睾酮经皮吸收制剂的实验研究

The research on transdermal testosterone replacement preparation

目的研究睾酮经皮吸收制剂的有效性、安全性及稳定性,即新药临床前试验。方法将睾酮制成软膏剂,对睾酮软膏进行动物药效学、毒理试验(局部刺激试验、皮肤过敏试验、急性毒性试验)。结果睾酮经皮吸收制剂可显著增加去势未成年雄性大鼠的前列腺和精囊重量,显著提高去势大鼠血浆睾酮水平;动物毒理试验表明该制剂对家兔脱毛后完整皮肤,破损皮肤无刺激性,对豚鼠皮肤无致敏作用,给大鼠皮肤涂抹该制剂达人用量300倍时无皮肤急性毒性反应,给小鼠灌喂该制剂最大耐受量达人用量4300倍以上,表明该制剂安全无毒。结论所研制的睾酮经皮吸收制剂能有效提高大鼠血浆睾酮水平,在靶器官表达出雄激素效应,并且具有良好的安全性。

Objective To evaluate the efficacy, safety and stability, i.e the preclinical tests, of transdermal testosterone replacement preparation. Methods Transdermal testosterone replacement preparation was made into ointment. Pharmaceutical tests and pharmacological tests including efficacy, toxicity （local stimulation, skin sensitization, acute toxicity） were done. Results The pharmacological tests demonstrated that it can increase the weight of prostate and seminal vesicle of young orchidectomized rats, enhance the serum testosterone concentration of orchidectomized rats. The preparation showed no irritant effect both on intact or broken skin of rabbit, no skin sensitization on guinea pigs. No acute toxicity was found in rat when 300 times equivalent dosage to man was used and the maximum tolerance dose reached 4300 times equivalent dosage to man. The toxicity tests revealed that the preparation is safe. Conclusion The transdermal testosterone replacement preparation can effectively increase serum testosterone concentration and is potent in target organs. Besides, the preparation is safe.