Application of disinfectant compositions for virus propagation prevention

Abstract

The present invention relates to the application of disinfectant compositions for virus propagation prevention. In particular, aspects of the present disclosure relate to a method of preventing transmission of enveloped RNA viruses. The method comprises administering, according to a treatment regimen, an effective amount of a disinfectant composition or a pharmaceutically acceptable salt thereof to mucosal tissue of a first mammalian subject that is substantially not colonized by the enveloped RNA virus. The first mammalian subject substantially not colonized by the enveloped RNA virus interacts with a second mammalian subject colonized by the enveloped RNA virus at a first viral load, the first mammalian subject having a second viral load based on the interaction, and the first mammalian subject is colonized with the enveloped RNA virus at the second viral load over the duration of the treatment protocol, compared to the initial viral load, and the first viral load is greater than the initial viral load. The second virus load is not greater than 0.5 log increase. The mucosal tissue is in the nasopharynx, nasal cavity or anterior nostril of the mammalian subject. The disinfectant composition comprises iodine, iodophor, or a combination thereof.

Description

[0001] This application is a divisional application of a Chinese patent application with an application date of August 28, 2020, an application number of 202080058644.X, and an invention title of "Prevention of Virus Transmission by Using a Disinfectant Composition".

[0002] Statement Regarding Federal Funds

[0003] This invention was made with government support under HR0011-19-3-0006, awarded by the Defense Advanced Research Projects Agency (DARPA) of the United States. The United States government has certain rights in this invention. TECHNICAL FIELD

[0004] The present invention relates to the prevention of virus transmission by using a disinfectant composition. Specifically, the present invention relates to the use of a disinfectant composition or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating or preventing an enveloped RNA virus in a mammalian subject. BACKGROUND ART

[0005] Viruses such as influenza, especially pandemic influenza viruses, can cause problems in populations, including significant morbidity and loss of productivity. It has been demonstrated that it is difficult to control influenza A using vaccination. On average, the vaccine is only 59% effective each year and is often significantly lower. Although the influenza virus itself may cause death, most influenza-related deaths are due to viral post-bacterial pneumonia caused by the lung invasion of Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae (and others) (from the nasopharyngeal reservoir of one or more of these pathogens) via the influenza-damaged trachea. SUMMARY OF THE INVENTION

[0006] Aspects of the present disclosure relate to a method of preventing the transmission of an enveloped RNA virus. The method includes administering an effective amount of a disinfectant composition or a pharmaceutically acceptable salt thereof to the mucosal tissue of a first mammalian subject that is substantially uncolonized by the enveloped RNA virus according to a treatment protocol. The first mammalian subject that is substantially uncolonized by the enveloped RNA virus interacts with a second mammalian subject that is colonized by the enveloped RNA virus at a first viral load. The first mammalian subject has a second viral load based on the interaction. During the duration of the treatment protocol, the second viral load is no greater than a 0.5 log increase compared to the initial viral load. The mucosal tissue is in the nasopharynx, oropharynx, nasal cavity, paranasal sinuses, or anterior nares of the mammalian subject. The disinfectant composition contains iodine, iodophor, or a combination thereof. In at least one example, the no greater than a 0.5 log increase can be defined as the area under the curve. In another example, the no greater than a 0.5 log increase can mean that on any given day, the second viral load cannot be greater than 0.5 log compared to day 0.

[0007] In another aspect, the treatment regimen can include administering the disinfectant composition to the (first and / or second) mammalian subject multiple times (i.e., multiple administrations).

[0008] In another aspect, administering the disinfectant composition to the first mammalian subject can include administering the disinfectant composition to the first mammalian subject at any time period (e.g., at least 1 hour, at least 4 hours, at least 8 hours, at least 24 hours, or greater than 24 hours) before interacting with the second mammalian subject.

[0009] Other aspects of the present disclosure relate to a method of preventing the transmission of an enveloped RNA virus from a mammalian subject. The method can include administering an effective amount of the disinfectant composition or a pharmaceutically acceptable salt thereof to the mucosal tissue of a mammalian subject having a first viral load for the duration of a treatment regimen. The mucosal tissue can be in the nasopharynx, oropharynx, nasal cavity, paranasal sinuses, or anterior nares of the mammalian subject. The method can include allowing the enveloped RNA virus to agglomerate in or on the mucosal tissue upon contact with the disinfectant composition. When a second mammalian subject that is substantially free of colonization by the enveloped RNA virus interacts with the mammalian subject, the mammalian subject does not transmit the enveloped RNA virus to the second mammalian subject during the duration of the treatment regimen. The disinfectant composition comprises iodine, iodophor, or a combination thereof and a thickening agent. The disinfectant composition can comprise 10 wt% iodophor. The thickening agent can be configured to allow the disinfectant composition to persistently remain on the mucosal tissue.

[0010] Other aspects of the present disclosure relate to a method of preventing the transmission of a virus (such as an enveloped RNA virus, e.g., influenza or coronavirus). The method includes administering an effective amount of the disinfectant composition or a pharmaceutically acceptable salt thereof to the mucosal tissue of a first mammalian subject colonized with a virus at a first viral load at ambient temperature according to a treatment regimen, wherein the first mammalian subject is colonized with the virus at the first viral load. In some examples, the first viral load does not cause symptoms in the first mammalian subject. In some examples, the first mammalian subject is the recipient and the second mammalian subject is the donor, or vice versa. The method can also include allowing a second mammalian subject colonized with the virus at a second viral load to interact with the first mammalian subject, wherein the first mammalian subject is colonized with the virus at a third viral load based on the interaction. During the course of the treatment regimen, the third viral load is no greater than a 0.5 log increase compared to the first viral load. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] To easily identify the discussion of any particular element or action, one or more of the most significant digits in a reference numeral refer to the figure number where the element was first introduced.

[0012] Figure 1 A diagram according to one embodiment is shown.

[0013] Figure 2 A diagram according to one embodiment is shown.

[0014] Figure 3 An experimental configuration according to one embodiment is shown.

[0015] Figure 4 A diagram according to one embodiment is shown.

[0016] Figure 5 A diagram according to one embodiment is shown. Detailed Description

[0017] Aspects of the present disclosure may relate to a method of treating or preventing a virus (such as influenza) using a film-forming iodine-containing composition. Even after treating a mammal with a film-forming povidone-iodine composition, the film-forming iodine-containing composition can reduce the transmission of virus from one mammal to another when the amount of virus in the nostrils of a mammal increases or remains substantially the same.

[0018] "Ambient temperature" refers to the temperature in the environment in which the method of the present invention is carried out. Generally, the ambient temperature will be from about 10°C to about 30°C, and more specifically 15°C to 25°C.

[0019] "Disinfectant" refers to a chemical agent that kills or inactivates pathogenic and non-pathogenic microorganisms (including, for example, bacteria and viruses). Disinfectants can be bactericides, virucides, and / or fungicides, which kill bacteria, inactivate viruses, and kill fungi, respectively. Disinfectants generally interfere extensively with cell metabolism and / or the cell envelope. Antimicrobial agents are sometimes referred to as disinfectants, especially when used to treat hard surfaces.

