A simple but powerful multi-purpose prevention technology (MPT) for the treatment and prevention of sexually transmitted disease and unplanned pregnancy.
Polyphenylene carboxymethylene (PPCM)
Polyphenylene carboxymethylene (PPCM) is a simple polymer derived from mandelic acid. PPCM polymer has received extensive preclinical evaluation by several major laboratories and is a promising candidate for contraception, and inhibiting sexually transmitted infections (STIs).
PPCM will be used in topical applications, such as a vaginal gel contraceptive and a low viscosity gel for topical treatment of genital herpes. We have preliminary formulas for PPCM in aqueous gels of varying viscosity, and a fast-dissolving film.
Mechanism Of Action: Antiviral example
PPCM prevents viral binding and fusion to a host cell by attaching to and blocking key viral binding sites. It has been demonstrated 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 in the presence of semen.
PPCM causes sperm to prematurely lose the acrosome and inhibits hyaluronidase, a critical enzyme needed for fertilization. Thus, sperm are unable to fertilize an ovum. PPCM promises to be an excellent non-hormonal 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 such as N-9 are irritating and promote transmission of sexually transmitted disease and other vaginal infections. PPCM is non-irritating and does not trigger an inflammatory response.
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.
Other Topical Applications
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.
(Note: PPCM Aka SAMMA)
Mandelic Acid Condensation Polymer: Novel Candidate Microbicide for Prevention of Human Immunodeficiency Virus and Herpes Simpex Virus Entry. B. C. Herold, et al Journal of Virology, Nov. 2002, p. 11236-11244
Use of mandelic _acid condensation polymer (SAMMA) a new antimicrobial contraceptive agent, for vaginal prophylaxis. Lourens J.D. Zaneveld et al Fertility and Sterility, vol. 78, No. 5, November 2002
Candidate Topical Microbicides Bind Herpes Simplex Virus glycoprotein B and Prevent Viral Entry and Cell-to-Cell Spread. Natalia Cheshenko et al, Antimicrobial Agents and Chemotherapy, June 2004, p. 2025-2036
SAMMA Induces Premature Human Acrosomal Loss by Ca2+ Signaling Dysregulation. Anderson RA et al, Journal of Andrology 2006 27:568-577
SAMMA a mandelic acid condensation polymer, inhibits dendritic cell-mediated HIV transmission. Chang T. et al, FEBS Letter 2007 581:4596-4602
Candidate Microbicides PPCM Blocks Human Immunodeficiency Virus type I Infection in Call and Tissue Cultures and Prevent Genital Herpes in a Murin Model. Mesquita P. et al, Journal of Virology 2008 82:6576-6584
Feasibility of Repurposing the Polyanionic Microbicide, PPCM, for Prophylaxis against HIV Transmission during ART. Anderson R. et al, ISRN Obstetrics and Gynecology, Vol 2011, ID 524365
Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 Lancet 2016; 388: 1545–602
The global roadmap for advancing development of vaccines against sexually transmitted infections: Update and next steps. Gottleib S., Deal C, Broutet N. et al, Vaccine 34(2016) 2939-2947
Sexually transmitted infections: challenges ahead. Unemo M., Bradshaw C. et al, Lancet Infect Dis 2017; 17: e235-79