ANALYSIS OF PHARMACEUTICAL WORKERS RECOMMENDATIONS FOR WOUND-HEALING DRUGS IN UKRAINE

. The occurrence of superficial wounds remains one of the most significant problems all the time among different types of household injuries. Up to 40 % persons annually have such damages of the skin like abrasions, scratches, cracks, suppurations, cuts, bedsores, and others. The problem of choosing a suitable drug arises acutely, since most pharmacists consider the issue of treatment by themselves. Patient’s referral to hospital departments for doctors advise remains minimal. Pharmacy specialists carry out pharmaceutical care and perform a personal analysis due to the given initial information about the mechanism, place of occur, size of wound and stage of the process of wound healing. Considering previous experience in fulfilling customer needs, they select optimal remedy, determine the majority of choice and thus, may be identified as the sales leaders. As for January 2021, the range of topical drugs used for the treatment of wounds numbered 270 trade names according to the State registry of medicines of Ukraine. They included 62 types of active pharmaceutical ingredients. Antimicrobial (antiseptic), anti-inflammatory, decongestant, protective and emollient action properties are underlined in their pharmaceutical inserts. It is similar for most of the medicines that are available on the Ukrainian pharmaceutical market. After all, their effectiveness to satisfy a patient need is as different as the price point. The choice of the optimal in composition and rational in the dosage form causes certain difficulties among the available wide range of medicines. Registrated semi-solid wound-healing drugs are represented by three groups of ATC classification: D03 – drugs for wounds and Questionnaire contained the same questions for the individual survey and online one. Questionnaire contained particular situational tasks and questions related to the practical experience of the phar maceutical specialists: 12 questions, among which 5 questions provided an answer in detail. Whole data was analyzed systematically and statistically. 342 reviews on 36 medicines trade names were re ceived while answering the question about the drug’s recommendation for quick healing of abrasions and scratches. Various drugs promoting rapid injury healing («Bepanten ® » ointment, «Levomekol» ointment, «Pantestin-Darnitsa ® » gel and «Riativnyk ® » cream) determined in the most mentioned requests. We found out that most pharmaceutical specialists chose semi-solid dosage forms contain ing dexpanthenol for light burn wounds healing («Bepanten ® » cream and ointment, «D-panthenol», «Pantecream», «Pantexol-Jadran», «HepiDerm-Zdorovye»). Pharmaceutical specialists recommend «Contractubex ® » and «Solcoseryl» mostly to improve wound healing and minimizing the develop ment of a cosmetic scar. Only 1/3 of respondents would recommend to a pharmacy visitor to exam skin defect by doctor or cosmetician and get reliable advice. The recommendations of pharmaceutical specialists for shallow cuts were predominantly determined by antiseptic drugs – most of them chose iodine solutions. 264 reviews were received for 32 trade names of medicines as effective treatment for bedsores. Respondents preferred zinc oxide preparations usage. According to the investigation, the opinions of the interviewed pharmaceutical specialists were focused on the semi-solid dosage forms (ointments, creams etc) for various wound care (abrasions and scratches, burns, scars, bedsores). Dosage forms of medicines for the treatment of cut wounds were an exception. Solutions and new kind of plasters – Skin glue, were the drugs of choice in this group. Phytomedicines practically did not appear among the respondents answers.

Questionnaire contained the same questions for the individual survey and online one. Questionnaire contained particular situational tasks and questions related to the practical experience of the pharmaceutical specialists: 12 questions, among which 5 questions provided an answer in detail. Whole data was analyzed systematically and statistically. 342 reviews on 36 medicines trade names were received while answering the question about the drug's recommendation for quick healing of abrasions and scratches. Various drugs promoting rapid injury healing («Bepanten ® » ointment, «Levomekol» ointment, «Pantestin-Darnitsa ® » gel and «Riativnyk ® » cream) determined in the most mentioned requests. We found out that most pharmaceutical specialists chose semi-solid dosage forms containing dexpanthenol for light burn wounds healing («Bepanten ® » cream and ointment, «D-panthenol», «Pantecream», «Pantexol-Jadran», «HepiDerm-Zdorovye»). Pharmaceutical specialists recommend «Contractubex ® » and «Solcoseryl» mostly to improve wound healing and minimizing the development of a cosmetic scar. Only 1/3 of respondents would recommend to a pharmacy visitor to exam skin defect by doctor or cosmetician and get reliable advice. The recommendations of pharmaceutical specialists for shallow cuts were predominantly determined by antiseptic drugs -most of them chose iodine solutions. 264 reviews were received for 32 trade names of medicines as effective treatment for bedsores. Respondents preferred zinc oxide preparations usage. According to the investigation, the opinions of the interviewed pharmaceutical specialists were focused on the semi-solid dosage forms (ointments, creams etc) for various wound care (abrasions and scratches, burns, scars, bedsores). Dosage forms of medicines for the treatment of cut wounds were an exception. Solutions and new kind of plasters -Skin glue, were the drugs of choice in this group. Phytomedicines practically did not appear among the respondents answers.
