US 2005O106267A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0106267 A1 Frykman et al. (43) Pub. Date: May 19, 2005

(54) ZEOLITE MOLECULAR SIEVES FOR THE Related U.S. Application Data REMOVAL OF TOXINS (60) Provisional application No. 60/512,395, filed on Oct. (75) Inventors: Gregory K. Frykman, Washington, DC 20, 2003. (US); Glenn H. Gruett, New London, WI (US) Publication Classification Correspondence Address: (51) Int. Cl...... A61K 33/06 FOLEY AND LARDNER (52) U.S. Cl...... 424/684 SUTE 500 3000 KSTREET NW WASHINGTON, DC 20007 (US) (57) ABSTRACT (73) Assignee: Framework Therapeutics, LLC Medical use of natural and Synthetic Zeolites for treatment, (21) Appl. No.: 10/965,799 prevention, and palliation in humans or animals of delete rious concentrations of ammonia, mercaptains, heavy metals (22) Filed: Oct. 18, 2004 and other toxins by oral administration.

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Patent Application Publication May 19, 2005 Sheet 2 of 3 US 2005/0106267 A1

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US 2005/0106267 A1 May 19, 2005

ZEOLITE MOLECULAR SEVES FOR THE Targeting Lead Paint Hazards; President’s Task Force on REMOVAL OF TOXINS Environmental Health Risks and Safety Risks to Children; Department of Health and Human Services and the Envi 0001. This application is based on U.S. Provisional ronmental Protection Agency; February, 2000) lead is most Patent Application No. 60/512,395, filed Oct. 20, 2003, the hazardous to the nation's 24 million children under six years entire contents of which are incorporated herein by refer old of which approximately 4.4% or 1 million have blood CCC. lead levels (BLL) >10 ug/dL. The spectrum and severity of 0002 The present invention relates to methods and com morbidity of lead poisoning increases as blood lead levels positions for treating, preventing, and palliating elevated increase: reduced IQ, decreased hearing, decreased growth levels of certain toxins in humans. and behavior problems in children can be observed at BLL as low as 10 ug/dL, impaired nerve function at 20 tug/dL, 0.003 Hepatic Encephalopathy Remains a Significant reduced Vitamin D metabolism at 30 lug/dL, damage to Health Problem hematopoiesis at 40 ug/dL, Severe Stomach cramps above 50 0004 Predominantly because of the large degree of alco tug/dL and Severe brain damage, kidney damage and Severe hol use in Society, chronic liver disease progressing to anemia between 50 and 100 tug/dL. Based on epidemiologi cirrhosis remains a burdensome health problem. While other cal models and estimates, a child is estimated to lose 2 IQ toxic liver insults are responsible to a lesser degree, the final (intelligence quotient) points for each 10 ug/dL increase in common pathway remains the Same: progressive hepatic blood lead level. fibrosis and decrease in the proportion of metabolically 0010 Current treatments include intravenous chelation active hepatocytes. These pathological changes result in therapy with EDTA (ethylenediamine tetraacetic acid) oral Systemic health effects related to poor detoxification of chelation therapy with drugs. Such as Succimer, penicillamine endogenously produced ammonia and exogenously admin and British anti-Lewisite (BAL). Chelation therapy with istered medications. Because of the cirrhotic liver's mark EDTA is indicated for severe lead poisoning and must be edly reduced ability to neutralize and remove ammonia, a administered-either three times daily or as a continuous natural waste product from the metabolism of proteins, its infusion-in combination with Succimer. Succimer, an oral blood level rises causing a decreased ability for affected drug, is administered on a Subchronic basis and is not patients to mentate, Sense and move normally. This decrease indicated for BLL <20 tug/dL. Penicillamine may also be in these functions when attributable to chronic liver disease used, but is known for a particularly troublesome side effect is known as hepatic encephalopathy. profile, which limits its chronic use. Additional details are 0005. It is estimated that the economic burden to society found below. related to just the costs of hospitalization for chronic liver disease is over S1 billion annually in the United States. A 0.011 EDTA (edetate, versenate; CAS 62-33-9) remains large portion of these costs is the daily charge for the difficult to administer despite its demonstrable lead-chelat hospital room; the average Stay is approximately 6 dayS. ing activity. It remains a component of Standard of care for Thus, if an intervention could be developed that would Severe cases of lead poisoning where rapid decrease in the decrease the average length of hospital stay and/or diminish BLL is desired and requires hospitalization. Key pharma the need for patients to be hospitalized, patients with chronic cological properties of EDTA include only intravenous administration and half-life of 20 to 60 minutes. Rapid liver disease would benefit and the economic burden to clearance results in only one-half the drug remaining one Society would decrease. hour following administration and only 5% of the adminis 0006 Current standard of care includes the use of Sup tered dose remains after 24 hours. The dose must be adjusted portive care (hydration, Vitamins, nutrition administered for decreased renal clearance. Substantial monitoring is parenterally, treatment of any gastrointestinal bleeding.) and required for cardiac changes, renal function and Serum the drug lactulose, a non-absorbed disaccharide that func electrolyte changes resulting in daily phlebotomy and tions to decrease the rate of absorption of and increase the attachment to a cardiac monitor. These precautions are rate of fecal elimination of ammonia. Lactulose, which is recommended because of potential decreases in Serum Zinc, Sold as a crystalline powder in a Single-dose plastic package, copper and iron, which are also chelated by EDTA. Because is inconvenient to use in the acute hospital Setting because EDTA may only be administered parenterally, local pain and of the need for Suspension/dissolution in a Sorbitol Solution. Swelling are a risk. Systemic adverse events include fever, Moreover, lactulose is only modestly effective and does not chills, malaise, nausea, Vomiting, anorexia, myalgias, appear to have been Subjected to randomized controlled arthralgias and a histamine-like reaction. Nephrotoxicity can trials prior to receiving marketing approval by the US Food manifest as acute tubular necrosis, microscopic hematuria, and Drug Administration. proteinuria and elevated blood urea nitrogen and Serum creatinine. The liver may be affected as evidenced by 0007 Lead Poisoning Remains a Significant Health transient mild elevations of the transaminases and the bone Problem marrow may also be affected as evidenced by the findings of 0008. Despite advances in the recognition and treatment anemia and thrombocytopenia. of clinical and Subclinical lead poisoning, a large number of 0012 Succimer (CHEMET, dimercaptosuccinic acid, children in the United States are considered lead poisoned. DMSA; CAS304-55-2) is a white crystalline powder with Effective therapy exists for lowering blood lead levels, an unpleasant odor and taste characteristic of mercaptains. It however the long-term adverse event risk of these treatments is administered orally in divided doses based on the size of limit their use, especially at the lower levels of blood lead. the patient thereby making administration easier and not 0009 AS taught in a recent government publication requiring hospitalization. It is indicated for blood lead levels (Eliminating Childhood Lead Poisoning: A Federal Strategy >45 lug/dL and is expressly not indicated for prophylaxis US 2005/0106267 A1 May 19, 2005

against lead poisoning in a lead laden environment. It is half-life is short Such that following intramuscular admin effective in reducing the blood lead level, although Several istration, dimercaprol is essentially all renally excreted features limit and complicate its use. It is recommended to within 4 hours. There are a number of pronounced and administer Succimer every 8 hours for the first 5 days dose-related Side effects which the amount or dimercaprol followed by twice daily for the next 14 days. A waiting that may be administered. Approximately 50% of patients period is recommended before a Second 19-day cycle should administered the 5 mg/kg dose will experience one of begin. Weekly monitoring of the blood counts is recom Several adverse events. Amongst the most common of the mended for proper management of the drug-induced neu Side effects is a rise in Systolic and diastolic blood preSSure tropenia. If the absolute neutrophil count decreases below by up to 50 mmHg. Nausea is commonly reported and to a 1200 ful, Succimer administration should stop until recov lesser degree Vomiting. Headache is reported less commonly ery to >1500 full. Drug-induced elevations of liver tran than nausea although further details about the headache are Saminases, which are mild and transient and Seen in up to not described in the references cited. A burning Sensation in 10% of patient, should be monitored for weekly. A particular the lips, mouth and throat accompanied with the feeling of toxicity in the form of recurrent mucocutaneous eruptions constriction is well known. Conjunctivitis, blepharospasm, has been described and requires cessation of therapy. SyS lacrimation, rhinorrhea and increased Salivation are also temic adverse events known with Succimer administration known to be associated with dimercaprol use. Other leSS include nausea, vomiting, diarrhea, anorexia, loose Stools, common Side effects include tingling of the feet and hands, metallic taste and occur Singly or in combination in up to abdominal pain, Sweating of the forehead and hands and 12% of children and 21% of adults. In addition, back pain, painful, Sterile abscesses at the injection Sites. Dimercaprol abdominal cramps, chills and flu-like Symptoms have been is known to cause hemolysis in patients with glucose-6- reported in 5% of children and 16% of adults. Succimer is phosphate dehydrogenase deficiency and a transient known to interact with various laboratory tests resulting in decrease in the percentage of polymorphonuclear leukocytes incorrect values of urine ketones, uric acid and creatine has been observed. The manufacturer recommends that the phosphokinase activity. urine be alkalinized to maintain the integrity of the metal 0013 Penicillamine (Cuprimine, D-Pen, beta,beta-dim drug complex during transport through the renal tubule. ethylcysteine, 3-mercaptovaline; CAS 52-67-5) is a chelat 0015. Although each of these interventions is effective at ing agent, which has found utility in treating Wilson's reducing the apparent blood level, following Such therapy, it disease, cystinuria and rheumatoid arthritis. It is a white, is well known that there is a rebound in the BLL, which crystalline powder, which is freely Soluble in water. Peni arises from unchelated tissue stores Such as the bone and Soft cillamine is known to interfere with normal tropocollagen tissues. There is at present no FDA-approved treatment for croSS-linking resulting in newly formed collagen fibrils, reducing the tissue Stores of lead. which are cleaved. To achieve maximum bioavailability and avoid chelation of metals within ingested foods or Vitamins, 0016 Wilson's Disease Contributes to the Burden of it is recommended that penicillamine be taken on an empty Heavy Metal Poisoning stomach 1 hour before or 2 hours after meals. Penicillamine 0017 Wilson's disease is a less common inborn error of is associated with a number of untoward reactions, which are copper metabolism in which the endogenous copper carrier potentially fatal. Serious blood dyscrasias including fatal protein, ceruloplasmin is decreased or absent. The result is aplastic anemia and fatal agranulocytosis have been elevated levels of tissue copper, which is responsible for the observed during chronic treatment and close monitoring of diseases neurological and hepatic complications. Effective white blood count, white cell differential and hemoglobin therapy exists; however, it is associated with moderate to are Strongly recommended by the manufacturer. Thromb Severe adverse effects that, in turn, limits its use. ocytopenia and eosinophilia are other hematological effects observed. Routine analysis of the urine is recommended to 0018. One additional treatment for Wilson's disease is the detect the insidious onset of proteinuria and microscopic use of Zinc acetate (Galzin). It acts on the intestinal epithe hematuria, which may be associated with the Goodpasture's lium to prevent the absorption of copper from dietary syndrome. Other adverse effects include several of the Sources, which is believed due to the Zinc ion by increasing described Subtypes of pemphigus (especially pemphigus the production of metallothionein in the enterocyte. Zinc foliaceous), increased skin friability at pressure points and acetate is administered orally in the form of gelatin capsules Sites of trauma, lupus-like Syndrome (not associated with though it should be separated from food and beverages by at hypcomplementemia) with elevated anti-nuclear antibody least one hour, preferably on an empty Stomach. Twenty-five (ANA) titer, aphthous ulceration of the oral mucous mem to 50 mg should be taken three times per day in adults and branes, myasthenia gravis and hypoguesia, or blunting of the Strict adherence to the Zinc regimen is essential for optimal Sense of taste. The manufacturer recommends close obser control of copper distribution. Zinc acetate is indicated for Vation and frequent follow-up of any patient receiving the maintenance of patients with Wilson's disease who have penicillamine. been initially treated with a chelating agent and is Specifi 0014) Dimercaprol (BAL, British anti-lewisite, 2,3- cally not recommended for the initial therapy of Symptom dimercapto-1-propanol; CAS 59-52-9) is a clear, colorless, atic patients because of the delay required for Zinc-induced Viscous oily fluid with a pungent odor typical of mercaptans. increase in enterocytic metallothionein and blockade of It is dissolved in and administered, intramuscularly, in copper uptake. Source: Galzin (Zinc acetate) package insert. peanut oil. Its mechanism of action appears to be complex 0019. As taught by Scheinberg (Scheinberg I H “Wil ation with and oxidation by heavy metal ions including lead, son's Disease” in Harrison's Principles of Internal Medi copper and arsenic. The dose administered is based on cine, 12" ed., Wilson J D, et al., eds, pp. 1843-1845) the achieving a 2:1 molar ratio of dimercaprol to the heavy prevalence of Wilson's disease is approximately 1/30,000 or metal and it may be used in combination with EDTA. The approximately 8700 individuals in the US with this disease. US 2005/0106267 A1 May 19, 2005

Clinical manifestations of copper exceSS are rare before age which the exposure took place (minutes, hours, days, weeks, 6 and half of untreated patients remain asymptomatic years or decades) and the degree of prior exposure to through adolescence. Liver manifestations of Wilson's dis arsenic. ease may include acute hepatitis, fulminant hepatitis, 0025 Adverse health effects of arsenic are legion and are chronic active hepatitis or cirrhosis. The only manifestation dependent on many of the factors listed above. Severe may be cirrhosis, which develops insidiously over decades. hemolysis followed by renal failure and death may compli Neurological or psychiatric disturbances may be the initial cate acute inhalational exposure to arsine gas (ASH). Hem presenting manifestation. orrhagic gastritis and gastroenteritis accompanied by nau 0020. The drug of choice is penicillamine and should be Sea, vomiting, diarrhea, convulsions and eventually death Started upon confirmation of the diagnosis and is adminis from circulatory collapse may occur within 12 to 24 hours tered in divided doses in conjunction with pyridoxine. of oral ingestion of arsenic trioxide (ASO) in the range of Additional information about the toxicity of penicillamine 1 to 3 mg/kg. There are also a number of neurologic Signs may be found above. It usually appears in the first 2 weeks and Symptoms that may be associated with oral arsenic and may cause a rash, fever, leukopenia, thrombocytopenia, trioxide exposure at the Same level including encephalopa lymphadenopathy and/or proteinuria. Penicillamine must be thy, headache, lethargy, confusion, hallucination, Seizure discontinued if these adverse events Supervene. Readminis and coma. Additional findings may include muscular tration with prednisone can be Successful. Lifelong and cramps, facial edema, cytopenias, renal insufficiency, pull continual treatment is required and non-compliance can be monary edema and hemorrhagic bronchitis. Electrocardio fatal. Successful treatment Suggests that continued copper graphic abnormalities Such as a prolonged QTc interval and lowering therapy could prevent virtually every manifesta T wave changes have been described. tion of Wilson's disease. Second-line therapy such as trien 0026 Chronic exposure may occur by the inhalational, tine is available for patients unable to tolerate penicillamine. oral, or dermal routes. Numerous organ Systems are affected 0021 Trientine hydrochloride (Syprine Capsules, causing a wide array of clinical Signs and Symptoms. Long bisaminomethylethanediamine dihydrochloride; CAS 112 term exposure may affect Small blood vessels, which can 24-3) is a white to pale yellow crystalline powder, which is manifest in Several different ways including Raynaud's freely Soluble in water. The mechanism appears to be phenomenon, acrocyanosis of the toes leading to gangrene increase cupriuresis though on a molar basis appears to be and Blackfoot disease requiring amputation. Post-mortem less effective than penicillamine. Trientine should be admin examination of children with cutaneous signs Suggesting istered on an empty Stomach at least one hour from ingestion arsenic exposure revealed marked thickening of Small- and of other drugs, food or milk. There have been reports of medium-sized arteries Specifically in the coronary, cerebral asthma, bronchitis and dermatitis following environmental and mesenteric arteries resulting in myocardial infarction in exposure to inhaled trientine. In addition, Systemic lupus 2 or 5 cases. Neurological signs and Symptoms are known to erythematosus, dystonia muscular spasm and myasthenia accompany Survivors of poisoning attempts including gravis have been reported in conjunction with trientine use. peripheral neuropathy and encephalopathy. The peripheral Other effects noted in four patients with biliary cirrhosis neuropathy begins as paresthesias, hyperesthesias and neu included heartburn, epigastric pain, thickening, fissuring and ralgias that may later develop into frank pain and muscle flaking of the skin, hypochromic microcytic anemia, acute weakneSS. Histopathological evidence of Wallerian degen gastritis, aphthous ulcers, myalgias, weakness and rhab eration exists, especially in the long-axon neurons. The domyolysis. findings tend to be bilaterally symmetrical. Recovery is slow and often incomplete. On clinical and electromyographic 0022 Arsenic Exposure and Arsenic Poisoning Is grounds, the diagnosis of arsenic-induced polyneuropathy Becoming More Frequently Diagnosed may be confused with Guillain-Barre syndrome. Workers from copper Smelters have noted a variety of upper respi 0023 Arsenic has recently become more widely dis ratory Signs and Symptoms-presumably from chronic inha cussed in the public media in terms of its exposure through lation of arsenic-laden Vapors and dusts-including rhinitis, drinking water. Although EPA limits for municipal water laryngitis and bronchitis. Extreme cases have resulted in Supplies exist, Some feel this level to be excessive. It appears perforation of the nasal Septum. Exposure in this same that the federal government will reduce the current 50 ppb context may results in a spectrum of gastrointestinal findings (parts per billion) limit to 10 ppb. In Some defined geo including nausea, vomiting, and diarrhea. Oral exposure graphic areas, extremely high levels of arsenic are found in may include the same findings in addition to abdominal pain. certain Wells. Chronic exposure to arsenic at elevated levels Hepatic injury is also known to correlate with chronic oral has been associated with skin diseases and Skin cancer. At arsenic exposure including Swollen and tender livers, eleva present, there are no FDA-approved treatments for chronic tions of hepatic enzymes, and may reveal portal fibrosis arsenic exposure. under histopathological examination. Renal effects of 0024. The health effects of arsenic are well known from arsenic are also known and include proteinuria, elevated Several Sources: epidemiological Studies, accidental expo creatinine, hematuria, pyuria and glycoSuria in patients with Sures, animal toxicological Studies and occupational and Sublethal oral exposure. therapeutic exposures. There are also a number of factors 0027) Although the specific mechanism has been con that must be considered when the toxicity Spectrum and Vincingly described, Several putative mechanisms have been Severity are reported. These include the form of the arsenic proposed for the finding of arsenic-induced anemia, leuko introduced in Vivo (inorganic VS. organic, Valence, the Salt penia and the myelodysplastic Syndrome. Arsenic may be form, the specific organic moiety), the route of exposure goiterogenic and diabetogenic. Skin effects of arsenic are (inhalational, transdermal, enteral or parenteral), the rate at well known and include both benign and malignant condi US 2005/0106267 A1 May 19, 2005

tions including hyperpigmentation interspersed with Small arsenic. Thus the invention relates to treatment, prevention, areas of hypopigmentation (the so-called "raindrop'-like and palliation in humans or animals of exceSS levels of lead, appearance) distributed on the neck, chest and back, palmar ammonia, copper, and arsenic, as well as other toxins. plantar hyperkeratosis with the characteristic Small corn-like elevations observed in Subjects exposed to arsenic through BRIEF DESCRIPTION OF THE DRAWINGS drinking water. Continued exposure may result in ulcerative lesions after Several decades. Basal cell carcinoma, epider 0033 FIG. 1 is a chart showing particle size distribution moid carcinomas, intraepidermal carcinomas and Bowen's for a Zeolite. disease associated with arsenic exposure are well described 0034 FIG. 2 is a chart showing the relationship between in the medical and epidemiological literature. Cancers of Zeolite particle size and ammonium absorption using a other organs have been reported to be found in patients Zeolite. living in near proximity to copper Smelters including kidney and bladder, in patients having received Fowler's Solution 0035 FIG.3 is an analysis of the effect of Zeolite particle (potassium arsenate) including lung cancer and in patients Size on ammonium absorption. exposed to high arsenic levels in their drinking water in Taiwan including bladder, kidney, liver, lung and colon DETAILED DESCRIPTION CCC. 0036) This invention relates specifically to a microporous or mesoporous Silicate, also known as a molecular Sieve, SUMMARY which is granular or powdered and which is administered 0028. The invention relates to a method of for treating, orally, topically or rectally to humans once, daily for Several preventing, and palliating elevated human blood lead levels, days, weeks, months or years, or more than once daily for comprising administering to a human in need thereof a days to years for the purpose of treating human diseases. The pharmaceutical formulation comprising a Synthetic Sodium Zeolitic Substance is administered in the form or a tablet, aluminosilicate and a pharmaceutically acceptable adjuvant, capsule or pharmaceutical Suspension. wherein: (a) the Synthetic Sodium aluminosilicate is particu 0037) Synthetic zeolites are preferred. As used herein, late and at least 90% of the particles are of particle size from “Synthetic Zeolite” means a Zeolite manufactured or Synthe about 90 um to about 150 um; (b) the formulation is sized by one or more chemical reactions involving breaking administered in doses of about 10 mg to about 1000 mg and/or making chemical bonds. "(W/w)” means percent by Sodium aluminosilicate. weight, as calculated based on the weight of the component 0029. The invention also relates to a method of treating, and the total weight of the composition or formulation. preventing, and palliating elevated human blood ammonia Generally, the terms used in this application are well known levels, comprising administering to a human in need thereof to perSons of skill in the art. a pharmaceutical formulation comprising a Synthetic Sodium 0038. The granules or powder particles are small enough aluminosilicate and a pharmaceutically acceptable adjuvant, that diffusion of a variety of ions or other organic or wherein: (a) the Synthetic Sodium aluminosilicate is particu inorganic toxins may freely pass in and through the rigid and late and at least 90% of the particles are of particle size from well-ordered crystalline structure. It is understood that water about 90 um to about 150 um; (b) the formulation is from may or may not comprise the Zeolitic material initially, but about 50% (w/w) to about 95% (w/w) water; and (c) the in an aqueous environment Such as the human digestive formulation is administered in doses of 2 g to 15 g Sodium tract, water will virtually completely fill the framework aluminosilicate. Structure. Based on the Specific details of the framework 0030 The invention also relates to a method including Structure, it has been shown that there is a Specificity of administering to a human in need thereof a pharmaceutical binding of ions, toxins and other classes of molecules. formulation comprising a Synthetic Sodium aluminosilicate 0039. In one embodiment, a gelatin capsule of the Zeolite and a pharmaceutically acceptable adjuvant, wherein: (a) the is Swallowed by a person with a glass of water. In the acidic Synthetic Sodium aluminosilicate is particulate and at least environment of the Stomach, the gelatin capsule dissolve 95% of the particles are of particle size from about 90 um to thereby releasing Several hundred milligrams of the Zeolite. about 150 um; (b) the formulation is administered in doses The Zeolite absorbs water to full Saturation and forms a of about 5 g to about 12 g Sodium aluminosilicate; and (c) Slurry. Aluminosilicates are known to be resistant to acidic the human has a higher than normal risk of elevated blood degradation at room temperature or body temperatures and levels of a toxic metal or has a higher than normal risk of therefore the framework Structure remains intact during hepatic encephalopathy. passage through the Stomach and is not Susceptible to the actions of oral cavity-, Stomach- or pancreas-, Small bowel 0031. The invention relates to a pharmaceutical formu and large-bowel-derived digestive enzymes and peristaltic lation, comprising: (a) a particulate Synthetic Sodium alu movements. In the intestinal juices found in the Stomach, minosilicate wherein at least 90% of the particles are of duodenum, jejunum, ileum and colon poisonous ions and particle size from about 90 um to about 150 um, (b) about toxins will bind to the Zeolite. These poisons or toxins 50% to about 80% by weight water; and (b) a microbial include heavy metals Such as lead, copper, potassium, preservative; and (c) a pharmaceutically acceptable adju ammonia, mercaptains and hydrogen Sulfide. Additional tox vant; wherein the formulation contains about 100 mg to ins include those that are plant-, marine organism- and about 10,000 mg by weight of sodium aluminosilicate. nuclear-derived. When a poisonous ion or molecule binds to 0.032 The invention also relates to methods and formu the Zeolite, it is prevented from exerting its toxic effects on lations identical to those described above, but targeting the intestinal lining or from being absorbed into the blood elevated levels of other toxins, in particular copper or Stream for Systemic deposition. An important feature is that US 2005/0106267 A1 May 19, 2005

