Intrapulmonary injections of warm alkaline hydrogen peroxide solutions in severe acute respiratory obstruction: history of discovery and experimental results

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Abstract

At the beginning of the 21st century, Professor Aleksandr Urakov and his colleagues from Russia discovered oxygen-producing antihypoxants and a method to alleviate tissue ischemia and/or hypoxia by injecting solutions of these agents directly into affected tissues. During the development of this research area, the team secured approximately 40 patents for related inventions. Oxygen-producing antihypoxants include warm alkaline hydrogen peroxide solutions (WAHPSs), which, upon injection into sputum, mucus, pus, blood, or other tissues, rapidly convert them into a soft oxygen foam. This occurs because many bodily tissues contain the enzyme catalase, which, in an alkaline environment under hyperthermic conditions, accelerates the decomposition of hydrogen peroxide into water and molecular oxygen by millions of times. Catalase-mediated cleavage of the H2O2 in 100 mL of a 3% hydrogen peroxide solution yields approximately 1.408 g of molecular oxygen, which, at standard atmospheric pressure, occupies a gaseous volume of about 1 L. Based on these findings, the researchers proposed intrapulmonary, endotracheal, or endobronchial administration of WAHPSs to rapidly oxygenate blood via the lungs in cases of severe acute respiratory obstruction due to asphyxia from sputum or blood. In experimental models of severe acute asphyxia induced by sputum or blood, a single intrapulmonary, endotracheal, or endobronchial injection of WAHPS transformed colloidal masses in the respiratory tract into soft white oxygen foam within 1–2 seconds, initiating blood oxygenation and fully resolving hypoxemia within 12 seconds. These theoretical and experimental results indicate that intrapulmonary, endotracheal, and endobronchial WAHPS injections could serve as an alternative to gaseous oxygen in mechanical ventilation or extracorporeal membrane oxygenation for treating patients with severe acute respiratory obstruction and hypoxemia.

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INTRODUCTION

The experience of fighting for the lives of patients with severe acute respiratory syndrome (SARS) caused by coronavirus 2 (SARS-CoV-2) has shown that hypoxemia, and not the coronavirus itself, poses a mortal danger to them [1–5]. Thanks to this, the researchers once again recalled that hypoxemia is a universal cause of the development of cerebral hypoxia and the biological death of patients in all critical conditions [6–8]. The fact is that in humans and warm-blooded animals, it is the brain cells that have the lowest resistance to lack of oxygen. Therefore, usually with hypoxemia, brain cells die first, and hypoxic damage to brain cells is a universal cause of biological death in humans, regardless of their age and health status [9–13]. That is why, in all critical conditions, all patients are immediately placed in the intensive care unit, where, to eliminate brain hypoxia, intensive care physicians around the world are trying to enrich the blood circulating in the general bloodstream with oxygen. To eliminate hypoxemia, oxygen gas is introduced everywhere into the lungs as part of respiratory gases. In this regard, molecular oxygen (oxygen gas) is the number one drug for maintaining the life of all patients in emergency departments, as well as for providing urgent self-help and mutual assistance to victims in all critical conditions [8, 14–16].

Unfortunately, oxygen is traditionally used all over the world to oxygenate blood through the lungs, but is not used for direct oxygenation of brain cells [8]. This is surprising, but despite the lack of oxygen in the blood and brain tissues, oxygen gas is still not injected directly into the blood inside the blood vessels of patients and is not injected into their brain tissue, even if there is a real threat of irreversible hypoxic damage to brain cells [17–20]. At the same time, traditional blood oxygenation through the lungs loses its effectiveness in case of respiratory obstruction. Extracorporeal membrane blood oxygenation (ECMO) was proposed instead of artificial ventilation of the lungs with oxygen gas for blood oxygenation in respiratory obstruction [21–24]. However, the ECMO procedure has a high risk and cost and low availability [25–27].

It is reported that at the beginning of the 21st century, a group of oxygen-producing antihypoxants was created in Russia, which are WAHPSs [6, 28–30]. It has been shown that when WAHPSs applied topically, such thick and viscous tissues as blood, pus, sputum, mucus, sulfur plug and meconium are urgently converted into a soft oxygen foam, since hydrogen peroxide can decompose very quickly into water and oxygen gas under the action of catalase, which is found in all this tissues [31–34]. It has been reported that the catalase cleavage of all H2O2 contained in 100 mL of a 3% hydrogen peroxide solution produces oxygen gas weighing 1.408 g and weighing about 1 L at normal atmospheric pressure [34–36].

In Russia, for the first time in the world, it was shown that intrapulmonary and endobronchial injections of WAHPSs can become an alternative to gaseous oxygen used by artificial lung ventilation (ALV) and ECMO in the fight for the lives of patients with severe hypoxemia [34, 37–42]. However, most researchers around the world have not paid attention to the discovery of this new possibility of oxygenation of blood through the lungs using intrapulmonary and endobronchial injections of WAHPSs [6, 43–50].

The study aimed to consider the possibilities of blood oxygen saturation through the lungs by intrapulmonary injection of warm alkaline hydrogen peroxide solutions in respiratory obstruction.

METHODOLOGY AND TERMINOLOGY

An unstructured review of scientific articles was conducted in the Yandex, Google, eLibrary, CyberLeninka, RSCI, Scopus, Web of Science, PubMed, MedLine, The Cochrane Library, EMBASE and Global Health databases using the search terms: medicinal solution, aerated solution, oxygenated solutions, injections, intrapulmonary injections, endotracheal injections, endobronchial injections, interstitial, lungs, oxygen, oxygen producer, oxygen content, oxygen tension, antihypoxants producing oxygen, antihypoxants, hydrogen peroxide, alkaline solution of hydrogen peroxide, antiseptics, detergents, sanitizers, pyolytics, mucolytics, hemolytics, expectorants, bleaching agents, heat, heating, warming medicine, temperature, local temperature, hyperthermia, local hyperthermia, medicines, pharmacological preparation, hypoxia, hypoxemia, lack of oxygen, ischemia and various combinations of the above keywords. All types of articles, dissertations, and descriptions of inventions in Russian and English were included. In addition, the information in the "References" section of the selected scientific articles was studied. The information contained in the description of inventions was searched using the following databases: FIIP (RF), RUPTO, USPTO, Google Patents, EAPATIS, Espacenet, PATENTSCOPE, PatSearch, and DWPI. In addition, analogues and prototypes indicated in the selected inventions were studied. No time limits were chosen for the research.

