Methods for treatment of lead poisoning

Abstract

Methods of treating lead poisoning are described. The methods involve administering to a patient in need thereof a therapeutically effective dose of a pharmaceutical composition comprising a particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of: AmTixMyOz where A is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion or 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+).

Description

METHODS FOR TREATMENT OF LEAD POISONINGRELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Patent Application Ser. No. 63 / 674,399, filed on July 23, 2024, the entirety of which is incorporated herein by reference.FIELD OF THE INVENTION

[0002] The present disclosure relates to treating, managing, or reducing the severity of lead poisoning by administering a pharmaceutical composition comprising a therapeutically effective dose of particulate metal titanate ion exchanger to a patient in need thereof.BACKGROUND

[0003] Lead has become widely distributed in the biosphere only in the past few thousand years, entirely as the result of human activity. Once introduced into the environment, lead persists. Investigations of human skeletal remains indicate that the body lead burden of today’s populations is 500-1000 times greater than that of their pre-industrial counterparts (See NE J. Med., vol. 326, no. 19, pp. 1293-1294, 1992). By far the largest contributor to global environmental lead contamination was the use of lead in gasoline, mainly between 1965 and 1990 (See Environ. Health Per sped., vol. 110, no. 7, pp. 721-728, 2002). With lead now removed from gasoline across the developed world, blood lead levels (BLLs) in the US and worldwide are expected to continue their slow decline (See Am. J. Med., vol. 129, pp. 1213- 1218, 2016). However, hot spots from smelting, mining, aging houses, water lines, highways, and metal recycling operations - some of them ongoing and others the legacy of the past - remain significant problems.

[0004] Despite a century of accumulated evidence about its danger to the health of children, lead often continues to be added to paints, pigments, toys, traditional medications, cosmetics, and other consumer products, especially as manufacturing shifts to developing countries that lack environmental and product content controls and policies. Dust from lead-based paint remains asignificant source of exposure (See J. Pediatrics, vol. 140, no. 1 , pp. 40-47, 2002). Soils in older areas of cities are often highly contaminated by lead.

[0005] Soils are not passive sources, and periodic re-suspension of fine lead-contaminated soil dust particulates create seasonal variations of lead exposure for urban dwellers (See Atmos. Environ., vol. 49, pp. 302-310, 2012). Furthermore, a coupling exists between inhaled and ingested lead. Inhalation studies examining lead particles (about 1 pm) deposited in the back of the nose have demonstrated that they are typically swallowed over time. In addition, particles deposited in the tracheobronchial region may be cleared from the lungs via the mucociliary escalator, reaching the gastrointestinal system via the esophagus (See Radiat. Prof. Dosim., vol. 127, pp. 31-34, 2007).

[0006] A change in water supply utilizing old, contaminated infrastructure brought lead- contaminated water to Flint, Michigan where significant elevation of blood lead levels (BLLs) was observed in children (See Am. J. Public Health, vol. 106, no. 2, pp. 283-290, 2016). A report released by the Natural Resources Defense Council in 2018 details how many other communities around the country are failing to adequately ensure that their water supplies remain free of lead (See E. Olson and K. P. Fedinick, Natural Resources Defense Council, New York, NY, 2016). Experts have estimated that 6 to 10 million lead service lines are being used in the US, serving 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).

[0007] Lead is highly toxic, it can harm the brain, kidneys, bone marrow and other bodily systems, especially those of young children. The Third National Health and Nutritional Examination (NHANES III, Phase 2, 1991-1994) found that 4.4% of children under 6 years old in the United States had BLLs above lOpg / dL, a level that is considered “poisoned.” (See Eliminating Childhood Lead Poisoning: A Federal Strategy Targeting Lead Paint Hazards,' President's Task Force on Environmental Health Risks and Safety Risks to Children, February 2000). Exposure via lead-containing paint is the main culprit, with the impact greater on children from low -income and minority families living in older housing, as 16% of these children are poisoned compared to the national average of 4.4% for all children (See Morbidity and Mortality Weekly Report, U.S. Department of Health and Human Services / Public Health Service, Vol 46, No.7, Feb 21, 1997, p. 141-146).

[0008] As BLLs increase in children, ill effects and morbidity associated with lead poisoning increases, including reduced IQ, decreased hearing, and decreased growth. Moreover, behavioral problems in children may occur at BLL = 10 pg / dL, impaired nerve function may occur at BLL = 20 pg / dL, reduced vitamin C metabolism may occur at BLL = 30 pg / dL, damage to hematopoiesis may occur at BLL = 40 pg / dL, severe stomach cramps may occur at BLL above 50 pg / dL, and severe brain and kidney damage and severe anemia may occur at BLL between 50 - 100 pg / dL. Even low-level elevations in children’s blood lead concentrations, such as at concentrations below 5 pg / dL, can result in decrements in cognitive functions, as measured by IQ scores and academic performance (See Public Health Rep., vol. 115, pp. 521-529, 2000; and Environ. Health P er sped., vol. 113, pp. 894-899, 2005).

[0009] For a given level of exposure, lead-associated IQ losses are proportionately greater at the lowest blood lead concentrations. While the average IQ decrease associated with an increase in blood lead concentration from less than 1 to 30 pg / dL was 9.2 IQ points, the decrease associated with an increase in blood lead concentration from less than 1 to 10 pg / dL was 6.2 IQ points. The population impact of lead on intellectual abilities is substantial, as lead toxicity accounts for an estimated total loss of 23 million IQ points among a 6-year cohort of contemporary US children (See Environ. Health Per spect., vol. 120, pp. 501-507, 2012). There is also an inverse relationship between early childhood exposure to lead and performance on tests of cognitive function and behavior 10 and 20 years after the blood lead levels were measured (See Pediatrics, vol. 90, pp. 855-861, 1992). Additionally, early exposures have been linked to increased rates of hyperactivity, inattentiveness, failure to graduate from high school, conduct disorderjuvenile delinquency, drug use, and incarceration (See P Los Medicine, vol. 5, p. elOl, 2008).

[0010] With respect to kidney damage, a study that examined the NHANES III (1988-1994) data reported that among 769 adolescents with a median blood lead concentration of 1.5 pg / dL (15 ppb), a doubling of the concentration of lead in blood led to a significant reduction in the glomerular filtration rate (See Arch Intern Med. , vol. 170, pp. 75-82, 2010).

[0011] Numerous experimental and epidemiological studies suggest that lead exposure is a risk factor for cardiovascular disease (CVD) and mortality. While a BLL in adults of 5 pg / dL is considered to be elevated, a recent study concluded that low-level environmental lead exposure (i.e., less than 5 pg / dL) is a risk factor for CVD mortality (See Lancet Public Health, vol. 3, pp.el 77-184, 2018). The authors tracked NHANES III (1988 - 1994) participants through 201 1 (-14,000 adults) and examined the relationship between lower levels of lead, down to a BLL of 1 pg / dL, and CVD and ischemic heart disease mortality. Analysis of the data suggested that about 400,000 US deaths annually are attributable to lead exposure in subjects having cardiovascular disease and / or diabetes, highlighting the potential risk factor of adult BLL concentrations of 1-5 pg / dL.

[0012] The treatment of chronic lead poisoning remains a widespread, persistent, and visible unmet medical need impacting millions of Americans. Over one million children in the United States have elevated blood lead levels. The American Academy of Pediatrics estimates that the annual cost of childhood lead exposure in the US is $50 billion. Further, as provided above, lead poisoning impacts adults as well.

[0013] The safe removal of lead from humans represents a significant on-going challenge for society. The Center for Disease Control (CDC) surveillance dataset and National Health and Nutritional Examination Survey (NHANES) data suggest that about 1 million US children have an elevated blood lead level (BLL) of greater than or equal to 5 pg / dL. However, most of these children have a BLL less than 25 pg / dL, with only about 0.03% having a BLL greater than 45 pg / dL, a level where treatment using potentially harmful chelation therapy is recommended by physicians.

[0014] NHANES data, a nationally representative US survey with random sampling of about 10,000 participants, and physician feedback suggest that lead poisoning rates are lower in the 6 - 17 age range (of one million children aged 0-17 with a BLL of greater than 5 pg / dL, about 50% are aged 0-5 based on NHANES data). CDC data and physician feedback also suggest that screening rates for lead exposure may be suboptimal. While Medicaid and select state protocols require universal screening, in practice screening rates are much lower. The National Committee for Quality Assurance (NCQA) data suggests that in 2017, only about 70% of Medicaid-covered children received at least one lead screening by 24 months. Lead screening and education may be regarded as a low priority in developmental check-ups, unless the child is considered as high risk. However, the Key Opinion Leaders (KOLs) did note that highly publicized environmental events (e.g., Flint, Michigan) may temporarily promote screening awareness.

[0015] NHANES data suggest that nearly half of U.S. adults may have a BLL greater than or equal to 1 pg / dL. A smaller number of U.S. adults have a BLL greater than or equal to 5 pg / dL,the reference blood lead level for adults designated by National Institute for Occupational Safety and Health (NIOSH) and Adult Blood Lead Epidemiology and Surveillance (ABLES), a CDC initiative focused on adult lead poisoning. Diagnosis of elevated BLL, even at high levels, is likely low because adults are typically only screened if they are symptomatic or in an occupation with a high-risk of lead exposure. State-reported data from the ABLES program estimated a national prevalence rate of 15.8 per 100,000 employed adults having a BLL greater than or equal to 10 pg / dL in 2016 (about 0.01% vs. 0.4% estimated by NHANES). Diagnosis rates of a BLL of less than 10 pg / dL are likely even lower given limited impetus and rationale to screen for lead today.

[0016] Chelation therapy has been used to remove lead from the blood. An optimal chelating drug should increase lead excretion, be administered easily, be affordable, and be safe. However, lead-chelate complexes may persist in tissues where the binding occurred, or may be redistributed to other tissues. Increased symptoms commonly reported with aggressive initiation of chelation therapies are cited as a contraindication to any use of chelators. Chelating agents effectively remove lead in the blood and are indicated for acutely affected patients with a BLL of greater than 45 pg / dL and are administered in consultation with a specialist ( ee 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 succimer).

[0017] EDTA, ethylenediaminetetraacetic acid, is used in the CaNa2EDTA form for chelation of lead to avoid hypocalcemia and possibly death due to its capability to bind calcium. It can also bind other bioavailable cations such as zinc, copper, and iron (See / / / / . J. Environ. Res. Public Health, vol. 7, pp. 2745-2788, 2010). It is often used in the treatment of severe lead poisoning and is administered intravenously in a hospital setting because substantial monitoring is required including renal function, cardiac activity, and daily phlebotomy to monitor serum electrolytes. Pain and swelling may result from the parenteral administration of CaNa2EDTA, while other adverse effects include fever, nausea, vomiting, and nephrotoxicity, such as microscopic hematuria and proteinuria. CaNa2EDTA has been reported to spread lead to other tissues and can increase lead concentrations in the central nervous system and may cause encephalopathy. After a single dose of CaNa2EDTA, urinary lead levels increase, blood lead levels decrease, and brain lead levels increase significantly due to redistribution of lead into the brain.

[0018] DMSA is indicated for BLLs of greater than 45 pg / dl. for treatment of acute lead poisoning situations, and it does not require administration in a hospital. Oral DMSA is dosed typically at 30 mg / kg / day for 5 days (See Med. Toxicol. Adverse Drug Exp., vol. 3, pp. 499-504, 1988), often followed by a 14-day course of 20 mg / kg / day, a treatment regimen that increases urine lead excretion and reduces blood lead concentrations significantly. Drug-induced neutropenia can occur, so weekly blood count is recommended, and treatment should be discontinued if neutrophil counts get too low. Adverse effects of DMSA treatment include nausea, vomiting, diarrhea, loose stool, metallic taste that are experienced singly or together by 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.

[0019] Dimercaprol, also known as British Anti-Lewisite (BAL) was originally developed as an experimental antidote to Lewisite, an arsenic-based poison gas. To administer dimercaprol to a patient, it is dissolved in peanut oil and injected into the muscles, a procedure not well tolerated by children. Dimercaprol, a small molecule, can penetrate the blood-brain barrier and can be used to treat encephalopathy, often in combination with CaNa2EDTA. The most common side effect of treatment with dimercaprol is a 50 mmHg rise in systolic and diastolic blood pressure among many others. In the 1960’s, dimercaprol was modified into DMSA, which has fewer side effects. Thus, dimercaprol has fallen out of favor for treatment of lead poisoning.

[0020] Chelation therapy with CaNa2EDTA, DMSA, and dimercaprol all are effective in reducing blood lead levels. However, a rebound in BLL often occurs following treatment, which likely results from absorbed lead emanating from bone and soft tissues. Considering the considerable side effects associated with chelation therapy, it is typically not practiced to address health problems associated with low level lead poisoning discussed above.

[0021] Zeolites, microporous aluminosilicate ion exchangers based on tetrahedral frameworks, have been proposed for treating chronic lead poisoning and are taken in pill form (See US 11,038,748). However, zeolites have limited stability in blood and the acidic environment of the gastrointestinal tract. In acidic solution, Al naturally has octahedral coordination and can be extracted from the tetrahedral zeolite framework. Indeed, treatment with acidic solution is one strategy to modify zeolite composition via dealumination, see US 6,982,074. Also, in US 11,038,748, a particulate sodium aluminosilicate is claimed with 90% of the particulates between a size of 90 and 150 microns (pm). A process is disclosed to achievethis particle size distribution that seems to involve screening using sieves. More recently, examples of microporous ion exchangers that are essentially insoluble in fluids, such as bodily fluids (especially blood), have been developed, including zirconium-based silicates 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 silicate or titanium-based silicate microporous ion exchangers to remove toxic ammonium cations from blood or dialysate is described in US 6,814,871; US 6,099,737; and US 6,332,985. Additionally, it was found that some of these compositions were selective in potassium ion exchange and could remove potassium ions from bodily fluids to treat the disease hyperkalemia. See 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. Ex-vivo applications of these materials, for instance in dialysis, are described in US 9,943,637. In particular, US 8,802,152 uses zirconium silicate compositions to treat hyperkalemia via the gastrointestinal tract and identifies particles smaller than 3 microns as undesirable, as these may be absorbed into the patient’s bloodstream causing adverse effects, including accumulation in the kidneys. Screening techniques are used to reduce or nearly eliminate particles less than 3 microns from the zirconium silicate product.

[0022] Many ion-exchangers have been developed for removal of “heavy metals” from various environments, often waste streams. The heavy metals removed by ion exchangers often include lead, mercury, cadmium, zinc, iron, chromium, copper, cobalt, nickel and even arsenic. Such metals are frequently considered to have the same ion-exchange properties, but, in fact, great variation exists among different metals. For example, the ability of a particular zeolite to remove Pb2+from solution does not necessarily remove Hg2+from solution. Indeed, in US 9,233,856 (“the ‘856 patent”), which is incorporated by reference herein in its entirety for all purposes, it is shown that the uptake of Hg2+by zeolites is highly dependent on the framework charge density or equivalently, the Si / Al ratio. High charge density Si / Al = 1 zeolites like X (FAU topology) and 4A (LTA topology) are shown to have very low affinity for Hg2+under the test conditions, while Ca2+and Mg2+are easily removed (See ’856 patent at Example 10). In the same test using UZM-9, a zeolite with Si / Al = 5.50 that has the same LTA zeolite topology as zeolite 4A, the situation is reversed and there is high selectivity for Hg2+, while the selectivity to Ca2and Mg2+is highly diminished. In the case of zeolite 4A and UZM-9, this result decouples structure from the framework charge density and shows the importance of the latter in ion-exchange selectivity (See ’856 patent at Example 1 1). Meanwhile, zeolite X is shown to be excellent at removing Pb2+from aqueous solution, while it performs poorly at removing Hg2+(See ‘856 patent at Comparative Example 13). Hence, to determine an ion exchanger’s cation selectivity, the relevant data must be collected for each remediated metal cation / resident metal cation / ion exchanger combination.

[0023] A process was disclosed for the removal of Sr2+ions from bodily fluids using Zr, Ti, Sn-based metallate ion exchangers, see US 11,577,014, which is incorporated by reference herein in its entirety for all purposes. The majority of the ion exchangers provided in the ‘014 patent are crystalline and amorphous metallosilicates, while a metal oxide was also disclosed, a commercial sodium nonatitanate sample. A process has also been disclosed for the removal of Hg2+from bodily fluids utilizing Ti metallates, see US 11,484,875, which is incorporated by reference herein in its entirety for all purposes. Ti was required in the compositions with Nb and Si optional. Very specific topology / composition combinations were required for efficient Hg2+removal, including metal silicates Ti-Nb sitinakite and acid treated zorite as well as a metal oxide, a commercial sodium nonatitanate from Allied-Signal. Also, US 11,964,266 (“the ‘266 application), which is incorporated by reference herein in its entirety for all purposes, discloses the use of metallosilicates and metal oxides for the removal of cobalt, lead, cadmium, and chromium ions from bodily fluids using Zr, Ti, Sn-based metallate ion exchangers. The majority of the ion exchangers of the ‘266 application are crystalline and amorphous metallosilicates while two metal oxides were disclosed, a commercial sample of sodium nonatitanate from Allied-Signal and a commercial potassium octatitanate product from Honeywell. Unlike the sodium nonatitanate, the potassium octatitanate was not effective for efficient Hg2+and Sr2+removal.

[0024] Since chronic lead poisoning in both children and adults remains an unmet medical need with no FDA-approved treatment, there exists a need for improved methods of removing lead which are low cost, effective, and easily implemented.SUMMARY

[0025] The present disclosure provides for, and includes, a method for treating, managing, or reducing the severity of lead poisoning in a subject in need thereof comprising a step of administering a pharmaceutical composition to the subject in need thereof, the pharmaceuticalcomposition comprising a therapeutically effective dose of particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTixMyOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion, and 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl-containing complexing agent (MHCA), wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm), and wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering.

[0026] The present disclosure provides for, and includes, a method for treating, ameliorating, or reducing the severity of lead poisoning in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTiOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, and a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl-containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is in a range of 25 to 125 microns (pm), wherein less than 3.0% of the particles of the macroporousparticulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is in a range of 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0027] The present disclosure provides for, and includes, a method for treating, ameliorating, or reducing the severity of lead poisoning in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTiOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, and a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl -containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is in a range of 25 to 125 microns (pm), wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is in a range of 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0028] The present disclosure also provides for, and includes, a method for reducing an elevated level of Pb2+in a subject in need thereof, the method comprising a step of administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a therapeutically effective dose of particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTixMyO; whereinA is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion, and 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl-containing complexing agent (MHCA), wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm), and wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering.

[0029] The present disclosure further provides for, and includes, a method for reducing an elevated level of Pb2+in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTiOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, or a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl-containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is in a range of 25 to 125 microns (pm), wherein less than 3.0% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surfacearea of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is in a range of 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0030] The present disclosure provides for, and includes, a method for reducing an elevated level of Pb2+in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis ofAmTiOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, and a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl -containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is in a range of 25 to 125 microns (pm), wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is in a range of 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0031] The present disclosure provides for, and includes, use of a particulate metal titanate ion exchanger for the manufacture of a medicament for treating, ameliorating, or reducing the severity of lead poisoning in a subject in need thereof, the particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTixMyOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.8, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl-containing complexing agent (MHCA), and wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm).

[0032] The present disclosure provides for, and includes, use of a particulate metal titanate ion exchanger for the manufacture of a medicament for reducing an elevated level of Pb2+in a human subject in need thereof, the particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTixMyOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1 ; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxy-containing complexing agent (MHCA), and wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm), and wherein the subject in need thereof comprises an elevated level of Pb2+prior to the administering.BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1, comprising Figures 1A-1F, shows scanning electron microscope images (SEM) of metal titanate products derived from syntheses in aqueous solution. In the presence of the MHCA d-sorbitol, large polycrystalline aggregates of the metal titanate ion exchangers were isolated from syntheses carried out in homogenous solution.

[0034] Figure 1A shows a scanning electron microscope image (SEM) of Nao.25Feo.2oTio.8o, from Example 5B having polycrystalline sphere morphology.

[0035] Figure IB shows an SEM image of Nao 25Feo 2oTi 080, Example 5B. Polycrystalline slab morphology.

[0036] Figure 1C shows an SEM of Nao33Feo38Tio.62, Example 7B. Poly crystalline interpenetrating spheres.

[0037] Figure ID shows an SEM of Nao.33Feo.38Tio.62, Example 7B. Polycrystalline interpenetrating spheres.

[0038] Figure IE shows an SEM of Nao.39Zro.o3Tio.97, Example 9. Polycrystalline interpenetrating spheres.

[0039] Figure IF shows an SEM ofK-Nb-Ti-O, Example 11. Slabs of polycrystalline interpenetrating spheres.

[0040] Figure 2, including Figures 2A-2L, shows that metal titanate ion exchangers consisting of large polycrystalline aggregates are synthesized from TiCh powders and preformed TiCh spheres in strongly alkaline media in the presence of multihydroxyl-containing complexing agents.

[0041] Figure 2A shows an SEM of Ko.2eTi, Example 17. Polycrystalline sponge-like morphology derived from TiCh powder in the presence of KOH / catechol solution.

[0042] Figure 2B shows an SEM of Na-Ti-O, Example 20A. Complex aggregates of very large polycrystalline interpenetrating spheres derived from preformed TiCh spheres hydrothermally treated in the presence of NaOH / d-sorbitol solution.

[0043] Figure 2C shows an SEM of Na-Fe-Ti-O, Example 21A. Na-Fe-Ti-0 polycrystalline spheres derived from preformed TiCh spheres treated hydrothermally with Fe(NO3)3 / citric acid / d-sorbitol / NaOH solution.

[0044] Figure 2D shows an SEM of Na-Fe-Ti-O, Example 21 A. Na-Fe-Ti-0 polycrystalline spheres derived from preformed TiCE spheres treated hydrothermally with Fe(NO3)3 / citric acid / d-sorbitol / NaOH solution.

[0045] Figure 2E shows an SEM of Ko.4oTi, Example 24A. Spongy macroporous poly crystalline aggregates derived from hydrothermal treatment of TiCE powder in the presence of d-sorbitol / KOH solution.

[0046] Figure 2F shows an SEM of Ko.4oTi, Example 24A. Close up of the spongy macroporous polycrystalline network in the aggregate. Derived from hydrothermal treatment of TiCE powder in the presence of d-sorbitol / KOH solution.

[0047] Figure 2G shows an SEM of Ko.soTi, composite sample, Example 24E. Spongy macroporous polycrystalline aggregates derived from hydrothermal treatment of TiO? powder in the presence of d-sorbitol / KOH solution.

[0048] Figure 2H shows an SEM of Ko.3oTi, composite sample, Example 24E. Close-up view of the spongy macroporous polycrystalline network in the aggregates. Derived from hydrothermal treatment of TiO2 powder in the presence of d-sorbitol / KOH solution.

[0049] Figure 21 shows an SEM of Ko.2sTi, composite sample, Example 25D. Field view of Ko.2sTi spheres derived from hydrothermal treatment of spray dried TiO2 spheres in the presence of d-sorbitol / KOH solution.

[0050] Figure 2J shows an SEM of Ko2sTi, composite sample, Example 25D. Close-up view of Ko.28Ti spheres derived from hydrothermal treatment of spray dried TiO2 spheres in the presence of d-sorbitol / KOH solution.

[0051] Figure 2K shows an SEM of Ko.ieTi, acid-treated composite sample, Example 25E.Field view of acid-treated composite sample of Example 25D. Spheres maintain structural integrity during acid treatment.

[0052] Figure 2L shows an SEM of Ko.ieTi, acid-treated composite sample, Example 25E. Close-up view of acid-treated composite sample of Example 25D. Spheres maintain structural integrity during acid treatment.

[0053] Figures 3 - 7 show particle size distribution data for selected examples and comparative examples of the prior art. Definition of terms: D3(pm): The smallest 3 volume percent of particles in the sample is smaller than the particle size D3(pm), measured in microns. Similarly, D10(pm) is the particle size under which the smallest 10 volume percent of the sampleoccurs. D50(pm) is equivalent to the median particle size, the particle size under which the smallest 50 volume percent of the sample occurs. D90(pm) is the particle size under which the smallest 90 volume percent of the sample occurs. The parameter < 3 pm (vol%), indicates the volume percent of the sample that is less than 3 pm in size. The Mean is the average particle size in the sample.

[0054] Figure 3 shows the particle size distribution of a sodium nonatitanate prior art material from comparative Example C 1.

[0055] Figure 4 shows the particle size distribution of potassium octatitanate prior art material from comparative Example C2.

[0056] Figure 5 shows the particle size distribution of Example 24F product prepared from TiCh powder treated hydrothermally in the presence of d-sorbitol / KOH solution followed by acid treatment.

[0057] Figure 6 shows the particle size distribution of the Example 25D product prepared from spray dried TiCh spheres treated hydrothermally in the presence of KOH / d-sorbitol solution.

[0058] Figure 7 shows the particle size distribution of the Example 25E product prepared from spray dried TiCh spheres treated hydrothermally in the presence of KOH / d-sorbitol solution followed by acid treatment.

[0059] Figure 8 is a graph of the average body mass of rats over time in the lead removal study.

[0060] Figure 9 is a graph of the average mass of feces of rats over time in the lead removal study.

[0061] Figure 10 is a graph of the average concentration of lead in feces samples of rats over time in the lead removal study.DETAILED DESCRIPTION

[0062] A. Secretion of Lead Ions

[0063] An individual with chronic lead poisoning includes those where the lead persists in having a significant amount of lead in his blood, organs, and soft tissue, even when that person no longer consumes lead from the environment. Bones can contain most of the lead, which isreleased into the blood persistently as the body naturally recycles calcium from bone. Once in circulation, lead and lead complexes partition into all tissues, including the liver.

[0064] Heavy metals, like lead, have been reported to undergo enterohepatic circulation. This process involves the blood, liver, and intestine. The liver is one of the main organs for the accumulation of lead. However, in enterohepatic circulation, certain amounts of hepatic heavy metals are released from the liver into the intestines via bile, absorbed by the blood vessels in the gut (more specifically the ileum), and finally re-transported to the liver.

[0065] Bile is a complex fluid containing water, electrolytes, and numerous organic molecules, including bile acids, cholesterol, phospholipids, and bilirubin, that flows through the biliary tract into the small intestine. Without being limited by theory, the functions of bile in all species include: 1) bile contains bile acids, which are essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine, and 2) many waste products are eliminated from the body by secretion into bile and elimination in feces. Adult humans produce 400-800 mL of bile daily, and other animals produce proportionately similar amounts.

[0066] Without being limited by theory, the secretion of bile can be considered to occur in two stages. Initially, hepatocytes in the liver secrete bile into canaliculi, from which it flows into bile ducts. This hepatic bile contains large quantities of bile acids, cholesterol, and other organic molecules. It is modified by addition of a watery, bicarbonate-rich secretion from ductal epithelial cells as it flows through the bile ducts. In species with a gallbladder (humans and most domestic animals except horses and rats), further modification of bile occurs in that organ. The gall bladder stores and concentrates bile during the fasting state. Typically, bile is concentrated five-fold in the gall bladder by absorption of water and small electrolytes; virtually all the organic molecules are retained.

