KR20230019105A - Aqueous antimicrobial compositions useful as therapeutic substances - Google Patents

Abstract

Provided herein are therapeutic substances active against SARS-CoV 2 and other microbial pathogens and methods of administering the same.

Description

Aqueous antimicrobial compositions useful as therapeutic substances

This application is filed on May 1, 2020, pending U.S. Provisional Application Serial No. 63/019,258, filed on February 1, 2021, and currently pending U.S. Provisional Application Serial No. 63/144,305, and filed on December 4, 2020 claims the benefit of priority to pending US Provisional Application Serial No. 63,121,856, filed on , the contents of which are incorporated herein by reference in their entirety.

The present disclosure relates to substances that are active against one or more microorganisms. More specifically, the present disclosure relates to aqueous materials that are active against microorganisms such as bacterial, viral or fungal microorganisms. Such microorganisms may include, but are not limited to, viruses such as SARS-CoV-2.

The need to identify and use antimicrobial compounds for use in reducing or eliminating infecting microorganisms cannot be underestimated. Such various types of microorganisms can cause infectious diseases that are a health, safety and well-being problem for people of all ages. Various viral and/or bacterial and/or fungal pathogens can easily spread through populations and infect large numbers of people. This is particularly problematic when a large number of individuals within an affected population lack natural or acquired immunity to a given pathogen.

The need for effective therapeutic substances and methods of treatment, particularly those capable of addressing, slowing or reducing the pathogenic burden of an individual in order to increase recovery or achieve a restorative effect, cannot be overstated. Similarly, cleaning and disinfecting surfaces, including but not limited to hard surfaces, can be a significant contributor to slowing the spread of infectious diseases. The need for compositions and materials that can be active against pathogens found on surfaces is therefore also critical.

For example, in certain circumstances the pathogen may be SARS-CoV-2. Severe acute respiratory coronavirus 2 [SARS-CoV-2; Coronavirus disease 2019 (COVID-19) caused by infection [also known as 2019 novel coronavirus (2019-nCoV)] occurred in Wuhan, China in December 2019 and resulted in a mortality rate of approximately 3%. Although this mortality rate is much higher than that of influenza (approximately 0.05%), influenza-related hospitalizations and deaths in the United States are nonetheless approximately 280,000 and 16,000, respectively, due to the much higher prevalence. COVID-19 has spread to all six major continents. To date, there is no known approved treatment or prevention for COVID-19. And in the case of SARS-CoV-2 viral infection, effective post-infection treatment is urgently needed to minimize both short- and long-term clinical consequences.

It would be desirable to provide a formulation or formulations that can be active against one or more pathogens in situ in a patient to reduce or eliminate one or more respiratory infection symptoms and/or pathogens causing infection. It would also be desirable to provide a method of treating a patient who tests positive for an infection or pathogen caused by one or more pathogens as present in or on tissue present in the respiratory tract. It would also be desirable to provide therapeutic compositions and methods capable of supporting tissue regeneration and healing in certain circumstances.

Disclosed herein are compositions that exhibit antimicrobial activity against at least one pathogen selected from the group comprising bacteria, viruses, fungi, or mixtures thereof, including compounds having the formula:

In the above formula, x is an odd integer of 3 or greater;

y is an integer from 1 to 20;

Z is either a monoatomic ion from groups 14 and 17 with a charge value of -1 to -3 or a polyatomic ion with a charge value of -1 to -3.

Also disclosed herein are therapeutic substance compositions and procedures that may be effective in treating upper and/or lower respiratory conditions triggered by viral and/or bacterial infection. More specifically, the disclosed therapeutic substance compositions and procedures may be used upon the onset of acute symptoms associated with infection by one or more viruses and/or bacteria. Also disclosed herein are compositions comprising one or more inorganic molecules that provide an associated therapeutic composition having a pH of less than 7. In certain embodiments, the composition may include at least one inorganic acid material. In certain embodiments, the composition may include at least one buffering ion such as calcium.

In addition, a volume of concentrated inorganic acid in liquid form having a molar concentration of at least 7, a density of 22 ° to 70 ° Baume and a specific gravity of 1.18 to 1.93 is contacted with an inorganic hydroxide present in a sufficient volume in the reaction vessel to form a precipitate or suspended solid. , producing a solid material present in the resulting composition as at least one of a colloidal suspension; and a product produced by a process comprising removing the solid material from the resulting liquid material, wherein the produced material is a viscous material having a molar concentration of 200 to 150 M. The therapeutic substance also includes water. The pH of the therapeutic substance may be less than 7, in certain embodiments less than 5, and in certain embodiments less than 3.

In certain embodiments, a therapeutic composition may include at least one compound having the formula:

In the above formula, x is an odd integer of 3 or greater;

y is an integer from 1 to 20;

Z is a polyatomic ion or a monoatomic ion;

If desired or necessary, component Z is either a monoatomic ion from groups 14 to 17 with a charge value of -1 to -3 or a polyatomic ion with a charge value of -1 to -3, and x is an integer from 3 to 11. And, y is an integer from 1 to 10.

Also disclosed is a method of treating a microbiological pathogen comprising introducing a composition as disclosed herein into contact with epithelial tissue during a contact interval, wherein the contact comprises at least one microbiological pathogen associated with human epithelial tissue. cause a decrease in In certain embodiments, the composition may be dispensed as a vaporized or atomized fluid via a suitable engineered device. In certain embodiments, a composition as disclosed herein can be administered by inhaling an amount of the composition as disclosed present in a vaporized carrier material over a suitable dosing interval. In certain embodiments, the therapeutic substance present in the composition may be present in a suitable carrier at a concentration greater than 0.1% by volume. Administration of one or more doses of the composition over a defined dose interval may reduce viral titers in the patient's respiratory system. Viruses that may respond to such treatment include SARS-CoV-2. Administration of one or more doses of a composition as disclosed herein over a defined dose interval may accelerate the reversal of virus-induced damage to respiratory tissue.

In addition, a volume of concentrated inorganic acid in liquid form having a molar concentration of at least 7, a density of 22 ° to 70 ° Baume and a specific gravity of 1.18 to 1.93 is contacted with an inorganic hydroxide present in a sufficient volume in the reaction vessel to form a precipitate or suspended solid. , producing a solid material present in the resulting composition as at least one of a colloidal suspension; and removing a solid material from the resulting liquid material, wherein the resulting material is a viscous material having a molar concentration of 200 to 150 M; The composition is used as a therapeutic agent against bacteria, viruses of fungal infections, especially infections wholly or partially present in the respiratory tract.

Various features, advantages and other uses of the device will become more apparent upon reference to the following detailed description and drawings.
1 shows dilute sulfuric acid (A) containing 400 ppm CaSO ₄ , dilute sulfuric acid (B), an embodiment as disclosed herein prepared according to the process outlined in Example I (C), and reverse osmosis water (Reverse Osmosis). Mass spectrum collected in positive ionization mode for Osmosis Water (D).
2 shows dilute sulfuric acid (A) containing 400 ppm CaSO ₄ , dilute sulfuric acid (B), and an embodiment as disclosed herein prepared according to the process outlined in Example I (C), and reverse osmosis water ( Mass spectrum collected in negative ionization mode for D).

Disclosed herein are compositions and methods for treating materials and media contaminated with pathogens such as SARS-CoV-2. Also disclosed herein are compositions and treatment regimens that can be used to treat and treat patients exhibiting symptoms associated with viral infections caused by coronaviruses, including but not limited to SARS-CoV-2. Such viruses include orthocoronaviruses ( Orthocoronavirinae ) subfamily Coronaviridea (eg, beta coronaviruses such as SARS-CoV, SARS-CoV-2, MERS-CoV) may be absent.