The structured approach proved impractical due to the wide scope of the review, which included both the results obtained before the advent of oxygen-producing antihypoxants and intrapulmonary injections of oxygenated solutions, and in the modern era, when monitoring the dynamics of blood oxygen saturation began to be widely used in laboratory, experimental studies and clinical trials.

Warnings and side effects of intrapulmonary injections

Despite experimental evidence that a single intrapulmonary injection of WAHPS urgently eliminates hypoxemia in respiratory obstruction, there is no direct clinical evidence for this yet. Laboratory and experimental studies have shown great prospects for the potential oxygen-producing activity of WAHPSs in their interaction with various biological tissues containing the enzyme catalase. The fact is that in an alkaline environment, catalase accelerates the process of splitting hydrogen peroxide into water and molecular oxygen by millions of times. Initially, such data were obtained in vitro studies using isolated portions of blood, pus, sputum, mucus, sulfur plugs, and meconium from patients. The condition of these biological objects was studied in numerous laboratory researches after a single injection of WAHPSs with different concentrations, pH and temperature (in the range from 0 to 45 °C). It was found that an increase in the concentration of H2O2 in solutions, heating, alkalinization and saturation of solutions with oxygen gas under excessive pressure increases their physical-chemical activity, providing them with the ability to dissolve, loosen and discolor biological masses. This physical-chemical activity is based on the ability to convert colloidal masses into fluffy white oxygen foam due to the rapid release of oxygen gas. It has been shown that the active release of oxygen gas forms many gas bubbles, which resembles the process of cold boiling, which not only loosens biological masses, but also increases their volume so intensively and greatly that under certain conditions it can explode them (Shabanov PD, et al., 2022; Urakov AL, et al., 2025; Osipov AN, et al., 2025).

To date, the pronounced antihypoxic activity of intrapulmonary injections of W#AHPSs has been convincingly confirmed in an experimental model of acute total asphyxia with artificial sputum and blood in mongrel rabbits and sheep. Due to the lack of clinical data, it is necessary to take into account the possible side effects that may occur due to the cessation of respiratory movements of the chest and ventilation of the lungs of patients due to hyperoxygenation, which is possible due to the filling of the airways with oxygen foam. Therefore, it is necessary to monitor the dynamics of the patient's condition, paying special attention to recording the dynamics of blood oxygen saturation. At the same time, short-term hyperoxygenation is less dangerous for patients than hypoxemia. With intrapulmonary injection of a WAHPSs, it should be assumed that the antihypoxic activity is determined by its dose, an increase in which can not only eliminate hypoxia, but also cause hyperoxia in case of overdose. In addition, injections of WAHPSs into the pleural cavity, into the heart cavity and into the blood vessels should be avoided, as this will cause the filling of these cavities with oxygen gas.

WARM ALKALINE HYDROGEN PEROXIDE SOLUTIONS (WAHPSS)

When providing emergency medical care to critically ill patients, inhalation of oxygen using ALV does not always eliminate hypoxemia and save their lives [51, 52]. Respiratory obstruction still remains one of the insurmountable obstacles to saturation of blood with oxygen gas through the lungs with ALV [35, 38]. ECMO, previously proposed for blood oxygenation instead of ALV, is able to eliminate hypoxemia in respiratory obstruction [53–56]. However, despite these advantages, ECMO has disadvantages. One of the disadvantages is that ECMO is not intended for use at the stage of providing self- and mutual assistance in rescuing victims in critical conditions requiring immediate oxygen saturation of the blood, such as drowning and hanging [57, 58]. In addition, ECMO is not intended for immediate oxygenation of blood in patients with sudden asphyxia. In particular, ECMO is not intended to save the lives of patients with sudden mechanical asphyxia, asphyxia with blood and food products [59–67].

As an alternative to ECMO to rescue victims in critical conditions at the stage of emergency care for suffocation caused by sudden respiratory obstruction, at the beginning of the 21st century, Russian researchers proposed an intrapulmonary injection of a WAHPSs [6, 28–43]. It has been shown that a warm alkaline solution of hydrogen peroxide, when interacting locally with colloidal biological tissues such as blood, pus, sputum, mucus, sulfur plug, plaque and meconium, immediately turns them into fluffy oxygen foam due to the instant catalase cleavage of hydrogen peroxide into water and molecular oxygen [68–72]. In this regard, Professor Aleksandr Urakov in Russia suggested that that hydrogen peroxide solutions can be converted into oxygen production antihypoxants, and injections of certain hydrogen peroxide solutions into tissues during their ischemia and hypoxia can eliminate the lack of oxygen in them and prevent hypoxic damage (RU 2538662, 10.01.2015; RU 2586292, 10.06.2016) [33–38].

