Antimicrobial solutions and methods of use thereof for treating or preventing infection

Abstract

The antimicrobial composition comprises a therapeutically effective amount of neem oil, an extract of a Hypericum plant, a polyunsaturated fatty acid (PUFA), carrageenan and / or chlorhexidine; and (optionally) in combination with one or more pharmaceutically acceptable carriers, additives and / or diluents. The antimicrobial composition is effective in treating or preventing upper respiratory tract infections, particularly upper respiratory tract infections caused by human coronaviruses, and the antimicrobial composition is included in a method for treating or preventing microbial pathogens from infecting the human upper respiratory tract.

Description

Technical Field

[0001] The present invention generally relates to antimicrobial solutions. More specifically, the present invention relates to antimicrobial solutions and methods for treating or preventing infection by microbial pathogens. Background Art

[0002] Infections can be caused by a variety of different microorganisms. Viruses are among the most common human pathogens, and there is a huge amount of diversity in the number and types of viruses that cause disease states in humans. Most viral illnesses are self-limited, do not cause any long-term morbidity to the host, and do not require specific treatment other than antipyretics and adequate fluid intake.

[0003] Specific treatments for viral infections are available for a small number of viruses, including herpes simplex and human immunodeficiency virus (HIV), but most viral infections are treated only symptomatically or with antiviral drugs aimed at reducing the number of days you are sick, such as oseltamavir for influenza.

[0004] The most common and effective strategy for preventing and / or treating viral infections is immunization. However, immunization is only available for a few viruses. This is partly due to the ever-evolving nature of many pathogenic viruses. Many viruses undergo some form of antigenic drift, making it difficult to identify and target conserved epitopes for immunotherapy.

[0005] Human upper respiratory tract infections are mainly caused by viral infections. Common pathogenic viruses include influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, rhinovirus, human metapneumovirus and enterovirus, as well as the coronavirus family that causes the common cold. For example, Figure 1 The complex viral etiology of the common cold is illustrated. Some viruses, such as the coronavirus family, have the additional risk of evolving into human pathogens that are often highly contagious, such as MERS-CoV, the causative agent of Middle East respiratory syndrome, SARS-CoV-1, the causative agent of severe acute respiratory syndrome, and SARS-CoV-2, the causative agent of the COVID-19 pandemic.

[0006] Every year, new or evolving pathogenic viral strains cause outbreaks of respiratory illnesses around the world, which are a major cause of morbidity and mortality worldwide. An estimated 5-10% of adults and 20-30% of children are infected with influenza each year, resulting in 3-5 million severe cases and approximately 1 million deaths worldwide. Unusual viral outbreaks, such as those caused by the SARS-CoV1 and SARS-CoV2 coronaviruses, have the potential to cause much higher morbidity and mortality than influenza.

[0007] In addition to influenza and the new coronavirus, acute viral respiratory tract infections (also known as the common cold) are the most common infectious diseases in humans, with children contracting upper respiratory tract infections an average of 4 to 8 times per year and adults contracting them an average of 2 to 4 times per year. In most cases, the common cold is caused by respiratory viruses such as rhinovirus, coronavirus, parainfluenza, influenza, respiratory syncytial virus, adenovirus, enterovirus, and metapneumovirus.

[0008] Although the common cold is considered a "self-limiting disease" with symptoms including runny nose, nasal congestion, sneezing, coughing, sore throat, malaise and fever, these symptoms are painful and uncomfortable, resulting in more than 20 million visits to doctors and 40 million people missing school and work each year. This has caused a huge global economic and social burden in the absence of effective treatment.

[0009] Another problem is the challenge of providing antiviral compositions that are effective against enveloped viruses (including those that enter the lipid bilayer membrane of the host cell by membrane fusion, including herpes viruses, pox viruses, hepatoviruses, coronaviruses, retroviruses and others) and non-enveloped viruses (those that lack a lipid bilayer membrane that enters the host cell by some form of membrane perforation, including rotavirus, poliovirus and others).

[0010] Unfortunately, there are currently no effective solutions to treat or prevent many viral infections, including, for example, upper respiratory tract infections, influenza, and the common cold caused by coronaviruses, particularly SARS-CoV-1 and / or SARS-CoV-2. Therefore, there is a need to address the many shortcomings of antimicrobial compositions and methods for treating or preventing microbial infections. Summary of the invention

[0011] Embodiments of the present disclosure solve one or more of the above or other problems in the art with antimicrobial solutions. Effective treatment of upper respiratory tract infections (e.g., infections caused by novel coronaviruses, influenza, and the common cold) must take into account the fact that humans can be infected with a variety of different viruses. Embodiments of the present disclosure advantageously exhibit broad antiviral capabilities without leading to the development of drug resistance.

[0012] In particular, one or more embodiments may include an antimicrobial solution having a therapeutically effective amount of neem oil and a Hypericum spp. plant extract, optionally in combination with one or more pharmaceutically acceptable carriers, additives and / or diluents. In other embodiments, the antimicrobial solution may have a therapeutically effective amount of polyunsaturated fatty acids (PUFA), neem oil and a Hypericum spp. plant extract, optionally in combination with one or more pharmaceutically acceptable carriers, additives and / or diluents. In other embodiments, the antimicrobial solution may include a therapeutically effective amount of polyunsaturated fatty acids (PUFA), optionally in combination with one or more pharmaceutically acceptable carriers, additives and / or diluents.

[0013] The disclosed antimicrobial solution can effectively treat or prevent infections caused by bacterial or viral pathogens, preferably upper respiratory tract infections caused by human coronaviruses, and is included in the method of treating or preventing human upper respiratory tract infections caused by microbial pathogens disclosed in the present invention.

[0014] This summary is provided to introduce a series of concepts in a simplified form, which are further described in the detailed description below. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to indicate the scope of the claimed subject matter.

[0015] Additional features and advantages of the present disclosure will be set forth in the following description, and in part will be apparent from the description, or may be known by the practice of the present disclosure. The features and advantages of the present disclosure may be realized and obtained by the means and combinations particularly indicated in the appended claims. These and other features of the present disclosure will become more apparent from the following description and the appended claims, or may be known by the practice of the disclosure described below. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to describe the manner in which the above and other advantages and features of the present disclosure can be obtained, the present disclosure briefly described above will be described in more detail by reference to specific embodiments of the present disclosure shown in the accompanying drawings. It should be understood that these drawings depict only typical embodiments of the present disclosure and, therefore, should not be considered to limit its scope. The present disclosure is described and explained with additional specificity and descriptiveness through the use of the accompanying drawings, in which:

[0017] Figure 1 A pie chart showing the proportion of colds caused by specific viruses.

[0018] Figure 2A bar graph showing coronavirus particle concentrations when treated with: (i) carrier alone; (ii) neem oil and Hypericum extract; and (iii) neem oil and Hypericum extract, optionally with a carrier, according to one or more embodiments of the present disclosure.

[0019] Figure 3 A bar graph showing coronavirus particle concentrations when treated with: (i) carrier alone; (ii) carrier plus one of polyunsaturated fatty acids (PUFAs), neem oil, and Hypericum extract; (iii) carrier plus two of polyunsaturated fatty acids (PUFAs), neem oil, and Hypericum extract; and (iv) an antimicrobial solution according to one or more embodiments of the present disclosure comprising carrier plus therapeutically effective amounts of PUFAs, neem oil, and Hypericum extract.

[0020] Figure 4 A graph showing the effect of the following treatments on coronavirus titers in human patients over time: (i) carrier alone; (ii) carrier plus one of polyunsaturated fatty acids (PUFAs), neem oil, and Hypericum extract; (iii) carrier plus two of polyunsaturated fatty acids (PUFAs), neem oil, and Hypericum extract; and (iv) an antimicrobial solution according to one or more embodiments of the present disclosure comprising carrier plus therapeutically effective amounts of PUFAs, neem oil, and Hypericum extract.

[0021] Figure 5 A graph showing the number and / or severity of symptoms associated with an upper respiratory tract viral infection that was untreated or treated with an antimicrobial solution according to one or more embodiments of the present disclosure that includes a carrier plus a therapeutically effective amount of PUFAs, neem oil, and a Hypericum plant extract. The dotted line indicates the time at which treatment was given to the patient (i.e., after the onset of symptoms).

[0022] Figure 6 A bar graph showing coronavirus particle concentrations when treated with: (i) a control solution with only an oxidative stabilizer and a carrier; (ii) polyunsaturated fatty acids (PUFAs) alone; (iii) PUFAs plus an oxidative stabilizer; and (iv) PUFAs plus an oxidative stabilizer and a carrier according to one or more embodiments of the present disclosure.

[0023] Figure 7 A graph showing human subject testing results of an antimicrobial solution according to one embodiment.

[0024] Figure 8A schematic diagram of a human subject study using an antimicrobial solution according to one embodiment without interruption is shown.

[0025] Fig. 9 Shows Figure 8 A graph showing preliminary results from ongoing testing in human subjects.

[0026] Fig.10 A schematic diagram of a planned animal subject study using an antimicrobial solution according to one embodiment is shown.

[0027] Fig.11 A schematic diagram of a planned human subject study using an antimicrobial solution according to one embodiment is shown. DETAILED DESCRIPTION

[0028] Various embodiments of the present disclosure may be better understood from the following description when read in conjunction with the accompanying drawings, in which like reference numerals refer to like elements.