Severe acute respiratory coronavirus 2 [SARS-CoV-2; Coronavirus disease 2019 (COVID-19), also known as 2019 novel coronavirus (2019-nCoV)], caused an outbreak in Wuhan, China in December 2019, resulting in a mortality rate of approximately 3%. Although this mortality rate is much higher than that of influenza (approximately 0.05%), influenza-related hospitalizations and deaths in the United States are nonetheless approximately 280,000 and 16,000, respectively, due to the much higher prevalence. COVID-19 has spread to all six major populated continents and is now a pandemic.

SARS-CoV-2 infection can lead to potentially lifelong or fatal consequences. The virus infects respiratory cells by targeting the receptor angiotensin converting enzyme (ACE). The onset of symptoms after exposure is about 4 days, and the rapid progression often leads to hospitalization within 1 to 4 days thereafter.

Common symptoms include fever, myalgia, headache, diarrhea, shortness of breath, and cough with sputum and possibly hemoptysis. In more severely affected patients, the resting respiratory rate may exceed 30 breaths per minute, C-reactive protein (CRP) levels may exceed 30 mg/L (normal values less than 3 mg/L), and blood Oxygen saturation can drop below 93% [11]. A computed tomography (CT) scan may show a rapidly developing subpleural ground-glass opacity (GGO) with potential development of fibrosis. A poor prognosis is also associated with abnormal clotting characteristics.

Early in this pandemic, there was no known approved treatment or prevention for COVID-19. And in the case of SARS-CoV-2 viral infection, while several have been proposed and made available in the months since, additional preventive measures and/or effective post-infection treatment are urgently needed to minimize both short- and long-term clinical consequences. do.

Also disclosed herein are compositions useful for combating infection by one or more other microbial pathogens. Non-limiting examples of such other microbiological pathogens include pathogens such as those in the Paramyxoviridae (eg, measles mobilivirus), Herpesviridae (eg, varicella zoster virus); Mycobacteriaceae (eg, Mycobacterium tuberculosis); Orthomyxoviridae (eg, influenzavirus type A, influenzavirus type B); Picornaviridae (eg, enterovirus, poliovirus, coxsackie type A virus, coxsackie type B virus, etc.); Caliciviridae (eg, norovirus); Adenoviridae ( Adenoviridae ) etc., Staphylococcaceae (eg, Staphylococcus aureus such as methicillin-resistant Staphylococcus aureus); Enterococcaceae (including vancomycin-resistant enterococci), Streptococcaceae (including streptococci ) at least one of the Gram-positive species such as Clostridioides difficile, Listeria, Corynebacterium, and the like.

In the case of SARS-CoV-2, the coronavirus belongs to the subfamily Orthocoronavirus, family Coronaviridae, Nidoviales . It constitutes the order, and the Riboviria family. They are enveloped viruses with positive sense single-stranded RNA genomes and helical symmetric nucleocapsids. The genome size of coronavirus is one of the largest among RNA viruses. They have a characteristic club-shaped spike protruding from their surface.

The present disclosure is directed to bronchial tissue, alveolar tissue, esophagus of individuals exhibiting bacterial, viral, or fungal infection such that vaporized or aerosolized substances as disclosed herein having a pH of less than 7 are associated with living tissue, eg, respiratory tissue. When introduced into contact with respiratory tissue, such as mammalian lung tissue, including but not limited to tissue, sinus tissue, and the like, experience a reduction in one or more symptoms, including but not limited to congestion, tissue inflammation, and the like. Based in part on findings. It has also been found that administration of vaporized or nebulized substances as disclosed herein can reduce the microbial pathogen load associated with the tissue in question. Also disclosed is a method of treating an infection in a subject comprising introducing an acidified vaporized composition into contact with lung tissue.

Also disclosed is a method of treating an infection caused in whole or in part by one of the aforementioned microbiological pathogens, which may comprise contacting at least one lung tissue region of a subject with a composition comprising a therapeutic substance. . In certain embodiments, the administered composition may have a pH of less than 7. The composition is selected from the group consisting of hydrochloric acid, nitric acid, phosphoric acid, chloric acid, perchloric acid, chromic acid, sulfuric acid, permanganic acid, hydrocyanic acid, hydrobromic acid, hydrobromic acid, hydrofluoric acid, iodic acid, fluoroboric acid, fluorosilicic acid, fluorotitanic acid and mixtures thereof. Selected dilute acids may be included. In certain embodiments, the composition may include sulfuric acid.

If desired or necessary, the therapeutic material may also contain 100 to 1000 ppm inorganic ions selected from the group consisting of calcium, magnesium and mixtures thereof. In certain embodiments, the concentration of inorganic ions is 100 to 900 ppm; 100 to 800 ppm; 100 to 700 ppm; 100 to 600 ppm; 100 to 500 ppm; 100 to 400 ppm; 100 to 300 ppm; 200 to 900 ppm; 200 to 800 ppm; 200 to 700 ppm; 200 to 600 ppm; 200 to 500 ppm; 200 to 400 ppm; 200 to 300 ppm; 300 to 900 ppm; 300 to 800 ppm; 300 to 700 ppm; 300 to 600 ppm; 300 to 500 ppm; 300 to 400 ppm.

In certain embodiments, the composition comprises dissociated sulfuric acid molecules and at least one inorganic buffering ion, such as calcium, and has a measured pH of less than 7; less than 6; less than 5; less than 4; less than 3; less than 2; is less than 1

In certain embodiments, a therapeutic substance comprising sulfuric acid and calcium ions may be produced by a process comprising the steps of:

In a reaction vessel, a volume of concentrated mineral acid in liquid form having a molar concentration of at least 7, a density of 22° to 70° Baume and a specific gravity of 1.18 to 1.93 is brought into contact with an inorganic hydroxide present in sufficient volume to form a precipitate, suspended solid, or colloid. producing a solid material present in the resulting composition as at least one of the suspensions; and

A step of removing a solid material from the produced liquid material, wherein the produced material is a viscous material having a molar concentration of 200 to 150 M.

A composition of matter as disclosed herein may be formed by adding a suitable inorganic hydroxide to a suitable inorganic acid. Mineral acids may have densities between 22° and 70° Baume; Specific gravity may be about 1.18 to 1.93. In certain embodiments, the mineral acid will have a density between 50° and 67° Baume; It is expected to have a specific gravity of 1.53 to 1.85. Inorganic acids can be unitary or multi-units.

The mineral acids used may be homogeneous or may be mixtures of various acid compounds falling within defined parameters. Further, an acid may be a mixture comprising one or more acid compounds not included in the contemplated parameters, but it is contemplated that in combination with other materials will provide an average acid composition value in a specified range. The mineral acids or acids used may be of any suitable grade or purity. In some cases, technical grade and/or food grade materials can be successfully used in a variety of applications. Higher purity grades of mineral acids or acids may be used, if desired.

In preparing the products herein, the mineral acid component may be contained in any suitable volume of liquid form in any suitable reaction vessel. In various embodiments, it is contemplated that the reaction vessel may be a non-reactive beaker of suitable volume. The volume of acid used may be as small as 50 ml. Larger volumes, including up to 5000 gallons or more, are also considered within the scope of this disclosure.

The mineral acid can be maintained in the reaction vessel at a suitable temperature, such as at or near ambient temperature. It is within the scope of the present disclosure to maintain the initial mineral acid in the range of about 23° C. to about 70° C. However, lower temperatures ranging from 15° C. to about 40° C. may also be used.

The mineral acid is agitated by suitable means to impart a mechanical energy in the range of about 0.5 HP to 3 HP, and agitation levels imparting a mechanical energy of 1 to 2.5 HP are used in certain applications of the process. Agitation may be imparted by a variety of suitable mechanical means including, but not limited to, DC servo drives, electric impellers, magnetic stirrers, chemical inductors, and the like.