[0020] "Antiviral agent" refers to an agent that inactivates a virus or inhibits its ability to replicate. Many antiviral agents are known. These antiviral agents include amantadine (which blocks the uncoating of viral particles in influenza A virus) and various nucleoside analogs that interfere with nucleic acid synthesis. Examples of nucleoside analogs include AZT, acyclovir, ganciclovir, and vidarabine. These drugs require viral replication for inactivation. Examples of suitable antiviral agents can include oseltamivir, zanamivir, and ribavirin, which are commercially available.

[0021] "Available iodine" refers to the iodine in povidone iodine that is available after it is finally released as free iodine (I2) from the polymer. Thus, it includes free iodine in solution, diatomic iodine obtainable from triiodide ions, and diatomic iodine retained within reservoirs formed by the polymer structure. Available iodine does not include iodide ions. According to the United States and British Pharmacopoeia monographs, available iodine is measured by thiosulfate titration.

[0022] "Colonized" or "colonization" means the presence of some virus, whether asymptomatic, pre-symptomatic, or symptomatic.

[0023] "Effective amount" means the amount of a pharmaceutical composition and / or enhancer component that, as a whole, provides virucidal activity to reduce, prevent, or eliminate one or more viruses, resulting in an acceptable level of viral load.

[0024] Typically, an effective amount of a disinfectant results in at least a 0.5 log reduction, at least a 1 log reduction, at least a 1.5 log reduction, or more preferably at least a 2 log reduction after 30 minutes of contact with a virus or bacterium, preferably after only 10 minutes of contact with a virus or bacterium, and most preferably after only 5 minutes of contact with a virus or bacterium.

[0025] It should be understood that the concentration or amount of a component in the compositions described herein (when considered separately) may not achieve an acceptable level of inactivating a virus, or may not inactivate such a broad spectrum of viruses, or may not inactivate a virus as quickly as the composition; however, when used together, such components provide enhanced (preferably synergistic) virucidal activity (as compared to the same components used alone under the same conditions).

[0026] "Enveloped RNA virus" refers to an RNA virus that has a viral envelope. Examples of enveloped RNA viruses include flaviviruses, alphaviruses, togaviruses, coronaviruses, hepatitis D, orthomyxoviruses (including influenza), paramyxoviruses, rhabdoviruses, bunyaviruses, and filoviruses.

[0027] "Film-forming" means a composition that forms a continuous layer when allowed to dry on intact skin under environmental conditions (e.g., 23 °C and 50% relative humidity (RH)), and the continuous layer does not flake off after simple flexion of the tissue.

[0028] "Infection" means the combination of the presence of a virus in a host and the host response to the virus. An infection can typically result in a symptomatic response from the host.

[0029] "Influenza" means influenza A, B, C, and D viruses. Influenza A viruses include at least H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7N3, H10N7, H7N9, H6N1.

[0030] "Inoculation" refers to the act or process of introducing a pathogen, such as a virus, into a living organism. Inoculation can generally refer to directly (including via contact transmission from another animal), indirectly, or passively (including via airborne transmission from another animal) exposing a mammalian subject to a virus. Inoculation occurs before symptoms are observable in the mammalian subject.

[0031] "Interaction" refers to contact transmission, or airborne transmission between at least two animal subjects, or transmission of a pathogen from a pathogen-laden surface to an animal.

[0032] "Limit of detection" refers to the lowest concentration of a virus that gives a response that is at least three times the average baseline noise.

[0033] "Mammalian subject" refers to a human, sheep, horse, cow, pig, dog, cat, guinea pig, ferret, rat, mouse, bat, or other mammal.

[0034] "Mucosal tissue" refers to the mucus-producing membranous surfaces of the nasal cavity (including the anterior nares, nasopharynx, etc.), vagina, and other similar tissues. Examples include mucosae such as those of the nasal cavity, rectum, urethra, ureter, vagina, cervix, and uterus.

[0035] "Retention" refers to the continued presence of a virus within or on mucosal tissue during normal physiological activities (e.g., breathing, sneezing, coughing, expectorating). Retention can occur by entrapment, aggregation, intracellular presence of the virus, or combinations thereof. "Aggregate" or "aggregation" refers to the clumping of virus particles that may occur when there is no effective means of separating virus particles from one another after their release from cells during infection (e.g., in the absence of an effective neuraminidase in influenza virus infection).

[0036] "Substantive" refers to a disinfectant composition (or a film-forming polymer in solution) that, when applied to human skin in an amount that forms a uniform wet film on the clean, dry skin of the inner forearm at about 4 milligrams per square centimeter (4 mg / cm 2 ), and is allowed to dry thoroughly (e.g., for at least 10 minutes at 23 °C and 50% relative humidity), resists removal under running tap water that falls from a height of 15 centimeters (cm) at a flow rate of about 2.4 - 2.5 liters per minute (L / min) at a temperature of about 23 °C to about 24 °C, impinging on the skin directly above the dried composition (without directly hitting the dried composition) and then flowing over the dried composition for at least about 15 seconds.

[0037] "Symptom" refers to a physiological characteristic that indicates a disease condition. Symptoms of influenza can include runny nose, fever, muscle aches, headache, chills, sweating, dry cough, fatigue, nasal congestion, sore throat, or a combination thereof. The viral load of influenza at symptom onset can be virus species-dependent and host species-dependent. For example, in humans, symptoms of influenza A can occur when the viral load is at least 100,000 PFU / mL, at least 500,000 PFU / mL, or at least 1,000,000 PFU / mL. In mice, the viral load of influenza A at symptom onset can be at least 100 PFU / mL.

[0038] "Thickener" refers to a substance that increases the viscosity of a liquid without substantially changing its other properties. Thickeners can be anionic, cationic, or neutral ionic. The thickened disinfectant composition does not include cross-linked polymers (i.e., gels).

[0039] "Treatment regimen" refers to a series of treatments. "Treat" or "treatment" means to improve the condition of a subject with respect to suffering, typically based on the clinical symptoms of a condition or the viral or bacterial load.

[0040] "Upper intake level" refers to the safe intake level of iodine as established by Leung AM, Avram AM, Brenner AV, et al. Potential risks of excessive iodine intake and exposure: Statement by the American Thyroid Association Public Health Committee, Thyroid. 2015; 25(2):145 - 146.

[0041] Aspects of the present disclosure relate to reducing the transmission of a virus (e.g., influenza) by an infected individual and reducing the transmission of a virus (e.g., influenza) by providing a protective barrier against infection to healthy individuals (i.e., prevention).

[0042] It should be understood (unless otherwise specified) that the concentrations of all listed components are for the "ready-to-use" or "as-used" composition. The composition can be in concentrated form. That is, certain embodiments of the composition can be in concentrate form, which is diluted by the user with a suitable carrier. However, this is generally not convenient for current applications.

