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 author’s 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 18°C–20°C (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.

Keywords

concentration of drug solution ingredients / drug repurposing / hyperthermia and hypothermia

References

[1] Frearson JA, Wyatt PG, Gilbert IH, et al. Target assessment for antiparasitic drug discovery. J Trends in Parasitology. 2007;23(12):589–595. DOI: 10.1016/j.pt.2007.08.019

[2] Frearson J.A., Wyatt P.G., Gilbert I.H., et al. Target assessment for antiparasitic drug discovery // Trends Parasitol. 2007. Vol. 23, No. 12. Р. 589–595. DOI: 10.1016/j.pt.2007.08.019

[3] Wyatt PG, Gilbert IH, Read KD, et al. Target validation: Linking target and chemical properties to desired product profil. Curr Top Med Chem. 2011;11(10):1275–1283. DOI: 10.2174/156802611795429185

[4] Wyatt P.G., Gilbert I.H., Read K.D., et al. Target validation: linking target and chemical properties to desired product profil // Curr. Top Med. Chem. 2011. Vol. 11. No. 10. P. 1275–1283. DOI: 10.2174/156802611795429185

[5] Brown M, Bennett P, Sharma P. Discovery and development of drugs. Churchill: Livingstone; 2012.

[6] Brown M., Bennett P., Sharma P. Discovery and development of drugs. Churchill: Livingstone; 2012. 777 р.

[7] Urakov AL, Pugach VN, Kravchuk AP, et al. Ispol’zovaniye tepla i kholoda dlya regulyatsii krovotoka i podderzhaniya gemostaza vnutrennikh organov. Patologicheskaya fiziologiya i eksperimental’naya terapiya. 1984;5:43–46. (In Russ.)

[8] Ураков А.Л., Пугач В.Н., Кравчук А.П., и др. Использование тепла и холода для регуляции кровотока и поддержания гемостаза внутренних органов // Патологическая физиология и экспериментальная терапия. 1984. Т. 28, № 5. С. 43–46.

[9] Urakov AL. Okhlazhdat’ ili nagrevat’? Priroda. 1986;9:121. (In Russ.)

[10] Ураков А.Л. Охлаждать или нагревать? // Природа. 1986. № 9. С. 121.

[11] Urakov AL. Retsept na temperaturu. Izhevsk: Udmurtiya; 1988. (In Russ.)

[12] Ураков А.Л. Рецепт на температуру. Ижевск: Удмуртия, 1988.

[13] Urakov AL. Retsept na temperature. Nauka i zhizn’. 1989;9:38–42. (In Russ.)

[14] Ураков А.Л. Рецепт на температуру // Наука и жизнь. 1989. № 9. С. 38–42.

[15] Urakov AL, Kravchuk AP, Kulik IA, et al. Farmakotermicheskiy sposob ostanovki krovotecheniy. Krovoobrashcheniye. 1989;1:51–53. (In Russ.)

[16] Ураков А.Л, Кравчук А.П., Кулик И.А., и др. Фармакотермический способ остановки кровотечений // Кровообращение. 1989. № 1. С. 51–53.

[17] Urakov AL, Kravchuk AP. Temperaturnyy rezhim ranevoy poverkhnosti kak faktor gemostaza. Voyenno-meditsinskiy zhurnal. 1991;8:65–66. (In Russ.)

[18] Ураков А.Л, Кравчук А.П. Температурный режим раневой поверхности как фактор гемостаза // Военно-медицинский журнал. 1991. № 8. С. 65–66.

[19] Urakov AL, Baranov AG, Sutyagin SP, et al. Uluchsheniye krovotoka v organakh i predotvrashcheniye tromboobrazovaniya s pomoshch’yu kholoda. Byulleten’ eksperimental’noy biologii i meditsiny. 1985;7:19–20. (In Russ.)

[20] Ураков А.Л, Баранов А.Г., Сутягин С.П., и др. Улучшение кровотока в органах и предотвращение тромбообразования с помощью холода // Бюллетень экспериментальной биологии и медицины. 1985. № 7. С. 19–20.

[21] Urakov AL. Ispol’zovaniye gipotermii dlya izyskaniya printsipial’nykh putey farmakologicheskoy zashchity miokarda ot povrezhdeniya v ranniy period ostroy ishemii. Byulleten’ eksperimental’noy biologii i meditsiny. 1984;4:512. (In Russ.)