History of the discovery of WAHPSs, physical-chemical repurposing of H2O2 from antiseptics to oxygen-producing pyolytics, mucolytics, hemolytics, and bleaches

Modernization of the standard 3–6% hydrogen peroxide solution in order to convert it from antiseptics to pyolytic, hemolytic, expectorant, bleaching and oxygen-producing antihypoxic agents began in Russia at the beginning of the 21st century. The initiator of this direction was Professor Aleksandr Urakov from Izhevsk. He suggested that the low biological activity and narrow scope of application of standard hydrogen peroxide solutions are due to their physical-chemical properties. Subsequent studies have confirmed this assumption. It turned out that changing the physical-chemical properties of hydrogen peroxide solutions really makes it possible to change their biological activity and expand the scope of application. In particular, it was shown that heating, alkalizing, and increasing the osmotic activity of hydrogen peroxide solutions with different concentrations made it possible to quickly and efficiently develop a new group of drugs that dissolve thick and viscous pus, which soon became known as antiseptic pyolytics [73, 74]. It was reported that the conversion of standard hydrogen peroxide solutions from antiseptics to pyolytics was achieved by replacing their acidic activity with alkaline activity within the pH range of 8.4, giving them isotonic activity in the range of 280–300 mosmol/L of water (or hypertonic activity exceeding 600 mosmol/L of water) while increasing the temperature to 42–45 °C.

Aleksandr Urakov and his students from Izhevsk have shown that standard solutions of hydrogen peroxide are used all over the world not with alkaline, but with acidic activity. The acid activity of hydrogen peroxide solutions was created specifically for the conservation of H2O2 and prolonging the shelf life of hydrogen peroxide solutions, since the splitting of H2O2 into H2O and O2 depends on the pH value and is therefore inhibited in an acidic environment (US 3801512A) [75]. In addition, it has been shown that the disadvantages of standard hydrogen peroxide solutions are their room temperature, which is more than 10 °C lower than normal human body temperature, and low osmotic activity, which approaches 0 mosmol/L of water [28, 30, 42, 74]. The fact is that low temperature reduces the biological activity of H2O2, since, according to the Arrhenius law, cooling by 10 °C reduces the rate of chemical reactions by an average of 2 times, and hypotonic activity of solutions is dangerous with a high probability of erythrocyte hemolysis during local interaction [31, 34, 42, 43, 74].

Initially, hydrogen peroxide solutions were purposefully upgraded to enhance their pyolytic and oxygenating activity when interacting with thick purulent masses, as this optimized the process of sanitation, tissue regeneration and accelerated healing in the treatment of chronic wounds [74, 76]. At the same time, it was found that the topical application of warm alkaline solutions of 3–6% hydrogen peroxide has a pronounced pyolytic, antiseptic, detergent, discoloring and oxygen-producing effects [6, 72, 73, 77–80]. Since, according to the developers, the goal of upgrading standard hydrogen peroxide solutions was to optimize the sanitation of chronic wounds covered with purulent masses, initially warm alkaline solutions of hydrogen peroxide were considered primarily as antiseptic pyolytics. Despite this, today this group of drugs is known by two names: pyolytics and WAHPSs [28, 30, 79].

The first patent for an invention using WAHPS was issued in Russia for a method of treating long-term non-healing wounds (RU 2187287) [81]. The essence of the invented treatment method consisted in daily course cleansing of chronic wounds from purulent masses by irrigating the wound surface with a solution of 3% hydrogen peroxide heated to a temperature of 37 °C. At the same time, in the interval between removing the old wound dressing and applying a new wound dressing, the wound was heated for up to 15 min using a Solux lamp until persistent hyperemia developed, but not exceeding the temperature of the wound surface 42 °C. Then a new wound dressing was applied to the wound with a hypertonic solution of 2–4% sodium chloride solution heated to a temperature of 42 °C, and a warming element was applied over the dressing, with which the temperature in the wound area was maintained at 37 °C throughout the period until the next change of the wound dressing.

A few years after that, a patent was issued for a method of treating pleural empyema (RU 2308894). The essence of this invention consists in injecting into the pleural cavity heated to a temperature of 42 °C alkaline solution of a surfactant drug, for example, a solution of 24% euphyllin, which had an alkaline activity in the pH range of pH 9.0–12.0 [82]. One year later, a method for the treatment of purulent peritonitis was invented using a warm carbonated antiseptic solution (RU 2336833). In this invention, it was proposed for the first time to saturate a hypertonic sodium chloride solution with carbon dioxide or other inert gas under excessive pressure and heat the solution to a temperature of 37 °C [83]. In parallel, patents were issued in Russia for a hypergassed and hyperosmotic antiseptic (RU 2331441) and a method of uterine lavage (RU 2327471). In this case, the hypergassed and hyperosmotic antiseptic agent was an aqueous antiseptic solution consisting of 2.7–3.3% hydrogen peroxide, 0.9–10.0% sodium chloride and carbon dioxide at an excess pressure of 0.2 atm [84]. In turn, a solution of 0.9% sodium chloride and 3% hydrogen peroxide, heated to a temperature of, was first proposed for washing the uterus 42–45 °C [85].

Then in 2009, in Russia, Aleksandr Urakov and his co-authors were granted a patent for an alkaline solution of hydrogen peroxide, which was designed to dilute thick and sticky pus (RU 2360685). This pyolytic was a solution of 2.7–3.3% hydrogen peroxide and 5.0–10.0% sodium bicarbonate [86]. At the same time, it was discovered that such an alkaline solution of hydrogen peroxide has a bleaching effect and can be used to whiten bloodstains on clothing (RU 2371532) [87].

In the following years, Russia continued to develop new pyolytic and hemolytic medicinal solutions containing hydrogen peroxide and/or sodium bicarbonate. Russia's priority in this area is indicated by the following invention patents:

  • A method for preventing thrombosis of vascular catheters by periodically filling them with a 4% sodium bicarbonate solution (RU 2387465) [88];
  • Method and drug for removing sulfur plug. In this invention, to eliminate hearing loss when the external auditory canal is blocked with a sulfur plug, it was proposed to inject a solution of 0.3–0.5% hydrogen peroxide and 1.7–2.3% sodium bicarbonate heated to 42 °C (RU 2468776) [89];
  • A remedy for fistula sanitation in infected pancreatic necrosis (RU 2455010). This preparation was an aqueous buffered hyperosmotic solution containing 0.9% sodium chloride, 0.142% sodium hydrophosphate and 0.120% sodium dihydrogen phosphate [90];
  • Multifunctional solution for epibulbar instillations (RU 2452478). In this invention, a solution of 0.55–1.0% hydrogen peroxide, 1.0–1.5% sodium bicarbonate, and 0.5–1.0% lidocaine hydrochloride was proposed as eye drops with antiseptic, anesthetic, and pyolytic activity [91].

