Clinical evaluation and monograph development for a Ghanaian polyherbal product (Eaf-2011) used in the management of superficial mycoses

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Herbal medicines are the most accessible form of healthcare product for majority of the world’s population and have been used over time to address the health needs of several societies. In the present study, a Ghanaian polyherbal product (ointment) from the Centre for Plant Medicine Research comprising: Alchornea cordifolia, Eugenia caryophyllata, Psidium guajava, Zanthoxylum zanthoxyloides and Tridax procumbens, coded EAF-2011 and used in the management of superficial fungal skin diseases was assessed for its quality, safety and effectiveness. Qualitative chemical fingerprinting of the ointment indicated the presence of phytochemicals including alkaloids, phenols, triterpenes and flavonoids. Thin layer chromatograms also produced three marker spots whose properties make them suitable for use as analytical markers. Quantitative chemical assay of three flavonoid compounds in the product EAF-2011 using High Performance Liquid Chromatography (HPLC) showed the presence of 8.6810% (w/w) of rutin (RU), 0.2670% (w/w) of quercetin (QE) and 0.0610% (w/w) of kaempferol (KA). A twelve (12) month stability study that assessed the product for its pharmaceutical quality using organoleptic and physicochemical tests, Thin Layer Chromatography (TLC), HPLC and an antimicrobial assay during the storage of the product under ambient conditions revealed marginal changes in chemical constituents with one of the spots obtained on thin layer analysis undergoing a colour change to purple compared to the baseline colour of brown. The concentration of quercetin was also undetectable after the 6th month of assay during the HPLC analysis. This change in chemistry was however considered insignificant as the biological activity of the product remained unaffected over the period of study based on the results of the antimicrobial assay. An in-vivo chronic toxicity and skin sensitisation test using male Sprague-Dawley rats showed that three concentrations of the herbal extracts [i.e. 2% (w/w), 5% (w/w) and 10% (w/w)] had no adverse effect on the haematological, biochemical and urine analytical iv parameters of the animals used. The ointment did not induce any histological changes in skin, liver, kidney and spleen of the animals used. In the clinical study involving 84 participants diagnosed with superficial mycoses, the 10% (w/w) concentration of the herbal product was most efficacious with 91.3% of participants randomised to the group achieving the primary outcome of complete cure compared to 30.0% achieved with the standard treatment of Whitfield ointment after 3 months. The efficacy of two (2) other concentrations of the herbal product tested [2% (w/w) and 5% (w/w)] was also comparable to Whitfield ointment. The products tested were also safe for human use as haematological, biochemical and urine biochemistry parameters were normal at the end of the study for all the treatment groups. Re-evaluation of the component raw materials of the product using a combination and interactive study to establish their contribution to the overall activity of the product showed that Eugenia caryophyllata, Alchornea cordifolia and Zanthoxylum zanthoxyloides had better activity individually than the total crude extract of five plants used in the formulation of the original product. The combination of Eugenia caryophyllata 60% (w/w) and Alchornea cordifolia 40% (w/w) was selected after further screening and analysis using the fractional inhibitory concentration (FIC) and an isobolographic analysis. A new product (RF-2013) formulated using this combination as the recipe at a concentration of 5% (w/w) was clinically evaluated against superficial fungal skin infections in another human trial. This product was subjected to a randomised controlled single blind study in 15 participants with the 10% (w/w) EAF-2011 as the control treatment. Primary outcome was achieved by all participants receiving the control treatment compared to the 60% attained in the 5% (w/w) RF-2013. Based on the number of participants and their time taken to achieve the primary outcome, the 10% (w/w) EAF-2011 which is the original formulation was proposed as the preferred treatment in the management of superficial fungal skin infections.
A thesis submitted in fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY (PHARMACOGNOSY OPTION).