Schemes 168 to 170, wherein the Ti source is TiO2 powder, including nano-sized TiO2, or pre-formed spray-dried TiO2 spheres.

[0387] Implementation Scheme 173. The method according to Implementation Scheme 172, wherein the Ti source further includes Ti(OiPr)4.

[0388] Implementation Scheme 174. The method according to any one of Implementation Schemes 168 to 173, wherein C is selected from the group consisting of citric acid, tartaric acid, EDTA, bipyridine, and any combination thereof.

[0389] Implementation Scheme 175. The method according to Implementation Scheme 174, wherein C is citric acid.

[0390] Implementation Scheme 176. The method according to any one of Implementation Schemes 168 to 175, wherein the hydrogen peroxide is a 30% by weight (wt%) aqueous solution of hydrogen peroxide.

[0391] Implementation Scheme 177. The method according to any one of Implementation Schemes 168 to 176, wherein the alkali metal base is potassium hydroxide.

[0392] Implementation Scheme 178. The method according to any one of Implementation Schemes 168 to 177, wherein the heating is performed at about 85°C to about 225°C.

[0393] Implementation Scheme 179. The method according to any one of Implementation Schemes 168 to 178, wherein the time period is between 0.5 days and 30 days.

[0394] Implementation Scheme 180. The method according to any one of Implementation Schemes 168 to 179, the method further comprising the step of treating the particulate metal titanate ion exchanger with acid after step (b).

[0395] Implementation Scheme 181. The method according to Implementation Scheme 180, wherein the acid is selected from the group consisting of nitric acid, hydrochloric acid, perchloric acid and sulfuric acid.

[0396] Implementation Scheme 182. The method according to Implementation Scheme 181, wherein the acid is nitric acid.

[0397] Implementation Scheme 183. The method according to any one of Implementation Schemes 180 to 182, wherein the particulate metal titanate ion exchanger is treated with acid at a pH between 1 and 3 for at least 15 minutes.

[0398] Implementation Scheme 184. The method according to any one of Implementation Schemes 168 to 183, the method further comprising the step of sterilizing the particulate metal titanate ion exchanger.

[0399] Implementation Scheme 185. The method according to Implementation Scheme 184, wherein the sterilization is performed by an autoclave.

[0400] Implementation Scheme 186. The method according to any one of Implementation Schemes 168 to 185, wherein forming the capsule or the tablet further includes adding an adhesive.

[0401] Implementation Scheme 187. The method according to Implementation Scheme 186, wherein the adhesive is zirconium oxide.

[0402] Implementation Scheme 188. The method according to any one of Implementation Schemes 168 to 187, wherein forming the capsule or the tablet comprises annealing the particulate metal titanate ion exchanger.

[0403] Implementation Scheme 189. The method according to any one of Implementation Schemes 168 to 188, the method further comprising the step of spray drying the particulate metal titanate ion exchanger to form an expanded aggregate of the particulate metal titanate ion exchanger prior to forming the capsule or the tablet.

[0404] Implementation Scheme 190. The method according to any one of Implementation Schemes 168 to 189, wherein A is a potassium ion, a hydrated hydrogen ion, or a mixture thereof.

[0405] Implementation Scheme 191. The method according to any one of Implementation Schemes 168 to 190, wherein A is a potassium ion.

[0406] Implementation Scheme 192. The method according to any one of Implementation Schemes 168 to 190, wherein A is a hydrated hydrogen ion.

[0407] Implementation Scheme 193. The method according to any one of Implementation Schemes 168 to 190, wherein A is a mixture of potassium and hydrated hydrogen ions.

[0408] Implementation Scheme 194. The method according to any one of Implementation Schemes 168 to 193, wherein the particulate metal titanate ion exchanger is a polycrystalline aggregate metal titanate ion exchanger.

[0409] Implementation Scheme 195. The method according to any one of Implementation Schemes 168 to 194, wherein the particulate metal titanate ion exchanger is macroporous.

[0410] Implementation Scheme 196. The method according to any one of Implementation Schemes 168 to 195, wherein the particulate metal titanate ion exchanger has a spherical morphology.

[0411] Implementation Scheme 197. The method according to any one of Implementation Schemes 168 to 195, wherein the particulate metal titanate ion exchanger has an amorphous morphology.

[0412] Implementation Scheme 198. The method according to any one of Implementation Schemes 168 to 197, wherein the particulate metal titanate ion exchanger is a powder.

[0413] Implementation Scheme 199. The method according to any one of Implementation Schemes 168 to 198, wherein the median particle size is between 25 micrometers (μm) and 125 micrometers.

[0414] Implementation Scheme 200. The method according to any one of Implementation Schemes 168 to 199, wherein less than 3% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (μm).

[0415] Implementation Scheme 201. The method according to Implementation Scheme 200, wherein less than 0.5% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (μm).

[0416] Implementation Scheme 202. The method according to any one of Implementation Schemes 168 to 201, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 5 micrometers (μm) and about 70 μm. 10 value.

[0417] Implementation Scheme 203. The method according to Implementation Scheme 202, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 12 μm and about 18 μm. 10 value.

[0418] Implementation Scheme 204. The method according to Implementation Scheme 203, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 15 μm. 10 value.

[0419] Implementation Scheme 205. The method according to Implementation Scheme 202, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 42 μm and about 48 μm. 10 value.

[0420] Implementation Scheme 206. The method according to Implementation Scheme 205, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 45 μm. 10 value.

[0421] Implementation Scheme 207. The method according to Implementation Scheme 202, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 51 μm and about 57 μm. 10 value.

[0422] Implementation Scheme 208. The method according to Implementation Scheme 207, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 54 μm. 10 value.

[0423] Implementation Scheme 209. The method according to any one of Implementation Schemes 168 to 208, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 25 micrometers (μm) and about 125 μm. 50 value.

[0424] Implementation Scheme 210. The method according to Implementation Scheme 209, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 48 μm and about 54 μm. 50 value.

[0425] Implementation Scheme 211. The method according to Implementation Scheme 210, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 51 μm. 50 value.

[0426] Implementation Scheme 212. The method according to Implementation Scheme 209, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 71 μm and about 77 μm. 50 value.

[0427] Implementation Scheme 213. The method according to Implementation Scheme 212, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 74 μm. 50 value.

[0428] Implementation Scheme 214. The method according to Implementation Scheme 209, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 89 μm and about 95 μm. 50 value.

[0429] Implementation Scheme 215. The method according to Implementation Scheme 214, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 92 μm. 50 value.

[0430] Implementation Scheme 216. The method according to any one of Implementation Schemes 168 to 215, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 55 micrometers (μm) and about 185 μm. 90 value.

[0431] Implementation Scheme 217. The method according to Implementation Scheme 216, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 99 μm and about 105 μm. 90 value.

[0432] Implementation Scheme 218. The method according to Implementation Scheme 217, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 102 μm. 90 value.

[0433] Implementation Scheme 219. The method according to Implementation Scheme 216, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 137 μm and about 143 μm. 90 value.

[0434] Implementation Scheme 220. The method according to Implementation Scheme 219, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 140 μm. 90 value.

[0435] Implementation Scheme 221. The method according to Implementation Scheme 216, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 156 μm and about 162 μm. 90 value.

[0436] Implementation Scheme 222. The method according to Implementation Scheme 221, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 159 μm. 90 value.

[0437] Implementation Scheme 223. The method according to any one of Implementation Schemes 168 to 222, wherein the particulate metal titanate ion exchanger is stable in a liquid environment with a pH of 1-2.

[0438] Implementation Scheme 224. The method according to any one of Implementation Schemes 168 to 223, wherein the particulate metal titanate ion exchanger has a concentration greater than 150 m² / g (m²). 2Bruno-Emet-Teller (BET) surface area ( / g).

[0439] Implementation Scheme 225. The method according to Implementation Scheme 224, wherein the particulate metal titanate ion exchanger has a density of approximately 197 m 2 / g of BET surface area.

[0440] Implementation Scheme 226. The method according to any one of Implementation Schemes 168 to 225, wherein the particulate metal titanate ion exchanger has a concentration greater than 200 m² / g (m²). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0441] Implementation Scheme 227. The method according to Implementation Scheme 226, wherein the particulate metal titanate ion exchanger has a density of approximately 203 μm. 2 / g of BET surface area.

[0442] Implementation Scheme 228. The method according to any one of Implementation Schemes 168 to 225, wherein the particulate metal titanate ion exchanger has a concentration greater than 230 m² / g (m²). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0443] Implementation Scheme 229. The method according to Implementation Scheme 228, wherein the particulate metal titanate ion exchanger has a particle size of approximately 236 μm. 2 / g of BET surface area.

[0444] Implementation Scheme 230. The method according to any one of Implementation Schemes 168 to 229, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-7.

[0445] Implementation Scheme 231. The method according to any one of Implementation Schemes 168 to 229, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 7-13.

[0446] Implementation Scheme 232. The method according to any one of Implementation Schemes 168 to 229, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-13.

[0447] Implementation Scheme 233. The method according to any one of Implementation Schemes 168 to 229, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0448] Implementation Scheme 234. The method according to any one of Implementation Schemes 168 to 229 and 233, wherein the particulate metal titanate ion exchanger is substantially insoluble at gastric pH.

[0449] Implementation Scheme 235. The method according to any one of Implementation Schemes 168 to 234, wherein the particulate metal titanate ion exchanger is substantially insoluble in one or more body fluids.

[0450] Implementation Scheme 236. The method according to Implementation Scheme 235, wherein the one or more bodily fluids are selected from the group consisting of blood, urine and gastrointestinal fluids.

[0451] Implementation Scheme 237. The method according to any one of Implementation Schemes 168 to 236, wherein the particulate metal titanate ion exchanger has a Pb-peptide ratio in solution between about 50,000 mL / g and about 5,500,000 mL / g. 2+ The allocation coefficient (K) d ).

[0452] Implementation Scheme 238. The method according to Implementation Scheme 237, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio between about 100,000 mL / g and about 2,500,000 mL / g. 2+ K d .

[0453] Implementation Scheme 239. The method according to Implementation Scheme 238, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 967,800. 2+ K d .

[0454] Implementation Scheme 240. The method according to Implementation Scheme 238, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 809,500. 2+ K d .

[0455] Implementation Scheme 241. The method according to Implementation Scheme 238, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 495,800. 2+ K d .

[0456] Implementation Scheme 242. The method according to Implementation Scheme 238, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 321,900. 2+ K d .

[0457] Implementation Scheme 243. The method according to any one of Implementation Schemes 168 to 242, wherein the particulate metal titanate ion exchanger comprises 0.01% by weight (w / w) to 4.0% by weight of the at least one MHCA.

[0458] Implementation Scheme 244. The method according to Implementation Scheme 243, wherein the particulate metal titanate ion exchanger comprises 0.01% w / w to 0.6% w / w of the at least one MHCA.

[0459] Implementation scheme 245. The method according to any one of implementation schemes 168 to 244, wherein x is 1 and y is 0.

[0460] Implementation Scheme 246. The method according to any one of Implementation Schemes 168 to 245, wherein m is between 0.10 and 0.50.

[0461] Implementation Scheme 247. The method according to Implementation Scheme 246, wherein m is approximately 0.40.

[0462] Implementation Scheme 248. The method according to Implementation Scheme 246, wherein m is approximately 0.30.

[0463] Implementation Scheme 249. The method according to Implementation Scheme 246, wherein m is approximately 0.28.

[0464] Implementation Scheme 250. The method according to any one of Implementation Schemes 168 to 249, wherein the X-ray diffraction (XRD) pattern of the particulate metal titanate ion exchanger has characteristic diffraction lines with a d-spacing of 3.00 Å to 3.11 Å.

[0465] Implementation Scheme 251. The method according to any one of Implementation Schemes 168 to 250, wherein the particulate metal titanate ion exchanger has an X-ray diffraction (XRD) pattern having characteristic diffraction lines within the range provided in Table A or Table B below:

[0466] .

[0467] Implementation Scheme 252. The method according to any one of Implementation Schemes 168 to 249, wherein the X-ray diffraction (XRD) pattern of the particulate metal titanate ion exchanger has characteristic diffraction lines with a d-spacing of 3.00 Å to 3.10 Å.

[0468] Implementation Scheme 253. The method according to any one of Implementation Schemes 168 to 249 and 252, wherein the particulate metal titanate ion exchanger has an X-ray diffraction (XRD) pattern having characteristic diffraction lines within the range provided in Table C or Table D below:

[0469]

[0470] Implementation Scheme 254. A method for selectively removing Pb from gastrointestinal fluids. 2+ A method for removing Pb from a fluid containing the toxin, the method comprising contacting the fluid containing the toxin with a particulate metal titanate ion exchanger to generate an ion-exchanged ion exchanger, thereby removing the Pb from the fluid. 2+ The toxin, the granular metal titanate ion exchanger, on an anhydrous basis, has the following empirical formula:

[0471] A m Ti x M y O z

[0472] in

[0473] A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.85.

[0474] The metal titanate ion exchanger described herein has been synthesized in the presence of at least one polyhydroxy complexing agent (MHCA), wherein the particulate metal titanate ion exchanger has a median particle size greater than 3 micrometers (μm), and wherein the particulate metal titanate ion exchanger minimally interferes with the Na+-selective fluid from the fluid. + Mg 2+ K + and Ca 2+ The level of any one or more ions.

[0475] Implementation Scheme 255. The method according to Implementation Scheme 254, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0476] Implementation Scheme 256. The method according to Implementation Scheme 254 or Implementation Scheme 255, wherein A is a potassium ion, a hydrated hydrogen ion, or a mixture thereof.

[0477] Implementation Scheme 257. The method according to any one of Implementation Schemes 254 to 256, wherein A is a potassium ion.

[0478] Implementation Scheme 258. The method according to any one of Implementation Schemes 254 to 256, wherein A is a hydrated hydrogen ion.

[0479] Implementation Scheme 259. The method according to any one of Implementation Schemes 254 to 256, wherein A is a mixture of potassium and hydrated hydrogen ions.

