The present invention concerns a nutriment preparation for humans and animals comprising an energy substrate which is suited in particular for uraemic patients and for clinical nutrition.
Patients who must be nourished clinically often display a poor standard of nutrition such as that obtaining in the case of severe trauma, for example severe and extensive burns, operative trauma, severe physical injuries, different forms of cancer or sepsis. In such conditions, the metabolism picture is complicated.
In the metabolism of the body a number of metabolites which are subject to further oxidation and thereby produce different amounts of energy are synthesized from carbohydrates and fats. The ketone bodies which represent important alternative energy substrates for the body are examples of such metabolites. In the condition of hunger they are created in large quantities, and in the case of a prolonged hunger condition they become more important than glucose as an energy source. The possibility of utilizing ketone bodies to prevent the damaging decomposition (catabolism) of muscular protein for gluconeogenesis thereby reduces the loss of valuable body protein and thus exerts an energy-saving effect.
In the peripheral protein depots (muscles) mainly the branched-chain amino acids leucine, isoleucine and valine, in the main leucine, are oxidized, which means that in these patients the pool of branched-chain amino acids is gradually exhausted, which in turn results in reduced protein synthesis in the liver.
Ketone bodies have thus become increasingly interesting as an energy substrate both in enteral and parenteral nutrition, beyond their current administration in dialysis patients resp. patients displaying restricted kidney function.
Numerous experiments have already been conducted to find a method by which ketone bodies and similar substances may be effectively administered to the body. The branched-chain keto-acids, in particular ketoleucine, ketoisoleucine and ketovaline, are of special interest in this regard.
However, for a number of reasons the possibility of administering keto-acids is limited. They are practically not processable in aqueous solution, since they display very minimal stability and, moreover, they also cause very considerable strain. In addition, they must be administered in the form of salts, which entails the risk that excessive quantities of cations, for example sodium cations and potassium cations, are ingested during their administration. Furthermore, keto-acids and their salts are soluble in water and thereby raise the osmotic pressure of the nutriment, which causes the corresponding deleterious effects, such as too rapid passage through the bowels and diarrhea.
A circumvention of these problems is achieved by the somewhat more stable branched-chain .alpha.-hydroxy acids, which, however, were initially only administered as unazotized amino acid substitutes. According to the PCT-Application WO 90/02547, .alpha.-hydroxy acids and their pharmaceutically acceptable metal salts are used as precursors of the branched-chain keto-acids. These .alpha.-hydroxy acids are used metabolically as an energy substrate in enteral and parenteral nutrition after respective metabolization.
In the EP 0 367 734 energy substrates for clinical nutrition were used, which contain at least one ester of glycerine and at least one branched-chain hydroxycarbon acid. L-.alpha.-hydroxyisocapronic acid, .alpha.-hydroxy-.beta.-methylvaleric acid and L-.alpha.-hydroxyisovaleric acid were named as examples of such hydroxycarbon acids.
The use of triglycerides with less calories in nutriments is proposed in the PCT-Application WO 91/03944, whereby the calory ingestion is to be reduced simultaneously with nutriment ingestion. In the triglycerides designed for this purpose, the hydroxy groups in position 1 and 3 of the glycerol are estered with saturated long-chain fatty acids (16-40 carbon atoms) and the hydroxy group in position 2 of the glycerol is estered with a short-chain acid (2-10 carbon atoms), which may be either saturated or unsaturated or straight- or branched-chain.
The use of glycerol esters in nutriment mixtures for the treatment of obesity is also known from the U.S. Pat. No. 3,579,548. The glycerol esters used there are glycerol esters of .alpha.-branched-chain carbon acid. With these triglycerides few calories are to be provided, i.e. these triglycerides are not to be digested and absorbed to the same extent as conventional triglycerides.
According to the FR-Patent 1.600,887 glycerine-triisobutyrate is proposed as a component of nutriments, in particular of nutriments for brood animals.
USPTO Backgrounds
USPTO Backgrounds