[22] Ураков А.Л. Использование гипотермии для изыскания принципиальных путей фармакологической защиты миокарда от повреждения в ранний период острой ишемии // Бюллетень экспериментальной биологии и медицины. 1984. № 4. С. 512.

[23] Urakov AL, Kravchuk AP. Vliyaniye lokal’noy giper- i gipotermii na gemodinamiku i zhiznesposobnost’ ishemizirovannoy kishki. Vestnik khirurgii imeni I.I. Grekova. 1987;3:43–45. (In Russ.)

[24] Ураков А.Л., Кравчук А.П. Влияние локальной гипер- и гипотермии на гемодинамику и жизнеспособность ишемизированной кишки // Вестник хирургии имени И.И. Грекова. 1987. № 3. С. 43–45.

[25] Urakov AL, Odiyankov YEG, Murav’yev MF, et al. Vliyaniye temperatury ishemizirovannoy konechnosti na techeniye i prognoz ishemicheskogo porazheniya. Krovoobrashcheniye. 1988;2:43–45. (In Russ.)

[26] Ураков А.Л., Одиянков Е.Г., Муравьев М.Ф., и др. Влияние температуры ишемизированной конечности на течение и прогноз ишемического поражения // Кровообращение. 1988. № 2. С. 43–45.

[27] Urakov AL, Odiyankov YeG, Odiyankov YuG, et al. Mestnaya gipotermiya v lechenii ostroy neprokhodimosti arteriy konechnosti. Vestnik khirurgii imeni I.I.Grekova. 1988;7:62–65. (In Russ.)

[28] Ураков А.Л., Одиянков Е.Г., Одиянков Ю.Г., и др. Местная гипотермия в лечении острой непроходимости артерий конечности // Вестник хирургии имени И.И. Грекова. 1988. № 7. С. 62–65.

[29] Murav’yev MF, Odiyankov YeG, Urakov AL, et al. Farmakokholodovaya terapiya pri tyazheloy khronicheskoy ishemii nizhnikh konechnostey. Khirurgiya. 1989;3:25–29. (In Russ.)

[30] Муравьев М.Ф., Одиянков Е.Г., Ураков А.Л., и др. Фармакохолодовая терапия при тяжелой хронической ишемии нижних конечностей // Хирургия. 1989. № 3. С. 25–29.

[31] Shabanov PD, Fisher EL, Urakov AL. Hydrogen peroxide formulations and methods of their use for blood oxygen saturation. Journal of Medical Pharmaceutical and Allied Science. 2022;11(6):5489–5493. DOI: 10.55522/jmpas.V11I6.4604

[32] Shabanov P.D., Fisher E.L., Urakov A.L. Hydrogen peroxide formulations and methods of their use for blood oxygen saturation // Journal of Medical Pharmaceutical and Allied Sciences. 2022. Vol. 11. No. 6. P. 5489–5493. DOI: 10.55522/jmpas.V11I6.4604

[33] Urakov A, Shabanov P, Lovtsova L. Development of new generation drugs by enriching them with gases. Journal of Pharmaceutical Research International. 2023;35(3):7–16. DOI: 10.9734/jpri/2023/v35i37315

[34] Urakov A., Shabanov P., Lovtsova L. Development of new generation drugs by enriching them with gases // Journal of Pharmaceutical Research International. 2023. Vol. 35. No. 3. P. 7–16. DOI: 10.9734/jpri/2023/v35i37315

[35] Urakov A, Urakova N, Sorokina Yu, et al. Targeted modification of physical-chemical properties of drugs as a universal way to transform “old” drugs into “new” drugs. In: Drug repurposing — advances, scopes and opportunities in drug discovery. Chapter 3. Ed. by M. Rudrapal. 2023. DOI: 10.5772/intechopen.110480

[36] Urakov A., Urakova N., Sorokina Y., et al. Targeted modification of physical-chemical properties of drugs as a universal way to transform “old” drugs into “new” drugs // Drug repurposing — advances, scopes and opportunities in drug discovery. Chapter 3. Ed. by M. Rudrapal. 2023. DOI: 10.5772/intechopen.110480

[37] Urakov A, Urakova N, Reshetnikov A, et al. Reprofiling hydrogen peroxide from antiseptics to pyolytics: a narrative overview of the history of inventions in Russia. Journal of Pharmaceutical Research International. 2023;35(6):37–48. DOI: 10.9734/jpri/2023/v35i67333