[0043] The term "comprising" and its variants do not have a limiting meaning where these terms appear in the specification and claims.

[0044] As used herein, the terms "a", "the", "at least one", and "one or more" are used interchangeably. The term "and / or" refers to one or all of the recited elements (e.g., preventing and / or treating an infection refers to preventing, treating, or both treating and preventing further infection).

[0045] In addition, herein, a numerical range expressed by endpoints includes all the values contained within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

[0046] The above Summary of the Invention is not intended to describe every disclosed embodiment or every implementation of the present invention. The following description more particularly illustrates exemplary embodiments. Throughout this application, guidance is provided through lists of examples, which can be used in various combinations. In each case, the recited lists are only used as representative groups and should not be construed as exclusive lists.

[0047] The pharmaceutical compositions of the present disclosure can include a disinfectant composition and an antiviral composition. Some disinfectant compositions and antiviral compositions are known and described herein.

[0048] Examples of disinfectant compositions can include those described in U.S. Patent Publication No. 20180207122 and U.S. Patent No. 8808722, which are incorporated herein by reference. Preferred disinfectant compositions are film-forming. For example, a film-forming polymer can retain the active antimicrobial component at the site of pain and / or at the site where an infection begins (e.g., the nostrils) for a longer period of time. This can be desirable for certain applications. For example, some film-forming polymers can produce a composition that cannot be easily eluted after application and drying.

[0049] In at least one embodiment, a pharmaceutical composition containing a broad-spectrum disinfectant can be used, such as iodine or povidone-iodine, hydrogen peroxide, hypochlorite, chlorhexidine salts, poly(hexamethylene biguanide), triclosan, small molecule quaternary amines (such as benzethonium chloride, methylbenzethonium chloride, benzalkonium chloride, and octenidine), antimicrobial metals (such as silver), and combinations thereof, optionally having an enhancer component.

[0050] Preferably, a disinfectant composition using iodine or iodophor (e.g., PVP-I) is employed. Some disinfectant compositions are also durable. Examples of durable disinfectant compositions are commercially available under the following trade names: 3M Skin and Nasal Disinfectant from 3M Company (3M, St Paul, MN). 3M Skin and Nasal Disinfectant contains about 0.5% available iodine and is about 5 wt% PVP-I. 3M Skin and Nasal Disinfectant may contain thickeners such as hydroxyethyl cellulose, surfactants, and buffers. Other suitable disinfectant compositions are commercially available under the following trade names: Betadine from Aviro Health, Profend from PDI Healthcare, or Nozin from Global Life Technologies.

[0051] Suitable iodophor concentrations can range from 0.25 wt% to 10 wt%, 2.5 wt% to 10.5 wt%, 3.5 wt% to 10.5 wt%, or 4.5 wt% to 5.5 wt% of the disinfectant composition. These concentrations are considered effective against various enveloped RNA viruses such as influenza, norovirus, rhinovirus, coronavirus, parainfluenza virus, respiratory syncytial virus (RSV), and combinations thereof. In at least one embodiment, the concentration of iodophor can be up to 5.5 wt% iodophor.

[0052] In at least one embodiment, the pharmaceutical composition can be administered according to a treatment protocol. The treatment protocol can include options for treatment after and before (prophylaxis) inoculation with the virus. For example, in one treatment protocol, the pharmaceutical composition can be administered (via the nostrils of a mammalian subject) to a mammalian subject before inoculation. In another treatment protocol, the pharmaceutical composition can be administered after inoculation with the virus (e.g., at the onset of any symptoms). In another treatment protocol, the pharmaceutical composition can be administered in response to another mammalian subject showing symptoms (i.e., prophylaxis) to prevent the spread of the virus from the mammalian subject showing symptoms to the mammalian subject. In another treatment protocol, the pharmaceutical composition can be administered to one or more mammalian subjects showing symptoms and one or more mammalian subjects in direct contact and / or indirect (through air flow) contact with one or more mammalian subjects showing one or more symptoms.

[0053] In at least one embodiment, a mammalian subject exposed to a mammalian subject colonized with the virus should not exhibit symptoms of viral infection. In at least one embodiment, the delay in a mammalian subject showing symptoms after exposure to a mammalian subject colonized with the virus can be at least 1 day, or can be at least 2 days or more.

[0054] In at least one embodiment, the treatment regimen can occur over a duration. The duration can be at least 6 hours, at least 1 day, at least 3 days, at least 5 days, or at least 7 days.

[0055] The treatment regimen can include multiple administrations of the disinfectant composition over the duration. The treatment frequency can range from once every 72 hours to 1 to 12 times per day. By way of example, the treatment frequency can be once every 72 hours, once every 60 hours, once every 48 hours, once every 36 hours, once every 25 hours, once every 24.5 hours (i.e., more than 24 hours elapse between administrations), once every 24 hours, once every 12 hours, once every 8 hours, once every 6 hours, or 5 times per day, 6 times per day, 7 times per day, or 8 times per day. The treatment frequency can occur generally evenly throughout the day. In at least one embodiment, the treatment can include administering as a concentrate (i.e., highly concentrated dose) during shorter intervals during the day. In at least one embodiment, the combination of the dose and treatment frequency will deliver to the mammalian subject less than the upper intake level of the pharmaceutical composition. Additionally, the treatment regimen will not allow for the available iodine to exceed the toxicity of iodine for an adult male (e.g., 2 g / day).

[0056] In at least one embodiment, the treatment regimen can include administering the pharmaceutical composition to the mucosal tissue of a mammalian subject. Aspects of administering the disinfectant composition are provided by Scholz et al., U.S. Patent Publication No. 20180207122 (published Jul. 26, 2018), which is incorporated herein by reference in its entirety. Preferably, the mucosal tissue refers to the mucosal tissue of the nostrils, nasopharynx, oral cavity, or the mucosal tissue of the nasal cavity and / or anterior nares. Administration of the pharmaceutical composition can include inserting a swab impregnated with the pharmaceutical composition into the nasal cavity and diffusing the pharmaceutical composition along the diameter of the nasal cavity. In at least one embodiment, the disinfectant composition can be administered to the nostrils at any depth. For example, the disinfectant composition can be administered to the posterior nares at a depth of at least 1 cm from the tip of the nose. In at least one embodiment, a second pharmaceutical composition can also be administered after the first pharmaceutical composition. For example, after administering the disinfectant, an antiviral agent can then be used in combination with the disinfectant (i.e., topically, orally, or by injection) for a period of time.

[0057] In at least one embodiment, administration of the disinfectant compound can cause retention of the enveloped RNA virus such that the mammalian subject does not transmit the enveloped RNA virus to another mammalian subject.