Key words: assortment, pharmacies, questionnaire of pharmaceutical specialists, semi-solid dosage forms, wound-healing medicines.
Introduction. There is no doubt that most of the damages are unintentional. Wounds should be called as skin injuries associated with a break of the skin integrity by mechanical factor. Wounds are characterized by gaping of the outer lining, bleeding and pain and may be classified into stabbed, cut, torn, bite, burn, gunshot etc wounds. Also, wounds are classified, based on how long they take to heal, as acute, and chronic ones (Ashalatha, Vaidya & Pooja, 2020). Most often, direct contact with a foreign body infects wounds. This can lead to suppuration, especially in advanced cases or when first aid has not been provided at time. Wounds healing is complicated due to increase of antibiotic-resistant microorganisms, extensive use of chemically active ingredients (Podorozhna, Gladukh & Stepanenko, 2020), which can lead to unwanted allergic (side) effects, and infrequent referral to the doctor for medical advice. Pharmaceutical specialists are primarily those who most often provide advice on the choice of a medicine depending on the nature of the wound surface and the stage of the process of wound healing: first phase -inflammation, second phase -regeneration and third phase -epithelialization of tissue (Datsenko, Belov & Tamm, 1985, Datsenko, 2007, as cited in Glushchenko, 2020. This was seen in Glushchenko (2020) study of wound-healing medicines assortment on pharmaceutical market of Ukraine for January 2020, that among medicines recommended for use in first phase of wound healing process, dominate drugs with antimicrobial action, in first-second phases of wound healing process -medicines with antimicrobial, analgesic, reparative and anti-inflammatory action; in second-third phases of wound healing process -antimicrobial and reparative action medicines.
Understanding the exact mechanisms which is involved in the process of wound formation is necessary to select the optimal type of therapy.
Abrasions are isolated lesions of the epidermis, clinically not manifested by bleeding. A disturbance of blood circulation and lymph flow slow the epithelialization and leads to the recurrence of skin defects. Mostly, they are the simplest of all injuries due to the terms of wound healing, and ability not to leave any scar after treatment. They are the most common form of injury in children accounting for 70.7 % of all injuries. Abrasions can be classified into linear or scratch, grazed and patterned types (Shrestha., Krishan & Kanchan, 2020).
This was seen in Zhong, Ahmad, Xing., Yamada & Hamel (2008) that «a bedsore or pressure ulcer is an area of localized damage to the skin and underlying tissue caused by pressure, shear, friction, or a combination of these factors». Areas exposed to long-term systematic pressure or which form due to the neurotrophic disturbances lead to the appearance of bedsores in weakened long-lying patients (ulcerative-necrotic, dystrophic changes). With bedsores, foci of inflammation are formed, the risk of infection increases.
Extreme temperature coagulates skin proteins, which leads to their death. Violation of microcirculation turns up, the skin surface becomes hyperemic, the interstitium swells. Skin lesion is deeper and thermal burns are significant with more critical temperature and longer time of exposure. It is always needed the «adequate fluid replacement, nutritional support, and immediate wound grafting» to reduce the risk of infection (Wardhanal & Halim, 2020). It is needed to understand, that «different causes lead to different injury patterns», which require different medicational treatment depending on the body's response to a burn, is it local or systemic one (Hettiaratchy & Dziewulski, 2004). And only if burn injuries are local and have a little area, patient can consider a pharmaceutical specialist's recommend of a medicational form for its healing. Eighty thousand cases of burns are registered in Ukraine every year (Glushchenko, 2020).
Any wound that is penetrating the dermis (injuries, surgeries, burns, acne) heals with scarring process. Sometimes wounds on the skin are subject to excessive scarring, which leads to hypertrophic and keloid scars obtaining. Their occurrence explains by the injury of the basement membrane and healing of the tissue by secondary tension. Most of such scars skin changes cause not only aesthetic, but also functional disorders that affect the quality of life (Avetikov, Stavytskyy, Trapova, & Rozkolupa, 2013). For example, scars after acne occur due to different factors, such as androgen, bacteria, immunology, genetics and external factors such as medicines and cosmetics that were used during treatment (Mascaro, 2000). This was seen in Avetikov et al. (2013) that «approximately 25 million people worldwide occur each year pathological scars».
Based on the analysis of numerous scientific medical sources, it was found that there is no single view on the etiology, pathogenesis, treatment and prevention of pathological scars.