[0480] Implementation Scheme 260. The method according to any one of Implementation Schemes 254 to 259, wherein the particulate metal titanate ion exchanger is a polycrystalline aggregate metal titanate ion exchanger.

[0481] Implementation Scheme 261. The method according to any one of Implementation Schemes 254 to 260, wherein the particulate metal titanate ion exchanger is macroporous.

[0482] Implementation Scheme 262. The method according to any one of Implementation Schemes 254 to 261, wherein the particulate metal titanate ion exchanger has a spherical morphology.

[0483] Implementation Scheme 263. The method according to any one of Implementation Schemes 254 to 261, wherein the particulate metal titanate ion exchanger has an amorphous morphology.

[0484] Implementation Scheme 264. The method according to any one of Implementation Schemes 254 to 263, wherein the particulate metal titanate ion exchanger is a powder.

[0485] Implementation Scheme 265. The method according to any one of Implementation Schemes 254 to 264, wherein the median particle size is between 25 micrometers (μm) and 125 micrometers.

[0486] Implementation Scheme 266. The method according to any one of Implementation Schemes 254 to 265, wherein less than 3% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (μm).

[0487] Implementation Scheme 267. The method according to Implementation Scheme 266, wherein less than 0.5% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (μm).

[0488] Implementation Scheme 268. The method according to any one of Implementation Schemes 254 to 267, wherein the particulate metal titanate ion exchanger has a particle size distribution between about 5 micrometers (μm) and about 70 μm. 10 value.

[0489] Implementation Scheme 269. The method according to Implementation Scheme 268, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 12 μm and about 18 μm. 10 value.

[0490] Implementation Scheme 270. The method according to Implementation Scheme 269, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 15 μm. 10 value.

[0491] Implementation Scheme 271. The method according to Implementation Scheme 268, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 42 μm and about 48 μm. 10 value.

[0492] Implementation Scheme 272. The method according to Implementation Scheme 271, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 45 μm. 10 value.

[0493] Implementation Scheme 273. The method according to Implementation Scheme 268, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 51 μm and about 57 μm. 10 value.

[0494] Implementation Scheme 274. The method according to Implementation Scheme 273, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 54 μm. 10 value.

[0495] Implementation Scheme 275. The method according to any one of Implementation Schemes 254 to 274, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 25 micrometers (μm) and about 125 μm. 50 value.

[0496] Implementation Scheme 276. The method according to Implementation Scheme 275, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 48 μm and about 54 μm. 50 value.

[0497] Implementation Scheme 277. The method according to Implementation Scheme 276, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 51 μm. 50 value.

[0498] Implementation Scheme 278. The method according to Implementation Scheme 275, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 71 μm and about 77 μm. 50 value.

[0499] Implementation Scheme 279. The method according to Implementation Scheme 278, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 74 μm. 50 value.

[0500] Implementation Scheme 280. The method according to Implementation Scheme 275, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 89 μm and about 95 μm. 50 value.

[0501] Implementation Scheme 281. The method according to Implementation Scheme 280, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 92 μm. 50 value.

[0502] Implementation Scheme 282. The method according to any one of Implementation Schemes 254 to 281, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 55 micrometers (μm) and about 185 μm. 90 value.

[0503] Implementation Scheme 283. The method according to Implementation Scheme 282, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 99 μm and about 105 μm. 90 value.

[0504] Implementation Scheme 284. The method according to Implementation Scheme 283, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 102 μm. 90 value.

[0505] Implementation Scheme 285. The method according to Implementation Scheme 282, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 137 μm and about 143 μm. 90 value.

[0506] Implementation Scheme 286. The method according to Implementation Scheme 285, wherein the particulate metal titanate ion exchanger has a particle size distribution of about 140 μm. 90 value.

[0507] Implementation Scheme 287. The method according to Implementation Scheme 282, wherein the particulate metal titanate ion exchanger has a particle size distribution d between about 156 μm and about 162 μm.90 value.

[0508] Implementation Scheme 288. The method according to Implementation Scheme 287, wherein the particulate metal titanate ion exchanger has a particle size distribution of approximately 159 μm. 90 value.

[0509] Implementation Scheme 289. The method according to any one of Implementation Schemes 254 to 288, wherein the particulate metal titanate ion exchanger is stable in a liquid environment with a pH of 1-2.

[0510] Implementation Scheme 290. The method according to any one of Implementation Schemes 254 to 289, wherein the particulate metal titanate ion exchanger has a concentration greater than 150 m² / g (m²). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0511] Implementation Scheme 291. The method according to Implementation Scheme 290, wherein the particulate metal titanate ion exchanger has a density of approximately 197 m 2 / g of BET surface area.

[0512] Implementation Scheme 292. The method according to any one of Implementation Schemes 254 to 289, wherein the particulate metal titanate ion exchanger has a concentration greater than 200 m² / g (m²). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0513] Implementation Scheme 293. The method according to Implementation Scheme 292, wherein the particulate metal titanate ion exchanger has a density of approximately 203 μm. 2 / g of BET surface area.

[0514] Implementation Scheme 294. The method according to any one of Implementation Schemes 254 to 289, wherein the particulate metal titanate ion exchanger has a concentration greater than 230 m² / g (m³). 2 Bruno-Emet-Teller (BET) surface area ( / g).

[0515] Implementation Scheme 295. The method according to Implementation Scheme 294, wherein the particulate metal titanate ion exchanger has a particle size of approximately 236 μm. 2 / g of BET surface area.

[0516] Implementation Scheme 296. The method according to any one of Implementation Schemes 254 to 295, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-7.

[0517] Implementation Scheme 297. The method according to any one of Implementation Schemes 254 to 295, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 7-13.

[0518] Implementation Scheme 298. The method according to any one of Implementation Schemes 254 to 295, wherein the particulate metal titanate ion exchanger is substantially insoluble in a pH range of 1-13.

[0519] Implementation Scheme 299. The method according to any one of Implementation Schemes 254 to 298, wherein the particulate metal titanate ion exchanger is substantially insoluble in the fluid.

[0520] Implementation Scheme 300. The method according to any one of Implementation Schemes 254 to 299, wherein the particulate metal titanate ion exchanger has a Pb-to-g ratio between about 50,000 mL / g and about 5,500,000 mL / g. 2+ The allocation coefficient (K) d ).

[0521] Implementation Scheme 301. The method according to Implementation Scheme 300, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio between about 100,000 mL / g and about 2,500,000 mL / g. 2+ K d .

[0522] Implementation Scheme 302. The method according to Implementation Scheme 301, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 967,800. 2+ K d .

[0523] Implementation Scheme 303. The method according to Implementation Scheme 301, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 809,500. 2+ K d .

[0524] Implementation Scheme 304. The method according to Implementation Scheme 301, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 495,800. 2+ K d .

[0525] Implementation Scheme 305. The method according to Implementation Scheme 301, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio of approximately 321,900. 2+ K d .

[0526] Implementation Scheme 306. The method according to any one of Implementation Schemes 254 to 305, wherein the at least one MHCA is selected from the group consisting of sugar alcohols, sugars, aromatic compounds, and any combination thereof.

[0527] Implementation Scheme 307. The method according to Implementation Scheme 306, wherein the at least one MHCA is a sugar alcohol.

[0528] Implementation Scheme 308. The method according to Implementation Scheme 307, wherein the sugar alcohol is selected from the group consisting of d-sorbitol, mannitol and xylitol.

[0529] Implementation Scheme 309. The method according to any one of Implementation Schemes 306 to 308, wherein the at least one MHCA is d-sorbitol.

[0530] Implementation Scheme 310. The method according to Implementation Scheme 306, wherein the at least one MHCA is a sugar.

[0531] Implementation Scheme 311. The method according to Implementation Scheme 310, wherein the sugar is glucose or fructose.

[0532] Implementation Scheme 312. The method according to Implementation Scheme 306, wherein the at least one MHCA is an aromatic compound.

[0533] Implementation Scheme 313. The method according to Implementation Scheme 312, wherein the aromatic compound is catechol.

[0534] Implementation Scheme 314. The method according to any one of Implementation Schemes 254 to 313, wherein the particulate metal titanate ion exchanger comprises 0.01% by weight (w / w) to 4.0% by weight of the at least one MHCA.

[0535] Implementation Scheme 315. The method according to Implementation Scheme 314, wherein the particulate metal titanate ion exchanger comprises 0.01% w / w to 0.6% w / w of the at least one MHCA.

[0536] Implementation scheme 316. The method according to any one of implementation schemes 254 to 315, wherein x is 1 and y is 0.

[0537] Implementation scheme 317. The method according to any one of implementation schemes 254 to 316, wherein m is between 0.10 and 0.50.

[0538] Implementation Scheme 318. The method according to Implementation Scheme 317, wherein m is approximately 0.40.

[0539] Implementation Scheme 319. The method according to Implementation Scheme 317, wherein m is approximately 0.30.

[0540] Implementation Scheme 320. The method according to Implementation Scheme 317, wherein m is approximately 0.28.

[0541] Implementation Scheme 321. The method according to any one of Implementation Schemes 254 to 320, wherein the X-ray diffraction (XRD) pattern of the particulate metal titanate ion exchanger has characteristic diffraction lines with a d-spacing of 3.00 Å to 3.11 Å.

[0542] Implementation Scheme 322. The method according to any one of Implementation Schemes 254 to 321, wherein the particulate metal titanate ion exchanger has an X-ray diffraction (XRD) pattern having characteristic diffraction lines within the range provided in Table A or Table B below:

[0543] .

[0544] Implementation Scheme 323. The method according to any one of Implementation Schemes 254 to 320, wherein the X-ray diffraction (XRD) pattern of the particulate metal titanate ion exchanger has characteristic diffraction lines with a d-spacing of 3.00 Å to 3.10 Å.

[0545] Implementation Scheme 324. The method according to any one of Implementation Schemes 254 to 320 and 322, wherein the particulate metal titanate ion exchanger has an X-ray diffraction (XRD) pattern having characteristic diffraction lines within the range provided in Table C or Table D below:

[0546]

[0547] Implementation Scheme 325. The method according to any one of Implementation Schemes 254 to 324, wherein the particulate metal titanate ion exchanger minimally interferes with Na + Mg 2+ K + and Ca 2+ The level of any one or more ions.

[0548] Implementation Scheme 326. The method according to Implementation Scheme 325, wherein the particulate metal titanate ion exchanger causes Na... + The ion level decreased by 12 mg / dL or lower.

[0549] Implementation Scheme 327. The method according to Implementation Scheme 325, wherein the particulate metal titanate ion exchanger makes K + The ion level decreased by 3.0 mg / dL or lower.

[0550] Implementation Scheme 328. The method according to Implementation Scheme 325, wherein the particulate metal titanate ion exchanger causes Mg 2+ The ion level decreased by 0.6 mg / dL or less.

[0551] Implementation Scheme 329. The method according to Implementation Scheme 325, wherein the particulate metal titanate ion exchanger causes Ca... 2+ The ion level decreased by 1.0 mg / dL or lower.

[0552] Implementation Scheme 330. The method according to Implementation Schemes 254 to 324, wherein the particulate metal titanate ion exchanger substantially does not reduce the amount of Na+ selected from Na+. + Mg 2+ K + and Ca 2+ The level of any one or more ions.

[0553] Implementation Scheme 331. The method according to any one of Implementation Schemes 254 to 330, wherein the one or more ions is Na + Mg 2+ K + and Ca 2+ .

[0554] Implementation Scheme 332. The method according to any one of Implementation Schemes 254 to 331, wherein the elemental composition selected from Na is measured by inductively coupled plasma (ICP) elemental analysis of the fluid. + Mg 2+ K + and Ca 2+ The level of any one or more of the ions.

[0555] Implementation Scheme 333. The method according to any one of Implementation Schemes 254 to 332, wherein, as measured by inductively coupled plasma (ICP) elemental analysis of the fluid, no unbound Pb is detected in the fluid after the contact. 2+ toxin.

[0556] Implementation Scheme 334. The method according to any one of Implementation Schemes 254 to 333, wherein the Pb 2+ The toxin is isolated within the ion-exchanged ion exchanger after the contact.

[0557] Implementation Scheme 335. The method according to any one of Implementation Schemes 254 to 334, wherein the selective removal is an in vivo method.

[0558] Example

[0559] 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. Diffraction patterns from copper K-α irradiation were obtained using suitable computer-based techniques. Flat, compressed powder samples were continuously scanned from 2° to at least 56° (2θ). The interplanar spacing (d), in angstroms, was obtained from the positions of the diffraction peaks, denoted as θ, where θ is the Bragg angle as observed from the digitized data. The intensity was determined by the integrated area of ​​the diffraction peaks after subtracting the background, “I…” o "I" represents the intensity of the strongest line or peak, and "I" represents the intensity of each of the other peaks.

[0560] As those skilled in the art will understand, without being limited by theory, the determination of parameter 2θ is subject to both human and mechanical errors, the combination of which can impart an uncertainty of approximately ±0.4° to each reported 2θ value. This uncertainty is also reflected in the reported d-spacing values, which are calculated from the 2θ value. This imprecision is common in the art and is insufficient to eliminate the differentiation between the crystalline materials of the present invention and compositions of the prior art. In the reported X-ray images, the relative intensity of the d-spacing is indicated by the symbols vs, s, m, and w, which represent very strong, strong, moderate, and weak, respectively. According to 100 × I / I o The above name is defined as:

[0561] w>0-15; m>15-60; s>60-80 and vs>80-100.

[0562] In some cases, the purity of a synthesized product can be assessed by referring to its X-ray powder diffraction pattern. Thus, for example, if a sample is described as pure, it is only intended to indicate that the sample's X-ray pattern does not contain lines attributable to crystalline impurities, not that amorphous material is absent.

[0563] Furthermore, while elemental analysis can be used to determine the stoichiometry of metals, the elements oxygen, hydrogen, and water are not determined by this analytical method. Oxidation stoichiometry is inferred by balancing the charges on the metals; therefore, the metal titanate ion exchanger compositions disclosed herein are described in their anhydrous state.

