Development of the polyurethane sponge as a delivery system for aryl 4-guanidinobenzoates.
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.
Quigg
J M
JM
Department of Obstetrics and Gynecology, Rush University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 660612-3864.
Miller
I F
IF
Mack
S R
SR
Saxena
S J
SJ
Kaminski
J M
JM
Zaneveld
L J
LJ
D001565:Benzoates / Q000494:pharmacology*; D003273:Contraceptive Devices; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D017137:Nonoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D011140:Polyurethanes / Q000494:pharmacology; D013081:Sperm Motility / Q000187:drug effects; D014357:Trypsin / Q000378:metabolism
D001565:Benzoates; D006146:Guanidines; D011140:Polyurethanes; D017137:Nonoxynol; D011092:Polyethylene Glycols; C058197:4'-carboxyphenyl 4-guanidinobenzoate; C058095:4'-acetamidophenyl 4-guanidinobenzoate; C058096:4'-carbomethoxyphenyl 4-guanidinobenzoate; D014357:Trypsin