TELOMERS AND COTELOMERS OF BIOLOGICAL AND BIOMEDICAL INTEREST .3. WATER-SOLUBLE TELOMERS WITH ACID CHROMONE-SYNTHESIS AND PHARMACOKINETIC STUDY

The work now reported deals with the synthesis and the pharmacokinetic study, after oral administration to rats, of a cotelomer carrying several chromone acid residues grafted to the hydrocarbon backbone. Chromone acid is a molecule known to improve blood circulation in veins and capillaries. The macromolecule tested (A) has an average molecular weight of 6000. It was prepared by cotelomerization, in the presence of decanethiol as chain transfer reagent, of two acrylic acid derivatives carrying respectively a molecule of glycine and a chromone acid residues attached to a molecule of lysine. Acryloylglycine was introduced into the macromolecule in order to improve the hydrosolubility of the whole polymer. Several other simple conjugates in which chromone acid is attached to either glycine, aspartic acid or serine were also tested and compared to A. Urinary and plasmatic kinetics revealed: (i) a limited release of chromone acid in the intestinal tract whatever the nature of the amide bond; (ii) the intestinal absorption of the chromone acid conjugate; (iii) the appearance of chromone acid into urine and/or blood with several hours delay compared to the commercial drug. © 1990.