[0067] Bile acids are derivatives of cholesterol synthesized in the liver. Cholesterol, ingested as part of the diet or derived from hepatic synthesis, is converted into the bile acids cholic and chenodeoxy cholic acids, which are then conjugated to an amino acid (glycine or taurine) to yield the conjugated form that is actively secreted into cannaliculi. Again, not limited by any particular theory, it should be noted that free cholesterol is virtually insoluble in aqueous solutions, but in bile, it is made soluble by bile acids and lipids like lecithin. Bile acids are facial amphipathic, that is, they contain both hydrophobic (lipid soluble) and hydrophilic faces. The cholesterolderived portion of a bile acid has one face with methyl groups (hydrophobic) and another withhydroxyl groups (hydrophilic). The amino acid conjugate is polar and hydrophilic. Their amphipathic nature enables bile acids to carry out various functions. Indeed, they provide emulsification of lipid aggregates; bile acids have detergent action on particles of dietary fat which causes fat globules to break down or be emulsified into minute, microscopic droplets. Emulsification is not digestion; instead, it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplets. Bile acids are lipid carriers and can solubilize many lipids by forming micelles, aggregates of lipids such as fatty acids, cholesterol, and monoglycerides, that remain suspended in water.

[0068] Again, not limited by any particular theory, bile acids are also involved in transport and absorption of fat-soluble vitamins. Hepatic synthesis of bile acids accounts for the majority of cholesterol breakdown in the body. In humans, roughly 500 mg of cholesterol are converted to bile acids and eliminated in bile every day. This route for elimination of excess cholesterol and endogenous elements functions in all animals, and particularly in situations of excessive consumption. Large amounts of bile acids are secreted into the small intestine every day, but only relatively small quantities are lost from the body. This is because approximately 95% of the bile acids delivered to the duodenum are absorbed back into blood within the ileum through enterohepatic circulation. Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver. Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into systemic circulation. Bile acids are then transported across the hepatocytes to be re-secreted into canaliculi. The net effect of this enterohepatic recirculation is that each bile salt molecule is reused about 20 times, often two or three times during a single digestive phase.

[0069] Heavy metals are reabsorbed from the ileum into the portal vein. However, studies of radiolabeled lead suggest that the reabsorbed lead redistributes throughout the body. The liver and kidneys filter lead from the blood and eliminate it from the body. The path of lead injected into small mammals, such as rats, rabbits, and dogs, has been tracked using radiolabeled lead (e.g.,203Pb,210Pb). Similar studies have tracked the distribution of lead in humans; some studies conducted in the mid-20th century actively dosed humans with lead salts.

[0070] Once lead accumulates in the liver, biliary excretion is a major route of removal of lead from the liver into the intestine for elimination in feces. However, a significant amount of lead undergoes enterohepatic circulation back into the bloodstream with the biliary secretionswith which it is associated. The disruption of this circulation provides a path to increase the elimination of heavy metals in feces. Biliary excretion via glutathione (GSH) has been reported to be the main excretory route of heavy metals.

[0071] Without being limited by theory, literature data are consistent with the involvement of at least two steps in the movement of heavy metals from liver cells to bile. The first step involves the formation of a metal-glutathione complex in the liver cell. It is assumed to happen naturally without the assistance of an enzyme. Numerous in vitro experiments demonstrate that heavy metals, like lead, form stable complexes with GSH (e.g., Pb-GSH). The concentration of glutathione, a tripeptide thiol, typically exists at micromolar concentrations in extracellular fluids. In bile, the concentration of glutathione is 1-6 mM, which is similar to that of intracellular levels.

[0072] Again, not limited by any particular theory, the second step involves the secretion of metal-GSH complexes from the liver into the intestine. An electrophoretic analysis of rat bile observed Pb21cations bound to the postalbumin zone (i.e., serum protein electrophoresis can be used to separate the serum protein components into major fractions by their size and electrical charge. The post-albumin zones comprise the alpha-1, alpha-2, beta, and gamma globulin fractions). This has been further refined using numerous GSH inducers and depletors to demonstrate that biliary excretion of heavy metals correlates closely with glutathione secretion. In particular, phenobarbital and pregnenolone- 16a-carbonitrile (PCN) have been demonstrated to increase both the transport of GSH into bile and the biliary excretion of metals, such as Zn, Hg, and Cd.

[0073] Again, not limited by any particular theory, identification of GSH as an endogenous complexing agent in the transport of metals between tissues and body fluids permits the design of therapeutic strategies aimed at exploiting this transport vehicle to improve the removal of heavy metals via physiological routes of excretion. An ion exchanger that can selectivity immobilize lead in the GI tract would enhance the fecal excretion of lead by disrupting its enterohepatic recirculation back into the bloodstream via recycled bile salts.

[0074] In clinical practice, lead measured in whole blood is a major biomarker of lead exposure for a patient and remains an important method used to determine the duration of treatment and assess its efficacy; however, the lead in whole blood accounts for only 1% to 5% of the total body lead burden (see J. Clin. Invest., vol. 58, pp. 260-270, 1976). Most lead in the body iscontained in bone and other calcified tissues. Bone lead is stored for longer durations and slowly exchanges with blood, which then exchanges lead with other tissues. This results in persistent lead exposure to the cardiovascular system, brain tissues, and kidneys over decades even after environmental lead exposure has ceased. Accordingly, caution should be used when using blood lead as a surrogate for the total body burden of lead, particularly during and immediately after treatment when reductions in blood lead levels overestimate reductions in other tissues (see Environ. Health Perspect., vol. 112, no. 3, pp. 302-308, 2004). Treatment may need to extend beyond the point at which a patient’s blood lead levels have dropped to an acceptable target value in order to effectively reduce the total body burden of lead.

[0075] B. Pharmaceutical Compositions

[0076] The present disclosure provides for, and includes, a pharmaceutical composition comprising a therapeutically effective dose of particulate metal titanate ion exchanger for treating, ameliorating, or reducing the severity of lead poisoning in a subject in need thereof. The present disclosure also provides for, and includes, a pharmaceutical composition comprising a therapeutically effective dose of particulate metal titanate ion exchanger for reducing an elevated level of Pb2+in a subject in need thereof. The pharmaceutical compositions used in the methods provided herein, in one aspect, comprise an effective amount of a particulate metal titanate ion exchanger and a pharmaceutically acceptable carrier, adjuvant or diluent. As used herein, a pharmaceutical composition may also be referred to as a metal titanate ion exchanger composition. A “pharmaceutically acceptable carrier, adjuvant or diluent” can refer to one or more compatible solid or liquid fillers or gel substances which are suitable for use in the human body. The “compatible” herein refers to that all ingredients in a composition can be mixed with each other and can be mixed with the compounds according to the present disclosure, while the medicinal effect of the compounds is not significantly reduced. Some non-limiting examples of the pharmaceutically acceptable carrier, adjuvant or diluents include cellulose and derivatives thereof (e.g., sodium carboxymethyl cellulose, sodium ethyl cellulose, and cellulose acetate), gelatin, talc, solid lubricants (e.g., stearic acid and magnesium stearate), calcium sulfate, plant oils (e.g., soybean oil, sesame oil, peanut oil, and olive oil), polyols (e.g., propylene glycol, glycerin, mannitol, and sorbitol), emulsifiers (e.g., Tween), wetting agents (e.g., sodium dodecyl sulfate), coloring agents, flavoring agents, stabilizing agents, antioxidants, preservatives,pyrogen-free water, and the like. Tn an aspect, the pharmaceutically acceptable carrier, adjuvant or diluent is sterile saline. In an aspect, the pharmaceutically acceptable carrier, adjuvant or diluent is phosphate-buffered saline (PBS).

[0077] Procedures for the selection and preparation of suitable pharmaceutical formulations, depending on the route of administration, are described in, for example, “Pharmaceuticals - The Science of Dosage Form Designs”, M. E. Aulton, Churchill Livingstone, 2nd Ed. 2002, which is incorporated by reference herein in its entirety for all purposes.

[0078] The present disclosure provides for, and includes, use of a pharmaceutical composition comprising a metal titanate ion exchanger which exhibits significant lead uptake and selectivity for lead over other electrolytes in bodily fluids (e.g., Na+, K+, Mg2+, Ca2+, etc.). Indeed, the pharmaceutical compositions comprising a metal titanate ion exchanger used in the methods provided herein, in one aspect, can reduce the concentration of lead pre-complexed to glutathione from simulated small intestinal fluid from 240 ppb to near the lower limit of quantification (less than 5 ppb by Inductively Coupled Plasma - Mass Spectrometry (ICP-MS)). Moreover, the pharmaceutical compositions comprising a metal titanate ion exchanger used in the methods provided herein, in one aspect, have been optimized for dosing them orally as a non-systemic drug Also, the pharmaceutical compositions comprising a metal titanate ion exchanger used in the methods provided herein, in one aspect, are stable in low pH environments and do not dissolve or lose their efficacy when exposed to simulated gastric fluid (HC1, pH about 1.5) for prolonged time periods (e.g., up to 6 hours). Preparation and characterization of the metal titanate ion exchangers used in the methods provided herein are disclosed in U.S.Provisional Application No. 63 / 528,801, which is incorporated by reference herein in its entirety for all purposes.

[0079] In an aspect, the metal titanate ion exchanger compositions used in the methods provided herein can be synthesized directly and / or meshed to achieve a particle size distribution (PSD) that meets the FDA standard for non-systemic solid particles (greater than 97% of the material by volume has a particle size greater than 3 micrometers). This avoids the particles perfusing out of the small intestine into the blood stream, which can result in the material accumulating in the liver and kidneys. The non-systemic metal titanate ion exchanger compositions of the present disclosure are designed to achieve minimal side effects above that of a placebo. As described in U.S. Pat. Nos. 8,802,152, 8,808,750, 9,844,567, and 10,335,432, ithas been theorized that small particles, less than 3 pm in diameter, of an insoluble powder could potentially be absorbed into a patient's bloodstream through the small intestine resulting in undesirable effects such as the accumulation of particles in the urinary tract of the patient, and particularly in the patient's kidneys. Indeed, the Label for LOKELMA® (sodium zirconium cyclosilicate), an FDA approved drug, describes it as a non-absorbed powder that includes no more than 3% of particles with a diameter below 3 pm. An in vivo pharmacokinetic study in rats showed that a dose of sodium zirconium cyclosilicate powder that meets this specification for particle size distribution was recovered in the feces with no evidence of substantial systemic absorption.

[0080] The methods provided herein use a pharmaceutical composition comprising a metal titanate ion exchanger which has a large capacity and strong affinity, i.e., selectivity, for Pb2+ions, both free and complexed. The metal titanate ion exchanger compositions used in the methods provided herein are synthesized in the presence of at least one multihydroxyl-containing complexing agent (MHCA), which enables facile chemistry of titanium and the M elements in highly basic aqueous solution and imparts properties such as favorable particulate size and particle size distribution that helps avoid undesirable absorption during treatment in the gastrointestinal tract. The metal titanate compositions used in the methods provided herein are identified as alkali metal titanate compositions as synthesized, which besides Ti4+may additionally contain Mn2+, Co2+, Fe2+, Fe3+, Sn4+, Zr4+, and Nb5+, or mixtures thereof and may additionally be modified by ion exchange. They are further identified by their composite empirical formula (on an anhydrous basis) which is:AmTixMyOzThe composition has a framework structure(s) composed of at least TiO<,noctahedral units where n may be 2 or 3 or both, or optionally may include MOe / n octahedral units where n may be 2 or 3 or both, although other coordination environments may occur for Ti and M. A is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.6, “x” is the mole fractionof total metal that is Ti and has a value from 0.5 to 1 .0, “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, where x + y = 1, and “z” is the mole ratio of O to total metal and has a value from 1.55 to 2.85.

[0081] In an aspect, metal titanate ion exchanger compositions used in the methods provided herein exhibit a median particle size greater than 3 microns. In an aspect to synthesize the metal titanate ion exchanger compositions used in the methods provided herein, novel chemistry is used to facilitate incorporation of M and Ti into the same network. In an aspect, metal titanates are cation exchange compositions, which require a negative charge on the metal oxide component. To obtain negatively charged metal oxide frameworks that can operate as ion exchangers, synthesis can occur at higher pHs than that associated with the point of zero charge of the metal oxides, the pH associated with neutral metal oxides. In an aspect, metal titanate compositions of the present disclosure, this necessitates synthesis in alkaline solution, usually highly alkaline solution. Ti and the M metals are insoluble in highly alkaline solution, which can be detrimental to successful incorporation of the metals into the same phase. Metals are often available as salts and form acidic solutions on dissolution in water. This is true for the M metals Sn, Zr, Co, Mn, and Fe. The solubility of these metals can be extended to basic pHs using complexing agents such as citric acid, amines, or EDTA, perhaps as high as pH 10 - 12, but these will precipitate when taken to the higher pHs required to synthesize the metal titanates of the present disclosure. Dissolving Ti and Nb reagents in aqueous solutions can be problematic, as salts such as TiCh or NbCE and alkoxides such as titanium isopropoxide, Ti(OiPr)4, and niobium ethoxide, Nb(OEt)s, can hydrolyze and precipitate immediately. Aqueous solutions of these Ti and Nb reagents can be formed in the presence of sufficient H2O2 in acidic solution. The solubility of these Ti and Nb solutions can be extended to higher pH via addition of a complexing agent such as citric acid, the case for Nb-peroxo-citrate solution formation at pH = 7.5 from poorly soluble niobium oxalate is documented, see Chem. Mater. 1997, 9, 580 - 587. Peroxo-citrato solutions of Nb and Ti also precipitate when further treated with hydroxide; solubility at high pH is not realized. With the addition of a multihydroxyl-containing complexing agent, an MHCA, such as d-sorbitol or catechol that have high pKa, to these metal citrate solutions or metal peroxo-citrate solutions, these solutions can retain their solution character as hydroxide is added to increase the pH, resulting in stable solutions of Ti and the M metals at very high pH, e.g., greater than pH = 14 if desired. Not to be bound by theory, at high pH, thehydroxyls of sugar alcohols like d-sorbitol or aromatic diols like catechol can be deprotonated, becoming strong complexing agents that can stabilize metals in highly basic aqueous solutions. The availability of Ti and the M metals in these highly basic solutions facilitates their mutual incorporation into the metal titanate ion exchanger compositions of the present disclosure during their synthesis. Hydrothermal digestion of these reaction mixtures form products comprising large polycrystalline aggregates, often spheres, interpenetrating spheres, slabs, and other morphologies; these particulates are often large enough (e.g., greater than 3 pm) to avoid absorption into the gastrointestinal tract.

[0082] In an aspect, MHCAs can be used to enhance the synthesis of the metal titanate ion exchanger compositions of the present disclosure from TiCh powder. Hydrothermal treatment of TiCh powders in alkaline solution in the presence of MHCAs facilitates the formation of macroporous polycrystalline aggregates that are larger than those observed in the solution syntheses. In an aspect, macroporous polycrystalline aggregates are large enough to avoid absorption into the gastrointestinal tract and M metals are incorporated into the TiCh powders by preparing a highly basic solution containing the M metal using the appropriate complexing agents such as H2O2, citric acid, and an MHCA to maintain the M metal in solution and help transport Ti, mixing the TiCh powder with the solution, and treating the resulting mixture hydrothermally, thereby forming a product comprised of large macroporous polycrystalline aggregates imparted by the presence of the MHCAs.

[0083] In an aspect, MHCAs can be applied to pre-formed TiCh powder starting materials, specifically spray dried spheres. Hydrothermal treatment of the TiCh spheres with alkaline solutions containing MHCAs yields macroporous spheres. The M metals are incorporated into the TiCh spheres in a similar manner as the TiCh powders, e.g., by preparation of a highly basic solution containing the M metal using the appropriate complexing agents such as H2O2, citric acid, and an MHCA, mixing the TiCh spheres with the M-containing alkaline solution, and treating the resulting mixture hydrothermally, thereby forming of a macroporous sphere. The product spheres are large enough to avoid absorption by the gastrointestinal tract.

[0084] The metal titanate ion exchanger compositions used in the methods provided herein are prepared by a hydrothermal crystallization of a reaction mixture prepared by combining a reactive source of titanium and optionally one or more M metal, at least one alkali metal, at least one complexing agent including at least one MHCA, optionally hydrogen peroxide and water.Without being limited by theory, an alkali metal can act as a framework charge balancing agent as well as a templating agent. Examples of titanium metal sources include, but are not limited to titanium alkoxides, titanium tetrachloride, titanium trichloride, amorphous titanium oxyhydroxide, titanium dioxide, nano-sized titanium dioxide (i.e., crystallite size about 100 nm or less), and spray dried TiO2spheres. Examples of M metal sources include, but are not limited to cobalt acetate, cobalt nitrate, cobalt chloride, manganese acetate, manganese nitrate, manganese chloride, manganese sulfate, iron (3+) nitrate, iron (3+) chloride, iron (2+) chloride, iron (2+) sulfate, iron (2+) acetate, tin (4+) chloride, zirconyl chloride, zirconyl nitrate, zirconium alkoxides, zirconium acetate, zirconium chloride, niobium oxalate, ammonium oxoniobium dioxalate, niobium chloride, and niobium alkoxides. Examples of A alkali sources include potassium hydroxide, sodium hydroxide, lithium hydroxide, sodium halide, potassium halide, lithium halide, sodium acetate, potassium acetate, and lithium acetate. Elydrogen peroxide is an optional complexing agent for which the preferred source is 30 wt.% aqueous solution. Examples of multihydroxyl-containing 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 multihydroxyl-containing aromatics such as catechol. MHCAs are understood to contain at least two hydroxyl groups. One or more complexing agents C may be employed in any reaction. Complexing agent sources include, but are not limited to carboxylates, like citric acid and tartaric acid, nitrogen-containing complexing agents like EDTA, and bipyridine, and mixtures thereof. In an aspect, the hydrothermal process used to prepare the titanium metallate ion exchange compositions of the present disclosure involves forming a reaction mixture which in terms of molar ratios of the oxides is expressed by the formula: p A2O : a TiO2: b MOq / 2: c H2O2: d MHCA : e C : f H2O where "p" has a value from about 4 to 40, "a" has a value from about 0.5 to 1, "b" has a value from 0 to 0.5, a + b = 1, "c" has a value from 0 to 6, “MHCA” is at least one multihydroxyl- containing complexing agent, "d" has a value from 0.2 to 4, “C” is at least one complexing agent, “e” has a value of 0 to 4, and "f1has a value from 20 to 1000. A reaction mixture can be prepared by mixing the desired sources of alkali metal, titanium, multihydroxyl-containing complexing agent MHCA, optionally hydrogen peroxide, optionally complexing agents C,optionally M metal and water to give the desired mixture. It is also necessary that the final reaction mixture have a basic pH and preferably a pH of at least 12.5. The basicity of the mixture is controlled by adding alkali hydroxide. Having formed the reaction mixture, it is next reacted at a temperature of about 85 °C to about 225 °C for a period of about 0.5 to about 30 days in a sealed reaction vessel under autogenous pressure. After the allotted time, the mixture is filtered or centrifuged to isolate the solid product which is washed with deionized water and dried in air. As stated, the compositions of the present disclosure can have a framework structure composed mostly of octahedral TiOe / n units, and optionally octahedral MOs n units, n = 2 or 3, but other coordination environments may be present. Metal titanate ion exchangers used in the methods provided herein may exhibit various levels of crystallinity or may be amorphous.

[0085] In an aspect, as-synthesized metal titanate ion exchanger compositions of the present disclosure may contain some of the alkali metal templating agent in the pores, between layers and chains, or in other charge balancing positions. These metals are described as exchangeable cations, meaning that they can be exchanged with other (secondary) A' cations. Generally, the A exchangeable cations can be exchanged with A' cations selected from other alkali metal cations (K+, Na+, Li+), alkaline earth cations (Mg2+, Ca2+), hydronium ion or mixtures thereof. It is understood that the A' cation is different from the A cation. The methods used to exchange one cation for another are well known in the art and involve contacting the compositions with a solution containing the desired cation (at molar excess) at exchange conditions. Exchange conditions include a temperature of about 25° C to about 100° C and a time of about 20 minutes to about 2 hours. The particular cation (or mixture thereof), which is present in the final product will depend on the particular use of the composition and the specific composition being used.

[0086] In an aspect, synthesized powder forms of the metal titanate ion exchanger compositions of the present disclosure are generally particles that are greater than 3 microns in size, since particles that are less than 3 microns in size can be absorbed by the body. However, it may be desirable to have a subset of the particles being smaller than 3 microns with an upper limit of 3% less than 3 microns in size by volume. In an aspect, a metal titanate ion exchanger of the present disclosure exhibits a median particle size greater than 3 microns. In an aspect, a metal titanate ion exchanger of the present disclosure has a median particle size ranging from 25 to 125 microns.

[0087] It is also within the scope of the present disclosure that ion exchange compositions can be used in the methods provided herein in an as-synthesized powder form or can be formed into various shapes by processes well known in the art. Examples of these various shapes include pills, extrudates, spheres, pellets, and irregularly shaped particles. See, e.g., US Patent Nos. 6579460B1 and 6814871B1. In an aspect, forming processes may include the addition of a binding agent, for example, zirconia, that may require annealing, which may occur by calcination in air at temperatures up to 35O°C for 2 to 6 hours. In an aspect forming may also occur at several scales, for instance at one scale for the synthesis of the metal titanate ion exchanger and at another scale for delivery of the metal titanate ion exchanger to the body. For instance, spray dried TiCh spheres of tens of microns in diameter may be used as the starting material for the synthesis of the metal titanate ion exchangers, which can then be formed into a larger pill for delivery to the body. Conversely, in an aspect, metal titanate ion exchanger compositions of the present disclosure may first be 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 may later be formed into a pill. In an aspect, formed pills or other shapes of the metal titanate ion exchangers used in the methods provided herein can be ingested orally and sequester toxins within the ion exchanger as it passes through the intestines and is finally excreted from the body. In an aspect it is possible to protect the ion exchangers used in the methods provided herein from the high acid content in the stomach by coating the shaped articles with various coatings which will not dissolve in the stomach but will dissolve in the intestines.

[0088] As provided herein, in an aspect, metal titanate ion exchanger compositions of the present disclosure can have particular utility in adsorbing various Pb2+-containing toxins, including free Pb2+ions and Pb2+from complexed Pb2+ions, from bodily fluids. The metal titanate ion exchanger compositions of the present disclosure are not limited to the treatment of gastrointestinal fluids; they may also be used to remove Pb2+from other bodily fluids, such as blood, blood plasma, urine, and dialysate solutions. In an aspect, metal titanate ion exchanger compositions of the present disclosure may also be used to remove Pb2+from feces. Also, in an aspect, pharmaceutical compositions of the present disclosure may be used to remove Pb2+content from any mammalian body, including but not limited to humans, cows, pigs, sheep, monkeys, gorillas, horses, dogs, etc. The instant process is particularly suited for removing toxins from a human body.

[0089] As provided herein, in an aspect, metal titanate ion exchanger compositions are synthesized with a variety of exchangeable cations ("A"), it is preferred to exchange the cation with secondary cations (A1) which are more compatible with blood or do not adversely affect the blood. Compositional requirements for the ion exchanger will vary with the needs of the patient. For this reason, preferred cations are potassium, sodium, lithium, calcium, magnesium, and hydronium. Preferred compositions are those containing potassium ions. In an aspect, other preferred compositions are those containing hydronium ions. Yet other preferred compositions are those containing a mixture of potassium and hydronium ions.

[0085] In an aspect, a pharmaceutical composition comprising a particulate metal titanate ion exchanger composition according to the present disclosure is in a solid dosage form. Solid dosage forms used for oral administration may include capsules, tablets, pills, powders, extrudates, spheres, pellets, granules, and irregularly shaped particles. Among these solid dosage forms, an active particulate metal titanate ion exchanger is mixed with at least one conventional inert excipient (or vehicle), such as sodium citrate or dicalcium phosphate, or mixed with any one or more of the following ingredients: (a) a filler or a compatibilizer, such as starch, lactose, sucrose, glucose, mannitol, and silicic acid; (b) a bonding agent, such as hydroxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, and gum arabic; (c) a moisturizer, such as glycerin; (d) a disintegrant, such as agar, calcium carbonate, potato starch or tapioca starch, alginic acid, some composite silicates, and sodium carbonate; (e) a slow solvent, such as paraffin; (f) an absorbing accelerator, such as quaternary amine compounds; (g) a wetting agent, such as cetyl alcohol and glyceryl monostearate; (h) an adsorbent, such as kaolin; and (i) a lubricant, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium dodecyl sulfate, or a mixture thereof. Dosage forms of capsules, tablets, and pills may also contain a buffer agent.

[0086] In an aspect, solid dosage forms such as tablets, sugared pills, capsules, pills, and granules may be prepared using coatings and shells, such as enteric coatings and other materials known in the art. The solid dosage forms may contain opacifiers, and moreover, active particulate metal titanate ion exchangers or particulate metal titanate ion exchangers in such compositions may be released in a portion of the digestive tract in a delayed manner. Nonlimiting examples of embedding components that can be employed are polymeric materials andwaxy materials. The active particulate metal titanate ion exchangers may also be formed into microcapsules with one or more of the above excipients.

[0087] In an aspect, a pharmaceutical composition comprising a particulate metal titanate ion exchanger composition according to the present disclosure is in tablet form. In an aspect, a pharmaceutical composition comprising a particulate metal titanate ion exchanger according to the present disclosure is in capsule form. In an aspect, a pharmaceutical composition in tablet form further comprises a tablet coating. In an aspect, a pharmaceutical composition in capsule form further comprises a capsule coating.

[0088] In an aspect, liquid preparations for oral application may be in the form of syrups, solutions or suspensions. Solutions, for example, may contain the compound used in the methods of the present disclosure, the balance being sugar and a mixture of ethanol, water, glycerol and propylene glycol. Optionally such liquid preparations may contain coloring agents, flavoring agents, saccharine and / or carboxymethylcellulose as a thickening agent. Furthermore, other excipients known to those skilled in art may be used when making formulations for oral use. In addition, liquid suspensions for oral application may contain a suspending agent, such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol, sorbitan ester, microcrystalline cellulose, aluminum methoxide, agar, or a mixture of these substances.

[0089] In an aspect, for oral administration, a particulate metal titanate ion exchanger according to the present disclosure may be admixed with one or more pharmaceutically acceptable adjuvants, diluents or carriers, for example, lactose, saccharose, sorbitol, mannitol; starch, for example, potato starch, com starch or amylopectin; cellulose derivative; binder, for example, gelatin or polyvinylpyrrolidone; disintegrant, for example cellulose derivative, and / or lubricant, for example, magnesium stearate, calcium stearate, polyethylene glycol, wax, paraffin, and the like, and then compressed into tablets. If coated tablets are required, the cores, prepared as described above, may be coated with a suitable polymer dissolved or dispersed in water or readily volatile organic solvent(s). Alternatively, the tablet may be coated with a concentrated sugar solution which may contain, for example, gum arabic, gelatin, talcum and titanium dioxide.

