Method of making phosphate-binding polymers for oral...

Details Method of making phosphate-binding polymers for oral... Method of making phosphate-binding polymers for oral...

2000-04-04

2003-01-21

Spear, James M. (Department: 1615)

Drug, bio-affecting and body treating compositions

Solid synthetic organic polymer as designated organic active...

Ion exchange resin

C424S078010, C424S078110

Reexamination Certificate

active

06509013

ABSTRACT:

BACKGROUND OF THE INVENTION
Hyperphosphatemia frequently accompanies diseases associated with inadequate renal function, hypoparathyroidism, and certain other medical conditions. Hyperphosphatemia is typically defined as possessing a serum phosphate levels of over about 6 mg/dL. The condition, especially if present over extended periods of time, leads to severe abnormalities in calcium and phosphorus metabolism and can be manifested by aberrant calcification in joints, lungs, and eyes.
Therapeutic efforts to reduce serum phosphate include dialysis, reduction in dietary phosphate, and oral administration of insoluble phosphate binders to reduce gastrointestinal absorption. Dialysis and reduced dietary phosphate are generally unsuccessful in adequately reversing hyperphosphatemia. Further difficulties in these therapeutic regimens include the invasive nature of dialysis and the difficulties in modifying dietary habits in the latter therapy.
The oral administration of certain phosphate binders has also been suggested. Phosphate binders include calcium or aluminum salts. Calcium salts have been widely used to bind intestinal phosphate and prevent absorption. The ingested calcium combines with phosphate to form insoluble calcium phosphate salts such as Ca
3
(PO
4
)
2
, CaHPO
4
, or Ca(H
2
PO
4
)
2
. Different types of calcium salts, including calcium carbonate, acetate (such as PhosLo® calcium acetate tablets), citrate, alginate, and ketoacid salts have been utilized for phosphate binding. This class of therapeutics generally results in hypercalcemia due from absorption of high amounts of ingested calcium. Hypercalcemia has been indicated in many serious side effects, such as cardiac arrhythmias, renal failure, and skin and visceral calcification. Frequent monitoring of serum calcium levels is required during therapy with calcium-based phosphate binders.
Aluminum-based phosphate binders, such as Amphojel® aluminum hydroxide gel, have also been used for treating hyperphosphatemia. These compounds complex with intestinal phosphate to form highly insoluble aluminum phosphate; the bound phosphate is unavailable for absorption by the patient. Prolonged use of aluminum gels leads to accumulations of aluminum, and often to aluminum toxicity, accompanied by such symptoms as encephalopathy, osteomalacia, and myopathy.
Selected ion exchange resins have also been suggested for use in binding phosphate. Those tested include Dowex® anion-exchange resins in the chloride form, such as XF 43311, XY 40013, XF 43254, XY 40011, and XY 40012. These resins have several drawbacks for treatment of hyperphosphatemia, including poor binding efficiency, necessitating use of high dosages for significant reduction of absorbed phosphate.
Thus a need exists for improved phosphate binders which can be administered orally in acceptable dosage levels without resulting in many of the serious side effects discussed above.
SUMMARY OF THE INVENTION
The invention relates to the discovery that a class of anion exchange polymers have improved phosphate binding properties. In general, the invention features a method of removing phosphate from a patient by ion exchange, which involves oral administration of a therapeutically effective amount of a composition containing at least one phosphate-binding polymer. The polymers of the invention may be crosslinked with a crosslinking agent.
The invention provides an effective treatment for decreasing the serum level of phosphate by binding phosphate in the gastrointestinal tract, without comcomittantly increasing the absorption of any clinically undesirable materials, particularly calcium or aluminum.
Other features and advantages will be apparent from the following description of the preferred embodiments and from the claims.


