| Use of rare earth compounds for the prevention of kidney stone disease -> Monitor Keywords |
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Use of rare earth compounds for the prevention of kidney stone diseaseRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Inorganic Active Ingredient Containing, Heavy Metal Or Compound ThereofUse of rare earth compounds for the prevention of kidney stone disease description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070116782, Use of rare earth compounds for the prevention of kidney stone disease. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. application Ser. No. 10/128,783, filed Apr. 22, 2002, which claims priority under 35 U.S.C. .sctn. 119(e) from Provisional Application 60/285,901, filed 23 Apr. 2001. The contents of these application are incorporated herein by reference. TECHNICAL FIELD [0002] This invention relates to a method of preventing or treating urolithiasis (kidney stone disease) by administering rare earth salts, e.g., Lanthanum salts, to bind dietary oxalate and preventing its absorption into the gastrointestinal tract. BACKGROUND OF THE INVENTION [0003] Nephrolithiasis or urolithiasis is a common disorder defined as the development of stones within the urinary tract such as the kidney stone disease. This disorder represents a serious health problem. Depending on local conditions, between 1 and 14% of the population suffers from this condition. The economic impact of urolithiasis in the U.S. was estimated to be $1.83 billion in 1993 (Grases, et al., International Urology and Nephrology, 31(5) pp. 591-600 (1999)). Current preventative/treatment for urolithiasis are not easy to take and not that effective, e.g., potassium citrate tablets. [0004] Calcium oxalate is the dominant component in kidney stones. The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and kidney stone formation (R. Holmes, et al., Kidney International, 59, pp. 270-276 (2001)). In addition, calcium oxalate is also known to be associated with arthritis (Reginato AJ, Kurnik BRC: "Calcium oxalate and other crystals associated with kidney disease and arthritis," Semin Arthirtis Rheum 18:198, 1989). [0005] PCT publication WO 99/22744 suggests the use of aliphatic polyamines to reduce the levels of oxalate in the digestive tract. This publication suggests that the polyamines be administered orally optionally in the presence of enzymes, such as oxalate decarboxylase or oxalate oxidase which can decompose oxalate. Various forms of oral dosage are described. The contents of this publication are incorporated herein by reference. [0006] Hydrates of lanthanum carbonate [La.sub.2(CO.sub.3).sub.3] are described in U.S. Pat. No. 5,968,976 and WO 96/30029 for treating hyperphosphataemia in patients with renal failure by removing elevated levels of phosphates. This treatment is especially useful in patients undergoing kidney dialysis. These compounds are particularly preferred. [0007] There exists a need for agents that bind oxalate and thereby inhibit or prevent stone formation in the kidneys. The present invention addresses this need by using rare earth compounds to lower levels of oxalate in animals, including humans. [0008] Citation of the above documents is not intended as an admission that any of the foregoing is pertinent prior art. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents. Further, all documents referred to throughout this application are hereby incorporated in their entirety by reference herein. DISCLOSURE OF THE INVENTION [0009] The invention concerns methods to control, prevent, or treat subjects who are at risk for or who exhibit the symptomology of oxalate deposits in the kidneys--i.e., kidney stones, through the oral administration of rare earth salts, e.g. lanthanum salts, with high affinity oxalate binding properties. [0010] Thus, in one aspect, the invention is directed to a method to inhibit the formation of kidney stones in a subject which method comprises administering to the gastrointestinal tract of said subject, an effective amount of a nontoxic rare earth salt, optionally in hydrated form. In typical embodiments, the rare earth salt is of the formula[RE].sub.a[X].sub.b.cH.sub.2O (1) wherein RE represents a rare earth cation, X represents a nontoxic anion, a and b are of suitable relative values so that a neutral salt is formed, and c has a value of 0-10. [0011] In another aspect, the invention is directed to a method to modulate the absorption of oxalate from the gastrointestinal tract of a subject which method comprises administering the compounds of formula (1) to a subject in need of such treatment. [0012] In another aspect, the invention is directed to the use of an optionally hydrated rare earth nontoxic salt to prepare a medicament for the treatment of subjects at risk for or exhibiting symptoms of oxalate-based kidney stones. BRIEF DESCRIPTION OF THE DRAWINGS [0013] FIGS. 1A and 1B show oxalate removal by 0.1 M lanthanum carbonate hydrates, i.e., lanthanum carbonate tetrahydrate (La.sub.2(CO.sub.3)hd 3.4H.sub.2O) (FIG. 1A), and lanthanum pentahydrate (La.sub.2(CO.sub.3).sub.3.5H.sub.2O) (FIG. 1B), at pH 7 using an oxalate solution containing 0.01 M sodium oxalate and 8.5 g/L sodium chloride. [0014] FIG. 2 shows a comparison of oxalate binding by lanthanum carbonate tetrahydrate at pH 3 to pH 7. [0015] FIGS. 3A and 3B show competitive binding of a 0.01 M oxalate and 0.1 M phosphate solution using 0.1 M lanthanum carbonate at pH 3 (FIG. 3A) and pH 7 (FIG. 3B). [0016] FIGS. 4A and 4B show oxalate binding by yttrium carbonate [Y.sub.2(CO.sub.3).sub.3.3H.sub.2O] (FIG. 4A) and cerium carbonate [Ce.sub.2(CO.sub.3).sub.3.XH.sub.2O] (FIG. 4B) (supplied by Aldrich) at pH 3 and pH 7. [0017] FIG. 5 shows oxalate removal by lanthanum chloride at pH 7. [0018] FIG. 6 shows removal of oxalate and phosphate by lanthanum carbonate as pH changes from pH 3 to pH 7. MODES OF CARRYING OUT THE INVENTION Continue reading about Use of rare earth compounds for the prevention of kidney stone disease... Full patent description for Use of rare earth compounds for the prevention of kidney stone disease Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Use of rare earth compounds for the prevention of kidney stone disease patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. 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