The disseratation is devoted to the development and introduction in veterinary medicine practice a new antifungal drug in the form of liniment with the composition of the soft medicinal form as the active substance thio-derivative 1,2,4-triazole ‒ (4-((5- decylthio)-4-methyl-4H-1,2,4-triazole-3-yl)methyl) morpholine, the standardized of the oil of Milk Thistle (Silybum marianum, L) was used as a forming base.
When studying the “VetMikoDerm” properties while prolonged storage it was confirmed that a freshly ready-made liniment 10% is transparent with a yellowish tint. During storage (12 months) the colour indicator intensity of the product was not higher than the standard B9, the pH was in the range of 5.9-6.1, the concentration of active liniment ingredient ranged from 9,7 to 10,17 %. In medicinal form it was not detected any mechanical impurities, and the percentage of related ones was negligible (0,17-0,35 %). The absence of chemical interaction between the thio-derivative triazole and Milk Thistle oil was confirmed by the mass spectra peaks for this substance which is an indicator of its stability.
In the experiments on the laboratory rats the safety of the new ready-made drug was confirmed. When determining the acute parameters toxicity of the "VetMikoDerm" drug it was established that for DL50 liniment intragastric administration is 15363,1 mg / kg bw., and according to the requirements of SOU 85.2-37-736: 2011 the test agent belongs to low-toxic substances (4th toxicity class), for skin application (according to the GHS requirements) – 5th toxicity class). The cumulation coefficient is 1,22 (do not have the ability to cumulate).
Clinical trial of the drug "VetMikoDerm" was performed on outbred dogs aged 1-6 years, selected on the principle of analogues and the presence of characteristic visually similar symptoms of skin lesions.
Positive dynamics of the animals has been already observed on the 3-4-th day of treatment (decreased redness, itching and signs of inflammation). On 10-14th days of the treatment it was manifested visible signs of skin regeneration and hair restoration. Talking about animals with a significant (area) skin involvement (50 %), treatment course was longer and full recovery was to be expected in 28-30 days. So, at the background of the effective fungicidal action new ready-made drug "VetMikoDerm" in the liniment form also shows anti-inflammatory, anti allergic, regenerative and healing effect.
The scientific novelty of the obtained results. It was developed a new drug with antifungal action, "VetMikoDerm". It was proved according to the technology of preparation of this liniment on the principle of a nonvolatile oil solution with the best possible recipes regarding specific weight and volume components. For the first time it was investigated the physico-chemical properties of the new drug, its resistance to delamination, stability during storage depending on the solvents. In terms of preclinical experiments on laboratory animals (rats), it was clarified the acute and subacute toxicity parameters of "VetMikoDerm" for intragastric and cutaneous application and its cumulating properties. According to the results of clinical trials on dogs for the first time the scheme of ringworm treatment including as the primary therapeutic agent of the drug "VetMikoDerm" –it’s recomended the most effective method of application and multiplicity of the therapeutic agent application that provides a positive outcome in the shortest possible terms.
The practical significance of the results obtained. Based on the experimental studies, it was established that the investigated drug “VetMikoDerm” is safe for both single and multiple intragastric and cutaneous application to its laboratory animals. According to the parameters of acute toxicity and cumulation coefficient, it belongs to the IV class of toxicity, or low-toxic compounds. It has been found that liniment “VetMikoDerm” has therapeutic efficacy for dogs with skin pathology of fungal nature. In this case, it has fungicidal, anti-inflammatory, antipruritic and wound healing effects. Healing of skin wounds with complete restoration of the dogs’ hair with dermatomycosis, under the action of the studied liniment, occurs on the 10-14th day. In the case of multiple injuries or complications caused by secondary pathogenic microflora, the course of treatment is somewhat longer (21-28 days). The regulatory documentation for the drug "VetMikoDerm" was developed according to the results of the research (TC, guidelines).
Keywords: liniment "VetMikoDerm", S-derivative of 1,2,4-triazole, milk thistle oil, fungi, dermatomycosis, dogs, laboratory rats, toxicity parameters, cumulation.