Agitation may begin in the interval just prior to the hydroxide addition and may continue in the interval for at least part of the hydroxide introduction step.

In a process as disclosed herein, the selected acidic material may be a concentrated acid having an average molar concentration (M) of at least 7 or greater. In certain procedures, the average molar concentration will be at least 10 or greater; An average molar concentration of 7 to 10 is useful in certain applications. The acidic material selected for use may be present as a pure liquid, a liquid slurry or an aqueous solution of dissolved acid in essentially concentrated form.

Suitable acidic substances may be aqueous or non-aqueous substances. Non-limiting examples of suitable acidic substances include hydrochloric acid, nitric acid, phosphoric acid, chloric acid, perchloric acid, chromic acid, sulfuric acid, permanganic acid, hydrochloric acid, hydrobromic acid, hydrobromic acid, hydrofluoric acid, iodic acid, fluoroboric acid, fluorosilicic acid, fluorotitanic acid. One or more may be included.

In certain embodiments, the defined volume of liquid concentrated strong acid used may be 55° to 67° Bormain sulfuric acid, specific gravity. This material may be placed in a reaction vessel and mechanically stirred at a temperature of 16° C. to 70° C.

In certain specific applications of the disclosed methods, a measured and defined amount of a suitable hydroxide material may be added to a stirring acid, such as concentrated sulfuric acid, present in a measured and defined amount in a non-reactive vessel. The amount of hydroxide added will be an amount sufficient to produce a solid material present in the composition as a precipitate and/or suspended solid or colloidal suspension. The hydroxide material used may be a water-soluble or partially water-soluble inorganic hydroxide. The partially water-soluble hydroxides used in processes as disclosed herein will generally be those which are miscible with the acidic material to which they are added. A non-limiting example of a partially suitable water soluble inorganic hydroxide would be one that exhibits at least 50% miscibility in the associated acid. Inorganic hydroxides can be anhydrous or hydrated.

Non-limiting examples of water-soluble inorganic hydroxides include water-soluble alkali metal hydroxides, alkaline earth metal hydroxides and rare earth hydroxides alone or in combination with each other. Other hydroxides are also considered within the scope of this disclosure. As a term defined with the hydroxide material to be used, "water solubility" is defined as a material exhibiting a dissolution characteristic of 75% or greater in water at standard temperature and pressure. A typically used hydroxide is a liquid substance that can be incorporated into an acidic substance. The hydroxide can be introduced as a true solution, suspension or supersaturated slurry. In certain embodiments, it is contemplated that the concentration of the inorganic hydroxide in the aqueous solution may depend on the concentration of the associated acid into which it is introduced. A non-limiting example of a suitable concentration for the hydroxide material is a hydroxide concentration of 5 to greater than 50% of a 5 molar material.

Suitable hydroxide materials include, but are not limited to, lithium hydroxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide, strontium hydroxide, barium hydroxide, magnesium hydroxide, and/or silver hydroxide. The inorganic hydroxide solution when used may have a concentration of inorganic hydroxide of 5 to 50% of 5 moles of material, with concentrations of 5 to 20% being used in certain applications. In certain processes, the inorganic hydroxide material may be calcium hydroxide in a suitable aqueous solution, such as present as slaked lime.

In a process as disclosed, an inorganic hydroxide in liquid or fluid form is introduced in one or more metered volumes over a defined interval into an agitated acid mass to provide a defined resonance time. In the process as outlined, the resonance time is considered to be the time interval necessary to promote and provide an environment in which a hydronium ionic material as disclosed herein develops. In a process as disclosed herein, resonant time intervals as used are typically 12 to 120 hours, and resonant time intervals of 24 to 72 hours and increments therein are used in certain applications.

In various applications of the process, the inorganic hydroxide is introduced into the acid in a plurality of metered volumes at the upper surface of the stirred volume. Typically, the total amount of inorganic hydroxide material will be introduced as a plurality of measured portions over the resonant time interval. In many cases forward load metered additions are used. As used herein, "front load metered addition" is taken to mean the addition of the total hydroxide volume, the larger portion of which is added during the initial portion of the resonance time. The initial percentage of the desired resonance time is considered to be the first 25% to 50% of the total resonance time.

It is to be understood that the proportion of each metered volume added may be the same or may vary based on such non-limiting factors as external process conditions, in-situ process conditions, specific material characteristics, and the like. It is contemplated that the number of metered volumes may be between 3 and 12. The interval between the addition of each metered volume may be from 5 to 60 minutes in certain applications of the process as disclosed. The actual interval between additions may be 60 minutes to 5 hours in certain applications.

In a specific application of the process, a 100 ml volume of 5% by volume of calcium hydroxide material is added to 50 ml of 66° Baume concentrated sulfuric acid in 5 meter increments at 2 ml per minute with or without the mixture. Addition of a hydroxide substance to sulfuric acid produces a substance that increases liquid turbidity. An increase in liquid turbidity indicates that calcium sulfate solids are forming as a precipitate. The calcium sulfate produced can be removed in a coordinated manner with the continued addition of hydroxide to provide a controlled concentration of suspended and dissolved solids.

Without wishing to be bound by any theory, adding calcium hydroxide to sulfuric acid in the manner defined herein can consume either the initial hydrogen protons or the protons associated with sulfuric acid, resulting in hydrogen proton oxygenation, as is generally expected with the addition of hydroxide. It is believed to keep the protons in question from outgassing. Instead, the proton or protons recombine with the ionic water molecular component present in the liquid material.

If desired or necessary, after a suitable resonance time as defined has elapsed, the resulting material is exposed to a non-polar magnetic field at values greater than 2000 Gauss; Magnetic fields in excess of 2 million gauss are used in certain applications. It is contemplated that magnetic fields of 10,000 to 2 million Gauss may be used in certain situations. The magnetic field may be produced by a variety of suitable means. One non-limiting example of a suitable magnetic field generator can be found in US 7,122,269 to Wurzburger, the disclosure of which is incorporated herein by reference.

Solid material produced during the process and present as a precipitate or suspended solid may be removed by any suitable means. Such removal means include, but are not limited to, gravimetry, forced filtration, centrifugation, reverse osmosis, and the like.

Solid material produced during the process and present as a precipitate or suspended solid may be removed by any suitable means. Such removal means include, but are not limited to, gravimetry, forced filtration, centrifugation, reverse osmosis, and the like.

A material produced by a process as disclosed may exist as a shelf-stable viscous liquid that is believed to be stable for at least one year when stored at ambient temperature and a relative humidity of 50 to 75%. The stable electrolyte composition of matter can be used neat in a variety of end-use applications. A stable electrolyte composition of materials may have 1.87 to 1.78 moles of material containing 8 to 9% of the total moles of uncharge balanced acid protons.

The material produced by the process disclosed herein has a molar concentration of 200 to 150 M intensity, and in certain cases 187 to 178 M intensity, as appropriately determined by hydrogen coulometry and FTIR spectral analysis. The gravimetric range of the material is greater than 1.15; In certain cases it is in the range of greater than 1.9 inches. Upon analysis, the material was shown to yield up to 1300 times the volume of orthohydrogen per cubic ml compared to the hydrogen contained in one mole of water.