[0564] Examples 1-15: Synthesis of Metal Titanates from Solution

[0565] Examples 1-15 provide examples of synthesizing the disclosed metal titanate ion exchangers from homogeneous solutions. In one aspect, a method uses three different complexing agents: hydrogen peroxide to provide initial dissolution of Ti in an acidic solution; a second complexing agent, such as citric acid, to help retain Ti and the M metal in solution as the pH increases to approximately 10; and an MHCA agent, such as d-sorbitol, to stabilize Ti and the M metal in a homogeneous solution at a very high pH suitable for the synthesis of the metal titanate ion exchanger. In each reaction mixture, it was demonstrated that the structure generally varies with reaction conditions, choice of base, base perturbation, and ion exchange. Examples including more than one X-ray diffraction pattern yield more than one crystal structure from the described reaction mixtures, depending on the reaction conditions initiated in a given example, demonstrating the diversity of structural results from this novel synthetic method. The results include large polycrystalline aggregate morphologies in the products, which are further illustrated in Examples 26 and 27.

[0566] Examples 1A and 1B

[0567] A Teflon-lined beaker containing 90.00 g of deionized water was fitted with a top-mounted mixer. Under vigorous stirring, 21.11 g of H₂O₂ (30 wt%), 17.89 g of citric acid, and 16.96 g of d-sorbitol were added and dissolved. Then, 13.35 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, and a dark red-orange solution formed after stirring for 2 minutes following the addition. Separately, 38.00 g of NaOH (98%) was dissolved in 75.00 g of deionized water and stirred and cooled. This NaOH solution was rapidly added dropwise under vigorous stirring, and after a series of color changes, a clear, almost colorless solution formed. The highly alkaline clear solution was partitioned into four Teflon-lined reaction vessels and statically digested at autogenous pressure at 175 °C and 190 °C for 49 h and 166 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. Powder X-ray diffraction (PXRD) was used to characterize the products. Characteristic diffraction lines of the products of Example 1A (175°C / 49 hours) and Example 1B (190°C / 166 hours) are provided in Table 1.

[0568] Table 1

[0569]

[0570] Example 2

[0571] A Teflon-lined beaker containing 90.00 g of deionized water was fitted with a top-mounted mixer. Under vigorous stirring, 21.11 g of H₂O₂ (30 wt%), 17.89 g of citric acid, and 16.96 g of d-sorbitol were added to obtain a clear, colorless solution. Then, 13.35 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise to form a dark orange-red solution. Separately, 59.97 g of KOH (87.1%) was dissolved in 100.00 g of deionized water and stirred and cooled. The KOH solution was rapidly added dropwise under vigorous stirring, resulting in a clear, almost colorless solution with a pale yellow hue after a series of color changes. The highly alkaline clear solution was partitioned into four Teflon-lined reaction vessels and statically digested at autogenous pressure at 175 °C and 190 °C for 49 h and 166 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the product, and the characteristic diffraction lines of Example 2 (190°C / 49 hours) are provided in Table 2.

[0572] Table 2

[0573]

[0574] Examples 3A and 3B

[0575] 450.00 g of deionized water was added to a 3 L polypropylene beaker and placed under a top-mounted mixer. Under vigorous mixing, 158.71 g of H₂O₂ (30 wt%), 67.24 g of citric acid, and 63.76 g of d-sorbitol were added and dissolved. Separately, 171.43 g of NaOH (98%) was dissolved in 250.0 g of deionized water and stirred and cooled. Then, 100.32 g of Ti(OiPr)₄ (16.7% Ti) was added to the 3 L beaker, forming an orange-red solution; some precipitate dissolved with stirring. NaOH solution was added in three equal portions, and the reaction mixture was stirred and cooled after each addition. The final reaction mixture was a highly alkaline, pale yellow solution. The reaction mixture was placed in a Teflon-lined 2 L Pal reactor and statically digested at 175 °C for 160 h under autogenous pressure. The solid product was separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the product. The characteristic diffraction lines of the product in Example 3A are shown in Table 3 below. Elemental analysis by ICP yielded the empirical metallic composition Na of the material in Example 3A. 0.36 Ti 1.00 .

[0576] 2.0 g of the product was ion-exchanged at room temperature using 100 mL of 0.5 M Mg(NO3)2 solution. The exchange was performed three times, and the product was then washed with deionized water and air-dried. The product of Example 3B was characterized by PXRD, and the characteristic diffraction lines are provided in Table 3. Mg 2+ The exchanged products exhibit different XRD patterns and have higher crystallinity than the parent compound.

[0577] Table 3

[0578]

[0579] Examples 4A and 4B

[0580] This embodiment provides an example of altering the structure of a metal titanate by perturbing a substance similar to the reaction mixture of Example 2 with LiCl. 90.00 g of deionized water was placed in a Teflon beaker under a top-mounted mixer. With vigorous stirring, 21.11 g of H₂O₂ (30 wt%), 17.89 g of citric acid, and 16.96 g of d-sorbitol were added and dissolved. Then, 13.35 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, forming a reddish-orange solution within minutes of the addition. Separately, 59.99 g of KOH (87.1%) was dissolved in 77.17 g of deionized water and stirred and cooled. The KOH solution was rapidly added dropwise to the reaction mixture, yielding a clear, colorless solution. Separately, 3.95 g of LiCl was dissolved in 12.00 g of deionized water. This solution was added dropwise while the reaction mixture was vigorously stirred; the solution remained clear and colorless. The highly alkaline, transparent solution was dispensed into eight Teflon-lined reaction vessels and statically digested at autogenous pressure at 125°C, 150°C, 175°C, and 190°C for 52 h and 168 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. The characteristic diffraction lines of the products of Example 4A (150°C / 52 h) and Example 4B (190°C / 168 h) are provided in Table 4.

[0581] Table 4

[0582]

[0583] Examples 5A and 5B

[0584] Pour 90.00 g of deionized water into a Teflon beaker and place it under a top-mounted mixer. While stirring vigorously, add 21.11 g of H₂O₂ (30 wt%), 17.89 g of citric acid, and 16.96 g of d-sorbitol and dissolve them. Then, slowly add 3.76 g of Fe(NO₃)₃. 9H₂O solid was reacted to form a yellow solution. Then, 10.68 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, yielding a dark red-orange solution. Separately, 38.01 g of NaOH (98%) was dissolved in 77.17 g of deionized water and stirred and cooled. The NaOH solution was rapidly added dropwise, during which the reaction mixture turned brown. The highly alkaline, clear solution was partitioned into eight Teflon-lined reaction vessels and statically digested at autogenous pressure at 125°C, 150°C, 175°C, and 190°C for 55 h and 171 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. Characteristic diffraction lines of the products of Example 5A (150°C / 55 h) and Example 5B (190°C / 171 h) are provided in Table 5. Elemental analysis by ICP yielded the material of Example 5B with a metallic stoichiometry of Na. 0.25 Fe 0.20 Ti 0.80 The experience component.

[0585] Table 5

[0586]

[0587] Examples 6A and 6B

[0588] 75.00 g of deionized water was placed in a Teflon beaker and placed under a top stirrer. Under vigorous stirring, 15.85 g of H₂O₂ (30 wt%) and 17.89 g of citric acid were added and dissolved. Then, 10.68 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, yielding a dark reddish-orange solution. Next, 3.76 g of Fe(NO₃)₃ was slowly added. 9H₂O solid was reacted to form a brownish-yellow solution. Then 16.96 g of d-sorbitol was added, which dissolved under stirring. Separately, 30.41 g of NaOH (98%) was dissolved in 50.85 g of deionized water and stirred and cooled. The NaOH solution was rapidly added dropwise to the reaction mixture, during which time the color remained substantially the same, and a dark brownish-yellow solution was obtained. The highly alkaline transparent solution was partitioned into six Teflon-lined reaction vessels and statically digested at autogenous pressure at 125 °C, 150 °C, and 175 °C for 52 h and 168 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. Characteristic diffraction lines of the products of Example 6A (150 °C / 52 h) and Example 6B (175 °C / 168 h) are provided in Table 6. Elemental analysis by ICP yielded the material of Example 6B with a metallic stoichiometry of Na. 0.28 Fe 0.18 Ti 0.82 The experience component.

[0589] Table 6

[0590]

[0591] Examples 7A and 7B

[0592] 75.00 g of deionized water was placed in a Teflon beaker and placed under a top stirrer. Under vigorous stirring, 13.47 g of H₂O₂ (30 wt%), 19.02 g of citric acid, and 18.02 g of d-sorbitol were added and dissolved. Then, 8.52 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, yielding a dark orange-red solution. Separately, 8.00 g of Fe(NO₃)₃ was added... 9H₂O was dissolved in 15.00 g of deionized water. This solution was added dropwise to the reaction mixture over a 3-minute interval, and the reaction mixture remained a dark orange-red solution. Separately, 40.41 g of NaOH (98%) was dissolved in 43.80 g of deionized water and stirred and cooled. This solution was rapidly added dropwise to the reaction mixture, during which a dark brown color appeared. After addition, stirring was performed, and the reaction mixture became a clear dark reddish-brown solution. The highly alkaline clear solution was partitioned into nine Teflon-lined reaction vessels and statically digested at autogenous pressure at 95°C, 125°C, 150°C, 175°C, and 190°C for 48 h and 169 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. Characteristic diffraction lines of the products of Example 7A (150°C / 169 h) and Example 7B (190°C / 48 h) are provided in Table 7. The empirical metallostoichiometry of Na in the material of Example 7A was obtained by elemental analysis via ICP.0.24 Fe 0.37 Ti 0.63 Na and the material of Example 7B 0.33 Fe 0.38 Ti 0.62 .

[0593] Table 7

[0594]

[0595] Example 8

[0596] This is another example illustrating how the structure of metal titanates can be altered even in the presence of a large excess of potassium by agitating the potassium iron titanate solution reaction mixture with LiCl. 90.00 g of deionized water was placed in a Teflon beaker under a top-mounted mixer. With vigorous stirring, 21.11 g of H₂O₂ (30 wt%), 17.89 g of citric acid, and 16.96 g of d-sorbitol were added and dissolved. Then, 3.76 g of Fe(NO₃)₃ was slowly added. 9H₂O solid was reacted to form a yellow solution. Then, 10.68 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, yielding a dark reddish-orange solution. Separately, 59.99 g of KOH (87.1%) was dissolved in 77.17 g of deionized water and stirred and cooled. This solution was rapidly added dropwise to the reaction mixture, yielding a dark brownish-red solution. Separately, 3.96 g of LiCl was dissolved in 12.00 g of deionized water and added dropwise to the reaction mixture, still yielding a reddish-brown solution. The highly alkaline, transparent solution was partitioned into eight Teflon-lined reaction vessels and statically digested at autogenous pressure at 125 °C, 150 °C, 175 °C, and 190 °C for 53 h and 169 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. The characteristic diffraction lines of the product from Example 8 (175 °C / 169 h) are provided in Table 8.

[0597] Table 8

[0598]

[0599] Example 9

[0600] Pour 90.00 g of deionized water into a Teflon beaker and place it under a top-mounted mixer. While stirring vigorously, add 21.11 g of H₂O₂ (30 wt%), 17.89 g of citric acid, and 16.96 g of d-sorbitol and dissolve them. Then, slowly add 3.00 g of ZrOCl₂. 8H₂O solid was reacted to form a clear, colorless solution. Subsequently, 10.68 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, yielding a dark red-orange solution. Separately, 38.01 g of NaOH (98%) was dissolved in 77.17 g of deionized water and stirred and cooled. The NaOH solution was rapidly added dropwise to the reaction mixture, initiating a series of color changes, eventually resulting in a clear, colorless solution. The highly alkaline clear solution was partitioned into eight Teflon-lined reaction vessels and statically digested at autogenous pressure at 125°C, 150°C, 175°C, and 190°C for 53 h and 170 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. The characteristic diffraction lines of the products from Example 9 (150°C / 170 h) are provided in Table 9. The empirical metallic composition Na of the material from Example 9 was obtained by elemental analysis via ICP. 0.39 Zr 0.03 Ti 0.97 .

[0601] Table 9

[0602]

[0603] Example 10

[0604] 75.00 g of deionized water was placed in a Teflon beaker under a top-mounted mixer. Under vigorous stirring, 21.13 g of H₂O₂ (30 wt%), 17.89 g of citric acid, and 16.96 g of d-sorbitol were added and dissolved. Next, 4.24 g of NH₄NbO(Ox)₂ (20.5% Nb, Ox = oxalate) solid was slowly added to form a suspension. Subsequently, 10.68 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, yielding a dark reddish-orange solution. Separately, 38.01 g of NaOH (98%) was dissolved in 50.85 g of deionized water and stirred and cooled. The NaOH solution was rapidly added dropwise to the reaction mixture, initiating a series of color changes, resulting in a transparent yellow solution. The reaction mixture was stirred for 90 minutes, then partitioned into six Teflon-lined reaction vessels and statically digested at autogenous pressure at 125°C, 150°C, and 175°C for 65 hours and 169 hours, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. Characteristic diffraction lines of the product from Example 10 (125°C / 65 hours) are provided in Table 10.

[0605] Table 10

[0606]

[0607] Example 11

[0608] 75.00 g of deionized water was placed in a Teflon beaker and placed under a top-mounted mixer. Under vigorous stirring, 21.13 g of H₂O₂ (30 wt%) and 17.89 g of citric acid were added and dissolved. Next, 4.24 g of NH₄NbO(Ox)₂ (20.5% Nb, Ox = oxalate) solid was slowly added to form a suspension. Then, 16.96 g of d-sorbitol was added to the suspension, followed by a rapid dropwise addition of 10.68 g of Ti(OiPr)₄ (16.7% Ti), yielding a dark red-orange solution / suspension. After stirring for one hour, the Ti / Nb reaction mixture was a red-orange solution. Separately, 59.98 g of KOH (87.1%) was dissolved in 50.85 g of deionized water and stirred and cooled. The KOH solution was slowly added dropwise to the reaction mixture, during which time the color changed to pale yellow. After the addition was complete, the reaction mixture was stirred for another 90 minutes, during which time it remained a clear yellow solution. The highly alkaline clear yellow solution was dispensed into six Teflon-lined reaction vessels and statically digested at autogenous pressure at 125°C, 150°C, and 175°C for 65 hours and 169 hours, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. The characteristic diffraction lines of the product of Example 11 (150°C / 169 hours) are provided in Table 11.