After that, the physical-chemical conversion of hydrogen peroxide solutions was aimed at developing new detergents and bleaching agents. Over the next few years, researchers in Russia have managed to invent several new products that urgently dissolve and whiten plaque, food residues, dead tissues and cells of animal origin, as well as dried plant milk juice on the surface of soft and hard tissues of patients, clothing, medical and household items for hygienic cleaning and skin whitening. teeth, dentures, washing clothes, bedding, skin and nail care. These goals were achieved by developing various WAHPSs, some of which were additionally saturated with oxygen gas under excessive pressure [34, 43, 69–71, 92–96].

Russia's priority in developing new bleaches and detergents created as a result of the modernization of WAHPSs is proved by patents obtained by pharmacologists from Izhevsk for the invention of bleaches for bruises and bloodstains, which are heated to 42–45 °C solutions of 0.01–0.03% hydrogen peroxide and 1.7–1.8% sodium bicarbonate [97]:

  • Bruise bleacher (RU 2539380, 20.01.2015);
  • Bleaching agent (RU 2589682, 10.07.2016);
  • Method for skin discoloration in bruising area (RU 2586278, 10.06.2016);
  • Agent for intradermal bruise whitening (RU 2573382, 20.01.2016);
  • Method for skin discoloration in bruising area (RU 2582215, 20.04.2016);
  • Method for emergency bleaching and blood crust removal from skin in place оf squeezed out acne (RU 2631593, 25.09.2017);
  • Method for whitening of sore under nail (RU 2631592, 25.09.2017);
  • Method for whitening of bruise under eye (RU 2639283, 20.12.2017);
  • Means for intravital skin whitening near blue eyes (RU 2639485, 21.12.2017).

In the following years, new WAHPSs were developed in Russia, designed for emergency bleaching of bloodstains and plaque. To achieve these goals, the hydrogen peroxide content in WAHPSs was increased to 0.75–3%, and the sodium bicarbonate content was increased to 10% [69, 97]:

  • Bleaching opener of dried blood for wrapping bandages adhered to a wound (RU 2653465, 08.05.2018);
  • Method for blue nail treatment (RU 2641386, 17.01.2018);
  • Decolorant of blood (RU 2647371, 15.03.2018);
  • Bleaching cleanser of dentures (RU 2659952, 04.07.2018);
  • Method of emergency bleaching of skin hematoma under eye (RU 2679334, 07.02.2019);
  • Frictional toothpaste. It is a solution of 9.5–10% sodium bicarbonate and 0.5–1.5% hydrogen peroxide at a temperature of 25–26 °C, which additionally contains crystalline sodium bicarbonate in a ratio of 5/1 by weight (RU 2626669, 31.07.2017) [98];
  • Aerated mouthwash. This solution will include sodium chloride, sodium hydrophosphate, sodium dihydrogen phosphate, hydrogen peroxide, water and helium gas until an overpressure of 0.2 atm is created (RU 2635992, 17.11.2017) [99];
  • Bleaching cleanser of dentures. This is an aqueous solution heated to a temperature of 37–42 °C, which contains 2.0–10.0% sodium bicarbonate, 3 ± 0.3% hydrogen peroxide and oxygen gas at an excess pressure of 0.2 atm (RU 2659952, 04.07.2018) [100];
  • Method of using plaque removal solution with irrigation agent. In this method, the irrigator is filled heated to a temperature of 43–65 °C solution of 2.0–10.0% sodium bicarbonate, 2.7–3.3% hydrogen peroxide, which is additionally carbonated with argon at an excess pressure of 3–4 atm (RU 2723138, 09.06.2020) [101].

In addition to this group of medical bleaches, in the same years Alexander Urakov and his students from Izhevsk invented other, more effective, but dangerous detergents, bleaching and hygienic liquids, which are alkaline solutions of hydrogen peroxide:

  • Peeling agent for foot hyperkeratosis. The product is a solution of 3.0–5.0% potassium hydroxide, 0.5–20.0% hydrogen peroxide at pH 13.0–14.0, osmotic activity 350–560 mosmol/L of water, temperature 38–42 °C, which is saturated with oxygen gas at an excess pressure of 0.2 atm. The invention provides rapid softening of the keratinized layer of the epidermis in the area of dry calluses and corns, softening of excess dead nail plate in fungal nail damage, restoration of elasticity, smoothness, skin color, shape and color of the deformed nail plate (RU 2730451) [102];
  • Dandelion milky juice stains bleaching agent. bleach relates to household detergents, in particular to stain removers, and is intended for emergency dissolution, decolouration and removal of stains of thickened and darkened milky juice of dandelion and other rubber plants on white clothes. Agent is a liquid stain remover containing 2–4 parts of solution of 3% hydrogen peroxide and 0.1% of a detergent, 1 part of solution of 10% ammonia and 3 parts of nefras, consisting of equal amounts of white spirit and rubber solvent (RU 2765469) [103];
  • Glass washing liquid. The invented glass washing liquid is an aqueous solution of 0.06–0.5% hydrogen peroxide, 0.1% colorless detergent and 0.08% ammonia (RU 2763882) [104].