In certain embodiments, this substance can be introduced into water to produce the therapeutic substances used herein. The resulting use solution is contemplated to contain between 0.5% and 10% by volume. In certain embodiments, the therapeutic agent is present in an amount of 0.5 to 8% by volume; 0.5 to 7% by volume; 0.5 to 6% by volume; 0.5 to 5% by volume; 0.5% by volume; 0.5 to 4% by volume; 0.5 to 3% by volume; 0.5 to 2% by volume; 0.5 to 1% by volume; 1 to 10% by volume; 1 to 8% by volume; 1 to 7% by volume; 1 to 6% by volume; 1 to 5% by volume; 1% by volume; 1 to 4% by volume; 1 to 3% by volume; 1 to 2% by volume; 2 to 10% by volume; 2 to 8% by volume; 2 to 7% by volume; 2 to 6% by volume; 2 to 5% by volume; 2 to 4% by volume; 2 to 3% by volume; 2 to 10% by volume; 2 to 8% by volume; 2 to 7% by volume; 2 to 6% by volume; 2 to 5% by volume; 2 to 4% by volume; 2 to 3% by volume.

A process as outlined so far can produce a compound having the formula:

x is an odd integer greater than or equal to 3;

y is an integer from 1 to 20;

Z is either a monoatomic ion from groups 14 to 17 with a charge of -1 to -3 or a polyatomic ion with a charge of -1 to -3.

In components as disclosed herein, monoatomic components that can be used as Z include Group 17 halides such as fluorides, chlorides, iodides, and bromides; Group 15 materials such as nitrides and phosphides and Group 16 materials such as oxides and sulfides are included. Polyatomic constituents include carbonate, bicarbonate, chromate, cyanide, nitride, nitrate, permanganate, phosphate, sulfate, sulfite, chlorite, perchlorate, hydrobromide, bromide, bromate, iodide, hydrogen sulphate, water sulfite Inflammation is included. It is contemplated that the composition of matter may consist of a single material to any of the above-listed materials or may be a combination of one or more of the listed compounds. In certain embodiments, Z is a sulfate.

Also, in certain embodiments, x is an integer from 3 to 9, and in some embodiments, x is considered to be an integer from 3 to 6.

In certain embodiments, y is an integer from 1 to 10; In other embodiments, y is an integer from 1 to 5.

In certain embodiments, x is an odd integer from 3 to 12; y is an integer from 1 to 20; As outlined above, Z is either a Group 14 to Group 17 monoatomic ion with a charge of -1 to -3 or a polyatomic ion with a charge of -1 to -3, and in some embodiments x is 3 to 9; y is an integer from 1 to 5;

When present, an ionic complex as disclosed herein is considered stable and can act as an oxygen donor in the presence of an environment created to produce it. The material is generally stable and may have any suitable structure and solvation capable of acting as an oxygen donor. Particular embodiments of the resulting solution will include an ion concentration as represented by the formula:

In the above formula, x is an odd integer greater than or equal to 3.

를 둘러싸는 분자의 클러스터로서 광범위하게 정의될 수 있고, 여기서 x는 3 이상의 정수이다. 하이드로늄 이온 복합체는 적어도 4개의 추가의 수소 분자와 이에 물 분자로서 착화된 산소 분자의 화학량론적 비율을 포함할 수 있다. 따라서, 본 명세서의 공정에서 사용될 수 있는 하이드로늄 이온 복합체의 비제한적인 예의 공식 표현은 하기 화학식으로 나타낼 수 있다:Ionic versions of compounds as disclosed herein are contemplated to exist in unique ionic complexes with more than 7 hydrogen atoms in each individual ionic complex, referred to herein as hydronium ion complexes. As used herein, the term "hydronium ion complex" refers to a cation

can be broadly defined as a cluster of molecules surrounding a , where x is an integer greater than or equal to 3. The hydronium ion complex may include a stoichiometric ratio of at least four additional hydrogen molecules and oxygen molecules complexed thereto as water molecules. Thus, a formal expression of a non-limiting example of a hydronium ion complex that can be used in the process herein can be represented by the formula:

In the above formula, x is an odd integer of 3 or greater;

y is an integer from 1 to 20, and in certain embodiments, y is an integer from 3 to 9.

In various embodiments disclosed herein, it is contemplated that at least a portion of the hydronium ion complex will exist as a solvated structure of hydronium ion having the formula:

In the above formula, x is an integer from 1 to 4;

y is an integer from 0 to 2.

코어는 다수의 H₂O 분자에 의해 양성자화된다. 본 명세서에 개시된 바와 같은 물질의 조성물에 존재하는 하이드로늄 복합체는 아이겐(Eigen) 복합체 양이온, 준델(Zundel) 복합체 양이온 또는 이 둘의 혼합물로서 존재할 수 있는 것으로 고려된다. 아이겐 용매화 구조는 하이드로늄 복합체가 3개의 이웃하는 물 분자에 강하게 결합되는 H₉O₄+ 구조의 중심에서 하이드로늄 이온을 가질 수 있다. 준델 용매화 복합체는 양성자가 2개의 물 분자에 의해 동일하게 공유되는 H₅O₂+ 복합체일 수 있다. 용매화 복합체는 전형적으로 아이겐 용매화 구조와 준델 용매화 구조 간의 평형 상태로 존재한다. 지금까지, 각각의 용매화 구조 복합체는 일반적으로 준델 용매화 구조를 선호하는 평형 상태로 존재하였다.In such a structure,

The core is protonated by a number of H ₂ O molecules. It is contemplated that a hydronium complex present in a composition of matter as disclosed herein may be present as an Eigen complex cation, a Zundel complex cation, or a mixture of the two. Eigen solvated structures can have a hydronium ion at the center of the H ₉ O ₄ + structure where the hydronium complex is strongly bound to three neighboring water molecules. A Jundel solvation complex can be a H ₅ O ₂ + complex in which a proton is shared equally by two water molecules. Solvation complexes typically exist in equilibrium between Eigen solvation structures and Jundel solvation structures. So far, each solvation structure complex has generally existed in equilibrium favoring the Jundel solvation structure.

The present disclosure is based, at least in part, on the unexpected discovery that stable materials can be produced in which hydronium ions exist in an equilibrium favoring the eigen complex. The present disclosure is also based on the unexpected discovery that increasing the eigencomplex concentration in a process stream can provide a class of novel enriched oxygen donor oxonium materials.

A process stream as disclosed herein may have a ratio of Eigen solvated state to Jundel solvated state in certain embodiments from 1.2 to 1 to 15 to 1; In other embodiments the ratio may be from 1.2 to 1 to 5 to 1.

The novel enriched oxygen donor oxonium materials as disclosed herein can generally be described as thermodynamically stable acidic aqueous solutions buffered with an excess of proton ions. In certain embodiments, the excess of proton ions can be an amount of hydrogen ions greater than 10% to 50% as measured by free hydrogen content.

In certain embodiments, the composition of matter may have the following chemical structure:

In the above formula, x is an odd integer from 3 to 11;

y is an integer from 1 to 10;

Z is a polyatomic ion or a monoatomic ion;

Polyatomic ions can be derived from ions derived from acids that have the ability to donate more than one proton. The associated acid may have a pK _a value of 1.7 or higher at 23°C. The ion used may have a charge of +2 or greater. Non-limiting examples of such ions include sulfate, carbonate, phosphate, oxalate, chromate, dichromate, pyrophosphate, and mixtures thereof. In certain embodiments, it is contemplated that the polyatomic ion may be derived from a mixture comprising a polyatomic ion mixture comprising an ion derived from an acid having a pK _a value of 1.7 or less.

In certain embodiments, the compound is hydrogen(1+), triaqua-μ3-oxotri sulfate (1:1); hydrogen(1+), triaqua-μ3-oxotricarbonate (1:1), hydrogen(1+), triaqua-μ3-oxotriphosphate, (1:1); hydrogen(1+), triaqua-μ3-oxotrioxalate (1:1); Hydrogen(1+), triaqua-μ3-oxotrichromate (1:1) Hydrogen(1+), triaqua-μ3-oxotridichromate (1:1), hydrogen(1+), triaqua-μ3 -Oxotripyrophosphate (1:1), and mixtures thereof mixed with water. In certain embodiments, the compound is hydrogen(1+), triaqua-μ3-oxotri sulfate (1:1).

