Clinical aplications of Trioxolane derivatives

Several laboratory, anecdotal and clinical studies have been performed using the patented derivatives of 1,2,4-Trioxolane during a period spanning over 20 years. Observations obtained demonstrate the uniqueness of this product. The product, when properly formulated can exhibit properties ranging from being a biological response modifier, antirheumatic, immunomodulator, anti-inflammatory, antiviral, and antimicrobial. These properties become handy in evaluating the product’s potential in the clinical management of various conditions such as infections and immune disorders [1]. Geraniol trioxolane, a trioxolane derivative of a terpene, has been assessed on the basis of its direct biological activity against certain target organisms in vitro. In Vivo assays have similarly been undertaken to assess the product's toxicity, safety, and in certain cases, efficacy. The studies have been conducted using the product manufactured using a synthesis protocol, and synthesized strictly in accordance with international guidelines and specifications, especially those issued by United States Food and Drug Administration, United States Pharmacopoeia and British Pharmacopoeia. The preparatory process met all requirements for the Code of Good Manufacturing Practices (cGMP). In addition, the trioxolane derivative of cis 3-hexene-1-ol, a non-terpene, was synthesized and compared with geraniol trioxolane for the purposes of assessing its comparative activity. Both geraniol Trioxolane and the trioxolane derivative of cis 3-hexene-1-ol are colorless liquids. Geraniol trioxolane is more viscous and less stable than the trioxolane derivative of cis 3-hexene-1-ol. After several trials, the more user-friendly and stable version is a patented product that contains methyl-5-octyl-1,2,4-trioxolane-3(8’-octanoate), a derivative of 1,2,4-trioxolane, as the active ingredient. This is a formulation manufactured and conveniently dissolved in Squalane (2,6,10,15,19,23hexamethyltetracosane), as a carrier, using liquid preparation containing 200mg/ml of 1,2,4-trioxolane. Studies so far conducted both in Mexico and Kenya have revealed that various formulations of this product have a place in the clinical management of a variety of conditions. Clinical trials have been done to assess the usefulness of this product in the clinical management of HIV/AIDS, rheumatoid arthritis and also in the improvement of blood circulation. No adverse effects were observed in all the studies so far undertaken. Because of its wide window of safety, two products have been developed and have received registration in Kenya: these are branded Alphamir for HIV/AIDS and Arthromir for rheumatoid arthritis. Except for the initial experimental studies and anecdotal observations, most of the clinical trials have been undertaken at the Kenya Medical Research Institute (KEMRI).