DE4133366A1 - Aminoacid compsn. for prevention of hypoxic cell damage - contains glycine, serine, alanine, aspartic acid or glutamic acid or mixt. - Google Patents

Abstract

Compsn. (A) contains 0.1-30 mmol/l of glycine, serine, alanine, aspartic acid or glutamic acid or a mixt. of these aminoacids. (A) pref. contains 0.2-10 mmol/l of the aminoacid(s). An esp. pref. compsn. (A) contains glycine and/or serine in a concn. of 0.1-10 mmol/l. USE - (A) is used to reduce or prevent hypoxic damage in human and animal tissue, e.g. liver kidney, intestine and pancreas. It is esp. effective during operations, including transplants, where it is perfused into the organs as a soln. In an example, the effect of glycine at 10 mmol/l on hypoxic cell damage to rat hepatocytes was tested using lactate dehydrogenase (LDH) liberation to measure damage. LDH liberation was 5%, 7% and 10% after 2, 4 and 6 hrs., compared with 50%, 65% and 75% for control over the same period.

Description

The invention relates to a composition by Sauer Undersupply of substances in animal or human tissues prevents damage occurring.

Undersupply of oxygen, hypoxia, arises in tissues for example with peripheral or cerebral circulatory disorders stakes, stroke, vascular occlusion or even during storage of transplant organs.

From T.S. Rao et al., Neuropharmacology 29 (1990), pages 1199 to 1204 is known opipramol, a tricyclic antidepres sivum to reduce or prevent damage from To use oxygen deficiency in the brain.

Furthermore, de Groot et al., Res. Commun. Chem. Pathol. Pharmacol. 68, pages 125 to 128, known that a protein free extract from calf blood a significant reduction causes hypoxic liver damage.

It was now unexpectedly found that certain Amino acids or their mixtures damage the Reduce or largely undersupply of oxygen in tissues prevent.

The invention therefore relates to a composition for Prevention of damage to animal or human tissues ben by oxygen deficiency, characterized by best content of 0.1-30 mmol / l of amino acid mixture starting from the amino acids glycine and / or serine and / or alanine and / or aspartic acid and / or glutamic acid.  

The amino acids mentioned show one alone or in a mixture excellent protective effect against damage caused by Undersupply of oxygen in animal or human ge weaving occur.

The amino acids are used alone or in combination in one Concentration of 0.1 to 30 mmol / l, preferably 0.2 to 10 mmol / l, the total concentration being 30 mmol / l should not exceed.

The composition according to the invention preferably contains the Amino acids glycine and / or serine alone or in combination with one or more amino acids from the group alanine, As paraginic acid and glutamic acid.

The composition according to the invention can be used, inter alia, for Prevention of hypoxic damage to the liver, kidney and other parenchymatous organs, such as. B. gut and pan kreas, can be used.

The compositions according to the invention are particularly suitable conditions for optimal care of such organs that during Transplants or other surgeries are temporarily unavailable can be adequately supplied with oxygen.

For example, the temporarily decommissioned organs be pre-perfused with the amino acid solutions, so that in the Ischemia constantly supplies the organ cells with the amino acids will.

Example 1

Investigation of the protective effect of amino acids on the hypo Xical cell damage to rat hepatocytes in primary culture.

The liver cells to be examined were derived from male Wistar rats by collagenase perfusion, as in Biol. Chem. Hoppe-Seyler (1991) 372, pages 34 to 41 wrote, isolated.

3 × 10 ⁶ cells were added to each culture bottle and cultured in Leibo witz L15 medium. Cultures 24 hours old were used to conduct the study. Krebs-Henseleit buffer, pH 7.4, which also contained 20 mmol / l Hepes and 83 µmol / l trypan blue, was used as the test medium. The temperature of the experimental set-up was 37 ° C. The amino acids dissolved in 0.5 ml incubation buffer were added immediately before the start of the hypoxic incubations. The total volume of incubation buffer was 5.5 ml. 0.5 ml incubation buffer was also added to the controls. The cell damage was determined by ingestion of trypan blue and by the release of lactate dehydrogenase.

The experiments showed that the rat hepatocytes in primary culture structure under hypoxic conditions after 2 hours showed significant damage. After 6 h of incubation 75% of the cells already lost their vitality. When adding of the amino acids, however, was able to reduce the Damages found. The protective effects of amino acids Glycine, serine, alanine, apariginic and glutamic acid are in the shown in the following tables.

The cell damage was caused by the release of the lac tat dehydrogenase (LDH) determined.

The control values give the LDH release without amino acid addition to.  

Table 1

Table 2

Table 3

Table 4

Table 5

Claims (4)

1. Composition for preventing damage in animal or human tissues by oxygen deficiency, characterized by a content of 0.1 to 30 mmol / l amino acid mixture consisting of the amino acids glycine and / or serine and / or alanine and / or aspartic acid and / or glutamic acid . 2. Composition according to claim 1, characterized in that it contains the amino acids glycine and / or serine. 3. Composition according to claim 1, characterized in that the sum of the concentration of amino acids 0.2 to 10 mmol / l. 4. Composition according to claim 1, characterized in that it contains 0.1 to 10 mmol / l glycine and / or serine.