[0090] In an aspect, an oral dosage form is a film-coated oral tablet. In an aspect, the dosage form is an immediate release dosage form with rapid dissolution characteristics under in vitro test conditions.

[0091] In an aspect, for the preparation of soft gelatin capsules, a pharmaceutical composition comprising a particulate metal titanate ion exchanger according to the present disclosure may be admixed with, for example, a vegetable oil or polyethylene glycol. Hard gelatin capsules may contain granules of the compound using pharmaceutical excipients like the above-mentioned excipients for tablets. Also, liquid or semisolid formulations of a particulate metal titanate ion exchanger may be filled into hard gelatin capsules.

[0092] In an aspect, a sustained-release preparation of a pharmaceutical composition comprising a particulate metal titanate ion exchanger of the present disclosure is administered. Examples of sustained-release preparations include semi -permeable matrices of solid hydrophobic polymers containing the particulate metal titanate ion exchanger, where the matrices are in the form of shaped articles, e.g., films or microcapsules. Examples of sustained- release matrices include polyesters, hydrogels, and polylactides.

[0093] In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger that is macroporous. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 50 angstroms (A) and about 500 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 50 A and about 400 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 50 A and about 300 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 50 A and about 200 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 50 A and about 100 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 50 A and about 75 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 100 A and about 500 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 200 A and about 500 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 300 A and about 500 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 400 A and about 500 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 100 A and about 350 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 200 A and about 300 A. Inan aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 225 A and about 275 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 240 A and about 260 A. In an aspect, the macroporous particulate metal titanate ion exchanger has a pore diameter in a range of about 350 A and about 450 A.

[0094] In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a median particle size in the range of 25 pm to 125 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 25 pm to 100 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 25 pm to 75 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 25 pm to 50 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 25 pm to 35 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 35 pm to 100 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 50 pm to 75 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 35 pm to 125 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 50 pm to 125 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 75 pm to 125 pm. In an aspect, the particulate metal titanate ion exchanger has a median particle size in the range of 100 pm to 125 pm. In an aspect, the particulate metal titanate ion exchanger is sufficiently large to prevent absorption in the gastrointestinal tract of the subject to which the pharmaceutical composition has been administered.

[0095] In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a particle size distribution dio value in a range of about 5 microns (pm) and about 70 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 5 pm and about 60 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 5 pm and about 50 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 5 pm and about 40 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 5 pm and about 30 pm. In an aspect, the particulate metal titanate ion exchanger has aparticle size distribution dio value in a range of about 5 pm and about 20 pm. Tn an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 20 pm and about 70 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 30 pm and about 70 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 40 pm and about 70 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 50 pm and about 70 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 10 pm and about 35 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 10 pm and about 25 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 15 pm and about 45 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 25 pm and about 45 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 35 pm and about 45 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 10 pm and about 20 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 12 pm and about 18 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value of about 15 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 40 pm and about 50 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 42 pm and about 48 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value of about 45 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 50 pm and about 60 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 51 pm and about 57 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dio value of about 54 pm.

[0096] In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a particle size distribution dso value in a range of about 40 microns (pm) and about 115 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 40 pm and about 90 pm.In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 40 pm and about 80 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 40 pm and about 70 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 40 pm and about 60 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 60 pm and about 115 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 70 pm and about 115 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 80 pm and about 115 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 90 pm and about 115 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 60 pm and about 90 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 60 pm and about 80 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 50 pm and about 80 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 50 pm and about 70 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 45 pm and about 55 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 48 pm and about 54 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value of about 51 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 70 pm and about 80 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 71 pm and about 77 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value of about 74 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 85 pm and about 95 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 89 pm and about 95 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dso value of about 92 pm.

[0097] In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a particle size distribution dgo value in a range of about 65 microns (pm) and about 185 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 65 pm and about 165 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution d9o value in a range of about 65 pm and about 145 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution d$>o value in a range of about 65 pm and about 135 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution d% value in a range of about 65 pm and about 125 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution d$>o value in a range of about 65 pm and about 115 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 65 pm and about 105 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 65 pm and about 95 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 65 pm and about 85 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 85 pm and about 185 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution d9o value in a range of about 105 pm and about 185 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 125 pm and about 185 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 145 pm and about 185 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution d9o value in a range of about 165 pm and about 185 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 75 pm and about 145 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 85 pm and about 145 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 95 pm and about 145 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 105 pm and about 145 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 115 pm and about 145 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 125 pm and about 145pm. Tn an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 95 pm and about 105 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 99 pm and about 105 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value of about 102 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 135 pm and about 145 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 137 pm and about 143 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value of about 140 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 155 pm and about 165 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 156 pm and about 162 pm. In an aspect, the particulate metal titanate ion exchanger has a particle size distribution dw value of about 159 pm.

[0098] In an aspect, less than 5% of the particles of the particulate metal titanate ion exchanger within a pharmaceutical composition of the present disclosure have a particle size of less than 3 pm. In an aspect, less than 4% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, less than 3% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, less than 2% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, less than 1% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, less than 0.5% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, less than 0.1% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, between about 5% and about 0.1% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, between about 5% and about 0.5% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, between about 5% and about 1% of the particles of the particulate metal titanate ionexchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, between about 5% and about 3% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, between about 3% and about 0.1% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, between about 1% and about 0.1% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm. In an aspect, between about 0.5% and about 0.1% of the particles of the particulate metal titanate ion exchanger within the pharmaceutical composition have a particle size of less than 3 pm.

[0099] In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Brunauer-Emmett-Teller (BET) surface area of greater than 150 square meters per gram (m2 / g). In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of greater than 160 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of greater than 170 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of greater than 180 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of greater than 190 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of greater than 200 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of greater than 210 m2 / g. In an aspect, the particulate metal titanate ion exchanger composition has a BET surface area of greater than 220 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of greater than 230 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of greater than 240 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area in a range of about 190 m2 / g and about 240 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area in a range of about 190 m2 / g and about 225 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area in a range of about 190 m2 / gand about 210 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area in a range of about 190 m2 / g and 200 about m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area in a range of 200 m2 / g and 240 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area in a range of about 210 m2 / g and about 240 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area in a range of about 225 m2 / g and about 240 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of about 236 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of about 203 m2 / g. In an aspect, the pharmaceutical composition comprises a particulate metal titanate ion exchanger having a BET surface area of about 197 m2 / g.

[0100] In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a distribution coefficient (Ka) for Pb2+in a range of about 50,000 to greater than 5,500,000 milliliters per gram (mL / g). In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a distribution coefficient (Ka) for Pb2+in a range of about 100,000 and about 2,500,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Ka for Pb2+in a range of about 200,000 mL / g and about 2,000,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Ka for Pb2+in a range of about 395,000 mL / g and about 1,600,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a K for Pb2+in a range of about 320,000 mL / g and about 1,100,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Ka for Pb2+in a range of about 320,000 mL / g and about 1,000,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a K for Pb2+in a range of about 320,000 mL / g and about 900,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Ka for Pb2+in a range of about 320,000 mL / g and about 800,000mL / g. Tn an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 320,000 mL / g and about 700,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 320,000 mL / g and about 600,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 320,000 mL / g and about 500,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 320,000 mL / g and about 400,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 400,000 mL / g and about 1,100,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 500,000 mL / g and about 1,100,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 600,000 mL / g and about 1,100,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 700,000 mL / g and about 1,100,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 800,000 mL / g and about 1,100,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 900,000 mL / g and about 1,100,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 1,000,000 mL / g and about 1,100,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 400,000 mL / g and about 1,000,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 500,000 mL / g and about 900,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Kd for Pb2+in a range of about 600,000 mL / g and about 800,000 mL / g. In an aspect, a pharmaceutical composition of thepresent disclosure comprises a particulate metal titanate ion exchanger having a Ka for Pb2+in a range of about 800,000 mL / g and about 850,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Ka for Pb2+in a range of about 950,000 mL / g and about 1,000,000 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Ka for Pb2+of about 321,900 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Ka for Pb2+of about 495,800 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger having a Ka for Pb2+of about 809,500 mL / g. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchange having a Ka for Pb2+of about 967,800 mL / g.

[0101] In an aspect, a pharmaceutical composition of the present disclosure comprises an acid-treated particulate metal titanate ion exchanger. In an aspect, a pharmaceutical composition of the present disclosure comprises a macroporous, acid-treated particulate metal titanate ion exchanger. In an aspect, a pharmaceutical composition of the present disclosure comprises a poly crystalline aggregate metal titanate ion exchanger. In an aspect, a pharmaceutical composition of the present disclosure comprises a macroporous, polycrystalline aggregate metal titanate ion exchanger. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger that has spherical morphology or amorphous morphology. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger that has spherical morphology. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger that has amorphous morphology.

[0102] In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger that is in powder form. In an aspect, a pharmaceutical composition of the present disclosure comprises a particulate metal titanate ion exchanger that is a powder. In an aspect, a pharmaceutical composition of the present disclosure is in tablet form. In an aspect, a pharmaceutical composition of the present disclosure is in capsule form. In an aspect, a pharmaceutical composition of the present disclosure in tablet form further comprises a tablet coating.

[0103] In an aspect, a pharmaceutical composition of the present disclosure comprising a particulate metal titanate ion exchanger is stable in a liquid environment at a pH of 1-2. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is substantially insoluble at a pH range of 1-7. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is substantially insoluble at a pH range of 7-13. In an aspect, the particulate metal titanate ion exchanger of the pharmacal composition is substantially insoluble at a pH range of 1-13. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is insoluble at physiological pH. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is substantially insoluble at physiological pH. As used herein, “physiological pH” refers to a pH range of 7.35-7.45. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is insoluble at stomach pH. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is substantially insoluble at stomach pH. As used herein, “stomach pH” refers to a pH range of 1-5. As used herein, “substantially insoluble” refers to a solubility of <1% (m / v) in a fluid (e.g., where mass is measured in g and volume is measured in mb, and 1% (m / v) is 1 gram per 100 milliliters). According to the 2015 CRC Handbook, a material is considered soluble in a solvent if a saturated solution contains more than 1% (m / v); any material in which 1 percent or less is dissolved is considered substantially insoluble. The solubility of a compound in body fluids will be quite different than its solubility in pure water because of the effect of proteins, pH, and other solutes in body fluids. When determining solubility of a material in gastrointestinal fluids and the bloodstream the pH of the biological fluids must be considered. Gastrointestinal body fluids vary considerably in their pH (See J. Pharm. Sci., vol. 104, no. 9, pp. 2855-2863, 2015 and J Indian Soc. Periodontal., vol. 17. No. 4, pp. 461-465, 2013). For example, the pH of the saliva is approximately neutral (mean values ranging from 6.2-7.6), stomach acid has an acidic pH (mean values ranging from 1.7-4.7). and the pH in the small intestine and colon is approximately neutral (mean values ranging from 5-8). Blood is approximately neutral, with a mean pH of about 7.4 (see Crit. Care, vol. 4, pp. 6-14, 2000). Therefore, a material is substantially insoluble in gastrointestinal bodily fluids if 1 percent or less dissolves in a simulated biological fluid across the pH range from 1.5-8. (CRC Handbook of Chemistry and Physics, 95thEd, CRC Press: Boca Raton. Fl, 2015, W. M. Haynes, Editor in Chief. ). In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is insoluble in one or more bodily fluids selected from the group consisting of blood, urine, and gastrointestinal fluid. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is insoluble in blood. In an aspect, the particulate metal titanate ion exchanger of the pharmacal composition is insoluble in urine (the pH of urine is typically in the range of 4.5-8). In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is insoluble in gastrointestinal fluid. In an aspect, the particulate metal titanate ionexchanger of the pharmaceutical composition is insoluble in both blood and urine. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is insoluble in both blood and gastrointestinal fluid. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is insoluble in both urine and gastrointestinal fluid. In an aspect, the particulate metal titanate ion exchanger of the pharmaceutical composition is insoluble in each of blood, urine, and gastrointestinal fluid.

[0104] In an aspect, “A” of “AmTixMyOz” is an exchangeable cation. In an aspect, “A” is optionally selected from the group consisting of potassium ion, sodium ion, lithium ion, magnesium ion, calcium ion, and hydronium ion. In an aspect, “A” is two or more exchangeable cations selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, and hydronium ion. In an aspect, “A” is three or more exchangeable cations selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, and hydronium ion. In an aspect, “A” is a potassium ion. In an aspect, “A” is a sodium ion. In an aspect, “A” is a calcium ion. In an aspect, “A” is a magnesium ion. In an aspect, “A” is a hydronium ion. In an aspect, “A” is a mixture of potassium and hydronium ions.

[0105] In an aspect, “M” of “ AmTixMyOz” is a framework metal. In an aspect, “M,” a framework metal, is optionally selected from the group consisting of Nb5+, Zr4+, Sn4+, Fe3+, Fe2+, Co2+, Mn2+. In an aspect, “M,” a framework metal, is optionally selected from two or more of the group consisting of Nb5+, Zr4+, Sn4+, Fe3+, Fe2+, Co2+, Mn2+. In an aspect, “M,” a framework metal, is optionally selected from three or more of the group consisting ofNb5, Zr41, Sn41, Fe3 1, Fe2+, Co2+, Mn2+. In an aspect, “M” is Nb5+. In an aspect, “M” is Zr4+. In an aspect, “M” is Sn4+. In an aspect, “M” is Fe3+. In an aspect, “M” is Fe2+. In an aspect, “M” is Co2+. In an aspect, “M” is Mn2+.

[0106] In an aspect, “m” of “AmTixMyOz” is the mole ratio of A to total metal (total metal = Ti + M). In an aspect, “m” has a value between about 0.10 to about 0.60. In an aspect, “m” has a value between about 0.10 to about 0.50. In an aspect, “m” has a value between about 0.10 to about 0.40. In an aspect, “m” has a value between about 0.10 to about 0.30. In an aspect, “m” has a value between about 0.10 to about 0.20. In an aspect, “m” has a value between about 0.20 to about 0.50. In an aspect, “m” has a value between about 0.30 to about 0.50. In an aspect, “m” has a value between about 0.40 to about 0.50. In an aspect, “m” has a value of about 0.28. In an aspect, “m” has a value of about 0.30. In an aspect, “m” has a value of about 0.40.

[0107] In an aspect, “x” of “AmTixMyOz” is the mole fraction of total metal that is titanium (Ti). In an aspect, “x” has a value between 0.50 to 1. In an aspect, “x” has a value between 0.60 to 1. In an aspect, “x” has a value between 0.70 to 1. In an aspect, “x” has a value between 0.80 to 1. In an aspect, “x” has a value between 0.90 to 1. In an aspect, “x” has a value between 0.50 to 0.90. In an aspect, “x” has a value 0.50 to 0.60. In an aspect, “x” has a value between 0.50 to 0.70. In an aspect, “x” has a value of 0.50. In an aspect, “x” has a value of 0.60. In an aspect, “x” has a value of 0.70. In an aspect, “x” has a value of 0.80. In an aspect, “x” has a value of 0.90. In an aspect, “x” has a value of 1.

[0108] In an aspect, “y” of “ AmTixMy0z” is the mole fraction of total metal that is “M”. In an aspect, “y” corresponds with “x” according to the stoichiometric equation “x + y = 1”. In an aspect, “y” has a value between zero to 0.50. In an aspect, “y” has a value between zero to 0.40. In an aspect, “y” has a value between zero to 0.30. In an aspect, “y” has a value between zero to 0.20. In an aspect, “y” has a value between zero to 0.10. In an aspect, “y” has a value between 0.10 to 0.50. In an aspect, “y” has a value between 0.20 to 0.50. In an aspect, “y” has a value between 0.30 to 0.50. In an aspect, “y” has a value between 0.40 to 0.50. In an aspect, “y” has a value of zero. In an aspect, “y” has a value of 0.10. In an aspect, “y” has a value of 0.20. In an aspect, “y” has a value of 0.30. In an aspect, “y” has a value of 0.40. In an aspect, “y” has a value of 0.50.

[0109] In an aspect, “x” is 1 and “y” is 0.

[0110] In an aspect, “z” of “AmTixMyOz” is the mole ratio of oxygen (O) to total metal (total metal = Ti + M). In an aspect, “z” has a value between about 1.55 to about 2.85. In an aspect, “z” has a value between about 1.55 to about 2.70. In an aspect, “z” has a value between about 1.55 to about 2.55. In an aspect, “z” has a value between about 1.55 to about 2.40. In an aspect, “z” has a value between about 1.55 to about 2.25. In an aspect, “z” has a value between about 1.55 to about 2. 10. In an aspect, “z” has a value between about 1.55 to about 1.95. In an aspect, “z” has a value between about 1.55 to about 1.80. In an aspect, “z” has a value between about 1.55 to about 1.65. In an aspect, “z” has a value between about 1.65 to about 2.85. In an aspect, “z” has a value between about 1.80 to about 2.85. In an aspect, “z” has a value between about 1.95 to about 2.85. In an aspect, “z” has a value between about 2.10 to about 2.85. In an aspect, “z” has a value between about 2.25 to about 2.85. In an aspect, “z” has a value between about 2.40 to about 2.85. In an aspect, “z” has a value between about 2.55 to about 2.85. In an aspect, “z” has avalue between about 2.70 to about 2.85. In an aspect, “z” has a value of about 1 .55. In an aspect, “z” has a value of about 1.65. In an aspect, “z” has a value of about 1.80. In an aspect, “z” has a value of about 1.95. In an aspect, “z” has a value of about 2.10. In an aspect, “z” has a value of about 2.25. In an aspect, “z” has a value of about 2.40. In an aspect, “z” has a value of about 2.55. In an aspect, “z” has a value of about 2.70. In an aspect, “z” has a value of about 2.85.

[0111] In an aspect, Ti of “AmTixMyOz” comprises Ti sourced from one or more Ti- containing compound, including but not limited to, Ti(OiPr)4, TiCU, TiCh and nano-sized TiCh (i.e., crystallite size of about 100 nm or less).

[0112] In an aspect, a multihydroxyl -containing complexing agent (MHCA) is a reaction complexing agent that contains at least two hydroxyl groups. In an aspect, MHCAs include but are not limited to sugar alcohols, such as d-sorbitol, mannitol, and xylitol, sugars such as glucose, and fructose, and multihydroxyl-containing aromatics such as catechol. In an aspect, the MHCA is d- sorbitol. In an aspect, the MHCA is mannitol. In an aspect, the MHCA is xylitol. In an aspect, the MHCA is catechol. In an aspect, the MHCA is glucose. In an aspect, the MHCA is fructose. In an aspect, the MHCA is a mixture of one or more of d-sorbitol, mannitol, xylitol, catechol, fructose, and glucose. In an aspect, the MHCA is a mixture of two or more of d-sorbitol, mannitol, xylitol, catechol, fructose, and glucose. In an aspect, the present disclosure provides for a pharmaceutical composition comprising a particulate metal titanate ion exchanger comprising between 0.01% to 4.0% weight per weight (w / w) of at least one MHCA. In an aspect, the present disclosure provides for a pharmaceutical composition comprising a particulate metal titanate ion exchanger comprising between 0.01% to 2.0% weight per weight (w / w) of at least one MHCA. In an aspect, the present disclosure provides for a pharmaceutical composition comprising a particulate metal titanate ion exchanger comprising between 0.01% to 1.0% weight per weight (w / w) of at least one MHCA. In an aspect, the present disclosure provides for a pharmaceutical composition comprising a particulate metal titanate ion exchanger comprising between 0.01% to 0.6% weight per weight (w / w) of at least one MHCA.

[0113] In an aspect, the present disclosure provides for a pharmaceutical composition comprising a particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of: AmTixMyOz wherein A is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl -containing complexing agent (MHCA), and wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm).

[0114] In an aspect, the present disclosure provides for a pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of AmTiOz, wherein A is an exchangeable cation that is a potassium ion, hydronium ion, or mixtures thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxylcontaining complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 3.0% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), and wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g).

[0115] In an aspect, the present disclosure provides for a pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of AmTiOz, wherein A is an exchangeable cation that is a potassium ion, hydronium ion, or mixtures thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxylcontaining complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), and wherein the macroporous particulate titanateion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g).

[0116] C. Methods and Uses

[0117] In an aspect, the present disclosure provides for a method of treating, ameliorating, or reducing the severity of lead poisoning in a subject in need thereof comprising a step of administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a therapeutically effective dose of particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of: AmTixMyOz, wherein A is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl -containing complexing agent (MHCA), wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm), and wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering. In an aspect, the administering is oral administration.

[0118] In an aspect, the present disclosure provides for a method for treating, ameliorating, or reducing the severity of lead poisoning in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of: AmTiOz, wherein A is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, and a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl-containing complexing agent (MHCA) that is d- sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 3.0% of the particles of themacroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0119] In an aspect, the present disclosure provides for a method for treating, ameliorating, or reducing the severity of lead poisoning in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of: AmTiOz, wherein A is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, and a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl-containing complexing agent (MHCA) that is d- sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0120] In an aspect, the present disclosure provides for a method for treating, ameliorating, or reducing the severity of lead poisoning in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having amorphous morphology and an empirical formula on an anhydrous basis of: AmTiOz, wherein A is an exchangeable cation that is a mixture of potassium and hydronium ions; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having beensynthesized in the presence of a multihydroxyl-containing complexing agent (MHCA) that is d- sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 3.0% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area in a range of 195 to 240 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0121] In an aspect, the present disclosure provides for a method for treating, ameliorating, or reducing the severity of lead poisoning in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having spherical morphology and an empirical formula on an anhydrous basis of: AmTiOz, wherein A is an exchangeable cation that is a mixture of potassium and hydronium ions; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl-containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area in a range of 190 to 250 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0122] In an aspect, the present disclosure provides for a method of reducing an elevated level of Pb2+in a subject in need thereof, the method comprising a step of administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a therapeutically effective dose of particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of: AmTixMyOz wherein A is an exchangeable cationselected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion, and 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl -containing complexing agent (MHCA), wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm), and wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering. In an aspect, the administering is oral administration.

[0123] In an aspect, the present disclosure provides for a method for reducing an elevated level of Pb2+in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of: AmTiOz, wherein A is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, or a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl-containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 3.0% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0124] In an aspect, the present disclosure provides for a method for reducing an elevated level of Pb2+in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical compositioncomprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of: AmTiOz, wherein A is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, and a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl-containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0125] In an aspect, the present disclosure provides for a method for reducing an elevated level of Pb2+in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having amorphous morphology and an empirical formula on an anhydrous basis of: AmTiOz, wherein A is an exchangeable cation that is a mixture of potassium and hydronium ions; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl-containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 3.0% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area in a range of 195 to 240 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0126] In an aspect, the present disclosure provides for a method for reducing an elevated level of Pb2+in a human subject in need thereof comprising a step of orally administering apharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having spherical morphology and an empirical formula on an anhydrous basis of: AmTiOz, wherein A is an exchangeable cation that is a mixture of potassium and hydronium ions; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl -containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area in a range of 190 to 250 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0127] In an aspect of the methods provided herein, a pharmaceutical composition of the present disclosure is administered orally to the subject in need thereof in tablet or capsule form. In an aspect the pharmaceutical composition is administered orally to the subject in need thereof in tablet form. In an aspect the pharmaceutical composition is administered orally to the subject in need thereof in capsule form. The dosage of the pharmaceutical composition administered orally may vary. In an aspect, the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day). In an aspect, the therapeutically effective dose is between 1 to 1500 mg / kg / day. In an aspect, the therapeutically effective dose is between 1 to 1000 mg / kg / day. In an aspect, the therapeutically effective dose is between 1 to 500 mg / kg / day. In an aspect, the therapeutically effective dose is between 1 to 250 mg / kg / day. In an aspect, the therapeutically effective dose is between 1 to 100 mg / kg / day. In an aspect, the therapeutically effective dose is between 50 to 2000 mg / kg / day. In an aspect, the therapeutically effective dose is between 50 to 1000 mg / kg / day. In an aspect, the therapeutically effective dose is between 50 to 500 mg / kg / day. In an aspect, the therapeutically effective dose is between 50 to 250 mg / kg / day. In an aspect, the therapeutically effective dose is between 50 to 100 mg / kg / day. In an aspect, the therapeutically effective dose is between 100 to 2000 mg / kg / day. In an aspect, the therapeutically effective dose is between 100 to 1000 mg / kg / day. In an aspect, the therapeutically effective dose is between100 to 500 mg / kg / day. In an aspect, the therapeutically effective dose is between 100 to 250 mg / kg / day. In an aspect, the therapeutically effective dose is between 500 to 2000 mg / kg / day. In an aspect, the therapeutically effective dose is between 500 to 1000 mg / kg / day.

[0128] In an aspect of the methods provided herein, a pharmaceutical composition of the present disclosure may be administered to the subject in needed thereof on an ongoing basis or for a discrete treatment period. In an aspect, the administration is for at least 7 days. In an aspect, the administration is for at least 2 weeks. In an aspect, the administration is for at least 3 weeks. In an aspect, the administration is for at least 1 month. In an aspect, the administration is for at least 2 months. In an aspect, the administration is for at least 3 months. In an aspect, the administration is for at least 6 months. In an aspect, the administration is for at least 9 months. In an aspect, the administration is for at least 1 year. In an aspect, the administration is for at least 1.5 years. In an aspect, the administration is for at least 2 years. In an aspect, the administration is for at least 3 years. In an aspect, the administration is for at least 4 years. In an aspect, the administration is for at least 5 years. In an aspect, the administration is for at least 10 years. In an aspect, the administration is for between 1 week and 1 month. In an aspect, the administration is for between 1 month and 6 months. In an aspect, the administration is for between 1 month and 1 year. In an aspect, the administration is for between 6 months and 1 year. In an aspect, the administration is for between 1 year and 5 years. In an aspect, the administration is for between 7 days and 1 year. In an aspect, the administration is for between 7 days and 2 years. In an aspect, the administration is for between 7 days and 5 years.

[0129] In an aspect, a pharmaceutical composition of the present disclosure is administered once daily. In an aspect, the pharmaceutical composition is administered once daily as an oral composition. In an aspect, the oral composition is administered once daily in tablet form at approximately the same time every day, e.g., prior to a breakfast. In an aspect, the oral composition is administered once daily in capsule form at approximately the same time every day.

[0130] In an aspect, a pharmaceutical composition of the present disclosure is administered twice daily. In an aspect, the pharmaceutical composition is administered twice daily as an oral composition. In an aspect, the oral composition is administered twice daily in tablet form at approximately the same times every day. In an aspect, the oral composition is administered twice daily in capsule form at approximately the same time every day.

[0131] In an aspect, a pharmaceutical composition of the present disclosure is administered three times a day. In an aspect, the pharmaceutical composition is administered three times a day as an oral composition. In an aspect, the oral composition is administered three times a day in tablet form at approximately the same times every day. In an aspect, the oral composition is administered three times a day in capsule form at approximately the same time every day.