Also included are orthocoronavirus subfamily (e.g. beta coronaviruses such as SARS-CoV, SARS-CoV-2, MERS-CoV). Disclosed herein are methods for addressing microbiological pathogenic infections caused by viruses, such as the absence of coronaviruses. The method includes introducing a composition as disclosed herein into contact with a tissue in the respiratory system, such as an epithelial tissue, during a contact interval. The contact interval is one that results in a reduction of microbiological pathogens associated with human epithelial tissue.

The therapeutic composition can be introduced into the respiratory system of a subject in such a way that at least a portion of the therapeutic composition contacts respiratory tissue proximate thereto. Introduction of at least a portion of a therapeutic composition as disclosed herein in contact with a target tissue is believed to result in a reduction in the viral load present in or on that tissue. Non-limiting examples of respiratory tissues include, but are not limited to, epithelial tissues such as those found in the alveoli, bronchi, esophagus, paranasal sinuses, nasal cavities, and the like.

Disclosed is a method of combating infection by a microbial pathogen comprising introducing a composition as disclosed herein into contact with epithelial tissue during a contact interval, wherein contact occurs with epithelial tissue as measured by pathogen load. cause a decrease in the associated at least one pathogen.

If desired, the therapeutic substance may be present and administered as a component of a liquid, gel, ointment, or the like. It is also contemplated that they may be nebulized, aerosolized, or atomized to facilitate administration to affected areas, as may occur in respiratory infections.

Methods as disclosed herein contemplate introducing one or more doses of a therapeutic composition into the respiratory system of a subject. Therapeutic compositions may be presented in a suitable carrier liquid capable of being rendered suitable for inhalation. If desired or necessary, the composition in a suitable carrier liquid material may be administered as a vapor material, spray material, aerosol material, particulate material, etc. to facilitate administration and absorption by inhalation. In certain embodiments, administration may occur by more direct application such as swabs, spray rinses, dipping, and the like.

When a substance is aerosolized or nebulized, it can be processed into droplets of a size suitable for inhalation absorption. Non-limiting examples of suitable droplet sizes include sizes ranging from 0.1 to 20 μm; 0.1 to 18 μm; 0.1 to 17 μm; 0.1 to 16 μm; 0.1 to 15 μm; 0.1 to 14 μm; 0.1 to 13 μm; 0.1 to 12 μm; 0.1 to 12 μm; 0.1 to 11 μm; 0.1 to 10 μm; 0.1 to 9 μm; 0.1 to 8 μm; 0.1 to 7 μm; 0.1 to 6 μm; 0.1 to 5 μm; 0.1 to 4 μm; 0.1 to 3 μm; 0.1 to 2 μm; 0.1 to 1 μm; 0.1 to 0.5 μm; 0.5 to 20 μm; 0.5 to 18 μm; 0.5 to 17 μm; 0.5 to 16 μm; 0.5 to 15 μm; 0.5 to 14 μm; 0.5 to 13 μm; 0.5 to 12 μm; 0.5 to 12 μm; 0.5 to 11 μm; 0.5 to 10 μm; 0.5 to 9 μm; 0.5 to 8 μm; 0.5 to 7 μm; 0.5 to 6 μm; 0.5 to 5 μm; 0.5 to 4 μm; 0.5 to 3 μm; 0.5 to 2 μm; 0.5 to 1 μm; 1 to 20 μm; 1 to 18 μm; 1 to 17 μm; 1 to 16 μm; 1 to 15 μm; 1 to 14 μm; 1 to 13 μm; 1 to 12 μm; 1 to 11 μm; 1 to 10 μm; 1 to 9 μm; 1 to 8 μm; 1 to 7 μm; 1 to 6 μm; 1 to 5 μm; 1 to 4 μm; 1 to 3 μm; 1 to 2 μm; 2 to 20 μm; 2 to 18 μm; 2 to 17 μm; 2 to 16 μm; 2 to 15 μm; 2 to 14 μm; 2 to 13 μm; 2 to 12 μm; 2 to 11 μm; 2 to 10 μm; 2 to 9 μm; 2 to 8 μm; 2 to 7 μm; 2 to 6 μm; 2 to 5 μm; 2 to 4 μm; 2 to 3 droplets are included.

Pathogen infections that can be treated and whose pathogen load can be reduced or eliminated include pathogens such as those in the Paramyxoviridae (eg, measles mobilivirus), herpesviridae (eg, varicella zoster virus); Mycobacteriaceae (eg Mycobacterium tuberculosis); Orthomyxoviridae (eg Influenzavirus type A, Influenzavirus type B); Picornaviridae (eg, Enterovirus, Poliovirus, Coxsackie A virus, Coxsackie B virus, etc.); caliciviridae (eg, norovirus); Staphylococci, such as adenoviridae (eg, Staphylococcus aureus, such as methicillin-resistant Staphylococcus aureus); Enterococci (including vancomycin-resistant enterococci), Streptococci (including streptococci) and Gram-positive species such as Clostridioides difficile, Listeria, Corynebacterium, and the like.

In the case of SARS-CoV-2 infection, SARS-CoV-2 infection can potentially lead to lifelong or fatal consequences. The virus infects respiratory cells by targeting the receptor angiotensin converting enzyme (ACE). The onset of symptoms after exposure is about 4 days, and the rapid progression often leads to hospitalization within 1 to 4 days thereafter. Common symptoms include fever, myalgia, headache, diarrhea, shortness of breath, and cough with sputum and possibly hemoptysis. In more severely affected patients, the resting respiratory rate may exceed 30 breaths per minute, C-reactive protein (CRP) levels may exceed 30 mg/L (normal values less than 3 mg/L), and blood Oxygen saturation can drop below 93%. A computed tomography (CT) scan may show rapidly developing subpleural ground glass opacities (GGO) with potential development of fibrosis. A poor prognosis is also associated with abnormal clotting characteristics.

Compositions as disclosed herein can be administered at low pH and do not cause damage or toxicity to affected tissues, local surrounding tissues, associated tissues or systems as a whole, such as those caused by SARS-CoV-2. It has been quite unexpectedly discovered that it can provide an effective treatment for a disease. Compositions as disclosed herein exhibit unique antiviral properties and are effective against viruses such as those that cause COVID-19.

Example I

To test the efficacy of a composition as disclosed herein, the material was a 50 ml portion of concentrated liquid sulfuric acid having an H ₂ SO ₄ mass fraction of 98%, an average molar concentration (M) greater than 7, and a specific gravity of 66° Baume. is placed in a non-reactive vessel, and maintained at 25° C. while stirring with a magnetic stirrer to impart mechanical energy of 1 HP to the liquid.

Once stirring is initiated, a measured amount of sodium hydroxide is added to the top surface of each portion of the stirring acid mass. The sodium hydroxide material used is a 20% aqueous solution of 5 M calcium hydroxide and is introduced in 5 metered volumes introduced at a rate of 2 ml per minute over an interval of 5 hours to give a resonance time of 24 hours. The introduction interval for each metered volume is 30 minutes.

Turbidity is produced by adding calcium hydroxide to sulfuric acid, which indicates the formation of calcium sulfate solids. The solid is allowed to precipitate periodically during the process, and the precipitate is removed from contact with the reaction solution.

Upon completion of the 24-hour resonance time, the resulting material is exposed to a non-polar magnetic field of 2400 Gauss to produce a precipitate and suspended solids observable over a 2-hour interval. The resulting material is centrifuged and forced filtered to isolate the precipitate and suspended solids.

