ANTIINFLAMMATORY AND ANTISHOCK WATER-SOLUBLE POLYESTERS OF GLUCOCORTICOIDS WITH LOW-LEVEL SYSTEMIC TOXICITY

Purpose. The objective of this study was to evaluate the pharmacologic al activity of glucocorticoid hormones incorporated into the structure of water-soluble carbochain polymers via the esterified 21-CH2OH grou p. Methods. Polymer analogs of glucocorticoids were prepared by radica l copolymerization of 1-vinyl-2-pyrrolidone with cortisol or dexametha sone 21-crotonates and crotonic acid or 2-(diethylamino) ethylcrotonat e which served as ionogenic comonomers. Anti-inflammatory, immunosuppr essive and catabolic activities for ionogenic tertiary copolymers and previously prepared non-ionogenic binary copolymers were evaluated in standard animal models. The antishock activity of some of the copolyme rs was evaluated using the ''declamping shock'' model. Results. Water- soluble tertiary copolymers with a steroid content up to 14 mol% and a n intrinsic viscosity up to 0.30 dl/g in ethanol were synthesized. It was shown that the copolymers were stable in aqueous solutions at pH 5 .2-7.3. All of the polymers studied suppressed inflammatory reactions at the level of free hormones when administered interperitoneally. The antishock activity was considerably higher compared to free steroids. The copolymers, unlike unmodified glucocorticoids, did not influence the physical development of young animals. They also caused much lower thymus hypotrophy than free hormones. No clear effect of the presence and nature of ionogenic units in copolymers on the pharmacological pe rformance of the copolymers was detected. Conclusions. The water-solub le polymers bearing glucocorticoid 21-residues in the side chains reta in the anti-inflammatory activity of free steroids and exhibit a highe r antishock, a lower immunosuppressive and no catabolic effect.