[0058] In at least one embodiment, "substantially free of viral colonization" means that a mammalian subject does not exhibit symptoms caused by a virus (i.e., asymptomatic or pre-symptomatic). Substantially free of viral infection or substantially free of viral colonization can also mean that a mammalian subject is substantially free of enveloped RNA virus colonization. In at least one embodiment, substantially free of colonization can mean that a recipient mammalian subject (without virus) can have a viral load at a level below the limit of detection or less than 100 pfu / mL.

[0059] In at least one embodiment, when the presence and / or severity of a disease is related to viral load, a virus can colonize a mammalian subject at a level above the limit of detection but below the level that causes the disease. In at least one embodiment, a mammalian subject colonized with an enveloped RNA virus can have a viral load of at least 1000 pfu / ml, at least 5000 pfu / ml, or at least 10000 pfu / ml, or otherwise exhibit symptoms of an enveloped RNA virus.

[0060] Examples :

[0061] In the following examples, a disinfectant composition of 3M Skin and Nasal Disinfectant (containing 5 wt% povidone-iodine) (referred to herein as "nasal preparation") was commercially available from 3M Company, St. Paul, Minnesota. Phosphate Buffered Saline (PBS), pH = 7.4, was commercially available from Thermo Fisher Scientific (catalog number 10010023). Disease-free animals were obtained from a commercial experimental animal supplier.

[0062] Example 1: Prevention of influenza virus infection in mice by treatment with a disinfectant composition.

[0063] For the following examples using mice, the following additional materials were used:

[0064] • 28 female C567BL / 6 mice, 8 - 10 weeks old, commercially available from a disease-free animal supplier

[0065] • Influenza A virus / PR / 8 / 38 (H1N1).

[0066] The mice were divided into three groups: Group 1, Group 2, and Group 3. There were 12 mice in Group 1, 12 mice in Group 2, and 4 mice in Group 3. The mice in Group 1 were treated with the disinfectant composition. The mice in Group 2 were treated with PBS (as a placebo). The mice in Group 3 served as untreated controls. At 0, 6, or 24 hours after the initial treatment with the disinfectant composition or placebo (or no treatment in the untreated control group), the mice were inoculated with 25,000 plaque-forming units (PFU) of influenza A / PR / 8 / 38 (H1N1). Three days after infection, the mice were euthanized, the euthanized mice were nasally flushed with PBS, and the virus levels were determined by plaque assay.

[0067] Example 1 :

[0068] The mice were anesthetized with ketamine, then the 3M Skin and Nasal Disinfectant was applied, and then the virus was inoculated. For each mouse in Group 1, the 3M Skin and Nasal Disinfectant was applied using a 2 µL pipette tip by spreading approximately 5 µL of the 3M Skin and Nasal Disinfectant onto the inner surfaces of both nostrils. Then each mouse in Group 1 was inoculated with the influenza virus (a total of 25,000 PFU) into the nostrils at one of the following time points: immediately after intranasal treatment with the 3M Skin and Nasal Disinfectant (4 animals), 6 hours after intranasal treatment (4 animals), and 24 hours after intranasal treatment (4 animals). Three days after virus inoculation, the animals were euthanized and the virus levels were determined by plaque assay using nasal wash fluid.

[0069] Comparative Example 1 :

[0070] The mice were anesthetized with ketamine, then the 3M Skin and Nasal Disinfectant was applied, and then the virus was inoculated. For each mouse in Group 2, PBS was applied using a 2 µL pipette tip by spreading approximately 5 µL of PBS onto the inner surfaces of both nostrils. Then each mouse was inoculated with the influenza virus (25,000 PFU) into the nostrils at one of the following time points: immediately after intranasal treatment (4 animals), 6 hours after intranasal treatment (4 animals), and 24 hours after intranasal treatment (4 animals). Three days after virus inoculation, the animals were euthanized and the virus levels were determined by plaque assay using nasal wash fluid.

[0071] Comparative Example 2 :

[0072] The mice were anesthetized with ketamine before virus inoculation. Each mouse in Group 3 was inoculated with the influenza virus (25,000 PFU) into the nostrils. Three days after virus inoculation, the animals were euthanized and the virus levels were determined by plaque assay using nasal wash fluid.

[0073] Figure 1It is a bar graph indicating that no live virus was recovered from any of the mice in Group 1, regardless of the length of time (up to 24 hours) between treatment with 3M Skin and Nasal Disinfectant and virus inoculation. Figure 1 It also shows the recovery of live virus from Group 2, whose individuals were inoculated with the virus 6 hours and 24 hours after administration of PBS. Figure 1 It also shows the recovery of live virus from Group 3, whose individuals were untreated before virus inoculation. Figure 1 Indicates 24-hour prevention of influenza infection with a single application of 3M Skin and Nasal Disinfectant.

[0074] Figure 2 It is a graph indicating that Group 2 had 50 PFU / ml of live virus in the nostrils when inoculated with the virus 6 hours after administration of PBS, and 100 PFU / ml of live virus in the nostrils when inoculated with the virus 24 hours after administration of PBS. Group 3 had 200 PFU / mL of live virus in the nostrils 24 hours after influenza virus inoculation. Thus, the animals in Group 1 did not have any live virus in their nostrils after treatment with 3M Skin and Nasal Disinfectant and then inoculation with influenza virus for up to 24 hours.

[0075] Example 2: Prevention of Airborne Transmission of Influenza Virus in Guinea Pigs 。

[0076] Female Hartley guinea pigs, five to six weeks old, were purchased from Charles River Laboratories (Wilmington, MA). The animal weights were between 350 g and 400 g. The animals were allowed free access to food and water and were housed on a 12-hour light-dark cycle.

[0077] Infection and monitoring of guinea pigs: Guinea pigs were anesthetized by intramuscular administration of a mixture of 175-µl of ketamine (30 mg / kg body weight) and xylazine (5 mg / kg). An inoculum of influenza virus “Pan99” (A / Panama / 2007 / 1999 (H3N2)) was instilled intranasally by administering a certain volume of the undiluted virus solution (3 × 10 4 pfu / mL) into each nostril.

[0078] Collection of guinea pig nasal wash samples: Before collecting nasal wash samples, guinea pigs were anesthetized as described above. Nasal lavage was performed by instilling a total of 1 mL of phosphate-buffered saline (PBS) into the guinea pigs' nostrils and allowing it to drain into a sterile petri dish with a lid. The supernatant was stored at -80 °C before analysis by plaque assay.

[0079] Treatment: Treatment with nasal preparations and PBS (phosphate-buffered saline).

[0080] Experiment: Sixteen animals were used in the experiment. Each animal was identified as one of a pair of animals, where the cages of each pair were connected by a duct that enabled the exchange of air between the two cages, as Figure 3 described.

[0081] For the airborne transmission experiment, the virus donor and virus recipient animals were physically separated by an air-permeable barrier that excluded direct contact transmission while allowing diffusion from the donor animal to the recipient animal via the airborne transmission route (droplets and aerosols).

[0082] One animal from each pair was infected with influenza A / Panama / 2007 / 1999 (H3N2) virus and the animals were then treated according to the treatment protocol described below.