Samples are collected for future use. Apply FFTIR spectral analysis to the test sample and titrate by hydrogen coulometric analysis. Molar concentrations of the sample materials ranged from 200 to 150 M intensity and 187 to 178 intensity. The gravimetric range of the material is greater than 1.15; greater than 1.9 in certain cases. The composition is stable and has 1.87 to 1.78 moles of material containing 8 to 9% of the total moles of uncharged acid protons. FTIR analysis indicates that the material has the formula hydrogen(1+), triaqua-μ3-oxotri sulfate (1:1). The material was also found to contain dilute sulfuric acid and 400 ppm calcium ions.

Example II

A second embodiment of a liquid material as disclosed herein is a 50 ml unit of concentrated liquid sulfuric acid having an H ₂ SO ₄ mass fraction of 98%, an average molar concentration (M) greater than 7, and a specific gravity of 66° Baume. It is prepared by introducing into a non-reactive vessel and holding each at 25° C. while stirring with a magnetic stirrer to impart mechanical energy of 1 HP to each liquid unit.

When stirring is started, a measured amount of sodium hydroxide is added to the upper surface of the stirring acidic mass of each liquid unit. The sodium hydroxide material used is a 20% aqueous solution of 5 M calcium hydroxide and is introduced in 5 metered volumes introduced at a rate of 2 ml per minute over an interval of 5 hours to give a resonance time of 24 hours. The introduction interval for each metered volume is 30 minutes.

Turbidity is produced by adding calcium hydroxide to sulfuric acid, which indicates the formation of calcium sulfate solids. The solids in each unit are allowed to settle periodically during the process, and the precipitates are removed from contact with the reaction solution.

At the completion of the 24 hour resonance time, the resulting material is centrifuged, forced filtered to isolate the precipitate and suspended solids from the liquid material, and each unit of produced material is collected for further use and analysis.

Example III

A 5 ml portion of the material produced according to the method outlined in Example I is mixed with a 5 ml portion of deionized and distilled water at standard temperature and pressure. The excess hydrogen ion concentration is measured as greater than 15% by volume, and the pH of the material is determined to be 1.

Example IV

To further evaluate the materials prepared in Examples I and II, samples of the materials were diluted with deionized water to provide materials containing 1% by volume of each material in water. These samples are evaluated for dilute sulfuric acid solution, dilute sulfuric acid solution with added calcium sulfate to obtain 300 ppm and dilute sulfuric acid solution containing 400 ppm calcium sulfate and reverse osmosis water conditioning.

All samples are diluted in acid matrix for analysis. Testing is completed using a Thermo iCAP 6300 Duo ICP-OES for calcium and sulfur content per EPA method 200.7.

Each test substance is initially prepared by simple dilution with a 5% nitric acid matrix. Calibration standards are prepared in the same acidic matrix to match the sample. However, this preparation leads to a high recovery for calcium which is believed to be the result of sulfuric acid present in the sample but not present in the calibration standard. Calibration standards were prepared again with a small amount of sulfuric acid to match the sample and the assay was repeated to give better QC recoveries closer to 100%.

To test the conductivity, the samples are individually diluted with deionized water and analyzed. Testing is completed using a Mettler Toledo Seven Excellence meter with conductivity probe per EPA Method 120.1. Expected conductivity results are presented in Table I.

Table I Summary of Conductivity Results

Samples are analyzed using a TA Instruments Q100 DSC equipped with an RCS-90 cooling system according to USP <891> to evaluate the freezing point. Expected results are presented in Table II.

Table II Freezing point results summary

Density and specific gravity of the samples are measured at 20°C using an Anton Paar digital density meter according to EPA method 830.7300. Expected results are presented in Table III.

Table III Summary of Density and Specific Gravity Results

Samples are also titrated for hydrogen ion content using acidity measured as pH 8.6 according to ASTM D1067 - Test Method A. Testing was completed using a Metrohm 826 Titrando equipped with a pH probe. Expected results are presented in Table IV.

Table IV Summary of acidity (titration) results

Solutions were analyzed by Agilent 1290/G6530 Q-TOF LC-MS using direct injection (no column) and electrospray ionization in positive and negative mode. Representative mass spectra collected in positive and negative ionization modes are shown in Figures 1 and 2 for dilute sulfuric acid w/400 ppm CaSO ₄ (A), dilute sulfuric acid (B), Tydracide (C), and reverse osmosis water (D). there is.

Example V

Each sample of Example I was diluted to produce 5% product by volume in water and was found to be room temperature storage for at least 12-18 minutes. The excess hydrogen ion concentration is measured to be greater than 15%, and the pH of the material is determined to be 1.

Example VI

Various studies have been conducted to analyze the use of the compounds and compositions as disclosed herein. It is determined that the material produced according to the process outlined in Example II can act as a polar solvent and, depending on its concentration, when introduced into pure water can be adjusted to an end result stable aqueous solution with a pH as low as zero. . Polar solvents containing the produced materials have been shown to exhibit the ability to destroy prokaryotic-based bacteria, viruses, and fungi after short periods of exposure, and are also safe against eukaryotic-based tissues known to maintain acid-base equilibrium.

Example VII

To confirm the performance of the material, solutions are prepared with final concentrations of the material in water of 2.5, 5, 15, 20 and 25% by volume, respectively, and added to media containing SARS-CoV-2. The solutions were incubated for selected time periods of 1 minute and 5 minutes. After incubation, serial dilutions were performed in Dulbecco's Modified Eagle's Medium (DMEM); Each dilution was screened using a viral plaque assay with VERO cells using saline as a control. Control saline did not appear to significantly affect SARS-CoV-2 survival as measured as plaque forming units per ml (PFU/ml) after 1 and 5 minutes of exposure time. All samples of Example II material from 2.5 vol% up to 25 vol% concentration showed efficacy against coronavirus, SARS-CoV-2, after exposure for both 1 and 5 minutes; Plaque forming units per ml (PFU/ml) were reduced by more than 5 logs (>99.999%) in each case, and no viability was detected. Results are presented in Table V.

Table V Stable Hydronium Test Results for SARS-CoV-2

Example VIII

Tests using the materials outlined in Example VI were tested against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and feline calicivirus (norovirus substitute) using standard cell culture or plaque assay techniques. ) and was found to inactivate the listed viruses.

Example IX

The Infectious Disease Society of America has identified a group of bacterial pathogens as a major cause of drug-resistant infections in health care facilities. The mnemonic “ESKAPE” readily identifies organisms that include this important group: Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, Pseudomonas, and ESBL (Enterobacter and E.coli). developed to identify Solutions as outlined in Example II were tested for their ability to neutralize the growth of the ESKAPE pathogen in a laboratory setting. Three concentrations of the composition of Example II at 2.5 vol%, 1.0 vol% and 0.3 vol%, respectively, were tested for inhibition of bacterial growth using methods outlined by the Clinical Laboratory Standards Institute. Growth inhibition of all multidrug-resistant ESKAPE pathogens tested as part of a comprehensive activity investigation against gram-positive and gram-negative organisms that cause clinically relevant infections, as well as other bacterial common/species (Haemophilus influenzae, Stenotropomonas maltobacteriaceae) phila, Citrobacter frundi, and Serratia marcescens) were achieved with stable hydronium solutions of 1% or 2.5% by volume.

Example X

Further studies conducted using the materials outlined in Example VII suggest that the action of materials as disclosed herein is not subject to the general mechanism of drug resistance. Laboratory experiments demonstrate the antibacterial activity of stable hydronium against stubborn clinical isolates of the ESKAPE pathogen and other disease-causing bacterial species of contemporaneous origin and phenotype.