It is necessary to take into account many pathological link and pathways to eliminate the decisive factors completely choosing the optimal composition of the medicine and dosage form.
Wound-healing medicines should have such characteristics, as safety (be not harmful not only to living tissue, but also the body in general), efficiency (be able to achieve the therapeutical purpose without affecting natural wound healing process), ease of use (Atiyeh et al., 2009, as cited in Ismail et al., 2015. The occurrence of superficial wounds remains one of the most significant problems all the time among different types of household injuries. Up to 40 % persons annually have such damages of the skin like abrasions, scratches, cracks, suppurations, cuts, bedsores, and others. The problem of choosing a suitable drug arises acutely, since most pharmacists consider the issue of treatment by themselves. Patient's referral to hospital departments for doctors advise remains minimal. Pharmacy specialists carry out pharmaceutical care and perform a personal analysis due to the given initial information about the mechanism, place of occur, size of wound and stage of the process of wound healing. Considering previous experience in fulfilling customer needs, they select optimal remedy, determine the majority of choice and thus, may be identified as the sales leaders (Sen, 2019).
As for January 2021, the range of topical drugs used for the treatment of wounds numbered 270 trade names according to the State registry of medicines of Ukraine. They included 62 types of active pharmaceutical ingredients. Antimicrobi-al (antiseptic), anti-inflammatory, decongestant, protective and emollient action properties are underlined in their pharmaceutical inserts. It is similar for most of the medicines that are available on the Ukrainian pharmaceutical market. After all, their effectiveness to satisfy a patient need is as different as the price point. The choice of the optimal in composition and rational in the dosage form causes certain difficulties among the available wide range of medicines.
Registrated semi-solid wound-healing drugs are represented by three groups of ATC classification: D03 -drugs for wounds and ulcers, D06antibiotics and chemotherapeutic drugs for use in dermatology, D08 -antiseptic and disinfectant drugs. Ointments predominate among semi-solid dosage forms with range 67.3 %, creams -26.5 %, gels -10.2 %, liniments -6.1 %, and jellies only 2.0 % of the market. 59.2 % of semi-solid wound-healing drugs are produced by domestic enterprises, and 40.8 % -by foreign manufacturers. The recommendations for the use of semi-solid drugs were distributed as follows: for the first phase of wound process -48.9 %, for the first and second phases -12.2 %, for the second phase -10.2 %, for the second and third phases -26.4 %, for the third phase -2.0 %.
The analysis of semi-solid wound-healing drugs by the origin of active substances proved the advantage of synthetic origin ones -89.7 %, only 8.1 % contain plant origin substances, only 2.2 % -animal origin substances. The majority of semi-solid wound-healing drugs are monocomponent -63.2 %.
The purpose of our work was to single out available and free sale wound-healing medicines among registered on the Ukrainian market, that are most promoted and recommended by pharmaceutical specialists. This would help to highlight the real picture of sales, to analyze the components of leading products and, as a result of additional research, to propose a model for the complex pharmaceutical development of a new wound-healing medicine in a rational dosage form with safe and effective active ingredients of plant origin, and, consequently, competitive for pharmaceutical manufacturers.

Materials and Methods.
The list of registered medicines was composed in accordance with the data from the State Register of Medicines of Ukraine (trade names of registrated active pharmaceutical ingredients were used). Besides, such service portals like tabletki.ua and compendium. com.ua were used too. The Anatomical Therapeutic Chemical (ATC) code assigned to each drug was listed appropriately to ATC classification system.
The total number of respondents was 176. Questionnaire survey was the main method of information's collecting: 46 respondents were interviewed individually (the survey was conducted in Kyiv pharmacies during the internship of O. О. Bogomolets National Medical University pharmaceutical faculty students), 130 persons of the target audience -by electronic form. The questionnaire contained the same questions for the individual survey and online one. Questionnaire contained particular situational tasks and questions related to the practical experience of the pharmaceutical specialists. The questionnaire contained 12 questions, among which 5 questions provided an answer in detail. Whole data was analyzed systematically and statistically using MS Access, MS Excel, and Power Quarry software.
Work experience and education level varied among the interviewed specialists (table 1).
Results and discussion. Different answers were received depended on the ownership of pharmacies, work experience, age, self-education of pharmaceutical specialists.
Analyzing the answers to the questions of situational tasks, we have received and structured the following results.
Question 1. A young man, who fell on the asphalt and injured a small area of his skin, comes to your pharmacy with a request to help to choose a needful medicine. What drug would you recommend for quick healing of abrasions and scratches?
In total 342 reviews on 36 medicines trade names were received. They can be conventionally divided into 3 categories: medicines containing antibiotics, antiseptics and various drugs promoting rapid injury healing.