[0083] Day -1: On day "-1" of the experiment, the animals were paired and designated as follows:

[0084] Four animals were designated "donor, nasal formulation", indicating that those animals so designated would be inoculated with influenza virus and treated with the disinfectant composition.

[0085] Four animals were designated "recipient, nasal formulation", indicating that each of those four animals was paired with one of the "donor, nasal formulation" animals. The recipient, nasal formulation animals were treated with the disinfectant composition and exposed to any influenza virus via the air from the duct of the donor, nasal formulation animals.

[0086] Four animals were designated "donor, placebo (PBS)", indicating that those animals so designated would be inoculated with influenza virus and treated with PBS.

[0087] Four animals were designated "recipient, placebo (PBS)", indicating that each of those four animals was paired with one of the "donor, placebo (PBS)" animals. The recipient, placebo (PBS) animals were treated with PBS and exposed to any influenza virus via the air from the duct of the donor, placebo (PBS) animal cages.

[0088] On day -1, all animals designated "nasal formulation" were treated with the disinfectant composition by instilling 50 μl of the disinfectant composition into each nostril of the awake, upright animals. Additionally, all animals designated "placebo (PBS)" were treated with PBS by instilling 50 μl of PBS into each nostril of the awake, upright animals.

[0089] On day 0, all animals marked as "donors" were inoculated in each nostril with 75 μL of "Pan 99" influenza virus (as described above) under ketamine anesthesia (as described above). Three hours later, all animals were treated with PBS or the disinfectant composition (as described above) according to their experimental designation.

[0090] On days +1, +3, +5, and +7, all animals were anesthetized, underwent nasal lavage (by dripping 1 mL of PBS sampling solution into the nostrils (while prone)), allowed to recover, and then treated with the disinfectant composition or placebo (PBS) according to their experimental treatment designation.

[0091] On days +2, +4, and +6, all animals were treated with the disinfectant composition or placebo (PBS) according to their experimental treatment designation.

[0092] The nasal lavage fluids collected on days +1, +3, +5, and +7 were diluted (1 to 10-fold) immediately after collection with PBS. (Earlier in vitro experiments showed that a 1 to 10-fold dilution was sufficient to prevent residual iodine (rinsed out of the nose during nasal lavage) from inactivating the virus in the nasal lavage fluid samples prior to titration by the plaque assay.) To quantify the live virus, the nasal lavage fluid samples were serially diluted and plated onto MDCK cells to quantify the virus. The virus amount was reported as plaque-forming units (pfu). Figure 4 The results of the transmission experiment are shown.

[0093] Results: Figure 4 A graph showing the mean virus titers across 4 groups of guinea pigs, where the LOD is the limit of detection of the plaque assay. The results of the experiments in Table 1 (where the unit is [log(pfu / mL)]) show that treatment with the disinfectant composition prevented airborne transmission of the influenza virus in 3 out of 4 tested recipient animals, while treatment with the placebo (PBS) prevented airborne transmission in only 2 out of 4 tested recipient animals.

[0094] Table 1 - Guinea Pig Transmission Data

[0095]

[0096] In addition, treatment of individual recipient animals infected by airborne transmission of the influenza virus with the disinfectant composition reduced the viral load (the amount of virus in the nostrils) of the infected recipient below the limit of detection within 48 hours after infection occurred, while treatment with PBS allowed the viral load to continue to increase in at least one of the PBS-treated animals to which the virus had spread during the same 48-hour time period.

[0097] In addition, 3 days after inoculation, the donor treated with the nasal preparation (Examples 1-4) had at least 1.5 log lower virus titer concentration compared to the placebo (Comparative Examples 5-8).

[0098] Example 3: Evaluation of Virus Counts in the Nostrils of Guinea Pigs Treated with Nasal Preparations 。

[0099] Infection and monitoring of guinea pigs: Before infecting with influenza virus, guinea pigs were anesthetized by intramuscular administration of a mixture of 175-µl ketamine (30 mg / kg body weight) and xylazine (5 mg / kg). An inoculum of "Pan99" influenza A virus was instilled intranasally by applying a certain volume of the undiluted solution of influenza virus (3 × 10 4 pfu / mL A / Panama / 2007 / 1999 (H3N2)) into each nostril. (The volume administered was indicated separately for each experiment described below).

[0100] Collection of guinea pig nasal wash samples: Before collecting nasal wash samples, guinea pigs were anesthetized as described above. Nasal lavage was performed by instilling a total of 1 mL of phosphate-buffered saline (PBS) into the guinea pigs' nostrils and allowing it to drain into a sterile covered Petri dish. The supernatant was stored at -80 °C before analysis by plaque assay.

[0101] Treatment: Animals were treated with the nasal preparation, the vehicle (3M ™ Skin and Nasal Disinfectant without povidone-iodine and sodium iodide), and PBS (phosphate-buffered saline).

[0102] Day -1: On the " -1" day of this experiment, ten guinea pigs were treated as follows:

[0103] Four guinea pigs were treated with the nasal preparation (while awake and upright) using a pipette, and 50 µL of the nasal preparation was delivered to each nostril (100 µL per guinea pig).

[0104] Four guinea pigs were treated with the vehicle (while awake and upright) using a pipette, and 50 µL of the vehicle was delivered to each nostril (100 µL per guinea pig).

[0105] Two guinea pigs were treated with PBS (while awake and upright) using a pipette, and 50 µL of PBS was delivered to each nostril (100 µL per guinea pig).

[0106] Day 0: All guinea pigs were anesthetized and then inoculated with 150 µL (75 µL / nostril) of a diluted undiluted solution of Pan99 influenza A virus at a concentration of 6.7 × 10 3 pfu / ml, equivalent to each animal receiving 1 × 10 3Influenza virus of pfu. After 6 hours, when the guinea pigs had fully recovered from anesthesia, the treatment was re-administered as described above (Day -1).

[0107] Day +1, Day +3, Day +5, and Day +7: All guinea pigs were anesthetized, underwent nasal lavage (1 mL PBS sampling solution), and then allowed to recover. On Day 1, Day 3, and Day 5, after recovery, the guinea pigs were treated with the nasal preparation, vehicle, or PBS as described above (Day -1).

[0108] Day 2, Day 4, Day 6: All guinea pigs were treated with the nasal preparation, vehicle, or PBS as described above (Day -1).

[0109] The nasal lavage fluid was diluted and plated onto Maden Darby Canine Kidney cells commercially available from Sigma - Aldrich (St. Louis, MO) for quantification of live virus.

[0110] Figure 5 The results of Example 3 are shown.

[0111] The results of Example 3 showed that for the animals treated with the nasal preparation (502, n = 4 animals), the amount of live virus increased steadily from Day 1 to Day 7, and for the animals treated with the vehicle (506, n = 4 animals) and the animals treated with PBS (504, n = 2 animals), the amount of live virus decreased continuously during this period.

