Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
1997-06-27
2004-09-28
Travers, Russell (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S563000, C514S763000, C514S474000, C514S455000
Reexamination Certificate
active
06797729
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the use of the amino acid glutamine in combination with antioxidants or other precursors (such as N-acetyl-cysteine) as a nutritional supplement for patients with certain conditions of the body.
2. Discussion of the Background of the Invention
Malnutrition and the wasting of protein-containing muscle mass are major clinical consequences of infection with human immunodeficiency virus (HIV). Both contribute to the progression, morbidity and mortality of the disease. The etiology of the malnutrition and skeletal muscle wasting is multifactorial and includes: 1) hypermetabolism (or other metabolic derangements), 2) gastrointestinal dysfunction particularly impaired nutrient absorption and 3)inadequate food intake. Because there remains no definitive cure for HIV and resulting acquired immunodeficiency syndrome (AIDS), the medical and nutritional management of these patients has focused on the preservation of skeletal muscle mass, limiting symptoms (e.g., diarrhea, malabsorption) associated with gastrointestinal dysfunction, the prevention of opportunistic infections, and the enhancement of host immune defense.
Normal Metabolic Functions of Glutamine
Glutamine is a non-essential amino acid which can be synthesized by most tissues. Unlike most amino acids, glutamine has two amine moieties: an alpha-amino group and an amide group. It is the presence of the amide group which enables glutamine to remove ammonia from the peripheral tissues of the body and transport nitrogen to visceral organs. In addition, it is common for tissues that remove glutamine from the circulation to utilize the carbon skeleton for energy.
Glutaminase and glutamine synthetase are the two principal enzymes involved in the regulation of glutamine metabolism. Glutaminase catalyzes the hydrolysis of glutamine to glutamate and ammonia, while glutamine synthetase catalyzes the synthesis of glutamine from glutamate and ammonia. While most tissues have both of these enzymes, usually one is more active than the other, depending on the particular tissue.
Glutamine synthesis and exportation occurs primarily in skeletal muscle and the brain. In turn, glutamine is consumed by such replicating cells as fibroblasts, lymphocytes, tumor cells and intestinal epithelial cells. Characteristically, these cells possess high levels of glutaminase activity and low levels of intracellular glutamine. This fact may also be clinically significant for patients having large wounds, inflammation associated with infection, or a gastrointestinal dysfunction which precludes normal enteral feeding since, in these cell types, the desirable proliferation of cells in these conditions may depend on the availability of sufficient levels of glutamine. Glutamine is the most abundant free amino acid in the body and is involved with a dynamic inter-organ network—being released from the skeletal muscle (the major site of glutamine synthesis) to be utilized and metabolized throughout the body. Rapidly replicating cells (e.g. enterocytes, lymphocytes, macrophages) remove glutamine from the circulation and often utilize its 5 carbon chain for energy. Metabolism of glutamine to alpha-ketoglutarate and subsequent complete oxidation via the Krebs cycle yields 30 moles of ATP per mole of glutamine. Glutamine also plays a pivotal role in whole body nitrogen metabolism due to its two amine moieties, an alpha-amino group and an amide group, and acts as a “nitrogen shuttle” among various organs. Glutamine serves as a vehicle for transporting ammonia in a nontoxic form from the peripheral tissues to the kidney to be excreted as ammonium, or to the liver to be converted to urea. Glutamine also provides nitrogen for the synthesis of purines and pyrimidines and other amino acids, and thus—proteins. In addition, glutamine serves as a precursor to glutathione, a potent antioxidant important to limiting tissue damage from radical attack.
Alterations in Glutamine Metabolism
The stress associated with infection, prolonged illness or severe injury results in profound alterations in whole body and inter-organ glutamine metabolism. These hypermetabolic conditions (e.g., AIDS) are characterized by severe catabolism, wasting of protein-containing skeletal muscle mass, impairment in vital organ function and immunosuppression. The hormonal and inflammatory mediator milieu creates a generalized response in which amino acids are mobilized from the skeletal muscle in order to provide energy and substrate to support inflammation, immune response and tissue repair, and to assist in the maintenance of organ function.
Glutamine is a primary amino acid released from the skeletal muscle during stressed states. This accelerated release of glutamine from the periphery is matched with increased uptake by the intestinal tract, lymphoid tissue, liver and kidney. When the stress is prolonged, glutamine is consumed at rates faster than it can be synthesized and released from the skeletal muscle; the wasting of body nitrogen and skeletal muscle mass ensues. Glutamine levels in both the plasma and tissue pools diminish, creating a “deficiency” state. This lack of adequate glutamine alters the structure and/or function of those cells (e.g., enterocytes, lymphocytes, macrophages) dependent upon glutamine. Thus, under conditions of prolonged stress (e.g., HIV infection, AIDS, injury) glutamine has been classified as a “conditionally” essential amino acid. Glutamine supplementation restores amino acid concentrations in the plasma towards normal, limits the loss of protein-containing mass, and enhances tissue structure and/or function.
Glutamine Supplementation and the Preservation of Body Protein
In adult patients with AIDS, the timing of death is related to the degree of depletion of the body's protein-containing, metabolically active, functioning cellular mass. The body's cellular mass (BCM) constitutes approximately 30-38% of total body weight and approximately 55% of total body protein—with the majority present in the skeletal muscle mass and visceral organs. AIDS is associated with an accelerated loss of protein-containing tissue which is out of proportion to the loss of weight and fat mass. Even in asymptomatic HIV-infected adults, there can be a loss of this functional, protein-containing mass without significant changes in body weight or body mass index.
Stress (e.g. prolonged or repeated infections) induces an accelerated release of glutamine from the skeletal muscle protein, resulting in a decrease in intracellular muscle glutamine concentrations. Under such conditions, glutamine supplementation can minimize this decrease in muscle glutamine content. Clinically, this is important because a statistically significant correlation between survival in septic patients and intracellular muscle glutamine concentrations has been demonstrated.
In addition to decreased skeletal muscle glutamine concentrations, prolonged stress (such as that which is associated with HIV infection and AIDS) can result in severe wasting of skeletal muscle protein (nitrogen), which in turn suits in a precipitous fall in physiologic function. Clinically this manifests as skeletal muscle and respiratory muscle weakness, poor wound healing, and further impairment in immune function.
Glutamine supplementation has been shown to improve nitrogen (protein) balance in stressed and immunocompromised patients. Others have shown that glutamine supplementation can reduce myofibrillar protein breakdown and enhance skeletal muscle protein synthesis. These findings suggest that glutamine supplementation contributes to the preservation of the protein-containing tissue mass; and thus, may limit the physical debility and immunosuppression associated with its loss.
Glutamine Supplementation and the Preservation of Gut Structure and Function
Gastrointestinal tract dysfunctions are common complications of HIV infection. Anorexia, early satiety, nausea, abdominal pain, mouth or esophageal infections, gastrointestinal dysmotility, etc., can prevent ad
Byrne Theresa A.
Somerville Joanne A.
Baxter International Inc.
Buonaiuto Mark J.
Kowalik Francis C.
Nichols Jeffrey C.
Travers Russell
LandOfFree
Therapeutic glutamine and N-actyl-cysteine composition does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Therapeutic glutamine and N-actyl-cysteine composition, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Therapeutic glutamine and N-actyl-cysteine composition will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3250767