Zeolites administered as described may be employed to remove toxic ions or molecules over the period of admin TABLE 1-continued istration of hours, days, weeks, months or years. The pur Recommended pose of the Zeolite is not only intended to prevent the Sieve Size (um) U.S. Sieve No. ASTM E-11* USP Sieves** deposition of toxic effects of a heavy metal or toxin that may 53 270 X be a contaminant of ingested food, but additionally it is 45 325 X X envisioned to be used in the emergency treatment of toxic Source: United States Pharmacopeia, 24 edition (USP 24/NF19), United ingestions, radioactive fallout (strontium and cesium), toxic States Pharmacopeial Convention, Inc., Rockville, MD; Method <786>, marine organism ingestions, poisoned food ingestions, etc. pp. 1969–1970. The Zeolite, which binds the adsorbed toxic ions or poison *American Society for Testing and Materials (ASTM) Specification E-11, U.S. Standard Sieve Series. Additional information may be found to ous Substances while coursing through the gastrointestinal ASTM procedure STP 447, “A Manual on Test Sieving Methods, avail tract, is eliminated from the body in the feces. An important able from the ASTM, 100 Bar Harbor Drive, West Conshohocken, PA 19428-2959 consideration is having the correct Surface area to weight **The equivalent ISO Standard sieves may be substituted. ratio for optimal absorption and minimal toxicity. If the Zeolite is powdered too finely, it could accumulate in unde 0041. The present invention relates to the use of Zeolite Sirable anatomical locations Such as the appendix or a molecular Sieves to bind, Sequester and eliminate heavy divertuculum, resulting in a pathologic condition. If the metals, potassium, ammonia and mercaptains, plant-, marine Zeolite is too large, the absorptive capacity as a function of organism- and fungus/mushroom-derived toxins, radioac weight decreases significantly and Substantially larger tive fallout contaminants and hydrogen Sulfide and hydrogen amounts of the Zeolite must be ingested to achieve the same Sulfide-related, endogenously produced chemicals from a amount of absorption. human that may be the Source of toxic effects. 0042. For treating, preventing, and palliating high blood 0040. The particle size distributions cited in this patent lead levels, preferably at least 95% of the particles are of are derived from a technique known as analytical Sieving. A particle size from 90 um to 150 lum. The formulation may full description may be found in the United States Pharma include from about 60% to about 95% by weight water. copeia, 24" edition (USP 24/NF 19) physical test number Preferably, the formulation is a capsule or tablet adminis <786> as described on pp. 1969-1970, Method 1, which was tered orally. The treatment is Suitable for a human Suffering followed to determine the particle size distribution of the from chronic lead poisoning. The human may have a blood CR-100 sodium aluminosilicate. The following table is lead level of at least about 10 ug/dL, at least about 20 tug/dL, illustrative. at least about 30 ug/dL, at least about 40 lig/dL, or even of at least about 50 tug/dL. The human may be between about TABLE 1. 2 and about 15 years of age, or may be under about 6 years of age. Dosages may be, e.g., about 10 mg to about 1000 mg Sodium aluminosilicate, or about 100 mg to about 900 mg, Recommended or about 200 mg to about 800 mg. Preferably, the formula Sieve Size (um) U.S. Sieve No. ASTM E-11* USP Sieves** tion further comprises an antimicrobial preservative or bac 4OOO 5 X X terioStat. 3350 6 X 0043. The present invention is preferably directed to 28OO 7 X X patients with blood lead levels of <10.0 ug/dL, 10.0-14.9 2360 8 X lug/dL, 15.0-19.9 tug/dL, 20.0-44.9 tug/dL, 45.0-59.9 tug/dL, 2OOO 1O X X or >60.0 lig/dL, in each case in combination with one or 1700 12 X more therapies recommended for use in the range by State or 1400 14 X X federal programs, as exemplified in the State of Minnesota 118O 16 X Department of Health’s Childhood Blood Lead Clinical 1OOO 18 X X Treatment Guidelines, March 2001. 850 2O X 710 25 X X 0044) For treating preventing, and palliating high human 6OO 3O X blood ammonia levels, preferably at least 95% of the par 500 35 X X ticles are of particle size from 90 um to 150 lum. The human 425 40 X may be Suffering from hepatic encephalopathy or cirrhosis 355 45 X X of the liver. The human may have a history of liver failure. 3OO 50 X Preferably the formulation is a liquid gel administered 250 60 X X orally. The human may have an elevated blood ammonia 212 70 X level or may be at risk for such an elevated level. The human 18O 8O X X may be a hospital in-patient. 150 1OO X 0045 While certain particle size ranges are preferred, this 125 12O X X is not meant to limit the Scope of the invention. For example, 106 140 X in certain circumstances very fine particles of <44 um may 90 170 X X be preferred. 75 2OO X 63 230 X X 0046) The term “elevated” blood lead level means a level of lead in the blood that is above normal, where normal is US 2005/0106267 A1 May 19, 2005

the Specified laboratory's normal range as determined on and reduce its consequences once established. The use of the blood from non-diseased, healthy volunteers in the local term prevention in this patent includes the following: pri area, using the local technique-of-choice for the laboratory mary prevention (which are actions directed towards pre performing the assay (which could include conventional venting the initial occurrence of a disorder); Secondary atomic absorption spectroScopy, graphite furnace atomic prevention (which are actions that seek to arrest or retard absorption spectroscopy, and anodic stripping Voltametry) existing disease and its effects through early detection and and processed according to the laboratory's procedure pre appropriate treatment); and tertiary prevention (which are cisely Specifying the type of collection container to use, actions intended to reduce the occurrence of relapses and the Specifying whether it should be placed immediately on ice, establishment of chronic conditions through, for example, the timeframe in which it is to be delivered to the laboratory, effective rehabilitation). and the use of a specified preservative, if any. A term 0051. “Palliation” means any form of medical care or frequently employed for the upper end of the normal range treatment that concentrates on reducing the Severity of the is the institutional upper limit of normal (IULN), and is Symptoms of a disease or slows its progreSS rather than intended to have the same meaning as normal for use in this providing a cure. It aims at improving quality of life, and patent. (Lewandrowski, pp. 820-821) particularly at reducing or eliminating pain. The definition 0047. By “hyerammonemia' or other terms used to indi Specifically focuses on the general unavailability of a cure in cate higher than normal levels of ammonia is meant higher that it emphasizes the active total care of patients whose levels than normal, where normal is the Specified laborato disease is not responsive to curative treatment. However, in ry's normal range as determined on blood from non-dis Some cases, palliation may involve alleviation of the Side eased, healthy Volunteers in the local area, using the local effects of curative treatments, Such as relieving the nausea technique-of-choice for that laboratory that performed the asSociated with chemotherapy. The term palliation is not assay (which could be venous blood, arterial blood, or Some intended for use in this patent to refer to a chronic disease, fraction of whole blood including plasma or Serum) and Such as diabetes which, although technically incurable, has processed according to the laboratory's procedure Specify available treatments that are (ideally) effective enough that ing whether it should be placed immediately on ice, the it is not considered a progressive or life-threatening disease timeframe in which it is to be delivered to the laboratory, in the same Sense as resistant or refractory cancer. using the Specified preservative, if any. A term frequently 0052 “Treatment” refers to the coordinated healthcare employed for the upper end of the normal range is the interventions and communications for individuals and popu institutional upper limit of normal (IULN), and is intended lations with disease conditions in which patient Self-care to have the Same meaning as normal for use in this patent. efforts are significant. The definition of treatment in this (Lewandrowski, pp. 733-735.) patent additionally refers to the identification of one or more 0.048. These definitions avoid the controversial nature of disease processes, use or modified use of evidence-based clinical laboratory assay performance which remains practice guidelines (when they exist), collaboration of phy unsettled for many reasons including that assay principles Sicians and Supportive-Service providers, patient Self-man vary; assay sites differ (hospital laboratory versus point-of agement education, outcome measurement, and communi care versus physician office laboratory versus home testing); cation with the patient and other relevant providers about the Specific reagents vary including proprietary reagents for outcome of the disease Stemming from the interventions commercially available assays, arterial or venous blood may applied. offer advantages or be specified by method; whole blood 0053. The present invention may also be used for the verSuS Specific fraction Such as plasma, Serum or erythro treatment of arsenic toxicity derived from arsenic trioxide cyte, Specific collection container that has been processed in therapy use in the treatment of acute promyelocytic leuke a specified manner; requirements exist for the Specific assay mia (APL). Although arsenic trioxide has been demonstrated for preservatives, special handling, temperature, and others, to be effective in the treatment of relapsed APL (one form of analytical instrument on which assay is performed may vary; acute myelogenous leukemia), cardiac conduction side Varying normal ranges for assay depending on geographical effects occur which appear to be related to the cumulative location; evolution of actual assay method based on the dose of arsenic administered and are exacerbated by other Same principle. Source: Lewandrowski K., ed. Clinical electrolyte abnormalities, Such as hypokalemia and hypo Chemistry: Laboratory Management and Clinical Correla magneSemia. If the electrolyte abnormalities are corrected tions, Lippincott Williams & Wilkins, 2002. and the patient continues to experienced a prolonged QTc 0049. For treating, preventing, and palliating high human (corrected QT) interval or abnormal heart rhythms or asso blood levels of copper or arsenic, the same methods and ciated rapid and irregular heartbeats develop, the manufac formulations may be used. Thus the invention relates to turer recommended that the drug be temporarily discontin treatment, prevention, and palliation in humans or animals ued until the QTc interval regresses to <460 milliseconds. of exceSS levels of lead, ammonia, copper, and arsenic, as Source: Trisenox (arsenic trioxide) package insert, March well as other toxins. 2001 revision. Because of sodium aluminosilicates’ ability to Selective bind metal and metalloid ions, Such Zeolites 0.050) “Prevention” means actions, which usually ema assist in the treatment of arsenic toxicity in the treatment of nate from the workers within the health sector that deals with APL. The present invention provides a formulation com individuals and populations identified as exhibiting identi prising a Synthetic aluminosilicate and arsenic trioxide with fiable risk factors for disease that may often be associated a pharmaceutically acceptable adjuvant, and a method for with different risk behaviors. Prevention also refers to mea treating APL by administering a Synthetic aluminosilicate Sures not only to mitigate against the occurrence of disease, together with arsenic trioxide whether formulated together Such as risk factor reduction, but also to arrest its progreSS or Separately. In this Setting, both acute and Subacute treat US 2005/0106267 A1 May 19, 2005 ment with 1-10 grams orally administered once to multiple may be used in the prevention, treatment, and palliation of times per day is envisioned. However, chronic therapy in the Alzheimer's disease, Specifically through the binding of range of 100-1000 milligrams once to several times per day gut-derived ammonia and preventing its uptake into the is possible. Systemic circulation and conferring its toxicity on the central nervous System over the course of many years. 0.054 Recently, arsenic trioxide, administered intrave nously, has become the FDA-approved Standard of care for 0058 A formulation containing the Zeolite may also relapsed acute promyelocytic leukemia (APL) following contain an antimicrobial preservative. The following Table therapy with all trans retinoic acid. Following conventional lists examples of antimicrobial preservatives Suitable for antineoplastic pharmaceutical development, it is likely that formulations of Zeolites intended for oral, gastric, enteral or arsenic trioxide use will become more common and be used rectal administration. earlier in the management of APL. Patients may achieve a complete remission of their disease, leaving them Suscep TABLE 2 tible to the health effects described above. At present, there is no described antidote for these effects beyond careful Antimicrobial Preservative Further Specification Reference monitoring and cessation of the therapy when complications benzalkonium chloride pp. 27-29 outweigh the benefit from continued treatment. benzoic acid pp. 32-34 benzyl alcohol pp. 35-37 0.055 Potassium regenerated sodium aluminosilicate is bronopol pp. 40-42 butylparaben pp. 49-5 an alternative for treatment of hepatic encephalopathy. An chlorhexidine as various salts pp. 106-110 important principle in the clinical management of hepatic chlorobutanol pp. 111-113 encephalopathy is treatment of the precipitating or underly chlorocresol pp. 114-116 ing cause of the encephalopathic episode. That is, while a cresol includes ortho-, meta- pp. 139-140 and para- isomers patient may have the established diagnosis of liver failure, ethanol pp. 7-9 only when his or her mental capacity declines is the diag ethylparaben b. 191-193 nosis of HE firmly established. However, often other dietary, imidurea includes monohydrate pp. 238-239 pharmacological, electrolyte or infectious influences alter methylparaben p. 310-313 phenol p. 336-337 the balance between normal mentation and encephalopathy. propionic acid as various salts pp. 459-461 Many times, however, the exacerbating factor is not deter propylparaben pp. 411-414 mined. While the treatment of HE remains Similar to that sodium benzoate pp. 433-435 described elsewhere in this Specification, Specific attention sorbic acid pp. 470-472 to the precipitating factor (Such as a large dietary load of triacetin pp. 534-535 protein, underlying infection, unexpected reaction from an Source: Wade A and Weller P.J. Handbook of Pharmaceutical Excipients, ingested drug or overuse of certain drugs leading to urinary 2d ed., American Pharmaceutical Association, Washington, DC; 1994 loss of potassium) is warranted by the treating physician. Because the use of the potassium-depleting drugs (namely 0059. The table below exemplifies microorganisms that Spironolactone and members of the same and different require reduction or eradication in a Zeolite formulation classes) is common in patients with liver failure, they can intended for oral, gastric, enteral or rectal administration. lead to total body loSS of potassium and thereby precipitate These include bacteria and fungi which are known to be an encephalopathic episode. The potassium form of Sodium more or leSS commonly pathogenic and are found in patients aluminosilicate may be used instead of the Sodium form to suffering from infections. It is therefore desirable to render treat patients with hepatic encephalopathy. In the manufac the Zeolite and associated pharmaceutical adjuvants Sterile turing process, potassium may be exchanged for Sodium in or with an acceptable low microorganism dose Such that the regeneration process. patients are not harmed. The list includes bacteria (gram 0056. The synthetic aluminosilicate is preferably charged positive, gram negative, anaerobic, aerobic, and others), with Sodium. Alternatively, the Synthetic aluminosilicate fungi and Spores in applicable species. may be charged with another alkali metal, e.g., Li, K, or Rb. The Synthetic aluminosilicate may alternatively be charged TABLE 3 with an alkali earth metals, e.g., Ca or Mg. The Synthetic Microorganisms aluminosilicate may be chemically modified by methods including pegylation, Silation, and glycosylation. The for Aeromonas aeorgenes Proteus vulgaris Aspergius niger Pseudomonas aeruginosa mulation may contain different particle Size distributions of Aspergius Oryzae Pseudomonas cepacia the Zeolite of interest, and may comprise mixtures of one or Bacilius cereus Pseudomonas fluorescens more Synthetic Zeolites. The formulation may contain vary Bacilius Subtilis Pseudomonas Stutzeri Candida albicans Rhizopus nigricans ing amounts of water, e.g., from about 40% or 50% (w/w) up Clostridium histolyticum Saccharomyces cerevisiae to about 70%, 80%, or 95%(w/w). Clostridium oedemnatiens Saimonelia enteritidis CloStridun Sporogenes Salmonella gallinarum 0057 The present invention may be used in diagnostic Clostridium tetani Salmonella paratyphi procedures, e.g., to determine the degree of metal poisoning, Clostridium weichi Salmonella typhosa as a carrier for X-ray contrast agents, gadolinium based Coynebacterium species Sarcina lutea magnetic resonance imaging contrast agents and positron Enterobacter cloacae Serratia narceScens Escherechia coli Shigella dysenteriae emitting metabolites for use in positron emission tomogra Klebsiella pneumoniae Staphylococcus aureus phy. The present invention may also be used to control Microsporum species Staphylococcus epidermidis diarrhea, especially in conjunction with lactulose in the Penicillium chrysogenium Streptococcus faecalis treatment of hepatic encephalopathy. The present invention US 2005/0106267 A1 May 19, 2005

0065) Leeper (U.S. Pat. No. 5,478,604) discloses a com TABLE 3-continued position and method for preventing lead intoxication by the use of a coating which contains polyethylene imine, a Microorganisms calcium compound and/or a Silicate that is applied to a Penicillium digitatum Streptococcus pyrogenes Surface which carries a coating of a lead based paint. The Penicillium notatum Trichoderma ignorum object of this invention is to reduce the digestion and Penicullium roqueforti Trichoderma mentagrophytes absorption of lead from the intestinal tract in case the lead Pityrosporum ovale Trichophyton mentagrophytes based paint is accidentally ingested. Specific features not Proteus mirabilis Vibrio cholerae found in this prior art is the use for treatment (as opposed to prevention) of lead poisoning, utility for heavy metals other 0060) Zeolites Offer an Unexploited Family of Sub than lead, months to years of administration, reduction of the stances to Remedy Hepatic Encephaolpathy and Heavy total body burden of lead and other heavy metals, and Metal Poisoning deliberate oral administration in the form of a capsule or 0061 Nagan (U.S. Pat. No. 6,190.561) discloses a tablet all with the goal of reversing partially or com method of water treatment using Zeolite crystalloid coagul pletely-adverse effects in heavy metal poisoned mammals. lants which is prepared by admixing aqueous Sodium Silicate Additional utility for the removal of ammonia, mercaptains and Sodium aluminate Solutions to form a reaction mixture and other plant-, marine organism- and nuclear-derived and allowing a reaction to proceed for a Sufficient time to toxins is not discussed. form a Zeolite crystalloid coagulant particles with Sizes of at 0.066 Perman and Schegel (U.S. Pat. No. 5,320,773) least 4 nanometers before the reaction is terminated. Dem disclose a composition and method for purifying water in the mel and Vierheilig (U.S. Pat. No. 6,103.949) disclose a form of a tablet containing betonite clay, attapulgite clay, family of alkaline phosphate-activated clay/Zeolite catalysts, polymeric coagulant and/or flocculent, biocide, Zeolite and which can be prepared by a process wherein a composition activated charcoal. The composition is added to contami of Zeolite-clay-phosphate is brought to a pH level of about nated water and removes turbidity, metal and organic con 7.0 to about 14.0. The resulting slurry is then age reacted for taminants. It is intended for personal use So that Safe % to 24 hours and finally dried to produce particles that are drinking water can be obtained by the Simple addition of the particularly characterized by their high levels of Zeolite composition to non-potable water. Schwarz, Putyera, Stability for utilization in the catalytic cracking of petro Jagiello and BandoSZ (U.S. Pat. No. 5,385,876) disclose a leum-based materials. Levy (U.S. Pat. No. 5,612,522) process and utility for molecularly engineered activated describes the use of a Zeolite gel to improve the quality and carbons which intercalates with a natural or Synthetic clay carbonation of water by the removal of dissolved gases and producing a highly microporous absorbent material. An minerals. Features not disclosed in these patents include any organic polymeric precursor is contacted there with to fill the application to the removal of heavy metals, ammonia, mer matrix interstices. The precursor is polymerized and carbon captains and other plant-, marine organism- and nuclear ized to yield the absorbent material in which the carbon is derived toxins and no use in humans or animals is discussed. intercalated into the mineral matrix. The material consists essentially of microporous sheets of active carbon Spaced 0062). As taught by Adams, et al. (U.S. Pat. No. 5,560, from one another to define Slit-like micropores of a Substan 829), aluminosilicates of the Zeolite P type may be used as tially uniform preselected width that is molecularly engi calcium binders in aqueous Solutions at low temperatures. neered Such that interstices between the sheets correspond to Rushmere and Moffett (U.S. Pat. Nos. 5,470,435; 5,482,693; a given target adsorbate. Only medical treatments Such as 5.543,014 and 5,503,820) describe the preparation of low "Selective Scavengers of ingested poisons' is mentioned as concentration water Soluble polyaluminosilicate microgels, a potential medical use and is too general and non-specific which are used in the papermaking industry. Neither disclo to grasp the Specific ideas the inventors had conceived of. Sure discusses any pharmaceutical or therapeutic use or Features not disclosed in these inventions include the use of additional utility in the removal of heavy metals, ammonia, the aforementioned compositions for biomedical use includ mercaptains and other plant-, marine organism- and nuclear ing the treatment of Specifically heavy metal poisoning by derived toxins from living animals. oral administration of one or more capsules worth of 0063 Miller and Bruenger (U.S. Pat. No. 5,494,935) material daily for months to years intended, or an a more discuss the use of lipophilic polyaminocarboxylic acids for acute basis with administration into the Stomach via naso the use of heavy metal chelation by oral application. These gastric tube for the remediation of the effects of heavy drugs can be targeted to various organs by modification of metals, ammonia, mercaptains and other plant-, marine the length of the alkyl side chain. Undiscussed in their organism- and nuclear-derived toxins and their removable disclosure is the utility of insoluble, finely powdered sub from the human body. stances which can tightly bind heavy metals, ammonia, 0067 Rainer (U.S. Pat. No. 5,096.946) describes a poly mercaptains and other plant-, marine organism- and nuclear mer product for the Selective absorption of dissolved ions, derived toxins existing in gastric or intestinal juices inside which is a water-swellable polymer which may be physi these Substances interstitial crystalline cavities and chan cally bound to an open celled cellulosic Sponge and which nels. The method of excretion is unaddressed. is produced by a thermal process, which induces amide 0064) Hu, et al. (U.S. Pat. No. 5,487,882) disclose a forming insolubilization of polyethyleneimine. It has a high method of producing crystalline Synthetic faujasite of the affinity for transition metal ions and may comprise a portion Zeolite “X” type. There is no disclosure of any medicinal, of a cellulosic Sponge that is permeable to water yet remains medical, or pharmaceutical uses or any application in the Substantially unaffected by water-borne Suspended matter. field of heavy metal binding, Sequestering or removal from The patent describes no utility as a pharmaceutical product living organisms. intended for use as an orally-administered drug in humans or US 2005/0106267 A1 May 19, 2005