[0132] In an aspect, a pharmaceutical composition of the present disclosure is administered l x per week, every other day, every third day, 2x per week, 3x per week, 4x per week, or 5x per week. In an aspect, the pharmaceutical composition is administered on an empty stomach. In an aspect, the pharmaceutical composition is administered before a meal. In an aspect, the pharmaceutical composition is administered after a meal. In an aspect, the pharmaceutical composition is administered without food. In an aspect, the pharmaceutical composition is administered with food.

[0133] In an aspect, a pharmaceutical composition of the present disclosure may be coadministered with a second agent. In an aspect, the second agent is CaNa2EDTA, DMSA, or dimercaprol.

[0134] In an aspect of the methods provided herein, the subject in need thereof has an elevated level of Pb2+content in the body prior to administration of the pharmaceutical composition. In an aspect of the methods provided herein, the elevated level of Pb2+content in the body prior to the administering is greater than 0.50 micrograms per deciliter (pg / dL). In an aspect of the methods provided herein, the elevated level of Pb2+content in the body prior to the administering the pharmaceutical composition is greater than 1 pg / dL. In an aspect of the methods provided herein, the elevated level of Pb2+content in the body prior to the administering the pharmaceutical composition is greater than 2 pg / dL. In an aspect of the methods provided herein, the elevated level of Pb2+content is measured in blood, feces, urine, gastrointestinal fluid, or any combination thereof. In an aspect of the methods provided herein, the elevated level of Pb2+content is measured in blood. In an aspect of the methods provided herein, the elevated level of Pb2+content is measured in feces. In an aspect of the methods provided herein, the elevated level of Pb2+content is measured in urine. In an aspect of the methods provided herein, the elevated level of Pb2+content in the body is reduced after the administering. In an aspect of the methods provided herein, the reduction of the elevated level of Pb2+content in the body is measured by excretion of Pb2+in the feces. In an aspect of the methods provided herein, theamount of Pb2+content excreted in the feces is greater than a pretreatment excretion level of Pb2+. In an aspect of the methods provided herein, the amount of Pb2+content excreted in the feces is at least 50% greater than the pretreatment excretion level of Pb2+. In an aspect of the methods provided herein, the amount of Pb2+content excreted in the feces is at least 100% greater than the pretreatment excretion level of Pb2. In an aspect of the methods provided herein, the amount of Pb2content excreted in the feces is at least 200% greater than the pretreatment excretion level of Pb2+. In an aspect of the methods provided herein, the amount of Pb2+content excreted in the feces is at least 500% greater than the pretreatment excretion level of Pb2+. In an aspect of the methods provided herein, the amount of Pb2+content excreted in the feces is at least 1000% greater than the pretreatment excretion level of Pb2+. In an aspect of the methods provided herein, the amount of Pb2+content excreted in the feces is at least 2000% greater than the pretreatment excretion level of Pb2. In an aspect of the methods provided herein, the amount of Pb2content excreted in the feces is between 100% to 200% greater than the pretreatment excretion level of Pb21. In an aspect of the methods provided herein, the amount of Pb2+content excreted in the feces is between 100% to 1000% greater than the pretreatment excretion level of Pb2+. In an aspect of the methods provided herein, the amount of Pb2+content excreted in the feces is between 200% to 1000% greater than the pretreatment excretion level of Pb2+. In an aspect of the methods provided herein, the amount of Pb2+content excreted in the feces is between 500% to 1000% greater than the pretreatment excretion level of Pb2+. In an aspect of the methods provided herein, the amount of Pb2+content excreted in the feces is between 500% to 2000% greater than the pretreatment excretion level of Pb2+. In an aspect of the methods provided herein, the reduction of the elevated level of Pb2+content in the body is measured by a reduction of Pb2+concentration in the blood. In an aspect of the methods provided herein, the Pb2+concentration in the blood is reduced at least 2-fold after the administration. In an aspect of the methods provided herein, the Pb2+concentration in the blood is reduced at least 3-fold after the administration. In an aspect of the methods provided herein, the Pb2+concentration in the blood is reduced at least 4-fold after the administration. In an aspect of the methods provided herein, the Pb2+concentration in the blood is reduced at least 5-fold after the administration. In an aspect of the methods provided herein, the Pb2+concentration in the blood is reduced at least 10-fold after the administration. In an aspect of the methods provided herein, the Pb2+concentration in the blood is reduced at least 15-fold after the administration. In anaspect of the methods provided herein, the Pb2+concentration in the blood is reduced between 2- fold to 5-fold after the administration. In an aspect of the methods provided herein, the Pb2+concentration in the blood is reduced between 2-fold to 10-fold after the administration. In an aspect of the methods provided herein, the Pb2+concentration in the blood is reduced between 5- fold to 10-fold after the administration. In an aspect of the methods provided herein, the Pb2+concentration in the blood is reduced to less than about 0.5 pg / dL after the administration. In an aspect of the methods provided herein, the Pb2+content in the body is measured by inductively coupled plasma (ICP) elemental analysis.

[0135] In an aspect of the methods provided herein, normal physiological levels of any one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration. In an aspect of the methods provided herein, the physiological levels of the one or more ions are measured in the blood of the subject in need thereof. In an aspect of the methods provided herein, normal physiological levels cations Na+, K', Mg21, and Ca21have unique concentrations in the body (blood) and unique ranges of concentrations in the body that are considered normal. Normal ranges for these cations are given in the table below. In an aspect of the methods provided herein, minimal disruption of the concentrations of these ions would be considered a change of less than about half the magnitude of the variation seen within the normal range. For instance, the normal Na+concentration ranges from 310 to about 333 mg / dL, a variation of 23 mg / dL; a minimal disruption in Na+concentration would in this case be less than ± 12 mg / dL. Minimal disruption values are given in the table below.Cation Normal Concentration Ranges in Blood Minimal DisruptionNa+310 - 333 mg / dL < ± 12 mg / dLK+14 - 20 mg / dL < ± 3.0 mg / dLMg2+1.5 - 2.6 mg / dL < ± 0.6 mg / dLCa2+8.5 - 10.5 mg / dL< ± 1.0 mg / dL

[0136] In an aspect of the methods provided herein, the physiological levels of the one or more ions are measured in the urine of the subject in need thereof. In an aspect of the methods provided herein, the physiological levels of the one or more ions are measured in the feces of the subject in need thereof. In an aspect, normal physiological levels of two one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereofafter the administration. In an aspect of the methods provided herein, normal physiological levels of three one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration. In an aspect of the methods provided herein, normal physiological levels of Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration. In an aspect of the methods provided herein, a normal physiological level of Na+is minimally disrupted in the subject in need thereof after the administration. In an aspect of the methods provided herein, a normal physiological level of Mg2+is minimally disrupted in the subject in need thereof after the administration. In an aspect of the methods provided herein, a normal physiological level of K+is minimally disrupted in the subject in need thereof after the administration. In an aspect of the methods provided herein, a normal physiological level of Ca2+is minimally disrupted in the subject in need thereof after the administration.

[0137] In an aspect of the methods provided herein, the subject in need thereof suffers from lead poisoning. In an aspect of the methods provided herein, the subject in need thereof is a human. In an aspect of the methods provided herein, the subject in need thereof is a human adult. In an aspect of the methods provided herein, the subject in need thereof is a human child.

[0138] In an aspect of the methods provided herein, lead poisoning may be acute lead poisoning or chronic lead poisoning. In an aspect of the methods provided herein, lead poisoning is acute lead poisoning. In an aspect of the methods provided herein, lead poisoning is chronic lead poisoning. In an aspect of the methods provided herein, one or more symptoms of lead poisoning are reduced or eliminated after the administering. In an aspect of the methods provided herein, one symptom of lead poisoning is reduced or eliminated after the administering. In an aspect of the methods provided herein, two or more symptoms of lead poisoning are reduced or eliminated after the administering. In an aspect of the methods provided herein, two symptoms of lead poisoning are reduced or eliminated after the administering. In an aspect of the methods provided herein, three or more symptoms of lead poisoning are reduced or eliminated after the administering. In an aspect of the methods provided herein, three symptoms of lead poisoning are reduced or eliminated after the administering. In an aspect of the methods provided herein, four or more symptoms of lead poisoning are reduced or eliminated after the administering. In an aspect of the methods provided herein, four symptoms of lead poisoning are reduced or eliminated after the administering. In an aspect of the methods provided herein, five or moresymptoms of lead poisoning are reduced or eliminated after the administering. In an aspect of the methods provided herein, five symptoms of lead poisoning are reduced or eliminated after the administering. In an aspect of the methods provided herein, the one or more symptoms of lead poisoning are selected from the group consisting of high blood pressure, abdominal pain, joint pain, constipation, nausea, vomiting, fatigue, hyperactivity, irritability, mood disorder, headache, insomnia, lack of concentration, memory loss, reduced sperm count, hearing loss, seizure, and any combination thereof. In an aspect of the methods provided herein, a symptom of lead poisoning is high blood pressure. In an aspect of the methods provided herein, a symptom of lead poisoning is abdominal pain. In an aspect of the methods provided herein, a symptom of lead poisoning is joint pain. In an aspect of the methods provided herein, a symptom of lead poisoning is constipation. In an aspect of the methods provided herein, a symptom of lead poisoning is nausea. In an aspect, a symptom of lead poisoning is vomiting. In an aspect of the methods provided herein, a symptom of lead poisoning is fatigue. In an aspect of the methods provided herein, a symptom of lead poisoning is hyperactivity. In an aspect of the methods provided herein, a symptom of lead poisoning is irritability. In an aspect, a symptom of lead poisoning is mood disorder. In an aspect of the methods provided herein, a symptom of lead poisoning is headache. In an aspect of the methods provided herein, a symptom of lead poisoning is insomnia. In an aspect of the methods provided herein, a symptom of lead poisoning is lack of concentration. In an aspect of the methods provided herein, a symptom of lead poisoning is memory loss. In an aspect of the methods provided herein, a symptom of lead poisoning is reduced sperm count. In an aspect of the methods provided herein, a symptom of lead poisoning is hearing loss. In an aspect of the methods provided herein, a symptom of lead poisoning is seizure. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning is reduced by at least 25% after the administration. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning is reduced by at least 50% after the administration. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning is reduced by at least 75% after the administration. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning is reduced by 100% after the administration. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning isreduced by between 25% to 50% after the administration. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning is reduced by between 25% to 75% after the administration. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning is reduced by between 25% to 100% after the administration. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning is reduced by between 50% to 75% after the administration. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning is reduced by between 50% to 100% after the administration. In an aspect of the methods provided herein, the severity or occurrence of each of the one or more symptoms of lead poisoning is reduced by between 75% to 100% after the administration.

[0139] D. Definitions

[0140] The term “and / or” when used in a list of two or more items, means that any one of the listed items can be employed by itself 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, / .e., A alone, B alone, or A and B in combination. The expression “A, B and / or C” is intended to mean A alone, B alone, C alone, A and B in combination, A and C in combination, B and C in combination, or A, B, and C in combination.

[0141] As used herein, terms in the singular and the singular forms “a,” “an,” and “the,” for example, include plural referents unless the content clearly dictates otherwise.

[0142] Where a range of values is provided, it is understood that each intervening value, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either both of those included limits are also included in the disclosure. Whenever the phrase “comprising” is used, variations such as “consisting essentially of’ and “consisting of’ are also contemplated.

[0143] Unless defined otherwise herein, terms are to be understood according to conventional usage by those of ordinary skill in the relevant art. Where a term is provided in thesingular, the inventors also contemplate aspects of the disclosure described by the plural of that term. Where there are discrepancies in terms and definitions used in references that are incorporated by reference, the terms used in this application shall have the definitions given herein. Other technical terms used have their ordinary meaning in the art in which they are used, as exemplified by various art-specific dictionaries, for example, “The American Heritage® Science Dictionary” (Editors of the American Heritage Dictionaries, 2011, Houghton Mifflin Harcourt, Boston and New York), or the “McGraw-Hill Dictionary of Scientific and Technical Terms” (6th edition, 2002, McGraw-Hill, New York).

[0144] As used herein, the term "about" refers to a range extending to + / - 10% of the specified value.

[0145] As used herein, “metallate” refers to a complex anionic compound comprising one or more metal atoms ligated to one or more non-metal atoms. A metallate may further comprise one or more cations. In an aspect, one or more metal atoms of a metallate are selected from titanium (Ti), niobium (Nb), zirconium (Zr), tin (Sn), cobalt (Co), iron (Fe), and manganese (Mn). In an aspect, one or more non-metal atoms are selected from oxygen (O) and sulfur (S). In an aspect, one or more cations of a metallate are selected from potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, and hydronium ion. In an aspect, a metallate is inorganic. In an aspect, a metallate comprises titanium, oxygen, and potassium.

[0146] As used herein, “ion exchanger” refers to a complex wherein one or more charged species may exchange with one or more charged species of the surrounding environment. In an aspect, an ion exchanger is a cation exchanger.

[0147] As used herein, “morphology” refers to form or shape of a particulate. A particulate’s morphology may include, but is not limited to, spheres, interpenetrating spheres, fibers, slabs, intertwined plates, and amorphous morphology.

[0148] As used herein, “spherical morphology” refers to particulate morphology that is substantially and discernibly spherical in form.

[0149] As used herein, “amorphous morphology” refers to particulate morphology that is substantially and discernibly absent of order or repeating form.

[0150] As used herein, “macroporous” refers to the porosity of a particulate wherein pore diameter is greater than about 50 angstroms (A).

[0151] As used herein, “polycrystalline” refers to the crystallinity of a material comprising multiple crystallites of varying orientation, morphology, and size.

[0152] As used herein, “poly crystalline aggregate” refers to the crystallinity of an aggregate material comprising several crystallites of varying orientation and size.

[0153] As used herein a “Brunauer-Emmett-Teller (BET)” surface area refers to the specific surface area of a solid porous material characterized by Brunauer-Emmett-Teller (BET) analysis which is based on gas adsorption measurements. See Brunauer etal, “Adsorption of Gas in Multimolecular Layers,” J. Am. Chem. Soc. 60(2):309-319. Without being by bound theory, in a BET analysis, the true or specific surface area of a porous solid particle, including surface irregularities and pore walls, is determined at an atomic level by adsorption of an unreactive gas. The BET equation calculates surface coverage 0, where p / p' o) is the relative pressure, and c is a BET C -constant related to the heat of adsorption:

[0154] As used herein “annealing” refers to a process of heat treating a material at one or more elevated temperatures for one or more pre-determined periods of time, where the annealing may alter one or more physical or chemical properties of the material, including, but not limited to, crystallinity, particle morphology, particle size distribution, composition, and porosity. Annealing parameters / conditions may selectively alter one or more physical or chemical properties of a material and may include, but are not limited to, ramp rate, peak temperature, holding time, cooling rate, and gas environment. A gas environment for an annealing process may be selected from, but is not limited to, atmosphere, and an inert gas, such as nitrogen (N2) or argon (Ar).

[0155] As used herein a “spray-drying” refers to a technique of forming a substantially homogenous dry powder from a liquid mixture or slurry, by drying a sprayed liquid mixture or slurry in the presence of a heated gas. The heated gas may be heated atmospheric gas or a heated inert gas, such as nitrogen (N2) or argon (Ar).

[0156] As used herein, “effective amount” or “therapeutically effective amount” refers to the amount of an active pharmaceutical agent sufficient to effectuate a desired physiological outcome in an individual in need of the agent. The effective amount can vary among individuals depending on the health and physical condition of the individual to be treated, the taxonomicgroup of the individuals to be treated, the formulation of the composition, assessment of the individual’s medical condition, and other relevant factors.

[0157] As used herein, “subject” or “patient” or “individual” refers to a human or non-human animal selected for treatment or therapy or receiving a pharmaceutical composition of the present disclosure.

[0158] As used herein, “pharmaceutical agent” refers to a substance that provides a therapeutic benefit when administered to an individual.

[0159] As used herein, “pharmaceutical composition” refers to a mixture of substances suitable for administering to an individual. For example, a pharmaceutical composition can comprise one or more active agents and a sterile aqueous solution.

[0160] As used herein, “treat” or “treatment” or “treating” refers to administering a pharmaceutical composition to affect an alteration or improvement of a disease, disorder, or condition.

[0161] As used herein, “co-admini strati on” refers to administration of two or more agents to an individual. The two or more agents can be in a single pharmaceutical composition or can be in separate pharmaceutical compositions. Each of the two or more agents can be administered through the same or different routes of administration. Co-administration encompasses simultaneous or sequential administration.

[0162] All publications, patents, and patent applications mentioned in this disclosure are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0163] Having now generally described the disclosure, the same will be more readily understood through reference to the following embodiments and examples that are provided by way of illustration and are not intended to be limiting of the present disclosure, unless specified.EMBODIMENTS

[0164] Embodiment 1. A method for treating, ameliorating, or reducing the severity of lead poisoning in a subject in need thereof comprising a step of administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a therapeutically effective dose of particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTixMyO; whereinA is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion, and 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl-containing complexing agent (MHCA), wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm), and wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering.

[0165] Embodiment 2. The method of Embodiment 1, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0166] Embodiment 3. The method of Embodiment 1 or Embodiment 2, wherein A is potassium ion, hydronium ion, or a mixture thereof.

[0167] Embodiment 4. The method of any one of Embodiments 1 to 3, wherein A is potassium ion.

[0168] Embodiment 5. The method of any one of Embodiments 1 to 3, wherein A is hydronium ion.

[0169] Embodiment 6. The method of any one of Embodiments 1 to 3, wherein A is a mixture of potassium and hydronium ions.

[0170] Embodiment 7. The method of any one of Embodiments 1 to 6A, wherein the particulate metal titanate ion exchanger is a polycrystalline aggregate metal titanate ion exchanger.

[0171] Embodiment 8. The method of any one of Embodiments 1 to 7, wherein the particulate metal titanate ion exchanger is macroporous.

[0172] Embodiment 9. The method of any one of Embodiments 1 to 8, wherein the particulate metal titanate ion exchanger has a spherical morphology.

[0173] Embodiment 10. The method of any one of Embodiments 1 to 8, wherein the particulate metal titanate ion exchanger has amorphous morphology.

[0174] Embodiment 11. The method of any one of Embodiments 1 to 10, wherein the particulate metal titanate ion exchanger is a powder.

[0175] Embodiment 12. The method of any one of Embodiments 1 to 11, wherein the median particle size is in a range of 25 to 125 microns (pm).

[0176] Embodiment 12A. The method of any one of Embodiments 1 to 12, wherein the particle size distribution is appropriate to prevent absorption or substantial absorption in the gastrointestinal tract of the subject in need thereof.

[0177] Embodiment 13. The method of any one of Embodiments 1 to 12A, wherein the median particle size is sufficiently large to prevent absorption or substantial absorption in the gastrointestinal tract of the subject in need thereof.

[0178] Embodiment 14. The method of any one of Embodiments 1 to 13, wherein less than 3% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 microns (pm).

[0179] Embodiment 15. The method of Embodiment 14, wherein less than 0.5% of the particles of the particulate metal titanate ion exchanger have a particle size less than 3 microns (pm).

[0180] Embodiment 16. The method of any one of Embodiments 1 to 15, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 5 microns (pm) and about 70 pm.

[0181] Embodiment 17. The method of Embodiment 16, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 12 pm and about 18 pm.

[0182] Embodiment 18. The method of Embodiment 17, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value of about 15 pm.

[0183] Embodiment 19. The method of Embodiment 16, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 42 pm and about 48 pm.

[0184] Embodiment 20. The method of Embodiment 19, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value of about 45 pm.

[0185] Embodiment 21. The method of Embodiment 16, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 51 pm and about 57 pm.

[0186] Embodiment 22. The method of Embodiment 21, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value of about 54 pm.

[0187] Embodiment 23. The method of any one of Embodiments 1 to 22, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 40 microns (pm) and about 115 pm.

[0188] Embodiment 24. The method of Embodiment 23, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 48 pm and about 54 pm.

[0189] Embodiment 25. The method of Embodiment 24, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 51 pm.

[0190] Embodiment 26. The method of Embodiment 23, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 71 pm and about 77 pm.

[0191] Embodiment 27. The method of Embodiment 26, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 74 pm.

[0192] Embodiment 28. The method of Embodiment 23, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 89 pm and about 95 pm.

[0193] Embodiment 29. The method of Embodiment 28, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 92 pm.

[0194] Embodiment 30. The method of any one of Embodiments 1 to 29, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 65 microns (pm) and about 185 pm

[0195] Embodiment 31 . The method of Embodiment 30, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 99 pm and about 105 pm.

[0196] Embodiment 32. The method of Embodiment 31, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value of about 102 pm.

[0197] Embodiment 33. The method of Embodiment 30, wherein the particulate metal titanate ion exchanger has a particle size distribution d9o value in a range of about 137 pm and about 143 pm.

[0198] Embodiment 34. The method of Embodiment 33, wherein the particulate metal titanate ion exchanger has a particle size distribution dgo value of about 140 pm.

[0199] Embodiment 35. The method of Embodiment 30, wherein the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 156 pm and about 162 pm.

[0200] Embodiment 36. The method of Embodiment 35, wherein the particulate metal titanate ion exchanger has a particle size distribution dgo value of about 159 pm.

[0201] Embodiment 37. The method of any one of Embodiments 1 to 36, wherein the particulate metal titanate ion exchanger is stable in a liquid environment at a pH of 1-2.

[0202] Embodiment 38. The method of any one of Embodiments 1 to 37, wherein the particulate metal titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of greater than 150 square meters per gram (m2 / g).

[0203] Embodiment 39. The method of Embodiment 38, wherein the particulate metal titanate ion exchanger has a BET surface area of about 197 m2 / g.

[0204] Embodiment 40. The method of any one of Embodiments 1 to 37, wherein the particulate metal titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of greater than 200 square meters per gram (m2 / g).

[0205] Embodiment 41. The method of Embodiment 40, wherein the particulate metal titanate ion exchanger has a BET surface area of about 203 m2 / g.

[0206] Embodiment 42. The method of any one of Embodiments 1 to 37, wherein the particulate metal titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of greater than 230 square meters per gram (m2 / g).

[0207] Embodiment 43. The method of Embodiment 42, wherein the particulate metal titanate ion exchanger has a BET surface area of about 236 m2 / g.

[0208] Embodiment 44. The method of any one of Embodiments 1 to 43, wherein the administering is oral administration.

[0209] Embodiment 45. The method of Embodiment 44, wherein the pharmaceutical composition is administered to the subject in need thereof in tablet, capsule, or liquid suspension form.

[0210] Embodiment 46. The method of any one of Embodiments 1 to 45, wherein the particulate metal titanate ion exchanger is not absorbed or substantially absorbed in the gastrointestinal tract of the subject in need thereof.

[0211] Embodiment 47. The method of any one of Embodiments 1 to 46, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-7.

[0212] Embodiment 48. The method of any one of Embodiments 1 to 46, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 7-13.

[0213] Embodiment 49. The method of any one of Embodiments 1 to 46, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-13.

[0214] Embodiment 50. The method of any one of Embodiments 1 to 46, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0215] Embodiment 51. The method of any one of Embodiments 1 to 46, and 50, wherein the particulate metal titanate ion exchanger is substantially insoluble at stomach pH.

[0216] Embodiment 52. The method of any one of Embodiments 1 to 51, wherein the particulate metal titanate ion exchanger is insoluble in one or more bodily fluids.

[0217] Embodiment 53. The method of Embodiment 52, wherein the one or more bodily fluids are selected from the group consisting of blood, urine, and gastrointestinal fluid.

[0218] Embodiment 54. The method of any one of Embodiments 1 to 53, wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0219] Embodiment 55. The method of Embodiment 54, wherein the therapeutically effective dose is between 100 to 1500 mg / kg / day.

[0220] Embodiment 55A. The method of Embodiment 55, wherein the therapeutically effective dose is between 200 to 1000 mg / kg / day.

[0221] Embodiment 56. The method of Embodiment 55 A, wherein the therapeutically effective dose is between 300 to 1000 mg / kg / day.

[0222] Embodiment 57. The method of any one of Embodiments 1 to 56, wherein the administration is for at least 7 days.

[0223] Embodiment 58. The method of any one of Embodiments 1 to 56, wherein the administration is for at least 6 weeks.

[0224] Embodiment 59. The method of any one of Embodiments 1 to 56, wherein the administration is for at least 6 months.

[0225] Embodiment 60. The method of any one of Embodiments 1 to 56, wherein the administration is for at least one year.

[0226] Embodiment 61. The method of any one of Embodiments 1 to 56, wherein the administration is for at least two years.

[0227] Embodiment 62. The method of any one of Embodiments 1 to 61, wherein the elevated level of Pb2 1content in the body prior to the administering is greater than 0.50 micrograms per deciliter ( g / dL).

[0228] Embodiment 63. The method of any one of Embodiments 1 to 62, wherein the elevated level of Pb2+content in the body is measured in blood, feces, urine, gastrointestinal fluid, or any combination thereof.

[0229] Embodiment 64. The method of any one of Embodiments 1 to 63, wherein the elevated level of Pb2+content in the body is reduced after the administering.

[0230] Embodiment 65. The method of Embodiment 64, wherein the reduction of the elevated level of Pb2+content in the body is measured by excretion of Pb2+in the feces.

[0231] Embodiment 66. The method of Embodiment 65, wherein the amount of Pb2+content excreted in the feces is greater than a pretreatment excretion level of Pb2+.

[0232] Embodiment 67. The method of Embodiment 66, wherein the amount of Pb2+content excreted in the feces is at least 100% greater than the pretreatment excretion level of Pb2+.

[0233] Embodiment 68. The method of Embodiment 67, wherein the amount of Pb2+content excreted in the feces is at least 200% greater than the pretreatment excretion level of Pb2+.

[0234] Embodiment 69. The method of Embodiment 68, wherein the amount of Pb2+content excreted in the feces is at least 1000% greater than the pretreatment excretion level of Pb21.

[0235] Embodiment 70. The method of any one of Embodiments 66 to 69, wherein the pretreatment excretion level is less than 2 parts per million (ppm).

[0236] Embodiment 71. The method of Embodiment 64, wherein the reduction of the elevated level of Pb2+content in the body is measured by a reduction of Pb2+concentration in the blood.

[0237] Embodiment 72. The method of Embodiment 71, wherein the reduction of Pb2+concentration in the blood is at least a two-fold reduction.

[0238] Embodiment 73. The method of Embodiment 72, wherein the reduction of Pb2+concentration in the blood is at least a five-fold reduction.

[0239] Embodiment 74. The method of Embodiment 73, wherein the reduction of Pb2+concentration in the blood is at least a ten-fold reduction.

[0240] Embodiment 75. The method of any one of Embodiments 71 to 74, wherein the Pb2+concentration in the blood is reduced to less than 0.5 pg / dL.

[0241] Embodiment 76. The method of any one of Embodiments 1 to 75, wherein the Pb2 1content in the body is measured by inductively coupled plasma (ICP) elemental analysis.