REFERENCES:
patent: 2456428 (1948-12-01), Parker
patent: 3104205 (1963-09-01), Hainer et al.
patent: 3980770 (1976-09-01), Ingelman et al.
patent: 4071478 (1978-01-01), Shen et al.
patent: 4143130 (1979-03-01), Imondi et al.
patent: 4181718 (1980-01-01), Mason et al.
patent: 4504640 (1985-03-01), Harada et al.
patent: 4605701 (1986-08-01), Harada et al.
patent: 4895621 (1990-01-01), Hassler
patent: 5053423 (1991-10-01), Liu
patent: 5302531 (1994-04-01), Bauer
patent: 5496545 (1996-03-01), Holmes-Farley et al.
patent: 5667775 (1997-09-01), Holmes-Farley et al.
patent: 6083495 (2000-07-01), Homes-Farley et al.
patent: 6274713 (2001-08-01), Sieviing et al.
patent: 0 162 388 (1985-11-01), None
patent: 0 375 350 (1990-06-01), None
patent: 2 232 563 (1975-01-01), None
patent: 2036048 (1978-11-01), None
patent: 2 090 605 (1982-07-01), None
patent: 62132830 (1987-06-01), None
patent: A-5-244915 (1993-09-01), None
patent: Hei 6-321786 (1994-11-01), None
patent: 7401543 (1974-08-01), None
patent: 7 603 653 (1976-10-01), None
patent: 93/05793 (1993-01-01), None
patent: 94/19379 (1994-01-01), None
patent: 94/04596 (1994-03-01), None
McGary, T.J. et al., “Polycation As an Alternative Osmotic Agent and Phosphate Binder in Peritoneal Dialysis,”Uremia Investigation,8(2):79-84 (1984-1985).
Physicians' Desk Reference, Consult 1992 Supplements for Revisions “Phoslo®”, Calcium Acetate Tablets.
Physicians' Desk Reference, Consult 1992 Supplements for Revisions “Amphojel®”, Suspension Tablets.
Burt et al., “Ion-Exchange Resins as Potential Phosphate-Binding Agents for Renal Failure Patients: Effect of the Physicochemical Properties of Resins on Phosphate and Bile Salt Binding,”Journal of Pharmaceutical Sciences,76(5):379-383 (1987).
Delmez, James A. et al., “Hyperphosphatemia: Its Consequences and Treatment in Patients with Chronic Renal Disease,”American Journal of Kidney Diseases,XIX(4):303-317 (1992).
Emmett, Michael et al., “Calcium Acetate Control of Serum Phosphorus in Hemodialysis Patients,”American Journal of Kidney Diseases,XVII(5):544-550 (1991).
Ghosh, J.P. et al., “Preparation and Properties of a New Chelating Resin Containing 2-Nitroso-1-naphthol,”Talanta,28:957-959 (1981).
Mai, Martin L. et al., “Calcium acetate, an effective phosphorus binder in patients with renal failure,”Kidney International,36:690-695 (1989).
Munson, Paul L., “Studies on the Role of the Parathyroids in Calcium and Phosphorus Metabolism,”Annals New York Academy of Sciences,pp. 776-795 (Jun. 1993).
Slausky, I.B. et al., “Aluminum Accumulation During Treatment with Aluminum Hydroxide and Dialysis in Children and Young Adults with Chronic Renal Disease,”The New England Journal of Medicine,324(8):537-531 (1991).
Slatopolsky, Eduardo et al., “Calcium Carbonate as a Phosphate Binder in Patients with Chronic Renal Failure Undergoing Dialysis,”The New England Journal of Medicine,315(3):157-161 (1986).
Warshawsky, A., in Ion Exchange and Sorption Processes in Hydrometallurgy Critical Reports on Applied Chemistry, vol. 15, Chapter 4:Chelating ion exchangers,pp. 166-225 M. Streat & D. Naden (Eds.), John Wiley & Sons, (1987).
Winston, Anthony and Kirchner, Darrell, “Hydroxamic Acid Polymers. Effect of Structure of the Selective Chelation of Iron in Water,”Macromolecules,11(3):597-603 (1978).
Winston, Anthony and McLaughline, Glenn R., “Hydroxamic Acid Polymers. II. Design of a Polymeric Chelating Agent for Iron,”Journal of Polymer Science,14:2155-2165 (1976).

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