[0112] The results of Example 3 obtained with the results of Example 2 showed a surprising result that the povidone - iodine composition used in the treatment method prevented the spread of the virus. Without being bound by theory, it is suspected that the virus particles may be retained by agglomeration in the nostrils in the presence of the thickened povidone - iodine composition and cannot be easily transferred from one animal to another. It is also suspected that nasal lavage during nostril sampling disrupted the presumed agglomeration and allowed the virions to replicate in MDCK cells, which led to plaques caused by the virus on the MDCK monolayer.

[0113] Example 4 - In Vitro Efficacy of Nasal Preparations Against SARS-CoV-2 Virus .

[0114] Procedure :

[0115] Viruses, Media, and Cells

[0116] The SARS - CoV - 2 virus stock solution was prepared by growing the virus in Vero 76 cells. The test medium was MEM supplemented with 2% FBS and 50 µg / mL gentamicin.

[0117] Virucidal Assay

[0118] Sterile water was used as a diluent and the nasal preparation (90% nasal preparation and 10% virus solution) was tested at three additional consecutive 10-fold dilutions at full strength. The SARS-CoV-2 virus stock solution was added to three tubes of each prepared concentration (prepared at a dilution of 1 / 10) such that the final concentration of the tested nasal preparation was 90% of full strength (0.45% w / w available iodine), 9% of full strength (0.045% w / w available iodine), 0.9% of full strength (0.0045% w / w available iodine), and 0.09% of full strength (0.00045% w / w available iodine). Culture medium was added to only one tube of the nasal preparation at each prepared concentration to serve as a cytotoxicity control. Ethanol (63%) (commercially available from Sigma Aldrich) was tested in parallel as a positive control for virucidal activity, and only water was tested as a virus control. The solutions and virus were incubated at room temperature for three contact times of 30 seconds, 1 minute, and 2 minutes. After the contact period, each solution was "neutralized" using a 1 / 10 dilution of 0.5% sodium thiosulfate in the test medium. (Sodium thiosulfate, Na2S2O3, reduces molecular iodine (I2) to colorless iodide anions (I - ), which do not have in vitro virucidal activity.)

[0119] Virus Quantification

[0120] The neutralized samples were serially diluted in eight half-log dilutions in the test medium. Each dilution was added to four wells of a 96-well plate that were 80%-100% confluent Vero 76 cells. The toxicity control was added to four additional wells, two of which were virus-infected to serve as neutralization controls, ensuring that any residual test samples remaining in the individual titer determinations plated did not inhibit the growth and detection of viable virus. All plates were incubated at 37 ± 2 °C in 5% CO2.

[0121] On day 6 post-infection, the plates were scored for the presence or absence of viral cytopathic effect (CPE). The Reed-Muench method was used to determine the endpoint titer of the samples (50% cell culture infective dose, CCID 50 50) and calculate the log reduction value (LRV) of the compound compared to the negative (water) control. The sample results were compared to the untreated control using GraphPad Prism (version 8) software by one-way ANOVA with Dunnett's multiple comparison test.

[0122] Controls

[0123] Viral controls were tested in water, and the reduction of virus in the test wells was compared to the viral controls and calculated as the log reduction value (LRV). Toxicity controls were tested with virus-free media to determine if the sample was toxic to the cells. Neutralization controls were tested to ensure that virus inactivation did not continue after the specified contact time and that any residual sample remaining in the titer plate did not inhibit the growth and detection of viable virus; this was done by adding the toxic sample to the titer test plate and then spiking each well with a small amount of virus particles (to a degree that would produce an observable level of cytopathic effect during incubation).

[0124] Results

[0125] The viral titers and log reduction values for the nasal preparations against the SARS-CoV-2 virus are shown in Table 2.

[0126] In 3M ™ Two of the eight half-log dilutions (1 / 10 and 1 / 100 dilutions) of the highest concentration (90% potency) of the skin and nasal disinfectant neutralized in 3M ™ Complete toxicity to Vero 76 cells was observed in the 1 / 10 dilution of the 9% potency of the skin and nasal disinfectant. Due to this toxicity, the presence of live virus could not be excluded in these wells, and thus the limit of detection was 2.7 log 10 and 1.7 log 10 CCID 50 virus / 0.1mL. Similarly, ethanol caused toxicity at the 1 / 10 dilution. After contact with the virus for 30 seconds, 1 minute, or 2 minutes at room temperature, the 9% solution of the nasal preparation reduced the virus count to below the limit of detection, i.e., >2 log 10 CCID 50 / 0.1mL (>99%, P<0.001). Although not inactivating all of the virus present, the 0.9% solution reduced the virus by >2 log 10 CCID 50 / 0.1mL (99%, P<0.0001) (after 1 or 2 minutes of contact time) and >1 log 10 CCID 50 / 0.1mL (90%, P<0.01) (after 30 seconds of contact time).

[0127] Due to cytotoxicity, for all three contact times, the level of virus reduction by the 90% solution of the nasal preparation was limited to >1 log 10 CCID 50 / 0.1mL (90%, P<0.05). The 0.09% solution of the nasal preparation did not reduce the virus during the contact times tested.

[0128] The neutralization control demonstrated that any residual iodine in the neutralized sample did not inhibit virus growth and that virus was not detected in the endpoint titer assay in wells that did not show cytotoxicity. The virus control and positive control proceeded as expected.

[0129] Thus, the virucidal efficacy of the nasal formulation against SARS-CoV-2 was as low as 0.9% (0.0045% w / w available iodine) during contact times as low as 30 seconds duration.

[0130] Table 2: Virucidal efficacy of the nasal formulation against SARS-CoV-2 after incubation of the virus at 22 ± 2 °C.

[0131]

[0132] Log of virus per milliliter 10 CCID 50 , mean of 3 replicates, "<" means limit of detection

[0133] b LRV (log reduction value) is the reduction of the virus compared to the virus control

[0134] List of Exemplary Embodiments :

[0135] 1. A method of treating or preventing an enveloped RNA virus in a mammalian subject, comprising:

[0136] administering an effective amount of a disinfectant composition or a pharmaceutically acceptable salt of the disinfectant composition to the mucosal tissue of the mammalian subject having a first viral load;

[0137] allowing the first viral load to decrease to a second viral load over the duration of a treatment regimen,

[0138] wherein during the duration of the treatment regimen, there is at least a 0.5 log reduction in the second viral load with use of the disinfectant composition compared to use of a placebo,

[0139] wherein the disinfectant composition comprises iodine, iodophor, or a combination thereof and a thickening agent.

[0140] 2. The method according to embodiment 1, wherein the first viral load is associated with the onset of symptoms of the virus.

[0141] 3. The method according to any of the preceding embodiments, further comprising: administering an effective amount of an antiviral agent to the mammalian subject.

[0142] 4. The method according to any of the preceding embodiments, wherein the placebo is phosphate buffered saline.

[0143] 5. A method according to any one of the foregoing embodiments, wherein the iodine or iodophor is present in a concentration sufficient to provide an available iodine concentration of 0.0045 wt% to 0.55 wt%.