[0029] Before describing in detail various embodiments of the present disclosure, it should be understood that the present disclosure is not limited to the parameters of the particularly illustrative systems, methods, devices, products, processes and / or kits, which parameters can of course vary. Therefore, although certain embodiments of the present disclosure are described in detail with respect to specific configurations, parameters, components, elements, etc., these descriptions are illustrative and should not be construed as limitations on the scope of the claimed invention. In addition, the terms used in the present invention are for the purpose of describing the embodiments and are not necessarily intended to limit the scope of the claimed invention.

[0030] In addition, it should be understood that for any given component or embodiment described herein, any possible candidate or substitute listed for that component can generally be used alone or in combination with each other, unless it is implicitly or explicitly understood or otherwise stated. In addition, it should be understood that any list of such candidates or substitutes is merely illustrative and not restrictive, unless it is implicitly or explicitly understood or otherwise stated.

[0031] In addition, unless otherwise stated, the numbers representing the quantity, composition, distance or other measured values ​​used in the specification and claims should be understood to be limited by the term "approximately", which is defined in the present invention. Therefore, unless otherwise indicated, the numerical parameters described in the specification and the appended claims are approximate values, which can vary according to the desired characteristics sought to be obtained by the subject matter of the present invention. At least, and not attempting to limit the application of the doctrine of equivalents within the scope of the claims, each numerical parameter should at least be interpreted according to the number of significant digits reported and by applying ordinary rounding techniques. Although the numerical range and parameters of the wide range of the subject matter of the present invention are similar, the numerical values ​​described in the specific examples should be reported as accurately as possible. However, any numerical value inherently contains certain errors, which are necessarily derived from the standard deviations found in the respective test measurements.

[0032] Although the present disclosure is susceptible to various modifications and alternative structures, certain illustrative embodiments are provided in the accompanying drawings described below. However, it should be understood that this is not intended to limit the present disclosure to the specific embodiments disclosed, but on the contrary, it is intended to cover all modifications, alternative structures, combinations and equivalents falling within the spirit and scope of the present disclosure.

[0033] Any headings and subheadings used in this disclosure are for organizational purposes only and are not intended to limit the scope of the description or the claims.

[0034] It should be understood that unless a term having a stated meaning is expressly defined in this application, no explicit or indirect limitation of the meaning of that term beyond its obvious or ordinary meaning is intended.

[0035] Any element in a claim that does not expressly recite a “means” for performing a specified function or a “step” for performing a specified function shall not be construed as a “means” or “step” clause under 35 U.S.C. 112.

[0036] Antiviral and antibacterial properties of polyunsaturated fatty acids

[0037] Polyunsaturated fatty acids, such as the omega-3 fatty acids arachidonic acid (AA), alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are known to have minor bacteriostatic and virostatic properties. For example, EPA has been shown to have antimicrobial activity against some Gram-positive (such as Bacillus subtilis, Listeria, and Staphylococcus aureus) and Gram-negative (such as Pseudomonas aeruginosa) bacteria, a variety of mycobacteria, various fungi, cyanobacteria, microalgae, protozoa, and optionally viruses.

[0038] In particular, EPA has been shown to effectively inhibit the growth of important foodborne pathogens, including three Gram-positive species (Bacillus subtilis, Listeria, and Staphylococcus aureus) and the Gram-negative Pseudomonas aeruginosa. EPA has been shown to be effective against methicillin-resistant Staphylococcus aureus strains, which is a leading cause of mortality in health care facilities worldwide. In addition, EPA has shown efficacy against Helicobacter pylori, a pathogen of peptic ulcers, and eliminated the growth of this pathogen at certain concentrations. EPA has also shown effective antibacterial activity against human oral pathogens such as Streptococcus mutans.

[0039] Several PUFAs, including AA, DHA, and EPA, have been shown to inhibit the growth of chronic hepatitis C, and incubation with PUFAs has been shown to reduce the infectivity of several enveloped viruses, including myxoviruses, paramyxoviruses, arboviruses, and herpesviruses. However, given the diversity of microorganisms, there has been mixed success in demonstrating the effectiveness of PUFAs as broad-spectrum antiviral / antibacterial compounds.

[0040] Providing increased concentrations of omega-3 polyunsaturated fatty acids to a commercial wound healing scaffold derived from fish skin (which itself retains a portion of naturally occurring omega-3 fatty acids) has been shown to act as a bacterial barrier 80% longer than unsupplemented products.

[0041] However, while PUFAs have had some success as antimicrobial compounds, they have not been demonstrated and are not expected to function alone as a broad-spectrum antimicrobial barrier, particularly within the oral mucosa. In addition, many polyunsaturated fatty acids are susceptible to oxidation, which can produce unpleasant tastes and odors. This makes it difficult to include them in oral or nasal compositions, except in a stabilized state. It can also shorten the shelf life and usability of the associated products.

[0042] Furthermore, while PUFAs have been shown to have some antiviral activity against a limited number of viruses, there is no evidence that PUFAs are effective against coronaviruses or have a significant effect on symptomatic upper respiratory tract infections.

[0043] Neem Oil’s Antiviral and Antibacterial Properties

[0044] Neem oil is an oil obtained by cold pressing of the seeds of neem (Azadirachta indica). It is well documented in the literature that neem oil has some limited antibacterial and antiviral activity. For example, neem oil has been shown to be an effective antibacterial agent against Vibrio vulnificus, Escherichia coli, Staphylococcus epidermidis, and Pseudomonas aeruginosa. In terms of its antiviral activity, neem oil has been shown to be effective against herpes simplex virus type I and dengue virus envelope proteins.

[0045] However, neem oil has not been shown and is not expected to act alone as an antibacterial barrier, particularly within the oral mucosa, nor is there any indication that its combination with other antimicrobial compounds would increase their efficacy or allow such use. In addition, there is no indication that neem oil is effective against coronaviruses on its own, nor is there any indication that its combination with other antimicrobial compounds would increase their efficacy or allow such use.

[0046] Antiviral and antibacterial properties of Hypericum walnut oil

[0047] Hypericum oil is an extract of the common St. John's wort (Hypericum perforatum, Hypericum spp.) and includes the compound hypericin, which can also be synthesized from the anthraquinone derivative rhein. Hypericin, as the main component of Hypericum perforatum, has been used throughout history in folk medicine. Hypericin has also been the subject of intensive biochemical research and has been shown to be a versatile agent in pharmaceutical and medical applications. Recent studies have reported antidepressant, antitumor, anticancer, and some limited antiviral activities of hypericin. For example, hypericin from Hypericum perforatum has been shown to significantly reduce mRNA expression and viral titers of bronchitis virus, and hypericin from Hypericum perforatum has been shown to have antiviral effects in patients with chronic hepatitis C infection. Extracts of Ligusticum erythrorhizium have been shown to inhibit Epstein-Barr virus and Kaposi's sarcoma-associated herpes virus.

[0048] However, like neem oil, extracts of Hypericum have not been shown and are not expected to function alone as an antimicrobial barrier, particularly within the oral mucosa, nor is there any indication that combination with other antimicrobial compounds such as neem oil would enhance their efficacy or allow such use.

[0049] Antiviral properties of carrageenan

[0050] Carrageenan belongs to the family of linear sulfated polysaccharides, which is the main component of the cell wall of red algae (belonging to the class of Rhodophyceae) and is extracted from red seaweed. It is widely used in industries such as food, beauty and pharmaceuticals as an additive for gelling, thickening and stabilizing compositions, because according to the U.S. Food and Drug Regulations, especially 21C.FR182.7255, carrageenan is generally considered to be safe. For example, carrageenan is used as an emulsifier and adhesive for products such as ice cream, jelly, toothpaste, etc. Carrageenan is a high molecular weight polysaccharide, including repeated galactose units and 3,6 dehydrated galactose connected by glycosidic bonds. Carrageenan accounts for 30% to 75% of the dry weight of algae in some red seaweed species (such as Chondrus, Gigartina, Hypnea and Eucheuma). Carrageenan can be classified according to structural characteristics, including sulfation patterns (kappa, iota and lambda variants including one, two and three sulfate groups, respectively).

[0051] Carrageenan has been found to form a mucoadhesive layer on the surface of the nasal mucosa and interact with many different viral particles. This is thought to form a shield on the surface of the viral particles that prevents interaction between the mucosa and infected host cells. This provides antiviral activity against a range of animal viruses and is even used as a component of spermicides for the prevention of sexually transmitted infections. In vitro and in vivo studies have shown that carrageenan is a potent inhibitor of viruses such as papillomavirus, rhinovirus, influenza A, respiratory syncytial virus, and human enterovirus 71.

[0052] However, there is no indication that combining carrageenan with other antimicrobial compounds such as neem oil, PUFAs, or Hypericum extracts will enhance its efficacy or allow for such applications.

[0053] Chlorhexidine's antiviral and antibacterial properties

[0054] 1,6-Bis(4'-chlorophenylbiguanide)hexane is a divalent cationic biguanide commonly known as chlorhexidine. Chlorhexidine (in the form of chlorhexidine gluconate, chlorhexidine digluconate, and chlorhexidine acetate) is a broad-spectrum disinfectant and antiseptic commonly used for skin disinfection, surgical instrument sterilization, wound cleaning, dental plaque prevention, and other purposes. Despite side effects, it is widely used in disinfectants, cosmetics, and pharmaceutical products due to its activity against Gram-positive and Gram-negative bacteria, anaerobes, fungi, and some viruses.

[0055] Chlorhexidine is thought to function by dissociating at physiological pH and releasing the positively charged chlorhexidine cation, which binds to the negatively charged bacterial cell wall and affects the bacterial osmotic balance, leading to bacteriostatic effects or cell death. That is, the biguanidine group of the chlorhexidine molecule binds to anionic sites on the cell wall, forming a bridge between adjacent acidic phospholipid head groups (due to the relatively small size of chlorhexidine - six carbons in length), replacing the divalent cations (i.e., Mg) that normally stabilize the cell membrane. 2+ and Ca 2+ ), causing the cell to leak potassium ions and protons. However, chlorhexidine is known to be less effective in the presence of organic matter such as serum. Chlorhexidine is also known to be ineffective against non-enveloped viruses.

