The study of the impact of herbal medicinal products in soft dosage forms on the burn wound progression in the

experiment The treatment of burns with topical preparations, namely ointments, which consist of herbal ingredients, becomes relevant among the population due to the fact that this dosage form is the most convenient to apply as self-medication; and biologically active substances that are part of these medicines are less toxic, and at the same time, they are not less effective than synthetic drugs against burn damages. Aim . To study the wound-healing effect of drugs containing biologically active herbal ingredients using the model of burn wound. Materials and methods . The study was conducted on 24 white female rats weighing 200-240 g. The experimental animals were divided into 4 groups: Group 1 – pathology (n = 6); Group 2 – animals treated with Wundahyl ointment (n = 6); Group 3 – animals treated with Spasatel Forte ointment (n = 6); Group 4 – animals treated with 2 % thiotriazoline ointment (n = 6). Results . When treating the burn wounds with Wundahyl ointment and 2 % thiotriazoline ointment the wound-healing progression was better. The burn wound area for the following two weeks of observation (Days 14-21) decreased faster compared to the application of Spasatel Forte ointment and much faster in compared to the group of pathology. On Day 28, the burn wound was epithelized completely. Conclusions . According to the results of the experiment, the effect of Wundahyl ointment was the most pronounced in relation to all the soft dosage forms under study.

Treatment of a local burn wound plays an important role in providing uncomplicated course of the wound process. Properly selected drugs for local treatment of burn wounds can reduce infections of wounds and create the optimal conditions for regeneration [4].
At present, the population more often chooses drugs containing plant biologically active substances that exhibit the multi-component effect [5].
Herbal medicinal products occupy almost one third of the world market of medicines [6]. Quite often, they are special, and it is almost impossible to replace them with synthetic drugs due to the complexity of the structure, and because the medicinal plant raw material contains a complex set of biologically active substances that collectively give the biological activity of a particular direction [7]. In this case, preference is given to herbal medicinal products that exhibit a wide spectrum of action, high therapeutic activity, and at the same time, they are less toxic and more cost effective than synthetic analogs [8,9,10].
The correct choice of a dosage form providing the penetration of active substances to one or another depth of the skin is also important for the success of external therapy. Local treatment of burn wounds is aimed at creating the most favorable conditions for their healing in optimal terms. Ointment is a topical dosage form that is mostly used in external burn therapy [11] and it is the most convenient treatment for burn wounds. The main advantage of soft dosage forms is the uniform distribution of the active substance and ease of use, which makes it possible to treat the affected areas individually daily. Ointments show mild effect and low toxicity against the background of high efficiency. Typically, the ointment contains a minimum amount of water, and it is an active substance dissolved in the fatty base. In addition, the ointment base softens and moisturizes the dry skin, softens scales and peels. Due to this there is an increase in microcirculation that helps to reduce infiltrates [12].
Therefore, the effectiveness of treating superficial thermal burns depends on the correct choice of the medicinal product and its dosage form.
The aim of this work was to study the effect of soft dosage forms of herbal ingredients on the progression of a burn wound in the experiment.