[0144] 6. A method according to embodiment 5, wherein the concentration of the PVP-I is not greater than 10 wt% (100 mg / ml).

[0145] 7. A method according to embodiment 6, wherein the concentration of the PVP-I is 4.5 wt% to 5.5 wt% (45 mg / ml to 55 mg / ml).

[0146] 8. A method according to any one of the foregoing embodiments, wherein the disinfectant composition comprises water, a surfactant, and a buffer.

[0147] 9. A method according to embodiment 8, wherein the disinfectant composition comprises a hydroxycarboxylic acid present at a concentration of at least 2.5 wt%; an amine oxide; and an iodide salt present at a concentration of at least 2.0 wt% and in an amount not greater than 10 wt%, wherein the composition is ready-to-use, and wherein the composition exhibits a reduction of no more than 5% weight / weight of available iodine when stored at 40 °C for about 6 months.

[0148] 10. A method according to embodiment 9, wherein the hydroxycarboxylic acid is present in an amount greater than 5 wt%.

[0149] 11. A method according to embodiment 9, wherein the amine oxide is present at a concentration of 0.25 wt% to 1.5 wt%.

[0150] 12. A method according to embodiment 9, wherein the disinfectant composition further comprises a monosaccharide, a sugar alcohol, or a combination thereof, wherein the monosaccharide, sugar alcohol, or combination thereof is present at a concentration greater than 5% weight / weight.

[0151] 13. A method according to embodiment 9, wherein the disinfectant composition comprises a surfactant; wherein the surfactant includes an anionic surfactant, an amphoteric surfactant, a nonionic surfactant, a zwitterionic surfactant, or a combination thereof; wherein the anionic surfactant includes phosphates, phosphonates, sulfates, sulfonates, or a combination thereof.

[0152] 14. A method according to embodiment 9, wherein the disinfectant composition comprises a carrier, wherein the carrier comprises water and polyethylene glycol having a weight average molecular weight of less than 1500.

[0153] 15. The method according to any one of the foregoing embodiments, wherein the disinfectant composition comprises a thickening agent.

[0154] 16. The method according to any one of the foregoing embodiments, wherein the disinfectant composition does not contain liposomes.

[0155] 17. The method according to any one of the foregoing embodiments, wherein the treatment regimen comprises administering the disinfectant composition at a frequency of 1 to 12 times per day.

[0156] 18. The method according to any one of the foregoing embodiments, wherein the treatment regimen does not exceed the upper intake level of the disinfectant composition.

[0157] 19. The method according to any one of the foregoing embodiments, wherein in the treatment regimen, at least 24 hours elapse between administrations.

[0158] 20. The method according to any one of the foregoing embodiments, wherein the duration is 1 day, 3 days, 5 days or 7 days.

[0159] 21. The method according to embodiment 18, wherein each subsequent treatment of the disinfectant composition in the treatment regimen increases the concentration of the disinfectant.

[0160] 22. The method according to embodiment 18, wherein each subsequent dose of the disinfectant composition in the treatment regimen decreases the concentration of the disinfectant.

[0161] 23. The method according to any one of the foregoing embodiments, wherein the disinfectant composition is administered into the nasal cavity for more than 1 cm.

[0162] 23a. The method according to any one of the foregoing embodiments, wherein the disinfectant composition is administered into the nasal cavity for less than 1 cm.

[0163] 24. The method according to any one of the foregoing embodiments, wherein the enveloped RNA virus is influenza or coronavirus.

[0164] 25. The method according to any one of the foregoing embodiments, wherein the first virus load is at least 1000 plaque forming units (PFU) per milliliter.

[0165] 26. The method according to any one of the foregoing embodiments, wherein the second virus load is not greater than 32 plaque forming units (PFU) per milliliter.

[0166] 27. The method according to any one of the foregoing embodiments, wherein the first viral load is not greater than 32 PFU per milliliter.

[0167] 28. The method according to embodiment 27, wherein the second viral load is not greater than 100 PFU per milliliter.

[0168] 29. The method according to any one of the foregoing embodiments, further comprising:

[0169] administering an effective amount of the disinfectant composition or a pharmaceutically acceptable salt thereof to the mucosal tissue of a second mammalian subject before exposure to the mammalian subject and according to the treatment protocol;

[0170] allowing the mammalian subject to interact with the second mammalian subject for a period of time, wherein the second mammalian subject has a viral load increase of not more than 0.5 log during the treatment protocol.

[0171] 30. The method according to embodiment 29, wherein the period of time is at least 1 hour, at least 2 hours, at least 3 hours, or at least 4 hours.

[0172] 31. The method according to any one of the foregoing embodiments, wherein interacting means contacting any body part.

[0173] 32. The method according to any one of the foregoing embodiments, wherein interacting means allowing airborne transmission of the enveloped RNA virus.

[0174] 33. The method according to any one of the foregoing embodiments, further comprising: cleaning the interior of the nostrils before administering the pharmaceutical composition.

[0175] 34. The method according to any one of the foregoing embodiments, wherein administering comprises spreading the disinfectant composition over the mucosal tissue.

[0176] 35. The method according to any one of the foregoing embodiments, wherein administering comprises dispensing the disinfectant composition onto the mucosal tissue with a swab.

[0177] 36. The method according to embodiment 35, wherein the swab is a cotton swab applicator or a brush.

[0178] 37. The method according to embodiment 35, wherein administering comprises allowing the disinfectant composition to remain in the mucosal tissue for at least 1 minute, at least 5 minutes, or at least 10 minutes.

[0179] 38. A method of preventing the transmission of an enveloped RNA virus, comprising:

[0180] Administering an effective amount of a disinfectant composition or a pharmaceutically acceptable salt thereof to the mucosal tissue of a first mammalian subject that is substantially uncolonized by the enveloped RNA virus, according to a treatment protocol;

[0181] Allowing the first mammalian subject that is substantially uncolonized by the enveloped RNA virus to interact with a second mammalian subject colonized by the enveloped RNA virus at a first viral load, wherein the first mammalian subject has a second viral load based on the interaction;

[0182] Wherein, during the duration of the treatment protocol, the second viral load is no greater than a 0.5 log increase compared to the initial viral load;

[0183] Wherein the mucosal tissue is in the nasopharynx, nasal cavity or anterior nares of the mammalian subject;

[0184] Wherein the disinfectant composition comprises iodine, iodophor or a combination thereof and a thickening agent.

[0185] 39. The method according to embodiment 38, further comprising:

[0186] Administering an effective amount of the disinfectant composition or a pharmaceutically acceptable salt thereof to the mucosal tissue of the second mammalian subject having the enveloped RNA virus at the first viral load, according to the treatment protocol.