[0056] However, there is no indication that the combination of chlorhexidine with other antimicrobial compounds such as neem oil, PUFAs, Hypericum extract, or carrageenan would increase the efficacy of chlorhexidine or allow such use.

[0057] Overview of antimicrobial compositions

[0058] Viruses are typically spread through respiratory droplets produced when an infected person coughs or sneezes. These droplets can then be inhaled by uninfected people. One strategy to prevent or minimize the spread of respiratory viruses is to provide a barrier at the point of entry, such as the oral mucosa.

[0059] To be effective, barrier films applied to the oral mucosa need to be non-water soluble to prevent them from immediately dispersing in the aqueous environment of the oral mucosa. Oral sprays are often glycerin-based because glycerin has minor antimicrobial and antiviral properties and is widely used in FDA-approved wound and burn treatments. Barriers should ideally be effective against both gram-positive and gram-negative bacteria, as well as enveloped and non-enveloped viruses.

[0060] Embodiments of the present disclosure include therapeutically effective concentrations of neem oil and Hypericum extract administered as a wash, hydrogel, oral spray, or nasal spray to create a synergistically beneficial antimicrobial barrier, particularly when applied to the oral mucosa.

[0061] Other embodiments of the present disclosure include the administration of therapeutically effective concentrations of PUFAs, neem oil, and Hypericum extract as a wash, hydrogel, oral spray, or nasal spray to produce a synergistically beneficial antimicrobial barrier, particularly when applied to the oral mucosa. Other embodiments of the present disclosure include the administration of therapeutically effective concentrations of PUFAs as a wash, hydrogel, oral spray, or nasal spray to produce a beneficial antimicrobial barrier, particularly when applied to the oral mucosa.

[0062] Other embodiments of the present disclosure include therapeutically effective concentrations of one or more of PUFAs, neem oil, and Hypericum extract in combination with one or more of carrageenan and chlorhexidine.

[0063] Other embodiments of the present disclosure include therapeutically effective concentrations of PUFA and carrageenan applied as a lotion, hydrogel, oral spray, or nasal spray to produce a beneficial antimicrobial barrier, particularly when applied to the oral mucosa. Other embodiments of the present disclosure include therapeutically effective concentrations of PUFA and one or more enzymes (as described in more detail below), the composition being applied as a lotion, hydrogel, oral spray, or nasal spray to produce a beneficial antimicrobial barrier, particularly when applied to the oral mucosa.

[0064] In some cases, the antimicrobial solutions of the present disclosure can reduce the titer of viral pathogens, and the synergistic benefits provided by the antimicrobial composition can extend to achieving a barrier function against microbial pathogens that the compounds alone cannot achieve.

[0065] For example, although the components of the disclosed antimicrobial composition may not provide barrier function to coronaviruses alone, the combination unexpectedly and beneficially provides barrier function. In some embodiments, although PUFAs (such as ALA, EPA, and DHA) alone may not provide barrier function to coronaviruses alone, the combination with PUFAs (preferably omega-3 fatty acids) unexpectedly and beneficially provides barrier function.

[0066] Particularly unexpectedly, the Food and Drug Administration considers PUFAs, neem oil, hypericum oil, and carrageenan as food additives and therefore do not consider them to have pharmacological effects or be toxic in themselves. However, their combination provides a transformative effect that enables their application as a microbial barrier, particularly within the oral mucosa. In addition, in some embodiments, the transformative effect of the disclosed combination can provide symptom relief of upper respiratory tract infections, particularly those caused by viruses. This can include reducing symptoms such as runny nose, sneezing, coughing, sore throat, and / or fatigue.

[0067] In some cases, the synergistic combination of neem oil, Hypericum extract, PUFA, carrageenan, and / or chlorhexidine disclosed according to various embodiments reduces inflammation during infection. This can be beneficial in reducing swelling within the airways to promote less labored breathing and / or reduce the feeling of congestion.

[0068] In some embodiments, the antimicrobial composition is configured to produce and maintain free fatty acids relative to fatty acids. It has been found that by providing a composition in which fatty acids (e.g., those from PUFAs and / or fatty acids naturally occurring in Hypericum extract) are oxidized to free fatty acids, the antiviral effect of the composition is improved. This is believed to be due to the ability of free fatty acids (which are much smaller than fatty acids) to fit between the spike proteins on the surface of the virus and interact with the viral membrane, breaking or dissolving the membrane and inactivating the virus in the process. Much larger fatty acids are hindered by the spike proteins and cannot provide this antiviral / virucidal property.

[0069] In addition to relieving symptoms during an infection / disease, embodiments of the present disclosure can reduce the total number of days an individual has symptomatic infection (e.g., Figure 5 shown).

[0070] As described in more detail in the examples provided herein, embodiments of the present disclosure may additionally or alternatively reduce viral load, or reduce the detection of viral particles in an infected individual.

[0071] When provided in the form of a spray, the disclosed antimicrobial (preferably antiviral) composition or at least its active component can be administered using an inert propellant known in the art. This can facilitate oral administration of the disclosed composition by the user and / or surrounding individuals in the form of a non-toxic propellant that can be safely inhaled.

[0072] Alternatively, the disclosed antimicrobial (preferably antiviral) compositions can be delivered as an aerosolized spray rather than using a propellant. In such embodiments, it may be necessary to adjust the viscosity of the composition by adding glycerol and / or water to obtain a desired viscosity capable of delivering a clinically effective amount of the active ingredient within the modified composition to have the disclosed benefits and health-promoting effects.

[0073] The method for treating or preventing human upper respiratory tract infection may include applying the antimicrobial compound disclosed in the present invention to the oral mucosa. This can be accomplished, for example, by using a throat or nasal spray. Spray devices known and used in the art can be used for this purpose. Such devices typically release 30-200 μL at each actuation, and the antimicrobial composition can be formulated according to efficacy and palatability.

[0074] As a non-limiting example, the disclosed spray formulation can be applied to one of the nasal mucosa and the oropharyngeal mucosa, or preferably both, by spraying into the nose and mouth of the affected individual. In some embodiments, the dose of the antimicrobial solution delivered is 50 μL–200 μL each time the oral spray and / or nasal spray is actuated. Although a dose of 50 μL–200 μL per actuation has been described, it should be understood that any suitable volume per actuation can be appropriately delivered according to the specific composition, the ingredients therein, and the needs of the user. The antimicrobial solution can be provided in a suitable container / dispenser (such as a spray bottle), which is configured to deliver a predetermined amount per actuation, such as 50 μL-200 μL, and in some embodiments, the container / dispenser can be configured independently for nasal and oral applications.

[0075] In some embodiments, antioxidants may be added to the antimicrobial composition to prevent oxidation of one or more components (eg, neem oil or Hypericum extract), thereby increasing the shelf life and performance of the composition over time.

[0076] In one embodiment, the disclosed antimicrobial composition can be used to prevent and / or treat infections caused by coronaviruses such as SARS-CoV-1 and SARS-CoV-2 (or their variants). The administration of the disclosed antimicrobial composition (e.g., by spraying to the nasal and oropharyngeal mucosa in the nose and oral cavity of the affected individual) is associated with shortening the duration of the pathogenic coronavirus infection suffered by the individual. In some cases, this administration is also associated with reducing the severity of the disease, which can beneficially reduce the viral load in the airway and reduce the risk or possibility of transmission to others.

[0077] Therefore, embodiments of the present disclosure can reduce the spread and contact contagiousness of disease pathogens. In addition, if drug administration slows or reduces symptomatic infection, the burden on the healthcare system can be reduced, including the use of emergency medical services and / or medical equipment (such as ventilators). In general, this can beneficially reduce morbidity and mortality in the community without overburdening the healthcare system or causing a reduction in available resources.

[0078] Various omega-3 fatty acids can be included in the disclosed compositions. In some embodiments, the omega-3 fatty acids include a combination of omega-3 fatty acids, such as a combination of ALA, EPA, and DHA. These can be included in the omega-3 fatty acid mixture at an average concentration found in cold water fish skin, preferably an average concentration found in Atlantic cod skin.

[0079] In some embodiments, the relative concentrations of PUFAs may be adjusted until the desired benefit is achieved.

[0080] Additional Implementation

[0081] Proteolytic enzymes applied to the mouth may reduce the severity and duration of the common cold. In a randomized study, an oral spray containing proteolytic enzymes was found to be effective in reducing the severity and duration of the common cold. The trial involved 267 participants with naturally occurring common colds who were randomly assigned to use the spray six times a day or receive no treatment. The spray is available under a variety of marketed brands, including and CortaGrip, and contains cod-derived trypsin from Zymetech of Iceland.

[0082] The researchers found that overall symptom scores on the Jackson Cold Scale were lower in the treatment group during the first seven days (area under the curve: 39.6 vs. 46.2). There were significant effects on individual symptoms of sore throat, nasal congestion and headache. Quality of life scores for all domains improved in the treatment group, and duration of illness was shortened.

[0083] The spray is a barrier solution containing glycerol and trypsin, an enzyme obtained from Atlantic cod. Previous in vitro studies have shown that it can inactivate 99% of viruses that cause the common cold, including influenza and rhinovirus. However, the problem for these products is the known cost and palatability of these compounds.