Materials and methods
To study wound-healing properties, soft dosage forms containing herbal ingredients -Wundahyl ointment, Spasatel Forte ointment were used. As a reference drug 2 % thiotriazoline ointment was used. We selected this drug as a reference drug since the wound-healing properties of thiotriazoline ointment were found in the experiment [13,14]. The therapeutic effect of 2 % thiotriazoline ointment is due to its membrane-stabilizing properties, inhibition of lipid peroxidation processes and activation of anti-radical defense enzymes in damaged tissues that are beneficial to wound-healing processes [15].
Wundahyl multi-component ointment is widely known as a stimulant for wound healing processes. When applying it pain, swelling, and necrosis are intensively removed. The ointment helps to normalize metabolic processes and to regenerate rapidly the tissues, has the anti-inflammatory, bactericidal and hemostatic effect due to the ingredients of the ointment. One of the ingredients of the ointment is caryophyllene (the extract of calendula) with the anti-inflammatory, wound-healing, bactericidal, antiseptic, capillary-aging activity. The action of the roots of northern cinquefoil (Potentilla maculata) is based on the rich content of tannins and causes the anti-inflammatory and hemostatic effects. The Sophora Japonica fruit contains a large amount of rutin, which reduces the permeability and fragility of blood vessels, has the hemostatic, bactericidal, anti-edema, anti-inflammatory effects. Vitamins, essential oils, esters, organic acids of the yarrow (Achillea millefolium) herb possess the anti-inflammatory, bactericidal, anti-allergic, and woundhealing effect. Propolis has a detrimental effect on a number of bacteria and exhibits a marked local analgesic effect [16].
The valuable therapeutic properties of Spasatel Forte ointment are its ability to activate the local immunity, and initiate regenerative processes. The ointment prevents the development of infections, has the analgesic activity. The drug composition includes vegetable oils, vitamins, and natural extracts. Sea buckthorn oil helps to accelerate the process of wound healing due to a mixture of active substances: sterols, phytoncides, carotenoids, organic acids. Chamomile essential oil has the antiinflammatory, analgesic, antiseptic effect. Lavender oil has the antiseptic, bactericidal effects, accelerates the regeneration of epidermis cells. Carotenoids, flavonoids, essential oils, organic acids of calendula have the anti-inflammatory, wound-healing effect, promotes the growth of granulation and epithelization [16].
The pharmacological activity of these medicinal products containing herbal ingredients, namely, theantipyretic and wound-healing effect, was determined on the model of thermal burn.
Modeling of burn wounds to animals was carried out under anesthesia on the depilated area of the skin of the right posterior thigh [15]. For this purpose a device with the adjusted temperature scale and an electric soldering tool with a circular metal plate of 2.5 cm in diameter attached at the end of it were used. The exposure time of the contact plate heated up to 2 °C was 5 seconds [17]. This method allowed obtaining standard burns with the area and depth of skin lesions corresponding to the degree II-А of clinical classification of burns. Experiments were conducted on 24 white female rats weighing 200-240 g. The experimental animals were divided into 4 groups: Group 1 -pathology (n = 6); Group 2animals treated with Wundahyl ointment (n = 6); Group 3 -animals treated with Spasatel Forte ointment (n = 6); Group 4 -animals treated with 2 % thiotriazoline ointment (n = 6), total 24, respectively. The ointments were applied with a thin layer to the wound surface immediately after the thermal action and within the experimental period. Visual monitoring of the condition of the animals and the state of the wound were performed on Days 4, 7, 14, 21, 28. The area of the wound was also measured these Days. The process of regeneration of skin wounds was assessed using planimetric indices.
The rate of healing wounds (V, mm/day) was measured on Days 1, 4, 7, 14, 21, 28 of the experiment and determined by the formula [18]: where S is an area of healing in mm 2 , n is a number of the treatment days.
The experimental data obtained were processed by the methods of variation statistics, the aver-age arithmetic value and its standard error were calculated [19]. In order to obtain statistical conclusions, mathematical calculations were applied with the use of "Statistica 6.0" analytics software package [20].
The experiments were performed on the experimental animals grown in the vivarium of the Central Research Laboratory of KhNMU equipped in accordance with the current sanitary and hygienic requirements. The experimental animals were kept on a standard diet. The animals always had free access to water. During the experiment, the animals were in the research room at t = 18-24 °С, humidity was not more than 55 %, light conditions of "day-night" were natural, the animals were in plastic cages, with the balanced feeding. The study was performed in compliance with the bioethics rules -humane treatment of animals in accordance with the provisions of the European Convention for the Protection of Vertebrate Animals (Strasbourg, 1986) and the National Congress of Bioethics IV (Kyiv, 2010).

Results and discussion
Observation over the healing process showed that the final formation of the burn wound in all experimental groups occurred on the second day. After the onset of the burn wound in all experimental animals a dense gray and brown scab appeared with a clearly restricted necrotic area and pronounced inflammatory changes in surrounding tissues. Starting from the third day there was a tendency to soften the central part of the thick scab; a serous-purulent exudate appeared when pressing the scab. On Day 7, the burn wound of the pathology group was a zone of necrotic nature filled with a serous-purulent exudate. The regenerative process was very slow and solely due to physiological mechanisms of the organism. Partial ecdysis occurred on Day 14, complete -on Day 21. The process of edge epithelization was slower than in the groups of animals receiving the treatment. On Day 28, the wounds in animals of the pathology group were not completely healed.
In the groups of treated animals, serous exudation was moderate, swelling and hyperemia of the wound were also less pronounced compared to the group of pathology. In animals treated with Wundahyl ointment and 2 % thiotriazoline ointment the wound process was better (Table). The area of necrotic nature in the center of the burn wound for the next two weeks of observation (Days Thus, in the second group of experimental animals (treated with Wundahyl ointment) the wound healing progress was more pronounced compared to the group treated with Spasatel Forte ointment, and it was almost the same compared to group 4 treated with the reference drug -2 % thiotriazoline ointment, and it had more significant indices in relation to the group of pathology without treatment of the experimental animals.
CONCLUSIONS As a result of the experimental studies in animals on the model of thermal burn, Wundahyl ointment revealed better burn wound-healing properties than Spasatel Forte ointment. Wundahyl ointment also exhibited better burn wound-healing properties compared to the reference drug -2 % thiotriazoline ointment.
Thus, it can be concluded that Wundahyl multicomponent ointment containing herbal biologically active ingredients has a pronounced anti-inflammatory and wound-healing effect, and it can be effectively used in the treatment of superficial burn wounds.
Conflict of interests: authors have no conflict of interests to declare. 2) ^ -significant difference in relation to the baseline, р < 0.05; 3) # -significant difference in relation to the group of pathology, р < 0.05.