Example XI

Tests were conducted to determine the performance of a material as disclosed herein for sulfuric acid at a similar pH given the low pH values the disclosed material may have. The material was prepared according to the process outlined in Example II. Current US EPA guidance (870.1000) requires that acute or short-term toxicity testing be performed for all registered chemicals, depending on possible routes of human exposure. Toxicology tests (known as standard "Six-Pack") are performed on laboratory animals to simulate the effects of chemicals on human health. Testing of solutions containing the materials disclosed in Example II was conducted in accordance with EPA guidelines at a concentration of 50% by volume.

An acute skin toxicity test was performed by directly attaching a patch containing the test solution to the skin of a healthy rat. According to the five-category classification Global Harmonized System (GHS), the stable hydronium solution is a Category 5 substance, i.e., substantially non-toxic, and according to the four-category US EPA classification, a Category 4 product. considered, and requires no risk statements to be present on the product label.

An acute oral toxicity study was conducted to determine the potential to cause toxicity from a single dose via oral administration to healthy rats. Data are consistent with the GHS oral toxicity classification of category 5 and the EPA classification designation of category 4 as essentially non-toxic.

An acute inhalation toxicity study was conducted in which rats were continuously exposed to test substance aerosols (1-4 micron particle size) over a period of 4 hours. All animals survived exposure to the test atmosphere saturated with the solution and gained weight during the study with no macroscopic abnormalities observed during necropsy.

The test substance solution was also evaluated in a primary skin irritation study using more sensitive rabbit species as test subjects. These data place the test substance solution in the lowest toxicity category for skin irritation on both the GHS and EPA scales.

Using a rabbit model, primary ocular irritation was measured by instilling a drop of 100 microliters of a 5% concentration test substance solution into one eye of a healthy animal. The total numerical score was 19.7, with a moderate eye irritation (EPA category) 3, GHS category 2B).

In order to determine the ability of the test substance solution to sensitize rodent skin, a Local Lymph Node Assay (LLNA) was performed in mice to directly measure immune cell proliferation in the lymph nodes. The results indicated that the test substance solution is not considered a contact skin sensitizer and does not require any classification by GHS or EPA.

The results of this pivotal study demonstrate that solutions containing substances as disclosed herein are effective against many viruses as well as bacteria. The solution is considered safe according to the "Six-PC" EPA toxicity testing paradigm. Unlike conventional acidic products, which are highly corrosive and highly toxic, solutions containing substances as disclosed herein can be assigned the lowest chemical toxicity rating in most categories and are only moderately irritating to the eye. Solutions containing materials as disclosed herein have the potential to be safely and effectively used as technical grade components for surface decontamination where low cost, environmentally friendly green chemicals are preferred. Due to the demonstrated safety profile on tissue surfaces, oral ingestion, and pulmonary inhalation, solutions containing substances as disclosed herein also have potential for therapeutic use in patients with COVID-19.

Example XII

5% by volume material from Example II is diluted with distilled deionized water at a ratio of 4 parts water to 1 part material and packaged in 2 oz/60 ml glass bottles with droppers.

Example XIII

Aliquots of 2 ml of each material as outlined in Example IV are introduced into a PARI nebulizer to produce a particle size of 2.5 μm that can be administered to each individual subject via inhalation as a suitable nebulizer mask. When the nebulizer is turned on, the material is properly nebulized.

Example XIV

100 individuals with confirmed COVID-19 confirmed by PCR test and various respiratory symptoms, including acute respiratory distress, were administered a PARI nebulizer 4 times a day for 7 days (10 minutes between each treatment interval), 2 every 3 to 4 hours. Administered at a dose of ml. To evaluate the efficacy of substances as disclosed herein, subjects were 33 condition and age with Arm A receiving the composition of Example IV (n = 67) or receiving Arm B while receiving normal saline placebo. Randomly assigned to matching subjects. Treatment for each individual begins immediately upon diagnosis of COVID 19, with follow-up visits 14 days after treatment, 3 weeks and 4 weeks after completion of treatment, and 3 months after treatment.

Subjects treated with the compositions of Examples II, XI, and XII are evaluated on Day 7, and at least 50% of the subjects do not exhibit respiratory symptoms. On day 14, these individuals will test negative for COVID-19 based on standard PCR tests.

Example XV

Each concentration value is 0.1% by volume; 0.5% by volume; 0.75% by volume; 1.0% by volume; An animal study was conducted to establish the safety of the composition comprising the composition prepared according to the procedure of Example II in normal saline at 2.0% and 5.0% by volume.

Test rats are used in the study, and each composition is delivered to the lungs of each test subject under conditions configured to simulate those produced by a human PARI nebulizer. A concentration specific to the test subject is administered at 10-minute intervals 4 times a day at 3-hour intervals for up to 14 days. Additional groups of test subjects under the same conditions are administered normal saline as a control. A control group that did not receive the inhalation dose was pooled.

A portion of each test cohort was euthanized on days 7, 10, and 14. Lung tissue is subjected to histological examination as well as macroscopic examination. No degradation of lung tissue is observed between subjects receiving the test substance and those receiving saline treatment.

Example XV

An adult male with a positive COVID test result as confirmed by a PCR nasopharyngeal swab has an oxygen saturation value between 20 and 30%. The subject is treated with an inhalation composition of 0.5% by volume hydrogen(1+), triaqua-μ3-oxotri sulfate (1:1) composition prepared according to the process of Example I. Substance is administered 4 times at 24 hour intervals in 10 ml aliquots at 10 minute intervals. At 24 hours, oxygen saturation is measured at 85%.

Treatment as outlined is continued for an additional 24 hours. PCR tests performed 48 hours after initiation of treatment, 72 hours after initiation of treatment, and 7 days after initiation of treatment and 14 days after initiation of treatment are negative for SARS-COV 2.

An adult female with symptoms of ARDS is diagnosed as having COVID by a PCR test. The subject's oxygen saturation is 50% as measured by pulse oximetry. The subject is treated with an inhalation composition of 0.75 vol % hydrogen(1+), triaqua-μ3-oxotri sulfate (1:1) composition prepared according to the process of Example I. Substance is administered 4 times at 24 hour intervals in 10 ml aliquots at 10 minute intervals. At 24 hours, oxygen saturation is measured at 90%.

Treatment as outlined is continued for an additional 24 hours. PCR tests performed 48 hours after initiation of treatment, 72 hours after initiation of treatment, and 7 days after initiation of treatment and 14 days after initiation of treatment are negative for SARS-COV 2.

Example XVI

An adult male with respiratory infection symptoms and fever is diagnosed as having COVID by a PCR test. The subject's oxygen saturation is 70% as measured by pulse oximetry. The subject is treated with an inhalation composition of 1% by volume hydrogen(1+), triaqua-μ3-oxotri sulfate (1:1) composition prepared according to the process of Example I. Substance is administered 4 times at 24 hour intervals in 10 ml aliquots at 10 minute intervals. At 24 hours, oxygen saturation is measured at 90%. Subjects are fever-free at 36 hours after initiation of treatment.

Treatment as outlined is continued for an additional 24 hours. PCR tests performed 48 hours after initiation of treatment, 72 hours after initiation of treatment, and 7 days after initiation of treatment and 14 days after initiation of treatment are negative for SARS-COV 2.

Example XVII

A randomized controlled study conducted to confirm the efficacy of a composition as disclosed herein is conducted by enrolling 100 adult subjects acutely infected with SARS-CoV 2. 67 subjects are treated according to a composition according to a method as disclosed herein administered by inhalation. Thirty-three condition and age-matched subjects are treated with normal saline administered by inhalation. Follow-up visits are performed daily for 14 days for each subject, at 3 and 4 weeks and 3 months after treatment.

Criteria for inclusion for registration include male or female or any race or ethnicity; at least 50 years of age; Factors for confirming a confirmed case of coronavirus infection are included. Exclusion criteria included a variety of pre-existing health conditions including respiratory or metabolic acidosis.