[0084] In some embodiments, the antimicrobial composition disclosed in the present invention may additionally include one or more enzymes, such as proteolytic enzymes, preferably marine-derived proteases or collagenases, to maintain or increase its effectiveness as an antimicrobial barrier. Because the antimicrobial composition already acts as an antimicrobial barrier (e.g., in the oral mucosa), this additional protease can be added at a lower concentration than before, which is probably at a concentration at which the protease itself is no longer effective as an antimicrobial agent. This can advantageously reduce the cost burden of using such compounds in commercial products, and can also increase palatability. Optionally added flavor enhancement additives, such as menthol, can also increase the palatability of the composition.

[0085] In some embodiments, one or more enzymes, such as protease and / or collagenase, can extend the effectiveness of antimicrobial composition to non-enveloped viruses and enveloped viruses. Although protease or collagenase have been described, it should be understood that any suitable enzyme or combination of enzymes can be added in any suitable amount. In some embodiments, enzyme or combination of enzymes include one or more of papain, ficin, bromelain, pepsin, chymosin, cathepsin, trypsin or any other suitable enzyme. One or more enzymes added advantageously provide broad spectrum efficacy for components derived from animals.

[0086] In some embodiments, the antimicrobial composition according to the embodiments may include ascorbic acid (also known as vitamin C), which can advantageously reduce the pH of the antimicrobial composition. It has been found that the stabilizers included in some embodiments work better at low pH. In some embodiments, the pH of the composition is maintained at about 6 to be consistent with the pH of the nose. In order to maintain the free fatty acids at a specific pH level (as described above), some embodiments may include trisodium citrate and / or citric acid.

[0087] Although the anti-coronavirus and coronavirus prevention applications of the antimicrobial composition have been described, it should be understood that the composition can be used for any suitable microbial disease and is by no means limited to sprays for the nose and mouth. The antimicrobial composition of the present disclosure can be advantageously configured to be effective against enveloped viruses (such as RSV, eye infections, oral infections including cold sores) and conventional non-enveloped viruses, and is used to fight the enveloped viruses and non-enveloped viruses.

[0088] in conclusion

[0089] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0090] Various aspects of the present disclosure, including devices, systems, and methods, may be described with reference to one or more embodiments or examples that are exemplary in nature. As used herein, the term "exemplary" means "serving as an example, instance, or illustration," and is not necessarily to be construed as superior to other embodiments disclosed herein. In addition, references to "an embodiment" of the present disclosure or invention include specific references to one or more embodiments thereof, and vice versa, and are intended to provide illustrative examples that do not limit the scope of the invention, which is determined by the appended claims rather than the following description.

[0091] The present disclosure may be embodied in other specific forms without departing from its spirit or essential features. The described embodiments are considered to be illustrative only and not restrictive in all respects. Therefore, the scope of the present invention is determined by the appended claims rather than the preceding description. Although certain embodiments and details have been included in the present invention and the attached disclosure for the purpose of illustrating the embodiments of the present disclosure, it is obvious to those skilled in the art that various changes may be made to the methods, products, devices and equipment disclosed in the present invention without departing from the scope of the present disclosure or the present invention. Therefore, although various aspects and embodiments are disclosed in the present invention, other aspects and embodiments are contemplated. All changes within the equivalent meaning and scope of the claims are included within their scope.

[0092] Example

[0093] The following examples as described herein are for illustrative purposes only and are not intended to limit the scope of the present disclosure in any way.

[0094] Examples 1-5

[0095] like Figure 2 As shown, the antimicrobial solution of the present disclosure may have a synergistic effect when including neem oil and an extract of a Hypericum plant (preferably hyperforin). In some cases, the synergistic effect may result in an increase in antimicrobial activity, preferably an increase in virucidal activity, but it may additionally or alternatively include extending the antimicrobial activity to one or more microorganisms that are not substantially affected by the individual components of the antimicrobial solution.

[0096] For example, when treated with neem oil or an extract of Hypericum alone, coronavirus or the disease caused thereby may not be substantially affected (e.g., neutralized, or rendered non-infectious, or the duration or incidence of symptomatic infection is reduced). However, when treated with an antimicrobial solution of the present disclosure comprising a combination of neem oil and a Hypericum extract (preferably hyperforin), coronavirus or the disease caused thereby can be affected.

[0097] These data demonstrate that the antimicrobial solutions of the present disclosure have unexpected synergistic effects. The synergistic effects are observed by reducing the number or concentration of viral titers and / or by extending the effectiveness against coronaviruses, such as Figure 2 As shown (e.g., results for "Neem + Hypericum" and "Neem + Hypericum + carrier").

[0098] Preparation and Figure 2 The antimicrobial solutions to which the results are related may include one or more solutions provided in Table 1 below (each antimicrobial solution corresponds to Examples 1-5, respectively). All percentages disclosed in Table 1 are volume ratios relative to the final volume of the antimicrobial solution.

[0099] Table 1

[0100]

[0101] The antimicrobial compositions of Examples 1-5 and Figure 2 The data shown are comparable in range (eg, results for "Neem + Hypericum").

[0102] As provided in Table 1 and other tables below, the term "carrier" is meant to include one or more pharmaceutically acceptable carriers, additives and / or diluents, preferably including at least glycerol, and in some embodiments, flavor enhancing additives such as menthol. The term "stabilizer" is intended to include antioxidants, preferably oil-based antioxidants, which are suitable for preventing oxidation of PUFAs in solution.

[0103] Embodiment 6-10

[0104] Table 2 below includes antimicrobial compositions containing different concentrations of carrier and mixtures of neem oil and Hypericum extract. In each of Examples 6-10, the relative concentrations of neem oil and Hypericum extract are kept proportional to each other. Each formulation is described as Examples 6-10, respectively, and is described in conjunction with Figure 2 The results shown are comparable in range (eg, results for "Neem + Hypericum + Vehicle").

[0105] Table 2

[0106] Example 6 Example 7 Example 8 Example 9 Example 10 Carrier 10％ 20％ 33％ 50％ 80％ Neem Oil 45％ 40％ 33％ 25％ 10％ Hypericum oil 45％ 40％ 33％ 25％ 10％

[0107] Examples 11-20

[0108] Table 3 below includes antimicrobial compositions having different concentrations of carrier, neem oil, and extract of Hypericum, wherein neem oil and extract of Hypericum are provided at different relative concentrations. Each formulation is as shown in Examples 11-20, respectively. Examples 11-20 and Figure 2 The data shown are comparable in range (eg, results for "Neem + Hypericum + Vehicle").

[0109] Table 3

[0110] Embodiment 11 Example 12 Example 13 Embodiment 14 Embodiment 15 Carrier 50％ 60％ 60％ 60％ 80％ Neem Oil 25％ 20％ 30％ 10％ 10％ Hypericum oil 25％ 20％ 10％ 30％ 10％ Example 16 Embodiment 17 Embodiment 18 Embodiment 19 Embodiment 20 Carrier 80％ 80％ 90％ 90％ 90％ Neem Oil 15％ 5％ 5％ 9％ 1％ Hypericum oil 5％ 15％ 5％ 1％ 9％

[0111] Examples 21-25

[0112] like Figure 3 As shown, the antimicrobial solution of the present disclosure may have a synergistic effect when including each of PUFA (preferably omega-3 fatty acids), neem oil, and an extract of a Hypericum plant (preferably hyperforin). In some cases, the synergistic effect may increase the antimicrobial activity, preferably the virucidal activity, but it may additionally or alternatively include extending the antimicrobial activity to one or more microorganisms that are not substantially affected by the individual components of the antimicrobial solution.

[0113] For example, coronavirus or the disease caused thereby may not be substantially affected (e.g., neutralized, or rendered non-infectious, or the duration or incidence of symptomatic infection is reduced) when treated with PUFA, neem oil, or Hypericum extract alone. However, coronavirus or the disease caused thereby can be affected when treated with an antimicrobial solution of the present disclosure comprising a combination of PUFA (preferably omega-3 fatty acids), neem oil, and Hypericum extract (preferably hyperforin).

[0114] These data demonstrate that the antimicrobial solutions of the present disclosure have unexpected synergistic effects. The synergistic effects are observed by reducing the number or concentration of viral titers and / or by extending the effectiveness against coronaviruses, such as Figure 4 and 5 As shown in the curve in (e.g. the results for “vector+3”).

[0115] Preparation and Figure 3 and Figure 4 The antimicrobial solution related to the results shown in , and may include one or more solutions provided in Table 4 below (each antimicrobial solution corresponds to Examples 21-25, respectively). All percentages disclosed in Table 4 are volume ratios relative to the final volume of the antimicrobial solution.

[0116] Table 4

[0117]

[0118] The antimicrobial compositions of Examples 21-25 and Figure 2 and 3 The data shown are comparable in range (e.g. results for "Vector+3").

[0119] Examples 26-30

[0120] Table 5 below includes antimicrobial compositions containing different concentrations of carrier and a mixture of PUFA, neem oil, and Hypericum extract. In each of Examples 26-30, the relative concentrations of PUFA, neem oil, and Hypericum extract are kept proportional to each other. Each formulation is illustrated in Examples 26-30, respectively, and is comparable in scope to Examples 26-30. Figure 2 and 3 The results shown are comparable (eg, results for "vector+3").

[0121] Table 5

[0122] Embodiment 26 Embodiment 27 Embodiment 28 Embodiment 29 Embodiment 30 Carrier 0％ 25％ 40％ 70％ 85％ PUFA 33％ 25％ 20％ 10％ 5％ Neem Oil 33％ 25％ 20％ 10％ 5％ Hypericum oil 33％ 25％ 20％ 10％ 5％

[0123] Examples 31-35

[0124] Table 6 below includes antimicrobial compositions having different concentrations of carrier, neem oil and Hypericum extract, wherein the compositions are significantly free of PUFAs. Each formulation is as described in Examples 31-35, respectively.