[0242] Embodiment 77. The method of any one of Embodiments 1 to 76, wherein the particulate metal titanate ion exchanger has a distribution coefficient (Ka) for Pb2+in a range of about 50,000 to greater than 5,500,000 milliliters per gram (mL / g).

[0243] Embodiment 78. The method of Embodiment 77, wherein the particulate metal titanate ion exchanger has a Ka for Pb2+in a range of about 100,000 to about 2,500,000 mL / g.

[0244] Embodiment 79. The method of Embodiment 78, wherein the particulate metal titanate ion exchanger has a K for Pb2+of about 967,800.

[0245] Embodiment 80. The method of Embodiment 78, wherein the particulate metal titanate ion exchanger has a K for Pb2+of about 809,500.

[0246] Embodiment 81. The method of Embodiment 78, wherein the particulate metal titanate ion exchanger has a K for Pb2+of about 495,800.

[0247] Embodiment 82. The method of Embodiment 78, wherein the particulate metal titanate ion exchanger has a Ka for Pb2+of about 321,900.

[0248] Embodiment 83. The method of any one of Embodiments 1 to 82, wherein the at least one MHCA is selected from the group consisting of a sugar alcohol, a sugar, an aromatic compound, and any combination thereof.

[0249] Embodiment 84. The method of Embodiment 83, wherein the at least one MHCA is a sugar alcohol.

[0250] Embodiment 85. The method of Embodiment 84, wherein the sugar alcohol is selected from the group consisting of d-sorbitol, mannitol, and xylitol.

[0251] Embodiment 86. The method of Embodiment 83, wherein the at least one MHCA is a sugar.

[0252] Embodiment 87. The method of Embodiment 86, wherein the sugar is glucose or fructose.

[0253] Embodiment 88. The method of Embodiment 83, wherein the at least one MHCA is an aromatic compound.

[0254] Embodiment 89. The method of Embodiment 88, wherein the aromatic compound is catechol.

[0255] Embodiment 90. The method of any one of Embodiments 1 to 89, wherein the particulate metal titanate ion exchanger comprises between 0.01% to 4.0% weight per weight (w / w) of the at least one MHCA.

[0256] Embodiment 91. The method of Embodiment 90, wherein the particulate metal titanate ion exchanger comprises between 0.01% to 0.6% w / w of the at least one MHCA.

[0257] Embodiment 92. The method of any one of Embodiments 1 to 91, wherein x is 1 and y is 0.

[0258] Embodiment 93. The method of any one of Embodiments 1 to 92, wherein m is between 0.10 to 0.50.

[0259] Embodiment 94. The method of Embodiment 93, wherein m is about 0.40.

[0260] Embodiment 95. The method of Embodiment 93, wherein m is about 0.30.

[0261] Embodiment 96. The method of Embodiment 93, wherein m is about 0.28.

[0262] Embodiment 97. The method of any one of Embodiments 1 to 96, wherein the x-ray diffraction (XRD) pattern of the particulate metal titanate ion exchanger has a characteristic diffraction line with a d-spacing of 3.00 to 3.11 A.

[0263] Embodiment 98. The method of any one of Embodiments 1 to 97, wherein the particulate metal titanate ion exchanger has an x-ray diffraction (XRD) pattern having characteristic diffraction lines within the ranges provided below in Table A or Table B:Table A | Table B11.11 - 10.78 7.96 -8.2 w-m 11.47 - 10.95 7.71 - 8.07 w-s25.43 -24.03 3.50 - 3.70 w-m 24.37 -23.97 3.65 - 3.71 m-s29.55 -28.68 3.02 - 3.11 Vs 29.76 -28.78 3.00 - 3.10 vs33.93 -33.15 2.64 -2.70 m-s 33.80 - 33.15 2.65 - 2.70 w-m43.36 -42.51 2.085 -2.125 w-m 43.47 -42.51 2.08 -2.125 m-s48.38 -47.31 1.88 - 1.92 m-s 48.51 -47.49 1.875 - 1.913 m - vs60.46 -59.18 1.53 - 1.56 w-m 66.93 -65.55 1.397 - 1.423 w-m67.03 -65.44 1.395 - 1.425 w-m

[0264] Embodiment 99. The method of any one of Embodiments 1 to 96, wherein the x-ray diffraction (XRD) pattern of the particulate metal titanate ion exchanger has a characteristic diffraction line with a d-spacing of 3.00 to 3.10 A.

[0265] Embodiment 100. The method of any one of Embodiments 1 to 96, and 99, wherein the particulate metal titanate ion exchanger has an x-ray diffraction (XRD) pattern having characteristic diffraction lines within the ranges provided below in Table C or Table D:Table C Table D11.87- 10.89 7.45 - 8.12 w-s 11.76- 10.82 7.52- 8.17 w-s24.50-23.71 3.63 -3.75 w-m 24.64-23.58 3.61 -3.77 w-m29.76-28.87 3.00-3.09 Vs 29.76-28.78 3.00-3.10 vs32.06-30.81 2.79-2.90 w-s 32.05 -30.38 2.79-2.94 w-s33.93 -33.15 2.64-2.70 m-s 34.06-33.15 2.63 -2.70 w-m43.26-42.61 2.09-2.12 w-s 43.36-42.51 2.085 -2.125 m-vs48.24-47.44 1.885 - 1.915 w-s 48.51 -47.44 1.875 - 1.915 m-vs60.03 -58.77 1.54- 1.57 w-m 60.24-58.76 1.535 - 1.57 w-m66.77-65.71 1.40- 1.42 w-m 66.76-65.70 1.40- 1.42 w-m

[0266] Embodiment 101. The method of any one of Embodiments 1 to 100, wherein the lead poisoning is acute lead poisoning.

[0267] Embodiment 102. The method of any one of Embodiments 1 to 100, wherein the lead poisoning is chronic lead poisoning.

[0268] Embodiment 103. The method of any one of Embodiments 1 to 102, wherein one or more symptoms of lead poisoning are reduced or eliminated after the administering.

[0269] Embodiment 104. The method of Embodiment 103, wherein the one or more symptoms of lead poisoning are selected from the group consisting of high blood pressure,abdominal pain, joint pain, constipation, nausea, vomiting, fatigue, hyperactivity, irritability, mood disorder, headache, insomnia, lack of concentration, memory loss, reduced sperm count, hearing loss, seizure, and any combination thereof.

[0270] Embodiment 105. The method of any one of Embodiments 1 to 104, wherein normal physiological levels of any one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration.

[0271] Embodiment 106. The method of Embodiment 105, wherein the physiological levels of the one or more ions are measured in the blood of the subject in need thereof.

[0272] Embodiment 107. The method of Embodiment 105, wherein the physiological levels of the one or more ions are measured in the urine of the subject in need thereof.

[0273] Embodiment 108. The method of Embodiment 105, wherein the physiological levels of the one or more ions are measured in the feces of the subject in need thereof.

[0274] Embodiment 109. The method of any one of Embodiments 1 to 108, wherein the subject in need thereof is a human.

[0275] Embodiment 110. The method of Embodiment 109, wherein the subject in need thereof is a human adult.

[0276] Embodiment 111. The method of Embodiment 109, wherein the subject in need thereof is a human child.

[0277] Embodiment 112. A method for treating, ameliorating, or reducing the severity of lead poisoning in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis ofAmTiOz wherein A is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, and a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl -containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25to 125 microns (pm), wherein less than 3.0% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2 1content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day)

[0278] Embodiment 113. The method of Embodiment 112, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0279] Embodiment 114. The method of Embodiment 112 or Embodiment 113, wherein A is potassium ion.

[0280] Embodiment 115. The method of Embodiment 112 or Embodiment 113, wherein A is hydronium ion.

[0281] Embodiment 116. The method of Embodiment 112 or Embodiment 113, wherein A is a mixture of potassium and hydronium ions.

[0282] Embodiment 117. The method of any one of Embodiments 112 to 116, wherein the macroporous particulate titanate ion exchanger is a polycrystalline aggregate titanate ion exchanger.

[0283] Embodiment 118. The method of any one of Embodiments 112 to 117, wherein the macroporous particulate titanate ion exchanger has amorphous morphology.

[0284] Embodiment 119. The method of any one of Embodiments 112 to 118, wherein the macroporous particulate titanate ion exchanger is a powder.

[0285] Embodiment 120. The method of any one of Embodiments 112 to 119, wherein the median particle size is sufficiently large to prevent absorption in the gastrointestinal tract of the subject in need thereof.

[0286] Embodiment 121. The method of any one of Embodiments 112 to 120, wherein about 3.0% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 microns (pm).

[0287] Embodiment 122. The method of any one of Embodiments 112 to 121, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 5 microns (pm) and about 30 pm.

[0288] Embodiment 123. The method of Embodiment 122, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 12 pm and about 18 pm.

[0289] Embodiment 124. The method of Embodiment 123, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value of about 15 pm.

[0290] Embodiment 125. The method of any one of Embodiments 112 to 124, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dso value in a range of about 40 microns (pm) and about 75 pm.

[0291] Embodiment 126. The method of Embodiment 125, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 48 pm and about 54 pm.

[0292] Embodiment 127. The method of Embodiment 126, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dso value of about 51 pm.

[0293] Embodiment 128. The method of any one of Embodiments 112 to 127, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d9o value in a range of about 80 microns (pm) and about 140 pm.

[0294] Embodiment 129. The method of Embodiment 128, wherein the particulate metal titanate ion exchanger has a particle size distribution d<;o value in a range of about 99 pm and about 105 pm.

[0295] Embodiment 130. The method of Embodiment 129, wherein the macroporous particulate titanate ion exchanger has a particle size distribution ds>o value of about 102 pm.

[0296] Embodiment 131. The method of any one of Embodiments 112 to 130, wherein the macroporous particulate titanate ion exchanger is stable in a liquid environment at a pH of 1-2.

[0297] Embodiment 132. The method of any one of Embodiments 112 to 131, wherein the macroporous particulate titanate ion exchanger has a BET surface area of about 197 m2 / g.

[0298] Embodiment 133. The method of any one of Embodiments 112 to 131, wherein the macroporous particulate titanate ion exchanger has a BET surface area of about 236 m2 / g.

[0299] Embodiment 134. The method of any one of Embodiments 112 to 133, wherein the pharmaceutical composition is administered to the subject in need thereof in tablet, capsule, or liquid suspension form.

[0300] Embodiment 135. The method of any one of Embodiments 112 to 134, wherein the macroporous particulate titanate ion exchanger is not absorbed or substantially absorbed in the gastrointestinal tract of the subject in need thereof.

[0301] Embodiment 136. The method of any one of Embodiments 112 to 135, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-7.

[0302] Embodiment 137. The method of any one of Embodiments 112 to 135, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 7-13.

[0303] Embodiment 138. The method of any one of Embodiments 112 to 135, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-13.

[0304] Embodiment 139. The method of any one of Embodiments 112 to 135, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0305] Embodiment 140. The method of any one of Embodiments 112 to 135, and 139, wherein the particulate metal titanate ion exchanger is substantially insoluble at stomach pH.

[0306] Embodiment 141. The method of any one of Embodiments 112 to 140, wherein the macroporous particulate titanate ion exchanger is substantially insoluble in one or more bodily fluids.

[0307] Embodiment 142. The method of Embodiment 141, wherein the one or more bodily fluids are selected from the group consisting of blood, urine, and gastrointestinal fluid.

[0308] Embodiment 143. The method of any one of Embodiments 112 to 142, wherein the therapeutically effective dose is between 100 to 1500 mg / kg / day.

[0309] Embodiment 143 A. The method of Embodiment 143, wherein the therapeutically effective dose is between 200 to 1000 mg / kg / day.

[0310] Embodiment 144. The method of Embodiment 143 A, wherein the therapeutically effective dose is between 300 to 1000 mg / kg / day.

[0311] Embodiment 145. The method of any one of Embodiments 112 to 144, wherein the administration is for at least 7 days.

[0312] Embodiment 146. The method of any one of Embodiments 112 to 144, wherein the administration is for at least 6 weeks.

[0313] Embodiment 147. The method of any one of Embodiments 112 to 144, wherein the administration is for at least 6 months.

[0314] Embodiment 148. The method of any one of Embodiments 112 to 144, wherein the administration is for at least one year.

[0315] Embodiment 149. The method of any one of Embodiments 112 to 144, wherein the administration is for at least two years.

[0316] Embodiment 150. The method of any one of Embodiments 112 to 149, wherein the elevated level of Pb2+content in the body prior to the administering is greater than 0.5 micrograms per deciliter (pg / dL).

[0317] Embodiment 151. The method of any one of Embodiments 112 to 150, wherein the elevated level of Pb2+content in the body is measured in blood, feces, urine, gastrointestinal fluid, or any combination thereof.

[0318] Embodiment 152. The method of any one of Embodiments 112 to 151, wherein the elevated level of Pb2+content in the body is reduced after the administering.

[0319] Embodiment 153. The method of Embodiment 152, wherein the reduction of the elevated level of Pb2+content in the body is measured by excretion of Pb2+in the feces.

[0320] Embodiment 154. The method of Embodiment 153, wherein the amount of Pb2+content excreted in the feces is greater than a pretreatment excretion level of Pb2+.

[0321] Embodiment 155. The method of Embodiment 154, wherein the amount of Pb2+content excreted in the feces is at least 100% greater than the pretreatment excretion level of Pb2+.

[0322] Embodiment 156. The method of Embodiment 155, wherein the amount of Pb2+content excreted in the feces is at least 200% greater than the pretreatment excretion level of Pb2+.

[0323] Embodiment 157. The method of Embodiment 156, wherein the amount of Pb2+content excreted in the feces is at least 1000% greater than the pretreatment excretion level of Pb2+.

[0324] Embodiment 158. The method of any one of Embodiments 154 to 157, wherein the pretreatment excretion level is less than 2 parts per million (ppm).

[0325] Embodiment 159. The method of Embodiment 152, wherein the reduction of the elevated level of Pb2+content in the body is measured by a reduction of Pb2+concentration in the blood.

[0326] Embodiment 160. The method of Embodiment 159, wherein the reduction of Pb2+concentration in the blood is at least a two-fold reduction.

[0327] Embodiment 161. The method of Embodiment 160, wherein the reduction of Pb2+concentration in the blood is at least a five-fold reduction.

[0328] Embodiment 162. The method of Embodiment 161, wherein the reduction of Pb2+concentration in the blood is at least a ten-fold reduction.

[0329] Embodiment 163. The method of any one of Embodiments 159 to 162, wherein the Pb2+concentration in the blood is reduced to less than 0.5 pg / dL.

[0330] Embodiment 164. The method of any one of Embodiments 112 to 163, wherein the Pb2+content in the body is measured by inductively coupled plasma (ICP) elemental analysis.

[0331] Embodiment 165. The method of any one of Embodiments 112 to 164, wherein the macroporous particulate titanate ion exchanger has a distribution coefficient (Ka) for Pb2+in a range of about 100,000 to about 2,500,000 milliliters per gram (mL / g).

[0332] Embodiment 166. The method of Embodiment 165, wherein the macroporous particulate titanate ion exchanger has a Kd for Pb2+of about 809,500.

[0333] Embodiment 167. The method of Embodiment 165, wherein the macroporous particulate titanate ion exchanger has a Kd for Pb2+of about 495,800.

[0334] Embodiment 168. The method of any one of Embodiments 112 to 167, wherein the macroporous particulate titanate ion exchanger comprises between 0.01% to 4.0% weight per weight (w / w) of the MHCA.

[0335] Embodiment 169. The method of Embodiment 168, wherein the particulate metal titanate ion exchanger comprises between 0.01% to 0.6% w / w of the MHCA.

[0336] Embodiment 170. The method of any one of Embodiments 112 to 169, wherein m is about 0.40.

[0337] Embodiment 171. The method of any one of Embodiments 112 to 169, wherein m is about 0.30.

[0338] Embodiment 172. The method of any one of Embodiments 112 to 171, wherein the lead poisoning is acute lead poisoning.

[0339] Embodiment 173. The method of any one of Embodiments 112 to 171, wherein the lead poisoning is chronic lead poisoning.

[0340] Embodiment 174. The method of any one of Embodiments 112 to 173, wherein one or more symptoms of lead poisoning are reduced or eliminated after the administering.

[0341] Embodiment 175. The method of Embodiment 174, wherein the one or more symptoms of lead poisoning are selected from the group consisting of high blood pressure, abdominal pain, joint pain, constipation, nausea, vomiting, fatigue, hyperactivity, irritability, mood disorder, headache, insomnia, lack of concentration, memory loss, reduced sperm count, hearing loss, seizure, and any combination thereof.

[0342] Embodiment 176. The method of any one of Embodiments 112 to 175, wherein normal physiological levels of any one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration.

[0343] Embodiment 177. The method of Embodiment 176, wherein the physiological levels of the one or more ions are measured in the blood of the subject in need thereof.

[0344] Embodiment 178. The method of Embodiment 176, wherein the physiological levels of the one or more ions are measured in the urine of the subject in need thereof.

[0345] Embodiment 179. The method of Embodiment 176, wherein the physiological levels of the one or more ions are measured in the feces of the subject in need thereof.

[0346] Embodiment 180. The method of any one of Embodiments 112 to 179, wherein the human subject in need thereof is a human adult or a human child.

[0347] Embodiment 181. A method for treating, ameliorating, or reducing the severity of lead poisoning in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTiOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, and a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl -containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25to 125 microns (pm), wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2 1content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0348] Embodiment 182. The method of Embodiment 181, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0349] Embodiment 183. The method of Embodiment 181 or Embodiment 182, wherein A is potassium ion.

[0350] Embodiment 184. The method of Embodiment 181 or Embodiment 182, wherein A is hydronium ion.

[0351] Embodiment 185. The method of Embodiment 181 or Embodiment 182, wherein A is a mixture of potassium and hydronium ions.

[0352] Embodiment 186. The method of any one of Embodiments 181 to 185, wherein the macroporous particulate titanate ion exchanger is a polycrystalline aggregate titanate ion exchanger.

[0353] Embodiment 187. The method of any one of Embodiments 181 to 186, wherein the macroporous particulate titanate ion exchanger has spherical morphology.

[0354] Embodiment 188. The method of any one of Embodiments 181 to 187, wherein the macroporous particulate titanate ion exchanger is a powder.

[0355] Embodiment 189. The method of any one of Embodiments 181 to 188, wherein the median particle size is sufficiently large to prevent substantial absorption in the gastrointestinal tract of the subject in need thereof.

[0356] Embodiment 190. The method of any one of Embodiments 181 to 189, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 30 microns (pm) and about 70 pm.

[0357] Embodiment 191. The method of Embodiment 190, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 42 pm and about 48 pm.

[0358] Embodiment 192. The method of Embodiment 191, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value of about 45 pm.

[0359] Embodiment 193. The method of Embodiment 190, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 51 pm and about 57 pm.

[0360] Embodiment 194. The method of Embodiment 193, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value of about 54 pm.

[0361] Embodiment 195. The method of any one of Embodiments 181 to 194, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dso value in a range of about 55 microns (pm) and about 115 pm.

[0362] Embodiment 196. The method of Embodiment 195, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 71 pm and about 77 pm.

[0363] Embodiment 197. The method of Embodiment 196, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 74 pm.

[0364] Embodiment 198. The method of Embodiment 195, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 89 pm and about 95 pm.

[0365] Embodiment 199. The method of Embodiment 198, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 92 pm.

[0366] Embodiment 200. The method of any one of Embodiments 181 to 199, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d$>o value in a range of about 120 microns (pm) and about 180 pm.

[0367] Embodiment 201. The method of Embodiment 200, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 137 pm and about 143 pm.

[0368] Embodiment 202. The method of Embodiment 201, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value of about 140 pm.

[0369] Embodiment 203. The method of Embodiment 200, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 156 pm and about 162 pm.

[0370] Embodiment 204. The method of Embodiment 203, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value of about 159 pm.

[0371] Embodiment 205. The method of any one of Embodiments 181 to 204, wherein the macroporous particulate titanate ion exchanger is stable in a liquid environment at a pH of 1-2.

[0372] Embodiment 206. The method of any one of Embodiments 181 to 205, wherein the macroporous particulate titanate ion exchanger has a BET surface area of about 203 m2 / g.

[0373] Embodiment 207. The method of any one of Embodiments 181 to 206, wherein the pharmaceutical composition is administered to the subject in need thereof in tablet, capsule, or liquid suspension form.

[0374] Embodiment 208. The method of any one of Embodiments 181 to 207, wherein the macroporous particulate titanate ion exchanger is not absorbed or substantially absorbed in the gastrointestinal tract of the subject in need thereof.

[0375] Embodiment 209. The method of any one of Embodiments 181 to 208, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-7.

[0376] Embodiment 210. The method of any one of Embodiments 181 to 208, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 7-13.

[0377] Embodiment 211. The method of any one of Embodiments 181 to 208, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-13.

[0378] Embodiment 212. The method of any one of Embodiments 181 to 208, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0379] Embodiment 213. The method of any one of Embodiments 181 to 208, and 212, wherein the particulate metal titanate ion exchanger is substantially insoluble at stomach pH.

[0380] Embodiment 214. The method of any one of Embodiments 181 to 213, wherein the macroporous particulate titanate ion exchanger is substantially insoluble in one or more bodily fluids.

[0381] Embodiment 215. The method of Embodiment 214, wherein the one or more bodily fluids are selected from the group consisting of blood, urine, and gastrointestinal fluid.

[0382] Embodiment 216. The method of any one of Embodiments 181 to 215, wherein the therapeutically effective dose is between 100 to 1500 mg / kg / day.

[0383] Embodiment 216A. The method of Embodiment 216, wherein the therapeutically effective dose is between 200 to 1000 mg / kg / day.

[0384] Embodiment 217. The method of Embodiment 216A, wherein the therapeutically effective dose is between 300 to 1000 mg / kg / day.

[0385] Embodiment 218. The method of any one of Embodiments 181 to 217, wherein the administration is for at least 7 days.

[0386] Embodiment 219. The method of any one of Embodiments 181 to 217, wherein the administration is for at least 6 weeks.

[0387] Embodiment 220. The method of any one of Embodiments 181 to 217, wherein the administration is for at least 6 months.

[0388] Embodiment 221. The method of any one of Embodiments 181 to 217, wherein the administration is for at least one year.

[0389] Embodiment 222. The method of any one of Embodiments 181 to 217, wherein the administration is for at least two years.

[0390] Embodiment 223. The method of any one of Embodiments 181 to 222, wherein the elevated level of Pb2+content in the body prior to the administering is greater than 0.5 micrograms per deciliter (pg / dL).

[0391] Embodiment 224. The method of any one of Embodiments 181 to 223, wherein the elevated level of Pb2+content in the body is measured in blood, feces, urine, gastrointestinal fluid, or any combination thereof.

[0392] Embodiment 225. The method of any one of Embodiments 181 to 224, wherein the elevated level of Pb2+content in the body is reduced after the administering.

[0393] Embodiment 226. The method of Embodiment 225, wherein the reduction of the elevated level of Pb2+content in the body is measured by excretion of Pb2+in the feces.

[0394] Embodiment 227. The method of Embodiment 226, wherein the amount of Pb2+content excreted in the feces is greater than a pretreatment excretion level of Pb2+.

[0395] Embodiment 228. The method of Embodiment 227, wherein the amount of Pb2+content excreted in the feces is at least 100% greater than the pretreatment excretion level of Pb2+.

[0396] Embodiment 229. The method of Embodiment 228, wherein the amount of Pb2+content excreted in the feces is at least 200% greater than the pretreatment excretion level of Pb2+.

[0397] Embodiment 230. The method of Embodiment 229, wherein the amount of Pb2+content excreted in the feces is at least 1000% greater than the pretreatment excretion level of Pb2+.

[0398] Embodiment 231. The method of any one of Embodiments 227 to 230, wherein the pretreatment excretion level is less than 2 parts per million (ppm).

[0399] Embodiment 232. The method of Embodiment 225, wherein the reduction of the elevated level of Pb2+content in the body is measured by a reduction of Pb2+concentration in the blood.

[0400] Embodiment 233. The method of Embodiment 232, wherein the reduction of Pb2+concentration in the blood is at least a two-fold reduction.

[0401] Embodiment 234. The method of Embodiment 233, wherein the reduction of Pb21concentration in the blood is at least a five-fold reduction.

[0402] Embodiment 235. The method of Embodiment 234, wherein the reduction of Pb2+concentration in the blood is at least a ten-fold reduction.

[0403] Embodiment 236. The method of any one of Embodiments 232 to 235, wherein the Pb2+concentration in the blood is reduced to less than 0.5 pg / dL.

[0404] Embodiment 237. The method of any one of Embodiments 181 to 236, wherein the Pb2+content in the body is measured by inductively coupled plasma (ICP) elemental analysis.

[0405] Embodiment 238. The method of any one of Embodiments 181 to 237, wherein the macroporous particulate titanate ion exchanger has a distribution coefficient (Kd) for Pb2+in a range of about 100,000 to about 2,500,000 milliliters per gram (mL / g).

[0406] Embodiment 239. The method of Embodiment 238, wherein the macroporous particulate titanate ion exchanger has a Kd for Pb2+of about 967,800.

[0407] Embodiment 240. The method of Embodiment 238, wherein the macroporous particulate titanate ion exchanger has a Kd for Pb2+of about 321,900.

[0408] Embodiment 241. The method of any one of Embodiments 181 to 240, wherein the macroporous particulate titanate ion exchanger comprises between 0.01% to 4.0% weight per weight (w / w) of the MHCA.

[0409] Embodiment 242. The method of Embodiment 241 , wherein the particulate metal titanate ion exchanger comprises between 0.01% to 0.6% w / w of the MHCA.

[0410] Embodiment 243. The method of any one of Embodiments 181 to 242, wherein m is about 0.28.

[0411] Embodiment 244. The method of any one of Embodiments 181 to 243, wherein the lead poisoning is acute lead poisoning.

[0412] Embodiment 245. The method of any one of Embodiments 181 to 243, wherein the lead poisoning is chronic lead poisoning.

[0413] Embodiment 246. The method of any one of Embodiments 181 to 245, wherein one or more symptoms of lead poisoning are reduced or eliminated after the administering.

[0414] Embodiment 247. The method of Embodiment 246, wherein the one or more symptoms of lead poisoning are selected from the group consisting of high blood pressure, abdominal pain, joint pain, constipation, nausea, vomiting, fatigue, hyperactivity, irritability, mood disorder, headache, insomnia, lack of concentration, memory loss, reduced sperm count, hearing loss, seizure, and any combination thereof.

[0415] Embodiment 248. The method of any one of Embodiments 181 to 247, wherein normal physiological levels of any one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration.

[0416] Embodiment 249. The method of Embodiment 248, wherein the physiological levels of the one or more ions are measured in the blood of the subject in need thereof.

[0417] Embodiment 250. The method of Embodiment 248, wherein the physiological levels of the one or more ions are measured in the urine of the subject in need thereof.

[0418] Embodiment 251. The method of Embodiment 248, wherein the physiological levels of the one or more ions are measured in the feces of the subject in need thereof.