History of conversion of hydrogen peroxide into oxygen-producing antihypoxants in Russia

The facts are that in 2015, Professor Aleksandr Urakov from Izhevsk discovered the way to use WAHPSs as oxygen-producing antihypoxants. In particular, in 2015, he was the first in the world to receive a patent for alkaline isotonic solution of hydrogen peroxide, designed for injection into donated venous blood in order to saturate it with oxygen before infusion into the patient's body. The invented solution was an aqueous solution of 0.85% sodium chloride, 0.10% sodium bicarbonate and 0.05–0.29% hydrogen peroxide. This drug ensures the rapid conversion of venous blood into arterial blood due to the breakdown of hydrogen peroxide by catalase to water and gaseous oxygen and the absorption of oxygen by red blood cells (RU 2538662) [105]. In the same year, Aleksandr Urakov and his students patented a method for preserving live fish during transportation and storage. In this invention, it was first proposed to introduce an antihypoxant into fish water, which is a therapeutic dose of a 6% solution of hydrogen peroxide, since hydrogen peroxide replaces oxygen gas. The fact is that fish absorb hydrogen peroxide, which immediately decomposes under the action of the catalase enzyme into water and oxygen gas (RU 2563151) [106].

To date, Aleksandr Urakov has patented about 40 WAHPSs in Russia [43]. It has been reported that when WAHPSs interacts with pus, sputum, mucus and serous fluid of the respiratory tract, blood, blood clots, dried blood spots, bruises, tear stones, sulfur plugs, meconium, keratinized epithelium, plaque, spots left on the surface of tissues by crushed insects and thickened dandelion milky juice, WAHPSs quickly dissolve and colloidal biological tissues are discolored, turning them into a soft oxygen-saturated foam [6, 28–34, 40]. It has been established that when WAHPSs interact with thick and/or colloidal liquids containing the enzyme catalase (sputum, mucus, pus of the respiratory tract, blood, sulfur plugs, plaque, etc.), WAHPSs cause alkaline saponification of protein-lipid complexes in these biological masses, which leads to their dissolution. At the same time, catalase breaks down hydrogen peroxide into oxygen gas and water. The released oxygen forms gas bubbles in biological masses, forms a cold boiling process that destroys ("explodes") thick colloidal masses and turns them into a soft white oxygen foam. It has been shown that small doses of oxygen are involved in the conversion of carbohemoglobin into oxyhemoglobin, and large doses are involved in the oxidative discoloration of hemoglobin and its colored metabolites, which is accompanied by heat generation [31, 71, 107, 108]. The scheme of the transformation of pus, mucus, and blood into a fluffy oxygen foam after an injection of an alkaline hydrogen peroxide solution is shown in Fig. 1.

 

Fig. 1. Scheme of the transformation of pus, mucus, and blood into a soft oxygen foam after an injection of an alkaline hydrogen peroxide solution. Figure borrowed from doi: 10.4103/mgr.medgasres-d-24-00058. © Osipov A.N., et al. 2025. Distributed under a CC BY 4.0 license.

Рис. 1. Схема трансформации гноя, мокроты и крови в мягкую кислородную пену после инъекции щелочного раствора перекиси водорода. Рисунок заимствован из doi: 10.4103/mgr.medgasres-d-24-00058. © Осипов А.Н., и соавт. 2025. Распространяется на условиях лицензии CC BY 4.0.

 

The use of hydrogen peroxide solutions as antihypoxants is based on oxygen gas released during its catalase cleavage. In 2016, Aleksandr Urakov received the first two patents for solutions of oxygen-producing antihypoxants intended for injection into the tissues of patients with ischemia and for oral administration in hypoxia for the purpose of urgent oxygen delivery [31, 42, 109]. The first such invention was lympho-subsitute for local maintaining viability of organs and tissues in hypoxia and ischemia (RU 2586292). This antihypoxant included 0.88% sodium chloride, 0.06–0.1% glucose and 0.01–0.02% hydrogen peroxide, the rest bidistilled water for injections with pH 7.4, with osmotic activity 280 mosmol/L of water. It has been shown that this lymph substitute, injected into organs and tissues, improves the quality of interstitial fluid, provides cells with oxygen and glucose, and preserves cell viability in conditions of hypoxia and ischemia [110]. The second invention was a drinking beverage designed to increase resistance to hypoxia (RU 2604129). This drink is a solution of 0.3–0.5% hydrogen peroxide, which is saturated with oxygen gas at an excess pressure of 0.2 atm [111].

In 2017, Aleksandr Urakov received a patent for a means to increase human physical endurance (RU 2634271). The invention consists in the fact that drinking water includes 7% glucose, 3% hydrogen peroxide and oxygen gas until an overpressure of 0.2 atm is created. The invented drink, when ingested, is absorbed into the bloodstream, providing it with water, oxygen and glucose, has a detoxifying effect, prevents dehydration, hypoxia, hypoglycemia, promotes the release of carbon dioxide and lactic acid from the circulating blood into the stomach and intestines, provides the cells of the cerebral cortex and skeletal muscles with oxygen and glucose, increases physical activity, endurance and optimizes the conscious performance of intense physical work when the reserves of adaptation are depleted [112]. In the same year, 2017, Aleksandr Urakov and Inna Gotz received a patent for an energy drink saturated with oxygen at an excess pressure of 0.2 atm, containing 7% glucose, 0.7% ethyl alcohol, 0.3–0.5% hydrogen peroxide, and citric acid — up to a pH of 4.0 ± 0.5 (RU 2639493). This drink was invented for children who are in a state of pulmonary, cardiac, and digestive insufficiency with deafened consciousness [113].

In 2020, a group of researchers from Izhevsk and Moscow, led by Aleksandr Urakov, received a patent for the use of WAHPSs in the form of an aerosol with microparticle sizes in the range of 0.5–2 µm for inhalation at a temperature of 41–55 °C (RU 2735502). It has been reported that WAHPSs aerosol for inhalation contains 0.3–0.5% hydrogen peroxide and 1.2% sodium bicarbonate. It has been shown that at the prehospital stage of treatment of a severe asthma attack in combination with purulent obstructive bronchitis, inhalation of the developed WAHPS aerosol provides an urgent expectorant and antihypoxic effect with a single application [31, 72, 78, 114].