[0125] Table 6

[0126] Embodiment 31 Embodiment 32 Embodiment 33 Embodiment 34 Embodiment 35 Carrier 33％ 50％ 60％ 80％ 90％ PUFA 0％ 0％ 0％ 0％ 0％ Neem Oil 33％ 25％ 20％ 10％ 5％ Hypericum oil 33％ 25％ 20％ 10％ 5％

[0127] Examples 36-40

[0128] Table 7 below includes antimicrobial compositions having different concentrations of carrier, PUFA and Hypericum extract, wherein neem oil is significantly absent from the composition. Each formulation is as described in Examples 36-40, respectively.

[0129] Table 7

[0130] Embodiment 36 Embodiment 37 Embodiment 38 Embodiment 39 Embodiment 40 Carrier 33％ 50％ 60％ 80％ 90％ PUFA 33％ 25％ 20％ 10％ 5％ Neem Oil 0％ 0％ 0％ 0％ 0％ Hypericum oil 33％ 25％ 20％ 10％ 5％

[0131] Examples 41-45

[0132] Table 8 below includes antimicrobial compositions having different concentrations of carrier, PUFA and neem oil, wherein the compositions are significantly free of Hypericum extract. Each formulation is as described in Examples 41-45, respectively.

[0133] Table 8

[0134] Embodiment 41 Embodiment 42 Embodiment 43 Embodiment 44 Embodiment 45 Carrier 33％ 50％ 60％ 80％ 90％ PUFA 33％ 25％ 20％ 10％ 5％ Neem Oil 33％ 25％ 20％ 10％ 5％ Hypericum oil 0％ 0％ 0％ 0％ 0％

[0135] Although the compositions associated with Examples 31-45 may affect the pathogenicity of microorganisms in some cases, it is not expected that these compositions will affect coronaviruses or other upper respiratory pathogens to the same extent as the compositions associated with Examples 21-30. Instead, the compositions associated with Examples 31-45 are expected to have a combined effect (if any) on the titer and / or pathogenicity of coronaviruses (or other upper respiratory pathogens), but without the synergistic effect seen with the compositions disclosed in Examples 21-30.

[0136] Examples 31-45 corresponding to Tables 6-8 are similar in scope to Figure 3 The data shown are comparable (eg, results for "Carrier + 2").

[0137] Embodiment 26

[0138] The odor and palatability of the antimicrobial composition of the present disclosure were tested. 10 samples were prepared according to the following formula:

[0139] 14 ml glycerin

[0140] 1.5 ml Neem Oil + Hypericum Extract Preparation

[0141] 1.5 ml omega-3 PUFA stock preparation

[0142] 3 ml water

[0143] <1mL concentrated flavoring (no flavoring added to the control)

[0144] Each recipe was labeled according to the flavors added. Five volunteers tasted and sniffed the blends and rated each blend on a scale of 0-10 (0 being the worst taste / smell and 10 being the best taste / smell). Between each taste and sniff test, participants sniffed the coffee and tasted the orange between the two samples to neutralize any previous pleasant / unpleasant taste and / or smell, thereby avoiding bias in subsequent taste and sniff tests.

[0145] The results are shown in Table 9 below. In each column, the first number from left to right indicates the smell score, and the second number indicates the taste score.

[0146] Table 9

[0147]

[0148] Table 9 (continued)

[0149]

[0150] As shown in Table 9 above, the most preferred flavorings included caramel with an average score of 7.2, lemon with an average score of 5.8, and almond or vanilla with an average score of 5.4 each.

[0151] Embodiment 27

[0152] The following formulation was used to prepare a composition capable of being nebulized and was found to be stable and not separate for at least 30 minutes after mixing:

[0153] 16 ml glycerol (85% v / v)

[0154] 1.5-2 ml of neem oil + Hypericum extract preparation (5%-10% v / v)

[0155] 0.5-1 ml omega-3 PUFA stock (5% v / v)

[0156] 3.0–3.5 ml water to obtain the correct viscosity

[0157] <1 ml flavoring (eg, those listed in Example 26, eucalyptus, or menthol).

[0158] The neem oil + Hypericum extract provided in the above example formula itself can include high content of saturated fatty acids and polyunsaturated fatty acids. For example, the neem oil + Hypericum extract stock formulation can include the concentrations of the fatty acids listed in Table 10 below.

[0159] Table 10

[0160] fatty acid illustrate content(%) Palmitic acid saturation 13.5–14.1 Sterile fatty acids saturation 8.3–11.4 Oleic acid Omega-9 polyunsaturated 57.8–61.4 Linoleic acid Omega-6 polyunsaturated 10.3–12.6 Linolenic acid Omega-3 polyunsaturated 0.7–1.0

[0161] Embodiment 28

[0162] In a clinical study, more than 70 patients with early symptoms of upper respiratory tract infection (e.g., runny nose and sore throat) were treated with a spray composition disclosed in the present invention, which included omega-3 PUFA, neem oil, and Hypericum extract. The attending physician applied the spray to the nasal and oropharyngeal cavities of each patient to reduce the effects of COVID-19 (or other pathogenic viruses) on the mucosa. After administration, the symptoms of the 70 patients were alleviated or completely resolved.

[0163] Examples of symptom relief experienced by patients in this study include Figure 5 As shown, after the onset of symptoms (indicated by the vertical dashed line 2 days after infection), the patient was administered repeated doses of a spray composition disclosed herein, comprising omega-3 PUFA, neem oil, and Hypericum extract. As shown, the number and / or severity of symptoms were significantly reduced in degree and duration compared to untreated individuals.

[0164] Examples 29-33

[0165] like Figure 6 As shown, when PUFA (preferably omega-3 fatty acids) are included in the spray composition, the antimicrobial solution of the present invention can have a microbial barrier effect. In some cases, this effect can increase the antimicrobial activity, preferably increase the virucidal activity, but it can additionally or alternatively include extending the antimicrobial activity to one or more microorganisms that are substantially not affected by the individual components of the antimicrobial solution.

[0166] For example, a coronavirus or a disease caused thereby may not be substantially affected (e.g., neutralized, or rendered non-infectious, or the duration or incidence of symptomatic infection is reduced) when treated with PUFAs alone. However, a coronavirus or a disease caused thereby can be affected when treated with an antimicrobial solution of the present disclosure that includes a combination of PUFAs, preferably a combination of omega-3 fatty acids.

[0167] These data demonstrate that the antimicrobial solution of the present disclosure achieves unexpected effects. The effects are observed by reducing the number or concentration of viral titers and / or by extending the effectiveness against coronaviruses, such as Figure 6 shown.

[0168] Preparation and Figure 6 The control solution to which the results are related may include one or more of the solutions provided in Table 11 below (each antimicrobial solution corresponds to Examples 29-33, respectively). All percentages disclosed in Table 11 are by volume relative to the final volume of the antimicrobial solution.

[0169] Table 11

[0170] Embodiment 29 Embodiment 30 Embodiment 31 Embodiment 32 Embodiment 33 Carrier 0％ 100％ 50％ 25％ 75％ Stabilizer 100％ 0％ 50％ 75％ 25％ PUFA 0％ 0％ 0％ 0％ 0％

[0171] The control solutions of Examples 29-33 and Figure 6 The data shown are comparable in scope (eg, results for "stabilizer + carrier only").

[0172] Examples 34-38

[0173] Table 12 below includes antimicrobial compositions with various concentrations of various PUFAs. In Example 34, the relative concentrations of the PUFAs are kept proportional to each other. The relative proportions can be equivalent proportions (e.g., each raw material contains 100 μg / mL of PUFA) or relative proportions observed in the setting environment (e.g., the relative abundance of each PUFA in Atlantic cod skin). In Examples 35-39, the relative concentrations of the PUFAs are different. Each formulation is as shown in Examples 34-38, respectively, and is Figure 6 The results shown are comparable in range (eg, "PUFA only" results).

[0174] Table 12

[0175] Embodiment 34 Embodiment 35 Embodiment 36 Embodiment 37 Embodiment 38 ALA 33％ 25％ 25％ 50％ 15％ EPA 33％ 25％ 50％ 25％ 15％ DHA 33％ 50％ 25％ 25％ 70％

[0176] Examples 39-43

[0177] Table 13 below includes antimicrobial compositions that contain, in addition to an oxidative stabilizer, each of the PUFAs of Examples 6-10 at different concentrations. Each formulation is as shown in Examples 39-43, respectively. Figure 6 The data shown are comparable in scope (eg, results for "PUFA + Stabilizer").

[0178] Table 13

[0179] Embodiment 39 Embodiment 40 Embodiment 41 Embodiment 42 Embodiment 43 PUFA 50％ 75％ 80％ 90％ 95％ Stabilizer 50％ 25％ 20％ 10％ 5％

[0180] Examples 44-53

[0181] Table 14 below includes antimicrobial compositions containing different concentrations of each PUFA of Examples 34-38 in addition to an oxidative stabilizer and a carrier. Each formulation is represented by Examples 44-53, respectively, and is Figure 6 The data shown are comparable in scope (eg, results for "PUFA+stabilizer+carrier").