[0187] 40. A method of preventing transmission of an enveloped RNA virus from a mammalian subject, comprising:

[0188] Administering an effective amount of a disinfectant composition or a pharmaceutically acceptable salt of the disinfectant composition to the mucosal tissue of the mammalian subject having a first viral load for the duration of a treatment protocol, wherein the mucosal tissue is in the nasopharynx, nasal cavity or anterior nares of the mammalian subject;

[0189] Allowing the enveloped RNA virus to remain in the mucosal tissue upon contact with the disinfectant composition;

[0190] Wherein when a second mammalian subject that is substantially uncolonized by the enveloped RNA virus interacts with the mammalian subject, the mammalian subject does not transmit the enveloped RNA virus to the second mammalian subject during the duration of the treatment protocol;

[0191] Wherein the disinfectant composition comprises iodine, iodophor or a combination thereof and a thickening agent.

[0192] 41. The method according to embodiment 38 or embodiment 40, wherein substantially free of enveloped RNA virus colonization means that the viral concentration of the enveloped RNA virus is below the detection limit.

[0193] 42. The method according to embodiment 41, wherein substantially free of enveloped RNA virus colonization means that the first mammalian subject or the second mammalian subject does not exhibit symptoms of the enveloped RNA virus.

[0194] 43. The method according to embodiment 38 or embodiment 40, wherein the first viral load is associated with the onset of symptoms of the enveloped RNA virus.

[0195] 44. The method according to embodiment 38 or embodiment 40, wherein the first viral load is at least 1000 PFU per milliliter.

[0196] 45. The method according to embodiment 44, wherein the first viral load is at least 10000 PFU per milliliter.

[0197] 46. The method according to embodiment 38 or embodiment 40, wherein the duration is at least 3 days.

[0198] 47. The method according to embodiment 46, wherein in the treatment regimen, more than 24 hours elapse between administrations.

[0199] 48. The method according to embodiment 46, wherein the enveloped RNA virus is selected from influenza or coronavirus.

[0200] 49. A method of using a disinfectant composition or a pharmaceutically acceptable salt thereof, comprising between 0.25% and 10.5% by weight, inclusive, of povidone iodine, for use in preventing influenza, the method comprising administering the disinfectant composition to the mucosal tissue of a mammalian subject according to a treatment regimen.

[0201] 49a. The method according to embodiment 49, wherein the disinfectant composition or a pharmaceutically acceptable salt thereof is between 3.5% and 10.5% by weight.

[0202] 50. The method according to embodiment 49, wherein the treatment regimen comprises administering the disinfectant composition at least 6 hours before influenza vaccination.

[0203] 51. The method according to any of the preceding embodiments, wherein the treatment regimen comprises administering the disinfectant composition at least 12 hours before influenza vaccination.

[0204] 52. A method according to any of the preceding embodiments, wherein the treatment regimen comprises administering the disinfectant composition at least 24 hours before influenza vaccination.

[0205] 53. A method according to any of the preceding embodiments, wherein the disinfectant composition comprises between 4.5 and 5.5 weight percent povidone iodine, inclusive.

[0206] 54. A method according to embodiment 53, wherein the disinfectant composition is film-forming.

[0207] 55. A method according to embodiment 53, wherein the disinfectant composition is durable.

[0208] 56. A method according to any of the preceding embodiments, wherein the mucosal tissue is the anterior nares.

[0209] 57. A method according to any of the preceding embodiments, wherein the influenza is H1N1.

[0210] 58. A method according to any of the preceding embodiments, wherein no observable increase in viral load occurs within 24 hours after influenza vaccination.

[0211] 59. A method of treating or preventing a virus in a mammalian subject, comprising:

[0212] administering an effective amount of a pharmaceutical composition or a pharmaceutically acceptable salt thereof to the mucosal tissue of a mammalian subject having a first viral load;

[0213] allowing the first viral load to decrease to a second viral load over the duration of a treatment regimen, wherein there is at least a 0.5 log decrease in viral load with use of the pharmaceutical composition compared to a placebo.

Claims

1. Use of a disinfectant composition or a pharmaceutically acceptable salt of the disinfectant composition in the preparation of a medicament for treating or preventing an enveloped RNA virus in a mammalian subject, wherein the treatment or prevention comprises: Administer an effective amount of the disinfectant composition or a pharmaceutically acceptable salt of the disinfectant composition to the mucosal tissue of the mammalian subject having a first viral load; Allow the first viral load to decrease to a second viral load over the duration of a treatment regimen, wherein during the duration of the treatment regimen, there is at least a 0.5 log decrease in the second viral load with use of the disinfectant composition compared to use of a placebo, wherein the disinfectant composition comprises: greater than 5 wt% hydroxycarboxylic acid; 0.25 wt% to 1.5 wt% amine oxide; 0.0045 wt% to 0.55 wt% available iodine concentration; 4.5 wt% to 5.5 wt% povidone-iodine; 2 wt% to 10 wt% iodide salt; a buffer; a surfactant; and water; wherein the composition exhibits no greater than a 5 wt% decrease in available iodine when stored at 40 °C for about 6 months; wherein the duration of the treatment regimen is at least 3 days; and wherein the treatment regimen comprises multiple administrations, with more than 24 hours elapsing between each administration.

2. Use according to claim 1, wherein the treatment or prevention further comprises: Administer an effective amount of an antiviral agent to the mammalian subject.

3. Use according to any one of the preceding claims, wherein the placebo is phosphate buffered saline.

4. Use according to claim 1, wherein the disinfectant composition further comprises a monosaccharide, a sugar alcohol or a combination thereof, wherein the monosaccharide, the sugar alcohol or the combination thereof is present at a concentration greater than 5% by weight.

5. Use according to claim 1, wherein the disinfectant composition comprises a surfactant; wherein the surfactant comprises an anionic surfactant, an amphoteric surfactant, a nonionic surfactant, a zwitterionic surfactant or a combination thereof; wherein the anionic surfactant comprises a phosphate, a phosphonate, a sulfate, a sulfonate or a combination thereof.

6. Use according to claim 1, wherein the disinfectant composition comprises a carrier, wherein the carrier comprises water and polyethylene glycol having a weight average molecular weight of less than 1500.

7. Use according to any one of the preceding claims, wherein the disinfectant composition comprises a thickening agent.

8. Use according to any one of the preceding claims, wherein the disinfectant composition does not contain liposomes.

9. Use according to any one of the preceding claims, wherein the treatment regime does not exceed the upper intake level of the disinfectant composition.

10. Use according to claim 1, wherein each subsequent treatment with the disinfectant composition in the treatment regime increases the concentration of the disinfectant.

11. Use according to claim 1, wherein each subsequent dose of the disinfectant composition in the treatment regime decreases the concentration of the disinfectant.

12. Use according to any one of the preceding claims, wherein the disinfectant composition is applied to the nasal cavity for more than 1 cm.

13. Use according to any one of the preceding claims, wherein the disinfectant composition is applied to the nasal cavity for less than 1 cm.

14. Use according to any one of the preceding claims, wherein the enveloped RNA virus is influenza or coronavirus.

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