Shortly after that, in 2021, Aleksandr Urakov received a patent for the invention of another aerosol. This aerosol contains WAHPS comprising 0.3–0.5% peroxide and 2–10% sodium bicarbonate at a temperature of 37–55 °C (RU 2742505). Inhalation of this aerosol optimizes artificial ventilation of the lungs in case of airway obstruction by thick sputum, mucus and pus at the terminal stage of nonspecific bilateral pneumonia in COVID-19. It has been reported that the developed inhalation drug WAHPS improves airway permeability for respiratory gases, increases blood oxygen saturation through the lungs during mechanical ventilation, and eliminates hypoxemia in patients in intensive care [115].

Intrapulmonary WAHPSs injections in experimental models of respiratory obstruction: chronology of invention development and investigation of the mechanism of action of intrapulmonary WAHPSs

In 2021, the Russian Journal of Biomechanics and Medicinski Casopis published the first articles on intrapulmonary injections of WAHPSs as a real possibility of urgent replacement of sputum and mucus in the respiratory tract with oxygen gas and on oxygen saturation of the blood through the lungs in respiratory obstruction [38, 39]. It was shown that the first intrapulmonary injections of warm alkaline solutions of hydrogen peroxide for sputum asphyxiation were performed in Izhevsk in 2020 under experimental conditions. Several series of experiments were conducted on live mongrel rabbits (in vivo) and on their isolated lungs (in vitro). In both cases, models of acute respiratory obstruction were created by subtotal filling of the airways with warm artificial sputum containing the enzyme catalase (RU 2748999) [116, 117]. The screening scheme for potential pyolytics and antihypoxants in the asphyxia model on isolated lungs is shown in Fig. 2.

 

Fig. 2. Scheme for screening potential pyolytics and antihypoxants in an isolated lung model of asphyxia. Figure borrowed from doi: 10.34172/bi.2022.23877. © Urakov A.L., et al. 2022. Distributed under a CC BY 4.0 license.

Рис. 2. Схема скрининга потенциальных пиолитиков и антигипоксантов в модели асфиксии на изолированных лёгких. Рисунок заимствован из doi: 10.34172/bi.2022.23877. © Ураков А.Л., и соавт. 2025. Распространяется на условиях лицензии CC BY 4.0.

 

It was reported that in vitro experiments on isolated rabbit lungs involved injecting 1 mL of an oxygen-producing antihypoxant solution into lung tissue when sputum filled their airways. A solution of 3% hydrogen peroxide and 1.8% sodium bicarbonate at a temperature of 42 °C was used as an oxygen-producing antihypoxant. It was shown that 1 s after the intrapulmonary injection, fluffy white oxygen foam was found in the trachea, which after 1.5 s began to erupt from the open end outward with a loud hissing and splashing of foam pieces. The main stages of the experiment on isolated lungs are shown in Fig. 3.

 

Fig. 3. Isolated rabbit lung. Isolated rabbit lung before (1), after endotracheal injection of 40 mL of artificial sputum (2), and 1 second after intrapulmonary injection of 2 mL of a warm alkaline hydrogen peroxide solution (3). The blue arrow indicates white foam. Figure borrowed from doi: 10.4103/mgr.MEDGASRES-D-25-00027. © Urakova A.L., et al. 2025. Distributed under a CC BY 4.0 license.

Рис. 3. Изолированное легкое кролика до (1), после эндотрахеального введения 40 мл искусственной мокроты (2) и через 1 секунду после внутрилёгочной инъекции 2 мл тёплого щелочного раствора перекиси водорода (3). Синяя стрелка указывает на пену белого цвета. Рисунок заимствован из doi: 10.4103/mgr.MEDGASRES-D-25-00027. © Уракова А.Л., и соавт. 2025. Распространяется на условиях лицензии CC BY 4.0.

 

Additionally, it was reported that in vivo, acute artificial sputum asphyxia and hypoxemia were created in a live mongrel rabbit. For asphyxiation, 20 mL of artificial sputum was injected into the trachea, after which the dynamics of blood oxygenation was recorded and it was shown that after 3 min the indicator decreased from 95 to 40%. At this point in time, a single injection of 1 mL of a solution of 3% hydrogen peroxide and 1.8% sodium bicarbonate was performed at a temperature of 37 °C into the tissue of the right lung. The injection was performed between the 7th and 8th ribs on the right in the projection area of the line located in the middle of the distance between the spine and the posterior axillary line. It was shown that after 1, 3, and 8 s after intrapulmonary injection, the blood oxygenation index was (respectively) 46, 50, and 79%, and after 12 s, hypoxemia was eliminated, and the rabbit remained alive [38].

The results confirmed the assumption that in conditions of sputum asphyxiation, a single intrapulmonary injection of a warm alkaline hydrogen peroxide solution allows sputum to be immediately converted into oxygen foam inside the respiratory tract. In addition, the results showed the possibility of urgent filling of the respiratory tract with oxygen gas in the composition of oxygen foam, which ensures the elimination of hypoxemia by saturating the blood with oxygen through the lungs. These data allowed the team of Professor Aleksandr Urakov to develop a "Method of lung oxygenation in COVID-19" (RU application No. 2021102618) [118]. The essence of the method consists in a single intrapulmonary injection of 1 ml of a solution of 3% hydrogen peroxide and 1.8% sodium bicarbonate at a temperature of 37–44 °C.

