THE Basic approacHEs To pHarmacoTHErapy of HElminTHiasEs anD prospEcTs of pHyTomEDicinEs DEVElopmEnT for THEir TrEaTmEnT

Parasitic infections are one of the most acute and urgent problems of modern global society. The fact that most cases of helminthiases of the digestive system falls on children of the preschool and early school age is of particular relevance. Pharmacotherapy of helminthoses of the digestive system involves the preparatory stage, causal treatment and elimination of complications of the past disease. It is important to observe the diet. Foreign treatment standards provide two stages of treatment: elimination of helminths (medicines based on mebendazole, albendazole, thiabendazole, niclozamine, praziquantel) and elimination of complications of the past disease. In addition, non-pharmacological treatment is recommended, it includes good nutrition and personal hygiene. The domestic market of antihelmintics is represented by drugs based on praziquantel, mebendazole, albendazole, piperazine, pyrantel, levamisole, and one drug in the form of medicinal plant raw material – tansy flowers. Most of these medicines are produced abroad (57.9%). The age limits vary from the 6th months to 14 years. The price proposals on antihelmintic medicines vary depending on the dose, type of a dosage form and producer. The folk medicine offers a variety of prescriptions for treating helminthoses based on medicinal plants. On the basis of the analysis of the folk medicine formulations 11 medicinal plants have been identified as promising for creation of the complex phytomedicine with the antihelmintic activity.

N owadays, parasitic infections are one of the most acute and urgent problems of the society. According to the World Health Organization approximately 1.2 billion people are infected with parasitic infections each year.
According to the recent findings helminthosis affect all, without exception, age groups. However, children are significantly more likely to become infected with helminths due to the lack of high-grade hygienic skills, and some studies prove greater sensitivity of the child's body to development of helminthiases since penetration of eggs or cysts of worms in the human body does not lead to development of helminthosis in all cases [4,5,15].
The share of children helminthoses of the digestive system is 92.3% of the cases of enterobiosis, 71.1% -ascariasis, 61.5%trichocephalosis and 66.2% -toxocariasis. Children of the preschool and primary school age are the most susceptible to helminth infections, children aged 2-10 years are the most susceptible to helminthosis [8, 15,17].
It is known that the larvae and eggs of helminths when in contact with the human body orally are exposed to enzymes and nonspecific protection factors, the gastric juice and local immunity of the intestines, and it usually causes their death. But when weakening of the body's defences larvae and eggs are able to penetrate into the intestine and grow to adult forms [8].
The clinical picture of the disease depends on many factors, including duration and intensity of helminthic infestations and the general condition of a patient. As a rule, the helminthiasis symptoms are nonspecific and varied. In many respects this diversity of clinical manifestations is associated with a huge list of potential pathogens: there are about 70 species of helminths in Ukraine of more than 250. Disorders of the hepatobiliary system and the gastrointestinal tract in general are the most often [8,18].
The main phases of the clinical course of intestinal helminthoses are: 1. Acute. It manifests with common allergic and toxic reactions.
2. Latent. Usually it is not accompanied by clinical symptoms.
Making an accurate diagnosis followed by the proper treatment is possible only on the basis of the laboratory diagnosis data. Usually feces, urine, duodenal contents, bile, perianal and rectal mucus, and blood are examined. It is also important to study the status of the patient's immune system as the nature of the immune response is determined by morphological and biological characteristics of each species of helminth. In a specific immune response circulating antibodies of classes IgG, IgM, IgE and IgA are involved. The IgE index increases significantly since it is the exact antibody K.V.Tolochko -PhD of Pharmacy, associate professor of the Department of Pharmaceutical Technology of Drugs of the National University of Pharmacy (Kharkiv) class, which together with eosinophils is the main defence mechanism of human body from helminthic invasion [6,8,16].
Pharmacotherapy of helminthosis usually consists of the preparatory stage, causal treatment and correction of the consequences and complications of recent helminthosis. Often the preparatory stage requires intake of antihistamines. It is also important to follow the rules of a balanced diet, the diet No. 4 is recommended [6,8].
Foreign experience in the treatment of helminthiases provides two goals of pharmacotherapy: elimination of helminths and elimination of the disease complications (anemia, metabolic disorders, etc.). The therapy with medicines (the level of evidence: B) on the basis of mebendazole, albendazo-le, thiabendazole, niclosamine, praziquantel is recommended. In addition, non-pharmacological treatment is recommended; it includes good nutrition and personal hygiene. It should be noted that any phytomedicines or herbal therapy as a whole are not mentioned in the US and British guidelines for helminth pharmacotherapy [19][20][21]. It is also indicated that the existing medicines can-  • the absence of the resorptive effect, the harmful effect on human organs and tissue; • a rapid clearance from the body; • the absence of cumulation.
In order to study the prospects of developing new domestic medicines to treat helminthosis on the basis of the medicinal plant raw material the main groups of antihelminthic medicines of the officinal medicine, as well as the medicinal plant raw material used in the folk medicine were analyzed.
The analysis of medicines presented at the Ukrainian pharmaceutical market to treat helminthoses was conducted on the basis of the data given in the compendium on-line and the Reference book of medicines of Ukraine [7,10].
The АТС classification of antihelminthic medicines is given in Figure. The group of anthelminthic medicines includes 19 medicines ( Table 1).
As it is seen from Table 1, 11 out of 19 medicines are manufactured abroad (57.9%), whereas only 8 drugs -in Ukraine (42.1%). However, only one drug (5.3%) is of the natural origin.
Price offers for these medicines vary ( Table 2). The study was carried out based on the price at http://medbrowse.com.ua/ site database with price offers for Kharkiv and the Kharkiv region, including Internet pharmacies offers with delivery from other regions of Ukraine (as of 06.15.2016).
As can be seen from the above data, price offers have significant fluctuations. These fluctuations depend on the dose, the dosage form and the availability of several manufacturers. Further, more in-depth market research of antihelmintic drugs is planned in order to calculate the average cost of treatment.
The main side effects of the digestive system, the central nervous system and allergic reactions of some active substances of antihelmintic medicines are presented in Table 3 [18].
In the folk medicine there are a lot of prescriptions to treat the different types of worms. Based on the analysis of the folk medicine formulations 11 medicinal plants have been identified as promising for creation of the complex phytomedicine with the antihelmintic activity (Table 4) [1-3, 9, 11-15].   Therefore, it can be concluded about the relevance of development of medicines based on the medicinal plant raw material for treating helminthoses. These medicines should provide the complex antihelmintic action, have low toxicity, good tolerability, and do not cause allergic reactions. Creation of herbal medicines to treat helminthoses is of particular current interest in pediatrics since most medicines of the synthetic origin have many side effects, contraindications for use in children. CONCLUSIONS 1. The characteristics of helminth infections of the digestive system as one of the most common diseases in the world are presented. The main approaches to the pharmacotherapy of helminthoses, including foreign recommendations, and the basic requirements for antihelmintic medicines have been studied.
2. The range of antihelmintic medicines represented at the domestic pharmaceutical market has been analyzed. It has been determined that medicines of the synthetic origin (94.7%) and of foreign production (57.9%) dominate. The age limits of this group of medicines vary from the 6 th months to 14 years. The price proposals on antihelmintic medicines have been also studied.
3. The basic groups of active substances, their pharmacological effects and the mechanism of action of medicinal plants commonly occurring in the folk medicine formulations on helminths have been studied.