Anti-inflammatory and antishock water-soluble polyesters of glucocorticoids with low level systemic toxicity.

PURPOSE

The objective of this study was to evaluate the pharmacological activity of glucocorticoid hormones incorporated into the structure of water-soluble carbochain polymers via the esterified 21-CH2OH group.

METHODS

Polymer analogs of glucocorticoids were prepared by radical copolymerization of 1-vinyl-2-pyrrolidone with cortisol or dexamethasone 21-crotonates and crotonic acid or 2-(diethylamino) ethylcrontonate which served as ionogenic comonomers. Anti-inflammatory, immunosuppressive 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 copolymers was evaluated using the "declamping shock" model.

RESULTS

Water-soluble tertiary copolymers with a steroid content up to 14 mol% and an 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 performance of the copolymers was detected.

CONCLUSIONS

The water-soluble polymers bearing glucocorticoid 21-residues in the side chains retain the anti-inflammatory activity of free steroids and exhibit a higher antishock, a lower immunosuppressive and no catabolic effect.