[0182] Table 14

[0183] Embodiment 44 Embodiment 45 Embodiment 46 Embodiment 47 Embodiment 48 PUFA 50％ 60％ 60％ 60％ 80％ Stabilizer 25％ 20％ 30％ 10％ 10％ Carrier 25％ 20％ 10％ 30％ 10％ Embodiment 49 Embodiment 50 Embodiment 51 Embodiment 52 Embodiment 53 PUFA 80％ 80％ 90％ 90％ 90％ Stabilizer 15％ 5％ 5％ 9％ 1％ Carrier 5％ 15％ 5％ 1％ 9％

[0184] According to one embodiment of the present disclosure, the retention of an antimicrobial spray in the oral cavity and nasal cavity was investigated. UV light was used to confirm that an embodiment of the antimicrobial solution was visible on the oropharyngeal mucosa and nasal cavity for at least two hours during fasting. This finding was determined by self-administering the antimicrobial solution to the nose and throat using two different bottles with applicators. Two sprays were applied to the back of the throat, once in each nostril, for a total of four sprays.

[0185] In the first test, the presence of the antimicrobial solution was observed by visualizing the spray with UV light in a dark room for a total of four times over a two-hour period on a single test subject, during which eating, drinking, exercising, showering, brushing teeth, and other activities that might disrupt the barrier function of the antimicrobial solution were avoided. This visualization was able to detect the spray fluorescence in the nose and throat. The UV light source used for these visualizations was a 9LED EFL41UV flashlight with a UV wavelength of 395-400nm, available from Velleman nv, Hargaray, Belgium.

[0186] Visible spray patterns and droplets were detectable in the throat and nostrils. The brightness was checked every 15-30 minutes, and decreased over time, but was still visible for more than an hour after application of the antimicrobial solution. About 90-120 minutes after application, the droplets darkened and there was a visible spray line running down the nasal cavity. The droplets and spray line remained visible up to 140 minutes after application. The results are shown in Table 15 below.

[0187] Table 15

[0188] date Mouth pump Nose pump (each) Duration of the experiment (minutes) 2020.10.10 1 1 90 2020.10.11 1 1 105 2020.10.12 1 1 140 2020.10.15 1 1 135

[0189] The four test results in Table 15 demonstrate that embodiments of antimicrobial solutions according to the present disclosure have the ability to adhere to and remain on the oropharyngeal mucosa and nasal cavity for a sustained period of time after application, and to a visibly detectable degree.

[0190] Seven human test subjects were tested a second time by applying a baseline antimicrobial spray and then visualizing the presence of the antimicrobial solution under ultraviolet light. The intensity of the emitted light was directly proportional to the amount of antimicrobial solution present in the oropharyngeal mucosa. The human test subjects were asked to avoid any food or drink for two hours and to check the intensity of the antimicrobial spray every 30 minutes. The amount of antimicrobial spray visible in each human test subject was graded as follows: 0 = not visible; 0.5 = very faint, low coverage; 1 = faint, but visible, low coverage; 1.5 = bright, visible, limited coverage; 2 = visible with some coverage; 2.5 = bright and clearly visible spray droplets, reduced coverage; 3 = bright and clearly visible spray pattern, and good coverage. The results of the second test are shown in Table 16 below.

[0191] Table 16

[0192] Subjects Mouth pump Nose pump (each) 0min 30min 60min 90min 120min A 2 1 3 NA 2 2 1 B 2 1 3 2 1.5 1.5 0 C 2 1 3 3 2.5 3 2 D 2 1 3 3 2 2 2 E 2 1 2 2 2 1.5 1 F 2 1 3 1 0 0 0 G 2 1 3 2 2 1 1

[0193] In the above test, subject A missed his appointment by 30 minutes, subject C reported an increase from 2.5 at 60 minutes to 3 at 90 minutes (possibly due to the release of the spray from the nasal reservoir), and subject E had a small drink at 120 minutes, but this data point was not excluded because the visible effect was negligible. Subject B gave a rating of "0" at 120 minutes, but could still detect the taste of the antimicrobial solution in the mouth and nose, which reappeared 15 minutes later with a spray from the nose, rating the quantity as "1".

[0194] The data in Table 16 are as follows Figure 7 The results of the present study show that the ratings (i.e., degree of retention) and visibility (i.e., the intensity of light emitted by the oropharyngeal mucosa) were high for almost all test subjects, with a median of 3 ("bright and clearly visible spray pattern with good coverage") immediately after application and declining over time. For all subjects, the degree of retention and visibility steadily declined over time, with most subjects (5 of 7) still being detectable 120 minutes after application, with an overall median of 1 ("faint, but visible, low coverage") at 120 minutes. Even many subjects who reported a throat mucosa score of "0" still reported a taste of the antimicrobial solution, suggesting that at least a residual amount of the spray was present in the nasal cavity.

[0195] Table 16 and Figure 7 The data show that the ability of the antimicrobial solution according to the embodiments to remain in the oropharyngeal mucosa can last for a period of time. In addition, the data show that, for example, a combination of an oral spray and a nasal spray applied to the mouth and nose, respectively, is suitable, wherein the oral spray can provide immediate protection in the back of the throat, and the nasal spray can provide long-term protection due to droplets falling from the nasal cavity. In some embodiments, the method of applying an antimicrobial solution according to the present disclosure includes applying an oral spray, for example, at the beginning of the day or the beginning of a shift, and then applying a nasal spray at one or more periods during the day or shift.

[0196] These data provide strong evidence that the disclosed antimicrobial solutions can be beneficial in treating symptomatic upper respiratory tract infections by remaining on or in the oropharyngeal mucosa and providing a synergistic antimicrobial and antiviral effect on any encountered viral particles or microorganisms. This advantageously prevents infection because infection of the host's tissues is prevented and the microorganisms and viral particles are neutralized in the mucosa.

[0197] The observed benefits of the disclosed antimicrobial solution include reduction or relief of symptoms and are believed to reduce inflammation within the upper respiratory tract. In addition, these data indicate that the application of the disclosed antimicrobial spray can reduce viral titers.

[0198] Embodiment 54

[0199] Table 17 below includes antimicrobial compositions that include, in addition to an oxidative stabilizer, a carrier, and other components, St. John's wort oil at specific concentrations in combination with neem oil.

[0200] Table 17

[0201]

[0202]

[0203] In Example 54 above, the antimicrobial composition comprises a combination of extracts of Hypericum plants, and in Example 54, for other uses, Hypericum oil (such as Hypericum perforatum oil), neem oil, Ω3 PUFA, and components for promoting the combined use of Hypericum oil, neem oil and PUFA are used as nasal and / or oral sprays. For example, the antimicrobial composition includes ascorbic acid (also known as vitamin C) to adjust the pH of the antimicrobial composition to a suitable level. In a non-limiting example, ascorbic acid can be provided in the range of 0.05-0.20% w / v. The antimicrobial composition may further comprise carrageenan (e.g., 5-20% w / v) and / or chlorhexidine (e.g., 0.05-0.2% w / w, i.e., 0.05 mg / L-0.2 mg / L). In some embodiments, carrageenan and / or chlorhexidine are included.

[0204] As described in U.S. Patent No. 10293011 issued on May 21, 2019, which is incorporated herein by reference in its entirety, neem oil has healing, repellent, antiseptic and anti-inflammatory properties, while oil extracts of Hypericum have healing, pain-relieving and antiseptic or antibiotic properties. Neem oil can be considered one of the best healing and disinfectants for skin diseases. Neem oil can also be used as an anti-inflammatory for joint and muscle pain, while Hypericum can treat many ailments, including cuts, scrapes, bruises, minor burns, sciatica, injured nerves, inflammation, ulcers, bites from venomous reptiles, kidney and lung diseases, allergic reactions, anxiety and depression.

[0205] Neem oil can be obtained from the mature seeds of the neem tree (Azadirachta indica (A. Juss)) by cold / heat assisted pressing or by solvent extraction. The obtained oil can be monitored for the presence of mycotoxins (aflatoxins).

[0206] The oil extract of St. John's wort (Hypericum perforatum) is obtained by macerating the corollas of St. John's wort in vegetable oil in a transparent glass container under sunlight for at least three to six weeks. The corollas are collected when they are at maximum maturity. After the maceration process is completed, the oil extract takes on a typical ruby ​​red color. The oil extract is subsequently filtered and stored in dark glass containers to avoid oxidative degradation processes caused by exposure to natural light or UV rays. This special procedure for the preparation of Hypericum perforatum oil extract guarantees its efficacy.

[0207] As shown in the following experimental results, the combination of the antimicrobial composition shows a variety of beneficial properties, including healing effects, repellent effects, anti-inflammatory effects, pain relief effects and antiseptic effects in some embodiments. Due to the synergistic effect, the performance of each component is improved compared to a single plant component. That is, the antimicrobial composition in some embodiments can show disinfection, anti-inflammatory, antimicrobial, pain relief, analgesia and / or other properties, and can provide broad-spectrum protection, including antibacterial, without the use of local antibiotics.

[0208] In some embodiments, Hypericum oil comprises naphthodianthrone-hyperforin-optionally phloroglucinol-hyperforin. In particular, hypericin can provide antibacterial effects against various Gram-positive bacteria and virucidal or virucidal effects against viruses (particularly enveloped viruses), as well as other benefits as described above. Hypericin is believed to advantageously inhibit the ability of viruses to fuse with cell membranes.

[0209] Carrageenan advantageously provides a plant-based component to prevent viruses from interacting with the user's mucous membranes and / or cells, and amplifies and synergistically increases the antiviral and antibacterial effects of Hypericum and Neem oils and omega 3 PUFAs. Chlorhexidine advantageously provides an antibacterial effect to the antimicrobial composition and synergistically expands the antimicrobial effect of the composition. In addition, chlorhexidine advantageously extends protection to non-enveloped or non-encapsulated viruses. Advantageously, carrageenan and chlorhexidine synergistically cooperate with Hypericum and Neem oils and omega 3 PUFAs to provide broad-spectrum protection while minimizing and reducing irritation to the user.

