A simple but powerful multipurpose drug for the reduction of sexually transmitted disease
Polyphenylene carboxymethylene (PPCM) is a simple polymer created from mandelic acid. This highly charged polymer has received extensive preclinical evaluation by several major laboratories and is considered a very promising candidate for inhibiting sexually transmitted infections (STIs), contraception and other viral infections.
PPCM will be used in topical applications, such as a vaginal gel contraceptive or a low viscosity gel for topical treatment of genital herpes. It can be incorporated into a number of aqueous based dosage forms. We have preliminary formulas for PPCM in aqueous gels of varying viscosity, a fast-dissolving film and a fast-dissolving gel cap. It can potentially be incorporated in eye drops, nasal spray, and, skin preparations.
Sexually Transmitted Infection
PPCM has been shown to prevent HSV-1 and HSV-2 in mice. In vitro studies of PPCM show promise to inhibit multiple clades of HIV. At high enough concentrations, PPCM irreparably inhibits HIV. PPCM has also shown promise against gonorrhea, chlamydia and trichomoniasis, in vitro. As a microbicide, PPCM has significant advantages in safety and effectiveness compared to other polyanion microbicides. In combination with a reverse transcriptase inhibitor (RTI), PPCM promises to offer significant STI protection in addition to HIV prevention.
PPCM promises to be an excellent vaginal contraceptive drug product. PPCM renders sperm infertile without damaging other cells. Currently approved spermicides are surfactants that attack lipids in sperm as well as vaginal tissue. Surfactants are irritating and promote transmission of sexually transmitted disease and other vaginal infections. PPCM is not irritating and does not trigger an inflammatory response. It causes sperm to prematurely lose the acrosomal coating and also inhibits hyaluronidase, a critical enzyme needed for fertilization. Thus, sperm remain motile but are unable to fertilize an ovum.
Mechanism Of Action
PPCM is a highly charged polymer, preventing viral binding and fusion to a host cell by attaching to and blocking key viral binding sites. It has been shown that PPCM binds gB on HSV-2 and gp120 on HIV. Published studies of PPCM in vitro and in animals shows promise that it will prevent HSV and HIV, even in the presence of semen. The image above shows enlarged herpes simplex virus, with glycoprotein B attachment sites in light blue. These sites find specific receptor sites on a host cell. PPCM stops virus from infecting by attaching to glycoprotein B before it reaches a cell, stopping the spread of infection.
Other Topical Application
PPCM's mechanism of action points to a general ability to inhibit heparan sulfate binding. We believe this potential to prevent binding of other pathogens that use these binding sites, including cytomegalovirus, Hepatitis C, Human Papillomavirus and Trichomoniasis.