Розробка складу та технології комбінованого гелю для лікування запальних захворювань суглобів

Abstract

Дисертація присвячена теоретичному й експериментальному обґрунтуванню складу та розробці технології оригінального лікарського засобу –комбінованого лікарського препарату з фітокомпозицією та метилсаліцилатом у формі гелю для лікування гострих та хронічних захворювань суглобів. Теоретично обґрунтовано і комплексними фізико-хімічними, структурномеханічними, фармакотехнологічними і біологічними дослідженнями підтверджено склад (верби білої кори та шавлії лікарської листя екстракти сухі – по 1,5 %, метилсаліцилат – 1,0 %, ГЕЦ – 2,5 %, ПЕГ-40 гідрогенізована рицинова олія – 2,0 %, ніпагін – 0,2 %, етанол – 1,0 %, вода очищена – до 100,0 %) і технологію розробленого препарату. Розроблено проєкти технологічного регламенту на виробництво Салікс гелю та методів контролю його якості.

Диссертация посвящена теоретическому и экспериментальному обос-нованию состава и разработке технологии оригинального лекарственного средства – комбинированного лекарственного препарата с фитокомпозицией и метилсалицилатом в форме геля для лечения острых и хронических заболеваний суставов. Теоретически обоснованы и комплексными физико-химическими, структурномеханическими, фармакотехнологическими и биологическими исследованиями подтверждены состав (ивы белой коры и шалфея лекарственного листьев экстракты сухие – по 1,5 %, метилсалицилат – 1,0 %, ГЭЦ – 2,5 %, ПЭГ-40 гидрогенизированное касторовое масло – 2,0 %, нипагин – 0,2 %, этанол – 1,0 %, вода очищенная – до 100,0 %) и технология разработанного препарата. Разработаны проекты технологического регламента на производство Саликс геля и методов контроля его качества.

The dissertation is devoted to the theoretical and experimental substantiation of the composition and development of the technology of the original drug – a combined drug with phytocomposition and methyl salicylate in the form of a gel for the treatment of acute and chronic joint diseases. The data of the scientific literature on the etiopathogenesis and modern methods of pharmacotherapy of inflammatory diseases of the joints were analyzed. Based on the study of the range of drugs for the treatment of this pathology in Ukraine, the expediency of expanding the range of gels for the local treatment of inflammatory diseases of the joints based on raw materials of natural origin was established. According to the results of research and analysis of scientific literature, the feasibility of using the phytocomposition of dry extracts of white willow bark and sage leaves and methyl salicylate as API in the creation of the original drug was substantiated. The marketing analysis of the pharmaceutical market of Ukraine identified a market segment (about 60 drugs) that covers various pharmacotherapeutic groups and a wide range of countries-manufacturers and pharmaceutical companies, such as «SANDOZ» (Germany), «KRKA» (Slovenia), «Novartis AG» (Switzerland), «Berlin-Chemie AG» (Germany), «Teva» (Israel), «Gedeon Richter» (Hungary), «Darnitsa» (Ukraine), «Zdorov’ya» (Ukraine). However, the original combined gel for the treatment of inflammatory diseases of the joints of domestic production is not presented on the pharmaceutical market of Ukraine. The physico-chemical properties of the selected APIs were studied in order to substantiate the method of their introduction into the drug. Pharmacotechnological and biological studies theoretically and experimentally substantiate the composition and concentration of active substances in the gel (dry extracts of white willow bark and sage leaves – 1,5 % and methyl salicylate – 1,0 %). Complex pharmacotechnological, biopharmaceutical and microbiological studies substantiated the type of carrier base and the quantitative content of excipients (HEC – 2,5 %, PEG-40 hydrogenated castor oil – 2,0 %, nipagin – 0,2 %, ethanol – 1,0 %, purified water – up to 100,0 %). On the basis of the conducted pharmacotechnological, physicochemical and rheological researches the technology of manufacturing of Salix gel is developed and proved. The method of introduction of active substances into the base was substantiated, the critical parameters of the drug production process were determined (mixing time – 30 min, the operation mode of the stirrer – 250 rpm). The organoleptic and physicochemical properties of the developed gel were determined, the methods of identification and quantitative determination of the active components of the preservative in it were developed. The main indicators of gel quality are determined and the projects of MQC and technological regulations for the production of Salix gel were developed. Biopharmaceutical studies have proven that selected composition of the developed combined gel has moderate osmotic activity at the level of the comparison drug, which meets the medical and biological requirements for its use, and long-term release of API (active for the first 3 hours, then slowly for another 3 hours). The stability of the developed Salix gel is proved and the term and conditions of its suitability were established – within 2 years of storage in aluminium tubes at a temperature no higher than 25 °C. Pharmacological studies have established anti-inflammatory, anti-exudative and immunomodulatory activity of the new combined gel by inhibiting autoimmune processes and increasing the activity of the cellular component of nonspecific immunity, as well as its safety.