[0210] The antimicrobial composition may include one or more diluents, such as water, sea water, vegetable oils, paraffin, combinations thereof, or others.

[0211] Surprisingly, it was found that ascorbic acid, an emulsifier (such as available from Palsgaard A / S, Juelsminde, Denmark) The combination of ammonium phosphatidate (AMP) 4455) with the Hypericum and neem oils and omega-3 PUFAs of the antimicrobial composition can advantageously maintain a pH suitable for both the nose and / or the mouth while maintaining proper emulsification of the oil-based and water-based components, particularly in view of the mild nature of the fatty acids and Hypericum and neem oils. Although AMP 4455 has been described, it should be understood that other emulsifiers, such as polyoxyethylene (20) sorbitan monooleate (also referred to as "polysorbate 80") or other emulsifiers, can also be used. In some embodiments, when polysorbate 80 is used to maintain the desired pH of the antimicrobial composition, for example, the amount of ascorbic acid can be adjusted. For example, when polysorbate 80 is provided as an emulsifier, the amount of ascorbic acid can be reduced accordingly relative to embodiments using AMP 4455 in view of the lower pH of polysorbate 80.

[0212] The ascorbic acid content in the antimicrobial composition of Example 54 is advantageously provided so that the pH of the antimicrobial composition is maintained at a desired level. In some embodiments, the pH of the composition is about 6, for example to reduce or alleviate irritation to sensitive nasal cavities. In some embodiments, the pH of the composition is about 5. It has been found that a pH of 5 can advantageously balance the amount of free fatty acids (from a solution of Hypericum walnut oil and / or omega 3 PUFAs) that can provide an antimicrobial effect while minimizing irritation to the user's nasal cavity and / or oral cavity. In other embodiments, the pH of the composition is about 4.5.

[0213] Although the above pH levels have been described, it should be understood that any suitable pH can be used and any pH adjusting component can be included in a suitable amount. For example, trisodium citrate can be used to adjust the pH of the composition to a desired level. In some embodiments, different nasal sprays and oral sprays can be provided, and considering the sensitivity of the nasal cavity relative to the oral cavity, the nasal spray may have a higher pH than the oral spray. For example, an oral spray may have a pH of about 4.5 (as low as a low value of, for example, 4.0, as high as a high value of, for example, 6.0), while a nasal spray may have a pH of about 5 (as low as a low value of, for example, 4.6 and as high as, for example, 6.0). In other embodiments, the same spray and composition are applied to the nasal cavity and the oral cavity.

[0214] It is advantageous for the antimicrobial composition of Example 54 to contain an antioxidant. The antioxidant of Example 54 is α-tocopherol (also known as vitamin E), but it should be understood that any suitable antioxidant may also be considered in other embodiments and examples. For example, other suitable vitamin E tocopherols may be provided, such as β-tocopherol, γ-tocopherol, δ-tocopherol, vitamin E tocotrienols (e.g., α-tocotrienol, β-tocotrienol, γ-tocotrienol, and δ-tocotrienol), or other suitable antioxidants. During storage, antioxidants may advantageously stabilize Hypericum oil and neem oil and Ω3 polyunsaturated fatty acids, extending the shelf life of the antimicrobial composition.

[0215] One or more components can be added to cover the taste of Hypericum oil and neem oil. In embodiment 54, extracts or components of eucalyptus oil and stevia are provided. In some embodiments, the stevia extract is rebaudioside A (Reb-A). In other embodiments, the stevia extract is stevioside. It has been surprisingly found that the flavor-related components advantageously make the antimicrobial composition palatable to the user, particularly for nasal and / or oral applications, without destroying the antimicrobial properties of the active ingredients (Hypericum oil and neem oil and Ω3PUFA, whose unpleasant smell is unexpectedly difficult to cover). Although extracts or components of eucalyptus oil and stevia have been described, it should be understood that any suitable component can be used to enhance the flavor and / or smell of the antimicrobial composition. For example, other sweeteners can be used, such as erythritol, xylitol, artificial sweeteners or any other suitable compounds.

[0216] For example, agar oil, agawan oil, angelica root oil, anise oil, asafoetida oil, Peru balsam oil, arborvitae oil, clove basil oil, bergamot oil, black pepper oil, black spruce oil, blue tansy oil, buchu oil, birch oil, camphor oil, hemp flower oil, calamodin oil, caraway seed oil, cardamom oil, carrot seed oil, cinnamon oil, cedar oil, celery seed oil, coriander leaf oil, geranium oil, cinnamon bark oil, Bark oil, labdanum oil, citronella oil, clary sage oil, coconut oil, clove oil, coffee oil, copaiba oil, coriander oil, tansy oil, zingiber officinale oil, cranberry seed oil, cubeb oil, fennel seed oil, cypress oil, cyperus oil, curry leaf oil, davana oil, dill oil, Douglas fir oil, inulin oil, elemi oil, frankincense oil, jasmine oil, lavender oil, magnolia oil, orange Flower oil, oregano oil, peppermint oil, rose oil, tea tree oil, fennel oil, fenugreek oil, fir oil, galangal oil, white pine oil, garlic oil, geranium oil, ginger oil, goldenrod oil, grapefruit oil, green tangerine oil, immortelle oil, henna oil, pecan oil, horseradish oil, hyssop oil, juniper berry oil, laurel oil, lavender oil, lemon oil, lemongrass oil, lime oil, litsea cubeba oil, agarwood oil, marjoram oil, bee Flower oil, Asian mint oil, moringa oil, myrrh oil, mountain balm oil, artemisia oil, mustard oil, myrtle oil, neroli oil, nutmeg oil, orange oil, iris oil, holy sandalwood oil, parsley oil, patchouli oil, perilla oil, mint oil, orange leaf oil, pine oil, pink pepper oil, eucalyptus oil, red cedar oil, Roman chamomile oil, rosehip oil, rosemary oil, rosewood oil, sage oil, sandalwood oil, sassafras oil, fragrant celery oil, five flavors One or more of the oils may be used as antioxidants, preservatives and / or fragrance agents.

[0217] In some embodiments where different antimicrobial compositions are provided in spray form for application to the nasal cavity and oral cavity, respectively, the nasal spray may include eucalyptus oil as a flavor enhancer, while the oral spray may include peppermint oil as a flavor enhancer. It should be understood that different components or combinations of components suitable for different nasal and oral sprays may be provided, taking into account the risk of irritation, the advantages of flavor and smell, and / or the ability of the spray to remain in the corresponding cavity as required.

[0218] The antimicrobial composition may include one or more preservatives, such as potassium sorbate. Although potassium sorbate has been described, it should be understood that other preservatives or combinations thereof may be used, including benzalkonium chloride, propylene glycol, antimicrobial peptides or others. The active ingredients, namely Hypericum oil and neem oil and omega 3 PUFAs can also synergistically provide preservative protection.

[0219] It was surprisingly found that the combination of active ingredients, namely, Hypericum and neem oil and omega-3 PUFA, is sensitive to temperature, and that providing Hypericum oil and neem oil in a v / v ratio of at least 60% can maintain the efficacy of the antimicrobial composition even when the temperature fluctuates. It was further surprisingly found that providing an antimicrobial composition of Hypericum oil and neem oil and omega-3 PUFA, wherein the neem oil is provided in a much smaller proportion than Hypericum oil, for example, a volume ratio of Hypericum:neem of greater than or equal to 10:1, in some embodiments greater than or equal to 100:1, in some embodiments greater than or equal to 500:1, in some embodiments greater than or equal to 1000:1, in some embodiments greater than or equal to 1200:1, the broad spectrum efficacy of the antimicrobial composition as well as the temperature stability is maintained.

[0220] Now turn to Figure 8 , which shows a schematic of an ongoing human subjects study. The human subjects study includes recruiting subjects to determine eligibility. This may include, for example, COVID-19 testing to determine if a potential subject is currently infected with COVID, or has antibodies that indicate a recent COVID-19 infection. After a baseline screening step, eligibility is confirmed and eligible subjects are enrolled and informed consent is obtained, ineligible subjects are excluded, for example, if the subject is already infected or has previously been infected with COVID-19. The ongoing study includes 142 subjects, randomized into a control group (71 subjects) and a study group (71 subjects).

[0221] Participants in both the control and study groups received daily dosing and symptom follow-up for 14 days, and polymerase chain reaction (PCR) testing of viral swabs to determine viral load was performed on days 3 and 5. The study also included long-term follow-up at 1, 3, and 6 months for patients who developed longer complications.

[0222] Fig. 9Preliminary data from four subjects in an ongoing human subject study are shown. Reference numeral 100 shows that the first subject 102 and the second subject 104 use an antimicrobial solution according to an embodiment, the third subject 106 and the fourth subject 108 use a control solution, and the cycle threshold (Ct) value is plotted on the y-axis, and the sample time is plotted on the x-axis, specifically, wherein 1 corresponds to the 0th day, 2 corresponds to the 3rd day, and 3 corresponds to the 5th day. A higher Ct value indicates a reduction in viral load. As shown in the figure, compared with the third and fourth control subjects 106, 108, the first and second subjects 102, 104 have experienced a reduction in viral load.

[0223] Fig.10 A schematic diagram of a planned animal subject study is shown. As shown, the animal subject study involved three different groups of subjects: the first group involved exposure to an antimicrobial solution according to one embodiment, the second group included a negative control, and the third group involved exposure to an antimicrobial solution available from Enzymatica AB, Lund, Sweden. Oral spray. Animal subjects can be ferrets, mice, monkeys, Syrian hamsters or other animals. For antimicrobial solutions and In the first group, the solution was sprayed once in the mouth and once in each nostril. All three groups were then inoculated with SARS-CoV-2.