[0419] Embodiment 252. The method of any one of Embodiments 181 to 251, wherein the human subject in need thereof is a human adult or a human child.

[0420] Embodiment 253. A method for reducing an elevated level of Pb2+in a subject in need thereof, the method comprising a step of administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a therapeutically effective dose of particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTixMyO; whereinA is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion, and 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl-containing complexing agent (MHCA), wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm), and wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering.

[0421] Embodiment 254. The method of Embodiment 253, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0422] Embodiment 255. The method of Embodiment 253 or Embodiment 254, wherein A is potassium ion, hydronium ion, or a mixture thereof.

[0423] Embodiment 256. The method of any one of Embodiments 253 to 255, wherein A is potassium ion.

[0424] Embodiment 257. The method of any one of Embodiments 253 to 255, wherein A is hydronium ion.

[0425] Embodiment 258. The method of any one of Embodiments 253 to 255, wherein A is a mixture of potassium and hydronium ions.

[0426] Embodiment 259. The method of any one of Embodiments 253 to 258, wherein the particulate metal titanate ion exchanger is a polycrystalline aggregate metal titanate ion exchanger.

[0427] Embodiment 260. The method of any one of Embodiments 253 to 259, wherein the particulate metal titanate ion exchanger is macroporous.

[0428] Embodiment 261 . The method of any one of Embodiments 253 to 260, wherein the particulate metal titanate ion exchanger has a spherical morphology.

[0429] Embodiment 262. The method of any one of Embodiments 253 to 260, wherein the particulate metal titanate ion exchanger has amorphous morphology.

[0430] Embodiment 263. The method of any one of Embodiments 253 to 262, wherein the particulate metal titanate ion exchanger is a powder.

[0431] Embodiment 264. The method of any one of Embodiments 253 to 263, wherein the median particle size is between 25 to 125 microns (pm).

[0432] Embodiment 265. The method of any one of Embodiments 253 to 264, wherein the median particle size is sufficiently large to prevent substantial absorption in the gastrointestinal tract of the subject in need thereof.

[0433] Embodiment 266. The method of any one of Embodiments 253 to 265, wherein less than 3% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 microns (pm).

[0434] Embodiment 267. The method of Embodiment 266, wherein less than 0.5% of the particles of the particulate metal titanate ion exchanger have a particle size less than 3 microns (pm).

[0435] Embodiment 268. The method of any one of Embodiments 253 to 267, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 5 microns (pm) and about 70 pm.

[0436] Embodiment 269. The method of Embodiment 268, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 12 pm and about 18 pm.

[0437] Embodiment 270. The method of Embodiment 269, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value of about 15 pm.

[0438] Embodiment 271. The method of Embodiment 268, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 42 pm and about 48 pm.

[0439] Embodiment 272. The method of Embodiment 271, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value of about 45 pm.

[0440] Embodiment 273. The method of Embodiment 268, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value in a range of about 51 pm and about 57 pm.

[0441] Embodiment 274. The method of Embodiment 273, wherein the particulate metal titanate ion exchanger has a particle size distribution dio value of about 54 pm.

[0442] Embodiment 275. The method of any one of Embodiments 253 to 274, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 40 microns (pm) and about 115 pm.

[0443] Embodiment 276. The method of Embodiment 275, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 48 pm and about 54 pm.

[0444] Embodiment 277. The method of Embodiment 276, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 51 pm.

[0445] Embodiment 278. The method of Embodiment 275, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 71 pm and about 77 pm.

[0446] Embodiment 279. The method of Embodiment 278, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 74 pm.

[0447] Embodiment 280. The method of Embodiment 275, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 89 pm and about 95 pm.

[0448] Embodiment 281. The method of Embodiment 280, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 92 pm.

[0449] Embodiment 282. The method of any one of Embodiments 253 to 281, wherein the particulate metal titanate ion exchanger has a particle size distribution doo value in a range of about 65 microns (pm) and about 185 pm.

[0450] Embodiment 283. The method of Embodiment 282, wherein the particulate metal titanate ion exchanger has a particle size distribution doo value in a range of about 99 pm and about 105 pm.

[0451] Embodiment 284. The method of Embodiment 283, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value of about 102 pm.

[0452] Embodiment 285. The method of Embodiment 282, wherein the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 137 pm and about 143 pm.

[0453] Embodiment 286. The method of Embodiment 285, wherein the particulate metal titanate ion exchanger has a particle size distribution d9o value of about 140 pm.

[0454] Embodiment 287. The method of Embodiment 282, wherein the particulate metal titanate ion exchanger has a particle size distribution d9o value in a range of about 156 pm and about 162 pm.

[0455] Embodiment 288. The method of Embodiment 287, wherein the particulate metal titanate ion exchanger has a particle size distribution dgo value of about 159 pm,

[0456] Embodiment 289. The method of any one of Embodiments 253 to 288, wherein the particulate metal titanate ion exchanger is stable in a liquid environment at a pH of 1-2.

[0457] Embodiment 290. The method of any one of Embodiments 253 to 289, wherein the particulate metal titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of greater than 150 square meters per gram (m2 / g).

[0458] Embodiment 291. The method of Embodiment 290, wherein the particulate metal titanate ion exchanger has a BET surface area of about 197 m2 / g.

[0459] Embodiment 292. The method of any one of Embodiments 253 to 289, wherein the particulate metal titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of greater than 200 square meters per gram (m2 / g).

[0460] Embodiment 293. The method of Embodiment 292, wherein the particulate metal titanate ion exchanger has a BET surface area of about 203 m2 / g.

[0461] Embodiment 294. The method of any one of Embodiments 253 to 289, wherein the particulate metal titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of greater than 230 square meters per gram (m2 / g).

[0462] Embodiment 295. The method of Embodiment 294, wherein the particulate metal titanate ion exchanger has a BET surface area of about 236 m2 / g.

[0463] Embodiment 296. The method of any one of Embodiments 253 to 295, wherein the administering is oral administration.

[0464] Embodiment 297. The method of Embodiment 296, wherein the pharmaceutical composition is administered to the subject in need thereof in tablet, capsule, or liquid suspension form.

[0465] Embodiment 298. The method of any one of Embodiments 253 to 297, wherein the particulate metal titanate ion exchanger is not absorbed or substantially absorbed in the gastrointestinal tract of the subject in need thereof.

[0466] Embodiment 299. The method of any one of Embodiments 253 to 298, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-7.

[0467] Embodiment 300. The method of any one of Embodiments 253 to 298, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 7-13,

[0468] Embodiment 301. The method of any one of Embodiments 253 to 298, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-13.

[0469] Embodiment 302. The method of any one of Embodiments 253 to 298, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0470] Embodiment 303. The method of any one of Embodiments 253 to 298, and 302, wherein the particulate metal titanate ion exchanger is substantially insoluble at stomach pH.

[0471] Embodiment 304. The method of any one of Embodiments 253 to 303, wherein the particulate metal titanate ion exchanger is substantially insoluble in one or more bodily fluids.

[0472] Embodiment 305. The method of Embodiment 304, wherein the one or more bodily fluids are selected from the group consisting of blood, urine, and gastrointestinal fluid.

[0473] Embodiment 306. The method of any one of Embodiments 253 to 305, wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0474] Embodiment 307. The method of Embodiment 306, wherein the therapeutically effective dose is between 100 to 1500 mg / kg / day.

[0475] Embodiment 307A. The method of Embodiment 307, wherein the therapeutically effective dose is between 200 to 1000 mg / kg / day.

[0476] Embodiment 308. The method of Embodiment 307A, wherein the therapeutically effective dose is between 300 to 1000 mg / kg / day.

[0477] Embodiment 309. The method of any one of Embodiments 253 to 308, wherein the administration is for at least 7 days.

[0478] Embodiment 310. The method of any one of Embodiments 253 to 308, wherein the administration is for at least 6 weeks.

[0479] Embodiment 311. The method of any one of Embodiments 253 to 308, wherein the administration is for at least 6 months.

[0480] Embodiment 312. The method of any one of Embodiments 253 to 308, wherein the administration is for at least one year.

[0481] Embodiment 313. The method of any one of Embodiments 253 to 308, wherein the administration is for at least two years.

[0482] Embodiment 314. The method of any one of Embodiments 253 to 313, wherein the elevated level of Pb2+content in the body is greater than 0.5 micrograms per deciliter (pg / dL).

[0483] Embodiment 315. The method of any one of Embodiments 253 to 314, wherein the elevated level of Pb2+content in the body is measured in blood, feces, urine, gastrointestinal fluid, or any combination thereof.

[0484] Embodiment 316. The method of any one of Embodiments 253 to 315, wherein the elevated level of Pb2+content in the body is reduced after the administering.

[0485] Embodiment 317. The method of Embodiment 316, wherein the reduction of the elevated level of Pb2+content in the body is measured by excretion of Pb2+in the feces.

[0486] Embodiment 318. The method of Embodiment 317, wherein the amount of Pb2+content excreted in the feces is greater than a pretreatment excretion level of Pb2+.

[0487] Embodiment 319. The method of Embodiment 318, wherein the amount of Pb2+content excreted in the feces is at least 100% greater than the pretreatment excretion level of Pb2+.

[0488] Embodiment 320. The method of Embodiment 319, wherein the amount of Pb2+content excreted in the feces is at least 200% greater than the pretreatment excretion level of Pb2+.

[0489] Embodiment 321. The method of Embodiment 320, wherein the amount of Pb2+content excreted in the feces is at least 1000% greater than the pretreatment excretion level of Pb2+.

[0490] Embodiment 322. The method of any one of Embodiments 318 to 321, wherein the pretreatment excretion level is less than 2 parts per million (ppm).

[0491] Embodiment 323. The method of Embodiment 316, wherein the reduction of the elevated level of Pb2+content in the body is measured by a reduction of Pb2+concentration in the blood.

[0492] Embodiment 324. The method of Embodiment 323, wherein the reduction of Pb2+concentration in the blood is at least a two-fold reduction.

[0493] Embodiment 325. The method of Embodiment 324, wherein the reduction of Pb2+concentration in the blood is at least a five-fold reduction.

[0494] Embodiment 326. The method of Embodiment 325, wherein the reduction of Pb2+concentration in the blood is at least a ten-fold reduction.

[0495] Embodiment 327. The method of any one of Embodiments 323 to 326, wherein the Pb2+concentration in the blood is reduced to less than 0.5 pg / dL.

[0496] Embodiment 328. The method of any one of Embodiments 253 to 327, wherein the Pb2+content in the body is measured by inductively coupled plasma (ICP) elemental analysis.

[0497] Embodiment 329. The method of any one of Embodiments 253 to 328, wherein the particulate metal titanate ion exchanger has a distribution coefficient (Ka) forPb2+in a range of about 50,000 to greater than 5,500,000 milliliters per gram (mL / g).

[0498] Embodiment 330. The method of Embodiment 329, wherein the particulate metal titanate ion exchanger has a Ka for Pb2+in a range of about 100,000 to about 2,500,000 mL / g.

[0499] Embodiment 331. The method of Embodiment 330, wherein the particulate metal titanate ion exchanger has a Ka for Pb2+of about 967,800.

[0500] Embodiment 332. The method of Embodiment 330, wherein the particulate metal titanate ion exchanger has a K for Pb2+of about 809,500.

[0501] Embodiment 333. The method of Embodiment 330, wherein the particulate metal titanate ion exchanger has a K for Pb2+of about 495,800.

[0502] Embodiment 334. The method of Embodiment 330, wherein the particulate metal titanate ion exchanger has a K for Pb2+of about 321,900.

[0503] Embodiment 335. The method of any one of Embodiments 253 to 334, wherein the at least one MHCA is selected from the group consisting of a sugar alcohol, a sugar, an aromatic compound, and any combination thereof.

[0504] Embodiment 336. The method of Embodiment 335, wherein the at least one MHCA is a sugar alcohol.

[0505] Embodiment 337. The method of Embodiment 336, wherein the sugar alcohol is selected from the group consisting of d-sorbitol, mannitol, and xylitol.

[0506] Embodiment 338. The method of Embodiment 335, wherein the at least one MHCA is a sugar.

[0507] Embodiment 339. The method of Embodiment 338, wherein the sugar is glucose or fructose.

[0508] Embodiment 340. The method of Embodiment 335, wherein the at least one MHCA is an aromatic compound.

[0509] Embodiment 341. The method of Embodiment 340, wherein the aromatic compound is catechol.

[0510] Embodiment 342. The method of any one of Embodiments 253 to 341, wherein the particulate metal titanate ion exchanger comprises between 0.01% to 4.0% weight per weight (w / w) of the at least one MHCA.

[0511] Embodiment 343. The method of Embodiment 342, wherein the particulate metal titanate ion exchanger comprises between 0.01% to 0.6% w / w of the at least one MHCA.

[0512] Embodiment 344. The method of any one of Embodiments 253 to 343, wherein x is 1 and y is 0.

[0513] Embodiment 345. The method of any one of Embodiments 253 to 344, wherein m is between 0.10 to 0.50.

[0514] Embodiment 346. The method of Embodiment 345, wherein m is about 0.40.

[0515] Embodiment 347. The method of Embodiment 345, wherein m is about 0.30.

[0516] Embodiment 348. The method of Embodiment 345, wherein m is about 0.28.

[0517] Embodiment 349. The method of any one of Embodiments 253 to 348, wherein the x- ray diffraction (XRD) pattern of the particulate metal titanate ion exchanger has a characteristic diffraction line with a d-spacing of 3.00 to 3.11 A.

[0518] Embodiment 350. The method of any one of Embodiments 253 to 349, wherein the particulate metal titanate ion exchanger has an x-ray diffraction (XRD) pattern having characteristic diffraction lines within the ranges provided below in Table A or Table B:Table A Table B11.1 1 - 10.78 7.96 - 8.2 w - m 1 1.47 - 10.95 7.71 - 8.07 w - s25.43 - 24.03 3.50 - 3.70 w - m 24.37 - 23.97 3.65 - 3.71 m - s29.55 -28.68 3.02 - 3.11 Vs 29.76 -28.78 3.00 - 3.10 vs33.93 -33.15 2.64 -2.70 m-s 33.80 -33.15 2.65 -2.70 w-m43.36 -42.51 2.085 -2.125 w-m 43.47 -42.51 2.08 -2.125 m-s48.38 -47.31 1.88 - 1.92 m-s 48.51 -47.49 1.875 - 1.913 m - vs60.46 -59.18 1.53 - 1.56 w-m 66.93 -65.55 1.397 - 1.423 w-m67.03 -65.44 1.395 - 1.425 w-m

[0519] Embodiment 351. The method of any one of Embodiments 253 to 348, wherein the x- ray diffraction (XRD) pattern of the particulate metal titanate ion exchanger has a characteristic diffraction line with a d-spacing of 3.00 to 3.10 A.

[0520] Embodiment 352. The method of any one of Embodiments 253 to 348, and 351, wherein the particulate metal titanate ion exchanger has an x-ray diffraction (XRD) pattern having characteristic diffraction lines within the ranges provided below in Table C or Table D:Table C Table D11.87- 10.89 7.45 - 8.12 w-s 11.76- 10.82 7.52- 8.17 w-s24.50-23.71 3.63 -3.75 w-m 24.64-23.58 3.61 -3.77 w-m29.76-28.87 3.00-3.09 Vs 29.76-28.78 3.00-3.10 vs32.06-30.81 2.79-2.90 w-s 32.05 -30.38 2.79-2.94 w-s33.93 -33.15 2.64-2.70 m-s 34.06-33.15 2.63 -2.70 w-m43.26-42.61 2.09-2.12 w-s 43.36-42.51 2.085 -2.125 m-vs48.24-47.44 1.885 - 1.915 w-s 48.51 -47.44 1.875 - 1.915 m-vs60.03 -58.77 1.54- 1.57 w-m 60.24-58.76 1.535 - 1.57 w-m66.77-65.71 1.40- 1.42 w-m 66.76-65.70 1.40- 1.42 w-m

[0521] Embodiment 353. The method of any one of Embodiments 253 to 352, wherein the subject in need thereof suffers from lead poisoning.

[0522] Embodiment 354. The method of Embodiment 353, wherein the lead poisoning is acute lead poisoning.

[0523] Embodiment 355. The method of Embodiment 353, wherein the lead poisoning is chronic lead poisoning.

[0524] Embodiment 356. The method of any one of Embodiments 353 to 355, wherein one or more symptoms of lead poisoning are reduced or eliminated after the administering.

[0525] Embodiment 357. The method of Embodiment 356, wherein the one or more symptoms of lead poisoning are selected from the group consisting of high blood pressure, abdominal pain, joint pain, constipation, nausea, vomiting, fatigue, hyperactivity, irritability,mood disorder, headache, insomnia, lack of concentration, memory loss, reduced sperm count, hearing loss, seizure, and any combination thereof.[005261 Embodiment 358. The method of any one of Embodiments 253 to 357, wherein normal physiological levels of any one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration.

[0527] Embodiment 359. The method of Embodiment 358, wherein the physiological levels of the one or more ions are measured in the blood of the subject in need thereof.

[0528] Embodiment 360. The method of Embodiment 358, wherein the physiological levels of the one or more ions are measured in the urine of the subject in need thereof.

[0529] Embodiment 361. The method of Embodiment 358, wherein the physiological levels of the one or more ions are measured in the feces of the subject in need thereof.

[0530] Embodiment 362. The method of any one of Embodiments 253 to 361, wherein the subject in need thereof is a human.

[0531] Embodiment 363. The method of Embodiment 362, wherein the subject in need thereof is a human adult.

[0532] Embodiment 364. The method of Embodiment 362, wherein the subject in need thereof is a human child.

[0533] Embodiment 365. A method for reducing an elevated level of Pb2+in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTiOzwhereinA is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, or a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl -containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 3.0% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporousparticulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0534] Embodiment 366. The method of Embodiment 365, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0535] Embodiment 367. The method of Embodiment 365 or Embodiment 366, wherein A is potassium ion.

[0536] Embodiment 368. The method of Embodiment 365 or Embodiment 366, wherein A is hydronium ion.

[0537] Embodiment 369. The method of Embodiment 365 or Embodiment 366, wherein A is a mixture of potassium and hydronium ions.

[0538] Embodiment 370. The method of any one of Embodiment 365 to 369, wherein the macroporous particulate titanate ion exchanger is a polycrystalline aggregate titanate ion exchanger.

[0539] Embodiment 371. The method of any one of Embodiments 365 to 370, wherein the macroporous particulate titanate ion exchanger has amorphous morphology.

[0540] Embodiment 372. The method of any one of Embodiments 365 to 371, wherein the macroporous particulate titanate ion exchanger is a powder.

[0541] Embodiment 373. The method of any one of Embodiments 365 to 372, wherein the median particle size is sufficiently large to prevent absorption in the gastrointestinal tract of the subject in need thereof.

[0542] Embodiment 374. The method of any one of Embodiments 365 to 373, wherein about 3.0% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 microns (pm).

[0543] Embodiment 375. The method of any one of Embodiments 365 to 374, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 5 microns (pm) and about 30 pm.

[0544] Embodiment 376. The method of Embodiment 375, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 12 pm and about 18 pm.

[0545] Embodiment 377. The method of Embodiment 376, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value of about 15 pm.

[0546] Embodiment 378. The method of any one of Embodiments 365 to 377, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dso value in a range of about 40 microns (pm) and about 75 pm.

[0547] Embodiment 379. The method of Embodiment 378, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dso value in a range of about 48 pm and about 54 pm.

[0548] Embodiment 380. The method of Embodiment 379, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dso value of about 51 pm.

[0549] Embodiment 381. The method of any one of Embodiments 365 to 380, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dgo value in a range of about 80 microns (pm) and about 140 pm.

[0550] Embodiment 382. The method of Embodiment 381, wherein the particulate metal titanate ion exchanger has a particle size distribution dgo value in a range of about 99 pm and about 105 pm.

[0551] Embodiment 383. The method of Embodiment 382, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dgo value of about 102 pm.

[0552] Embodiment 384. The method of any one of Embodiments 365 to 383, wherein the macroporous particulate titanate ion exchanger is stable in a liquid environment at a pH of 1-2.

[0553] Embodiment 385. The method of any one of Embodiments 365 to 384, wherein the macroporous particulate titanate ion exchanger has a BET surface area of about 197 m2 / g.

[0554] Embodiment 386. The method of any one of Embodiments 365 to 384, wherein the macroporous particulate titanate ion exchanger has a BET surface area of about 236 m2 / g.

[0555] Embodiment 387. The method of any one of Embodiments 365 to 386, wherein the pharmaceutical composition is administered to the subject in need thereof in tablet, capsule, or liquid suspension form.

[0556] Embodiment 388. The method of any one of Embodiments 365 to 387, wherein the macroporous particulate titanate ion exchanger is not absorbed or substantially absorbed in the gastrointestinal tract of the subject in need thereof.

[0557] Embodiment 389. The method of any one of Embodiments 365 to 388, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-7.

[0558] Embodiment 390. The method of any one of Embodiments 365 to 388, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 7-13.

[0559] Embodiment 391. The method of any one of Embodiments 365 to 388, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-13.

[0560] Embodiment 392. The method of any one of Embodiments 365 to 388, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0561] Embodiment 393. The method of any one of Embodiments 365 to 388, and 392, wherein the particulate metal titanate ion exchanger is substantially insoluble at stomach pH.

[0562] Embodiment 394. The method of any one of Embodiments 365 to 393, wherein the macroporous particulate titanate ion exchanger is substantially insoluble in one or more bodily fluids.

[0563] Embodiment 395. The method of Embodiment 394, wherein the one or more bodily fluids are selected from the group consisting of blood, urine, and gastrointestinal fluid.

[0564] Embodiment 396. The method of any one of Embodiments 365 to 395, wherein the therapeutically effective dose is between 100 to 1500 mg / kg / day.

[0565] Embodiment 396A. The method of Embodiment 396, wherein the therapeutically effective dose is between 200 to 1000 mg / kg / day.

[0566] Embodiment 397. The method of Embodiment 396A, wherein the therapeutically effective dose is between 300 to 1000 mg / kg / day.

[0567] Embodiment 398. The method of any one of Embodiments 365 to 397, wherein the administration is for at least 7 days.

[0568] Embodiment 399. The method of any one of Embodiments 365 to 397, wherein the administration is for at least 6 weeks.

[0569] Embodiment 400. The method of any one of Embodiments 365 to 397, wherein the administration is for at least 6 months.

[0570] Embodiment 401. The method of any one of Embodiments 365 to 397, wherein the administration is for at least one year.

[0571] Embodiment 402. The method of any one of Embodiments 365 to 397, wherein the administration is for at least two years.

[0572] Embodiment 403. The method of any one of Embodiments 365 to 402, wherein the elevated level of Pb2+content in the body prior to the administering is greater than 0.5 micrograms per deciliter (pg / dL).

[0573] Embodiment 404. The method of any one of Embodiments 365 to 403, wherein the elevated level of Pb2+content in the body is measured in blood, feces, urine, gastrointestinal fluid, or any combination thereof.

[0574] Embodiment 405. The method of any one of Embodiments 365 to 404, wherein the elevated level of Pb2+content in the body is reduced after the administering.

[0575] Embodiment 406. The method of Embodiment 405, wherein the reduction of the elevated level of Pb2+content in the body is measured by excretion of Pb2+in the feces.

[0576] Embodiment 407. The method of Embodiment 406, wherein the amount of Pb2+content excreted in the feces is greater than a pretreatment excretion level of Pb2+.

[0577] Embodiment 408. The method of Embodiment 407, wherein the amount of Pb2+content excreted in the feces is at least 100% greater than the pretreatment excretion level of Pb2+.

[0578] Embodiment 409. The method of Embodiment 408, wherein the amount of Pb2+content excreted in the feces is at least 200% greater than the pretreatment excretion level of Pb2+.

[0579] Embodiment 410. The method of Embodiment 409, wherein the amount of Pb2+content excreted in the feces is at least 1000% greater than the pretreatment excretion level of Pb2+.

[0580] Embodiment 411. The method of any one of Embodiments 407 to 410, wherein the pretreatment excretion level is less than 2 parts per million (ppm).

[0581] Embodiment 412. The method of Embodiment 405, wherein the reduction of the elevated level of Pb2+content in the body is measured by a reduction of Pb2+concentration in the blood.

[0582] Embodiment 413. The method of Embodiment 412, wherein the reduction of Pb2+concentration in the blood is at least a two-fold reduction.

[0583] Embodiment 414. The method of Embodiment 413, wherein the reduction of Pb2+concentration in the blood is at least a five-fold reduction.

[0584] Embodiment 415. The method of Embodiment 414, wherein the reduction of Pb2+concentration in the blood is at least a ten-fold reduction.

[0585] Embodiment 416. The method of any one of Embodiments 412 to 415, wherein the Pb2+concentration in the blood is reduced to less than 0.5 pg / dL.

[0586] Embodiment 417. The method of any one of Embodiments 365 to 416, wherein the Pb2+content in the body is measured by inductively coupled plasma (ICP) elemental analysis.

[0587] Embodiment 418. The method of any one of Embodiments 365 to 417, wherein the macroporous particulate titanate ion exchanger has a distribution coefficient (Ka) for Pb2+in a range of about 100,000 to about 2,500,000 milliliters per gram (mL / g).

[0588] Embodiment 419. The method of Embodiment 418, wherein the macroporous particulate titanate ion exchanger has a Ka for Pb2+of about 809,500.

[0589] Embodiment 420. The method of Embodiment 418, wherein the macroporous particulate titanate ion exchanger has a K for Pb2+of about 495,800.

[0590] Embodiment 421. The method of any one of Embodiments 365 to 420, wherein the macroporous particulate titanate ion exchanger comprises between 0.01% to 4.0% weight per weight (w / w) of the MHCA.

[0591] Embodiment 422. The method of Embodiment 421, wherein the particulate metal titanate ion exchanger comprises between 0.01% to 0.6% w / w of the MHCA.

[0592] Embodiment 423. The method of any one of Embodiments 365 to 422, wherein m is about 0.40.

[0593] Embodiment 424. The method of any one of Embodiments 365 to 422, wherein m is about 0.30.

[0594] Embodiment 425. The method of any one of Embodiments 365 to 424, wherein the subject in need thereof suffers from chronic or acute lead poisoning.

[0595] Embodiment 426. The method of Embodiment 425, wherein one or more symptoms of lead poisoning are reduced or eliminated after the administering.

[0596] Embodiment 427. The method of Embodiment 426, wherein the one or more symptoms of lead poisoning are selected from the group consisting of high blood pressure, abdominal pain, joint pain, constipation, nausea, vomiting, fatigue, hyperactivity, irritability, mood disorder, headache, insomnia, lack of concentration, memory loss, reduced sperm count, hearing loss, seizure, and any combination thereof.

[0597] Embodiment 428. The method of any one of Embodiments 365 to 427, wherein normal physiological levels of any one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration.

[0598] Embodiment 429. The method of Embodiment 428, wherein the physiological levels of the one or more ions are measured in the blood of the subject in need thereof.