Some pharmaceutical specialists gave exceptional advice in proposed simulated situation. For example, this was washing wounds with a hypertonic solution of sodium chloride or using laundry soap as a treatment.
Question 2. A young woman touched a hot kettle at home. She developed a mild burn. The next day, she asks help to find a medicine. What would you suggest to a customer with burns? Specific trade names of medicines («Contractubex ® » gel manufactured by Merz Pharma GmbH& Co.KGaA, Germany; «Solcoseryl» gel and ointment manufactured by Legacy Pharmaceuticals Sweetseland GmbH, Switzerland), instruction to indicate other answer option and instruction to consult a doctor were the answers to this situation task question.
Question 4. The young man cut superficially the back of his forearm during washing the dishes. The damage was minor, the bleeding stopped. Which of the drugs, in your opinion, is preferable and will accelerate the healing of the cut wound?
The recommendations of pharmaceutical specialists for shallow cuts were predominantly determined by antiseptic medicines (68.2 % of the received responses). Most of the specialists chose iodine solutions -42 requests (23.9 %). Hydrogen peroxide solutions 3 % also did not lose demand -17 requests (9.7 %). Dilute ethanol solu-tion of brilliant green, calendula tincture, etc. occurred in the minority of questionnaires (1-2 responses of respondents).
The most part of young pharmaceutical specialists (with work experience up to 5 years) hold the opinion, that skin glue is one of the perspective dosage forms for healing of shallow cuts (21.9 % of the received responses).
Question 5. What do you think is the most effective treatment for bedsores?
Bedsores were shown as typical variant of purulent (septic) wound. Generally, 264 reviews were received for 32 trade names of medicines. The obtained survey data showed the advantage of antiseptics as drugs of choice over antibiotic containing ones (56.4 %). In particular, 69 requests (26.1 %) of respondents preferred zinc oxide preparations usage. Among this group of drugs «Sudocrem» (manufactured by Tosara Pharma Ltd, Ireland) become most common in all answers -15.5 %.
Additionally, some pharmaceutical specialists noted among other answers usage of such means and methods as herbal ointment «Woundaheal», aerosol «Kadefort», «Dioxizol-Darnitsa ® » solution, chlorophyllipt oil solution, camphor alcohol solution, application of hydrocolloid bandage and tampons moistened with calendula tincture.
A separate point of our research was to study the demand for various types of dosage forms in the treatment of cut wounds. This question was interesting for us, for future choice of optimal and rational dosage form as an object of new wound-healing medicine's pharmaceutical development. We have received 222 answers. Pharmaceutical specialists recommended skin glue (liquid plaster) in 25.7 %, bactericidal adhesive plaster -19.8 % and antiseptic solutions for cure of surficial injuries (19.4 %). The respondents answers with the indication of semi-solid dosage forms were 24.9 % in total (cream -9.5 %, ointment -8.6 %, liniment -6.3 %, gel -0.5 %).
Answering the question for what did the pharmaceutical specialists guided for advising wound healing agents, the majority of respondents indicated frequent prescriptions by doctors (40.3 %), recommendations of colleagues in their pharmacy (31.8 %) and their own experience (23.9 %).
The last question in the questionnaire was about compliance with the recommendations or providing an alternative choosing of a wound-healing medicine by a pharmacy visitor. We received 97 responses (55.1 % of the total number of reviews) regarding the fact that the patient always follows the recommendations of a specialist working in a pharmacy while choosing a wound-healing drug. It was determined that the most amount of these requests (55.7 %) were given by pharmaceutical specialists with work experience over 10 years. 52 respondents (29.5 %) noted that a pharmacy visitor often follow a specialist's advice. And 13.1 % of all interviewed pharmaceutical specialists requests (23 respondent's answers) showed that despite recommendations and advice the pharmacy visitor choose another medicine.
All pharmaceutical specialists noted that the provision of pharmaceutical care, and given recommendations for choosing optimal in safety, effectiveness and price wound-healing medicine, can be carried out only in the case of a small level of the patient's body tissue injuries. . Their share was 82.6 % of the obtained requests. Dosage forms of medicines for the treatment of cut wounds were an exception. Solutions and new kind of plasters -Skin glue, were the drugs of choice in this group. Phytomedicines practically did not appear among the respondents answers. We consider that develop of wound-healing effective preparations with active herbal components is actual and promising direction of research.

Conclusions
Funding. This study has no external funding.

Conflict of interest.
None of the authors received research grants, speaker's fees from any companies and is not a member of commissions.
Consent to publication. All authors have read and approved the final version of the manuscript. All authors have agreed to publish this manuscript.