Method and technology for drug repurposing based on changes in the physicochemical properties of dosage forms: experience of use in Russia

Abstract

Controlled local hyperthermia and hypothermia are important factors in drug pharmacodynamics and pharmacokinetics because changing the temperature of drugs changes their physicochemical properties. In this regard, a controlled change in the temperature of the drug and/or the body part with which the drug interacts, relative to the level of human body temperature (hyperthermia or hypothermia) forms the basis of temperature pharmacology. To analyze the authors publications on the problem of methodology and technology for repurposing drugs based on changes in the physicochemical properties of dosage forms. A controlled change in the temperature of the drug and/or the part of the body with which the drug interacts; a change in acid (alkaline), osmotic activity, and the degree and quality of carbonation and/or oxygen-forming activity of medicinal solutions; and a change in the concentration of medicinal solution ingredients. On the basis of the used methods, the reprofiling of a number of drugs has been achieved. The author proposed reprofiling a 4% potassium chloride solution from the group of macroelements and microelements used to regulate acid-base balance with a resorptive effect (when administered intravenously to the whole body) into a group of vasoconstrictive drugs used to stop bleeding when applied to by a single irrigation of the bleeding surface. Cooling certain drugs and tissues at their interaction sites to 18C20C (via an ice pack or its substitute) inhibits metabolism and function, ensuring the conversion of many drugs into anti-ischemic drugs by reducing the need for tissues in oxygen. A targeted change in the physicochemical properties of known drugs combined with local hyperthermia allows them to be converted into expectorant, pyrolytic (astringent), hemolytic, thrombolytic (hemostatic), detergent, bleaching, cleaning, and other drugs, including antiseptic and cauterizing (necrotizing) drugs, very reliably, quickly, and inexpensively. Thus, 40 years ago, pharmacologists of the Russian Federation established the foundation for a novel method of drug development known today as repurposing of existing drugs. Today, it is evident that reprofiling may rapidly, inexpensively, and effectively give existing drugs a new purpose.

Pyolytics as a product of the physical–chemical repurposing of antiseptics and an alternative to larval therapy for chronic wounds

“…Многие авторы сообщают, что местное действие лекарственных препаратов на биологические ткани, включая гнойные массы, зависит не столько от специфической фармакологической активности ингредиентов, сколько от неспецифической физико-химической активности лекарств [47,[49][50][51][52][53][54]. Исходя из этого, было предложено учитывать не только специфическую активность лекарственных средств, входящих в состав готовых лекарственных препаратов (таблеток, растворов, аэрозолей и пр.…”

“…Полученные результаты позволили предложить локальную гипертермию и защелачивание лекарственных растворов в роли дополнительных факторов локального взаимодействия антисептиков с густыми и твердыми биологическими массами, включая гнойные, для более быстрого и эффективного их разжижения и растворения. Это позволило в последующем сформировать новое направление поиска и разработки новых лекарств, получившее название «физико-химическое перепрофилирование лекарств» [51,52,54].…”