[0609] Table 11

[0610]

[0611] Example 12

[0612] 75.00 g of deionized water was placed in a Teflon beaker under a top-mounted mixer. While stirring vigorously, 15.85 g of H₂O₂ (30 wt%) and 17.89 g of citric acid were added and dissolved. Then, 10.68 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, yielding a dark reddish-orange solution. Next, 3.76 g of Fe(NO₃)₃ was slowly added. 9H₂O solid was formed, resulting in a dark brown solution. Then 16.96 g of d-sorbitol was added and dissolved, and with further stirring, the reaction mixture became a transparent dark brownish-yellow solution. Separately, 47.98 g of KOH (87.1%) was dissolved in 50.85 g of deionized water. This solution was rapidly added dropwise to the reaction mixture, yielding a transparent dark brown solution with a light red hue. The highly alkaline transparent brown solution was partitioned into six Teflon-lined reaction vessels and statically digested at autogenous pressure at 125 °C, 150 °C, and 175 °C for 52 h and 168 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. The characteristic diffraction lines of the product of Example 12 (175 °C / 168 h) are provided in Table 12. The empirical metallic composition K of the material of Example 12 was obtained by elemental analysis via ICP. 0.19 Fe 0.29 Ti 0.71 .

[0613] Table 12

[0614]

[0615] Example 13

[0616] 100.00 g of deionized water was placed in a Teflon beaker and placed under a top-mounted mixer. Under vigorous stirring, 27.21 g of H₂O₂ (30 wt%), 15.37 g of citric acid, and 14.57 g of d-sorbitol were added and dissolved. Then, 18.34 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, yielding a dark reddish-orange solution. Next, 3.99 g of solid Co(OAc)₂ was added... 4H₂O was slowly added to the reaction mixture, which turned into a reddish-purple solution. Separately, 39.18 g of NaOH (98%) was dissolved in 44.16 g of deionized water and stirred and cooled. This solution was rapidly added dropwise to the reaction mixture, yielding a dark green solution. The highly alkaline dark green solution was partitioned into nine Teflon-lined reaction vessels and statically digested at autogenous pressure at 95 °C, 125 °C, 150 °C, 175 °C, and 190 °C for 55 h and 171 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. Characteristic diffraction lines of the products from Example 13 (150 °C / 171 h) are provided in Table 13. All products from the reactions at 150 °C, 175 °C, and 190 °C showed the same XRD pattern. Elemental analysis of the 175 °C / 171 h product by ICP yielded the empirical metallic composition Na. 0.26 Co 0.20 Ti 0.80 .

[0617] Table 13

[0618]

[0619] Examples 14A and 14B

[0620] 320.00 g of deionized water was placed in a 1 L Teflon beaker under a top-mounted mixer in an ice bath. With vigorous stirring, 95.23 g of H₂O₂ (30 wt%), 53.80 g of citric acid, and 51.01 g of d-sorbitol were added and dissolved. Then, 64.20 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, resulting in some precipitate and a dark red-orange solution. The solid dissolved under further stirring. Next, 13.95 g of Co(OAc)₂ was added... 4H₂O was slowly added to the reaction mixture and dissolved after stirring for 10 minutes. Separately, 137.14 g of NaOH (98%) was dissolved in 184.56 g of deionized water and placed in an ice bath. The cooled NaOH solution was rapidly added dropwise to the reaction mixture, forming a deep blue-green solution. The reaction mixture was stirred further, and when it reached room temperature, the clear solution turned green with some blue tinge. The highly alkaline green-blue solution was transferred to a 1 L Teflon-lined Parr reactor and statically digested at 150 °C for 168 hours under autogenous pressure. The solid product was separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the product. The characteristic diffraction lines of the product of Example 14A are provided in Table 14. The empirical metallic composition Na was obtained by elemental analysis via ICP. 0.40 Co 0.19 Ti 0.81 .

[0621] 2.0 g of the product was ion-exchanged at room temperature using 100 mL of 0.5 M Mg(NO3)2 solution. The exchange was performed three times, and the product was then washed with deionized water and air-dried. The product of Example 14B was characterized by PXRD, and the characteristic diffraction lines are provided in Table 14. Mg 2+ The exchanged products exhibit different XRD patterns and have higher crystallinity than the parent compound.

[0622] Table 14

[0623]

[0624] Examples 15A and 15B

[0625] 100.00 g of deionized water was placed in a Teflon beaker and placed under a top-mounted mixer. Under vigorous stirring, 27.21 g of H₂O₂ (30 wt%), 15.37 g of citric acid, and 14.57 g of d-sorbitol were added and dissolved. Then, 18.34 g of Ti(OiPr)₄ (16.7% Ti) was rapidly added dropwise, yielding a dark reddish-orange solution. Next, 3.92 g of solid Mn(OAc)₂ was added... 4H₂O was slowly added to the reaction mixture, which turned into a reddish-purple solution. Separately, 39.18 g of NaOH (98%) was dissolved in 44.16 g of deionized water and stirred and cooled. This solution was rapidly added dropwise to the reaction mixture, initially yielding a dark orange-brown solution that darkened to brown. The highly alkaline dark brown solution was partitioned into nine Teflon-lined reaction vessels and statically digested at autogenous pressure at 95°C, 125°C, 150°C, 175°C, and 190°C for 54 h and 170 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. Characteristic diffraction lines of the products of Example 15A (125°C / 170 h) and Example 15B (150°C / 170 h) are provided in Table 15. The empirical composition Na of the material of Example 15B was obtained by elemental analysis via ICP. 0.25 Mn 0.20 Ti 0.80 .

[0626] Table 15

[0627]

[0628] Examples 16-26: Synthesis of metal titanates from TiO2 powder and formed TiO2 spheres

[0629] The performance of hydrogen peroxide and complexing agents including at least one MHCA in dissolving and stabilizing Ti-M-containing substances in a highly alkaline reaction mixture and promoting the formation of metal titanate ion exchange compositions was investigated by applying MHCA to an alkali metal hydroxide solution to convert various solid TiO2 sources (including TiO2 powder and formed spray-dried TiO2 spheres) into alkali metal titanates and alkali metal titanate ion exchangers. For pure alkali metal titanates, only an alkali metal hydroxide solution containing MHCA is required for the conversion. For incorporating M metal into solid TiO2, combinations of complexing agents such as hydrogen peroxide, citric acid, and MHCA such as d-sorbitol, as seen in Examples 1-15, are used to dissolve the M metal in an alkali metal hydroxide solution; when the reaction mixture is adjusted to the very high pH required for the hydrothermal synthesis of metal titanate ion exchange compositions, citric acid is needed to stabilize the M metal in a moderately alkaline solution, while d-sorbitol retains the M metal in solution. Similar to the homogeneous solution method disclosed in Examples 1-15, metal incorporation was observed, and the product consisted of large polycrystalline particles of the desired size, thus avoiding absorption in the gastrointestinal tract. Examples 26 and 27 describe the product particle size.

[0630] Synthesis of spray-dried TiO2 spheres

[0631] Spray-dried TiO2 spheres were synthesized using a Yamato DL-41 spray dryer. Typically, a slurry containing 20% ​​by weight of titanium dioxide powder in DIH2O was prepared in 500 g. 100 g of vapor-phase TiO2 powder (Degussa D-6000) was added to 400 g of deionized water and mixed at 500 RPM using an overhead mixer. The mixture was stirred for 10 minutes. The suspension was then Eiger milled for 15 minutes and spray-dried. Larger agglomerates were removed by passing the suspension through a 100-mesh (150 µm) sieve. The suspension was continuously stirred to prevent particle settling. The spray dryer chamber temperature reached 110 °C, and the drying air flow rate was 80 SCFH. The ejector flow rate was 0.8 cm⁻¹. 3 The feed rate was 16 cc / min, with a pressure head of 10 psi. The slurry feed rate used in this process was 16 cc / min. The collected product was sieved through 60 mesh (250 µm), 100 mesh (150 µm), and 200 mesh (75 µm) sieves; the final collected sample had particles finer than 200 mesh (75 µm). Spray-dried TiO2 spheres from a typical formulation were characterized in Example C5.

[0632] Example 16

[0633] The preparation began with a freshly precipitated titanium dioxide source. In a 1L flask equipped with a top stirrer, 192.5 g of NH4OH (28% NH3) was diluted in 365.25 g of deionized water with stirring. 50.00 g of TiCl4 was added and loaded into a dry, pressure-balanced dropping funnel. TiCl4 was added dropwise and intermittently to avoid overheating the reaction mixture. A white solid formed in the flask, which was then filled at the end of the addition. After the addition, the reaction mixture was stirred again and cooled for 45 minutes, then partitioned into centrifuge flasks for separation and washed with deionized water. The wet filter cake, containing 11.2% Ti, was stored in a sealed container and used as the starting material for the next step.

[0634] 10.74 g of NaOH (98%) was dissolved in 34.77 g of deionized water in a small beaker placed under a top stirrer and cooled. Then, 1.45 g of catechol was added, forming a greenish-yellow solution upon dissolution. Titanium dioxide (11.2% Ti) from the freshly prepared precipitate was added, forming a greenish-yellow suspension. After further stirring, the highly alkaline reaction mixture was partitioned into three Teflon-lined reaction vessels and statically digested at 95°C and 150°C for 96 hours under autogenous pressure, and then statically digested at 190°C for 49 hours. The solid products were separated by centrifugation, washed with deionized water, and dried at room temperature. PXRD was used to characterize the products. The characteristic diffraction lines of the product from Example 16 (190°C / 49 hours) are provided in Table 16. The empirical metallic composition Na of the material from Example 16 was obtained by elemental analysis via ICP. 0.37 Ti 1.00 .

[0635] Table 16

[0636]

[0637] Example 17

[0638] 12.88 g of 8.5 M KOH solution was added to a Teflon beaker. 0.69 g of catechol reagent was added and dissolved under magnetic stirring, producing a clear, light brown solution. After mixing for 5 minutes, 1 g of TiO2 powder was added to make the mixture opaque. The reaction mixture was mixed for 30 minutes to obtain a creamy brown opaque mixture. The highly alkaline solution was loaded into a 45 cc Teflon-lined reaction vessel and digested at 200 °C for 20 hours under autogenous pressure with tumbling (40 rpm). The solid product was separated by filtration, washed with copious amounts of deionized water, and dried at 100 °C. PXRD was used to characterize the product. The characteristic diffraction lines of the product are provided in Table 17. The metal stoichiometry K was obtained by elemental analysis via ICP. 0.26 Ti1.00 .

[0639] Table 17

[0640]

[0641] Example 18

[0642] Pour 5.00 g of deionized water into a Teflon beaker and place it under a top-mounted mixer. While stirring vigorously, add 0.48 g of citric acid, 1.60 g of d-sorbitol, and 1.01 g of Fe(NO3)3. Dissolve the product in 9H₂O to produce a transparent purple solution. Then, under vigorous stirring, add 14.12 g of cooled 8.5 M KOH solution dropwise over 7 minutes to obtain a transparent dark green solution. Finally, add 1.00 g of TiO₂ powder to the resulting dark green solution and homogenize it over a 30-minute period. Dispense the resulting dark green, highly alkaline suspension into a Teflon-lined 45 mL reaction vessel and statically digest it at 200 °C for 4 days under autogenous pressure. Separate the solid product by centrifugation, wash with deionized water, and dry at 100 °C. PXRD was used to characterize the product. The characteristic diffraction lines of the product from Example 18 are provided in Table 18. The metal stoichiometry K was obtained by elemental analysis via ICP. 0.31 Fe 0.18 Ti 0.82 .

[0643] Table 18

[0644]

[0645] Example 19

[0646] Pour 5.00 g of deionized water into a Teflon beaker and place it under a top-mounted mixer. While stirring vigorously, add 0.48 g of citric acid, 1.60 g of d-sorbitol, and 1.01 g of Fe(NO3)3. Dissolve the product in 9H2O to obtain a transparent purple solution. Then, under vigorous stirring, add 15.02 g of cooled 7.5M NaOH solution dropwise over 7 minutes to obtain a green solution. Finally, add 1.00 g of TiO2 powder to the resulting pale green solution and homogenize it over a 30-minute period. The resulting green, opaque, highly alkaline suspension is partitioned into Teflon-lined reaction vessels and statically digested at 200°C for 1 day and 4 days under autogenous pressure. The solid products are separated by centrifugation, washed with deionized water, and dried at 100°C. PXRD is used to characterize the products. Characteristic diffraction lines of the products of Example 19A (200°C / 1 day) and Example 19B (200°C / 4 days) are provided in Table 19. The stoichiometry of Na in the product of Example 19A was obtained by elemental analysis via ICP. 0.33 Fe 0.18 Ti 0.82 Na and the product of Example 19B 0.46 Fe 0.17 Ti 0.83 .

[0647] Table 19

[0648]

[0649] Example 20

[0650] 5.00 g of deionized water was added to a Teflon beaker and a magnetic stir bar was added. Under vigorous stirring, 1.14 g of d-sorbitol was added and dissolved to form a clear solution. Next, 15.71 g of cooled 7.5 M NaOH solution was added dropwise over 7 minutes with continued stirring. Finally, 1.00 g of spray-dried TiO2 spheres was added to the resulting highly alkaline solution and gently homogenized over 2 minutes. The resulting suspension was transferred to a Teflon-lined 45 ml reaction vessel and statically digested at 200 °C for 4 days under autogenous pressure. The solid product was separated by filtration, washed with deionized water, and dried at 100 °C. PXRD was used to characterize the product of Example 20A, and the characteristic diffraction lines are provided in Table 20. A portion of the resulting novel Example 20A sphere product was acid-treated with dilute nitric acid solution at room temperature to adjust the slurry to a stable pH of ~2. This product is Example 20B.