animals. The number of metals that it has utility in removing properties of a novel Synthetic crystalline Zeolite of the further limits it. Yet another limitation is the absence of any molecular Sieve type, designated "LZ-200”, and envisioned description of other non-transition metal toxic Substances to be used as an absorbent with demonstrated ability to that it binds Such as drugs, organic toxins, heavy metals and absorb carbon dioxide, water and methanol. There is not the toxic moieties of plant and animal material accidentally remotest Suggestion of any biomedical uses, therapeutic uses ingested. or pharmacological uses of this material, especially in the 0068. Withiam (U.S. Pat. No. 5,085,705) discloses a treatment of toxin-based and heavy metal poisoning in method of preparation and numerous compositions of alu humans is not discussed in the disclosure. mina-Silica-Sulfates wherein the Sulfate is present as a bound 0.073 Etzel and Anand (U.S. Pat. No. 4,343,706) disclose network. The compositions include articles of manufacture a method of removing heavy from industrial waste Streams in the form of catalysts, rubber, plastics, paint and paper. by flocculation using a Source of ferric ions and an alkaline Specifically, hollow microSpheres containing a porous net material at a basic pH. Heavy metals are recovered by work are formed by Spray drying a gelled composition acidifying the floc in a narrow pH range, which liberates the followed by calcining of the spray-dried hollow micro heavy metals back into Solution while leaving the floc Spheres to eliminate the Sulfate network. particles intact and thus reusable. The concentrated heavy 0069 Dodwell and Smith (U.S. Pat. No. 5,053,139) metals Solution may also be recycled or disposed of in an describe a process for the removal of heavy metals from acceptable manner. The use of this methods and material in aqueous Systems containing competing ions utilizing amor humans, as pharmaceutical compositions or in any in vivo phous tin and titanium Silicates. The basic principle of cation biomedical use is not even remotely described and is unde eXchange, which is a property of certain specific tin- and Sirable for Several reasons including the administration of titanium-based molecular Sieve Zeolites, is exploited in the ferric ions and the basic pH which is required for this eXchange of Several heavy metals with calcium and/or method to work and which is incompatible with adminis magnesium cations. This invention Suffers from no discus tration by several routes into the human body. Sion about pharmaceutical applications or biomedical uses 0.074) Williams and Mays (U.S. Pat. No. 4,213,874) and does not discuss any utility in removal of toxins from the describe the Synthesis of and Several physicochemical prop bodies of animals or humans. Furthermore, the tin- and erties of amorphous Sodium aluminosilicate base exchange titanium-based molecular Sieves discussed have an amor materials with ion exchange capacities equal or Superior to phous Structure differing Substantially from the present known crystalline base exchangers and which may be used invention in which the crystalline Structure is an important in water softening and detergents. Murrell, et al (U.S. Pat. feature. No. 6,004,527) disclose a method for making molecular 0070 Kuznicki and Thrush (U.S. Pat. No. 4,994,191) Sieves with large pores and further describe novel molecular disclose a process for the removal of heavy metals from sieve compositions. Heller, Conger and Fitting (U.S. Pat. aqueous Solutions through the use of the crystalline molecu No. 5,994.933) disclose a method for distributing molecular lar sieve having the X-ray diffraction pattern of ETS-10 or Sieve powder having a median particle size of less than about ETAS-10. They provide examples of the lead absorbing 350 microns, a method for maintaining the moisture content utility of these molecular Sieves showing how the rate of of the Zeolite particles to greater than about 3 percent, and lead binding increases with the framework type used. Impor a method for refining the powder to reduce the Size of the tant features of the present invention that are missing from agglomerated clusters. The use of these materials in humans, this cited prior art is any utility as a pharmaceutical product, as pharmaceutical compositions or in any in Vivo biomedical envisioned for internal ingestion by a human, that it may be use is not even remotely described. utilized to remove lead absorbed in the tissueS of an animal 0075) MacDougall, et al (U.S. Pat. No. 5,882,625) or human or that it may be used to remove other non describe a faujasite-like aluminosilicate, having a non-uni metallic toxins found in plant and/or animal materials which form aluminum distribution, which is synthesized by crys are accidentally ingested by humans. tallizing the Zeolite from a mixture of alkali metal aluminate 0071 Wason (U.S. Pat. No. 4,812.299) describes a family and alkali metal Silicate wherein the mixture has an alkali of novel and unique Synthetic alkali metal alumino-Silicates, metal oxide ratio of at least 37. This zeolite has utility as a also known as SAMS, which essentially comprises altered gas Separation absorbent Such as Separating oxygen from kaolin clay platelets with an integral rim or protuberance of nitrogen in the air. Otterstedt, Sterte and Schoeman (U.S. essentially amorphous alkali Silicate-kaolin reaction prod Pat. No. 5,863,516) describe colloidal suspensions of dis uct. The unique SAMS compositions are Structured materi crete particles of colloidal Zeolite and a method for prepar als in which the Structure can be controlled and are useful as ing Such Zeolite from clear tetraalkylammonium Stabilized functional fillers, as titanium dioxide extenders, as Silica aluminum Silicate Solutions. The colloidal Suspensions are extenders or as reinforcing agents for paper, paint, rubber, characterized by an average particle Size of less than 250 plastics and Specialty products. This references does not nanometers and a particle size distribution, expressed as a even remotely Suggest the utility of these materials for use geometric Standard deviation, of less than 1.30 nanometer. in the pharmaceutical industry, as excipients or active prod These Zeolite sols exhibit Tyndall light scattering and very ucts in the manufacture of medications for human and low rate of Sedimentation owing to their Small particle size. animal use, as active components in the removal of harmful There is no Suggestion of any biomedical, pharmaceutical or Substances Such as heavy metals and/or animal or plant medical toxicology use. borne toxins. 0.076 Ueshima, et al (U.S. Pat. Nos. 5.810,920 and 0072 Hinchey (U.S. Pat. No. 4,348,369) discloses the 5,769,938) describe a method for treating fly ash waste discovery of, Synthesis of and Some chemical and physical containing harmful metals in which the waste is mixed with US 2005/0106267 A1 May 19, 2005 a treating agent containing Solid acids and/or cement and which are characterized by low oil absorption values, high additionally a caking inhibitor, which is then kneaded with total pore Volume and increased differential pore Volumes. water where necessary and Solidified by curing. Harmful The products are useful as coating pigments for paper, metals, including lead, cadmium, mercury, chromium, cop paperboard, paper fillers, paint pigments and as reinforcing per, nickel and Zinc are Stabilized in Solidified cakes from pigments for rubber. There is not even the remotest Sugges which they are not released. Reimers, Akers and Lo (U.S. tion of utility in biomedicine, pharmaceuticals, or that the Pat. No. 4,853,208) disclose a method of binding wastes in products could be used in the remediation of heavy metal alkaline Silicate matrix as a means of detoxifying wastes poisoning or toxic metal ingestion in humans or animals. containing heavy metals including mercury, Zinc, Selenium, arsenic, antimony, copper and thallium. The alkaline Silicate 0080) Li, et al (U.S. Pat. No. 5,584,912) describe a matrix binds the aforementioned metals and prevents their composition, a Synthesis of a composition and a method of leaching out and contaminating the environment. There is using the composition for Selectively adsorptively Separat not even a remote Suggestion that the method and compo ing nitrogen from oxygen wherein the composition is a nents described in this patent is intended for use in any crystalline EMT with a Si/Al ratio less than 2.0 and a biomedical, pharmaceutical or medical toxicology context micropore volume of at least 0.20 cm/g and a lithium cation for any of the metals, ammonia, mercaptains and other plant-, eXchange of at least 80%. No pharmaceutical, biomedical or marine organism- and nuclear-derived toxins disclosed or human medicinal or therapeutic use is described in this others not mentioned. disclosure. 0077. Titterton and Summers (U.S. Pat. No. 5,744,404) 0081 Tissler, et al (U.S. Pat. No. 5,578,195) describe a describe a process and an article for delivering or applying Synthetic crystalline aluminosilicate of the pentasil type and a Zeolitic molecular Sieve to an odorous Surface. The proceSS method for using the same as catalysts or catalyst compo involves contacting the Surface with a porous article, which nents in petrochemical processes for the catalytic conversion contains a slurry of a Zeolitic molecular Sieve having a of hydrocarbons and their derivatives into useful organic SiO/Al2O, ratio of at least 18. The slurry also contains compounds and intermediates. Pryor and Chi (U.S. Pat. No. water, ethanol, a Suspending agent, a preservative and 4,424,144) describe the preparation of binderless 3A zeolite optionally an emollient. The porous article can be woven or absorbents, in the form of beads or extrudates and are non-woven and includes wipes, pads, foams and towelettes. envisioned for use in drying a mixture of a hydrocarbon, The patent describes a biomedical application in which said Such as ethylene, and water. No pharmaceutical, biomedical method and resultant slurry is used to control foot odor. or human medicinal or therapeutic use is described in this There is not even the remotest Suggestion that this invention disclosure. could be used internally or in the remediation of heavy metal 0082 Kuhrts (U.S. Pat. No. 5,641.511) discloses a granu poisoning or toxic metal ingestion in humans or animals. lar drug delivery System comprising a gel-forming dietary 0078 Henriksen (U.S. Pat. No. 6,136,859) discloses a fiber that can be made into an orally-ingestible dispersion by pharmaceutical formulation for treating liver disorders admixture with a liquid that can deliver an effective dose of which is comprised of Selenium, beta-caroteine or VitaminA, a pharmaceutically-active compound. Although this System ascorbic acid in its Salt or ester form, alpha-tocopherol, appears useful in delivering desired amounts of a drug to the methionine and coenzyme Q10 with a pharmaceutically gastrointestinal tract, it is not envisioned for use in removing acceptable carrier Suitable for treating Such diseases as toxic or deleterious Substances from the gut. Luck and Crabb primary biliary cirrhosis, Viral hepatitis, Steatohepatitis, (U.S. Pat. No. 6,074,689) disclose a method and composi alcoholic cirrhosis and related hepatic and biliary disorders. tion for delivering an active protein or peptide to the colon What is not appreciated in this disclosure is that primary comprising an aqueous Solution of polyethylene glycol biliary cirrhosis is associated with an elevated Serum copper (PEG), the active protein or peptide, and an outer enteric level. The underlying reason for this is unknown. This coating. The intended use for this method and composition disclosure does not offer the remotest Suggestion that ame is for treatment of antibiotic induced Clostridium dificile lioration of certain clinical findings of primary biliary cir induced diarrhea where the active protein is hyperimmune rhosis are achievable by reduction of the elevated serum bovine colostrum immunoglobulin (HBCIg) against the copper level. One method by which this may be achieved is toxin elaborated by CloStridium dificile. by chelation therapy, either intravenously or enterally. 0083) Bleim and Steffier (U.S. Pat. No. 5,500,212) dis 0079 Nilsson and Stendahl (U.S. Pat. No. 5,662,826) close the composition of and preparation of a crosslinked describe a process for the preparation of a coagulating amine-containing polymer with a polyfunctional amine chemical comprising dissolving a Solid Zeolite in a Solution reactive compound Such that water insolubility is achieved of trivalent metal salt. The composition described is a and bile acid Sequestering capacity is enhanced over coagulant for water purification in the fields of treating cholestyramine alone. Dhal, Holmes-Farley and Petersen Sewage water, in pulp and paper manufacture, in dewatering (U.S. Pat. No. 6,294,163) disclose polymers containing organic matter, and in concentrating minerals. Kuhm, Salz guanidinium groups as bile acid Sequestrants envisioned for and Blasey (U.S. Pat. No. 5,645,811) describe a process for use in lowering Serum cholesterol levels. Figuly and Matos the production of very fine-particle Zeolitic alkali metal (U.S. Pat. No. 5,874.522) disclose crosslinked polymeric aluminum Silicates. Following a mixture of alkali metal ammonium Salts comprised of n-alkylene or alkyl-SubSti Silicate and alkali metal aluminate, in the presence of a tuted n-alkylene groupS and hydrocarbylene radicals con Stoichiometrically excessive amount of alkali metal hydrox taining one or more hydroxyl, ether, amino, thioether, keto ide a gel is obtained and matured. Freeman, et al (U.S. Pat. or silyl groups envisioned for use in bile acid binding and No. 5,591,256) describe methods, uses and compositions of serum cholesterol lowering. Goto and Meno (U.S. Pat. No. high-performance Synthetic alkali metal alumino-Silicates 6,022,533) disclose a pharmaceutical composition compris US 2005/0106267 A1 May 19, 2005 ing an anion exchange resin, Silicon dioxide, crystalline 0085 Porath (U.S. Pat. No. 5,183,313) discloses an cellulose and a pharmaceutical carrier. This disclosure absorbent for metal ions, proteins and other inorganic and relates primarily to the finding that formulation of non organic Substances which is based upon a ligand with an crosslinked anion exchange resins, which had been consid atomic sequence of N-C-C-N where the specific ered impossible without water, is achievable with the use of Sequence comprises part of a heteroaromatic ring System Silicon dioxide and crystalline cellulose. The tablets con which is covalently bonded to a polymerS Such as a polysac taining the anion eXchange resin are envisioned for use in charide, polyvinyl alcohol or other organic hydrophilic lowering cholesterol. Howard (U.S. Pat. No. 4,041,153) polymer. The invention suffers from no description about discloses methods and a pharmaceutical preparation for the any in Vivo biomedical use Such as may be effected by oral administration of a capsule or tablet. There is a further treatment of hypercholesterolemia, which contains clofi absence of any description of this material being employed brate, a basic anion eXchange resin and a metal ion whose in a heavy metal chelating mode for other heavy metals, function is to form insoluble metal bile acid salts. The including lead, uranium, and others, ammonia, mercaptains ingestible non-toxic metallic compound is capable of dis and other plant-, marine organism- and nuclear-derived Solving in the gastrointestinal juices to yield a metallic Salt toxins. or ion that can react with bile acids to form an insoluble or poorly soluble metal salt of these bile acids. Huval, Holmes 0.086 Hider, Kontoghiorghes and Silver (U.S. Pat. No. Farley, Petersen and Dhal (U.S. Pat. No. 6,264,938) disclose 4.585,780) disclose a series of pharmaceutical compositions a combination therapy for hypercholesterolemia, which is containing a 3-hydroxypyrid-2-one or 3-hydroxypyrid-4- comprised of a conventional HMG-CoA reductase inhibitor one in which the atom attached to the nitrogen atom is and an unsubstituted polydiallylamine polymer, which acts replaced by an aliphatic acyl group, by an aliphatic hydro as a bile acid sequestrant. Johnson (U.S. Pat. No. 4,649,048) carbon group, or by a Substituted aliphatic hydrocarbon discloses that quaternized vinylimidazole-ethylene glycol group to be used for the removal of toxic amounts of metals dimethacrylates useful to Sequester non-absorbed bile acids from the body. in the intestinal tract to form a complex, which is then 0087. These materials differ substantially from the excreted in the feces. Jaxa-Chamiec, Hickey and Shah (U.S. present invention in that they are of an organic nature Pat. Nos. 4,594,339; 5,230,885 and 5,273,740) disclose designed to permeate cellular membranes. In addition, the Several classes of anion eXchange polymers envisioned for mode of action of these compounds is to enhance the water use in treating hypercholesterolemia by binding free bile Solubility and urinary excretion of metals. Such as iron, acids in gastrointestinal juice and Sequestering them for copper and aluminum. Yet another important difference from eventual excretion out of the body with the feces. The Specific anion exchange polymers disclosed include N,N- the present invention is the Solubility of the chelating dimethyl-N-dodecylammoniomethyl-substituted polysty compound itself and its properties of Systemic distribution. rene, N,N-dimethyl-N-dodecyl-ammoniomethylstyrene 0088 Wieder (U.S. Pat. No. 4,352,751) discloses a series ethyl methacrylate-divinylbenze and 6-(N,N-dimethyl-N- of Species-linked diamine triacetic acids and their metal octylammonio)hexanoylated polystyrene chloride. Shaw chelates whose general Structure is comprised of an organic and Sharma (U.S. Pat. No. 4,790,991) disclose ingestible Species containing at least one amine, hydroxyl or thiol aggregates comprising a pre-Swelled anhydrous hydrocol functional group and a two or more atom long covalent loid and a Substrate and are envisioned for use in treating a bridge. Very different than the present invention, the utility number of diseases including hypercholesterolemia and proposed is in the monitoring the level of biologically and/or mineral deficiencies, in combination with the appropriate medically important molecules. This is achieved by incor active pharmaceutical ingredient. Yang, Sharma, Sheu and porating into the metal binding Sites, rare earth metal ions Shaw (U.S. Pat. No. 4,778,676) disclose a chewable con capable of forming fluorescent chelates that may be used in fectionery delivery System for active pharmaceutical ingre a fluorometric assay. No therapeutic intent is even remotely dients and Specifically cholestyramine intended for improve Suggested in addition to the extremely Small capacity to bind palatability in the treatment of hypercholesterolemia with a toxic metal or other toxins of medical interest for the bile salt binding resin. Schulz (U.S. Pat. No. 5,167,965) purpose of their elimination. discloses the composition of and method of producing palatable cholestyramine granules and tablets to be used in 0089 Hinckley (U.S. Pat. No. 4,346,216) teaches the use the treatment of hypercholesterolemia. These disclosures do of osmium carbohydrate complexes as pharmaceutical com not address any use in heavy metal poisoning and do not positions for the treatment of heavy metal poisoning, arthri address any compositions Such as Zeolite molecular Sieves. tis and as a diagnostic aid as a radiographic contrast agent. OSmium-glucose complexes are proposed to be adminis 0084 McClelland and Zentner (U.S. Pat. No. 5,350,584) tered to mammals Suffering from heavy metal poisoning disclose a proceSS for Spheronization of charged resins, which will result in a chelation of the heavy metal within the which produces multiparticulates 0.3-3 mm in diameter and oSmium complex in a harmless form which is then excreted which is microcrystalline free. Active pharmaceutical agents from the system without further toxic effects on the treated envisioned for incorporation into a granulation that is then animal. This approach Suffers numerous disadvantages Spheronized include cholestyramine and trientine. Although including the unavoidable and potentially deleterious depo each active pharmaceutical ingredient is used in Specific Sition of osmium metal in tissues, unevaluated ability of the circumstances, there is no specific mention of this proceSS or material to be absorbed from the gastrointestinal tract, and these compositions to be used in the long-term remediation the need for multiple, frequent, chronic injections and undis of heavy metal poisoning and removal of the heavy metal closed method of elimination from the body of a mammal. itself, nor is there any discussion about the use of Zeolite The mechanism of action also varies significantly from the molecular Sieves. present invention in that in that only lead is discussed as one US 2005/0106267 A1 May 19, 2005 of the heavy metals Susceptible to this approach. Addition poisoning or toxic ingestions in man including preparation ally, osmium is generally regarded as toxic to the human using the cell wall of yeasts which may contain unknown body and strict federal limits on the amount of osmium that and/or undesirable contaminants or biologically active mol may be deposited limits the utility of this approach. ecules and no description of any kind that Said composition may be useful in other toxins Such as heavy metals, ammo 0090. Mandeville and Holmes-Farley (U.S. Pat. No. nia, mercaptains and other plant-, marine organism- and 5,702,696) disclose a family of hydrophilic anionic nuclear-derived toxins. eXchange resins for use in treating iron overload Syndromes by decreasing the absorption of dietary iron. Sasaki and Ishii 0094) Casas and Mosstam (U.S. Pat. No. 5,837,238) (U.S. Pat. No. 6,180,094) disclose a medicament, which disclose a therapeutic method of treating rotavirus induced comprises as an active ingredient a weakly basic anion diarrhea by the administration of lyophilized and reconsti eXchange resin chelating with ferric ion, which adsorbs tuted Lactobacillus reuteni whose mechanism of action is phosphate ions in Vivo and is used for prevention and unknown although it may be related to the elaboration of a treatment of hyperphosphatemia. In this disclosure, the iron Substance named reuterin or improving the indigenous gas binding properties of cholestryamine are mentioned and the trointestinal microflora. Willoughby and Yolken (U.S. Pat. Suggestion that iron deficiency anemia may be caused by its No. 5,192,551) disclose a neutral glycolipid GA1 (asialo and other similar resins's use. Although there are certain GM1 or asialo-gangliotetraosylceramide) as an adsorbent, advantages to this approach, there is no mention of any use either alone or bound to a non-absorbable resin or matrix, for of this method in the removal of heavy metals, ammonia, the neutralization of enteric viral pathogens representing mercaptains and other plant-, marine organism- and nuclear either prophylaxis in the case of a localized outbreak, or as derived toxins nor is there mention that Zeolite molecular a treatment in the case of florid gastroenteritis. Delivery Sieves can be employed in the same manner. modality is dependent on location, pharyngeal colonizing Viruses is proposed to be accomplished by nebulization or 0091 Rosenberg (U.S. Pat. No. 4,107,331) describes a gargling whereas gastrointestinal infection is treated Specifi Zinc chelating fungicidal composition in which Zinc ions cally with internally ingested naked GA1 or GA1 bound to which are required by certain Species of fungi for growth beads, resins, natural or Synthetic polymerS although yet is Sequestered in the chelating agent thereby preventing additional delivery methods and pharmaceutical dosage growth of human fungal infections. The chelating or Seques forms are mentioned. This invention does not specifically tering agents described include water Soluble Salts of one of claim to work by Sequestration or ion exchange, it is not Several EDTA-like organic compounds which is mixed with directed toward remediation of any toxic effect produced by an aqueous jelly and administered vaginally for the treat heavy metal ingestion and it does not involve the use of ment of common yeast infections. This disclosure Suffers Zeolite molecular Sieves. from a number of disadvantages for the treatment of chronic heavy metal poisoning including its use as a topical treat 0095 Several disclosures reveal similar methods of ment and the use of organic and toxic chemicals about which increasing the nutritional value of mycotoxin-contaminated little toxicity information in man is known. Additionally, animal feed by feeding the animal montmorillonite clay oral administration for months in the form of a capsule, Beggs (U.S. Pat. No. 5,149,549) or an acid-activated tablet, Suspension or slurry for the purpose of removing montmorillonite clay Turk, Music and Beall (U.S. Pat. No. heavy metals, ammonia, mercaptains and other plant-, 5,639,492) simultaneously with the contaminated animal marine organism- and nuclear-derived toxins from the body feed. The clay, itself which is not absorbed in the gas is not even remotely Suggested. trointestinal tract but which absorbs or adsorbs any one of Several known toxins (aflatoxin, fumonisin, vomitoxin, och 0092 Bergwitz-Larsen and Ulf (U.S. Pat. No. 5,643,560) ratoxin, Zearalenone, ergot, and ergotamine). Taylor, disclose a drug formulation with ion exchangers of the Delaney and Phillips (U.S. Pat. Nos. 5,165,946 and 5,165, carrageenan type for use in reducing toxic side effects and 946) disclose a dry solid animal feed composition in which lethality when overdosing psychotropic medications. The biodegradable feed is contaminated with a mycotoxin and is drug and the carrageenan are administered together, but the admixed with a mycotoxin inactivating agent comprising carrageenan, through the process of ion eXchange, in con particles of a phyllosilicate mineral capable of inactivating junction with an additional Salt, minimizes absorption as mycotoxins. The particles are coated with a Sequestering reflected in animal model Serum levels of clomipramine. agent in an amount Sufficient to enhance the mycotoxin This disclosure, however, fails to address the use of Zeolite inactivating capacity of the phyllosilicate. These inventions molecular Sieves in Vivo nor does it address the issue of Suffer from Several deficiencies including no mention of the chronic toxicity from tissue absorbed heavy metals, ammo use of Zeolite molecular Sieves, no mention of the chronicity nia, mercaptains and other plant-, marine organism- and of administration, no mention of any additional nutritional nuclear-derived toxins, nor does it address use ranging from deficiencies that may result from the clay administration and months to years. no mention of Specificity of toxin binding within the frame work Structure. Specific pharmaceutical preparation for 0093. Howes and Newman (U.S. Pat. No. 6,045,834) disclose compositions and methods for the removal of human use is not discussed. Moreover, human use was not mycotoxins from animal feed whereby a combination of described in these disclosures. modified yeast cell wall extract and mineral clay is fed to 0096 Geneix, Alafourcade and Ribereau-Gayon (U.S. animals in amounts Sufficient to inactivate mycotoxins Pat. No. 4,765,992) disclose a method of improving the present in the feeds. These compositions are intended to be alcoholic fermentation yield by the addition of cell walls that admixed with feeds, incorporated directly into pelleted feeds have been boiled or autolysed and washed. The cell walls act or fed directly to animals. This invention Suffers from to bind the offending substances which include certain fatty Several deficiencies for use in the treatment of heavy metal acids and their ethyl esters, pesticide residues and Sub US 2005/0106267 A1 May 19, 2005 stances Secreted by microorganisms. There is not even the phate, designated AlPO-33, although it is distinct from the remotest Suggestion that this invention has utility in bio aforementioned AlPO family described above. Chang, Chu, medicine, pharmaceuticals or could be used in the remedia Dessau, Higgins, Lutner and Schlenker (U.S. Pat. No. 5,091, tion of heavy metal poisoning or toxic metal ingestion in 073) disclose a crystalline molecular sieve composition, humans or animals. designated MCM-37, which may be used in the catalytic conversion of organic compounds. Breck and Acara (U.S. 0097) Robbins and Seely (U.S. Pat. No. 4,251,519) dis Pat. No. 4,950,952) disclose a crystalline Zeolite, designated close a process of lowering or preventing an increase in the T, and Breck, Blass, and Skeels (U.S. Pat. No. 4,503,023) level of cholesterol and triglycerides in the blood of mam disclose Silicon Substituted Zeolite compositions which are mals by including a yeast glycan in the daily diet in an contacted with an aqueous Solution of a fluorosilicate Salt amount of up to 30% of the total food intake. There is not using controlled proportions and temperature and pH con even the remotest Suggestion that this invention has utility in ditions which avoid aluminum extraction. Casci, Lowe and biomedicine, pharmaceuticals or could be used in the reme Whittam (U.S. Pat. No. 4,537,754) disclose the composition diation of heavy metal poisoning or toxic metal ingestion in of and the method of producing zeolite EU-1 which is useful humans or animals. in catalytic processes Such as Xylenes isomerization. Grose 0.098 Coe, Gafffiey, Srinivasan, Kirner, Pierantozzi and and Flanigen (U.S. Pat. No. 4,124,686) disclose a crystalline White (U.S. Pat. Nos. 4.925,460; 5,152,813 and 5,258,058) Zeolite, designated phi, which is prepared hydrothermally disclose different methods by which to achieve improved from aqueous gels, exhibits large-pore adsorption charac gas Separation including the use of a lithium exchanged teristics and is envisioned for use in hydrocarbon conversion chabazite, a binary exchanged X-Zeolite containing lithium, processes exemplified by isoparaffin alkylation, hydrocrack calcium and/or strontium ions, and additional divalent cation ing isomerization and reforming. Morimoto, Takatsu and exchanged lithium X-Zeolites. Maurer (U.S. Pat. No. 5,171, Sugimoto (U.S. Pat. No. 4,578,259) disclose a crystalline 333) discloses a process for methane purification by pressure aluminosilicate and its structural variations, collectively Swing absorption employing a faujasite type of Zeolite designated ISI-6, which are envisioned for use as catalysts containing divalent and alkali metal and alkaline earth metal for the conversion of oxygen-containing organic compounds cations. Fitch, Bulow and Ojo (U.S. Pat. No. 5,464,467) Such as alcohols and ethers into hydrocarbons. Plank, Ros disclose type X Zeolites with charge compensating cations inski and Rubin (U.S. Pat. No. 4,016,245) disclose a crys comprised of lithium, aluminum, cerium, lanthanum and/or talline Zeolite, designated ZSM-35, which is envisioned for mixed lanthanides are useful in gas separations. Chao, use as an absorbent or a catalyst. Sand and Dodwell (U.S. Sherman, Mullhaput and Bolinger (U.S. Pat. No. 5,413,625) Pat. No. 4,081,514) disclose a process for producing acid disclose lithium/alkaline earth metal A and X Zeolites are Stable, fluidizable mordenite particles in the size range of 20 useful in Separating oxygen and nitrogen from gas mixtures to 150 nanometers and envisioned for use as an absorbant, owing to their high absorptive capacity and high thermal catalyst Support and ion-exchange medium. Sand (U.S. Pat. Stability. There is not even the remotest Suggestion that the No. 4,093,699) independently discloses a method for mak object of any of these inventions has utility in biomedicine, ing Synthetic offretite, which is acid treated, and is capable pharmaceuticals or could be used in the remediation of of intercrystalline absorption of benzene and molecules heavy metal poisoning or toxic metal ingestion in humans or greater than 5 A. Cormier and Sand (U.S. Pat. No. 4,017, animals. 590) disclose the preparation of synthetic ferrierite by a hydrothermal process in which there is co-precipitation of 0099. A number of microporous compositions are Silica-alumina gels and Sodium and potassium carbonates described in the patent literature. Vaughan, Barrett, Strohm and bicarbonates and which is envisioned for use in Sepa aier, Treacy and Newsam (U.S. Pat. Nos. 4,091,079; 4,333, rating molecules 6.2 A and smaller from larger molecules. 859; 4.879,103 and 5,116,590) disclose the synthesis of Kuznicki and Whyte (U.S. Pat. No. 5,011,667) disclose a Several new materials including a Synthetic large pore crys process of forming Self-bound Sodium chabazite and desig talline metalsilicate Zeolite composition designated ECR-35, nated EC-20 which shows Superiority in absorption and a crystalline aluminosilicate Zeolite comprised of potassium ion-exchange capacity when compared to the natural form. and Vanadium ions present in the reaction mixture desig Velten and Demmel (U.S. Pat. No. 4,826,793) disclose a nated VK-2, a high Silica faujasite polymorph designated method of incorporating Small crystalline catalytic ingredi CSZ-3 which has claimed utility in Sorption, Separation and ents into an attrition-resistant matrix by the use of binder catalytic applications, and a Zeolite characterized by triethyl formulations prepared from amorphous Silica, alumina, and methyl ammonium being entrapped in Supercages of the Zirconia. The particles are less than 4 um and contain the aluminosilicate and designated ECR-30. Delprato, Guth, catalyst component ZSM-5, low-Soda eXchanged type Angelrot, Didier and Zivkov (U.S. Pat. No. 5,393,511) Y-Zeolite or ultra-stable type Y Zeolite. The resulting mate disclose the Synthesis of faujasite class Zeolites in which rial is spray-dried and calcined and which has shown resis numerous crown ethers and other carbon-containing tance to attrition and particle density change. In each of macropolyrings of the polyoxadiazabicycloalkane class are these disclosures there is not even the remotest Suggestion employed as Structuring agents. Wilson, Lok and Flanigen that these inventions have utility in biomedicine, pharma (U.S. Pat. No. 4,310,440) disclose a family of crystalline ceuticals or could be useful in the remediation of heavy microporous aluminophosphate compositions, designated metal poisoning or toxic metal ingestion in humans or the AlPO family of Zeolites, the members of which are Synthesized by hydrothermal crystallization at elevated tem animals. peratures of aluminophosphate gels containing a molecular 0100 Bacon Kurtz and Fitzpatrick (U.S. Pat. No. 6,270, Structure-forming template and which are envisioned for use 755) disclose a Series of anionic polymers as toxin binders as catalysts or catalyst bases. Patton and Gajek (U.S. Pat. intended for use in binding pathogenic toxins elaborated by No. 4,473,663) disclose another crystalline aluminophos microorganisms including bacteria and protozoa. Kurtz and US 2005/0106267 A1 May 19, 2005