[38] Urakov A., Urakova N., Reshetnikov A., et al. Reprofiling hydrogen peroxide from antiseptics to pyolytics: a narrative overview of the history of inventions in Russia // Journal of Pharmaceutical Research International. 2023. Vol. 35, No. 6. P. 37–48. DOI: 10.9734/jpri/2023/v35i67333

[39] Urakov A, Shabanov P, Gurevich K, et al. Intrapulmonary use of hydrogen peroxide in respiratory obstruction: Initial results demonstrate the possibility of airway recanalization and blood reoxygenation through the lungs: an update. Journal of Pharmaceutical Research International. 2023;35(9):33–37. DOI: 10.9734/jpri/2023/v35i97348

[40] Urakov A., Shabanov P., Gurevich K., et al. Intrapulmonary use of hydrogen peroxide in respiratory obstruction: Initial results demonstrate the possibility of airway recanalization and blood reoxygenation through the lungs: an update // Journal of Pharmaceutical Research International. 2023. Vol. 35, No. 9. P. 33–37. DOI: 10.9734/jpri/2023/v35i97348

[41] Urakov AL, Urakova NA, Shubina ZV, et al. Hypertonic Activity of Injection Solutions Can Cause Post-injection Complications (Review). Drug development & registration. 2023;12(2):164–173. (In Russ.) DOI: 10.33380/2305-2066-2023-12-2-164-173

[42] Ураков А.Л., Уракова Н.А., Шубина З.В., и др. Гипертоническая активность растворов для инъекций может являться причиной постинъекционных осложнений // Разработка и регистрация лекарственных средств. 2023. Т. 12, № 2. С. 164–173. DOI: 10.33380/2305-2066-2023-12-2-164-173

[43] Urakov AL, Shabanov PD, Gurevich KG, et al. Supplementing traditional drug formulation with the “needed” gases opens the way for the development of a new generation of drugs. Psychopharmacology & biological narcology. 2023;14(1):5–14. (In Russ.) DOI: 10.17816/phbn321616

[44] Ураков А.Л., Шабанов П.Д., Гуревич К.Г., и др. Дополнение традиционной рецептуры лекарственных препаратов «нужными» газами открывает путь к разработке лекарств нового поколения // Психофармакология и биологическая наркология. 2023. Т. 14, № 1. С. 5–14. DOI: 10.17816/phbn321616

[45] Urakov AL, Urakova NA, Stolyarenko AP. How to turn an old medicine into a new medicine. Journal of Bio Innovation. 2020; 9(5):774–777. DOI: 10.46344/JBINO.2020.v09i05.13

[46] Urakov A.L., Urakova N.A., Stolyarenko A.P. How to turn an old medicine into a new medicine // Journal of Bio Innovation. 2020. Vol. 9, No. 5. P. 774–777. DOI: 10.46344/JBINO.2020.v09i05.13

[47] Urakov AL, Urakova NA, Kozlova TS. Lokal’naya toksichnost’ lekarstv kak pokazatel’ ikh veroyatnoy agressivnosti pri mestnom primenenii. Vestnik Ural’skoy meditsinskoy akademicheskoy nauki. 2011;1(33):105–108.

[48] Ураков А.Л., Уракова Н.А., Козлова Т.С. Локальная токсичность лекарств как показатель их вероятной агрессивности при местном применении // Вестник Уральской медицинской академической науки. 2011. Т. 1, № 33. С. 105–108.

[49] Viter VI, Urakov AL, Pozdeev AR, et al. Evaluation of post-injection complications in forensic medical practice. Sudebnaya ekspertiza. 2013;1(33):79–89. (In Russ.)

[50] Витер В.И., Ураков А.Л., Поздеев А.Р., и др. Оценка постинъекционных осложнений в судебно-медицинской практике // Судебная экспертиза. 2013. Т. 1, № 33. С. 79–89.

[51] Miroshnichenko II, Valdman EA, Kuz’min II. Old drugs, new indications (review). Drug development & registration. 2023;12(1):182–190. (In Russ.) DOI: 10.33380/2305-2066-2023-12-1-182-190

[52] Мирошниченко И.И., Вальдман Е.А., Кузьмин И.И. Новое предназначение старых лекарств (обзор) // Разработка и регистрация лекарственных средств. 2023. Т. 12, № 1. С. 182–190. DOI: 10.33380/2305-2066-2023-12-1-182-190

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