Subcutaneous Administration of Cortin Compounds in Solid Form to the Rat

Abstract

Numerous substances having a low solubility in the body fluids have been administered experimentally by implanting them in solid form within the body tissues. We have administered to rats solid forms of extracts of adrenal cortex and 3 pure crystalline compounds which are identified in the literature as A, B, and E. 1

In Experiment 1, ten male rats having a range in body weight of from 100 to 110 g were matched into pairs and were all adrenalectomized in single-stage aseptic operations. At the time of adrenalectomy a single crystal of compound E which did not exceed 2 mg in weight was implanted subcutaneously into one animal of each pair. The 5 untreated control animals developed symptoms of adrenal insufficiency and died at intervals of 5, 6, 10, 10, and 12 days after operation. The animals which had received the single implants of compound E died at intervals of 15, 20, 23, 23, and 28 days after operation.

For Experiment 2, a total extract of cortin was prepared for implantation. Compounds A, B, E, and some biologically inactive compounds were removed by fractionation. A sample of 330 cc was evaporated to dryness in a vacuum at 40°C. It was redissolved in absolute alcohol and again dried. This was repeated with acetone and the residue of 105 mg was dissolved in alcohol with 400 mg of cholesterol. The mixture was dried by warming in a stream of air. The residue was moistened with alcohol and thoroughly mixed. It was dried in a vacuum desiccator, again moistened with alcohol and compressed into pellets. Twelve male rats having body weights of from 60 to 70 g were closely matched into pairs and all were completely adrenalectomized.