[0651] Table 20

[0652]

[0653]

[0654] Example 21

[0655] Add 5.00g of deionized water and a magnetic stir bar to a Teflon beaker. Under vigorous stirring, dissolve 0.48g of citric acid and 1.60g of d-sorbitol to form a clear solution. Then, while continuing stirring, add 1.01g of Fe(NO3)3. 9H₂O yields a clear, pale purple solution. 15.02 g of cooled 7.5 M NaOH solution is added dropwise to this reaction mixture over 7 minutes. Finally, 1.00 g of spray-dried TiO₂ spheres is added to the resulting highly alkaline green solution, and the mixture is gently homogenized over 2 minutes. The resulting neon lime green slurry is loaded into a Teflon-lined 45 ml reaction vessel and statically digested at 200 °C for 4 days under autogenous pressure. The solid product is separated by filtration, washed with deionized water, and dried at 100 °C. PXRD was used to characterize the product of Example 21A, and the characteristic lines are provided in Table 21. A portion of the sphere product of Example 21A is acid-treated with dilute nitric acid at room temperature to adjust the slurry to a stable pH of ~2. This product is Example 21B.

[0656] Table 21

[0657]

[0658] Example 22

[0659] 31.42 g of 7.5 M NaOH solution was added to a 100 ml polypropylene beaker and placed under a top-mounted mixer. Under vigorous mixing, 2.28 g of d-sorbitol was added and mixed until dissolved. Then, 2 g of spray-dried TiO2 spheres were added. After stirring the reaction mixture for 5 minutes, the reaction mixture was transferred to two 45 ml Teflon-lined Pallas's containers and digested at autogenous pressure at 175 °C with tumbling (40 rpm) for 24 h and 96 h, respectively. The solid products were separated by centrifugation, washed with deionized water, and dried overnight at 100 °C. PXRD was used to characterize the products. The characteristic diffraction lines of the product from Example 22 (175 °C / 96 h) are provided in Table 22.

[0660] Table 22

[0661]

[0662]

[0663] Example 23

[0664] 25.75 g of 8.5 M KOH solution was placed in a 100 ml polypropylene beaker and placed under a top-mounted mixer. Under vigorous mixing, 2.28 g of d-sorbitol was added and mixed until dissolved. Then, 2 g of spray-dried TiO2 pellets were added. After stirring the reaction mixture for 5 minutes, the reaction mixture was transferred to two 45 ml Teflon-lined Pallas's containers and digested at autogenous pressure at 200 °C with tumbling (40 rpm) for 24 h and 96 h, respectively. The solid product was separated by centrifugation, washed with deionized water, and dried overnight at 100 °C. PXRD was used to characterize the product. The characteristic diffraction lines of the product of Example 23A (200 °C / 96 h) are provided in Table 23. 1.0 g of the product of Example 23A was acid-treated with 10 g of deionized water, and the pH was adjusted to 3 using 1 M HNO3 solution. Once the powder was added to the pH 3 solution, the pH of the mixture was adjusted to pH 1.5–2.0 by adding 1 M HNO3 solution with stirring. The mixture was stirred at room temperature for 30 minutes, then the product was washed with deionized water and dried overnight at 80°C. The product of Example 23B was characterized by PXRD, and the characteristic diffraction lines are provided in Table 23.

[0665] Table 23

[0666]

[0667] Example 24

[0668] 901.6 g of 8.5 M KOH solution was added to a 2 L polypropylene beaker and placed under a top-mounted mixer. 79.8 g of d-sorbitol was added and mixed until dissolved while vigorously mixing at 300 rpm. Then 70 g of TiO2 powder (Degussa) was added, and the reaction mixture was stirred for 15 minutes. The reaction mixture was placed in a 2 L Paler stirred reactor and digested at 200 °C under autogenous pressure for 18 hours with stirring at 40 rpm. The solid product was separated by centrifugation, washed with deionized water, and dried overnight at 80 °C. PXRD was used to characterize the product. The characteristic diffraction lines of the product of Example 24A are provided in Table 24. The metal stoichiometry K of the product of Example 24A was obtained by elemental analysis via ICP. 0.40 Ti 1.00 The preparation was repeated 10 times, and the products were mixed to prepare a product exhibiting metal stoichiometry K. 0.30 Ti composite sample (Example 24E). Characteristic PXRD diffraction lines of the composite product of Example 24E are provided in Table 24.

[0669] 5.0 g of the product from Example 24A was acid-treated with 50 g of deionized water, and the pH was adjusted to 3 using 1 M HNO3 solution. Once the addition of the Example 24A powder to the stirred pH 3 solution was complete, the pH was further adjusted to 1.5–2.0 by adding 1 M HNO3 solution. The mixture was stirred at room temperature for 30 minutes, then the product was washed with deionized water and dried overnight at 80°C. The product from Example 24B was characterized by PXRD, and the characteristic diffraction lines are provided in Table 24. A portion of the composite product from Example 24E was also acid-treated in the same manner to obtain the product from Example 24F. The metal stoichiometry K of the product from Example 24F was obtained by elemental analysis via ICP. 0.15 The TiO2 acid-treated product of Example 24F was also characterized by PXRD, and the characteristic diffraction lines are provided in Table 24.

[0670] 4.0 g of the product from Example 24A was calcined at 350 °C for 2 h in a stream of clean, dry air at a flow rate of 300 SCFH. The product from Example 24C was characterized by PXRD, and the characteristic diffraction lines are provided in Table 24. The calcined product exhibited a similar XRD pattern to the parent sample of Example 24A, showing a similar degree of crystallinity.

[0671] 2.0 g of the calcined product of Example 24C was acid-treated with 20 g of deionized water, and the pH was adjusted to 3 by adding 1 M HNO3 solution while stirring. Once the powder of Example 24C was added to the pH 3 solution, the pH of the mixture was adjusted to 1.5-2.0 by adding 1 M HNO3 solution while continuing to stir. The mixture was stirred at room temperature for another 30 minutes, and then the product was washed with deionized water and dried overnight at 80°C. The product of Example 24D was characterized by PXRD, and the characteristic diffraction lines are provided in Table 24.

[0672] Table 24

[0673]

[0674] Table 24 (continued)

[0675]

[0676] Example 25

[0677] A standard 8.5M KOH solution was prepared by dissolving 560g of KOH (85%) in 500g of deionized water, stirring and cooling the resulting solution. The solution was transferred to a 1-liter volumetric flask and diluted to 1000ml. This standard KOH solution was used in the following preparations, and the process was repeated when more solution was needed.

[0678] A 2L static Pal reactor equipped with a Teflon liner was used for the following synthesis, which was performed three times. 811.40 g of standard KOH solution was charged into the Teflon liner. 71.96 g of sorbitol was added to this solution, and the mixture was stirred until all solids dissolved. Once a clear solution was obtained, 63.30 g of pre-formed spray-dried TiO2 spheres were charged into the reaction mixture. The mixture was gently stirred with a stir bar for 15 minutes. The stir bar was then removed from the reaction mixture, and the Teflon liner containing the reaction mixture was placed in the 2L Pal reactor. The reactor was sealed, and the reaction mixture was statically digested at 200°C under autogenous pressure for 4 days. After digestion, the reaction mixture was cooled, the mother liquor was decanted, and the solid product was separated by filtration. The solid product was washed with 6 L of deionized water and dried at 100°C. This reaction was performed three times, Examples 25A, 25B, and 25C. These products were characterized by PXRD and found to be nearly identical. Characteristic diffraction lines are provided in Table 25. Samples from Examples 25A, 25B, and 25C were mixed to form a composite product (Example 25D). The metal stoichiometry K of the composite product of Example 25D was obtained by elemental analysis via ICP. 0.28 Ti. A portion of the composite product was acid-treated to form the product of Example 25E. 205.74 g of the composite product of Example 25D was suspended in 2100 g of deionized water with stirring in a 4 L beaker. The pH was adjusted to 3 by dropwise addition of concentrated nitric acid. The pH was further adjusted by adding 1 M HNO3 until it stabilized at pH=2. The resulting slurry was stirred at room temperature for about one hour, with the pH periodically adjusted to maintain it at 2. The solid product of Example 25E was separated by filtration, washed with 4 L of deionized water, and dried at 100 °C. The products of Examples 25D and 25E were characterized by PXRD, and representative diffraction lines are provided in Table 25. Elemental analysis by ICP yielded a Kx stoichiometry for the parent product of Example 25D. 0.28 The metal stoichiometry of Ti and the acid-treated product of Example 25E is K. 0.16 Ti.

[0679] Table 25

[0680]

[0681] Example 26

[0682] This example uses nano-sized titanium dioxide powder as the Ti source. 40 g of pre-prepared 8.5 M KOH solution was placed in a 100 ml polypropylene beaker and placed under a top-mounted mixer. 4.56 g of D-sorbitol was added to the KOH solution and stirred until dissolved. Under vigorous mixing, 4 g of pure anatase nano-sized TiO2 powder (Kemira) was added, and the reaction mixture was stirred for 30 minutes. A portion of the reaction mixture was placed in a 45 ml Teflon-lined Parl container and statically digested at 200 °C for 24 hours under autogenous pressure. The solid product was separated by centrifugation, washed with deionized water, and dried overnight at 100 °C. The particle size distribution of the product in Example 26 is as follows: Figure 8 It is shown in the figure and discussed in Example 27.

[0683] Comparative Examples C1-C6

[0684] The following comparative examples are described.

[0685] Example C1

[0686] Example 4 of US 11,964,266 discloses a sodium nonatantinate sample from AlliedSignal for Pb uptake from body fluids. Characterization of the sample by PXRD was consistent with that of sodium nonatantinate. Representative X-ray diffraction lines of the sample are provided in Table 26. Elemental analysis by ICP yielded the stoichiometry for Na. 0.5 Ti.

[0687] Table 26

[0688]

[0689] Example C2

[0690] US 11,964,266, Example 17, discloses a method for removing Pb from bodily fluids. 2+ The sample was taken from commercial potassium octatitanate, product number HON393, from Honeywell Specialty Chemicals, Seelze GMBH. The sample was prepared from potassium octatitanate K₂Ti₈O₃. 17 The complex consists of anatase and potassium hexatitanate (K2Ti6O). 13 The samples were characterized by PXRD, and their representative X-ray diffraction lines are provided in Table 27. Elemental analysis by ICP yielded potassium octatitanate K₂Ti₈O₃. 17 The expected stoichiometry is consistent with the metal stoichiometry K. 0.26 Ti.

[0691] Table 27

[0692]

[0693] Example C3

[0694] The reaction was carried out using the procedure disclosed herein (such as Examples 24 or 25), except that MHCA, such as d-sorbitol, was not present. 46 g of a pre-prepared 7.5 M NaOH solution was placed in a 100 mL polypropylene beaker and placed under a top-mounted mixer. Under vigorous mixing, 4 g of pure anatase TiO2 powder (Sigma-Aldrich) was added, and the reaction mixture was stirred for 5 minutes. A portion of the reaction mixture was placed in a 45 mL Teflon-lined Parl container and statically digested at 200 °C for 24 hours under autogenous pressure. The solid product was separated by centrifugation, washed with deionized water, and dried overnight at 100 °C. PXRD was used to characterize the product, and representative diffraction lines are provided in Table 28.

[0695] Table 28

[0696]

[0697] Example C4

[0698] The reaction was carried out using the procedure disclosed herein (such as Examples 24 or 25), except that MHCA was not present. 40 g of a pre-prepared 8.5 M KOH solution was placed in a 100 mL polypropylene beaker and placed under a top-mounted mixer. Under vigorous mixing, 4 g of pure anatase TiO2 powder (Sigma-Aldrich) was added, and the reaction mixture was stirred for 5 minutes. A portion of the reaction mixture was placed in a 45 mL Teflon-lined Parl container and statically digested at 200 °C for 24 hours under autogenous pressure. The solid product was separated by centrifugation, washed with deionized water, and dried overnight at 100 °C. PXRD was used to characterize the product, and representative diffraction lines are provided in Table 29.

[0699] Table 29

[0700]

[0701] Example C5

[0702] The general procedure for synthesizing the spray-dried TiO2 spheres provided above was used. These spheres are characterized by establishing baseline properties of the spheres prior to their conversion to metal titanates in a hydroxide medium. The properties of these starting material spheres were compared with those converted in a hydroxide medium in the presence and absence of MHCA (Example 29). The spray-dried TiO2 spheres were characterized by PXRD, revealing a mixture of anatase and rutile TiO2 topologies. Characteristic diffraction lines are provided in Table 30.

[0703] Table 30

[0704]

[0705] Example C6

[0706] The reaction using spray-dried TiO2 spheres was carried out using the procedure disclosed herein (such as Examples 24 or 25), except that MHCA was not present. 40 g of 8.5 M KOH solution was placed in a 100 mL polypropylene beaker and placed under a top-mounted mixer. Under vigorous mixing, 4 g of spray-dried TiO2 spheres were added, and the reaction mixture was stirred for 5 minutes. A portion of the reaction mixture was placed in a 45 mL Teflon-lined Pallet container and digested at 225 °C for 1 day, during which time it was tumbled at 30 rpm under autogenous pressure. The solid product was separated by centrifugation, washed with deionized water, and dried overnight at 100 °C. PXRD was used to characterize the product. Representative diffraction lines of the product are provided in Table 31.

[0707] Table 31

[0708]

[0709] Example 27 - SEM of metal titanate ion exchangers

[0710] One result of the synthesis of metal titanates disclosed herein is the aggregation of microcrystals into fairly large, robust polycrystalline particles, typically hundreds of times the size of a single crystal. While not bound by theory, the synthetic chemistry from solution is engineered to transport the metal under highly alkaline conditions (conditions under which the metal would otherwise exist as a poorly reactive gel). Another result is the formation of Pb that is favorable for the gastrointestinal tract. 2+ Large polycrystalline aggregates are removed because they tend to be large enough to avoid absorption and the resulting adverse effects.

