Quigg J M, Miller I F, Mack S R, Saxena S J, Kaminski J M, Zaneveld L J
Department of Obstetrics and Gynecology, Rush University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 660612-3864.
Contraception. 1988 Oct;38(4):487-97. doi: 10.1016/0010-7824(88)90089-3.
The Today Contraceptive Sponge was evaluated as a vehicle for the delivery of aryl 4-guanidinobenzoates (AGs) which are highly active sperm acrosin inhibitors. Studies in animals have shown that several AGs are more potent vaginal contraceptives and less irritating to the vagina than nonoxynol-9 (N-9), the most frequently used active ingredient in commercial vaginal contraceptive formulations. Neither nonoxynol-9 nor the material that could be solubilized from the sponge matrix altered the enzyme-inhibitory activity of 4'-acetamidophenyl 4-guanidinobenzoate HCl (AGB), 4'-carboxyphenyl 4-guanidinobenzoate HCl (EGB) or 4'-carbomethoxyphenyl 4-guanidinobenzoate HCl (MSGB). Besides being acrosin inhibitors, all three AGs exhibited antimotility activity towards human spermatozoa, EGB being as potent as N-9. The antimotility effects of the AGs and N-9 were additive. For subsequent studies, AGB was used as the model compound. Manufacture of the AGB-containing sponges did not affect the chemical structure of AGB. Good release rates of AGB were obtained from the sponges over a 7-day period. The release rates were 20-50% higher when the sponges also contained N-9. These results indicate that certain AGs exert a dual contraceptive action on spermatozoa by inhibiting both the sperm enzyme acrosin and sperm motility. Furthermore, the polyurethane sponge appears to be a convenient and satisfactory long-term delivery system for the AGs. A mixture of N-9 and AG can be used clinically because these compounds have no adverse effects on each other.
今日避孕海绵被评估为一种用于递送芳基4-胍基苯甲酸酯（AGs）的载体，这些化合物是高效的精子顶体蛋白酶抑制剂。动物研究表明，几种AGs作为阴道避孕药比壬苯醇醚-9（N-9）更有效，对阴道的刺激性也更小，壬苯醇醚-9是商业阴道避孕制剂中最常用的活性成分。壬苯醇醚-9和可从海绵基质中溶解的物质均未改变盐酸4'-乙酰氨基苯基4-胍基苯甲酸酯（AGB）、盐酸4'-羧基苯基4-胍基苯甲酸酯（EGB）或盐酸4'-甲氧羰基苯基4-胍基苯甲酸酯（MSGB）的酶抑制活性。除了是顶体蛋白酶抑制剂外，所有三种AGs对人类精子均表现出抗运动活性，EGB的活性与N-9相当。AGs和N-9的抗运动作用是相加的。在后续研究中，AGB被用作模型化合物。含AGB海绵的制造不影响AGB的化学结构。在7天时间内，AGB从海绵中获得了良好的释放率。当海绵中也含有N-9时，释放率提高了20-50%。这些结果表明，某些AGs通过抑制精子酶顶体蛋白酶和精子运动对精子发挥双重避孕作用。此外，聚氨酯海绵似乎是一种方便且令人满意的AGs长期递送系统。N-9和AG的混合物可用于临床，因为这些化合物对彼此没有不良影响。