In addition to appropriate safety endpoints, each subject is evaluated for one or more of the following endpoints; time to return to normal oxygen saturation (SPO2) levels as well as time to negative RT-PCR tests; Pneumonia severity index, time from fever to normal body temperature; time to clinical improvement after infection; and various serum biomarkers such as C-reactive peptide (CRP); D-dimer; troponin; ferritin; surfactant protein D; Angiopoietin-2 (Ang-2); macrophage migration inhibitory factor (MIF); extracellular nicotinamide phosphoribosyltransferase (eNAMPT); sphingosine 1-phosphate receptor 3 (S1PR3); cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α); Interleukin-1 receptor antagonist (IL-1ra).

Each enrolled subject is randomized to either Arm 1 or Arm 2. Subjects randomized to Arm 1 were administered 0.5% by volume hydrogen (1+), Tris, prepared according to the process of Example I in normal saline via nebulizer every 3 to 4 hours (10 min each treatment) for a period of 7 days. 2 cc of aqua-μ3-oxotri sulfate (1:1) composition will be received 4 times daily. Subjects randomized to Arm 2 will receive 2 cc of normal saline delivered via nebulizer every 3 to 4 hours (10 minute treatment each) three times daily for a period of 7 days. Administration will be by means of a PARI nebulizer.

Subjects enrolled in Cancer 1 who receive a composition as disclosed herein generally experience relief of symptoms within 7 days of initiation of treatment, including a negative PCR test.

Example XVIII

The procedure outlined in Example XVII was repeated for concentrations of the composition as disclosed herein at 0.75% and 1.0% by volume with similar results.

Example XIX

S. aureus ATCC 6538, S. aureus ATCC 33951, P. aeruginosa ATCC,1544, and P. aeruginosa ATCC BAA 2018 was performed using the material as prepared in Example I. The results are presented in Tables VI and VII and support the MIC potency of the materials as disclosed herein.

Table VI Serial dilution of 10% solution with distilled water

Table VII MIC result

Although the present invention has been described in relation to what is presently considered to be the most practical and preferred embodiment, the present invention is not intended to be limited to the disclosed embodiments, but on the contrary is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. It should be understood that this is intended, and that the above ranges are to be interpreted the broadest to include all such modifications and equivalent structures permitted by law.

Claims (21)

As a therapeutic substance,
In a reaction vessel, a volume of concentrated mineral acid in liquid form having a molar concentration of at least 7, a density of 22° to 70° Baume and a specific gravity of 1.18 to 1.93 is brought into contact with an inorganic hydroxide present in sufficient volume to form a precipitate, suspended solid, or colloid. producing a solid material present in the resulting composition as at least one of the suspensions; and
removing solid material from the liquid material produced
A product produced by a method comprising: wherein the produced material is a viscous material having a molar concentration of 200 to 150 M; and
water
and wherein the pH is less than 7. The therapeutic substance according to claim 1 , wherein the pH is less than 5. The method according to claim 1 or 2, wherein the substance is hydrochloric acid, nitric acid, phosphoric acid, chloric acid, perchloric acid, chromic acid, sulfuric acid, permanganic acid, hydrocyanic acid, hydrobromic acid, hydrobromic acid, hydrofluoric acid, iodic acid, fluoroboric acid, fluorosilicic acid, A therapeutic substance further comprising a dilute acid selected from the group consisting of fluorotitanic acid and mixtures thereof. 3. The therapeutic substance according to claim 2, wherein the dilute acid is sulfuric acid. 5. A therapeutic material according to any one of claims 1 to 4, wherein the product of the process further comprises 100 to 1000 ppm inorganic ions selected from the group consisting of calcium, magnesium and mixtures thereof. 6. The therapeutic material of claim 5, wherein the product is present in water at a concentration of 0.25% to 5% by volume. 6. The therapeutic substance of claim 5, wherein the product is present in water at a concentration of 0.5% to 2% by volume. The therapeutic substance according to claim 1, wherein the product is a compound having the formula:

In the above formula, x is an odd integer of 3 or greater;
y is an integer from 1 to 20;
Z is a polyatomic ion or a monoatomic ion; 9. The method of claim 8, wherein Z is one of monoatomic ions from groups 14 to 17 with charge values of -1 to -3 or polyatomic ions with charges of -1 to -3, and x is an integer from 3 to 11. , wherein y is an integer from 1 to 10. 9. The therapeutic substance according to claim 8, wherein Z is selected from the group consisting of sulfates, carbonates, phosphates, oxalates, chromates, dichromates, pyrophosphates and mixtures thereof. The method according to any one of claims 1 to 4, wherein hydrogen(1+), triaqua-μ3-oxotri sulfate (1:1); hydrogen(1+), triaqua-μ3-oxotricarbonate (1:1), hydrogen(1+), triaqua-μ3-oxotriphosphate (1:1); hydrogen(1+), triaqua-μ3-oxotrioxalate (1:1); Hydrogen(1+), triaqua-μ3-oxotrichromate (1:1), hydrogen(1+), triaqua-μ3-oxotridichromate (1:1), hydrogen(1+), triaqua- A therapeutic substance comprising a stoichiometrically balanced chemical composition of at least one of μ3-oxotripyrophosphate (1:1), and mixtures thereof. 12. A therapeutic substance according to any one of claims 1 to 4, 8 and 11, wherein the therapeutic substance is active against one or more microbiological pathogens present in the human body. 13. The therapeutic substance of claim 12, wherein the one or more microbiological pathogens are present at one or more locations in the mammal's respiratory system. A method of treating a microbiological pathogenic infection in a patient, wherein the microbiological pathogenic infection is caused by at least one microbiological pathogen,
introducing the composition of claims 1 to 4, 8 or 11 into contact with an epithelial tissue during a contact interval, wherein the contact causes a reduction of at least one microbiological pathogen associated with the human epithelial tissue. step
A method for treating a patient's microbiological pathogenic infection comprising a. 14. The method of claim 13, wherein the composition is introduced as a liquid in at least one dose. 15. The method of claim 14, wherein the composition is introduced in at least one dose administration contacting the epithelial tissue as droplets having an average droplet size between 0.1 and 20 μm. 15. The method of claim 14, wherein the epithelial tissue is present in the mammalian respiratory system. 18. The method of claim 17, wherein the epithelial tissue is present in at least one of the patient's sinus cavity, bronchus, and alveoli. 15. The method of claim 14, wherein the microbiological pathogen is a pathogen such as those in the Paramyxoviridae (eg, measles mobilivirus), Herpesviridae (eg, varicella zoster virus); Mycobacteriaceae (eg, Mycobacterium tuberculosis); Orthomyxoviridae (eg, Influenzavirus type A, Influenzavirus type B); Picornaviridae (eg, enterovirus, poliovirus, coxsackie type A virus, coxsackie type B virus, etc.); Caliciviridae (eg, norovirus); Orthocoronavirus ( Orthocoronavirinae ) subfamily Coronaviridea (eg, beta coronaviruses such as SARS-CoV, SARS-CoV-2, MERS-CoV); Staphylococcaceae (eg, Staphylococcus aureus, such as methicillin-resistant Staphylococcus aureus), such as Adenoviridae ; Enterococcaceae (including vancomycin-resistant enterococci), Streptococcaceae (including streptococci ) at least one of Gram-positive species such as Clostridioides difficile, Listeria, Corynebacterium, and the like. 15. The method of claim 14, wherein the microbiological pathogen is SARS-CoV-2. Hydrogen(1+), triaqua-μ3-oxotrisulphate (1:1) as a therapeutic substance with activity against SARS-CoV-2 manifested as a respiratory disease.

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