[0711] Scanning electron microscopy (SEM) was used to illustrate these properties, namely the formation of large polycrystalline aggregates. Figure 1A shows the product from Example 5B, namely Na prepared from solution. 0.25 Fe0.20 Ti 0.80 The product is an aggregate of numerous well-formed, plate-like crystals arranged in spherical form. These plates provide ion exchange capacity due to their small size, which makes it easier to access ion exchange sites than in cases where the crystals are larger. Figure 1B shows the same Example 5B material similarly formed in larger blocks from numerous entangled plates. Figures 1C and 1D show the Na product of Example 7B. 0.33 Fe 0.38 Ti 0.62 SEM images of (another iron titanate synthesized from solution). These materials form different morphologies, namely polycrystalline aggregates composed of interpenetrating spheres of smaller plate-like crystals. Figure 1E shows Na, the product of Example 9, also synthesized from a homogeneous solution. 0.39 Zr 0.03 Ti 0.97 The SEM images of the product show that it also forms aggregates of interpenetrating spheres, which are less defined than those in the product in Figure 1C, forming smoother, larger polycrystalline aggregates. Figure 1F SEM images of the K-Ti-Nb-O product of Example 11, synthesized again from solution, are shown. The observed morphology of this material is horizontal blocks of interpenetrating spheres, and the spheres are again composed of plate-like crystals. These blocks are 10 micrometers thick and tens of micrometers wide, thus having a size sufficient to avoid absorption via the gastrointestinal tract.

[0712] Solution chemistry methods for dissolving metals in highly alkaline solutions facilitate the preparation of the mixed metal titanate ion exchangers of this disclosure and provide a method conducive to the removal of Pb from the gastrointestinal tract. 2+ Unexpected benefits of large polycrystalline aggregates. Specifically, in one aspect, the observed solubility property of MHCA in Ti can promote the chemochemical reaction of TiO2 powder in highly alkaline solutions, and in another aspect, it can provide the particle size benefits seen in solution chemistry. SEM images of the products obtained from TiO2 powder are shown in Figure 2. Figure 2A shows the potassium titanate product K from Example 17 prepared from TiO2 powder in the presence of KOH and MHCA (catechol, 1,2-dihydroxybenzene). 0.26SEM images of Ti. The SEM images show sponge-like polycrystalline aggregates, with most aggregates ranging in size from 5 micrometers to tens of micrometers. Figure 2B shows the product of Example 20A, produced by hydrothermal treatment of pre-formed spray-dried TiO2 spheres in the presence of a d-sorbitol / NaOH solution. The polycrystalline nature of the spheres is clearly visible, showing aggregates of plate-like crystals reminiscent of those observed in solution chemistry products, as shown in Figures 1A and 1C. Furthermore, the pre-formed spheres have been agglomerated by hydrothermal treatment with NaOH / d-sorbitol, resulting in larger aggregates typically well over 100 micrometers in size. Figures 2C and 2D are SEM images of the product of Example 21A, a Na-Fe-Ti-O composition obtained from pre-formed spray-dried TiO2 spheres hydrothermally treated with a ferric nitrate / citric acid / d-sorbitol / NaOH solution. The polycrystalline nature of the intact spheres is visible, and the spheres range in size from about 20 micrometers to 70 micrometers. Many spheres are individual, while some are interpenetrating. Figure 2E and Figure 2F Example 24A shows product K obtained by hydrothermal treatment of TiO2 powder in the presence of KOH / d-sorbitol solution. 0.40 SEM of Ti. Figure 2E is a field-view showing a sponge-like polycrystalline aggregate with a size of about 50 micrometers. Figure 2F The macroporous properties of the aggregated particles are shown in a close-up view. The procedure used to prepare the product of Example 24A was repeated 10 times to produce the composite sample of Example 24E formed by mixing these batches. Figures 2G and 2H depict composite sample K. 0.30 SEM images of Ti, showing characteristics very similar to a single batch from Example 24A, including aggregates of tens of micrometers in size (Fig. 2G) and a sponge-like macroporous network (Fig. 2H). Figs. 2I and 2J show the hydrothermal conversion of three batches to K in the presence of a KOH / d-sorbitol solution. 0.30 SEM images of the composite sample of Example 25D obtained by mixing pre-formed spray-dried TiO2 spheres. The field of view in Figure 2I shows the size range of the potassium titanate spheres from tens of micrometers, while at higher magnification in Figure 2J, the diameter of the spheres ranges from approximately 20 to 80 micrometers. The composite K of Example 25D was treated with acid. 0.30 Ti spheres were used to prepare product K in Example 25E. 0.16 Ti. Figure 2K and Figure 2L The SEM image of the acid-treated product from Example 25E showed that its appearance was similar to that of the initially synthesized K. 0.30The Ti sample is similar, indicating that the formed spheres remain intact through the acid treatment process. These examples demonstrate that the hydrothermal synthesis of metal titanates in the presence of MHCA produces large polycrystalline aggregates much larger than 3 micrometers, and therefore may not be absorbed by the body via the gastrointestinal tract.

[0713] Example 28

[0714] Particle size distribution (PSD) measurements were also performed to determine the size characteristics of the selected examples and some comparative examples. Light scattering diffraction techniques were used to analyze individual batches of powder samples in an LS 13 320 XR particle size analyzer. The powder samples were dispersed in water and briefly sonicated before measurement. Particle size distribution and other measurement parameters were... Figures 3-8 The values ​​D(3), D(10), D(50), and D(90) represent particle size values ​​in micrometers, at which the smallest 3%, 10%, 50%, and 90% of the samples appear in the particle size distribution. The D(50) value is equivalent to the median of the particle size distribution. Without being theoretically constrained, particles smaller than 3 micrometers can be absorbed by the body, so it is desirable to have very few of these particles, but 3% can be considered an acceptable upper limit. In the figure, the parameter <3µm (volume%) gives the volume percentage of samples with particles smaller than 3µm. The mean or average particle size for each sample is also reported.

[0715] Figure 3 Comparative Example C1 (US 11,964,266, Example 4) is shown for the removal of Pb from body fluids. 2+ The particle size distribution of sodium titanate (a sample from Lianxin Company containing other metals) was compared. For this sample, D(3) showed that 3% by volume of the sample had a particle size of less than 0.98 µm and 18.74% by volume of the sample had a particle size of less than 3 µm. Similarly, Figure 4 Comparative Example C2 (US 11,964,266, Example 17) is shown for the removal of Pb from body fluids. 2+The particle size distribution of Honeywell's potassium octatate product (and other metals) was compared. For this sample, D(3) showed that 3% by volume of the sample had a particle size of less than 0.11 μm, and 27.04% by volume of the sample had a particle size of less than 3 μm. For each of the materials in Comparative Example C1 and Example C2, the particle size distribution was multimodal and broad, with a relatively significant fraction of samples where the particle size range exceeded two orders of magnitude. The broad distribution was characterized by an average particle size that was almost twice the median particle size. Furthermore, for each of these samples, the large fraction of samples with a particle size of less than 3 µm (18.74% by volume for Example C1 and 27.04% by volume for Example C2) made these samples unacceptable for treatments involving the gastrointestinal tract, as these small particles could be absorbed by the body and cause adverse reactions. In contrast, similar to Comparative Examples C1 and C2, as Figure 5 The material of Example 24F was obtained by hydrothermal treatment of TiO2 powder in the presence of an alkali metal hydroxide solution, particularly KOH, but also containing MHCA d-sorbitol. Visually, the particle size distribution is more uniform, falling under one main peak and two secondary peaks, with the two sub-parts of the sample having larger and smaller particle sizes. D(3) shows that 3 vol% of the Example 24F sample has a particle size of less than 4.39 µm and 2.01 vol% of the sample has a particle size of less than 3 µm, making the sample more acceptable for use in gastrointestinal-based therapies. The average particle size exceeds the median particle size by about 25% compared to the large differences seen in the average and median particle sizes of Examples C1 and C2. In the presence of MHCA d-sorbitol, the median particle size of the Example 24F material, 50.64 µm, is much larger than the 8.302 µm seen in the Example C2 sample, which is potassium octatitanate prepared from TiO2 powder in KOH solution. The presence of d-sorbitol provides a more uniform particle size distribution, and larger particle sizes are more suitable for gastrointestinal-based treatments.

[0716] Figure 6 The particle size distribution of composite Example 25D material is shown, which was obtained from spray-dried TiO2 spheres as the starting material and treated with a KOH / d-sorbitol solution to prepare a metal titanate ion exchanger. Most notably, the particle distribution is unimodal, with a shoulder peak at larger particle sizes and a very small peak at lower particle sizes. The strategy of preparing metal titanates from spray-dried TiO2 spheres significantly alters the particle size distribution, particularly for smaller particles. For this sample, D(3) is 36.32 µm, and the minimum 3% by volume of particles smaller than this size is present. The absence of a measurable fraction of particles smaller than 3 µm makes this material a good candidate for gastrointestinal therapy. Similarly, Figure 7 The particle size distribution of the sample in Example 25E is shown, which was obtained by analyzing the particle size distribution of the sample. Figure 6The composite material of Example 25D discussed herein was obtained by acid treatment. Not bound by theory, in one respect, if the patient has certain sensitivities, limitations, or conditions, such as hyperkalemia or calcium deficiency, it may be necessary to change the cationic form of the ion exchanger used to treat the patient. The material of Example 25E has undergone an acid treatment process, and... Figure 7 The results show that for the sample of Example 25E, D(3) is 43.79 µm, and the smallest 3% by volume is smaller than this size. Similar to the parent sample (Example 25D), there is no measurable fraction of particles smaller than 3 µm. Thus, the metal titanate spheres survive the ion exchange process without breaking down to form undesirable smaller particles.

[0717] Figure 8 The particle size distribution of the product of Example 26 is shown. This product was obtained from nanoscale pure anatase TiO2 powder and digested in d-sorbitol / KOH solution at 200°C for 24 hours. The PSD of this sample is unimodal with a slight shoulder on the smaller particle side and is quite narrow and symmetrical, as the average particle size of 54.77 µm is almost identical to the median particle size of 54.08 µm. Despite being made from nanoscale TiO2 reagent, the material has a D(3) of 17.17 µm and the volume percentage of samples smaller than 3 µm is 0.55%. This product is homogeneous and suitable for treating the gastrointestinal tract.

[0718] Example 29

[0719] MHCA is used in the synthesis of the metal titanate ion exchangers disclosed herein, providing high porosity to the products. Macroporous products with high surface areas improve the immediate availability of ion exchange sites. The BET surface areas of some metal titanate ion exchangers and comparative examples are listed in Table 32.

[0720] Table 32

[0721]

[0722] Example 24E is a composite sample obtained by mixing 11-2L of TiO2 powder, which has undergone hydrothermal conversion in a KOH / d-sorbitol solution, with a surface area of ​​197 m². 2 / g, while the surface area of ​​the acid-extracted complex (Example 24F) is even higher, at 236m². 2 / g. Similarly, the composite sample of Example 25D, containing TiO2 spheres hydrothermally treated in KOH / d-sorbitol solution, had a density of 203 μm. 2 / g surface area. Pb from US 11,964,266 for use in body fluids, not synthesized in the presence of MHCA. 2+The prior art titanates (sodium nonatitanate and potassium octatitanate, respectively) removed in Examples C1 and C2 showed 44m 2 / g and 8m 2 The surface areas of these materials are significantly smaller than those of the materials disclosed herein. For comparison, and to illustrate the benefits of synthesis in the presence of MHCA, the surface areas of Examples C3 and C4 were collected, representing the conversion rates of TiO2 powder in the presence of NaOH and KOH solutions but without MHCA. The surface areas of these materials were 74 m² / g. 2 / g (Example C3) and 100m 2 / g (Example C4), still half or less of the surface area of ​​the metal titanates of Examples 24E, 24F, and 25D synthesized in the presence of d-sorbitol complexing agent. The surface area of ​​the starting material TiO2 spheres was also determined (Example C5) and the surface area of ​​the same TiO2 spheres converted to titanates in the presence of KOH but in the absence of MHCA (Example C6). The surface area of ​​the TiO2 sphere starting material in Example C5 was 46 m². 2 / g, while after conversion in a KOH solution without d-sorbitol (Example C6), the surface area increased to 119m². 2 / g. The surface area of ​​the material in Example C6 is less than 60% of that of the corresponding Example 25D sample converted in KOH / d-sorbitol solution. In these direct comparisons with Examples C3, C4, C5 and C6 without a complexing agent, the conversion in the presence of the d-sorbitol complexing agent produces macroporous materials with significantly higher surface areas.

[0723] Example 30

[0724] The metal titanate materials disclosed in Examples 1-25 and Comparative Examples C1-C6 were tested to determine the distribution of residues in the solution state between the adsorption of each metal on the solid and the adsorption of each metal in the solid state. d To determine its adsorption of Pb 2+ Mg 2+ Ca 2+ K + and Na + The ability of ions to react. The test solution was prepared from the source compounds provided in Table 33:

[0725] Table 33

[0726]

[0727] The concentrations in the table are the concentrations of metallic elements, for example, 25 ppm Ca. 2- 300ppm K +Etc. Total Na produced from NaNO3 and sodium acetate + The target concentration is 3000 ppm. The solution is buffered with an acetate / sodium acetate buffer; the target acetate concentration is 2500 ppm. The target acetate / sodium acetate ratio is 2.9. A standard 10,000 ppm Pb solution is used to achieve the target Pb concentration of 15 ppm.

[0728] For this test, 0.1000 g of solid metal titanate was mixed with 100 ml of test solution to obtain a liquid / solid ratio (L / S) of 1000. The uptake experiment was conducted in 125 ml HDPE vials placed in a New Brunswick Innova 40 incubator with a fixed-track shaker, which was run at 25°C and 120 rpm for 2-2.5 hours. After exposure, 10 ml aliquots of the ion exchange solution and the untreated starting feed were passed through a 0.2 µm Thermo Scientific filter. TM Target 2 TM Filtered using a Nylon / GMF filter. Pb elemental analysis was performed using ICP-MS (PerkinElmer NexION 300D) by taking 0.1000 mL of solution and diluting it to 200 mL. Indium was added as an internal standard for counting, while Sc and Bi were added as additional mass monitors. Two mL of nitric acid was also added to the final solution. The detection level for Pb was 0.003 ppm or 3 ppb.

