Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-08-21
2004-03-30
Travers, Russell (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S561000, C514S567000, C514S419000, C514S562000
Reexamination Certificate
active
06713501
ABSTRACT:
BACKGROUND
The invention relates to an amino acid supplement for dialysis patients.
Patients on dialysis in the U.S. exhibit a 24% mortality per year. The best predictor of mortality identified to date is the serum albumin concentration. Small differences in serum albumin concentration predict substantial changes in mortality. For example, dialysis patients with a 0.2 g/dl higher serum albumin experience a mortality rate which is 25% lower (Owen et al., NEJM 329: 1001-6, 1993). Hypoalbuminemia is common at the onset of dialysis and during dialysis. It is not Amenable to dietary counseling in most cases. Its mechanism is unknown.
It has previously been shown that patients who have been prescribed a very low protein diet supplemented by either essential amino acids or ketoanalogues thereof for at least six months prior to dialysis rarely exhibit hypoalbuminemia at the onset of dialysis (Walser, M., Kidney Internat 44: 1139, 1993), in contrast to the national experience. It has also been shown that such patients have a substantially lower mortality on dialysis, in comparison with the national experience, at least for the first two years, despite consuming the usual dialysis diet (Coresh, J., M. Walser, and S. Hill; J Amer Soc Nephrol 6: 1379, 1995). Whether or not this reduction in mortality can be explained by higher levels of serum albumin could not be ascertained, because these patients were dialyzed at many facilities in several states.
The foregoing observations raise the possibility that supplementation of the diet of the dialysis patients with essential amino acids may protect against hypoalbuminemia, even in patients consuming normal or nearly normal quantities of dietary protein. No mechanism for such an effect is apparent, but similarly, no mechanism for the prevalence of hypoalbuminemia in this population has been identified, although several abnormalities of plasma and intracellular amino acid concentrations have been observed.
There are at least seven small clinical trials of oral supplementation with essential amino acids in dialysis patients reported (1-7). However none of these studies is definitive or well controlled. In reviewing these studies, Kaysen (8) states “Oral nutritional supplementation does not reverse hypoalbuminemia in this patient population”; Wolfson (9) states “However, despite a number of studies (reviewed subsequently) of the use of amino acid supplements, the impact on overall nutritional status has remained controversial”; Ikizler and Hakim (10) state “Furthermore, most of these studies are not controlled and are small in scope and the degree of success is variable”.
Intravenous supplementation has been studied more extensively, but the expense of this treatment is prohibitive, and according to Wolfson (9), “ . . . there are numerous flaws in many of these studies”.
Furst et al. (11) designed a new formula of essential amino acids, with a higher proportion of valine, lower proportions of leucine and isoleucine, and the inclusion of tyrosine, in an attempt to correct the extracellular and intracellular abnormalities of amino acid concentration that they found in predialysis uremic patients. They have shown that this mixture maintains nitrogen balance while improving abnormalities of amino acid concentrations (11-14). This formula was also used in the Feasibility Phase of a large NIH-supported study entitled “Modification of Diet in Renal Disease”, and was found to maintain nutrition in these patients with advanced chronic renal failure (15). This mixture has neither been used nor advocated in patients on dialysis.
SUMMARY OF THE INVENTION
The invention is based on the concept that a mixture of amino acids in tablet form and comprising, in each tablet, L-histidine 45 mg, L-isoleucine 60 mg, L-leucine 90 mg, L-lysine 65 mg, L-methionine 90 mg, L-phenylalanine 70 mg, L-threonine 65 mg, L-tryptophan 25 mg, L-tyrosine 75 mg, and L-valine 135 mg, administered in a dose of 8 to 18 tablets per day, will prevent and/or correct hypoalbuminemia in patients on dialysis (either hemodialysis or peritoneal dialysis), and will therefore improve their survival.
REFERENCES:
patent: 3764703 (1973-10-01), Bergstrom et al.
Furth et al, The Americal Journal of Clinical Nutrition, vol. 33, pp. 1387-1395, Jul. 1980.*
115CA:142315, Takagi et al, 1991.*
Furst et al, Effects of nutrition and catabolic stress on intracellular amino acid pools in uremia. The American Journal of Clinical Nutrition, vol. 33, Jul. 1980, pp. 1387-1395, see entire document.
Morgan & Lewis & Bockius, LLP
The Johns Hopkins University
Travers Russell
LandOfFree
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