Fitzpatrick (U.S. Pat. No. 6,290,946) disclose a series of CIT-1 (CON), Chiral Zincophosphate (CZP), DAF-1 (DFO), polystyrene Sulfonate-based polymerS also intended for use EMC-2 (EMT), Faujasite (FAU), Gmelinite (GME), GUS-1 in binding pathogenic toxins from microorganisms. Fitz (GON), ITQ-4 (IFR), ITQ-7 (ISV), Linde Type L (LTL), patrick, Huval, Bacon Kurtz, Mandeville and Neenan (U.S. Mazzite (MAZ), ZSM-18 (MEI), Mordenite (MOR), ZSM Pat. Nos. 6,007,803 and 6,290,947) disclose a cationic 12 (MTW), Offretite (OFF), UiO-6 (OSI), Roggianite polymer comprised of a monomer having a pendant ammo (RON), STA-1 (SAO), UCSB-8Co (SBE), UCSB-6GaCo nium group and a hydrophobic monomer envisioned for use (SBS), UCSB-10GaZn(SBT), SSZ-48 (SFE), VPI-8 (VET); in binding pathogenic toxins elaborated by microorganisms the 10-ring structures AlPO-11 (AEL), AlPO-41 (AFO), including bacteria and protozoa. HeerZe and Armstrong AlPO-H2 (AHT), Co-Ga-Phosphate-5 (CGF), Co-Ga-Phos (U.S. Pat. No. 6,107.282) disclose prevention and/or treat phate-6 (CGS), Dachiardite (DAC), Epistilbite (EPI), EU-1 ment of antibiotic associated diarrhea and pseudomembra (EUO), Ferrierite (FER), Heulandite (HEU), Laumontite nous enterocolitis arising from CloStridium difficile toxin B (LAU), ZSM-11 (MEL), ZSM-5 (MFI), ZSM-57 (MFS), using 8-methoxycarbonyl oligosaccharides. These compo ZSM-23 (MTT), MCM-22 (MWW), NU-87 (NES), Sitions bind the toxin and neutralize it thereby mitigating and Partheite (PAR), SSZ-44 (SFF), SSZ-35 (STF), Stilbite potentially preventing the toxin's pathological effects. Such (STI), Terranovaite (TER), Theta-1 (TON), Weinebenite oligosaccharides have been shown to be eliminated com (WEI), Wenkite (WEN). The specific zeolite isotypic groups pletely and rapidly from the rat gastrointestinal tract. These considered to be useful in the wide spectrum of heavy metal inventions Suffer from no description of any use in removing intoxication also include the 9-ring Structures designated by heavy metals, ammonia, mercaptains and other plant-, the terms and abbreviations: Chiavennite (CHI), Lovdarite marine organism- and nuclear-derived toxins either recently (LOV), Natrolite (NAT), RUB-17 (RSN), SSZ-23 (STT), ingested or absorbed into tissue from chronic exposure. VPT-7 (VSV). The specific zeolite isotypic groups consid ered to be useful in the wide spectrum of heavy metal 0101. Other forms of heavy metal detoxification are intoxication also include the 8-ring Structures designated by clearly needed for chronic administration. the terms and abbreviations: Li-A (ABW), ACP-1 (ACO), 0102) The inorganic structural class of molecular sieves AIPO-18 (AEI), AIPO-EN3 (AEN), AIPO-14 (AFN), AIPO or zeolites is comprised of more than 1000 members, many 52 (AFT), SAPO-56 (AFX), Analcime (ANA), AlPO-C of which we believe possess useful medicinal, pharmaco (APC), AlPO-D (APD), MAPO-39 (ATN), AIPO-12-TAMU logical and biopharmaceutical properties in this therapeutic (ATT), AIPO-25 (ATV), AIPO-21 (AWO), AIPO-22 C. (AWW), Bikitaite (BIK), Brewsterite (BRE), Cesium Alu minosilicate (CAS), Chabazite (CHA), Deca-dodecasil 3R 0103) Zeolites are a class of inorganic crystalline (DDR), DAF-2 (DFT), TMA-E (EAB), Edingtonite (EDI), microporous Solids comprised mostly of Silicates and phos Erionite (ER1), ERS-7 (ESV), Gismondine (GIS), phates although arsenates and germanates are also repre Goosecreekite (GOO), ITQ-3 (ITE), Naj (JBW), ZK-5 sented. Zeolites possess a framework density (FD) of (KFI), Levyne (LEV), Linde Type A (LTA), Merlinoite approximately 12.1 to 20.6 tetrahedrally coordinated atoms (MER), Montesommaite (MON), MCM-35 (MTF), Pauling (also known as T-atoms) per 1000 A(cubic angstroms). ite (PAU), Phillipsite (PHI), Rho (RHO), RUB-3 (RTE), Such frameworks are comprised of a number of repeated RUB-13 (RTH), STA-6 (SAS), STA-2 (SAT), Mg-STA-7 identical or different Structural components termed Second (SAV), Thomsonite (THO), Tschortnerite (TSC), VPI-9 ary building units (SBU). To date, approximately 20 SBUs (VNI), Yugawaralite (YUG), ZAPO-MI (ZON). These Zeo have been described. The framework for a specific zeolite lites are described by Baerlocher and colleagues (Baerlocher defines the pore and channel sizes; these pore and channel Ch., Meier, W M and D H Olson. Atlas of Zeolite Frame diameters vary acroSS different Zeolites. The pore and chan work Types, 5" revised ed., Elsevier, 2001, pp. 3-18). nel diameters, also termed “crystallographic free diameters,” influence the rate of diffusion of water and dissolved ions 0105. One related mineral, magnesium aluminum silicate through the framework. A number of Zeolite groups with 1327-43-1 also termed aluminum magnesium silicate 20-, 18-, 14-, 12-, 10-, 9-, and 8-ring Structures are known 12511-31-8) is available commercially as a pharmaceutical to exist. Depending on the relative molecular charge in the excipient. It is used in a range concentrations in the phar Space Surrounding the pores positively or negatively charged maceutical industry and functioning as an absorbent, a ions are attracted or repelled. Ions of Similar charge and size binding agent, a disintegrant, an oral or topical emulsion may be substituted for each other or “exchanged” thereby Stabilizer, an oral or topical Suspending agent, a Stabilizing producing the “ion eXchange' phenomenon for which Zeo agent and a Viscosity modifier. It is obtained from the Silicate lites are well known. ores of the montmorillonite group and occurs as an off-white to creamy white, odorless, tasteless, Soft, slippery Small 0104 Zeolites offer a unique approach to treating heavy flakes or as fine micronized powder. It is practically metal poisoning because of their intrinsic chemical and insoluble in alcohols, water and organic Solvents. It can physical Stability and their general biological inertneSS. The Swell to many times its original Volume in water and may be Specific Zeolite isotypic groups considered to be useful in the dried and rehydrated many times. It is stable indefinitely wide spectrum of heavy metal intoxication include the 20-, when Stored under dry conditions and is stable over a wide 18- and 14-ring Structures designated by the terms and pH range. It absorbs Some organic Substances but appears to abbreviations: Cloverite (-CLO), VPI-5 (VFI), AlPO-8 be compatible with organic Solvents. It is generally regarded (AET), CIT-5 (CFI), UTD-1F (DON), OSB-1 (OSO); the as nontoxic and nonirritating at levels employed as a phar 12-ring structures AlPO-5 (AFI), SAPO-40 (AFR), maceutical excipient. Subacute animal feeding Studies in MAPSO-46 (AFS), CoAPO-50 (AFY), ASU-7 (ASV), rats and dogs fed magnesium aluminum Silicate at 10% of AlPO-31 (ATO), MAPO-36 (ATS), Beta (BEA), Boggsite their diet for 90 days were negative including autopsy and (BOG), Beryllophosphate-H (BPH), Cancrinite (CAN), histopathological examination. The oral LDso for the rat is US 2005/0106267 A1 May 19, 2005

16 g/kg. Magnesium aluminum Silicate is included in the 510; 1991); Cs-Mg-P-O-ABW (Rakotomahanina Food and Drug Administration's (FDA) Inactive Ingredients Raloisoa E. L., Ph.D. Thesis, U. Grenoble, 1972); Cs Guide. Al-Si-O-ABW (Klaska R, et al. Naturwiss. 60:299, 0106 The present invention relates to the use of Zeolites, 1973; Klaska R, et al. Z. Kristallogr. 142:225-238, 1975); both natural and artificial, in the treatment of diseaseS related Cs-Al-Ti-O-ABW (Gatehouse BM, et al. Acta Crys to heavy metals and ammonia in humans. Based on the tallogr. C45:1674-1677, 1989); Li-Al-Si-O-ABW relative affinities and diameters of the metallic ions, certain (Ghorbarkar H, Cryst. Res. Technol. 27: 1071-1075, 1992); metals will bind preferentially to certain Zeolites, thus cre Li-Zn-P-O-ABW (Harrison W T A, et al. J. Solid ating the ability to design lattice Structures of precise dimen State Chem. 114:249-257, 1995); Li-Al-Ge-O-ABW Sions for each of the heavy metals that are known poisons in (Tripathi A, et al., Microporous and Mesoporous Materials, man. The Specific metals known to cause human disease in 34:273-279, 2000); Na-Co-P-O-ABW (Chippindale elevated quantities include lead, copper, tin, arsenic, anti A M, et al., Acta Crystallogr., C55: 845-847, 1999); Rb mony, beryllium, bismuth, boron, cadmium, chromium, Co-P-O-ABW (Rakotomahanina Raloisoa E L., Ph.D. cobalt, copper, iron, lead, lithium, magnesium, nickel, Sele Thesis, U. Grenoble, 1972); Rb-Al-Si-O-ABW nium, Silver, Strontium, thallium, tin, titanium, Vanadium, (Klaska R, et al., Naturwiss., 60: 299, 1973; Klaska R, et al., Zinc, mercury. It is envisioned that the Zeolite would be Z. Kristallogr. 142:225-238, 1975); Tl-Al-Si-O- administered orally in the form of a capsule, tablet, powder ABW (Krogh Anderson E, et al., Zeolites, 11: 149-154, or slurry daily or multiple times daily for weeks to months 1991); ACP-1 (Feng PY, et al., Nature, 388: 735-741, 1997); duration. Zeolites are generally insoluble in the aqueous AlPO-18 (Simmen A, et al., Zeolites, 11:654–661, 1991; environments present in the human gastrointestinal tract U.S. Pat. No. 4,310,440, 1982); AlPO-11 (Bennett J M, et Such as acid pH in the Stomach, alkaline pH of the duodenum al., Zeolites, 7:160-162, 1987, Richardson Jr J.W., et al., Acta for the few hours of normal transit time. Dealuminization is Crystallogr., B44: 367-373, 1988; Wilson ST, et al., U.S. known to occur in acidic environments with Some Zeolites. Pat. No. 4,310,440, 1982); MnAPO-1 (Pluth JJ, et al., J. The neutral pH of the jejunum, ileum, cecum, colon and Phys. Chem., 92: 2734-2738, 1988); SAPO-11 and compo rectum do not pose a dealuminization or Solubility risk. It is sitional variants (Flanigen E. M., et al., Pure Appl. Chem., 58: known to bind lead and copper when administered orally in 1351-1358, 1986; Flanigen E M, et al., In Proc. 7" Int. an in Vivo System. Zeolite Conf, Japan, 103-112, 1986); AlPO-EN3 (Parise JB, 0107 Although zeolites and similar ion exchange, inor Stud. Surf Sci. Catal., 24: 271-278, 1985); Ga-P-O- ganic, relatively insoluble materials are claimed, the Specific AEN (Glasser FP, et al., Acta Crystallogr., C50:848-850, Zeolite to be employed is the Sodium aluminum Silicate, 1994); AlPO-53(A) (Kirchner RM, et al., Microporous and CAS 12141-46-7). As shown in the Material Safety Data Mesoporous Materials, 39: 319-332, 2000); AlPO-53(B) Sheet (Material Safety Data Sheet for sodium aluminum (Kirchner RM, et al., Microporous and Mesoporous Mate silicate, CAS 12141-46-7 manufactured by Mineral-Right, rials, 39:319-332, 2000); CFSAPO-1A(He H, et al., J Incl. Inc., Phillipsburg, Kans. Revised Mar. 22, 1995) it consists Phenom., 5:591-599, 1987); JDF-2 (Chippindale AM, et al., in its physical State as a Solid in the form of granular crystals, Acta Crystallogr., C50: 1537-1540, 1994); MSC-1 (Simmen which are white-opaque in color. The Specific gravity of A, et al., Ph.D. Thesis, ETH Zurich, Switzerland, 1992); Sodium aluminum silicate is 0.80. It is insoluble in pH UiO-12-500 (Kongshaug KO, et al., Microporous and neutral aqueous Solution. It is formed from two ingredients: Mesoporous Materials, 39: 333-339, 2000); UiO-12-as hydrated alumina 1344-28-1 21% and sodium silicate (Kongshaug K O, et al., Microporous and Mesoporous 134409-868%. It is known to be non-toxic to ingestion. It Materials, 39: 333-339, 2000); AlPO-8 (Dessau RM, et al., is Subject to the following environmental protection proce Zeolites, 10:522-524, 1990; Richardson Jr J W, Zeolites, 12: dures: conventional housekeeping methods. It is to be 13-19, 1992); MCM-37 (Chu C T W, U.S. Pat. No. 5,091, handled Similar to earth. This material demonstrates tem 073, 1992); Afghanite (Barian P, et al. Bull. Soc. Fr. Mineral. perature-dependent weight loSS upon heating which appears Cristallogr. 91: 34-42, 1968; Merlino S, et al. Zeolite 1976, to be unchanged in the temperature range between approxi Program and Abstracts, Tucson Ariz., 1976; Pobedimskaya E A, et al. DOkl. Akad. Nauk SSSR 320: 882-886, 1991; mately 350 F. and 1200° F (Research Report Covering Ballirano P, et al. Eur: J. Mineral 9:21-31, 1997); AlPO-5 High Temperature Tests on the MR-1 Synthetic Zeolite, (Bennett J M, et al. ACS Sym. Ser218: 109-118, 1983; U.S. Baumbach Labs, Appleton, Wis.; Dec. 30, 1993). At higher Pat. No. 4,310,440, 1982); CoAPO-5 (Chao KJ, et al. J. temperatures, the “Zeolite Reflection Phenomenon” has Chem. Soc., Faraday Trans. 88: 2949-2954, 1992); been observed. CrAPO-5 (Radaev S, et al. J Mater. Chem. 6:1413-1418, 0108 Examples of Zeolites useful in the present invention 1996); SAPO-5 and its compositional variants (Flanigen E include Zeolite Li-A (Barrer and White) (Barrer RM, et al., M, et al. Pure Appl. Chem 58: 1351-1358, 1986; Flanigen J. Chem. Soc. 1267-1278, 1951; Kerr I S, Z. Kristallogr. EM, et al. In Proc. 7" Int. Zeolite Confi, Japan, pp. 103-112, 139:186-195, 1974; Krogh Anderson E, et al. Z. Kristallogr. 1986); SSZ-24 (Bialek R, et al., Zeolites 11:438-442, 1991); 176:67-73, 1986); Be-As-O-ABW (Gier T E, et al. TPAF AIPO-5 (Qiu S, et al. Zeolites 9:440-444, 1989); Nature 349:508-510, 1991; Harrison W T A, et al., Acta AlPO-14 (Broach RW, et al. In Proc. 12" Int. Zeolite Conf, Crystallogr. C51:181-183, 1995); Be-P-O-ABW (Gier USA, pp. 1715-1722, 1999); GaPO-14 (Parise J B, et al. T E, et al., Nature 349:508-510, 1991; Harrison WTA, et Acta Crystallogr. C42: 670-673, 1986); AlPO-41 (Kirchner al., Acta Crystallogr. C51:181-183, 1995; Robl C, et al. J. R M, et al. Zeolites 14:523-528, 1994); SAPO-40 (Ester Chem. Soc. Dalton Trans. 1911-1912; 1993); Ga-Si-O- mann MA, et al. J. Appl. Crystallogr. 25:539-543, 1992; ABW (Newsam J. M., J. Phys. Chem. 92:445-452; 1988); Dumont N, et al. Microporous Materials 1: 149-160, 1993; Zn-As-O-ABW (Gier T E, et al. Nature 349:508-510; McCusker LB, et al. Microporous Materials 6:51-54, 1996); 1991); Zn-P-O-ABW (Gier TE, et al. Nature 349:508 AlPO-40 (Ramaswamy V, et al. Microporous and Mesopo US 2005/0106267 A1 May 19, 2005 rous Materials 31:1-8, 1999); CoAPSO-40 and ZnAPSO-40 ??vol??:606-607, 1985); AlPO-21 (Bennett J M, et al. Inorg. (Lourence J. P. et al. ??Journal??38:267-278, 2000); Chem. 24:188-193, 1985; Parise JB, et al. Acta Crystallogr. MAPSO-46 (Bennett J M, et al. Stud. Surf Sci. Catal. C41:515-520, 1985); Ga-P-O-ATV (Parise JB, Chem. 37:269-279, 1988); AlPO-52 (Bennett J M, et al. Stud. Surf. Communic. 606-607, 1985); AlPO-22 (Richardson Jr JW, et Sci. Catal. 49:731-739, 1989; McGuire N K, et al. Zeolites al. Naturwiss. 76:467-469, 1989); Beta (Higgins J B, et al. 15:460-469, 1995); SAPO-56 (Wilson S T, et al. Zeolites 8:446-452, 1988; Newsam J M, et al. Proc. R. SOc. Microporous and Mesoporous Materials 28:125-137, 1999); Lond. A 420:375-405, 1988); B-Si-O-* BEA (Marler B, SSZ-16 (Lobo R F, et al. Chem. Mater. 8:2409-2411, 1996); et al. In Proc. 9" Int. Zeolite Conf., pp. 425-432, 1993; CoAPO-50 (Bennett J M, et al. Stud. Surf Sci. Catal. 37: Reddy K S N, et al. J Incl. Phenom. Mol. Recogn. Chem. 269-279, 1988); MgAPO-50 (Akolekar D B, et al. Zeolites 20:197-210, 1994); Ga-Si-O-BEA (Reddy K S N, et 15:583-590, 1995); AlPO-H2 (Li H X, et al. Chem. Com al. J Incl. Phenom. Mol. Recogn. Chem. 20:197-210, 1994); mun. ??Vol??: 403-405, 1993; Kennedy GJ, et al., Solid CIT-6 (Takewaki T, et al. Topics in Catalysis 9:35-42, 1999); State Nuc. Mag. Res 4: 173-178, 1995); Analcime (Taylor W Tschernichite (Boggs R C, et al. Am. Mineral. 78:822-826, H Z.Z. Kristallogr 74:1-19, 1930; Knowles CR, et al. Indian 1993); Bikitaite (Kocman V, et al., Am. Mineral. 59:71-78, Mineral. 6:127-, 1965; Ferraris G, et al. Z. Kristallogr. 135: 1974; Stahl K, et al. Zeolites 9:303-311, 1989); Ca-Al 240-252, 1972); Al-Co-P-O-ANA (Feng P Y, et al. Si-O-BIK (Annehed H, et al. Z. Kristallogr. 166:301-306, Nature 388: 735-741, 1997); Al-Si-P-O-ANA (Artioli 1984); Triclinic bikitaite (Bissert G, et al. N. Jb. Miner. Mh. G, et al. Acta Crystallogr. C40:214-217, 1984); Ga-Ge ??vol??:241-252, 1986); Boggsite (Pluth J J, et al. Am. O-ANA (Bu X, et al. J. Am. Chem. Soc. 120:13389-13397, Mineral. 75:501-507, 1990); Beryllophosphate-H (Harvey 1998); Cs-Na-(HO)Ga-Si-O-ANA (Yellon WB, et G, Z. Kristallogr. 182:123-124, 1988; Harvey G, et al. Z. al. Zeolites 10:553-558, 1990); CsCusSiOo-ANA (Heinrich AR, et al. Acta Crystallogr. C47:237-241, 1991); Kristallogr. 201:113-123, 1992); Linde Q (Andries KJ, et al. K-B-Si-O-ANA (Millini R, et al. Microporous Mate Zeolites 11:124-141, 1991); STA-5 (Patinec V, et al. Chem. rials 1:9-15, 1993); AlPO-24 (Wilson S T, et al. J. Am. Mater: 11:2456-2462, 1999); Brewsterite (Perrotta AJ, et al. Chem. Soc. 104:1146-1147, 1982); AlPO-pollucite (Keller Acta Crystallogr. 17:857-862, 1964; Schlenker J. L., et al. E B, Ph.D. Thesis, ETH Zurich, Switzerland, 1987); Ammo Acta Crystallogr. B33:2907-2910, 1977); Ba-dominant nioleucite (Hori H, et al. Am. Mineral. 71:1022-1027, 1986); brewsterite (Cabella R, et al. Eur: J. Mineral. 5:353–360, Ca-D (Ames LL, et al. Am. Mineral. 43:476-480, 1958); Cs 1993); CIT4 (Khodabandeh S, et al. Microporous and beryllosilicate pollucite (Torres-Martines LM, et al., J Solid Mesoporous Materials 11: 87-95, 1997); Synthetic bewster State Chem. 51: 100-103, 1984); Cs, Fe silicate pollucite ite (Ghobarker H, et al. German Patent AZ 19824 1844-41, (Kopp O C, et al. Am. Mineral. 48:100-109, 1963); Hsiang 1997); Cancrinite (Pauling L, Proc. Natl. Acad. Sci. 16:453 hualite (Wen-Hui H, et al. Am. Mineral. 44:1327-1328, 459, 1930; Jarchow O, Z. Kristallogr. 122:407-422, 1965); 1959); Kehoeite (McConnell D, et al. Can. Mines. 12:352-, Al-Ge-O-CAN (Belokoneva E L, et al. Sov. Phys. 1974); Leucite (Peacor D R, Z. Kristallogr. 127: 213-224, Crystallogr. 31:516-519, 1986); Ga-Si-O-CAN 1968); Na-B (Barrer R M, et al. J. Chem. Soc. ??vol??: (Newsam J. M., et al. Zeolites 7:569-573, 1987); Zn-P- 1561-1571, 1952); Pollucite (Nel H J, Am. Mineral. 29: O-CAN (Yakubovich O V, et al. Crystallogr. Reports 443-451, 1944); Synthetic analcime (Ghobarker H, et al. 39:564-568, 1994); Basic cancrinite (Barrer R M, et al. J. Cryst. Res. Technol. 1071-1075, 1986); Synthetic hsinghua Chem. Soc. 1561-1571, 1952; Bresciana Pahor N, et al. Acta lite (Ghobarker H, et al. Annal. Chemie, Science Materiaux Crystallogr. B38:893-895, 1982); Cancrinite hydrate (Wyart 24:209-215, 1999); Synthetic wairakite (Ghobarker H, et al. J, et al. Compt. Rend. 229:131-, 1949); Davyne (Hassan I, et Cryst. Res. Technol. K90-92, 1985); Wairakite and addi al. Can. Mineral. 28:341-349, 1990); ECR-5 (Vaughn DE tional compositional variants (Takeuchi Y. et al. Am. Min W. E. Patent A-190,90; 1986); Microsommite (Bonaccorsi eral, 64: 993-1001, 1979); AilPO-C (Bennett J. M., et al. E, et al. Phys. Chem. Mineral. 22:367-374, 1995); Synthetic Zeolites 6:349-359, 1986; Keller E B, et al. Solid State cancrinite (Smolin Y I, et al. Kristallografiya 26:63-66, Ionics 43:93-103(?), 1990; AIPO-H3 (Pluth JJ, et al. Acta 1981); Tiptopite (Peacor D R, et al., Am. Mineral.., 72:816 Crystallogr. C42:1118-1120, 1986); AlPO-D (Keller E B, et 820, 1987); Vishnevite (Hassan I, et al. Can. Mineral. al. Solid State Ionics 43:93-103, 1990); AlPO-16 (Bennett J 22:333-340, 1984); Cesium aluminosilicate (Araki T Z, Z. M, et al., Zeolites 11:502-506, 1991); Octadecasil (Caullet P. Kristallogr. 152:207-213, 1980); CIT-5 (Wagner P, et al. et al. Eur: J. Solid State Inorg. Chem. 28:345-361, 1991); Chem. Commun. 2179-2180, 1997; Yoshikawa M, et al. J ASU-7 (Li H, et al. J. Am. Chem. Soc. 120:10569-10570, Phys. Chem. B 102:7139-7147, 1998); C-Ga-Phosphate-5 1998); MAPO-39 (McCusker LB, et al. Acta Crystallogr. (Chippindale AM, et al. Zeolites 18:176-181, 1997); C-Ga A46:C59(?), 1990; Baur W H, et al. Z. Kristallogr. 214:154 Phosphate-6 (Cowley AR, et al. Microporous and Mesopo 159, 1999); AlPO-31 (Bennett J. M., et al. Zeolites 12:338 rous Materials 28:163–172, 1999); Zn-Ga-P-O-CGS 342, 1992; Baur W H, et al. Acta Crystallogr. B50: 290–294, (Cowley AR, et al. Microporous and Mesoporous Materials 1994); SAPO-31 (Flanigen E. M., et al. Pure Appl. Chem. 28:163–172, 1999); TNU-1 (Hong SB, et al. J. Mater. Chem. 58:1351-1358, 1986; Flanigen E M, et al. In Proc. 7 Int. 9:2287–2289, 1999); Ga-Si-O-CGS (Hong S B, et al. J Zeolite Conf, Japan, pp. 103-112, 1986; Baur W H, et al. Mater. Chem. 9:2287–2289, 1999); TSG-1 (Lee YJ, et al. J Acta Crystallogr. B50:290–294, 1994); MAPO-36 (Smith J Mater. Chem. 11:879-880, 1999); Ga-Si-O-CGS (Lee Y V, et al. Zeolites 13: 166-169, 1993); AlPO-12-TAMU J, et al. J Mater. Chem. 11:879-880, 1999); Chabazite (Dent (Rudolf PR, et al. J Phys. Chem. 90:6122-6125, 1986); LS, et al. Nature 181:1794-1796, 1958; Smith JV, et al. Acta AlPO-33 (Smith J V, et al. PRIVATE COMMUNIC; Patton Crystallogr. 16:45-53, 1963); Al-Co-P-O-CHA (Feng RL, et al. U.S. Pat. No. 4,473,663, 1984); AlPO-25 (Rich PY, et al. Nature 388:735-741, 1997); Co-Al-P-O- ardson Jr J. W., et al., J Phys. Chem. 94; 3365-3367, 1990); CHA (Feng PY, et al. Nature 388:735-741, 1997; Feng P, et Ga-P-O-ATV (Parise J B, Chem. Communic. al. Microporous and Mesoporous Materials 23:221-229, US 2005/0106267 A1 May 19, 2005 17

