115: The Effectiveness of Anmarin, an Antimycotic Herbal Drug: Preclinical & Clinical Studies

Statement of Purpose, Innovation or Hypothesis: Cutaneous mycoses are often caused by one of the fungal genera (e.g., Trichophyton or Microsporum). These infections can be classified based on the site of infection: Tinea capitis (scalp), Tinea corporis (arms, legs, and trunk), Tinea cruris (groin), Tinea pedis (feet), and Tinea unguium (nails). Dermatophytic cutaneous infections are the most common among mycotic infections. The standard of treatment for these infections usually requires weeks of treatment with antimycotic drugs (e.g., Clotrimazole, Terbinafine or  Tolnaftate). Anmarin is a novel drug of herbal origin that was developed at the  VILAR. It comprises of two bioactive constituents: 51-isopropenyl-41-51-dihydropsoralen (constituting ~70-80% Anmarin) and isopropyl psoralen (constituting ~20-30% Anmarin) [1]. This study aims to evaluate the anti-dermatophytic activity of Anmarin in vitro, on animal models and in clinical trials.

Description of Methods & Materials: In vitro activity was evaluated by the initial dilution of Anmarin in DMSO, followed by a serial dilution of the drug in Sabouraud-Dextrose broth. The broth was inoculated with appropriate concentrations of dermatophytes: Microsporum lanosum, Trichophyton rubrum, Trichophyton mentagrophytes granulosum and Trichophyton interdigitale. Minimal inhibitory concentrations (MIC) were determined. Animal model: Microsporum Ianosum was ribbed into the shaved side of guinea pigs. Animals were treated with 1% Anmarin ointment daily starting days 13-15 when signs of infections were obvious. The control group received an ointment base without Anmarin. The effectiveness of treatment was evaluated by the number of cured animals and the time when they were cured. Clinical trials: The efficacy of Anmarin was evaluated in 90 patients with confirmed Trichophyton and 59 patients with Microsporum. The trial was an open-label study conducted in three different dermatological clinics. Patients with laboratory-confirmed dermatomycoses were treated with 1% Anmarin ointment or 0.25% lotion. Patients receiving standard of care,  Clotrimazole, were used as a comparison group. The effectiveness of the treatment was evaluated by the time when symptoms disappeared, and three dermatophyte-negative tests were received.

Data & Results: MIC of tested dermatophytes for 5¹-isopropenyl-4¹-5¹-dihydropsoralen ranged 3.9-7.8 ug/ml and for isopropyl psoralen – 250-1000ug/ml. The antimycotic activity of Anmarin ranged from 7.8 to 31.2 ug/ml. Guinea pigs treated with Anmarin were cured on 26.7+0.43 days after treatment initiation, evidenced by no luminescent glow under Wood’s light and negative culture test, while control animals were cured on 32.2+2.12. When 100% of Anmarin-treated animals were cured, only 60-70% of control animals were disease-free. All patients with Tinea cruris (n=25), Tinea pedis (n=16), and Tinea capitis (N=12) caused by Trichophyton spp. were cured on average in 5.0+0.3 weeks of treatment with 1% Anmarin ointment evidenced by symptoms disappearance and triple-negative culture. The success of treatment of a combined Tinea pedis + Tinea unguium (n=37) with 0.25% Anmarin lotion was 97%. Patients with Tinea corporis (n=29) and Tinea capitis (n=30) caused by Microsporum spp. were disease-free on  3.4+0.3 weeks of ointment treatment. The effectiveness of the Anmarin treatment of Tinea corporis was comparable with the effectiveness of the Clotrimazole.

Interpretation, Conclusion or Significance: Anmarin was effective for the treatment of skin dermatomycoses in animals and humans. Clinical studies presented herein lay a foundation for randomized, double-blind, placebo-control studies.

Disclosures: None

Citations/References: 1. Komkova, S.P.; Kulyak, O.Y.; Dzhavakhyan, M.A. ELABORATING AND VALIDATING THE METHOD OF QUANTITATIVE ASSESSMENT OF THE SUM OF FUROCOUMARINS IN THE «ANMARIN®». The Journal of Scientific Articles Health and Education millennium 2018, 20, 198-201, doi:10.26787/nydha-2226-7425-2018-20-1-198-201.

Additional Information/Authors: None