[0729] The partition coefficient K of a metal between solution and solid d The value is calculated using the following formula:

[0730]

[0731] Where: V = volume of the body fluid simulant (mL)

[0732] Ac = the concentration of cations absorbed by the ion exchanger (g / mL)

[0733] W = the mass (g) of the ion exchanger being evaluated.

[0734] Sc = the cation concentration (g / mL) in the supernatant after the reaction.

[0735] Pb of the material in each embodiment 2+ The results of the intake test are given in Table 34A and in terms of the allocation coefficient K. d This is indicated. Similarly, Table 34B gives the Na content of the selected samples. + K + Mg 2+ and Ca 2+ The results of intake.

[0736] Table 34A

[0737]

[0738]

[0739]

[0740] The metal titanates disclosed herein exhibit robust Pb content from the test solution. 2+ Intake. The first 15 examples in Table 34A are materials prepared from homogeneous solutions. Two different sodium titanate structures (Examples 1A and 1B) and a potassium titanate composition (Example 2) prepared from solution removed Pb below detectable levels. 2+ It exhibits a K content close to 5,000,000 mL / g. d This indicates that 99.98% of Pb has been removed. 2+ The scale-up of sodium titanate using less complexing agent and NaOH (Example 3A) is also effective, and it works for Mg with different structures. 2+ In the ion-exchange form (Example 3B), this effectiveness is improved. This illustrates the effect of Li... + The powerful structural orientation influence is achieved through the presence of a large number of K + In the case of Li + Adding perturbations to modify the metal titanate structure produces Pb values ​​of approximately 1,000,000 for both low-temperature (Example 4A) and high-temperature (Example 4B) structures. 2+ Allocation coefficient K d The product. Example 5, sodium iron titanate, illustrates that products obtained from the same reaction mixture can exhibit different levels of Pb. 2+ Intake. In fact, the low-temperature structure of sodium iron titanate (Example 5A) exhibits Pb... 2– K d =1,752,000 (after removing 99.94% of Pb) 2+ The high-temperature structure (Example 5B) exhibits reduced performance in terms of its distribution coefficient, K. d =29,100 (removing 96.67% of Pb) 2+ For sodium iron titanate synthesized from solution at lower hydroxide levels, the same trend was observed in Example 6, where the lower-temperature structure (Example 6A) was superior to the higher-temperature structure (Example 6B). d The value changed nearly tenfold. Increasing the iron content in sodium iron titanate reversed this trend, as the high-temperature product (Example 7B) exhibited nearly five times the Pb content of the low-temperature product (Example 7A). 2+ K dExample 8: Potassium iron titanate removes 99.57% of Pb. 2+ Its performance was lower than that of the low-temperature sodium iron titanate in Examples 5A and 6A. The performance of the materials in Examples 9 and 10 (sodium zirconate and sodium niobate titanate, respectively) was recorded as having lower Pb content in the tests. 2+ Removed to undetectable levels, exhibiting at least 4,800,000 Pb. 2+ K d The K observed for potassium niobate titanate (Example 11) d It is the minimum possible K of sodium niobate in Example 10. d Approximately 1 / 10, but in Example 11, potassium niobate still removed 99.80% of Pb in the test. 2+ The performance of the material in Example 12 (potassium iron titanate with 50% more iron than that in Example 8) followed the previously observed trend that potassium iron titanate performance was not at the level of sodium iron titanate performance (compare the results of high-iron examples 7A / 7B and Example 12 in Table 34A), and the titanates with higher iron content (Sodium iron titanate and potassium iron titanate, respectively, in Examples 7B and 12) were not as effective as the corresponding titanates with lower iron content (Sodium iron titanate in Examples 5A and 6A and potassium iron titanate in Example 8). Nevertheless, the potassium iron titanate of Example 12 with high iron content removed 98.67% of Pb from the test solution. 2+ Examples 13-15 demonstrate the effect of incorporating M. 2+ To prepare metal titanates, wherein M 2+ =Co 2+ and Mn 2+ This is achieved through the novel chemical method disclosed in this application. The properties of the two sodium cobalt titanate samples in Table 34A (Examples 13 and 14A) are recorded as having Pb values ​​of 1,821,000 and 3,264,000, respectively. 2+ K d When sodium cobalt titanate in Example 14A is mixed with Mg 2+ When ion exchange is performed (Example 14B), the performance is slightly lower than that for Mg in Example 3B. 2+ Conversely, the exchanged sodium titanate showed improved performance superior to the parent sodium titanate (Example 3A). Nevertheless, the material in Example 14B exhibited Pb... 2+ K d =744,000, removing 99.87% of Pb from the test solution. 2+ The sodium manganese titanate of Example 15 was recorded as having K d =5,466,000, Pb 2+ K d The highest measured value corresponds to the removal of 99.98% of Pb from the test solution. 2+High pH chemistry in a homogeneous solution, achieved using multiple complexing agents including MHCA, provides efficient removal of Pb from the test solution. 2+ Various alkali metal titanate compositions.

[0741] Examples 16-25 in Table 34A are Pb materials obtained from TiO2 powder and spray-dried TiO2 spheres. 2- Intake test results. Unlike Examples 1-15 obtained through solution chemistry, these materials are typically obtained from TiO2 powder in the presence of hydroxide and at least one complexing agent, MHCA (the same reaction medium required in the synthesis of all metal titanates of this disclosure). When additional metals (such as Fe or Co) are incorporated into the metal titanate ion exchanger, additional complexing agents, such as citric acid, are required, and in some cases, hydrogen peroxide is required. Example 16 illustrates the synthesis of sodium titanate from freshly precipitated titanium hydroxide in the presence of a NaOH / catechol solution, wherein MHCA is catechol, also known as 1,2-dihydroxybenzene. This material Na 0.37 Ti removes detectable levels of Pb below 3 ppb. 2+ The allocation coefficient Pb is obtained. 2+ K d >5,165,000. Example 17 Material K 0.26 Ti can also be obtained in the presence of catechols, but using KOH solution and TiO2 powder. This material also provides readily available Pb. 2+ Intake, with Pb 2+ K d =1,426,000, corresponding to the removal of 99.93% of Pb. 2+ Example 18 illustrates the synthesis of mixed metal titanates from TiO2 powder, with a composition of K. 0.31 Fe 0.18 Ti 0.82 The Fe was prepared using citric acid and MHCA d-sorbitol. 3+ The solution is kept in a concentrated KOH solution. For this material, Pb... 2+ K d =128,600, corresponding to the removal of 99.23% of Pb from the test solution. 2+ Similarly, in NaOH solution, again in the presence of Fe... 3+ Citric acid and d-sorbitol (used to retain Fe) 3+ Sodium iron titanate (Na₂O₂) with different structures was prepared from TiO₂ powder at 200℃ after 1 day and 4 days, respectively, under the condition of a complexing agent soluble in strong NaOH solution. 0.33 Fe 0.18 Ti 0.82 (Example 19A) and Na0.46 Fe 0.17 Ti 0.83 (Example 19B). Performance of the material Pb in Example 19A 2+ K d =260,400 compared to the performance of potassium iron titanate from Example 18 obtained from KOH and the material from Example 19B prepared under more demanding conditions. 2+ K d =73,900 is more robust, indicating 98.7% removal of lead from the test solution. Pb depends on synthesis conditions. 2+ This change in uptake properties reflects the changes observed in sodium iron titanate obtained from the solutions of Examples 5A / 5B and 6A / 6B. The high crystallinity of sodium titanate of Example 20A, formed from spray-dried TiO2 spheres, is evident in Figure 2B, and this material exhibits Pb... 2+ K d =100,900, while after acid extraction (Example 20B), Pb 2+ K d The value dropped to 89,960. Iron-containing metal titanate spheres (Example 21A) formed from TiO2 spheres and iron / citric acid / d-sorbitol / NaOH solution exhibited Pb... 2+ K d =200,300, almost twice the value seen in sodium titanate spheres in Example 20A, while acid extraction (Example 21B) also showed Pb values ​​of 200,300, almost double the values ​​seen in sodium titanate spheres in Example 20A, and acid extraction also showed Pb values ​​of 200,300, almost double the values ​​seen in sodium titanate spheres in Example 20A, while acid extraction (Example 21B) also 2+ K d The value decreased to 164,900, indicating that 99.4% of Pb was removed from the test solution. 2+ Similar to Example 20A, Example 22 is a highly crystalline sodium titanate prepared from spray-dried TiO2 spheres by tumbling rather than static reaction stirring and a d-sorbitol / NaOH solution, and has Pb 2+ K d =456,600, which is more effective than the material in Example 20A. The potassium titanate in Example 23A was also prepared by tumbling spray-dried TiO2 spheres in a KOH / d-sorbitol solution. Observed Pb 2+ K d =1,257,000, which is greater than those observed for the corresponding sodium titanate spheres in Examples 20A and 22. Upon acid treatment, it produces the product of Example 23B, and Pb was observed. 2+ K d =443,100. Example 24A product was derived from a single 2L batch scale-up process of TiO2 powder treated with KOH / d-sorbitol in a stirred reactor. This material exhibits Pb... 2+ K d=1,589,000. Acid treatment of this material yields the product of Example 24B, which has Pb 2+ K d =396,500, similar to the acid-treated product of Example 23B. A portion of the product of Example 24A was calcined in clean, dry air at 350°C for 2 hours, a process that can be used to anneal the metal titanate exchanger with the binder or simply to anneal the metal titanate ion exchanger itself. The calcined product of Example 24C exhibited Pb 2+ K d =1,012,000, indicating that the material withstood typical conditions for bonding and still performed well. Acid extraction of the calcined product of Example 24C yielded the product of Example 24D, which was obtained in Pb 2+ K d The test also showed good results at values ​​of 505,700. The 2L reaction mixture used to prepare the product of Example 24A was repeated 10 times, and the products were mixed to form a single composite product (Example 24E). The composite sample exhibited Pb... 2+ K d =809,500, which corresponds to the removal of 99.9% of Pb from the test solution. 2+ The acid extraction product of the composite sample (Example 24F) showed Pb 2+ K d =495,800, which is lower than the parent product. Synthesis starting with spray-dried TiO2 spheres was also scaled up in KOH / d-sorbitol solution (Example 25 series), similar to the series obtained from TiO2 powder in Examples 24. Examples 25A, 25B, and 25C are products of individual 2L static reactions, exhibiting Pb values ​​of 1,099,000, 699,000, and 961,500, respectively. 2+ K d These products were mixed to form the composite sample of Example 25D, which exhibited Pb 2+ K d =967,800, a slight improvement in Pb compared to the composite sample of Example 24E obtained from TiO2 powder. 2+ Uptake performance. Acid extraction of the product from Compound Example 25D yielded a product with reduced Pb. 2+ K d The product of Example 25E, with a value of 321,900, corresponds to the removal of 99.7% of Pb from the test solution. 2+ The material in Example 26, prepared from nanoscale anatase titanium dioxide reagent, not only exhibits a uniform particle size distribution, but also shows high Pb content. 2+ It showed excellent performance in terms of uptake, demonstrating Pb 2+ K d=1,539,000. Typically, this type of TiO2 powder yields metal titanate ion exchangers in Pb... 2+ They performed well in terms of intake.

[0742] Examples C1-C6 are comparative examples provided to illustrate the progress presented in this disclosure. Example C1 is a sodium nonatannate product (disclosed in Example 4 of US 11,964,266 for the removal of Pb from bodily fluids). 2+ (Sample from Lianxin Company). This disclosure relates to tests conducted on this material obtained by treating titanium dioxide with NaOH and yielding Pb. 2+ K d =258,700. In contrast, as in Example 16 of this application, titanium dioxide powder converted to sodium titanate in the presence of NaOH and MHCA agents such as catechol exhibited improved Pb. 2+ K d >5,165,000. As seen in Examples 27 and 28, the product of Example C1 has a low surface area (44 m²). 2 The unacceptable particle size distribution ( / g) makes it unsafe for human use. Similarly, Example C2 is disclosed in Example 17 of US 11,964,266 for the removal of Pb from bodily fluids. 2+ The product is potassium octatitanate from Honeywell. This material yields Pb. 2+ K d =504,300. In contrast, the eleven 2L formulations of Example 24E composite samples (potassium titanate obtained by treating TiO2 powder in the presence of KOH / d-sorbitol solution) exhibited improved Pb. 2+ K d =809,500. As seen in Examples 27 and 28, Example C2 potassium octatitanate has a 196m composite with the potassium titanate complex of Example 24E. 2 / g lower surface area (8m 2 / g) and unacceptable particle size distribution for gastrointestinal-based treatments (27.0 vol% of the sample less than 3 µ). Examples C5 and C6 demonstrate the benefits of using MHCA when applied to the hydrothermal conversion of TiO2 spray-dried spheres. The spray-dried TiO2 spheres of Example C5 have the same type (Pb) used to prepare the product of Example 25. 2+ (Measurement of background performance) and obtained Pb 2+ K d =1074, which is a limited performance. In Example C6, the TiO2 spheres spray-dried in Example C5 were converted to potassium titanate only in the presence of potassium hydroxide, similar to the preparation methods used in Examples C1 and C2 in the absence of MHCA. The Pb of this material 2+K d =296,100, lower than the Pb of the composite sample of Example 25D formed from transformed titanium dioxide spheres in the presence of KOH and additional MHCA d-sorbitol. 2+ K d =967,800. Furthermore, the material in Example C6 has 119m... 2 / g of surface area, while for potassium titanate obtained by KOH / d-sorbitol treatment, the surface area is much higher (203m²). 2 / g).