1998); Mg-Al-P-O-CHA (Feng P. et al. Microporous GaPO-34 (Schott-Darie C, et al. Stud. Surf Sci. Catal. and Mesoporous Materials 23:221-229, 1998); AlPO-34 84:101-108, 1994); LZ-218 (Breck D. W., et al. U.S. Pat. No. (Harding M M, et al. Acta Crystallogr.C50:852-854, 1994); 4.333,859, 1982); Linde D (Breck D. W., et al. U.S. Pat. No. CoAPO-44 (Bennett J M, et al. Stud. Surf Sci. Catal 2,950,952, 1960; Lillerud KP, et al. J. Chem. Soc., Faraday 37:269-279, 1988); CoAPO-47 (Bennett J M, et al. Stud. Transactions 90:1547-1551, 1994); and/or the other frame Surf Sci. Catal. 37:269-279, 1988); Dehydrated Na-Chaba work minerals, both natural and Synthetic, a table of which zite (Mortier WJ, et al. Mater. Res. Bull. 12:241-250, 1977); appears below.

TABLE 4 Page or Name of Zeolite First Author Cited Citation Vol. Number Year Linde R Milton RM British Patent 841,812 96.O MeAPO-47 Bennett J M, et al. Stud. Surf. Sci. Catal. 37: 269-279 988 Flanigen E M, et al. Pure Appl. Chem. 58: 1351-1358 986 Flanigen E M, et al. In Proc. 7 Int. Zeolite 103-112 986 Conf., Japan MeAPSO-47 Bennett J M, et al. Stud. Surf. Sci. Catal. 37: 269-279 988 Flanigen E M, et al. Pure Appl. Chem. 58: 1351-1358 986 Flanigen E M, et al. In Proc. 7 Int. Zeolite 103-112 986 Conf., Japan Phil Lillerud K. P. et al. J. Chem. Soc., Faraday 90: 1547-1551 994 Transactions Grose RW, et al. U.S. Pat. No. 4,124,686 978 SAPO-34 Lok, BM, et al. J. Am. Chem. Soc. 106: 6092-6093 984 SAPO-37 Pluth JJ, et al. J. Phys. Chem. 93: 6516-6520 989 Si-CHA Diaz-Cabanas M J, et Chem. Commun. 1881-1882 998 al. Wilhendersonite Tillmanns E, et al. N. J. Miner. Mh. 547-558 984 ZK-14 Kuehl G. H. PRIVATE COMMUNICATION Kuehl G. H. In Molecular Sieves, 85-91 968 (ed. R. M. Barrer) ZYT-6 Ito M, et al. Acta Crystallogr. C41: 1698-17OO 985 Herschelite Discredited Chiavennite Tazzoli V, et al. Eur. J. Mineral. 7: 1339-1344 995 Cloverite Esterman M, et al. Nature 352: 320-323 991 CT1 Lobo R F, et al. J. Am. Chem. Soc. 117: 3764-3779 995 SSZ-26 Lobo R F, et al. J. Am. Chem. Soc. 117: 3764-3779 995 Lobo R F, et al. Science 262: 1543-1546 993 SSZ-33 Lobo R F, et al. J. Am. Chem. Soc. 117: 3764-3779 995 Lobo R F, et al. Science 262: 1543-1546 993 Chiral Rajic N, et al. Zeolites 5: 672-678 995 Zincophosphate Harrision WTA, et al. Chem. Mater. 8: 145-151 996 Dachiardite Gottardi G, et al. Z. Kristallogr. 119: 53-64 963 Vezzalini G Z Z. Kristallogr. 1.66: 63-71 984 Svetlozarite Discredited Gellens L. R, et al. Mineral. Mag. 45: 157-161 982 Deca-dodecasil 3R Gies H. Z. Kristallogr. 175: 93-104 986 Sigma-1 Stewart A, et al. Stud. Surf. Sci. Catal. 37: 57-64 988 ZSM-58 Valyocsik EW U.S. Pat. No. 4,698,217 987 Ernst S, et al. In Zeolites for the 8th IZO 55-56 989 Nineties, Recent Progress Reports - Abstracts DAF-1 Wright PA, et al. Chem. Commun. 633-635 993 DAF-2 Chen J, et al. Angew. Chem., Int. Ed. 33: 639-640 994 ACP-3 Bu X, et al. J. Solid State Chem. 136: 210-215 998 UCSB-3GaGe Bu X, et al. J. Am. Chem. Soc. 12O: 13389-13397 998 UCSB-3ZnAS Bu X, et al. J. Solid State Chem. 136: 210-215 998 UO-2O Kongshuang KO, et al. Chem. Mater. 12: 1095-1099 2OOO Dodecasil 1H Gierke H, et al. Z. Kristallogr. 1.66: 11-22 984 UTD-1F Wessels T, et al. J. Am. Chem. Soc. 121: 6242-6247 999 UTD-1 Lobo R F, et al. J. Am. Chem. Soc. 119: 8474-84.84 997 TMA-E (Aiello and Aiello R, et al. J. Chem. Soc. (A). 1470-1475 970 Barrer) Meier W M, et al. J. Solid State Chem. 37: 2O4-218 981 Bellbergite Ridinger B, et al. Miner. Petrol. 48: 147-152 993 Edingtonite Taylor W H, et al. Z. Kristallogr. 86: 53-64 933 Galli E Acta Crystallogr. B32: 1623-1627 976 Kvick A, et al. J. Chem. Phys. 79: 2356-2362 983 Co-Al-P-O-EDI Bu X, et al. Chem. Mater. 10: 2546-2551 998 Co-Ga-P-O-EDI Bu X, et al. Chem. Mater. 10: 2546-2551 998 K-F Barrer RM, et al. J. Chem. Soc. 2882-2891 956 Baerlocher Ch, et al. Z. Kristallogr. 140: 10-26 974. US 2005/0106267 A1 May 19, 2005 18

TABLE 4-continued Page or Name of Zeolite First Author Cited Citation Vol. Number Year Linde F Sherman J D ACS Sym. Ser. 40: 30-42 977 Synthetic Ghobarker H, et al. Cryst. Res. Technol. 32: 653-657 997 edingtonite Tetragonal Mazzi F, et al. N. Jb. Miner. Mh. 373-382 984 edingtonite Zeolite N Christensen AN, et al. Acta Chemica Scand. 51: 969-973 997 EMC-2 Delprato F, et al. Zeolites 10: 546-552 990 Baerlocher Ch, et al. Microporous Materials 269-28O 994 CSZ-1 Barrett MG, et al. UK Patent GB 2,076,793 981 ECR-30 Vaughn D. EW E Patent 0.351,461 989 ZSM-2O Newsam J. M., et al. Chem. Commun. 493-495 989 ZSM-3 Kokotailo GT, et al. Adv. Chem. Ser. 101: 109-121 971 Epistilbite Kerr IS Nature 2O2: 589 964 Perrotta AJ Mineral. Mag. 36: 480-490 967 Alberti A, et al. Z. Kristallogr. 173: 257-265 985 Yang P. et al. Eur. J. Mineral. 263-271 996 Synthetic Ghobarkar H Cryst. Res. Technol. 151-1573(2) 984 epistilbite Erionite Staples L. W., et al. Mineral. Mag. 32: 261-281 959 Kawahara A, et al. Bull. Soc. Fr. Mineral. 92: 250-256 969 Cristallogr. Gard JA, et al. In Proc. 3rd Int. Cong. 94-99 973 Molecular Sieves AIPO-17 Pluth JJ, et al. Acta Crystallogr. C42: 283-286 986 Flanigen E M, et al. Pure Appl. Chem. 58: 1351-1358 986 Flanigen E M, et al. In Proc. 7" Int. Zeolite 103-112 986 Conf. LZ-220 Breck D. W., et al. U.S. Pat. No. 4,503,023 985 Linde T Breck D W Zeolite Molecular 73 974. Sieves ERS-7 Campbell B J, et al. Chem. Commun. 1725-1726 998 Millini R, et al. In Proc. 12" Int. Zeolite 541-548 999 Conf. EU-1 Casci J. L., et al. U.S. Pat. No. 4,537,754 985 Briscoe NA, et al. Zeolites 74-76 988 TPZ-3 Sumitani K, et al. E Patent EP 51318 982 ZSM-50 Rohrbaugh WJ Private communication Faujasite Bergerhoff G, et al. N. Jb. Miner. Mh. 193-200 958 Baur W H Am. Mineral. 49: 697-704 964 Al-Ge-O-FAU Barrer RM, et al. 195-208 959 Co-Al-P-O-FAU Feng PY, et al. 388: 735-741 997 Ga-Ge-O-FAU Barrer RM, et al. 195-208 959 Beryllophosphate Gier TE, et al. 12: 770-775 992 CSZ-1 Barrett MG, et al. UK Patent BG 2,076,793 981 ECR-30 Vaughn D. EW E Patent 0.351,461 989 LZ-210 Breck D. W., et al. U.S. Pat. No. 4,503,023 985 Linde X Milton RM U.S. Pat. No. 2,882,244 959 Olson DH, et al. J. Phys. Chem. 74: 2758-2764 970 Linde Y Breck D W U.S. Pat. No. 3,130,007 964 Costenoble M L, et al. J. Chem. Soc., Faraday 72: 1877-1883 976 Trans. I SAPO-37 Lok B M, et al. J. Am Chem. Soc. 106: 6092-6093 984 Siliceous Na-Y Hrilac JJ, et al. J. Solid State Chem. 106: 66-72 993 ZSM-2O Newsam J. M., et al. Chem. Commun. 493-495 989 ZSM-3 Kokotailo GT, et al. Adv. Chem. Ser. 101: 109-121 971 Zincophosphate X Gier TE, et al. Zeolites 12: 770-775 992 Ferrierite Vaughn PA Acta Crystallogr. 21: 983-990 966 Ga-Si-O-FER Jacob NE, et al. Zeolites 13: 430-434 993 Si-O-FER Gies H, et al. Zeolites 442-445 987 Morris RE, et al. J. Am. Chem. Soc. 116: 11849-11855 994 Seddon D, et al. E Patent B-55,529 985 ISI-6 Morimoto N, et al. U.S. Pat. No. 4,578,259 986 Monoclinic Gramlich-Meier R, et Am. Mineral. 70: 619-623 985 ferrierite al. NU-23 Whittan TV E Patent A-103-981 984 Barrer RM, et al. J. Chem. Soc. 2296-2305 964 Plank C J, et al. U.S. Pat. No. 4,016,245 977 Franzinite Ballirano P, et al. Can. Mineral. 38: 657-668 2OOO Gismondine Fischer K, et al. Adv. Chem. Ser. 101: 250-258 971 Al-Co-P-O-GIS Feng PY, et al. Nature 388: 735-741 997 Co-Al-P-O-GIS Feng P. et al. Microporous and 23: 221-229 998 Mesoporous Materials US 2005/0106267 A1 May 19, 2005 19

TABLE 4-continued Page or Name of Zeolite First Author Cited Citation Vol. Number Co-Ga-P-O-GIS Cowley A R, et al. Chem. Commun. 673-674 Co-P-O-GIS Yuan H. M., et al. Inorg. Chem. 39: 1476-1479 Ga-Si-O-GIS Cho H. H., et al. Chem. Mater. 12: 2292-23OO Mg-Al-P-O-GIS Feng P. et al. Microporous and 23: 221-229 Mesoporous Materials Zn-Ga-P-O-GIS Chippindale A M, et al. Microporous and 24: 133-141 998 Mesoporous Materials Kniep R, et al. Angew. Chem. Int. Ed. 38: 3642-3644 999 |CsIZnBPsOs-GIS Kniep R, et al. Angew. Chem. Int. Ed. 38: 3642-3644 999 RbZn BPO-GIS Kniep R, et al. Angew. Chem. Int. Ed. 38: 3642-3644 999 Amicite Alberti A, et al. Acta Crystallogr. B35: 2866-2869 979 Garronite Artioli G Am. Mineral. 77: 189-196 992 Artioli G, et al. Powder Diffraction 14: 190-194 999 Gobbinsite McCusker LB, et al. Z. Kristallogr. 171: 281-289 985 High-silica Na-P Hakansson U, et al. Acta Crystallogr. C46: 1361-1362 990 Low-silica Na-P Albert B R, et al. Microporous and 21: 133-142 998 (MAP) Mesoporous Materials MAPO-43 Pluth JJ, et al. J. Am. Chem. Soc. 111: 1692-1698 989 MAPSO-43 Flanigen E M, et al. Pure Appl. Chem. 58: 1351-1358 986 Flanigen E M, et al. In Proc. 7 Int. Zeolite 103-112 986 Conf. Baerlocher Ch, et al. Z. Kristallogr. 135: 339-354 972 Hansen S, et al. Acta Crystallogr. C46: 1361-1362 990 Helliwell M, et al. Acta Crystallogr. B49: 413-420 993 Schropfer L, et al. Eur. J. Mineral. 53-65 997 Synthetic amicite Ghobarkar H, et al. Mater. Res. Bull 34: 517-525 999 Synthetic garronite Ghobarkar H, et al. Mater. Res. Bull 34: 517-525 999 Synthetic Ghobarkar H, et al. Mater. Res. Bull 34: 517-525 999 gobbinsite TMA-gismondine Baerlocher Ch, et al. Helv. Chim. Acta 53: 1285-1293 970 Gismondite discredited Synthetic zeolite B disused Gmelimite Fischer K. N. Jb. Miner. Mh. 1-13 966 K-rich gmelinite Vezzalini G, et al. N. Jb. Miner. Mh. 504-516 990 Synthetic fault-free Daniels R H, et al. J. Am. Chem Soc 3097-31OO 978 gmelinite Sarcolite Discredited GUS-1 Plevert J, et al. Chem. Commun. 2363-2364 Goosecreekite Rouse R C, et al. Am. Mineral. 71: 1494-15O1 Heulandite Merkle A B, et al. Am. Mineral. 52: 273-276 Alberti A Tschermarks Min. Petr. 18: 129-146 Min. Clinoptilolite Koyama K, et al. Z. Kristallogr. 145: 216-239 977 Dehydrated Mortier WJ, et al. Am. Mineral. 66: 309-314 981 Ca, NH-Heulandite LZ-219 Breck D. W., et al. U.S. Pat. No. 4,503,023 985 ITO-4 Barrett PA, et al. Chem. Mater. 1713-1715 997 MCM-58 Valyo, EW WOP 9511196 995 SSZ-42 Chen CY, et al. Chem. Commun. 1775-1776 997 ITO-7 Villaescusa L. A., et al. Angew. Chem. Int. Ed. 38: 1997-2OOO 999 ITO-3 Camblor, MA, et al. Angew. Chem. Int. Ed. 36: 2659-2661 997 Na-J (Barrer and Hansen S, et al. Zeolites 162-166 982 White) Nepheline hydrate Rheinhardt A, et al. Fortsch. Mineral. 60: 175-176 982 Synthetic Na-Al-Si-O-JBW Ragimov KG, et al. Sov. Phys. Dokl. 23: 697-698 978 Meier W M, et al. Z. Kristallogr. 121: 211-219 965 Robson HE U.S. Pat. No. 3,270,753 973 Parise J B, et al. Z. Kristallogr. 165: 175-190 983 P Barrer RM, et al. Z. Kristallogr. 135: 374-390 972 O Barrer RM, et al. Z. Kristallogr. 135: 374-390 972 Laumontite Bartl H, et al. Jb. Miner. Mh. 33-42 967 Amirov ST, et al. Dokl. Akad. Nauk SSSR 174: 667 967 Schramm V, et al. Adv. Chem. Ser. 101: 259-265 971 Artioli G, et al. Zeolites 17: 249-255 993 Co-Ga-P-O-LAU Chippindale A M, et al. Chem. Commun. 2453-24.54 994 Bond AD, et al. Zeolites 19: 326-333 997 Fe-Ga-P-O-LAU Bond AD, et al. Zeolites 19: 326-333 997 Mn-Ga-P-O-LAU Bond AD, et al. Zeolites 19: 326-333 997 Synthetic Ghorbarkar H, et al. Microporous and 23: 55-60 998 laumontite Mesoporous Materials Leonhardite Lapham DL Am. Mineral. 48: 683-689 963 (discredited) US 2005/0106267 A1 May 19, 2005 2O

