European Pharma Congress

Biography

Biography: Joseph Jampilek

Abstract

Alaptide, 8-methyl-6, 9-diazaspiro [4.5] decan-7, 10-dione, is an original Czech compound. Substituted piperazine-2,5-diones were designed as analogues of Melanocyte-Stimulating Hormone Release-Inhibiting Factor (MIF-1), and thus it is supposed that they are able to influence the creation and function of keratinocytes. During biological assays, it was found that alaptide demonstrated significant skin curative activity without any observed toxicity. Based on these facts and structural analogy with other transdermal Chemical Permeation Enhancers (CPEs), it was suggested to investigate alaptide as a potential CPE of many anti-inflammatory drugs, antimicrobial chemotherapeutic, sex hormones/genital system modulators or drugs of central/vegetative nervous system. Based on the excellent enhancement and skin curative effect and no toxicity of alaptide other 8-substituted derivatives were designed. New compounds were prepared by a multi-step synthetic pathway from modified amino acids and then investigated on their biological effects. All discussed 8-aryl-6, 9-diazaspiro [4.5] decan-7, 10-diones were tested for their in vitro transdermal permeation enhancement effect using a vertical Franz diffusion cell and full-thickness pig ear skin. They showed a promising enhancement effect with respect to various drug substances from different types of formulations/transdermal therapeutic systems. They also expressed no toxicity or skin irritability.