The first oral report on the discovery of intrapulmonary WAHPSs was also made in 2021. It happened at the 1st "International conference on emerging global trends in agricultural, biological and pharmaceutical sciences" (on June 12, 2021 in India). At this scientific conference, Professor Aleksandr Urakov gave a plenary lecture entitled: "COVID-19: Mucus, pus and sputum with streaks of blood as a cause of airway obstruction and pus solvent solution as a drug for urgent lung reoxygenation, blood oxygenation and elimination of hypoxia in atypical pneumonia". In this lecture, an alkaline hydrogen peroxide solution was first proposed to save the lives of patients with severe acute respiratory syndrome (SARS) in COVID-19.

Then on July 7, 2022 in Geneva, Professor Aleksandr Urakov participated in the Virtual Summit on Healthcare & Patient Safety "Emerging Prospects on Healthcare and Patient Safety". At this summit, he gave a lecture entitled "COVID-19: Intrapulmonary us of alkaline hydrogen peroxide solution as an alternative to ECMO". In this lecture, he was the first to report on the possibility of using hydrogen peroxide solution not only for inhalation as an aerosol, but also as an intrapulmonary injection. It was reported that until 2021, intrapulmonary injections were absent from the well-known list of injections of drug solutions. The fact is that previously intrapulmonary WAHPSs was reported only as expectorant drugs injected into the respiratory tract in the form of aerosols by inhalation during an attack of bronchial asthma and/or purulent bronchitis [78, 114, 115, 119].

In 2023, new reports appeared confirming that WAHPSs can be attributed to inhaled and intrapulmonary injected as a oxygen producing expectorants, mucolytics, pyolytics, hemolytics, bleaches and antihypoxants suitable for urgent replacement of sputum, mucus, pus, blood, serous fluid in the respiratory tract with oxygen gas [32, 38, 42, 78]. In addition, in 2023, a team led by Professor Aleksandr Urakov received a patent for a new original drug designed for intrapulmonary injection in severe acute respiratory obstruction. This preparation is a warm solution of 4.5% hydrogen peroxide and 1.8% sodium bicarbonate, which was named "Warm alkaline solution of hydrogen peroxide for intrapulmonary injection" (RU 2807851) [120]. The developed drug is the world's first medicinal solution that contains oxygen gas at an excess pressure of 0.2 atm. and before intrapulmonary injection, it is heated to a temperature of 42 °C.

In 2024, the inventors upgraded this drug and received a patent for a new drug intended for intrapulmonary injection in severe acute respiratory obstruction — "Oxygenated warm alkaline hydrogen peroxide solution for intrapulmonary injection" (RU 2831821) [121]. This drug is a solution of 4.5% hydrogen peroxide and 1.8% sodium bicarbonate saturated with oxygen gas at an excess pressure of 0.3 atm, which is heated to a temperature of 45 °C before intrapulmonary injection. It was reported that in an experimental model of severe acute asphyxia in live mongrel rabbits, 3 min after filling the respiratory tract with artificial sputum, the blood oxygenation index in animals decreased to an average of 81 ± 4.3% (n = 5, p < 0.05). At this point, intrapulmonary injections of 0.5 mL of the invented drug were performed in each lobe of the lungs. The procedure of intrapulmonary injections was completed in an average of 9 ± 0.5 s (n = 5, p < 0.05). It was found that injection into the first lobe of the lung caused the immediate transformation of sputum into oxygen-saturated foam inside the respiratory tract. Foam filled the trachea and was released from the upper respiratory tract to the outside 1–2 s after the first intrapulmonary injection. It turned out that the blood oxygenation index began to increase within a second after the first injection and reached normal values on average 8 ± 0.5 s (n = 5, p < 0.05) after the start of the injection series, namely, during intrapulmonary injection into the 5th lobe of the lungs. After the experiment was completed, the value of blood oxygenation in rabbits remained at 95%.

In 2025, research in this area was continued in Russia. New reports have emerged about the possibility of urgent elimination of severe acute respiratory obstruction and ensuring immediate oxygen saturation of the blood through the lungs by intrapulmonary injection of warm alkaline solutions of hydrogen peroxide [33–35, 122]. Thus, Professor Aleksandr Urakov and Professor Peter Shabanov received patents for 2 inventions dedicated to the emergency elimination of asphyxia by injecting warm alkaline solutions of hydrogen peroxide:

  • Method of endobronchial injection of drug for emergency elimination of asphyxia (RU 2833321) [123];
  • Alkaline solution of hydrogen peroxide and method of application there of for elimination of blood asphyxia (RU 2840645) [124].

Finally, in mid-2025, a team led by Aleksandr Urakov received a patent for "Method for simulating induced asphyxia for screening antihypoxic drugs for local administration and pulmonary expansion" (RU 2843475) [125]. It follows that Russia has developed a new original method for modeling artificial asphyxia, which can be used to search for and develop new medicines capable of inflating the lungs (increasing their volume).

CONCLUSION

Professor Aleksandr Urakov and colleagues from Russia have pioneered a novel class of antihypoxants, termed oxygen-producing antihypoxants, along with an innovative method for their administration in cases of severe acute respiratory obstruction to achieve rapid blood oxygenation. These agents are based on warm alkaline hydrogen peroxide solutions (WAHPSs), which are introduced via direct injections into oxygen-deprived tissues. Over the course of this research, the team obtained approximately 40 patents for related inventions. Injections of WAHPSs into sputum, mucus, pus, blood, or other tissues rapidly convert them into a soft oxygen foam. This transformation is facilitated by the enzyme catalase, present in many bodily tissues, which accelerates the decomposition of hydrogen peroxide into water and molecular oxygen by orders of magnitude in alkaline and hyperthermic conditions. Theoretical calculations indicate that catalase-mediated cleavage of the H2O2 in 100 mL of a 3% hydrogen peroxide solution generates approximately 1.408 g of molecular oxygen, occupying a gaseous volume of about 1 L at standard atmospheric pressure.