[0599] Embodiment 430. The method of Embodiment 428, wherein the physiological levels of the one or more ions are measured in the urine of the subject in need thereof.

[0600] Embodiment 431. The method of Embodiment 428, wherein the physiological levels of the one or more ions are measured in the feces of the subject in need thereof.

[0601] Embodiment 432. The method of any one of Embodiments 365 to 431, wherein the human subject in need thereof is a human adult or a human child.

[0602] Embodiment 433. A method for reducing an elevated level of Pb2+in a human subject in need thereof comprising a step of orally administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a macroporous particulate titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTiOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, hydronium ion, and a mixture thereof; “m” is the mole ratio of A to Ti and has a value from 0.10 to 0.60; and "z" is the mole ratio of O to Ti and has a value from 2.05 to 2.60, wherein the macroporous titanate ion exchanger having been synthesized in the presence of a multihydroxyl -containing complexing agent (MHCA) that is d-sorbitol, wherein the macroporous particulate titanate ion exchanger exhibits a median particle size that is between 25 to 125 microns (pm), wherein less than 0.5% of the particles of the macroporous particulate titanate ion exchanger have a particle size less than 3 microns (pm), wherein the macroporous particulate titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of at least 150 square meters per gram (m2 / g), wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering, and wherein the therapeutically effective dose is between 1 to 2000 milligrams per kilogram per day (mg / kg / day).

[0603] Embodiment 434. The method of Embodiment 433, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0604] Embodiment 435. The method of Embodiment 433 or Embodiment 434, wherein A is potassium ion.

[0605] Embodiment 436. The method of Embodiment 433 or Embodiment 434, wherein A is hydronium ion.

[0606] Embodiment 437. The method of Embodiment 433 or Embodiment 434, wherein A is a mixture of potassium and hydronium ions.

[0607] Embodiment 438. The method of any one of Embodiments 433 to 437, wherein the macroporous particulate titanate ion exchanger is a polycrystalline aggregate titanate ion exchanger.

[0608] Embodiment 439. The method of any one of Embodiments 433 to 438, wherein the macroporous particulate titanate ion exchanger has spherical morphology.

[0609] Embodiment 440. The method of any one of Embodiments 433 to 439, wherein the macroporous particulate titanate ion exchanger is a powder.

[0610] Embodiment 441. The method of any one of Embodiments 433 to 440, wherein the median particle size is sufficiently large to prevent absorption in the gastrointestinal tract of the subject in need thereof.

[0611] Embodiment 442. The method of any one of Embodiments 433 to 441, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 30 microns (pm) and about 70 pm.

[0612] Embodiment 443. The method of Embodiment 442, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 42 pm and about 48 pm.

[0613] Embodiment 444. The method of Embodiment 443, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value of about 45 pm.

[0614] Embodiment 445. The method of Embodiment 442, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value in a range of about 51 pm and about 57 pm.

[0615] Embodiment 446. The method of Embodiment 445, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dio value of about 54 pm.

[0616] Embodiment 447. The method of any one of Embodiments 443 to 446, wherein the macroporous particulate titanate ion exchanger has a particle size distribution dso value in a range of about 55 microns (pm) and about 115 pm.

[0617] Embodiment 448. The method of Embodiment 447, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 71 pm and about 77 pm.

[0618] Embodiment 449. The method of Embodiment 448, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 74 pm.

[0619] Embodiment 450. The method of Embodiment 447, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value in a range of about 89 pm and about 95 pm.

[0620] Embodiment 451. The method of Embodiment 450, wherein the particulate metal titanate ion exchanger has a particle size distribution dso value of about 92 pm.

[0621] Embodiment 452. The method of any one of Embodiments 433 to 451, wherein the macroporous particulate titanate ion exchanger has a particle size distribution d$>o value in a range of about 120 microns (pm) and about 180 pm.

[0622] Embodiment 453. The method of Embodiment 452, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 137 pm and about 143 pm.

[0623] Embodiment 454. The method of Embodiment 453, wherein the particulate metal titanate ion exchanger has a particle size distribution dgo value of about 140 pm.

[0624] Embodiment 455. The method of Embodiment 452, wherein the particulate metal titanate ion exchanger has a particle size distribution dw value in a range of about 156 pm and about 162 pm.

[0625] Embodiment 456. The method of Embodiment 455, wherein the particulate metal titanate ion exchanger has a particle size distribution dgo value of about 159 pm.

[0626] Embodiment 457. The method of any one of Embodiments 433 to 456, wherein the macroporous particulate titanate ion exchanger is stable in a liquid environment at a pH of 1-2.

[0627] Embodiment 458. The method of any one of Embodiments 433 to 457, wherein the macroporous particulate titanate ion exchanger has a BET surface area of about 203 m2 / g.

[0628] Embodiment 459. The method of any one of Embodiments 433 to 458, wherein the pharmaceutical composition is administered to the subject in need thereof in tablet, capsule, or liquid suspension form.

[0629] Embodiment 460. The method of any one of Embodiments 433 to 459, wherein the macroporous particulate titanate ion exchanger is not absorbed or substantially absorbed in the gastrointestinal tract of the subject in need thereof.

[0630] Embodiment 461. The method of any one of Embodiments 433 to 460, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-7.

[0631] Embodiment 462. The method of any one of Embodiments 433 to 460, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 7-13.

[0632] Embodiment 463. The method of any one of Embodiments 433 to 460, wherein the particulate metal titanate ion exchanger is substantially insoluble at a pH range of 1-13.

[0633] Embodiment 464. The method of any one of Embodiments 433 to 460, wherein the particulate metal titanate ion exchanger is substantially insoluble at physiological pH.

[0634] Embodiment 465. The method of any one of Embodiments 433 to 460, and 464, wherein the particulate metal titanate ion exchanger is substantially insoluble at stomach pH.

[0635] Embodiment 466. The method of any one of Embodiments 433 to 465, wherein the macroporous particulate titanate ion exchanger is substantially insoluble in one or more bodily fluids.

[0636] Embodiment 467. The method of Embodiment 466, wherein the one or more bodily fluids are selected from the group consisting of blood, urine, and gastrointestinal fluid.

[0637] Embodiment 468. The method of any one of Embodiments 433 to 467, wherein the therapeutically effective dose is in a range of 100 to 1500 mg / kg / day.

[0638] Embodiment 468 A. The method of Embodiment 468, wherein the therapeutically effective dose is in a range of 200 to 1000 mg / kg / day.

[0639] Embodiment 469. The method of Embodiment 468A, wherein the therapeutically effective dose is in a range of 300 to 1000 mg / kg / day.

[0640] Embodiment 470. The method of any one of Embodiments 433 to 469, wherein the administration is for at least 7 days.

[0641] Embodiment 471. The method of any one of Embodiments 433 to 469, wherein the administration is for at least 6 weeks.

[0642] Embodiment 472. The method of any one of Embodiments 433 to 469, wherein the administration is for at least 6 months.

[0643] Embodiment 473. The method of any one of Embodiments 433 to 469, wherein the administration is for at least one year.

[0644] Embodiment 474. The method of any one of Embodiments 433 to 469, wherein the administration is for at least two years.

[0645] Embodiment 475. The method of any one of Embodiments 433 to 474, wherein the elevated level of Pb2+content in the body prior to the administering is greater than 0.5 micrograms per deciliter ( g / dL).

[0646] Embodiment 476. The method of any one of Embodiments 433 to 475, wherein the elevated level of Pb2+content in the body is measured in blood, feces, urine, gastrointestinal fluid, or any combination thereof.

[0647] Embodiment 477. The method of any one of Embodiments 433 to 476, wherein the elevated level of Pb2+content in the body is reduced after the administering.

[0648] Embodiment 478. The method of Embodiment 477, wherein the reduction of the elevated level of Pb2+content in the body is measured by excretion of Pb2+in the feces.

[0649] Embodiment 479. The method of Embodiment 478, wherein the amount of Pb2+content excreted in the feces is greater than a pretreatment excretion level of Pb2+.

[0650] Embodiment 480. The method of Embodiment 479, wherein the amount of Pb2+content excreted in the feces is at least 100% greater than the pretreatment excretion level of Pb2+.

[0651] Embodiment 481. The method of Embodiment 480, wherein the amount of Pb2+content excreted in the feces is at least 200% greater than the pretreatment excretion level of Pb2+.

[0652] Embodiment 482. The method of Embodiment 481, wherein the amount of Pb2+content excreted in the feces is at least 1000% greater than the pretreatment excretion level of Pb2+

[0653] Embodiment 483. The method of any one of Embodiments 479 to 482, wherein the pretreatment excretion level is less than 2 parts per million (ppm).

[0654] Embodiment 484. The method of Embodiment 477, wherein the reduction of the elevated level of Pb2+content in the body is measured by a reduction of Pb2+concentration in the blood.

[0655] Embodiment 485. The method of Embodiment 484, wherein the reduction of Pb2+concentration in the blood is at least a two-fold reduction.

[0656] Embodiment 486. The method of Embodiment 485, wherein the reduction of Pb2+concentration in the blood is at least a five-fold reduction.

[0657] Embodiment 487. The method of Embodiment 486, wherein the reduction of Pb2+concentration in the blood is at least a ten-fold reduction.

[0658] Embodiment 488. The method of any one of Embodiments 484 to 487, wherein the Pb2+concentration in the blood is reduced to less than 0.5 pg / dL.

[0659] Embodiment 489. The method of any one of Embodiments 433 to 488, wherein the Pb2+content in the body is measured by inductively coupled plasma (ICP) elemental analysis.

[0660] Embodiment 490. The method of any one of Embodiments 433 to 489, wherein the macroporous particulate titanate ion exchanger has a distribution coefficient (Ka) for Pb2+in a range of about 100,000 to about 2,500,000 milliliters per gram (mL / g).

[0661] Embodiment 491. The method of Embodiment 490, wherein the macroporous particulate titanate ion exchanger has a Ka for Pb2+of about 967,800.

[0662] Embodiment 492. The method of Embodiment 490, wherein the macroporous particulate titanate ion exchanger has a Ka for Pb2+of about 321,900.

[0663] Embodiment 493. The method of any one of Embodiments 433 to 492, wherein the macroporous particulate titanate ion exchanger comprises in a range of 0.01% to 4.0% weight per weight (w / w) of the MHCA.

[0664] Embodiment 494. The method of Embodiment 493, wherein the particulate metal titanate ion exchanger comprises in a range of 0.01% to 0.6% w / w of the MHCA.

[0665] Embodiment 495. The method of any one of Embodiments 433 to 494, wherein m is about 0.28.

[0666] Embodiment 496. The method of any one of Embodiments 433 to 495, wherein the subject in need thereof suffers from chronic or acute lead poisoning.

[0667] Embodiment 497. The method of Embodiment 496, wherein one or more symptoms of lead poisoning are reduced or eliminated after the administering.

[0668] Embodiment 498. The method of Embodiment 497, wherein the one or more symptoms of lead poisoning are selected from the group consisting of high blood pressure, abdominal pain, joint pain, constipation, nausea, vomiting, fatigue, hyperactivity, irritability, mood disorder, headache, insomnia, lack of concentration, memory loss, reduced sperm count, hearing loss, seizure, and any combination thereof.

[0669] Embodiment 499. The method of any one of Embodiments 433 to 498, wherein normal physiological levels of any one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration.

[0670] Embodiment 500. The method of Embodiment 499, wherein the physiological levels of the one or more ions are measured in the blood of the subject in need thereof.

[0671] Embodiment 501. The method of Embodiment 499, wherein the physiological levels of the one or more ions are measured in the urine of the subject in need thereof.

[0672] Embodiment 502. The method of Embodiment 499, wherein the physiological levels of the one or more ions are measured in the feces of the subject in need thereof.

[0673] Embodiment 503. The method of any one of Embodiments 433 to 502, wherein the human subject in need thereof is a human adult or a human child.

[0674] Embodiment 504. Use of a particulate metal titanate ion exchanger for the manufacture of a medicament for treating, ameliorating, or reducing the severity of lead poisoning in a subject in need thereof, the particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTixMyOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85,wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl -containing complexing agent (MHCA), and wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm).

[0675] Embodiment 505. The use of Embodiment 504, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0676] Embodiment 506. The use of Embodiment 504 or Embodiment 505, wherein A is potassium ion, hydronium ion, or a mixture thereof.

[0677] Embodiment 507. The use of any one of Embodiments 504 to 506, wherein A is potassium ion.

[0678] Embodiment 508. The use of any one of Embodiments 504 to 506, wherein A is hydronium ion.

[0679] Embodiment 509. The use of any one of Embodiments 504 to 506, wherein A is a mixture of potassium and hydronium ions.

[0680] Embodiment 510. The use of any one of Embodiments 504 to 509, wherein the particulate metal titanate ion exchanger is a polycrystalline aggregate metal titanate ion exchanger.

[0681] Embodiment 511. The use of any one of Embodiments 504 to 510, wherein the particulate metal titanate ion exchanger has a spherical morphology or an amorphous morphology.

[0682] Embodiment 512. The use of any one of Embodiments 504 to 511, wherein the median particle size is in a range of 25 to 125 microns (pm).

[0683] Embodiment 513. The use of any one of Embodiments 504 to 512, wherein the particulate metal titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of greater than 150 square meters per gram (m2 / g).

[0684] Embodiment 514. The use of any one of Embodiments 504 to 513, wherein the particulate metal titanate ion exchanger comprises in a range of 0.01% to 4.0% weight per weight (w / w) of the at least one M14CA.

[0685] Embodiment 515. The use of any one of Embodiments 504 to 514, wherein the at least one MHCA is selected from the group consisting of d-sorbitol, mannitol, xylitol, catechol, fructose, glucose, and mixtures thereof.

[0686] Embodiment 516. The use of Embodiment 515, wherein the at least one MHCA is d- sorbitol.

[0687] Embodiment 517. The use of any one of Embodiments 504 to 516, wherein x is 1 and y is 0.

[0688] Embodiment 518. The use of any one of Embodiments 504 to 517, wherein m is in a range of 0.10 to 0.50.

[0689] Embodiment 519. The method of Embodiment 518, wherein m is about 0.40.

[0690] Embodiment 520. The method of Embodiment 518, wherein m is about 0.30.

[0691] Embodiment 521. The method of Embodiment 518, wherein m is about 0.28.

[0692] Embodiment 522. The use of any one of Embodiments 504 to 521, wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to administration of the medicament to the subject in need thereof.

[0693] Embodiment 523. The use of Embodiment 522, wherein the elevated level of Pb2+content in the body is reduced after the administration.

[0694] Embodiment 524. The use of Embodiment 523, wherein the reduction of the elevated level of Pb2+content in the body is measured by excretion of Pb2+in the feces.

[0695] Embodiment 525. The use of Embodiment 524, wherein the amount of Pb2+content excreted in the feces is greater than a pretreatment excretion level of Pb2+.

[0696] Embodiment 526. The use of Embodiment 525, wherein the amount of Pb2+content excreted in the feces is at least 100%, at least 200%, or at least 1000% greater than the pretreatment excretion level of Pb2+.

[0697] Embodiment 527. The use of Embodiment 525 or Embodiment 526, wherein the pretreatment excretion level is less than 2 parts per million (ppm).

[0698] Embodiment 528. The use of any one of Embodiments 522 to 527, wherein the elevated level of Pb2+content in the body is measured by inductively coupled plasma (ICP) elemental analysis.

[0699] Embodiment 529. The use of any one of Embodiments 522 to 528, wherein the administration is for at least 7 days, at least 6 weeks, at least 6 months, at least one year, or at least two years.

[0700] Embodiment 530. The use of any one of Embodiments 504 to 529, wherein the particulate metal titanate ion exchanger has a distribution coefficient (Ka) forPb2+in a range of about 50,000 to greater than 5,500,000 milliliters per gram (mL / g).

[0701] Embodiment 531. The method of Embodiment 530, wherein the particulate metal titanate ion exchanger has a Ka for Pb2+in a range of about 100,000 to about 2,500,000 mL / g.

[0702] Embodiment 532. The use of any one of Embodiments 504 to 531, wherein the subject in need thereof is a human.

[0703] Embodiment 533. Use of a particulate metal titanate ion exchanger for the manufacture of a medicament for reducing an elevated level of Pb2+in a human subject in need thereof, the particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTixMyOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0.10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1 ; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl-containing complexing agent (MHCA), and wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm), and wherein the subject in need thereof comprises an elevated level of Pb2+prior to the administering.

[0704] Embodiment 534. The use of Embodiment 533, wherein the particulate metal titanate ion exchanger is an acid-treated particulate metal titanate ion exchanger.

[0705] Embodiment 535. The use of Embodiment 533 or Embodiment 534, wherein A is potassium ion, hydronium ion, or a mixture thereof.

[0706] Embodiment 536. The use of any one of Embodiments 533 to 535, wherein A is potassium ion.

[0707] Embodiment 537. The use of any one of Embodiments 533 to 535, wherein A is hydronium ion.

[0708] Embodiment 538. The use of any one of Embodiments 533 to 535, wherein A is a mixture of potassium and hydronium ions.

[0709] Embodiment 539. The use of any one of Embodiments 533 to 538, wherein the particulate metal titanate ion exchanger is a polycrystalline aggregate metal titanate ion exchanger.

[0710] Embodiment 540. The use of any one of Embodiments 533 to 539, wherein the particulate metal titanate ion exchanger has a spherical morphology or an amorphous morphology.

[0711] Embodiment 541. The use of any one of Embodiments 533 to 540, wherein the median particle size is in a range of 25 to 125 microns (pm).

[0712] Embodiment 542. The use of any one of Embodiments 533 to 541, wherein the particulate metal titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of greater than 150 square meters per gram (m2 / g).

[0713] Embodiment 543. The use of any one of Embodiments 533 to 542, wherein the particulate metal titanate ion exchanger comprises in a range of 0.01% to 4.0% weight per weight (w / w) of the at least one MHCA.

[0714] Embodiment 544. The use of any one of Embodiments 533 to 543, wherein the at least one MHCA is selected from the group consisting of d-sorbitol, mannitol, xylitol, catechol, fructose, glucose, and mixtures thereof.

[0715] Embodiment 545. The use of Embodiment 544, wherein the at least one MHCA is d- sorbitol.

[0716] Embodiment 546. The use of any one of Embodiments 533 to 545, wherein m is in a range of 0.10 to 0.50.

[0717] Embodiment 547. The method of Embodiment 546, wherein m is about 0.40.

[0718] Embodiment 548. The method of Embodiment 546, wherein m is about 0.30.

[0719] Embodiment 549. The method of Embodiment 546, wherein m is about 0.28.

[0720] Embodiment 550. The use of any one of Embodiments 533 to 549, wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to administration of the medicament to the subject in need thereof.

[0721] Embodiment 551. The use of Embodiment 550, wherein the elevated level of Pb2+content in the body is reduced after the administration.

[0722] Embodiment 552. The use of Embodiment 551, wherein the reduction of the elevated level of Pb2+content in the body is measured by excretion of Pb2+in the feces.

[0723] Embodiment 553. The use of Embodiment 552, wherein the amount of Pb2+content excreted in the feces is greater than a pretreatment excretion level of Pb2+.

[0724] Embodiment 554. The use of Embodiment 553, wherein the amount of Pb2+content excreted in the feces is at least 100%, at least 200%, or at least 1000% greater than the pretreatment excretion level of Pb2+.

[0725] Embodiment 555. The use of Embodiment 553 or Embodiment 554, wherein the pretreatment excretion level is less than 2 parts per million (ppm).

[0726] Embodiment 556. The use of any one of Embodiments 550 to 555, wherein the elevated level of Pb2+content in the body is measured by inductively coupled plasma (ICP) elemental analysis.

[0727] Embodiment 557. The use of any one of Embodiments 550 to 556, wherein the administration is for at least 7 days, at least 6 weeks, at least 6 months, at least one year, or at least two years.

[0728] Embodiment 558. The use of any one of Embodiments 533 to 557, wherein the particulate metal titanate ion exchanger has a distribution coefficient (Ka) forPb2+in a range of about 50,000 to greater than 5,500,000 milliliters per gram (mL / g).

[0729] Embodiment 559. The method of Embodiment 558, wherein the particulate metal titanate ion exchanger has a Ka for Pb2+in a range of about 100,000 to about 2,500,000 mL / g.

[0730] Embodiment 560. The use of any one of Embodiments 533 to 559, wherein the subject in need thereof is a human.EXAMPLES

[0731] The x-ray patterns presented in the following examples were obtained using standard x-ray powder diffraction techniques. The radiation source was a high-intensity, x-ray tubeoperated at 45 kV and 35 mA. The diffraction pattern from the copper K-alpha radiation was obtained by appropriate computer-based techniques. Flat compressed powder samples were continuously scanned at 2° to at least 56° (29). Interplanar spacings (d) in Angstrom units were obtained from the position of the diffraction peaks expressed as 9 where 9 is the Bragg angle as observed from digitized data. Intensities were determined from the integrated area of diffraction peaks after subtracting background, “Io” being the intensity of the strongest line or peak, and “I” being the intensity of each of the other peaks.

[0732] As will be understood by those skilled in the art, without being limited by theory, the determination of the parameter 29 is subject to both human and mechanical error, which in combination can impose an uncertainty of about ±0.4° on each reported value of 29. This uncertainty is also manifested in the reported values of the d-spacings, which are calculated from the 29 values. This imprecision is general throughout the art and is not sufficient to preclude the differentiation of the present crystalline materials from each other and from the compositions of the prior art. In the x-ray patterns reported, the relative intensities of the d-spacings are indicated by the notations vs, s, m, and w which represent very strong, strong, medium, and weak, respectively. In terms of 100 x I / Io, the above designations are defined as: w > 0-15; m > 15-60: s > 60-80 and vs > 80-100

[0733] In certain instances, the purity of a synthesized product may be assessed with reference to its x-ray powder diffraction pattern. Thus, for example, if a sample is stated to be pure, it is intended only that the x-ray pattern of the sample is free of lines attributable to crystalline impurities, not that there are no amorphous materials present.

[0734] Additionally, while elemental analyses can be used to determine the metal stoichiometry, the elements oxygen and hydrogen and water are not determined by this analysis method. Oxygen stoichiometry is inferred by balancing the charges on the metals, thus the compositions of the present disclosure are described in their anhydrous state.Examples 1 - 15: Synthesis of Metal Titanates from Solution

[0735] Examples 1 - 15 provides examples of the synthesis of Metal Titanate ion exchangers of the present disclosure from homogenous solution. In an aspect, a process uses three different complexing agents, hydrogen peroxide to provide initial dissolution of Ti in acidic solution, a second complexing agent like citric acid to help Ti and the M metals remain in solution as the pH is increased to about 10, and an MHCA agent like d-sorbitol that will stabilize Ti and the M metals in homogenous solution at very high pHs appropriate for the synthesis of the metal titanate ion exchangers. Within each reaction mixture it is demonstrated that structure often changes with reaction conditions, choice of alkali, perturbations with alkali, and ion exchange. Examples that include more than one X-ray diffraction pattern yield more than one crystal structure from the described reaction mixture, depending on reaction conditions elicited in the given example, showing the diversity of structural outcomes from this synthetic approach. Results include large polycrystalline aggregate morphologies in the product, which are further addressed in Examples 26 and 27.Examples 1A & IB

[0736] A Teflon beaker containing 90.00 g deionized water is fitted with an overhead mixer. With vigorous stirring, 21.11 g H2O2 (30 wt. %), 17.89 g citric acid and 16.96 g d-sorbitol were added and dissolved. Then 13.35 g Ti(OiPr)4 (16.7% Ti) is added fast dropwise forming a dark red-orange solution after stirring for 2 minutes post addition. Separately, 38.00 g NaOH (98%) is dissolved in 75.00 g deionized water and allowed to stir and cool. This NaOH solution is added fast dropwise with vigorous stirring, forming a clear, nearly colorless solution after going through a series of color changes. The highly basic clear solution is distributed among 4 Teflon- lined reaction vessels and digested quiescently at 175 and 190°C for 49 and 166 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. Powder X-ray Diffraction (PXRD) is used to characterize the products. Characteristic diffraction lines for the Example 1 A (175°C / 49 hr) and Example IB (190°C / 166 hr) products are provided in Table 1.Table 1Example 1A Example IB9.06 9.75 vs (br) 9.70 9.11 vs (br)24.32 3.66 m (br) 24.20 3.68 m (br)28.14 3.17 m (br) 28.54 3.12 vs (br)48.22 1.89 s (br) | 48.34 1.88 s (br)Example 2

[0737] A Teflon beaker containing 90.00 g deionized water is fitted with an overhead mixer. With vigorous stirring, 21.11 g H2O2 (30 wt. %), 17.89 g citric acid, and 16.96 g d-sorbitol are added resulting in a clear colorless solution. Then 13.35 g Ti(OiPr)4 (16.7% Ti) is added fast dropwise to form a dark orange-red solution. Separately, 59.97 g KOH (87.1%) is dissolved in 100.00 g deionized water and allowed to stir and cool. The KOH solution is added fast dropwise with vigorous stirring forming a clear nearly colorless solution with a slight yellow tint after going through a series of color changes. The highly basic clear solution is distributed among 4 Teflon-lined reaction vessels and digested quiescently at 175 and 190°C for 49 and 166 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products, and characteristic diffraction lines for Example 2 (190°C / 49 hr) are provided in Table 2.Table 22-0 d(A) I / Ip%10.44 8.47 vs23.91 3.72 w28.18 3.16 vs47.66 1.91 m48.75 1.87 wExamples 3A & 3B

[0738] A 34iter polypropylene beaker is charged with 450.00 g deionized water and placed under an overhead mixer. With vigorous mixing, 158.71 g H2O2 (30 wt.%), 67.24 g citric acid, and 63.76 g d-sorbitol are added and dissolved. Separately, 171.43 g NaOH (98%) is dissolved in 250.0 g deionized water and allowed to stir and cool. Then 100.32 g Ti(OiPr)4 (16.7 % Ti) is added to the 3 -liter beaker, forming an orange-red solution with some precipitate that dissolved with stirring. The NaOH solution is added in 3 aliquots, allowing the reaction mixture to stir and cool after each aliquot added. The final reaction mixture is a highly basic, slightly yellow solution. The reaction mixture is placed in a Teflon-lined 2 L Parr reactor and digested quiescently at 175°C for 160 hr at autogenous pressure. The solid product is isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used tocharacterize the product. Characteristic diffraction lines for the Example 3 A product are shown in Table 3 below. Elemental analysis via ICP yields the empirical metals composition Nao.36Tii.oo for the Example 3A material.