[0743] Table 34B shows two K-type samples from Examples 24F and 25E. + -H + Na of titanate ion exchangers + K + Mg 2+ Ca 2+ Intake allocation coefficient (K) d K d In the range of tens to hundreds, rather than for Pb 2+ The uptake of hundreds of thousands or millions of ions is observed. The low affinity of these ion exchangers for biologically important cations is a significant advantage, as it helps treat elevated Pb levels in vivo. 2+ Other physiological processes will not be interrupted during this process. Ideally, it would be suitable for Pb. 2+ The removed ion exchanger will "minimally interfere" with the concentration of other cations in the body.

[0744] Example 31

[0745] Competitive Pb 2+ intake

[0746] Pb disclosed in Example 30 2+ The uptake study involved the uptake of free Pb from the test solution. 2+ Ions. Not limited by theory, Pb in body fluids 2+ The uptake and test of Pb in the solution 2– The intake of Pb is more challenging compared to other substances, because Pb... 2+It can be complexed with components present in the blood or gastrointestinal tract. One identified component is L-glutathione (L-GSH), which is widely distributed in animal tissues, plant cells, and microorganisms (see *Journal of Biol. Chem.*, 263, 17205–17208, 1988). Studies on workers with occupational lead exposure have shown that with increasing BLL, blood glutathione levels and the activity of enzymes utilizing glutathione decrease (see *Science of the Total Environment*, 170(1-2), 95-100, 1995). The L-GSH / Pb ratio was examined under biologically relevant conditions. 2+ Pb with a ratio varying between 2 and 10 2+ The nature of the -glutathione complex formation reveals that at least three different complexes may exist in vivo (see Inorganic Chemistry, 51(11), 6285-6298, 2012). Here, competitive Pb is used. 2+ Adsorption studies were conducted to determine the Pb uptake by metal titanate ion exchangers in the presence of L-GSH. 2+ The efficacy was determined. The testing procedure was the same as that disclosed in Example 30, except that the test solutions were modified in two ways. First, the two test solutions were modified by adding L-GSH to obtain L-GSH / Pb ratios of 10 and 1. 2+ The ratio. Secondly, for L-GSH / Pb 2+ =1 test, the adsorption part was carried out at 37°C (i.e. body temperature). The results are provided in Table 35.

[0747] Table 35

[0748]

[0749] To establish a baseline, the material of Example 24F was retested in the absence of L-GSH. This retest consisted of an acid-treated composite sample obtained from the hydrothermal conversion of titanium dioxide powder in a KOH / d-sorbitol solution, yielding K... d =534,700. L-GSH / Pb was also tested in the absence of any adsorbent. 2+ =10% L-GSH-containing feed to ensure Pb 2+ The glutathione complex was confirmed to be stable during the adsorption process. Even in the presence of a 10-fold excess of L-GSH complexing agent, the material of Example 24F still removed 70% of Pb from the test solution. 2+ K d =2,326. This result indicates that when the ion exchanger is complexed, it can compete with Pb. 2+When L-GSH / Pb 2+ When the concentration is 1, the results for the materials in Examples 24F and 25E (acid-treated composites of metal titanate spheres) are similar to those for materials completely free of L-GSH. Therefore, ion exchangers can be used to make Pb... 2+ It functions in a complexed environment.

Claims

1. A granular metal titanate ion exchanger, wherein the granular metal titanate ion exchanger, on an anhydrous basis, has the following empirical formula: And m Those x M y About z in A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.

85. The particulate metal titanate ion exchanger has been synthesized in the presence of at least one multi-hydroxy complexing agent (MHCA), and the particulate metal titanate ion exchanger has a median particle size of greater than 3 micrometers (µm).

2. The ion exchanger according to claim 1, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

3. The ion exchanger according to claim 1, wherein A is potassium ion, hydrated hydrogen ion, or a mixture thereof.

4. The ion exchanger according to claim 1, wherein the particulate metal titanate ion exchanger is a polycrystalline aggregate metal titanate ion exchanger.

5. The ion exchanger according to claim 1, wherein the particulate metal titanate ion exchanger is macroporous.

6. The ion exchanger according to claim 1, wherein the particulate metal titanate ion exchanger has a spherical morphology.

7. The ion exchanger according to claim 1, wherein the particulate metal titanate ion exchanger has an amorphous morphology.

8. The ion exchanger according to claim 1, wherein the particulate metal titanate ion exchanger is a powder.

9. The ion exchanger according to claim 1, wherein the median particle size is between 25 micrometers (µm) and 125 micrometers.

10. The ion exchanger according to claim 1, wherein less than 3% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 micrometers (µm).

11. The ion exchanger according to claim 1, wherein the particulate metal titanate ion exchanger has... Particle size distribution between approximately 5 micrometers (µm) and approximately 70 µm. 10 value; Particle size distribution between approximately 25 µm and approximately 125 µm 50 Value; and Particle size distribution between approximately 55 µm and approximately 185 µm 90 value.

12. The ion exchanger according to claim 1, wherein the particulate metal titanate ion exchanger is stable in a liquid environment with a pH of 1-2; substantially insoluble in a pH range of 1-13; or both.

13. The ion exchanger according to claim 1, wherein the particulate metal titanate ion exchanger has a concentration greater than 150 m² / g (m³). 2 / g), greater than 200m 2 / g or greater than 230m 2 / g of Bruno-Emet-Teller (BET) surface area.

14. The ion exchanger of claim 1, wherein the particulate metal titanate ion exchanger has a Pb-to-Pb ratio in solution between about 50,000 mL / g and about 5,500,000 mL / g. 2+ The allocation coefficient (K) d ).

15. The ion exchanger according to claim 1, wherein the at least one MHCA is selected from the group consisting of sugar alcohols, sugars, aromatic compounds and any combination thereof, optionally wherein the at least one MHCA is d-sorbitol.

16. The ion exchanger according to claim 1, wherein x is 1 and y is 0, and m is between 0.10 and 0.

50.

17. A macroporous granular titanate ion exchanger, wherein the macroporous granular titanate ion exchanger has the following empirical formula on an anhydrous basis: THE m Uncle z in A is an exchangeable cation selected from the group consisting of potassium ions, hydrated hydrogen ions, and mixtures thereof; "m" is the molar ratio of A to Ti and has a value of 0.10 to 0.60; and "z" is the molar ratio of O to Ti and has a value of 2.05 to 2.

60. The macroporous titanate ion exchanger described herein has been synthesized in the presence of a polyhydroxy complexing agent (MHCA), namely d-sorbitol. The macroporous particulate titanate ion exchanger has a median particle size between 25 micrometers (µm) and 125 micrometers, with less than 3.0% of the particles having a particle size of less than 3 micrometers (µm), and the macroporous particulate titanate ion exchanger having a particle size of at least 150 m² / g. 2 Bruno-Emet-Teller (BET) surface area ( / g).

18. The ion exchanger according to claim 17, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

19. The ion exchanger according to claim 17, wherein the macroporous particulate titanate ion exchanger has an amorphous morphology.

20. The ion exchanger according to claim 17, wherein the macroporous particulate titanate ion exchanger has one or more of the following: Particle size distribution between approximately 5 micrometers (µm) and approximately 45 µm. 10 value; Particle size distribution between approximately 25 µm and approximately 75 µm 50 Value; and Particle size distribution between approximately 55 µm and approximately 140 µm 90 value.

21. The ion exchanger of claim 17, wherein the macroporous particulate titanate ion exchanger has a median particle size between 25 micrometers (µm) and 125 micrometers, and wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size of less than 3 micrometers (µm).

22. The ion exchanger according to claim 21, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

23. The ion exchanger according to claim 21, wherein the macroporous particulate titanate ion exchanger has a spherical morphology.

24. The ion exchanger according to claim 21, wherein the macroporous particulate titanate ion exchanger has Particle size distribution between approximately 30 micrometers (µm) and approximately 70 µm 10 value; Particle size distribution between approximately 55 µm and approximately 125 µm 50 Value; and Particle size distribution between approximately 120 µm and approximately 180 µm 90 value.

25. A method for selectively removing Pb from gastrointestinal fluids. 2+ A method for removing Pb from a fluid containing the toxin, the method comprising contacting the fluid containing the toxin with a particulate metal titanate ion exchanger to generate an ion-exchanged ion exchanger, thereby removing the Pb from the fluid. 2+ The toxin, the granular metal titanate ion exchanger, on an anhydrous basis, has the following empirical formula: And m Those x M y About z in A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.

85. The metal titanate ion exchanger described herein has been synthesized in the presence of at least one polyhydroxy complexing agent (MHCA), the particulate metal titanate ion exchanger having a median particle size greater than 3 micrometers (µm), and the particulate metal titanate ion exchanger having minimal interference selected from Na. + Mg 2+ K + and Ca 2+ The level of any one or more ions.

26. The method of claim 25, wherein the Pb 2+ The toxin is isolated within the ion-exchanged ion exchanger after the contact.

27. A method for removing Pb from gastrointestinal fluids 2+ An in vivo method for removing a toxin, the method comprising contacting a fluid containing the toxin with a particulate metal titanate ion exchanger to generate an ion-exchanged ion exchanger, thereby removing the toxin from the fluid, the particulate metal titanate ion exchanger having the following empirical formula on an anhydrous basis: And m Those x M y About z in A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.

85. The particulate metal titanate ion exchanger described therein has been synthesized in the presence of at least one polyhydroxy complexing agent (MHCA).

28. A method for preparing particulate metal titanate ion exchangers, wherein the particulate metal titanate ion exchangers have the following empirical formula on an anhydrous basis: And m Those x M y About z in A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to the total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of the total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of the total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to the total metal and has a value of 1.55 to 2.

85. The method includes the following steps: (a) Forming a reaction mixture comprising a reactive A source, a Ti source, at least one polyhydroxy complexing agent (MHCA) source, an M source, a hydrogen peroxide source, a complexing agent (C) source, and water, and (b) The reaction mixture is heated at a temperature of about 85°C to about 225°C for a period of 0.5 days to 30 days to form the particulate metal titanate ion exchanger. The reaction mixture therein has a molar ratio of the following oxides. composition: p A2O : a TiO2 : b MO q / 2 : c H2O2 : d MHCA : e C : f H2O Where "p" has a value of approximately 4 to 40; "a" has a value of approximately 0.5 to 1; "b" has a value of 0 to 0.5, a+b=1; "q" is the charge on M and has a value of 2 to 5; "c" has a value of 0 to 6; "d" has a value of 0.2 to 4; "e" has a value of 0 to 4; and "f" has a value of 20 to 1000.

29. The method of claim 28, wherein the MHCA source is d-sorbitol, mannitol, xylitol, catechol, fructose, glucose, or mixtures thereof.

30. The method of claim 28, wherein the C source is citric acid, tartaric acid, EDTA, bipyridine, or mixtures thereof.

31. The method of claim 28, wherein the initial reaction mixture contains hydrogen peroxide, complexing agent C, polyhydroxy complexing agent MHCA, Ti(OiPr)4 and optional M and is a homogeneous solution.

32. The method of claim 28, wherein the Ti source is TiO2 powder, nano-sized TiO2 powder or pre-formed spray-dried TiO2 spheres, and optionally the Ti source further comprises Ti(OiPr)4.

33. The method according to claim 28, wherein the Ti source is TiO2 powder, nano-sized TiO2 or pre-formed spray-dried TiO2 spheres, MHCA is d-sorbitol, M is Fe, Mn, Co, Zr or a mixture thereof, and the C source is citric acid.

34. The method of claim 28, wherein the primary Ti source is TiO2 powder, nano-sized TiO2, or pre-formed spray-dried TiO2 spheres, optionally wherein the Ti source further comprises Ti(OiPr)4, MHCA is d-sorbitol, the hydrogen peroxide source is 30% by weight of hydrogen peroxide, M is Fe, Mn, Co, Zr, Nb, or a mixture thereof, and the C source is citric acid.

35. A method for manufacturing tablets or capsules or for oral administration, said tablets or capsules comprising a particulate metal titanate ion exchanger having the following empirical formula on an anhydrous basis: And m Those x M y About z in A is an exchangeable cation selected from the group consisting of potassium ions, sodium ions, lithium ions, calcium ions, magnesium ions, hydrated hydrogen ions, or mixtures thereof; M is optionally at least one framework metal selected from niobium (5+), zirconium (4+), tin (4+), iron (3+), iron (2+), cobalt (2+), and manganese (2+); "m" is the molar ratio of A to total metal (total metal = Ti + M) and has a value of 0.10 to 0.60; "x" is the molar fraction of total metal Ti and has a value of 0.5 to 1; "y" is the molar fraction of total metal M and has a value of 0 to 0.5, where x + y = 1; and "z" is the molar ratio of O to total metal and has a value of 1.55 to 2.85, wherein the particulate metal titanate ion exchanger has a median particle size greater than 3 micrometers (µm). The method includes the following steps: (a) Forming a reaction mixture comprising a reactive A source, a Ti source, at least one polyhydroxy complexing agent (MHCA) source, an M source, a hydrogen peroxide source, a complexing agent (C) source, and water. (b) The reaction mixture is heated for a certain period of time to form a metal titanate ion exchanger. (c) The synthesized metal titanate ion exchanger is treated by acid extraction and / or ion exchange with alkali metals, alkaline earth metals, or mixtures thereof to form the particulate metal titanate ion exchanger having the desired composition. (d) Optionally, the metal titanate ion exchanger is mixed with one or more pharmaceutically acceptable adjuvants, diluents, or carriers to form a metal titanate ion exchanger drug. (e) Forming capsules or tablets containing the particulate metal titanate ion exchanger. The reaction mixture therein has a molar ratio of the following oxides. composition: p A2O : a TiO2 : b MO q / 2 : c H2O2 : d MHCA : e C : f H2O Where "p" has a value of approximately 4 to 40; "a" has a value of approximately 0.5 to 1; "b" has a value of 0 to 0.5, a+b=1; "q" is the charge on M and has a value of 2 to 5; "c" has a value of 0 to 6; "d" has a value of 0.2 to 4; "e" has a value of 0 to 4; and "f" has a value of 20 to 1000.

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