TABLE 4-continued Page or Name of Zeolite First Author Cited Citation Vol. Number Year Levyne Barrer RM, et al. Trans. Faraday Soc. 55: 1915-1923 959 Merlino S, et al. Min. Petr. Mitt. 22: 117-129 975 AIPO-35 Zhu G S, et al. Microporous Materials 11: 269-273 997 CODAF-4 Barrett PA, et al. Phys. Chem. Chem. 407-412 2OOO Phys. LZ-132 Tvaruzkova Z. et al. Int. Zeolite Sym., 988 Wurzburg, Extended Abstracts NU-3 McCusker LB Mater. Sci. Forum 133-136: 423-433 993 SAPO-35 Lok B M, et al. J. Am. Chem. Soc. 106: 6092-6093 984 ZK-20 Kerr GT U.S. Pat. No. 3,459,676 969 Liottite Merlino S, et al. Am. Mineral. 62: 321-326 977 Ballirano P, et al. Can. Mineral. 34: 1021-1030 996 LOSod Sieber W, et al. Helv. Chim. Acta 57: 1533-1549 974. Schicker P Ph. D. Thesis, ETH 988 Zurich, Switzerland Al-Ge-O-LOS Sokolov Yu.A., et al. Sov. Phys. Dokl. 23: 789-791 978 Li-Be-P-O-LOS Harrison WTA, et al. Zeolites 13: 242-248 993 Bystrite Pobedimskaya E A, et Sov. Phys. Dokl. 36: 553-555 991 al. Lovdarite Merlino S Acta Crystallogr. A37: C189 981 (Suppl.) Merlino S Eur. J. Mineral. 809-817 990 Synthetic lovdarite Ueda S, et al. Preprints of Poster 986 Papers, 7" Int. Zeolite Conf. Linde Type A Reed T B, et al. J. Am. Chem. Soc. 78: 5972-5977 956 Gramlich V, et al. Z. Kristallogr. 1.33: 134-149 971 Al-Ge-O-LTA Barrer RM, et al. J. Chem. Soc. 195-208 959 Ga-P-O-LTA Simmen A, et al. In Proc. 9" Int. Zeolite 433-440 993 Conf. Alpha Wadlinger RL, et al. U.S. Pat. No. 3,375,205 968 LZ-215 Breck D. W., et al. U.S. Pat. No. 4,503,023 985 N-A Barrer RM, et al. J. Chem. Soc. 971-982 961 SAPO-42 Lok B M, et al. J. Am. Chem. Soc. 106: 6092-6093 984 ZK-21 Kuehl G. H. Inorg. Chem. 10: 2488-2495 971 ZK-22 Kuehl G. H. Inorg. Chem. 10: 2488-2495 971 ZK-4 Kerr GT Inorg. Chem. 1537-1539 966 Linde Type L Barrer RM, et al. Z. Kristallogr. 128: 969 (K.Ba)-G, L Baerlocher Ch., et al. Z. Kristallogr. 136: 972 Gallosilicate L Wright PA, et al. Nature 318: 985 Newsam J. M., et al. Mater. Res. Bull. 21: 986 LZ-212 Breck D. W., et al. U.S. Pat. No. 4,503,023 985 Perialite Menshikov YP Vses. Mineral. O-va 113: 607-612 984 Artioli G, et al. Eur. J. Mineral. 749-759 990 Linde Type N Falth L, et al. Z. Kristallogr. 160: 313-316 982 NaZ-21 Sheplev Yu F, et al. Dokl. Akad. Nauk SSSR 272: 1133-113 7 983 Mazzite Galli E Cryst. Struct. Comm. 339-344 974. Galli E Rend. Ital. Mineral. 31: 599-612 975 Petrol. Ga-Si-O-MAZ Newsam J. M., et al. Mater. Res. Bull. 25-136 985 LZ-2O2 Breck D. W., et al. U.S. Pat. No. 4,503,023 985 Omega Galli E Cryst. Struct. Comm. 339-344 974. Rubin M K, et al. U.S. Pat. No. 4,021,447 977 ZSM-18 Lawton SL, et al. Science 247: 1319-1321 990 ZSM-11 Kokotailo GT, et al. Nature 275: 19-12O 978 Fyfe CA, et al. J. Am. Chem. Soc. 111: 2470-2474 989 Van Koningveld H, et In Proc. 12" Int. Zeolite 2419-2424 999 al. Conf. Bor-D (MFI/MEL Perego G, et al. J. Appl. Crystallogr. 17: 403-410 984 intergrowth) Boralite D Taramasso M, et al. GB Patent 2,024,790 98O SSZ-46 Terasaki O, et al. Chem. Mater. 463-468 996 Nakagawa Y, et al. U.S. Pat. No. 5,968,474 999 Silicalite 2 Bibby D M, et al. Nature 280: 664-665 979 TS-2 Reddy J S, et al. Zeolites 12: 95-100 992 Melanophlogite Gies H. Z. Kristallogr. 164: 247-257 983 Gies H, et al. N. Jb. Miner. Mh. 19-124 982 Merlinoite Passaglia E, et al. N. Jb. Miner. Mh. 355-364 977 N. Jb. Miner. Mh. 1-9 979 Al-Co-P-O-MER Feng PY, et al. Nature 388: 735-741 997 Ba-Al-Si-O- Gottardi G, et al. Natural Zeolites (book) 157 985 MER US 2005/0106267 A1 May 19, 2005 21

TABLE 4-continued Page or Name of Zeolite First Author Cited Citation Vol. Number Year Ba-Cl-Al-Si-O- Soloveva L. P. et al. Sov. Phys. Crystallogr. 16: 1035-1038 972 MER NH4-Be-P-O- Bu X, et al. Microporous and 26: 61-66 998 MER Mesoporous Materials Gottardi G, et al. Natural Zeolites (book) 157 985 Barrer RM, et al. J. Chem. Soc. 2882-2891 956 Linde W Gottardi G, et al. Natural Zeolites (book) 157 985 Sherman J D ACS Sym. Ser. 40: 30-42 977 Synthetic Barrett PA, et al. J. Mater. Chem. 2263-2268 998 Merlinoite Zeolite W Bieniok A, et al. J. Mater Chem. 271-275 996 ZSM-5 Kokotailo GT, et al. Nature 272: 437-438 978 Olson DH, et al. J. Phys. Chem. 85: 2238-2243 981 Van Koningsveld H, et Acta Crystallogr. B43: 127-132 987 al. As-Si-O-MFI Bhaumik A, et al. Chem. Commun. 869-87O 995 Fe-Si-O-MFI Patarin J, et al. Zeolites 10: 674-679 990 Ga-Si-O-MFI Awate S V, et al. J. Inc. Phenom. 13: 2O7-218 992 AMS-1B Klotz, MR U.S. Pat. No. 4,269,813 981 AZ-1 Chono M, et al. E. Patent B-113,116 984 Bor-C Taramasso M, et al. In Proc. 5". Int. Zeolite 40-48 98O Conf. Boralite C Taramasso M, et al. GB Patent 2,024,790 98O Encilite Ratnasamy P. et al. E. Patent A-160,136 985 FZ-1 Suzuki T, et al. E. Patent B-31,255 981 LZ-105 Grose RW, et al. U.S. Pat. No. 4,257,885 981 Monoclinic H Van Koningsveld H, et Zeolites 10: 235-242 990 ZSM-5 al. Mutinaite Vezzalini G, et al. Zeolites 19: 323-325 997 NU-4 Whittan TV E. Patent B-65,401 986 NU-5 Whittan TV B-54,386 982 Silicalite Flanigen E M, et al. 271: 512-516 978 TS-1 Taramasso M, et al. 4,410,501 983 TSZ, Ashibe K, et al. A-101.232 984 TSZ-III Sakurada S, et al. A-170,751 986 TZ-O1 Iwayama K, et al. A-57,016 982 USC-4 Young DA 4,325,929 982 US-108 Hinnenkamp JA, et al. 4,423,020 983 ZBH Holderich W, et al. B-77,946 986 ZKO-1B Kee Kwee L S L A-148,038 984 ZMO-TB Kee Kwee L S L A-104,107 983 ZSM-57 Schlenker J. L., et al. 10: 293-296 990 Montesommaite Rouse R C, et al. 75: 1415-1420 990 Mordenite Meier WM Z. Kristallogr. 115: 439-450 961 Ga-Si-O-MOR Eapen M J, et al. J. Inc. Phenom. 14: 119-129 992 Ca-O Koizumi M., et al. J. Geol. 68: 41-53 96.O LZ-211 Breck D. W., et al. U.S. Pat. No. 4,503,023 985 Large pore Sand LB In Molecular Sieves 71-77 968 mordenite (ed. R M Barrer) Maricopalite Rouse R C, et al. Am. Mineral. 79: 175-184 994 (interrupted framework) Na-D Barrer RM, et al. J. Chem. Soc. 1561-1571 952 Ptilolite Discredited Arduinite Discredited Flokite Discredited MCM-61 Valyosik EW U.S. Pat. No. 5,670,131 997 Shantz, DF, et al. Microporous and 31: 61-73 999 Mesoporous Materials MCM-35 Barrett PA, et al. Chem. Mater. 11: 2919-2927 999 UTM-1 Plevert J, et al. J. Phys. Chem. B 1O3: 8647-8649 999 ZSM-39 Schlenker J. L., et al. Nature 29.4: 340-342 981 CF-4 Long Y, et al. J. Inc. Phenom. 355-362 987 Dodecasil-3C Gies H. Z. Kristallogr. 167: 73-82 984 Holdstite Smith J. V. et al. Nature 3O3: 223-225 983 ZSM-23 Schlenker J. L., et al. Private communication Rohrman Jr. A C, et al. Zeolites 352-354 985 Marler B, et al. J. Appl. Crystallogr. 636-644 993 EU-13 Araya A, et al. U.S. Pat. No. 4,581,211 986 ISI-4 Kakatsu K, et al. Eur. Pat. Appl. EPA 102,497 984 Parker LM, et al. Zeolites 8-11 983 ZSM-12 LaPierre R B, et al. Zeolites 346-348 985 Fyfe CA, et al. J. Phys. Chem. 3718-3721 990 US 2005/0106267 A1 May 19, 2005 22

TABLE 4-continued Page or Name of Zeolite First Author Cited Citation Vol. Number Year Ga-Si-O-MTW Zhi Y X, et al. Zeolites 12: 138-14 992 CZH-5 Hickson DA, et al. UK Pat. Appl. GB2O79735A 981 NU-13 Whittan TV Eur. Pat. Appl. EPAO059059 982 Sumitani K, et al. U.S. Pat. No. 4,557,919 985 Theta-3 Barlow TM E. Patent A-162,719 985 VS-12 Reddy KM, et al. Chem. Commun. 1491-1492 994 MCM-22 Leonowicz, ME, et al. Science 264: 1910-1913 994 ERB-1 Belussi G, et al. Eur. Pat. Appl. EPA293032 988 ITO-1 Camblor MA, et al. Chem. Mater. 2415-2417 996 Camblor MA, et al. J. Phys. Chem. B 1O2: 44-51 998 PSH-3 Puppe L, et al. U.S. Pat. No. 4,439,409 984 SSZ-25 Zones S I E. Patent 231,860 987 Natrolite Pauling L Proc. Nat. Acad. Sci. 16: 453-459 930 Meier WM Z. Kristallogr. 113: 430-444 96.O Al-Ge-O-NAT Tripathi A, et al. J. Mater. Chem. 10: 451-455 2OOO Ga-Si-O-NAT Xie D, et al. In MRS Sym. Proc. 111: 147-154 988 (Materials Res. Soc.) Rb-Ga-Ge-O-NAT Klaska KH, et al. Z. Kristallogr. 172: 167-174 985 Gonnardite Mazzi F, et al. N. Jb. Miner. Mh. 219-228 986 High natrolite Baur W H, et al. N. Jb. Miner. Mh. 171-187 996 Mesolite Artioli G, et al. Acta Crystallogr. C42: 937.942 986 Metanatrolite Joswig W, et al. N. Jb. Miner. Mh. 26-38 995 Scolecite Taylor W H, et al. Z. Kristallogr. 86: 53-64 933 Falth L, et al. Acta Crystallogr. B35: 1877-1880 979 Smith J. V. et al. In Proc. 6" Int. Zeolite 842-850 984 Conf. Synthetic Ghorbarkar H, et al. Zeolites 19: 259-261 997 gonnardite Synthetic mesolite Ghorbarkar H, et al. Cryst. Res. Technol. 31: K67-69 996 Synthetic natrolite Ghorbarkar H, et al. Cryst. Res. Technol. 31: K67-69 996 Synthetic scolecite Ghorbarkar H, et al. Cryst. Res. Technol. 31: K67-69 996 NU-87 Shannon MD, et al. Nature 353: 417-42O 991 Gottardite Alberti A, et al. Eur. J. Mineral. 69-75 996 Nonasil Marler B, et al. J. Inc. Phenom. 339-349 986 B-Si-O-NON Marler B, et al. Zeolites 15: 517-525 995 (Co(C5H5)2), F4 Vandegoor G, et al. Z. Anorg. Allg. Chemie 621: 311-322 999 SissO76-NON CF-3 Long Y-C, et al. J. Inc. Phenom. 121-127 986 Rohrbaugh WJ Private communication Offretite Bennett J M, et al. Nature 214: 1005-1006 967 Gard JA, et al. Acta Crystallogr. B28: 825–834 972 LZ-217 Breck D. W., et al. U.S. Pat. No. 4,503,023 985 Linde T (ERI-OFF Breck D. W., et al. Zeolite Molecular 173 974. structural Sieves (book) intermediate) Synthetic offretite Ghobarkar H, et al. Cryst. Res. Technol 31: K29-31 996 TMA-O Aiello R, et al. Trans. Faraday Soc. 66: 1610-1617 970 Akporiaye DE, et al. Chem. Commun. 1553-1554 996 OSB-1 Kongshaug KO, et al. Private communication Parthetite Engel N, et al. Z. Kristallogr. 169: 65-175 984 Paulingite Gordon E K, et al. Science 154: 1004-1007 966 ECR-18 Vaughn D. E. W., et al. U.S. Pat. No. 4,661,332 987 Phillipsite Steinfink H. Acta Crystallogr. 15: 644-651 962 Rinaldi R, et al. Acta Crystallogr. B30: 2426-2433 974. Al-Co-P-O-PHI Feng PY, et al. Nature 388: 735-741 997 Harmotome Rinaldi R, et al. Acta Crystallogr. B30: 2426-2433 974. Sadanaga R, et al. Acta Crystallogr. 14: 1153-1163 961 ZK-19 Kuehl G. H., et al. Am. Mineral. 54: 1607-1612 969 Wellsite Cerny P, et al. N. Jb. Miner. Abh. 128: 312-330 977 (discredited) Rho Robson HE, et al. Adv. Chem. Ser. 121: 06-115 973 McCusker LB, et al. In Proc. 6 Int. Zeolite 812-822 984 Conf. Be-As-O-RHO Gier TE, et al. Nature 349: SO8-510 991 Be-P-O-RHO Harvey G, et al. Stud. Surf. Sci. Catal. 49: 411-420 989 Co-Al-P-O-RHO Feng P. et al. Microporous and 23: 315-322 998 Mesoporous Materials Mg-Al-P-O-RHO Feng P. et al. Microporous and 23: 315-322 998 Mesoporous Materials Mn-Al-P-O-RHO Feng P. et al. Microporous and 23: 315-322 998 Mesoporous Materials Deuterated Parise J B, et al. J. Phys. Chem. 88: 1635-1640 984 Gallosilicate ECR-10 Newsam J. M., et al. J. Phys. Chem. 99: 9924-9932 995 US 2005/0106267 A1 May 19, 2005 23

TABLE 4-continued Page or Name of Zeolite First Author Cited Citation Vol. Number Year LZ-214 Breck D. W., et al. U.S. Pat. No. 4,503,023 985 Pahasapaite Rouse R C, et al. N. Jb. Miner. Mh. 433-440 987 Rouse R C, et al. Am. Mineral. 74: 1195-1202 989 Roggianite Giuseppetti G, et al. N. Jb. Miner. Mh. 307-314 991 RUB-17 Rohrig C, et al. Angew. Chem. Int. Ed. 34: 63-65 995 RUB-3 Marler B, et al. Zeolites 15: 388-399 995 Marler B, et al. Microporous and 26: 49-59 998 Mesoporous Materials RUB-13 Vortmann S, et al. Microporous Materials 111-121 995 RUB-10 Gies H, et al. U.S. Pat. No. 4,060,590 977 |TMA-Si-O-RUT Broach RW, et al. J. Phys. Chem. Solids 56: 1363-1368 995 B-NU-1 Belluse G, et al. Zeolites 10: 642-649 990 Fe-NU-1 Belluse G, et al. Zeolites 10: 642-649 990 Ga-NU-1 Belluse G, et al. Zeolites 10: 642-649 990 NU-1 Whittam TV, et al. U.S. Pat. No. 4,060,590 977 STA-1 Noble G. W., et al. Angew. Chem. Int. Ed. 36: 81-83 997 STA-6 Patinec V, et al. J. Chem. Soc. Dalton 3909-3911 999 Trans. STA-2 Noble G. W., et al. J. Chem. Soc. Dalton 4.485-4490 997 Trans. Mg-STA-7 Wright PA, et al. J. Chem. Soc. Dalton 1243-1248 Trans. Co-STA-7 Wright PA, et al. J. Chem. Soc. Dalton 1243-1248 2OOO Trans. Zn-STA-7 Wright PA, et al. J. Chem. Soc. Dalton 1243-1248 2OOO Trans. UCSB-8CO Bu X H, et al. Science 278: 2080-2085 997 UCSB-8Mg Bu X H, et al. Science 278: 2080-2085 997 UCSB-8M Bu X H, et al. Science 278: 2080-2085 997 UCSB-87 Bu X H, et al. Science 278: 2080-2085 997 UCSB-6GaCO Bu X H, et al. Science 278: 2080-2085 997 UCSB-6CO Bu X H, et al. Science 278: 2080-2085 997 UCSB-6GaMg Bu X H, et al. Science 278: 2080-2085 997 UCSB-6GaZn Bu X H, et al. Science 278: 2080-2085 997 UCSB-6Mg Bu X H, et al. Science 278: 2080-2085 997 UCSB-6Mn Bu X H, et al. Science 278: 2080-2085 997 UCSB-6Zn Bu X H, et al. Science 278: 2080-2085 997 UCSB-10GaZn Bu X H, et al. Science 278: 2080-2085 997 UCSB-1OCO Bu X H, et al. Science 278: 2080-2085 997 UCSB-10Mg Bu X H, et al. Science 278: 2080-2085 997 UCSB-1OZn Bu X H, et al. Science 278: 2080-2085 997 SSZ-48 Wagner P. et al. J. Phys. Chem. B. 1O3: 8245-82SO 999 SSZ-48 Wagner P. et al. Angew. Chem. Int. Ed. 38: 1269-1272 999 Sigma-2 McCusker LB, et al. J. Appl. Crystallogr. 21: 305-310 988 Sodalite Pauling L Z. Kristallogr. 74: 213-223 930 Loens J, et al. Acta Crystallogr. 23: 434-436 967 Al-Co-P-O-SOD Feng PY, et al. Nature 388: 735-741 997 Al-Ge-O-SOD Bu X, et al. J. Am. Chem. Soc. 12O: 13389-13397 998 Be-As-O-SOD Gier TE, et al. Angew. Chem., Int. Ed. 30: 1169-1171 991 Be-P-O-SOD Gier TE, et al. Angew. Chem., Int. Ed. 30: 1169-1171 991 Be-Si-O-SOD Dann SE, et al. Inorg. Chem. 35: 555-558 996 Co-Ga-P-O-SOD Bu X, et al. Microporous and 2O: 371-379 998 Mesoporous Materials Ga-Co-P-O-SOD Feng PY, et al. Nature 388: 735-741 997 Ga-Ge-O-SOD Bu X, et al. J. Am. Chem. Soc. 12O: 13389-13397 998 Ga-Si-O-SOD McCusker LB, et al. Zeolites 388-391 986 Zn-As-O-SOD Nenoff TM, et al. J. Am. Chem. Soc. 113: 378-378 991 Zn-Ga-As-O-SOD Bu X, et al. Microporous and 2O: 371-379 998 Mesoporous Materials Zn-Ga-P-O-SOD Bu X, et al. Microporous and 371-379 998 Mesoporous Materials Nenoff TM, et al. J. Am. Chem. Soc. 113: 378-378 991 Depmeier W Acta Crystallogr. C40: 226-231 984 AIPO-20+ Wilson ST, et al. J. Am. Chem. Soc. 104: 1146-1147 982 compositional variants Flanigen E M, et al. In Proc. 7 Int. Zeolite 986 Conf. Basic sodalite Barrer RM, et al. J. Chem. Soc. 1267-1278 951 Hassan I, et al. Acta Crystallogr. C39: 3-5 983 Bicchulite Sahl K, et al. Z. Kristallogr. 146: 35-41 977 Danalite Glass JJ, et al. Am. Mineral. 29: 163-191 944 G Shishakova TN, et al. IZV. Akad. Nauk SSSR 1303 965 US 2005/0106267 A1 May 19, 2005 24

TABLE 4-continued Page or Name of Zeolite First Author Cited Citation Vol. Number Year

Genthelvite Merlino S In Feldspars and 435-470 983 Feldspathoids (ed. W L Brown) Hauyn Loehn J, et al. N. Jb. Miner. Abh. 109: 2O1-210 968 Helvin Glass JJ, et al. Am. Mineral. 29: 163-191 944 Hydroxo sodalite Felsche J, et al. Zeolites 367-372 986 Nosean Schulz, H., et al. Tschermaks Min. Petr. 10: 225-232 965 Mitt. Silica sodalite Bibby D M, et al. Nature 317: 157-158 985 TMA sodalite Baerlocher Ch, et al. Helv. Chim. Acta 1853-1860 969 Tugtupite Sorensen H Am. Mineral. 48: 1178 963 Hassan I, et al. Can. Mineral. 29: 385-390 991 SSZ-35 Wagner P. et al. Angew. Chem., Int. Ed. 38: 1269-1272 999 ITO-9 Villaescusa L. A., et al. Chem. Commun. 21: 2329-2330 998 Stilbite Galli E, et al. Miner. Petrogr. Acta 12: 1-10 966 Slaughter M Am. Mineral. 55: 387-397 970 Galli E Acta Crystallogr. B27: 833-841 971 Barrerite Galli E, et al. Bull. Soc. Fr. Mineral. 98: 331-340 975 Cristallogr. Stellerite Galli E, et al. Bull. Soc. Fr. Mineral. 98: 11-18 975 Cristallogr. Synthetic barrerite Ghobarkar H, et al. J. Solid State Chem. 142: 451-454 999 Synthetic stellerite Ghobarkar H, et al. J. Solid State Chem. 142: 451-454 999 Synthetic stilbite Ghobarkar H, et al. J. Phys D: Appl. Phys. 31: 3172-3176 998 Desmine (discredited) Epidesmine (obsolete) SSZ-23 Camblor MA, et al. Angew. Chem. Int. Ed. 37: 2122-2126 998 Terranovaite Galli E, et al. Am. Mineral. 82: 423-429 997 Thomsonite Taylor W H, et al. Z. Kristallogr. 84: 373-398 933 Alberti A, et al. Zeolites 91-97 981 Pluth JJ, et al. Zeolites 74-8O 985 Al-Co-P-O-THO Feng PY, et al. Nature 388: 735-741 997 Ga-Co-P-O-THO Feng PY, et al. Nature 388: 735-741 997 Na-V Barrer RM, et al. J. Chem. Soc. 195-208 959 Synthetic Ghobarkar, et al. Cryst. Res. Technol. 32: 653-657 997 thomsonite Theta-1 Barri SAI, et al. Nature 312: 533-534 984 Highcock R M, et al. Acta Crystallogr. C41: 1391-1394 985 IS-1 Kozo T, et al. E Patent A-170,003 986 KZ-2 Parker LM, et al. Zeolites 8-11 983 NU-10 Araya A, et al. Zeolites 28O-286 984 ZSM-22 Kokotailo GT, et al. Zeolites 349-351 985 Marler B Zeolites 393-397 987 Tscöhrtnerite Effenberger H, et al. Am. Mineral. 83: 607-617 998 VP-8 Freyhardt C C, et a. J. Am. Chem. Soc. 118: 7299-7310 996 VP-5 Davis ME, et al. Nature 331: 698-699 988 Richardson Jr. J. W., et J. Phys. Chem. 93: 8212-8219 989 al. McCusker LB, et al. Zeolites 11: 308-313 991 AIPO-54 Richardson Jr. J. W., et J. Phys. Chem. 93: 8212-8219 989 al. H1 dYvoire F Bull. Soc. Chim. France 1762-1776 961 MCM-9 Derouane E G, et al. Appl. Catal. L13-20 989 VP-9 McCusker LB, et al. Microporous Materials 295-309 996 VP-7 Annen MJ, et al. Chem. Commun. 1175-1176 991 Röhrig C, et al. Zeolites 14: 498-SO3 994 Gaultite Ercit TS, et al. Can. Mineral. 32: 855-863 994 WSV-7# Röhrig C, et al. J. Phys. Chem. Solids 56: 1369-1376 995 Weinebeneite Walter F Eur. J. Mineral. 1275-1283 992 Wenkite Wenk H-R Z. Kristallogr. 137: 113-126 973 Merlino S Acta Crystallogr. B30: 1262-1266 974. Yugawaralite Kerr IS, et al. Z. Kristallogr. 125: 220-225 967 Kerr IS, et al. Acta Crystallogr. B25: 1183-1190 969 Leimer HW, et al. Z. Kristallogr. 130: 88-111 969 Hawkins DB Mater. Res. Bull. 951-958 967 Kvick A Z. Kristallogr. 174: 265-281 986 US 2005/0106267 A1 May 19, 2005 25

