Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1996-10-10
1999-12-14
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
A61K 31195
Patent
active
06001878&
DESCRIPTION:
BRIEF SUMMARY
The invention relates to a method of treating disorders of the animal or human body which require increasing blood flow to intestinal organs as well as to a method of treating disorders which can be treated by administering arginine.
The present invention relates in particular to the use of glutamine in the diseased state where there is a decreased blood flow to the liver or where there are low arginine plasma levels.
The splanchnic bed consists of several organs all of which drain into the portal vein. A liver receives its blood supply from both the portal vein and the hepatic arteria. 70-80% of the blood flow to the liver is received by the portal vein and therefore most of the nutrients and oxygen is taken out of the blood coming from the portal vein and is thus insufficient during a decrease in blood flow. Glutamine is capable of increasing blood flow through the liver by increasing splanchnic blood flow.
During periods of decreased blood flow (systemic inflammation, hypovolemia, cardiac shock, decreased peripheral resistance), blood flow to the liver is lower.
After normalisation of the blood flow, the liver passes into the stage of reperfusion damage which compromises blood flow in the liver, which further deteriorates liver function. Blood flow then is mostly maintained in the liver by increased nitric oxide (NO) production. Arginine is the substrate for NO. When there is an increased demand for NO, there may not be sufficient arginine as a substrate, or there may be an increased demand for arginine.
Those diseased states are during low arginine level e.g. endotoxemia, systemic inflammation, high arginase content in plasma, bacteremia, obstructive jaundice, other types of jaundice, liver transplantation, liver resection, inflammatory bowel disease, transplantation in general, increased cytokine production, steatosis of the liver.
Thus the invention is specifically directed at the use of glutamine or a glutamine equivalent for preparing a medicinal or nutritional composition for the treatment of diseased states where there is a decreased blood flow to the liver or where there are low arginine plasma levels. These diseased states can be those mentioned above, especially endotoxemia, systemic inflammation, high plasma arginase level, bacteremia, jaundice, liver transplantation, liver resection, inflammatory bowel disease, or increased cytokine production.
A glutamine equivalent is understood to be a substance which can be converted to glutamine, such as a glutamine dipeptide or a 2-acylaminoglutaric acid monoarnide. The glutamine or glutamine equivalent in the medicinal or nutritional composition may be supplemented by arginine or an arginine equivalent, e.g. to an amount of 0-50%, especially 1-25% of the combined amounts of glutamine and arginine and their equivalents. The medicinal or nutritional composition preferably contains an amount of glutamine or glutamine equivalent such as to provide a daily glutamine dosage of 0.2-4 g/kg body weight. This means that glutamine or its equivalent is administered in amount of e.g. 10-200 g/day for a subject having a body weight of 50 kg, or 20-400 g/day for a subject having a body weight of 100 kg. Below, the levels to be used are given on the basis of an assumed average body weight of 75 kg, but adaptations can be made as necessary.
The medicinal and nutritional compositions according to the invention are preferably formulated as enteral compositions. The composition may be a complete artificial food, i.e. which does not require additional food, or a food supplement. The further components of a complete food are preferably based on the recommended daily allowances (RDA) as generally accepted; the protein fraction may be based on a protein source rich in glutamine, or its hydrolysates. A supplement may be a glutamine contrate, e.g. obtained by hydrolysis of raw materials rich in glutamine, such as wheat protein. The enteral food may then be obtained by mixing, before use, of the concentrate with a basic food, e.g. according to the RDA. The composition preferabl
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Houdijk Alexander Petrus Jacobus
Van Leeuwen Paulus Aloisius Marie
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