Pharm/Biotech
Resources

Outsourcing Guide

Cont. Education

Software/Reports

Training Courses

Web Seminars

Jobs

Buyer's Guide

Home Page

Pharm Patents /
Licensing

Pharm News

Federal Register

Pharm Stocks

FDA Links

FDA Warning Letters

FDA Doc/cGMP

Pharm/Biotech Events

Consultants

Advertiser Info

Newsletter Subscription

Web Links

Suggestions

Site Map
 

 

 

 

Title:  Method of administration of a nutritional product to a person having renal failure

United States Patent:  6,288,116

Inventors:  Lowry; Carol Jo (Minneapolis, MN); Sass; Kathy Marie (Forest Lake, MN)

Assignee:  Novartis Nutrition AG (Berne, CH)

Appl. No.:  078165

Filed:  May 13, 1998

Abstract

L-arginine found essential to enhance the glomerular function of the kidneys is used to formulate a low viscosity, calorie-dense, nutritional product for a person having renal failure. In a product free of citric acid or citrates, for oral ingestion, the taste of arginine is counteracted by lactic, malic or adipic acid; in a formulation for tube-feeding, citric acid and citrates in a specified ratio controls the product's stability. The ratio of calcium to phosphorus is controlled, as is the caloric distribution and water content; the amounts of vitamins and minerals included provide a nutritionally complete formulation.

SUMMARY OF THE INVENTION

L-arginine, which is known to be a non-essential amino acid, is critical for enhancing the glomerular function of the kidneys; and, at least as much elemental arginine is added in a liquid formulation as is present in protein incorporated in the liquid, typically contributing at least about 0.5% of total calories, and preferably from 0.75% to 7% of total calories in the formulation. Because of the combination of a carboxylic acid with elemental arginine, the presterilized liquid formulation has a pH in the range from 6 to 8, preferably from 6.5 to 7.5; a viscosity less than 100 cp, preferably 30 to 70 cp; and an osmolality of less than about 1000 mOsm/kg water, preferably from about 500 to 900 mOsm/kg water. Unexpectedly, combining the L-arginine with one or more specific carboxylic acids not only lowers the pH into the desirable range, but also imbues the product for oral ingestion with a pleasant taste which may be enhanced by other ingredients of the nutritionally complete composition. In the "oral" formulation, neutralizing the arginine with lactic, adipic or malic acids, which are examples of "arginine-neutralizing acids", suppresses the bad taste of arginine, lowers the pH and provides a key ingredient which controls viscosity; varying the levels of staple nutrient components within allowable ranges has surprisingly little effect on the taste, but influences other properties substantially. The formulation is stabilized without the use of commonly used protein stabilizers, and is aseptically sterilized at a temperature below 300oF. for from 3 to 10 sec. In the formulation for a retorted product, neutralizing the arginine with a combination of citric acid and citrates (which act as a buffer), in a citric/citrate ratio in the range from 2 to 8, preferably from 2.5 to 6, both lowers the pH into the desired range as well as stabilizes the protein so that it survives high temperature sterilization in the range from 250oF. to 270oF. for from 10 to 20 min.

This nutritional product is calorie and nutrient-dense, has moderate to high protein content, and a high calcium to phosphorus ratio of at least 1:1, preferably in the range from about 1:1 to 2:1. The product contains about 100 g fat/L, about 200 g carbohydrate/L, and essentially no sugars such as sucrose, lactose or fructose which have an inordinately high adverse effect on osmolality. If desired, a small amount of fructose, contributing less than 1.5% of total calories, may be added provided the desired osmolality of the formulation is maintained. In addition, 8 fl oz of the product which provides about 475 cal, contains from 25 mg to 75 mg of magnesium, and 1 liter meets at least 100% of the RDI (reference daily intake) for vitamins and minerals with the exception of chloride, vitamin D, vitamin A, phosphorus, magnesium, chromium and molybdenum. Yet, the product meets the nutritional requirements of a renal patient. Specifically the product is low in phosphorus content and contains L-arginine to help maintain a desirable normal level for each patient.

A specific product which provides about 2 cal/ml is characterized by having less than 80% by weight water, and the addition of enough elemental arginine to contribute from about 0.75% to 3% total calories. The balance of arginine may be derived from caseinates. The caloric distribution for such a product is as follows: from all arginine 1.2% to 3%; from protein, 12 to 18%; from fat, 40 to 46%; the balance from carbohydrates. In one preferred formulation flavored for oral use, containing essentially no sucrose, lactose or fructose, and lactic acid as taste-suppressant, for those patients who tend to absorb aluminum-containing phosphate binders which are prescribed, no citric acid or citrates are present; in another formulation for tube feeding, containing a combination of citric acid and citrates as taste-suppressant, essentially no lactose, sucrose or fructose is present. Citrates are chosen from the salts of sodium, potassium and calcium to provide a desired balance of the levels of each. Most preferably, a citric acid and citrates-containing formulation is packaged in a retortable container for tube feeding, being hermetically sealed, sterilized and shelf-stabilized at about 256oF. for 13 min. An aseptically sterilized container is sterilized at about 280oF. for 4.5 sec, for oral or tube feeding a product with no citric acid or citrates. In each product, changing the order of addition of the arginine relative to the protein and carbohydrates, and that of the oils relative to the foregoing, produces an undesirable product.

Claim 1 of 7 Claims

We claim:

1. A method of treating a patient suffering from renal failure comprising administering to said patient

a composition comprising L-arginine, an arginine-neutralizing acid, protein, fat, carbohydrates,

vitamins and minerals,

wherein the arginine-neutralizing acid is selected from the group consisting of lactic acid, malic acid, adipic acid, and mixtures thereof, and wherein the composition has a pH of from 6 to 8, an osmolality of less than 1000 mOsm/kg water, and a viscosity of less than 100 centipoise as determined by a Brookfield viscometer using spindle #1 at 60 rpm.


____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.

 

 

[ Outsourcing Guide ] [ Cont. Education ] [ Software/Reports ] [ Training Courses ]
[ Web Seminars ] [ Jobs ] [ Consultants ] [ Buyer's Guide ] [ Advertiser Info ]

[ Home ] [ Pharm Patents / Licensing ] [ Pharm News ] [ Federal Register ]
[ Pharm Stocks ] [ FDA Links ] [ FDA Warning Letters ] [ FDA Doc/cGMP ]
[ Pharm/Biotech Events ] [ Newsletter Subscription ] [ Web Links ] [ Suggestions ]
[ Site Map ]