Building on these insights, the researchers proposed intrapulmonary, endotracheal, or endobronchial injection of WAHPSs to enable urgent pulmonary blood oxygenation in severe acute respiratory obstruction resulting from asphyxia due to sputum or blood accumulation. This hypothesis was validated through animal experiments modeling severe acute asphyxia induced by sputum or blood. Results demonstrated that a single intrapulmonary, endotracheal, or endobronchial WAHPS injection transforms colloidal masses in the respiratory tract into fluffy white oxygen foam within 1–2 s, thereby initiating blood oxygenation and fully resolving hypoxemia within 12 s.

The theoretical and experimental findings substantiate that intrapulmonary, endotracheal, and endobronchial WAHPS injections may offer a viable alternative to gaseous oxygen in mechanical ventilation or extracorporeal membrane oxygenation for managing patients with severe acute respiratory obstruction and hypoxemia. Furthermore, intrapulmonary WAHPS injection holds potential as the foundation for novel first-aid protocols in emergency settings.

ADDITIONAL INFO

Author contributions: A.L. Urakov: conceptualization, investigation, formal analysis, writing — original draft; O.N. Ergashev: investigation, writing — review & editing; V.O. Olaiya: investigation, formal analysis; N.A. Urakova: investigation; P.D. Shabanov: conceptualization, writing — review & editing. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding sources: This research was part of State Assignment FGWG-2025-0020 "Search for molecular targets for pharmacological intervention in addictive and neuroendocrine disorders aimed at creating new pharmacologically active substances acting on central nervous system (CNS) receptors" of the Ministry of Science and Higher Education of Russia.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: This work used images published earlier: "The scheme of the transformation of pus, mucus, and blood into a soft oxygen foam after an injection of an alkaline hydrogen peroxide solution" in Fig. 1 [doi: 10.4103/mgr.medgasres-d-24-00058]; Screening scheme of potential pyolytics and antihypoxants in an isolated lung model of asphyxia in Fig. 2 [doi: 10.34172/bi.2022.23877]; Isolated rabbit lung in Fig. 3 [doi: 10.4103/mgr.MEDGASRES-D-25-00027] (distributed under a CC-BY 4.0 license).

Data availability statement: All data obtained in this study are available in the article.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer-review: This article was submitted unsolicited and reviewed following the standard procedure. The peer-review process involved one external reviewer, a member of the Editorial Council, and the in-house science editor.

Disclaimer: This article is published as submitted by the authors. The authors are solely responsible for the content and style of the manuscript.

ДОПОЛНИТЕЛЬНАЯ ИНФОРМАЦИЯ

Вклад авторов. А.Л. Ураков — определение концепции, проведения исследования, анализ данных, написание черновика рукописи; О.Н. Эргашев – проведение исследования, пересмотр и редактирование рукописи; В.О. Олайа — проведение исследования, анализ данных; Н.А. Уракова — проведение исследования, П.Д. Шабанов — определение концепции, пересмотр и редактирование рукописи. Все авторы одобрили рукопись (версию для публикации), а также согласились нести ответственность за все аспекты настоящей работы, гарантируя надлежащее рассмотрение и решение вопросов, связанных с точностью и добросовестностью любой её части.

Источники финансирования. Исследование выполнено в рамках государственного задания Минобрнауки России FGWG-2025-0020 "Поиск молекулярных мишеней для фармакологического воздействия при аддиктивных и нейроэндокринных нарушениях с целью создания новых фармакологически активных веществ, действующих на рецепторы ЦНС".

Раскрытие интересов. Авторы заявляют об отсутствии отношений, деятельности и интересов за последние три года, связанных с третьими лицами (коммерческими и некоммерческими организациями), интересы которых могут быть затронуты содержанием статьи.

Оригинальность. При создании настоящей работы использованы изображения: схема трансформации гноя, мокроты и крови в мягкую кислородную пену после инъекции щелочного раствора перекиси водорода на рис. 1, заимствовано из работы doi: 10.4103/mgr.medgasres-d-24-00058; схема скрининга потенциальных пиолитиков и антигипоксантов в модели асфиксии на изолированных лёгких на рис. 2, заимствовано из работы doi: 10.34172/bi.2022.23877; изолированное лёгкое кролика на рис. 3, заимствовано из работы doi: 10.4103/mgr.MEDGASRES-D-25-00027. Распространяется на условиях лицензии CC-BY 4.0.

Доступ к данным. Все данные, полученные в настоящем исследовании, представлены в статье.

Генеративный искусственный интеллект. При создании статьи технологии генеративного искусственного интеллекта не использовали.

Рассмотрение и рецензирование. Настоящая работа подана в журнал в инициативном порядке и рассмотрена по обычной процедуре. В рецензировании участвовали один внешний рецензент, член редакционного совета и научный редактор издания.

Дисклеймер. Эта статья публикуется в том виде, в каком она была представлена авторами. Авторы несут полную ответственность за содержание и стиль рукописи.

×

About the authors

Natalya A. Urakova

Institute of Experimental Medicine; Izhevsk State Medical Academy

Author for correspondence.
Email: urakovanatal@mail.ru
ORCID iD: 0000-0002-4233-9550
SPIN-code: 4858-1896

Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Saint Petersburg; Izhevsk

Oleg N. Ergashev

Institute of Experimental Medicine

Email: ergashew@mail.ru
ORCID iD: 0009-0003-5188-8900
SPIN-code: 2970-2672

Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

Aleksandr L. Urakov

Izhevsk State Medical Academy

Email: alurakov@bk.ru
ORCID iD: 0000-0002-9829-9463
SPIN-code: 1613-9660

Dr. Sci. (Medicine), Professor

Russian Federation, Izhevsk

Victor O. Olaiya

Izhevsk State Medical Academy

Email: olamummyvicky@gmail.com
ORCID iD: 0009-0000-0746-8552
Russian Federation, Izhevsk

Petr D. Shabanov

Institute of Experimental Medicine

Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477

Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

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