Product containing growth factor and glutamine and use of growth

Details Product containing growth factor and glutamine and use of growth Product containing growth factor and glutamine and use of growth

1993-02-23

1995-10-31

Warden, Jill

Textiles: spinning, twisting, and twining

514 21, C07K 500, A61K 3800

Patent

active

054629241

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to a product having anabolic effects and which also can be used for the treatment or prevention of malfunction or diseases of the intestinal mucosa. The product contains a growth factor together with glutamine and a fatty acid. The invention also comprises a procedure for the prevention or treatment of impaired function of the gut wall after, for example, trauma, sepsis, burn injuries, radiation therapy or cytotoxic chemotherapy, as well as different inflammatory conditions such as ulcerative colitis or morbus Chron. Thereby can growth factors optionally together with glutamine and/or a fatty acid be given by oral, intravenous, peritoneal, rectal, intramuscular or subcutaneous administration.


BACKGROUND

In trauma and sepsis, in addition to the conspicuous injuries or signs of infection, there are also metabolic changes. These changes can be divided into an early so-called ebb phase followed later by a so-called flow phase. In the ebb phase (shock phase), which can last for 1-3 days after the incidence of the injury, there exists a reduced energy turnover, increased lipolysis, hyperglycaemia, elevated catecholamine release and hormonal maladaptation, circulatory effects with decreasing blood pressure, reduced tissue perfusion and oxygen consumption, hypoxia, acidosis, increased body weight as a result of fluid and urine retention and a reduced body temperature. Protein synthesis is also reduced as well as blood albumin and amino acid concentrations.
After about 3 days, the flow phase appears which can last for 1-4 weeks. The flow phase is characterised by an increased energy turnover, increased release of substrates, negative nitrogen balance, rise in blood pressure, increased oxygen consumption and elevation of body temperature. Protein synthesis is reduced in mild trauma whilst both synthesis and breakdown increase in major trauma. Breakdown dominates resulting in a negative nitrogen balance which can reach 0.3-0.6 g nitrogen per kg body weight and day. This is equivalent to approximately 1.2-2.4 kg muscle wastage per day in a normal individual.
If the catabolic component of the flow phase continues for too long, a life threatening situation can develop with substantial losses of fat and muscle tissue as well as impaired wound healing and defence against infection (Ljusk S Eriksson, Mossberg T, Wahren J; pp 99-117, Klin Nutr Almq & Wiks 1987).
The concentration of glycogenic amino acids (such as alanine, glycine, serine and glutamic acid) drops in the plasma whilst a simultaneous increase in the plasma levels of branched chain amino acids (such as leucine, isoleucine and valine), aromatic amino acids (such as phenylalanine, tyrosine and tryptophan) as well as methionine, is observed. An approximately 50% reduction of the intracellular glutamine concentration is also typical. The above mentioned changes can partly be explained as disturbances in transport over the cell membrane. Alanine and glutamine are taken up and metabolised by the gut mucosa and the liver. In the liver they are utilised for, amongst other things, gluconeogenesis. In burn patients the splanchnic (liver and gut) uptake of amino acids is increased approximately 2-6-fold compared to a healthy control. The protein catabolism, which is evident mainly as increased urea production, not only affects striated muscles and visceral proteins but also smooth muscles such as those found in the gut wall and in the respiratory pathways. This situation can negatively affect vital bodily functions as well as secretory transport in the bronchii, with secretory stagnation and development of pneumonia, a common post-traumatic complication.
The gut mucosa is important not only for the selective and active absorption of different nutrients, but also as a barrier against foreign organisms and toxins. In recent years, it has been shown that the barrier function of the gut mucosa deteriorates in association with major trauma and sepsis. Furthermore, both cytotoxic chemotherapy and radiation therapy have a deleterious effect on g

REFERENCES:
patent: 5164370 (1992-11-01), Ballard et al.
Low-dose growth hormone and hypocaloric nutrietion attenuate the protein-catabolic response after major operation, Dialog Information Services, File 155, Medline 66-91/May, Dialog Accession No. 07118481, Jiang ZM et al., Ann Surg Oct. 1989, 210 (4) pp. 513-524.

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