TABLE 4-continued Page or Name of Zeolite First Author Cited Citation Vol. Number Year ZAPO-M1 Marler B, et al. Microporous Materials 5: 151-159 1995 GapO-DAB-2 Meden A, et al. Z. Kristallogr. 212: 801-807 1997 UO-7 Akporiaye DE, et al. Chem. Commun. 6O1-6O2 1996 Akporiaye DE, et al. J. Phys. Chem. 1OO: 16641-16646 1996 CSZ-3 Vaughn D. E. W., et al. U.S. Pat. No. 4,333,859 1982

0109 The Zeolites may be used for oral chelation therapy which is either slowly or rapidly desorbed out of the Zeolite for heavy metal poisoning, either by natural means Such as and absorbed by the gastointestinal tract on a predictable Wilson's disease and primary biliary cirrhosis, or from customizable basis. environmental exposure Such as lead poisoning and intoxi 0114. The Zeolites may be used for treating osteoporosis cation by other various heavy metals Such as arsenic, chro based on the observation that eggshell thickness increases in mium, cesium and Strontium including also ammonia, mer hens fed a Small percentage of their diet as Zeolite. captains and other plant-, marine organism- and nuclear derived toxins and involving multiple administrations 0115 The use of Zeolites as the active component for a during a single day, Single daily, or Sequential daily admin hemoperfusion device in which blood-borne toxins, whether istrations for months to years to slowly remove tissue-bound from an endogenous or exogenous Source, are Selectively toxins from the bodies of humans. depleted based on the relative affinity of certain zeolites for certain toxins may be used to advantage in a similar way as 0110. The Zeolites may be used for therapy for hepatic charcoal is currently used in the hemoperfusion devices. encephalopathy as an adjunct or alternative to other thera 0116. The Zeolites may be used to mitigate against toxic pies currently used by binding up chemical mediators of consequences of acrolein exposure in humans. hepatic encephalopathy, which include at least ammonia and mercaptains which are elevated due to poor function of the 0117 The Zeolites may be used for mitigation, minimi liver because of its diseased State, which are bound to the Zation, treatment and prevention of noxious and Odoriferous Zeolite in the gastrointestinal tract and are then removed flatulence exploiting the properties of Zeolites to selectively from the body by fecal elimination. Examples of mercaptains absorb hydrogen Sulfide, the most odoriferous component of include hydrogen Sulfide and alkyl Sulfides. flatulence. 0111. The Zeolites may be used in the event of radioactive 0118. The Zeolites may be used for treating hemachro contamination of food (specifically strontium or cesium, but matosis alone or in combination with complementary thera also other contaminating radionuclides) Such that the Zeolite pies including therapeutic phlebotomy, erythropoietin is ingested and the radionuclide is adsorbed by the Zeolite administration, desferroxamine, and other experimental oral and carried out of the body (the radionuclide thereby not and intravenously administered chelating agents. being absorbed and finding its way into bone or Soft tissue 0119) The Zeolites may be used to remove arsenic and where the half-life is substantially prolonged). decrease toxicity from therapeutic arsenic-containing medi cations used in the treatment of cancer and infections 0112 The Zeolites may be used for treating potassium Specifically the cardiac arrhythmia-inducing effects of depletion for patients with elevated potassium in the outpa arsenic. tient or hospital by exploiting their ion-exchange properties 0120) The Zeolites may be used for therapy of acute in the intestinal juices whereby exceSS potassium is elimi poisonings from a wide variety of plant, animal, industrial nated with the Zeolite in the feces. and environmental toxins. These include the mitigation, 0113. The Zeolites may be used for oral drug delievery in minimization and elimination of toxin-induced clinical Syn which the Specific framework Structure, or mixture of Struc dromes affecting the cardiovascular, respiratory, gastrointes tures chosen, or Size of particles, to provide a temporally tinal, hepatic, renal, hematopoietic and nervous Systems predictable gastrointestinal absorption profile whereby the from the following list of plants by their common name, Zeolite acts a carrier of an active pharmaceutical ingridient Scientific name, toxic part and Specific poison:

TABLE 5 Plants, toxic parts, and specific poison

Common Scientific Name Name Toxic part Toxin Symtoms/syndrome Akee Blighia Sapida Fruit Hypoglycins A, B “Jamaica vomiting sickness' with hypoglycemia, convulstions, coma, lethal Apricot, Prunus species Pitfseed, Amygdalin Cyanide liberation in gut and peach, etc foliage glycoside cyanide poisoning Autumn Colchicum autumnale All parts of Colchicine alkaloid Vomiting, diarrhea, shock, COCS plant death US 2005/0106267 A1 May 19, 2005 26

TABLE 5-continued Plants, toxic parts, and specific poison

Common Scientific Name Name Toxic part Toxin Symtoms/syndrome Meadow Colchicum autumnale All parts of Colchicine alkaloid Vomiting, diarrhea, shock, saffron plant death Bird of Casealpinia gilliesii Pods Unidentified Vertigo, vomiting, paradise diarrhea, dehydration Black locust Robinia pseudoacacia Inner bark, Robin (phytotoxin), Vomiting, diarrhea, young leaves, robitin (glycoside) shock, CNS depression seeds Bleeding-heart Dicentra formosa Foliage, roots Apomorphine, Tremors, staggering gait, protoberberine, labored breathing, salivation, protopine, other convulsions, death due to isoquinoline-type paralysis alkaloids Buckeye Aesculus species Leaves, Esculin (glycoside) Vomiting, diarrhea, flowers, seeds pupillary dilatation, ms. Twitching, weakness, ataxia, CNS depression, paralysis Castor bean Ricinius communis All parts, esp. Ricin, ricinine Nausea, vomiting, violent seeds (phytotoxins, purging, hemolysis, renal toxalbumins) failure, oral burning sensation Century plant Agave annericana Sap Unknown Skin exposure causes dermatitis associated with leukocytosis and fever Chinaberry Melia azedarach Fruit Probably a resinoid Severe gastroenteritis Christmas rose Helleborus niger Rootstock and Helleborin, Numbing sensation in leaves belleborein mouth, vomiting, diarrhea, (glycosides) convulsions, CNS effects Daphne Daphne mezereum Berries, bark, Daphnin, mezerenic Burning oral sensation, leaves acid anhydride vomiting, blood and mucus in diarrhea, renal failure, weakness, convulsions, death Desert potato Jatropha macrorhiza Plant root Phytotoxins Nausea, vomiting, abdominal cramps, watery diarrhea Dumb cane Diefenbachia Seguine All parts of Calcium oxalate Burning sensation of or picta plant induing crystals, toxic tongue, mouth, larynx; Sap protein breathing affected Fava bean Vicia faba Bean, plant (G6PD Headache, nausea, vomiting, pollen deficiencient abdominal pain, icterus individuals) hyperthermia, hemolytic anemia, hemogloinuria Four o'clock Mirabilis jalapa Root, seeds Trigonelline Skin, mouth, throat alkaloid irritant causing purgation Foxglove Digitalis purpurea Leaves and Digitoxin, digitalin, Cardiac arrhythmia seeds digitonin glycosides Golden chain Laburnum anagyroides Beanlike Quinolizidine Dysphagia, incoordination, capsules in alkaloid cytisine vomiting, renalir failure, which seeds convulsions, coma, death by are suspended asphyxiation Holly Ilex species Berries Ilicin Nausea, abdominal pain, severe vomiting, diarrhea Hyacinth Hyacinthus Orientalis Bulb Narcissine-like Digestive upset, alkaloid(s) vomiting, diarrhea Hydrangea Hydrangea species All parts of Hydrangin (a Cyanide liberation in gut and plant cyanogenic glycoside) cyanide poisoning Indian tobacco Loebelia inflata All parts of Lobeline and Nausea, vomiting, plant lobelamine weakness, tremors, alkaloids convulsions, coma, death Iris (blue flag) Iris versicolor Leaves and Irisin, inidin, GI tract, liver, pancreas; root stalks irigenin purging and congestion of GI tract Jack-in-the Arisaema triphyllium Rhizome Calcium oxalate Burning sensation of pulpit (Indian crystals tongue, mouth, larynx; turnip) breathing affected Jerusalem Soianium pseudocapsicum Berries Solanine and related Headache, abdominal pain, cherry alkaloids vomiting, diarrhea, circulatory collapase, convulsions; CNS, resp. depression US 2005/0106267 A1 May 19, 2005 27

TABLE 5-continued Plants, toxic parts, and specific poison

Common Scientific Name Name Toxic part Toxin Symtoms/syndrome Jimson weed Datura Stranonium, All parts of Atropine, Intense thirst, urinary metel, inoxia, plants, hyoscyamine, retention, Xerostomia, Suaveolens, other species especially scopolamine tachycardia, delirium, seeds (solanaceous incoherence, pyrexia, alkaloids) confulsions, coma, death Lantana Lantana Canara Berries Lantadene A Extreme muscular (unripe) (a polycyclic weakness, GI irritation, triterpinoid) lethargy, cyanosis, circulatory collapse Larkspur Delphinium ajacis, Young plant, Delphinine (other Digestive upset, respiratory other species seeds poisonous depression, parestieias, alkaloids) salivation, headache, hypotension, cardie arrhythmias Lilly of the Convailaria maialis Leaves, Convallarin, Dizziness, vomiting, valley flowers, roots convallamarin, Cardiac arrhythmias convallatoxin (cardiac glycosides) Mistletoe Phoradendron species Berries b Acute gastroenteritis, phenylethylamine, circulatory collapse, nausea, tyramine, choline vomiting, diarrhea, respiratory difficulties, bradycardia, delirium, hallucinations, coma Monkshood Aconitum napeius Roots, seeds, Aconitine (a Vagal stimulation, leaves polycyclic diterpene bradycardia, irregular pulse, and other alkaloids) diminess of vision, nausea, vomiting, diarrhea, respiratory failure, tingling/numbing of lips, tongue Morning glory Ipomoea violacea Seeds Ergine, isoergine, Pychotomimetic effects, elymoclavine (other hallucinations, euphoria, Olavine alkaloids nausea, uterine related to LSD) stimulation Mountain Kalmia latifolia All parts of Andromedotoxin Stimulation then paralysis of laurel and augustifolia plant skeletal muscle (curare-like effects), cardiac tissue inhibition, CNS depression, respiratory depression, death Narcissus/daffodil Narcissus species Bulb narcissine, lycorine Severe gastroenteritis, (other alkaloids) Vomiting, purging, trembline, convulsions, hypotension, hepatic degeneration Nightshade Solanum species Varies with Solanine alkaloids See Jerusalem cherry family specie Oleander Nerium oleander All parts oleandroside, Local irritation to mucous oleandrin nerioside membranes, mouth, (cardiac glycosides) stomach; nausea, vomiting, diarrhea, slow and irregular pulse changing to rapid/thready pulse, ventricular fibrillation, death Pencil tree Euphorbia tirucalli Leaves, stems, Unidentified irritant Irritation to lips, tongue, milky sap in sap mouth; skin blisters Peyote Lophophora williamsii All parts Mescaline and other Sensory distortion, visual and diffusa especially alkaloids hallucinations cactus “button Philodendron Philodendron species Entire plant Calcium oxalate Local irritation to mucous membranes, swelling of lips, tongue, excessive salivation, difficulty with swallowing: Swelling of tongue, pharynx, inhibits respiration US 2005/0106267 A1 May 19, 2005 28

TABLE 5-continued Plants, toxic parts, and specific poison

Common Scientific Name Name Toxic part Toxin Symtoms/syndrome Caladium Caladium bicolor Entire plant Calcium oxalate Local irritation to mucous membranes, swelling of lips, tongue, excessive salivation, difficulty with swallowing: Swelling of tongue, pharynx, inhibits respiration Elephant ear Colocasia antiquorum Entire plant Calcium oxalate Local irritation to mucous membranes, swelling of lips, tongue, excessive salivation, difficulty with swallowing: Swelling of tongue, pharynx, inhibits respiration Hemlock Conium maculatum All parts of Conium (alkaloid) Nausea, vomiting, early (poison) plant CNS stimulation followed by severe CNS depression, assoc. muscle paralysis, repiratory failure Poison ivy Toxicodendron radicans All parts of Urushiol (comprised Severe dermatitis with (erroneously or Rhus toxicodendron plant of phenolic substances inflammation, vesicles, called poison including including 3-N- blistering oak) smoke from pentadecylcatechol burning Pokeweed Phytolacca amnericana Roots, leaves Saponin, a Burning sensation in mouth, (also called and decandra and fruit glycoprotein, GI cramps, vomiting, pigeonberry, phytolaccine, diarrhea; visual disturbance, inkberry) phytolaccotoxin amblyopia, perspiration, (alkaloids) salivation, lassitude, prostration, weakend respiration and pulse, death Privet Ligustrum japonicum All parts Possible Vomiting, colic, diarrhea, andromedotoxin, death probably unknown Red squill Urginea maritima Bulb Cardiac glycosides (see Oleander) Rhododendron Rhododendron All parts Andromedotoxin Salivation, nasal discharge, (azaela) species nausea, vomiting, diarrhea, muscle weakness, labored breathing, coma; dullness of vision, paralysis, hypotension, lacrimation, anorexia Rhubarb Rheum rhaponticum Leaf blade Oxalic acid Severe intermittent (not petiole) abdominal pains, vomiting, diarrhea, headache, weakness, hemorrhages; hypocalcemia causing muscular cramps, tetany; convulsions, coma, death by renal failure Rosary pea Abrus precatorius Seeds Abrin (phytotoxin), Burns to mouth, esophagus; (crabseye, abric acid (tetanic like castor bean; nausea, precatory glycoside) vomiting, severe diarrhea, bean, jequirity weakness, shock, trembling bean, Indian hands, oliguria, hemolytic licorice) anemia, hallucinations, fatal uremia Star-of Ornithogalum umbrellatum All parts Colchicine-related Nausea, nervous Bethlehem alkaloids symptoms, general (snowdrop) disturbances of GI tract Sweet pea Lathyrus Odoratus Seeds Aminopropionitrile Skeletal deformity and growth suppression; muscle paralysis Texas Sophora Secundiflora Entire plant Cytisine Increased salivation, nausea, mountain vomiting, headache, vertigo, laurel confusion, hallucinations, excessive thirst, muscle fasciculation, convulsion, respiratory stimulation then failure US 2005/0106267 A1 May 19, 2005 29

TABLE 5-continued Plants, toxic parts, and specific poison Common Scientific Name Name Toxic part Toxin Symtoms/syndrome Threadleaf Senecio longilobus Entire plant Pyrrolizidine Chronic ingestion causes groundsel (ingested as alkaloids enlarged liver, ascites, herbal tea) abdominal pain, headache, apathy, emaciation; major cause of veno-occlusive disease Tobacco Nicotiana species Possibly all Nicotine and related Nausea, vomiting, parts alkaloids muscular fasciculations, early CNS stimulation followed by severe CNS depression assoc. with muscle paralysis and respiratory failure Water Cicuta maculata All parts, Cicutoxin Severe stomach pain, hemlock and other species mostly the great mental excitation (cowbane) rOOtS and frenzy, vomiting, salivation, violent spasmodic convulsions alternating with periods of relaxation, dilated pupils, delirium, death Wisteria Wisteria floribunda Seeds or pods Wisterin (glucoside) Mild to severe (Japanese); W. Sinensis gastroenteritis, vomiting, (Chinese) abdominal pain, diarrhea Yellow Geismium Semperviren Whole plant, Gelsemine and Depress and paralyze jessamine berries gelseminine nerve motor endings in (Carolina (alkaloids) brain and spinal cord, jessamine) respiratory arrest Yellow Thevetia peruviana All parts; fruit Thevetin A, B; Similar to Oleander; Local oleander “lucky nut thevetoxin (cardiac irritation to mucous glycosides) membranes, mouth, stomach; nausea, vomiting, diarrhea, slow and irregular pulse changing to rapid/thready pulse, ventricular fibrillation, death Yew Taxus beccata All parts, esp. Taxine (alkaloid) Nausea, vomiting, diarrhea, and T. Canadensis seeds abdominal pain, circulatory failure, difficulty breathing; depresses heart function; dermatitis

0121 The Zeolites may be used for treating the following failure and the general gastroenteritis Syndromes of nausea, food-borne toxin-induced diseases: cholera, botulism and Vomiting, abdominal cramping and diarrhea, binding of one food poisoning due to Bacillus cereuS and Staphylococcal or more of the following mushroom poisonous Substances poisons and Escherecia coli, the following toxic marine including the cyclopeptides amatoxins and phallotoxins, ingestions: (1) paralytic shellfish poisoning from the inges muscimol, ibotenic acid 2552-55-8), gyromitrin monom tion of mussels (Mytilus edulis and Mytilus californianus), ethyl hydrazine, muscarine, coprine, indole Species, Orelline, clams (Saxidomus gigantus the Alaskan butter clam and orellanine, psilocin, psilocybin; for one or more of Several Mya arenaria the “soft-shell clam'), scallops (Placopecten different mushroom species including Amanita muscaria magellanicus), oysters which had previous fed upon certain (also known as “fly agaric').pantherina, gemata, cokeri, Gonyaulux species (which comprise the so-called “red tide') cothurnata, phalloides (also known as the “death cap”), and elaborate Saxitoxin 1, neoSaxitoxin 2, gony autoxin 3, Verna (also known as the “death angel”), Virosa (also known gony autoxin 4 and gonyautoxin 5; (2) pufferfish poisoning as the “destroying angel”), bisporigera, ocreata, Suballiacae, ("fugu" in Japan, tambore puffer in China); and (3) tenuifolia; Galerina autumnaluis, marginata, Venerata; Lepi ciguatera, from certain fish (Such as barracuda, amberjack, ota helveola, VOSSe-randii, Conocybe filaris, Gyromitra kingfish and dolfin) exposed to the benthic dinoflagellate eSculenta (also known as the "false morel'), gigas, ambigua, Gambierdiscus toxicus, and minimization, mitigation and infula, cardiniana, brunnea, Paxina Species, Sarcosphera treatment of any one of the Several Sydromes arising from coronaria, Boletus calopus, luridus, pulcherimus, Satanas, the ingestion of toxic mushrooms including Stages I, II and Clitocybe clavipes, cerruSata, dealbata, illudens, riululosa; III gastroenteritis and hepatorenal Syndrome, the anti-cho Inocybe fastigiata, geophylla, lilocina, patuoillaridi, purica, linergic Syndrome, delayed gastroenteritis with CNS abnor rimosis, Psilocybe cubensis, caerulescens, cyanescens, malities, cholinergic Syndrome, the disulfiram-like reaction baeocystis, fimentaria, mexicana, pellulolosa, Semilanceata, with alcohol, hallucinations, delayed gastritis and renal Silvatica; Conocybe cyanopus, Gymnopilus aeruginosa, US 2005/0106267 A1 May 19, 2005 30

Spectabilis, validipes, Panaeolus SubbalteatuS andfoenisecii amounts could vary Substantially depending on conventional (also known as the “mowers mushroom'); Stropharis criteria. Preferably, a zeolite formulation would be admin coronillal. Cortinarius Orellanus, Speciosissimus, Splen istered between meals. doma, gentilis; Chlorophyllum molybdites; and Orphalates illudens (also known as the "jack-o-lantern' mushroom). 0125) The particle size graphs of FIGS. 1-2 show the 0122) Dosage and Administration binding of ammonia using the Same mass of Sodium alumi nosilicate, but with different particle size distributions. It 0123 Preferred dosages are 100-1000 mg Sodium alumi shows that the Smaller the particle, the poorer the ammonia nosilicate Zeolite to a 5-20 kg weight of the human for binding. Hence, the larger the particle, the more active the treating lead poisoning. If the drug is administered to drug in binding ammonia. However, there is a practical children, the preferred formulation would be as a gelatin upper limit for particle size, and that upper limit is palat capsule with minimal to no water. The number of times it would be administered could be up to 4x per day and could ability. One must Strike the right balance that optimizes the go on daily for more than 1 year. Actual dosage amounts trade-off between ammonia binding palatibility. Preferably, could vary Substantially depending on conventional criteria. at least 90% of the particles are of particle size from about 90 um to about 150 lum. More preferably, at least 95% of the 0.124 For treating excess ammonia, preferred dosages particles are in that range. may be about 10 grams to a 70 kg human. This could be up to 4x per day and would be used for up to about 7 days per 0.126 The following table present toxicology data on episode of ammonia-induced encephalopathy. Actual dosage Sodium aluminosilicates.