[0224] 30 minutes after inoculation, antimicrobial solution and The group received another spray in the mouth and one spray in each nostril. An additional 60 minutes after inoculation, the antimicrobial solution and The group received another spray in the mouth, and once in each nostril. Then, all three groups (90 minutes after inoculation) received nasal washes to determine the viral load. After 24 hours, another nasal wash for viral determination was performed. Although exposure to SARS-CoV-2 is described, the test may also include enveloped viruses (e.g., coronaviruses, RSV, influenza), non-enveloped viruses (rhinoviruses), or other microorganisms. In this test or other tests related to the antimicrobial composition of some disclosed embodiments, the antimicrobial composition is evaluated as being able to prevent one or more microorganisms, such as specific viruses.

[0225] Fig.11A schematic diagram of a planned human subject study is shown. The planned human subject study includes recruiting 82 healthy volunteers for screening and narrowing down to 42 healthy volunteers. The selected volunteers will be divided into a test group (receiving an antimicrobial solution according to an embodiment) and a control group, each with 21 participants. On day 1 of the study, the test group received the antimicrobial solution and both groups were vaccinated with SARS-CoV-2. Each day from day 3 to day 10, the subjects were tested for viral load using a swab by PCR.

[0226] Because the active ingredients of the disclosed antimicrobial sprays are generally safe for ingestion at the concentrations provided and are approved by the FDA and other international food safety organizations, the disclosed formulations can be advantageously provided over-the-counter for preventive and / or symptomatic use. Therefore, the disclosed therapeutic compositions can be easily and widely distributed. This can advantageously reduce the spread of infectious upper respiratory viral pathogens within the community and help combat epidemics and / or pandemics, such as COVID-19 or similar outbreaks.

[0227] By providing an antimicrobial solution according to some disclosed embodiments, the problem of existing treatments being unsuitable for preventing and addressing microorganisms and viruses such as the novel coronavirus is advantageously addressed. The disclosed solution embodiments provide an antimicrobial solution that has a broad spectrum of effectiveness against Gram-positive and Gram-negative bacteria, enveloped and non-enveloped viruses, and other microorganisms.

[0228] Without departing from the spirit and scope of the invention as defined in the claims, various changes and / or modifications may be made to the inventive features shown in the illustrated embodiments, as well as additional applications of the principles shown in the invention, which changes and / or modifications and additional applications are within the scope of the present disclosure and are within the scope of the present disclosure. Therefore, although various aspects and embodiments are disclosed in the present invention, other aspects and embodiments are contemplated. Although many methods and components similar or equivalent to the methods and components described in the present invention can be used to practice the embodiments of the present disclosure, the present invention only describes certain components and methods.

[0229] It will also be understood that the systems, devices, products, kits, methods and / or processes according to certain embodiments of the present disclosure may include, incorporate or otherwise include the properties, features (e.g., components, members, elements, parts and / or parts) described in other embodiments disclosed and / or described by the present invention. Therefore, the various features of certain embodiments may be compatible, combined, included therein and / or incorporated therein with other embodiments of the present disclosure. Therefore, the disclosure of certain features relative to a specific embodiment of the present disclosure should not be interpreted as limiting the application of the features or the inclusion of the features to a specific embodiment. On the contrary, it should be understood that other embodiments may also include the features, members, elements, parts and / or parts without having to depart from the scope of the present disclosure.

[0230] In addition, unless a feature is described as requiring another feature to be combined with it, any feature in the present invention can be combined with any other feature of the same or different embodiments disclosed in the present invention. In addition, in order to avoid obscuring aspects of the exemplary embodiments, the present invention does not particularly describe various well-known aspects of illustrative systems, methods, devices, etc. in detail. However, the present invention also contemplates these aspects.

[0231] It should be understood that not all objects or advantages may be achieved under one embodiment of the present disclosure. Those skilled in the art will recognize that the exoskeleton and method for making an exoskeleton may be embodied or implemented in a manner that achieves or optimizes one advantage or a group of advantages taught by the present invention without achieving other objects or advantages taught or disclosed by the present invention.

[0232] Those skilled in the art will recognize the interchangeability of the various disclosed features. In addition to the variations described herein, those of ordinary skill in the art can mix and match other known equivalents of each feature to provide an antimicrobial solution according to the principles of the present disclosure. Those skilled in the art will appreciate that the features described herein are applicable to other types of solutions.

[0233] Although the present disclosure describes certain exemplary embodiments and examples of antimicrobial solutions, it will be appreciated by those skilled in the art that the present disclosure extends beyond the specifically disclosed antimicrobial solution embodiments and extends to other alternative embodiments and / or uses of the present disclosure and obvious modifications and equivalents thereof. The present disclosure should not be limited to the above disclosed embodiments and may extend to other applications that may employ the features described herein.

Claims

1. An antimicrobial solution for treating or preventing an upper respiratory tract infection in a subject, comprising The extract of Hypericum plant accounts for 5% to 60% (v / v) of the total volume of the antimicrobial solution, wherein: The Hypericum plant extracts include extracts from Hypericum perforatum ( Hypericum perforatum ), wherein the extract of the Hypericum plant comprises hypericin as a main active ingredient; Neem oil; and a pharmaceutically acceptable carrier, additive, and / or diluent that configures the antimicrobial solution to form an antimicrobial barrier on one or more of the nasal mucosa, oral mucosa, or oropharyngeal mucosa of the subject, Wherein, the pharmaceutically acceptable carrier includes glycerol, or Wherein, pharmaceutically acceptable additives include flavor enhancing additives, or Wherein, the antimicrobial solution further comprises one or more of polyunsaturated fatty acids, carrageenan and chlorhexidine.

2. The antimicrobial solution of claim 1, wherein the neem oil comprises two or more of linoleic acid, oleic acid, palmitic acid, stearic acid, α-linoleic acid or palmitoleic acid.

3. The antimicrobial solution of claim 2, wherein the neem oil comprises 6-16% linoleic acid, 25-54% oleic acid, 16-33% palmitic acid and 9-24% stearic acid.

4. The antimicrobial solution of claim 1, wherein the neem oil and the extract of Hypericum are present in equal proportions (v / v) in the antimicrobial solution.

5. The antimicrobial solution according to claim 1, wherein The neem oil is contained in the antimicrobial solution in an amount of up to 10% (v / v) of the total volume of the antimicrobial solution.

6. The antimicrobial solution of claim 1, wherein the Hypericum extract and the neem oil are provided in a volume ratio greater than 100:

1.

7. The antimicrobial solution according to claim 1, wherein The extract of the Hypericum plant is contained in the antimicrobial solution in an amount of at most 5% (v / v) based on the total volume of the antimicrobial solution.

8. The antimicrobial solution according to claim 1, wherein The extract of the Hypericum plant is contained in the antimicrobial solution in an amount of at most 10% (v / v) of the total volume of the antimicrobial solution.

9. The antimicrobial solution according to claim 1, wherein The antimicrobial solution comprises carrageenan.

10. The antimicrobial solution according to claim 1, wherein The antimicrobial solution comprises chlorhexidine.

11. The antimicrobial solution of claim 1, wherein the pharmaceutically acceptable carrier comprises glycerol.

12. The antimicrobial solution of claim 1, wherein the flavor enhancing additive comprises menthol.

13. The antimicrobial solution of claim 1, wherein: The volume proportion of the pharmaceutically acceptable carrier, additive and / or diluent contained in the antimicrobial solution is at least 10% (v / v) of the total volume of the antimicrobial solution.

14. The antimicrobial solution of claim 1, wherein: The volume proportion of the pharmaceutically acceptable carrier, additive and / or diluent contained in the antimicrobial solution is at least 33% (v / v) of the total volume of the antimicrobial solution.

15. The antimicrobial solution of claim 1, wherein the antimicrobial solution is in the form of a lotion, a hydrogel, an oral spray, and / or a nasal spray.

16. The antimicrobial solution of claim 15, wherein: The antimicrobial solution is in the form of an oral spray and / or a nasal spray, and The antimicrobial solution is delivered in a dose of 50 μL to 200 μL per actuation of the oral spray and / or nasal spray.

17. The antimicrobial solution of claim 1, wherein: The antimicrobial solution includes one or more polyunsaturated fatty acids.

18. The antimicrobial solution of claim 1, wherein: The neem oil is contained in the antimicrobial solution in an amount of 0.05% to 45% (v / v) based on the total volume of the antimicrobial solution.

19. Use of an antimicrobial solution in the preparation of a medicament for treating or preventing an upper respiratory tract infection in a subject, wherein: The antimicrobial solution comprises: The extract of the Hypericum plant accounts for 5% to 60% (v / v) of the total volume of the antimicrobial solution, wherein the extract of the Hypericum plant includes Hypericum perforatum ( Hypericum perforatum ), wherein the extract of the Hypericum plant comprises hypericin as a main active ingredient; Neem oil; and a pharmaceutically acceptable carrier, additive, and / or diluent that configures the antimicrobial solution to form an antimicrobial barrier on one or more of the nasal mucosa, oral mucosa, or oropharyngeal mucosa of the subject, Wherein, the pharmaceutically acceptable carrier includes glycerol, or Wherein, pharmaceutically acceptable additives include flavor enhancing additives, or Wherein, the antimicrobial solution further comprises one or more of polyunsaturated fatty acids, carrageenan and chlorhexidine.

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