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Methods for reducing phosphate absorption

a phosphate absorption and absorption technology, applied in the field can solve the problems of increased risk of death, convulsions and cardiac arrest, severe pathophysiology of calcium and phosphate homeostasis, etc., and achieve the effect of reducing phosphate absorption and maintaining the serum phosphate concentration

Inactive Publication Date: 2010-06-10
CYCTOCHROMA INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0014]In one aspect, the present invention relates to a method for reducing phosphate absorption in a human or non-human animal subject wherein the subject consumes a diet containing phytic acid or phytate and either has or is at risk of developing hyperphosphatemia. The method includes the step of administering orally to the subject an anti-phytic acid (C6H6[OPO(OH)2]

Problems solved by technology

Severe hyperphosphatemia can cause paralysis, convulsions and cardiac arrest.
Hyperphosphatemia occurs at serum phosphate concentrations above 5 mg / dl, which is associated with an increased risk of death (Block G et al., J. Am. Soc. Nephrol.
Hyperphosphatemia associated with chronic kidney disease leads to severe pathophysiologies in calcium and phosphate homeostasis, especially if present over extended periods of time.
For individuals who exhibit renal insufficiency, an elevation of serum phosphate within the normal range has been associated with progression of renal failure and increased risk of cardiovascular events.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Reducing Serum Phosphate Levels Increased by 1α-Hydroxyvitamin D3

[0042]Materials and Methods

[0043]Animals used for antibody production: Single Comb White Leghorn laying hens were used for antibody production (3 hens). The phytate antigen was prepared by conjugating phytic acid to bovine gamma globulin using standard glutaraldehyde procedure.

[0044]Conjugation preparation: While the procedure for conjugation of antigens to carrier proteins can vary considerably (a number of kits for conjugation can be obtained from Pierce Scientific), as well as the nature of the carrier proteins, the method used in the studies described in this example involved the use of the glutaraldehyde procedure for conjugation of phytic acid to the carrier protein bovine gamma globulin (BgG). BgG (4 mg) in 0.8 ml of 0.1 M sodium acetate buffer (pH=7) was mixed with 4 mg phytic acid (Sigma Chemical). 0.52 ml of 0.02 M glutaraldehyde (in 0.1 M sodium acetate buffer) was added dropwise (to avoid foaming) to the p...

example 2

Reducing Serum Phosphate Level in Adenine-Induced Uremic Animals

[0055]The animal model used in this example is the adenine-induced uremic rat model (see e.g., Yokazawa et al., Nephron 1986, 44:230-234; Katsumata et al., Kid Intl 2003, 64:441-450; and Levi R et al., J Am Soc Nephrol 2006, 17:107-112, each of which is herein incorporated by reference in its entirety).

[0056]Rats (e.g., male Sprague Dawley rats approximately 175-250 g, up to 10 rats per group) are fed a control diet or a uremia-inducing adenine diet (e.g., containing 0.75% adenine) containing both inorganic phosphate and phytic phosphate for a period of weeks (e.g., 3 to 5 weeks or longer). Rats fed the adenine diet will develop hyperphosphatemia with level of serum phosphate higher than 4.4 mmol / L. These rats will also develop vitamin D3, (1α-hydroxyvitamin D3 and 1α, 25-dihydroxyvitamin D3) deficiency. The daily oral treatment of these rats fed the adenine diet with increasing amount of anti-phytic acid or anti-phytat...

example 3

Reducing Serum Phosphate Level in 5 / 6 Nephrectomized Rats

[0059]For 5 / 6 nephrectomy (see e.g., Cozzolino M et al., Kidney Int. 2003, 64:1653-61), several branches of the left renal artery were ligated and the right kidney excised. 5 / 6 nephrectomized rats (e.g., male Sprague Dawley rats, approximately 175-250 g, up to 10 rats per group) are fed a high phosphate diet (e.g., 0.9% phosphate) containing both inorganic phosphate and phytic phosphate. These rats will become uremic weeks after surgery (e.g., 4 to 8 weeks) and develop renal failure, hyperphosphatemia, and active vitamin D3 (1α-hydroxyvitamin D3 and 1α, 25-dihydroxyvitamin D3) deficiency. The daily oral treatment of these 5 / 6 nephrectomized rats fed the high phosphate diet with increasing amount of anti-phytic acid or anti-phytate antibody will reduce the serum phosphate level in a dose dependent manner in these rats. If the antibodies are given within the first few weeks following surgery and thereafter they will either preve...

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Abstract

It is disclosed here a method for reducing phosphate absorption in a human or non-human animal subject wherein the subject consumes a diet containing phytic acid or phytate and either has or is at risk of developing hyperphosphatemia. The method includes the step of administering orally to the subject an anti-phytic acid (C6H6[OPO(OH)2]o) antibody or an anti-phytate antibody in an amount effective to reduce or maintain the serum phosphate concentration in the subject.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. provisional application Ser. No. 60 / 854,550, filed on Oct. 26, 2006, which is herein incorporated by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]Not applicable.BACKGROUND OF THE INVENTION[0003]Phosphorus is an essential element in human nutrition and plays essential structural and functional roles in the biochemistry, cellular integrity, and physiological processes of the body. In foods comprising animal or vegetable matter, phosphorus can be found as inorganic phosphate (Pi) (e.g., in its pentavalent form in combination with oxygen as phosphate (PO43−)), which can be readily absorbed from the gastrointestinal tract. Also, phosphate can be found as a constituent of bio-macromolecules such as proteins, nucleic acids, lipids and sugars. Plant material can also be enriched in phytic acid (C6H6[OPO(OH)2]6), which is the principal storage form of pho...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P3/00
CPCA61K2039/505C07K16/40C07K2317/23C07K2317/11C07K2316/96C07K2317/76A61P13/02A61P13/12A61P3/00A61P3/12A61P31/04A61P43/00A61P7/00
Inventor COOK, MARKPETKOVICH, MARTINHELLESTAD, ERICA
Owner CYCTOCHROMA INC
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