TABLE 6 Toxicology Studies by Oral Gavage Performed with Sodium Aluminosilicate Study Animal Authorf Toxico Company Ogy Dose Report Model Schedule Range Findings Notes References Degussa, Rat Single 5,000 mg/kg to No Degussa A G - US IT No. 78-0012 978 dose 31,800 mg/kg Mortality DKT (unpublished data, 1978) observed Gloxhuber, Rat Gloxhuber Ch, Potokar M, 983 Pittermann W., et al. Food Chem. Toxic. 21: 209–220 (1983) Gaynor, Rat Gaynor T. Klusman L. Procter & 973 Gamble Company; Human Safety Appendices on Sodium Aluminosilicate, A.2 (1973) Thomas, Rat Thomas J, Ballantyne B: J. of Am. 992 Coll. Of Tox. 11(3): 259-273 (1992) Moore, Rat Moore G. E., Huntingdon Research 974. Center, Project No. 747-129 in: Procter & Gamble Company; Human Safety Appendices on Sodium Aluminosilicate, A.2 (1974) Moulton, Rat Moulton R H, Scientific Associates, 1974 Inc., S. A. No. 201935 in: Procter & Gamble Company; Human Safety Appendices on Sodium Aluminosilicate, A.2 (1973) Degussa, Rat Degussa A G - US IT No. 88-0207 1988 DKT (unpublished data, 1988 A) Litton, Rat Litton Bionetics, Inc. “Mutagenic 1974 evaluation of compound FDA 71 45, synthetic sodium silicoaluminate, prep, for FDA; NTIS, US Dept. of Commerce, Springfield, VA; PB 245 468 (1974) Huber, Rat J. M. Huber Corporation; Report 1973 date January 12, 1973 (unpublished data) Degussa, Rat 5,110 mg/kg Degussa AG - US IT No. 90-0146 1990A (GLP) DGT (unpublished data, 1990 A) Degussa, Degussa AG - US IT No. 90-0149 1990B DGT (unpublished data, 1990 D) Litton, Rat Single LDs is 5000 Identical BgVV (Bundesinstitut fur gesund 1974a dose mg/kg protocol and heitlichen Verbraucherschutz und laboratory as Veterinarmedizin), Artzliche study below Mitteilung bei Vergiftungen 1999, ISBN 3-93.1675-59-9 US 2005/0106267 A1 May 19, 2005 31

TABLE 6-continued Toxicology Studies by Oral Gavage Performed with Sodium Aluminosilicate Study Animal Authorf Toxico Company logy Dose Report Model Schedule Range Findings Notes References Rat Single LDso Results BgVV (Bundesinstitut fir gesund dose 1OSO deemed NOT heitlichen Verbraucherschutz und mg/kg RELIABLE by Veterinarmedizin), Artzliche HERAPanel Mitteilung bei Vergiftungen 1999, ISBN 3-93.1675-59-9 Rat D x 5 5,000 mg/kg/d No signs Reference not provided in HERA of toxicity documentation or abnormal behavior Mouse Single 10,000 mg/kg infa Henkel KgaA, Archive No. TBD dose 7801.04 (Akute Toxizitat an der Maus, 11/1978) Sturm RN, Procter & Gamble Dog Single infa Company; Human Safety dose Appendices on Sodium Aluminosilicate, A.3 (1973) Rat D. x 14 O.OOO% (wfw) No change in Henkel KgaA, Archive-No. R (Fischer O.625% (wfw) food consump 0100197 (External Report, Tracor 344) 1.25% (wfw) tion, no marked Jitco, Inc., June 28, 1979, 2.5% (wfw) signs of unpublished data) 5.0% (wfw) toxicity on 10.0% (wfw) gross necropsy Henkel, Mouse D. x 14 O.OOO% (wfw) No change in Henkel KgaA, Archive-No. R 1979b O.625% (wfw) food 0100196 (External Report, Tracor 1.25% (wfw) consumption, no Jitco, Inc., June 28, 1979, 2.5% (w/w) marked signs of unpublished data) 5.0% (wfw) toxicity on 10.0% (wfw) gross necropsy Henkel, Rat D x 90 O ppm High dose group: Henkel KgaA, Archive-No. TBD 1977 (Wistar) (wfw) hyperplastic 770012 Subacute orale Toxizitat an 1,000 ppm reaction of Ratten, 90-Tage-Test, Jan. 1977, (wfw) tranansitional unpublished data). 5,000 ppm epithelium with (wfw) calculi: kidneys 10,000 ppm of male higher (wfw) silicate content vs. ctrls: NOAEL 5,000 ppm (250–300 mg/kg/d; 1500-1800 mg/m/d) Henkel, Rat D. x 163 O.O% (wfw) D28 sac: no A: Henkel KgaA, Archive-No. TBD 1975 (COX-SD) 0.5% (wfw) D84, D85: 1 EXO143 (External Report, Procter & 1.0% (wfw) death/day: bladder Gamble, Sept., 1975, 2.0% (wfw) tox, stones: D91 unpublished data) sac: bladder stones; high dose only; D163 sac bladder stones 1 animal each in 1.0% and 0.5% groups Henkel, Rat D. x 160 O.O% (wfw) UA: No A treated Henkel KgaA, Archive-No. TBD 1976a (COX-SD) or O.125% (wfw) vs. Ctrl; bladder EXO127 (External Report, Procter & D. x 200 2.0% (wfw) tox, stones, Xtals Gamble; June, 1976, in high dose unpublished data) group; no A in urine parameter or kidney function; Histopath: interstitial nephritis, regenerative epithelium and renal pelvic epithelial hyperplasia; bladder: transitional epithelium US 2005/0106267 A1 May 19, 2005 32

TABLE 6-continued Toxicology Studies by Oral Gavage Performed with Sodium Aluminosilicate Study Animal Authorf Toxico Company logy Dose Report Model Schedule Range Findings Notes References hyperplasia in high dose group. No histopath. A in low dose group; NOAELO.125% (~69 mg/kg/d; ~420 mg/m/d) Henkel, Rat D. x 168 0.0% (w.fw) Regarding Two citations for this study: 1976b 0.125% (w.fw) mortality, physical (1) Henkel KgaA, Archive-No. (Long (24 wk) 0.5% (w.fw) appearance, feed TBD EXO129 (External Report, Evans) 2.0% (w.fw) efficiency, body Procter & Gamble, May, 1976, Weights, organ unpublished data); weights and (2) Henkel KgaA, Archive-No. organ?body ratios TBD EXO137 (External Pathology no toxic effects Report 13 weeks. Procter & observed. Gamble, March, 1976, Histopath: unpublished data) microscopic alternations in the kidneys at 0.5% and 2.0% groups; NOAELO.125% (-69 mg/kg/d; ~420 mg/m/d) Henkel, Rat D x 728 ppm Mortality, feed & Same study as Henkel KgaA, Archive-No. SAS 1979c (Wistar) (104 wk) ppm water consumption, below, this is 7900017 (Prüfung auf ppm BW monitored; part 2 with chronischtOXische und ppm Ophth, blood, part 1 below. tumorerzeugende Wirking von urinary, bio Sasil bei einer Versuchsdauer von chemical params 2 Jahren Teil II, Sept., 1979, eval.: 104 wk sac: unpublished data) all organs gross/micro eval. No significant test ariticle related etects were observed on histolopath; no A in types or incid.of neoplasms. NOEL 60 mg/kg/d (360 mg/m/d) Henkel, Rat D x 728 ppm Mortality, feed & Henkel KgaA, Archive-No. SAS 1979d (Wistar) (104 wk) ppm water consumption, 7900016 (Prüfung auf ppm BW monitored; chronischtOXische und ppm Ophth, blood, tumorerzeugende Wirking von urinary, bio Sasil bei einer Versuchsdauer von chemical params 2 Jahren Teil I, Sept., 1979, eval.: 104 wk unpublished data) sac: all organs gross/micro eval. No significant test ariticle related effects were observed on histolopath; no A in types or incid. of neoplasms. NOEL 60 mg/kg/d (360 mg/m/d) US 2005/0106267 A1 May 19, 2005 33

O127)

TABLE 7

Table of Genotoxicity Studies Performed with Sodium Aluminosilicate Study Authorf Company Report Test Schedule Strains Findings Notes References

Zeiger, 1987 Ames S. typhimurium No mutagenicity Zeiger E, Anderson B, Haworth S, activation TA 98 detected in any et al. Environmental Mutagenesis 9 TA100 strain (suppl. 9): 1-110 (1987) TA 1535 TA 1537 TA 1538 Prival, 1991 Ames S. typhimurium No mutagenicity Two sources cited TA 98 detected in any (1) Prival MJ, Simmon V F, TA100 strain Mortelmans KE, Mutat. Res TA 1535 260: 321-329 (1991); TA 1537 (2) Simmon V F and Eckford SL TA 1538 Microbial mutagenesis testing of substances. Compound report: F76 001, sodium aluminum silicate. prep. for FDA; NTIS, US Dept. of Commerce, Springfield, VA; PB89 193650 (1989) Prival, 1991 Reverse E. coli WP2 Two sources cited mutation activation (1) Prival MJ, Simmon V F, Mortelmans KE, Mutat. Res 260: 321-329 (1991); (2) Simmon V F and Eckford SL Microbial mutagenesis testing of substances. Compound report: F76 001, sodium aluminum silicate. prep. for FDA; NTIS, US Dept. of Commerce, Springfield, VA; PB89 193650 (1989) Litton, 1974 S. cerevisiae Mutagenic Litton Bionetics, Inc.'Mutagenic potential not evaluation of compound FDA 71 reported 45, synthetic sodium silicoaluminate, prep, for FDA; NTIS, US Dept. of Commerce, Springfield, VA; PB 245 468 (1974) Litton, 1974 H. Sapiens No clastogeic Litton Bionetics, Inc.'Mutagenic embryonic lung potential observed evaluation of compound FDA 71 cell cultures 45, synthetic sodium W 38 silicoaluminate, prep. for FDA; NTIS, US Dept. of Commerce, Springfield, VA; PB 245 468 (1974) FASEB, 1977 DNA-repair Negative Federation of American Societies of assay Experimental Biology (FASEB), “Tentative evaluatin of the health aspects of certain silicates as food ingredients' (1977), cited in How M and Solbe J, Unilever Research, Document ref. D/93/021 (1993) Litton, 1974 Male albino 4.25 mg/kg Single dose & No mutagenic Observation Litton Bionetics, Inc.'Mutagenic rat (10-12 42.5 mg/kg D x 5 potential observed time points: evaluation of compound FDA 71 wk old) 425 mg/kg & 6, 24, 48 hrs: 45, synthetic sodium 5000 mg/kg No A in type silicoaluminate, prep, for FDA; or number of NTIS, US Dept. of Commerce, chromosomal Springfield, VA; PB 245 468 (1974) aberrations observed; (+) ctrl -> (+) US 2005/0106267 A1 May 19, 2005 34

0128

TABLE 8 Table of Developmental Toxicology and Teratogenicity Studies Performed with Sodium Aluminosilicate Study Authorf Company Report Model Schedule Dose Levels Findings Notes References Henkel, 1978 Rat D x 10 on 0 mg/kg D20 sac: high Henkel KgaA, Archive-No. R (Charles gestational 74 mg/kg conception rates; 0100168 (External Report, Procter River; days 6-15 1600 mg/kg no maternal, & Gamble, May, 1978 unpublished pregnant) (gavage) embryo or fetal tox data) noted; no diff in incidence of soft tissue malformations or skeletal defects vs. ctrl NOAEL 1,600 mg/kg (9,600 mg/m) FDRL, 1973 Rat D x 10 on 0 mg/kg D20 sac: no effect Food and Drug Research (Wistar, gestational 16 mg/kg on midation, Laboratories, Inc. Teratologic pregnant) days 6-15 74 mg/kg maternal, or fetal Evaluation of FDA 71-45 (sodium 345 mg/kg survival noted; no silicoaluminate) prep. for FDA, 1,600 mg/kg diff in incidence of NTIS, US Dept. of Commerce, soft tissue USA, PB 223 810 (1973) malformations or (gavage) skeletal defects vs. ctrl NOAEL 1,600 mg/kg (9,600 mg/m) FDRL, 1973a Mouse D x 10 on 0 mg/kg D17 sac: no effect Food and Drug Research (CD-1, gestational 16 mg/kg on midation, Laboratories, Inc. Teratologic pregnant) days 6-15 74 mg/kg maternal, or fetal Evaluation of FDA 71-45 (sodium 345 mg/kg survival noted; no silicoaluminate) prep. for FDA, 1,600 mg/kg diff in incidence of NTIS, US Dept. of Commerce, (gavage) soft tissue USA, PB 223 810 (1973) malformations or skeletal defects vs. ctrl NOAEL 1,600 mg/kg (4,800 mg/m) FDRL, 1973b Rabbit (Dutch: D x 14 on 0 mg/kg D29 sac: no effect Food and Drug Research pregnant) gestational 16 mg/kg on midation, Laboratories, Inc. Teratologic days 6-18 74 mg/kg maternal, or fetal Evaluation of FDA 71-45 (sodium 345 mg/kg survival noted; no silicoaluminate) prep. for FDA, 1,600 mg/kg diff in incidence of NTIS, US Dept. of Commerce, (gavage) soft tissue USA, PB 223 810 (1973) malformations or skeletal defects vs. ctrl NOAEL 1,600 mg/kg (??? conversion mg/m) Henkel, 1978 Rabbit (New D x 14 on 0 mg/kg D29 sac: no effect Henkel KgaA, Archive-No. R Zealand; gestational 16 mg/kg on maternal 0100169 (External Report, Procter & pregnant) days 6-18 74 mg/kg toxicity or effect on Gamble, June, 1978 unpublished 345 mg/kg survival noted; no data) 1,600 mg/kg diff in incidence of (gavage) soft tissue malforma-tions or skeletal defects vs. ctrl; NOAEL 1,600 mg/kg (??? conversion mg/m) FDRL, 1973c Hamster D x 5 on 0 mg/kg D14 sac: no effect Food and Drug Research (Syrian; gestational 16 mg/kg on midation, Laboratories, Inc. Teratologic pregnant) days 6-10 74 mg/kg maternal, or fetal Evaluation of FDA 71-45 (sodium 345 mg/kg survival noted; no silicoaluminate) prep. for FDA, US 2005/0106267 A1 May 19, 2005 35

TABLE 8-continued Table of Developmental Toxicology and Teratogenicity Studies Performed with Sodium Aluminosilicate Study Authorf Company Report Model Schedule Dose Levels Findings Notes References 1,600 mg/kg diff in incidence of NTIS, US Dept. of Commerce, (gavage) soft tissue USA, PB 223 810 (1973) malformations or skeletal defects vs. ctrl NOAEL 1,600 mg/kg (??? conversion mg/m)

0129. The following examples are offered by way of illustration and not by way of limitation to the scope of the TABLE 9-continued claims. Step Process EXAMPLES Step III Size Reduction and Selection of the Sodium Aluminosilicate Step IV Temporary Packaging and Transfer for Second Size Selection Example 1 Step V Second Size Selection of Sodium Aluminosilicate Step VI Clarification of Sodium Aluminosilicate Step VII Regeneration into the Sodium form of Aluminosilicate General Manufacturing Process Step VIII Drying of the Regenerated Sodium Aluminosilicate 0130. The synthesis of sodium aluminosilicate consists of Step IX Temporary Packaging and Storage of Bulk Drug Substance one Synthetic reaction of aluminum oxide (AlO4) (which is dissolved in hot sodium hydroxide in Step I) with liquid Sodium Silicate (NaSiO) at ambient temperature, to yield Example 3 the crude Sodium aluminosilicate crystalline Substance (Step 0133. Three particle size analyses were performed on the II). The crude crystals are then size reduced by conventional CR-100 zeolite manufactured by Mineral-Right, Inc. The roller milling and size Selected (Step III) yielding a uniform raw data are shown in the table below. FIG. 1 shows a granular material. The material is collected in 40 cu. ft. bulk graphic representation of the data. bags (Step IV) and manually transferred to a second size Selection step for final size Selection (Step V). The resulting Size Selection process yields a still more uniform particle TABLE 10 size distribution of ca. 95% of the crystalline material US Std. Pre- Post ranging between 90 and 150 micrometers (um). Sieve Size regeneration (%) regeneration (%) 0131 The properly size selected material is washed in a Bed #7 8O 0.525 1.24 1OO 4.65 1236 clarification Step in which an optimized retrograde flow rate 12O 43.81 44.57 of reverse osmosis (RO) water partially purifies and pH 140 37.15 30.52 adjusts the crystalline material (Step VI). The material is 170 11.79 8.65 then gravity-drained and dried with vacuum assistance. The 230 O.9 1.21 325 O.22 O.37 partially purified, pH adjusted, and moist Sodium alumino Pan O.43 O.12 Silicate crystalline material is rehydrated with a Saturated Bed #10 8O 1.17 2.34 Saline Solution for additional removal of residual alkali and 1OO 4.24 1812 alkaline-earth cations (Step VII). The material is re-dried 12O 41.4 38.6 140 38.1 29.73 (Step VIII), and temporarily packaged and stored in fiber 170 12.11 8.83 drums (Step IX) as the bulk investigational drug Substance 230 1.05 1.06 for shipment to the Selected contractor for manufacture of 325 O34 O.3 the drug product. Pan O.62 O.04 Bed #11 8O O.64 0.72 1OO 9.38 5.37 Example 2 12O 35.33 39.22 140 34.7 36.57 0132) The following table provides summary and manu 170 15.4 16.28 facturing capacity for each Synthetic and production Step. 230 2.45 3.42 325 O.67 O31 TABLE 9 Pan O.64 O1 Step Process Step I Dissolution of Aluminum into Sodium Hydroxide 0134) “Pan” in the table refers to the bottommost item in Step Ia Transfer Truck Tank Filling and Reaction Process the vertical Series of Sieves which is a Solid bottom designed Step II Synthesis of Crude Crystalline Substance to collect all particles, regardless of size, that pass through Step IIa Maturation and Drying of the Sodium Aluminosilicate the Smallest Sieve, which is generally the Sieve Second to the bottom. Pre- and post-regeneration refers to the particle size US 2005/0106267 A1 May 19, 2005 36 distribution before and after exposure to a Saturated brine solution of USPsalt. Only the post-regeneration product is TABLE 11-continued envisioned to be used clinically. Particle size distributions may change minimally or Substantially with use of other mg/kg (ppm counterions Such as potassium, calcium and others cited Practical Difference above. quantification between new Cation/Anion limit “new” “used and used Example 3 cadmium O.8 C C 0135 An experiment was performed to measure sodium calcium 560 14,000 2,800 chromium 1.5 C C aluminosilicate binding of undesirable ions, especially cobalt 1.O C C heavy metals, from man. The Sodium aluminosilicate was copper 2.7 O 13 manufactured according to the previously described manu iron 1,300 C C facturing process. A man, weighing approximately 90 kilo lead 1.8 C 4.7 lithium 3.4 3.7 C grams, orally Self-administered a size 0 conventional phar magnesium 350 3,200 1,405 maceutical-grade hard gelatin capsule containing manganese 14.O C C approximately 500 milligrams of Sodium aluminosilicate mercury O.3 C C (CR-100, manufactured by Mineral-Right, Inc., Phillips molybdenum 0.4 C C nickel 2.4 C C burg, Kans.). The capsule was ingested with approximately ammonia nitrogen 5 C C 200 milliliters of tap water and was immediately Swallowed. (mg/L) The Subject did not complain of any adverse gastrointestinal potassium 150 3,300 16,000 effects Such as constipation, diarrhea, pain, bloating, nausea, selenium 12 C C silicon 8.4 730 1,900 Vomiting, or bloody Stools. The Sodium aluminosilicate silver O.3 C C remained in the Subject for approximately 24 hours until the sodium 410 63,000 290,000 Subject Spontaneously experienced a bowel movement and strontium 8.4 170 72 thallium 1.3 C C produced a well-formed brown stool. This material was tin O.1 O.2 0.4 collected (before it was deposited into toilet and flushed) titanium 5.1 8 19 manually with clean, washed rubber gloves and was visually vanadium 1. C C inspected for Small white Specks of Sodium aluminosilicate Zinc 21 C 41 material. *(lowest quantifiable limit of the instrument) 0.136 Specks of white, granular material that was observed in the stool was carefully teased out by the use of 0.138 Lead was found in greater concentration after the fine plastic tweezers, briefly dipped in deionized water to aluminosilicate had transited the gastrointestinal tract. The wash off any potentially contaminating fecal material, and Sodium aluminosilicate manufactured by Mineral-Right, placed in a plastic container that had been previously Inc. may therefore be used as a therapeutic agent for removal washed with deionized water and air dried. The amount of of lead in patients with abnormally high levels or toxic Sodium aluminosilicate that was recovered was approxi burdens of lead. The subject of this experiment was tested mately 50 mg. The sodium aluminosilicate collected from for elevated blood lead level. The subject's blood lead level the stool (designated “After” in the table below) and sodium was 7.5 ug/dL which is within normal limits of <10 ug/dL. aluminosilicate from the same manufacturing process that Sodium aluminosilicate thus possesses utility in treating had not been administered to the Subject (designated lead poisoning, and other metals with toxic effects, given “Before” in the table below) were analyzed for metallic ion that the Sodium aluminosilicate was able to extract the toxic content with atomic absorption spectrophotometry. metal from an individual who was not suffering from lead 0.137 The following tabulated results were noted for poisoning. The same conclusion applies to copper poison Sodium aluminosilicate manufactured by the method ing, which occurs Spontaneously though rarely as a clinical described above with the exception that the material was not entity known as Wilson's disease or hepatolenticular degen fully regenerated with sodium and extensively clarified with eration. deionized water. The table thus reflects analysis of sodium aluminosilicate following passage through the human gas Example 4 trointestinal tract. Sorbitol Verses Sorbitol-Zeolite Ammonia Removal Study TABLE 11 013:9 CR-100 is used through out this study. The study mg/kg (ppm compares Sorbitol effect on ammonia to Sorbitol with 2 Zeolite partical sizes, pan, and Standard fines. Ammonia Practical Difference quantification between new challenge solution is approx. 100 Mg/L (100 P.P.M.). Cation/Anion limit “new” “used and used aluminum 2,400 540,000 420,000 antimony O.7 ind ind Sample # 1 Sample # 2 Sample # 3 Sample # 4 Sample # 5 arsenic 7.0 ind ind barium 3.5 9.3 5.8 10 Gr. Pan 10 Gr. Fines 20 Gr. Pan 20 Cr. Fines Control; no beryllium O.7 O.8 ind crystal bismuth 1.1 ind ind 100 ML. Same Same Same Same boron 50 ind ind Sorbitol US 2005/0106267 A1 May 19, 2005 37

8. The method of claim 1, wherein the human is between -continued about 2 and about 15 years of age. 9. The method of claim 1, wherein the human is about 6 Sample # 1 Sample # 2 Sample # 3 Sample # 4 Sample # 5 years of age or younger. 100 ML. 95 Same Same Same Same 10. The method of claim 1, wherein the formulation PP.M. NH4 further comprises a bacterioStat. 11. A method of treating, preventing, or palliating elevated human blood ammonia levels, comprising admin 0140. Each sample is weighed dry, then wetted and added istering to a human in need thereof a pharmaceutical for to the 100 mL Sorbitol Solution spiked with 95 ppm ammo mulation comprising a Synthetic Sodium aluminosilicate nia. The experiment took place in a 250 mL Erlenmeyer Zeolite and a pharmaceutically acceptable adjuvant, flask that was shaken overnight and tested for ammonia the wherein: next morning. The concentration of the ammonia in the (a) the Synthetic Sodium aluminosilicate is particulate and Solution is shown below for each Sample. at least 90% of the particles are of particle size from about 90 um to about 150 um; (b) the formulation is from about 50% (w/w) to about 95% Sample # 1 Sample # 2 Sample # 3 Sample # 4 Sample # 5 (w/w) water; and 2 PPM 2 PPM 1 PPM 2 PPM 90 PPM. (c) the formulation is administered in doses of about 2 g to about 15 g Sodium aluminosilicate. 12. The method of claim 11, wherein at least about 95% 0141 All publications and patent applications cited in of the particles are of particle size from about 90 um to about this specification are herein incorporated by reference as if 150 lum. each individual publication or patent application were spe 13. The method of claim 11, wherein the human is cifically and individually indicated to be incorporated by Suffering from hepatic encephalopathy or cirrhosis of the reference. liver. 0142. The invention has been described in some detail by 14. The method of claim 11, wherein the human has a way of illustration and example for purposes of clarity of history of liver failure. understanding. However the description is not meant to limit 15. The method of claim 11, wherein the formulation is a the Scope of the claims. The invention being thus described, liquid gel administered enterally. it will be apparent to those skilled in the art that the same 16. The method of claim 11, wherein the human's blood may be varied in many ways without departing from the ammonia level is above normal. Spirit and Scope of the invention. Such variations are 17. A method, comprising administering to a human in included within the Scope of the following claims. need thereof a pharmaceutical formulation comprising a Synthetic Sodium aluminosilicate Zeolite and a pharmaceu We claim: tically acceptable adjuvant, wherein: 1. A method of treating, preventing, or palliating elevated (a) the Synthetic Sodium aluminosilicate is particulate and human blood lead levels, comprising administering to a at least about 95% of the particles are of particle size human in need thereof a pharmaceutical formulation com prising a Synthetic Sodium aluminosilicate Zeolite and a from about 90 um to about 150 um; pharmaceutically acceptable adjuvant, wherein: (b) the formulation is administered in doses of from about 5 g to about 12 g Sodium aluminosilicate; and (a) the Synthetic Sodium aluminosilicate is particulate and at least 90% of the particles are of particle size from (c) the human has a higher than normal risk of elevated blood levels of a toxic metal or has a higher than about 90 um to about 150 um; normal risk of hepatic encephalopathy. (b) the formulation is administered in doses of about 10 18. The method of claim 17, wherein the human is a mg to about 1000 mg Sodium aluminosilicate. hospital in-patient. 2. The method of claim 1, wherein at least about 95% of 19. A pharmaceutical formulation, comprising: the particles are of particle size from about 90 um to about 150 lum. (a) a particulate Synthetic Sodium aluminosilicate Zeolite 3. The method of claim 1, wherein the formulation is from wherein at least about 90% of the particles are of about 50% (w/w) to about 95% (w/w) water. particle size from about 90 um to about 150 lum, 4. The method of claim 1, wherein the formulation is a (b) from about 50% (w/w) to about 80% (w/w) water; and capsule or tablet administered enterally. (c) a microbial preservative; and 5. The method of claim 1, wherein the human is suffering from chronic lead poisoning. (d) a pharmaceutically acceptable adjuvant; 6. The method of claim 1, wherein the human has an wherein the formulation contains from about 100 mg to elevated blood lead level. about 10,000 mg by weight of sodium aluminosilicate. 7. The method of claim 1, wherein the human has a blood lead level of at least about 10 ug/L. k k k k k