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A study was begun to develop a contraceptive delivery system that would free the user from precoital or daily administration and utilize a nonhormonal agent as the active ingredient. Testing of such a system in rabbits has led to the development of a device that will release a controlled level of an acrosin and hyaluronidase inhibitor into the vagina. This toroidal device is composed of a core of tetradecyl sodium sulfate (TDSS) incorporated in polyurethane surrounded by a rate-limiting membrane of polyurethane. Such devices had a sustained in vitro TDSS release rate of greater than or equal to 400 micrograms/day for over 30 days. These devices had a complete contraceptive effect in 15 rabbits bred weekly for 4 weeks. The contraceptive effect is due to release of the TDSS into the vagina and the subsequent binding of the TDSS to spermatozoa in the female reproductive tract. TDSS has a very low toxicity profile in the rat, dog, and rabbit.

Acrosin and acrosomal hyaluronidase were inhibited by tetradecyl sodium sulphate (TDSS) in vitro at concentrations of less than 10(-4) M. TDSS prevented the removal in vitro of the cumulus oophorus by testicular hyaluronidase and the zona pellucida by acrosin. TDSS had a contraceptive effect in rabbits when administered intravaginally before coitus or released at levels of 1-3 micrograms/day from intrauterine silicone rubber devices.

Four 3 beta-hydroxy-delta 5-steroid sulphates were found to be potent and specific inhibitors of the sperm acrosomal proteinase, acrosin. Two of these acrosin inhibitors, desmosteryl sulphate and cholesteryl sulphate, occur naturally in spermatozoa. Desmosteryl sulphate, an inhibitor of the in-vitro capacitation of hamster spermatozoa, has a Ki of 3.5 x 10(-6) M for the inhibition of acrosin. The mechanism of inhibition of sperm capacitation by sterol sulphates is probably due to their inhibition of acrosin.