[0739] A 2.0 g portion of the product is ion-exchanged using 0.5 M Mg(NOa)2 solution (100 mb) at room temperature. The exchange is carried out 3 times before washing the product with deionized water and drying in air. The Example 3B product is characterized by PXRD, and characteristic diffraction lines are provided in Table 3. The Mg2+exchanged product exhibits a different XRD pattern and has higher crystallinity than the parent.Table 3Example 3A Example 3B, Mg2+IX2-0 d(A) I7Io% 2-0 d(A) EIo%9.02 9.80 Vs 7.86 1 1.24 vs24.22 3.67 M 15.76 5.62 m28.68 3.11 M 17.90 4.95 w48.26 1.88 M 24.22 3.67 w26.38 3.38 w48.44 1.85 mExamples 4 A & 4B

[0740] This example provides an example of an alteration of the metal titanate structure via perturbation of what is similar to the Example 2 solution reaction mixture with LiCl. A Teflon beaker is charged with 90.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 21.11 g H2O2 (30 wt. %), 17.89 g citric acid, and 16.96 g d-sorbitol are added and dissolved. Next, 13.35 g Ti(OiPr)4 (16.7% Ti) is added fast dropwise forming a red-orange solution within minutes after the addition was complete. Separately, 59.99 g KOH (87.1%) is dissolved in 77.17 g deionized water and allowed to stir and cool. The KOH solution is added fast dropwise to the reaction mixture resulting in a clear, colorless solution. Separately, 3.95 g LiCl is dissolved in 12.00 g deionized water. This solution is added dropwise while vigorously stirring the reaction mixture, which remains a clear, colorless solution. The highly basic, clear solution is distributed among 8 Teflon-lined reaction vessels and digested quiescently at 125, 150, 175 and 190°C for 52 and 168 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used tocharacterize the products. Characteristic diffraction lines for the Example 4A (150°C / 52 hr) and Example 4B (190°C / 168 hr) products are provided in Table 4.Table 4Example 4 A Example 4B2-0 d(A) VIo% 2-0 d(A) EIo%10.68 8.28 vs 11.10 7.96 vs23.94 3.71 w 23.98 3.71 w28.44 3.14 s 28.82 3.10 vs31.75 2.82 w 32.15 2.78 w36.92 2.43 s 37.74 2.38 m38.54 2.33 w 43.38 2.08 s44.52 2.03 m 47.60 1.91 m47.62 1.91 m49.00 1.86 w54.96 1.67 mExamples 5 A & 5B

[0741] A Teflon beaker is charged with 90.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 21.11 g H2O2 (30 wt. %), 17.89 g citric acid, and 16.96 g d-sorbitol are added and dissolved. Next, 3.76 g Fe(NO3)3*9H2O solid is added slowly forming a yellow solution. This is followed by the fast dropwise addition of 10.68 g Ti(OiPr)4 (16.7% Ti), yielding a dark red-orange solution. Separately, 38.01 g NaOH (98%) is dissolved in 77.17 g deionized water and allowed to stir and cool. The NaOH solution is added fast dropwise, during which the reaction mixture changed color to a brownish solution. The highly basic clear solution is distributed among 8 Teflon-lined reaction vessels and digested quiescently at 125, 150, 175 and 190°C for 55 and 171 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 5A (15O°C / 55 hr) and Example 5B (190°C / 171 hr) products are provided in Table 5. Elemental analysis via ICP yields the empirical composition with metals stoichiometry Nao 25Feo2oTio 8o for the Example 5B material.Table 5_ Example 5A _ Example 5B _ 2-0 d(A) VIo% 2-0 d(A) VIo%84)2 11.02 vs <400 vs24.42 3.64 w 19.60 4.52 w28.04 3.18 s 24.15 3.68 m33.72 2.66 m 28.02 3.18 m38.46 2.34 m 29.73 3.00 w48.00 1.89 s 33.46 2.68 w39.12 2.30 w39.76 2.27 w46.56 1.95 w48.44 1.88 w49.50 1.84 wExamples 6 A & 6B[00742J A Teflon beaker is charged with 75.00 g deionized water and placed under an overhead stirrer. With vigorous stirring, 15.85 g H2O2 (30 wt. %) and 17.89 g citric acid are added and dissolved. This is followed by the fast dropwise addition of 10.68 g Ti(OiPr)4 (16.7% Ti) yielding a dark red-orange solution. Next, 3.76 g Fe(NO )3*9H2O solid is added slowly, forming a brownish-yellow solution. Then 16.96 g d-sorbitol is added, which dissolves while stirring. Separately, 30.41 g NaOH (98%) is dissolved in 50.85 g deionized water and allowed to stir and cool. The NaOH solution is added fast dropwise to the reaction mixture, during which the color largely remains the same, and a dark brown-yellow solution results. The highly basic, clear solution is distributed among 6 Teflon-lined reaction vessels and digested quiescently at 125, 150, and 175°C for 52 and 168 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 6A (150°C / 52 hr) and Example 6B (175°C / 168 hr) products are provided in Table 6. Elemental analysis via ICP yields the empirical composition with metals stoichiometry Nao.28Feo.i8Tio.82 for the Example 6B material.Table 6Example 6 A _ Example 6B2-0 d(A) vio% 2-0 d(A) vio%8.12 10.88 100 8.04 10.99 w (sh)24.49 3.63 3.6 9.02 9.80 vs28.26 3.16 23.2 9.65 9.16 m (sh)33.61 2.66 6.7 24.20 3.68 s38.34 2.35 4.1 27.94 3.19 vs47.94 1.90 31.3 33.48 2.67 s39.12 2.30 s48.32 1.88 m49.42 1.84 wExamples 7A & 7B

[0743] A Teflon beaker is charged with 75.00 g deionized water and placed under an overhead stirrer. With vigorous stirring, 13.47 g H2O2 (30 wt. %), 19.02 g citric acid, and 18.02 g d-sorbitol are added and dissolved. Next, 8.52 g Ti(OiPr)4 (16.7% Ti) is added fast dropwise resulting in a dark orange-red solution. Separately, 8.00 g Fe(NOs)3*9H2O is dissolved in 15.00 g deionized water. This solution is added to the reaction mixture dropwise over a period of 3 minutes, and the reaction mixture remains a dark orange-red solution. Separately, 40.41 g NaOH (98%) is dissolved in 43.80 g deionized water and allowed to stir and cool. This solution is added to the reaction mixture fast dropwise, during which a dark brown color develops. Stirring postaddition, the reaction mixture becomes a clear dark red-brown solution. The highly basic, clear solution is distributed among 9 Teflon-lined reaction vessels and digested quiescently at 95, 125, 150, 175 and 190°C for 48 and 169 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 7A (150°C / 169 hr) and Example 7B (190°C / 48 hr) products are provided in Table 7. Elemental analysis via ICP yields the empirical metals stoichiometries Nao.24Feo.37Tio.63 for the Example 7A material and Nao.33Feo.38Tio.62 for the Example 7B material.Table 7Example 7 A Example 7B2-0 d(A) VIo% 2-0 d(A) VIo%7.72 11.44 vs 9.70 9.11 vs15.35 5.77 w 24.10 3.69 w24.75 3.59 w 27.90 3.20 m28.20 3.17 m 29.91 2.99 w33.70 2.66 m 33.40 2.68 w35.38 2.54 w 35.34 2.54 m38.18 2.36 m 39.22 2.30 m39.10 2.30 w 42.84 2.11 w43.48 2.080 w 46.59 1.95 w48.04 1.89 m 48.40 1.88 w50.03 1.82 w49.34 1.84 wExample 8

[0744] This is a further example that illustrates alteration of the metal titanate structure via perturbation of what is a potassium iron titanate solution reaction mixture with LiCl, even though potassium is present in large excess. A Teflon beaker is charged with 90.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 21.11 g H2O2 (30 wt. %), 17.89 g citric acid, and 16.96 g d-sorbitol are added and dissolved. Next, 3.76 g Fe(NO3)3*9H2O solid is added slowly, forming a yellow solution. This is followed by the fast dropwise addition of 10.68 g Ti(OiPr)4 (16.7% Ti), yielding a dark red-orange solution. Separately, 59.99 g KOH (87.1%) is dissolved in 77.17 g deionized water and allowed to stir and cool. This solution is added to the reaction mixture fast dropwise, resulting in a dark brown-red solution. Separately, 3.96 g LiCl is dissolved in 12.00 g deionized water and added dropwise to the reaction mixture, which remains a red-brown solution. The highly basic clear solution is distributed among 8 Teflon-lined reaction vessels and digested quiescently at 125, 150, 175 and 190°C for 53 and 169 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 8 (175°C / 169 hr) product are provided in Table 8.Table 82-0 d(A) EIo%10.58 8.36 vs24.02 3.70 w28.42 3.14 s31.68 2.82 w36.84 2.44 m38.63 2.33 w44.24 2.05 m47.84 1.90 w49.09 1.85 w54.84 1.67 wExample 9

[0745] A Teflon beaker is charged with 90.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 21.11 g H2O2 (30 wt. %), 17.89 g citric acid, and 16.96 g d-sorbitol are added and dissolved. Next, 3.00 g ZrOCh*8H2O solid is added slowly forming aclear, colorless solution. This is followed by the fast dropwise addition of 10.68 g Ti(OiPr)4 (16.7% Ti), yielding a dark red-orange solution. Separately, 38.01 g NaOH (98%) is dissolved in 77.17 g deionized water and allowed to stir and cool. The NaOH solution is added to the reaction mixture fast dropwise, initiating a series of color changes that ultimately became a clear, colorless solution. The highly basic clear solution is distributed among 8 Teflon-lined reaction vessels and digested quiescently at 125, 150, 175 and 190°C for 53 and 170 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 9 (150°C / 170 hr) product are provided in Table 9. Elemental analysis via ICP yields the empirical metals composition Nao.39Zro.o3Tio.97 for the Example 9 material.Table 92-0 d(A) J / Io%8.96 9.86 vs24.43 3.64 m28.18 3.16 w48.14 1.89 vsExample 10

[0746] A Teflon beaker is charged with 75.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 21.13 g H2O2 (30 wt. %), 17.89 g citric acid, and 16.96 g d-sorbitol are added and dissolved. Next, 4.24 g NH4NbO(Ox)2 (20.5 % Nb, Ox = oxalate) solid is added slowly forming a suspension. This was followed by the fast dropwise addition of 10.68 g Ti(OiPr)4 (16.7% Ti), yielding a dark red-orange solution. Separately, 38.01 g NaOH (98%) is dissolved in 50.85 g deionized water and allowed to stir and cool. The NaOH solution is added to the reaction mixture fast dropwise, initiating a series of color changes that become a clear yellow solution. The reaction mixture is stirred for 90 minutes before it is distributed among 6 Teflon- lined reaction vessels and digested quiescently at 125, 150, and 175°C for 65 and 169 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 10 (125°C / 65 hr) product are provided in Table 10.Table 102-0 d(A) VIo% 9.60 9.21 vs (br)24.25 3.67 m (br)28.21 3.16 s (br)48.02 1.89 s (br)Example 11

[0747] A Teflon beaker is charged with 75.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 21.13 g H2O2 (30 wt. %) and 17.89 g citric acid are added and dissolved. Next, 4.24 g NH4NbO(Ox)2 (20.5 % Nb, Ox = oxalate) solid is added slowly forming a suspension. Then 16.96 g d-sorbitol is added to the suspension, followed by the fast dropwise addition of 10.68 g Ti(OiPr)4 (16.7% Ti), yielding a dark red-orange solution / suspension. After stirring for an hour, the Ti / Nb reaction mixture is a red-orange solution. Separately, 59.98 g KOH (87.1%) is dissolved in 50.85 g deionized water and allowed to stir and cool. The KOH solution is added slow dropwise to the reaction mixture during which the color changes to light yellow. After the addition is completed, the reaction mixture is stirred an additional 90 minutes during which it remains a clear yellow solution. The highly basic clear yellow solution is distributed among 6 Teflon-lined reaction vessels and digested quiescently at 125, 150, and 175°C for 65 and 169 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 11 (150°C / 169 hr) product are provided in Table 11.Table 112-0 d(A) VIo%10.48 8.44 s23.84 3.73 w28.10 3.17 vs47.60 1.91 m48.88 1.86 wExample 12

[0748] A Teflon beaker is charged with 75.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 15.85 g H2O2 (30 wt. %) and 17.89 g citric acid are added and dissolved. This is followed by the fast dropwise addition of 10.68 g Ti(OiPr)4 (16.7% Ti) yielding a dark red-orange solution. Next, 3.76 g Fe(NO3)s*9H2O solid is added slowly forming a dark brown solution. Then 16.96 g d-sorbitol is added and dissolved and, with furtherstirring, the reaction mixture becomes a clear dark brown-yellow solution. Separately, 47.98 g KOH (87.1%) is dissolved in 50.85 g deionized water. This solution is added fast dropwise to the reaction mixture, yielding a clear dark brown solution with a slight red tint. The highly basic clear brown solution is distributed among 6 Teflon-lined reaction vessels and digested quiescently at 125, 150, and 175°C for 52 and 168 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 12 (175°C / 168 hr) product are provided in Table 12. Elemental analysis via ICP yields the empirical metals composition Ko 19Feo 29Tio71 for the Example 12 material.Table 129.70 9.11 vs19.39 4.57 w24.17 3.68 w27.74 3.21 m29.37 3.04 w33.44 2.68 w38.79 2.32 w48.30 1.88 w49.24 1.85 wExample 13

[0749] A Teflon beaker is charged with 100.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 27.21 g H2O2 (30 wt. %), 15.37 g citric acid, and 14.57 g d-sorbitol are added and dissolved. This is followed by the fast dropwise addition of 18.34 g Ti(OiPr)4 (16.7% Ti), yielding a dark red-orange solution. Next, 3.99 g solid Co(OAc)2*4H2O is added slowly to the reaction mixture, which becomes a red-purple solution. Separately, 39.18 g NaOH (98%) is dissolved in 44.16 g deionized water and allowed to stir and cool. This solution is added fast dropwise to the reaction mixture, yielding a dark black-green solution. The highly basic black-green solution is distributed among 9 Teflon-lined reaction vessels and digested quiescently at 95, 125, 150, 175 and 190°C for 55 and 171 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 13 (150°C / 171 hr) product are provided in Table 13. All products from the 150, 175and 190°C reactions exhibit this same XRD pattern. Elemental analysis via TCP on the 175°C / 171 hr product yields the empirical metals composition Nao.26Coo.20Tio.80.Table 137.72 11.44 vs15.40 5.75 w24.62 3.61 w28.04 3.18 m33.66 2.66 m38.16 2.36 m43.60 2.07 w47.80 1.90 m50.00 1.82 wExamples 14A & 14B

[0750] A I L Teflon beaker is charged with 320.00 g deionized water and placed under an overhead mixer in an ice bath. With vigorous stirring, 95.23 g H2O2 (30 wt. %), 53.80 g citric acid, and 51.01 g d-sorbitol are added and dissolved. This is followed by the fast dropwise addition of 64.20 g Ti(OiPr)4 (16.7% Ti), yielding some precipitation and a dark red-orange solution. The solids dissolve with further stirring. Next, 13.95 g Co(OAc)2*4H2O is slowly added to the reaction mixture and dissolve after 10 minutes of stirring. Separately, 137.14 g NaOH (98%) is dissolved in 184.56 g deionized water and placed in an ice bath. The cooled NaOH solution is added fast dropwise to the reaction mixture, forming a dark blue-green solution. The reaction mixture is stirred further, the clear solution becoming green with some blue tint by the time it reached room temperature. The highly basic green-blue solution is transferred to a 1 L Teflon-lined Parr reactor and digested quiescently at 150 °C for 168 hr at autogenous pressure. Solid product is isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the product. Characteristic diffraction lines for the Example 14A product are shown in Table 14. Elemental analysis via TCP yields the empirical metals composition Nao.40Coo.19Tio.8i.

[0751] A 2.0 g portion of the product is ion-exchanged using 0.5 M Mg(NCh 2 solution (100 m ) at room temperature. The exchange is carried out 3 times before washing the product with deionized water and drying in air. The Example 14B product is characterized by PXRD,characteristic diffraction lines are provided in Table 14. The Mg2+exchanged product exhibits a different XRD pattern and has higher crystallinity than the parent.Table 14Example 14A Example 14B2-Theta d(A) VI0% 2-Theta d(A) EI0%10.14 8.72 vs 7.84 11.26 vs20.33 4.36 w 15.82 5.60 m24.00 3.71 m 23.80 3.74 w28.12 3.17 s 26.28 3.39 m30.92 2.89 w 30.80 2.90 w33.66 2.66 m 31.94 2.80 w38.32 2.35 w 35.84 2.50 w39.66 2.27 m 41.08 2.20 w47.90 1.90 m 47.96 1.90 w49.14 1.85 w 50.62 1.80 w49.86 1.83 wExamples 15A & 15B

[0752] A Teflon beaker is charged with 100.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 27.21 g H2O2 (30 wt. %), 15.37 g citric acid, and 14.57 g d-sorbitol are added and dissolved. This is followed by the fast dropwise addition of 18.34 g Ti(OiPr)4 (16.7% Ti), yielding a dark red-orange solution. Next, 3.92 g solid Mn(OAc)2*4H2O is added slowly to the reaction mixture, which becomes a red-purple solution. Separately, 39.18 g NaOH (98%) is dissolved in 44.16 g deionized water and allowed to stir and cool. This solution is added fast dropwise to the reaction mixture, and initially yields a dark orange-brown solution that darkens to brown. The highly basic dark brown solution is distributed among 9 Teflon-lined reaction vessels and digested quiescently at 95, 125, 150, 175 and 190°C for 54 and 170 hr at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for the Example 15A (125°C / 170 hr) and Example 15B (150°C / 170 hr) products are provided in Table 15. Elemental analysis via ICP yields the empirical composition Nao.25Mno.2oTio.8o for the Example 15B material.Table 15_ Example 15A _ Example 15B _ 2-Theta d(A) VI0% 2-Theta d(A) EI0%8.74 10.11 vs 7.70 11.47 vs9.08 9.73 vs 8.51 10.38 m24.43 3.64 w 8.90 9.93 w27.94 3.19 m 15.33 5.78 w27.94 3.19 m 24.52 3.63 w33.62 2.66 w 28.06 3.18 m38.68 2.33 w 33.56 2.67 w47.80 1.90 m 38.10 2.36 w38.56 2.33 w43.52 2.08 w47.64 1.91 w49.96 1.82 wExamples 16 - 26: Synthesis of Metal Titanates from TiCh Powders and Formed TiCh Spheres

[0753] Performance of hydrogen peroxide and complexing agents, including at least one MHCA, in dissolving and stabilizing Ti-M-containing species in highly alkaline reaction mixtures, as well as facilitating the formation of the metal titanate ion exchange compositions, are further investigated by applying MHCAs in alkali hydroxide solutions to hydrothermally transform various solid TiCh sources, including TiCh powders and preformed spray dried TiCE spheres, to alkali titanate and alkali metal titanate ion exchangers. In the aspect of pure alkali titanates, only alkali hydroxide solutions containing the MHCA are required to carry out the transformation. In the aspect of incorporation of the M metals into the solid TiCh, the M metal is dissolved in the alkali hydroxide solution using a combination of complexing agents as seen in Examples 1 - 15, such as hydrogen peroxide, citric acid and a MHCA such as d-sorbitol; the citric acid is required to stabilize the M metal in moderately basic solution, while d-sorbitol keeps the M metal in solution as the reaction mixture is adjusted to the very high pH required to hydrothermally synthesize the metal titanate ion exchange composition. Similar to the homogenous solution approach provided in Examples 1 - 15, metal incorporation is seen, and the product consists of large polycrystalline particulates of desirable sizes, such that absorption in the gastrointestinal tract would be avoided. Examples 26 and 27 describe product particulate size.Synthesis of Spray Dried TiCh Spheres

[0754] Spray dried TiCL spheres are synthesized with the Yamato Spray Drier Model DL-41 . Typically, 500 grams of a slurry with 20 wt. % titanium dioxide powder in DI H2O is prepared.To 400 g of deionized water, 100 g of fumed TiCh powder (e.g., Degussa D-6000) is added while mixing with an overhead mixer at 500 RPM. The mixture is stirred for 10 minutes. The suspension is then Eiger milled for 15 minutes before spray drying. Larger agglomerates are removed by passing the suspension through a 100-mesh (150pm) sieve. The suspension is stirred continuously to avoid settling of particles. The spray drier chamber temperature reaches 110°C with a drying air flow of 80 SCFH. The aspirator flow is 0.8 cm3 / min with a 10 psi head pressure. The slurry feeding speed used for this process is 16 cc / min. The collected product is screened through 60-mesh (250pm), 100-mesh (150pm), and 200-mesh (75pm) sieves; the final sample collected has particles finer than 200-mesh (75pm). Spray dried TiCh spheres from a typical preparation are characterized in Example C5.Example 16

[0755] This preparation starts with a freshly precipitated titania source. In a IL flask equipped with an overhead stirrer, 192.5 g NH4OH (28% NH3) is diluted in 365.25 g deionized water with stirring. A dry pressure-equalizing dropping funnel is added and charged with 50.00 g TiCL. The TiCL is added dropwise and intermittently to avoid excessive heating of the reaction mixture. White solid forms in the flask, filling the flask by the end of the addition. The reaction mixture is stirred and cooled for an additional 45 minutes post addition before distributing the mixture into centrifuge bottles for isolation and washing with deionized water. The wet cake is stored in a sealed vessel, it contained 11.2% Ti. This is used as the starting material for the next step.

[0756] To a small beaker placed under an overhead stirrer, 10.74 g NaOH (98%) is dissolved in 34.77 g deionized water with stirring and allowed to cool. Then 1.45 g catechol is added, forming a green-yellow solution as it dissolved. Freshly precipitated titania (11.2% Ti) from the prep above is added, forming a greenish yellow suspension. After further stirring, the highly basic reaction mixture is distributed among 3 Teflon-lined reaction vessels and digested quiescently at 95 and 150°C for 96 hr, and at 190°C for 49 hr, at autogenous pressures. Solid products are isolated by centrifugation, washed with deionized water, and dried at room temperature. PXRD is used to characterize the products. Characteristic diffraction lines for theExample 16 (190°C / 49 hr) product are provided in Table 16. Elemental analysis via ICP yields the empirical metals composition Nao.37Ti1.oo for the Example 16 material.Table 162-0 d(A) I / Io%9.21 9.60 w (sh)9.82 9.00 vs15.86 5.58 w19.71 4.50 w24.96 3.56 w28.98 3.08 w29.46 3.03 m34.48 2.60 m35.08 2.56 m38.82 2.32 w42.80 2.11 w45.49 1.99 w48.38 1.88 w49.50 1.84 w52.66 1.74 w Example 17

[0757] A Teflon beaker is charged with 12.88 g of 8.5 M KOH solution. With magnetic bar stirring, 0.69 g catechol reagent is added and dissolved, creating a clear, light-brown solution. After 5 minutes of mixing, 1 g of TiO powder is added, rendering the mixture opaque. Reaction contents are mixed for 30 minutes resulting in a cream-brown opaque mixture. The highly basic solution is loaded into a Teflon-lined 45cc reaction vessel and digested at 200°C for 20 hours with tumbling (40 rpm) at autogenous pressure. The solid product is isolated via filtration, washed with copious amount of deionized water, and dried at 100°C. PXRD was used to characterize the product. Characteristic diffraction lines for the product are provided in Table 17. Elemental analysis via ICP yields the metals stoichiometry Ko.26Tii.oo. Table 172-0 d(A) I / Io%10.86 8.14 m24.11 3.69 m29.15 3.06 vs33.66 2.66 m42.94 2.10 m47.80 1.90 m59.15 1.56 w65.66 1.42 wExample 18

[0758] A Teflon beaker is charged with 5.00 g deionized water and placed under an overhead mixer. With vigorous stirring, 0.48 g citric acid, 1.60 g d-sorbitol, and 1.01 g Fe(NO3)3*9H2O are added and dissolved creating a clear purple solution. Next, with vigorous stirring, 14.12 g of a cooled 8.5 M KOH solution is added dropwise over 7 minutes resulting in a clear dark green solution. Finally, to the resulting dark green solution, 1.00 g TiO2 powder is added and allowed to homogenize over a 30-minute period. The resulting dark green, highly basic suspension is distributed into Teflon-lined 45 ml reaction vessels and digested quiescently at 200°C for 4 days at autogenous pressures. Solid product is isolated by centrifugation, washed with deionized water, and dried at 100°C. PXRD was used to characterize the product. Characteristic diffraction lines for the Example 18 product are provided in Table 18. Elemental analysis via ICP...

Claims

1. What is claimed is:

1. A method for treating, ameliorating, or reducing the severity of lead poisoning in a subject in need thereof comprising a step of administering a pharmaceutical composition to the subject in need thereof, the pharmaceutical composition comprising a therapeutically effective dose of particulate metal titanate ion exchanger having an empirical formula on an anhydrous basis of:AmTixMyOz whereinA is an exchangeable cation selected from the group consisting of potassium ion, sodium ion, lithium ion, calcium ion, magnesium ion, hydronium ion, and 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 mole ratio of A to total metal (total metal = Ti + M) and has a value from 0. 10 to 0.60; “x” is the mole fraction of total metal that is Ti and has a value from 0.5 to 1; “y” is the mole fraction of total metal that is M and has a value from zero to 0.5, wherein x + y = 1; and "z" is the mole ratio of O to total metal and has a value from 1.55 to 2.85, wherein the particulate metal titanate ion exchanger having been synthesized in the presence of at least one multihydroxyl -containing complexing agent (MHCA), wherein the particulate metal titanate ion exchanger exhibits a median particle size of greater than 3 microns (pm), and wherein the subject in need thereof comprises an elevated level of Pb2+content in the body prior to the administering.

2. The method of claim 1, wherein A is potassium ion, hydronium ion, or a mixture thereof.

3. The method of any one of claims 1-2, wherein the particulate metal titanate ion exchanger is a polycrystalline aggregate metal titanate ion exchanger.

4. The method of claim 4, wherein the particulate metal titanate ion exchanger is macroporous and has a spherical morphology.

5. The method of claim 4, wherein the particulate metal titanate ion exchanger is macroporous and has an amorphous morphology.

6. The method of any one of claims 1-2, wherein the median particle size is in a range of 25 to 125 microns (pm) and wherein less than 3% of the particles of the particulate metal titanate ion exchanger have a particle size of less than 3 microns (pm).

7. The method of any one of claims 1-2, wherein the particulate metal titanate ion exchanger has a Brunauer-Emmett-Teller (BET) surface area of greater than 150 square meters per gram (m2 / g).

8. The method of any one of claims 1-2, wherein the therapeutically effective dose is in a range of 1 to 2000 milligrams per kilogram per day (mg / kg / day).

9. The method of any one of claims 1-2, wherein the particulate metal titanate ion exchanger comprises in a range of 0.01% to 4.0% weight per weight (w / w) of the at least one MHCA.

10. The method of claim 1, wherein one or more symptoms of lead poisoning are reduced or eliminated after the administering, wherein normal physiological levels of any one or more ions selected from Na+, Mg2+, K+, and Ca2+are minimally disrupted in the subject in need thereof after the administration, and wherein the one or more symptoms of lead poisoning are selected from the group consisting of high blood pressure, abdominal pain, joint pain, constipation, nausea, vomiting, fatigue, hyperactivity, irritability, mood disorder, headache, insomnia, lack of concentration, memory loss, reduced sperm count, hearing loss, seizure, and any combination thereof.

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