Use of L-carnitine and alkanoyl L-carnitines in the storage of blood for transfusions and stabilizing solutions containing them

#The present invention consists in a new non-therapeutic use of L-carnitine, alkanoyl L-carnitines and their pharmacologically acceptable salts as preservative agents for blood transfusions.

#The present invention also consists in new stabilizing solutions for the storage of blood containing L-carnitine, alkanoyl L-carnitines or their pharmacologically acceptable salts.

#What is meant by alkanoyl L-carnitines are acetyl, propionyl, butyryl, isobutyryl, valeryl and isovaleryl L-carnitine. Hereinafter, for reasons of simplicity, we shall refer only to L-carnitine, in the understanding, however, that the description also applies to the above-mentioned alkanoyl L-carnitines and their pharmacologically acceptable salts.

#The efficacy of L-carnitine in the use envisaged in this invention is verified by numerous studies, one of which is reported here below with reference to the attached diagrams, where:

#FIG. 1 is a graph representing the osomotic fragility of eythrocytes as a function of storage time (expressed in weeks);

#FIG. 2 is a graph representing the haemoglobin concentration (in mg/dL) in the storage medium as a function of storage time (expressed in weeks);

#Admitted to this study were volunteers who were habitual blood donors and who were perfectly healthy at the time the blood samples were taken. The blood samples were collected in special quadruple bags normally used for blood storage Baxter, Fenwal Division, La Chatre, France) containing CPDA-1 (CPDA-1 composition: 110 mM glucose; 55 mM mannitol; 25.8 mM K.sub.2 HPO.sub.4 ; 14.7 mM KH.sub.2 PO.sub.4 ; 17.9 mM potassium citrate), an iso-osmolar fluid commonly used for the storage of blood at 5.degree. C. The blood was poured into the above-mentioned bags by means of a centrifuge which allowed the formed elements of the haematic mass to be separated from the erythrocytes. In addition to the above-mentioned CPDA-1, some of the bags contained L-carnitine, which was always introduced under conditions of maximum sterility. The ratio of the volume of the storage fluid to the volume of the erythrocytes was close to 1:1. The bags were then placed in refrigerators at a constant temperature of 5.degree. C.

#In the course of storage, aliquots of erythrocytes were collected at weekly intervals for the purpose of conducting a number of microscopic and biochemical examinations. The eryrocyte suspension was immediately examined under a phase-contrast microscope to estimate the percentage content of burr cells, which are pathological erythrocytes with a star-type morphology. Later, the eryrthocyte suspension was centrifuged, and the buffy coat was used to determine the haemoglobin content according to a method involving the derivatization of the latter to cyanomethaemoglobin (International Committee for Standardization in Haematology, S. Clin. Pathol. (1978), 31:139-145). The haemoglobin content measured is an indicator of the degree of haemolysis the erythrocyte undergoes in the course of storage in the bags. Lastly, erythrocyte osmotic fragility was evaluated according to the method of Dacie and Lewis (Dacie J. V. and Lewis S. M., Practical Haematology, New York: Churchill Livingstone, 1984: 152-6). The osmotic fragility was calculated as the amount of sodium chloride necessary (in mM/L) to obtain 50% haemolysis.