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WO2019046664A1 - Compositions et méthodes de protection contre des agents pathogènes et irritants - Google Patents

Compositions et méthodes de protection contre des agents pathogènes et irritants Download PDF

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Publication number
WO2019046664A1
WO2019046664A1 PCT/US2018/048985 US2018048985W WO2019046664A1 WO 2019046664 A1 WO2019046664 A1 WO 2019046664A1 US 2018048985 W US2018048985 W US 2018048985W WO 2019046664 A1 WO2019046664 A1 WO 2019046664A1
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Prior art keywords
targeted
component
extract
targeted component
pharmaceutical composition
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Ceased
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PCT/US2018/048985
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English (en)
Inventor
Nazlie LATEFI
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Applied Biological Laboratories Inc
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Applied Biological Laboratories Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/727—Heparin; Heparan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/34—Copper; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A61K38/1729—Cationic antimicrobial peptides, e.g. defensins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Definitions

  • the disclosure relates to compositions and methods of augmenting the health and filtering capabilities of upper respiratory epithelial and mucous membranes.
  • the disclosure relates to compositions and methods for protecting the upper respiratory epithelial and mucous membranes of a subject from infection by airborne or ingested pathogens, such as viruses, bacteria, and fungi, and irritation from undesirable airborne particles such as allergens, irritants, or odorants.
  • the disclosure further relates to compositions for application to the respiratory tract (e.g.
  • the nasal and/or oral mucosa, etc.) of a human for prophylaxis of microbial and viral infections particularly human rhinovirus (HRV), human influenza virus infections, coronavirus infections, adenovirus infections, enterovirus infections, coxsackievirus infections, and/or infections caused by bacterium from the genus Streptococcus (e.g. , Streptococcus pyogenes, etc.).
  • HRV human rhinovirus
  • human influenza virus infections coronavirus infections
  • adenovirus infections enterovirus infections
  • coxsackievirus infections coxsackievirus infections
  • infections caused by bacterium from the genus Streptococcus e.g. , Streptococcus pyogenes, etc.
  • Respiratory infections typically occur when airborne pathogens come into contact with mucous membranes (e.g., nasal membranes, nasal hairs, esophageal membranes, oral membranes, membranes of the throat, membranes of the mouth, etc.) via inhaled aerosol droplets or via contact of the membranes with foreign objects.
  • mucous membranes e.g., nasal membranes, nasal hairs, esophageal membranes, oral membranes, membranes of the throat, membranes of the mouth, etc.
  • mucosa of the airway tract come into direct contact with the external environment and act as a barrier by preventing invasion of various environmental agents.
  • the barrier function of airway epithelium prevents the spread of infection by using mucociliary escalators which trap and remove inhaled foreign particles from the airways, intercellular tight and adherens junctions which regulate epithelial paracellular permeability, and secreted antimicrobial products which kill and/or slow the growth of pathogens.
  • mucociliary escalators which trap and remove inhaled foreign particles from the airways, intercellular tight and adherens junctions which regulate epithelial paracellular permeability, and secreted antimicrobial products which kill and/or slow the growth of pathogens.
  • pathogens are able to subvert the natural barrier function of mucosal membranes and lead to a variety of respiratory infections.
  • pathogens may enter the lungs after inhalation or ingestion, or they may bind receptors found on nasal, oral, and other membranes throughout the upper and lower respiratory tracts.
  • Certain pathogens e.g., virus, bacteria, etc.
  • pathogens may enter cells through specific receptors which mediate pathogenic cellular recognition.
  • the infection of specific cells by these pathogens often begins with receptor recognition of cells by viruses and bacteria.
  • Cellular receptors used for pathogenic recognition belong to different families of proteins, carbohydrates, or lipids, often in complex cell surface matrix structures.
  • a residue of influenza virus hemagglutinin found on the surface of influenza viruses, confers specificity for sialic acid linked to galactose by either an a2,6 or an a2,3 linkage to facilitate binding the virus to cells.
  • mucosal membranes serve as an entry points by which pathogens can enter into the bloodstream and cause respiratory and other types of infection.
  • pharmaceutical compositions may not be able to prevent pathogenic integration into the mucosa.
  • compositions which protect against airborne pathogens, allergens and irritants have been developed, but these compositions typically alter the conditions of the mucous membranes and may further affect the barrier function. Such alteration may occur because of the incorporation of various ingredients into the pharmaceutical composition which alter the natural properties of the membrane surface upon application to the mucosa. For example, alcohols and peroxides may change the pH and/or osmolarity of mucous or mucous membranes resulting in a decrease in membrane integrity. There is also a need to develop compositions and methods which do not use these ingredients and are able to maintain membrane integrity (infected and/or uninfected) following application.
  • compositions such as nasal sprays, oral sprays, oral rinses, lozenges, and the like, and associated methods of using such compositions for enhancing the ability of the epithelial membranes to filter and remove certain pathogens.
  • the disclosure provides pharmaceutical compositions that prevent and treat respiratory infections and allergies caused by irritants, allergens, bacteria, including bacteria from the genus Streptococcus, fungi, and viruses including rhinovirus, influenza virus, parainfluenza virus, coronavirus, coxsackievirus, enterovirus, or adenovirus.
  • the compositions protect a subject from viral infections, particularly from human rhinovirus and/or human influenza virus and/or coronavirus and/or enterovirus and/or adenovirus and/or coxsackievirus.
  • compositions disclosed herein are able to treat or prevent infection of mucosa through the application of active ingredients to the surface of the mucosa.
  • active ingredients may be targeted to specific infections (e.g., infections caused by specific virions or bacteria, etc.) and/or provide general anti-mi crobial and/or anti-inflammatory benefit.
  • the targeted component may be anti-viral or anti-bacterial.
  • the targeted component may offer a competitive binding site for pathogens therefore preventing cellular recognition of the specific pathogens resulting in inhibition of infection.
  • pharmaceutical compositions with a targeted antiviral component will comprise a soluble peptide that mimics the amino acid sequence of receptors to which virus bind prior to cell entry.
  • compositions with a targeted anti-bacterial component may comprise a soluble peptide that mimics the amino acid sequence of receptors to which bacteria bind.
  • the targeted antibacterial component will comprise modulators of cellular functions which specific bacterium use to evade the immune response.
  • the pharmaceutical compositions may further comprise non-targeted antimicrobials. Non-targeted anti-microbials may kill microorganisms responsible for infection and/or inhibit their growth.
  • the non-targeted anti-microbials may be derived from anti-bacterials typically secreted by mucosa (e.g., mucins, protease inhibitors including secretory leukocyte protease inhibitor ("SLPI"), ⁇ -microseminoprotein, secretory phospholipidases including secretory phospholipidase A2 (“sPLA2”), statherin, etc.).
  • mucosa e.g., mucins, protease inhibitors including secretory leukocyte protease inhibitor (“SLPI”), ⁇ -microseminoprotein, secretory phospholipidases including secretory phospholipidase A2 (“sPLA2”), statherin, etc.
  • the pharmaceutical compositions may comprise antiinflammatory agents may decrease the inflammatory response to infection which often results in mucus hypersecretion, obstruction of airways, and decrease in the barrier function of the mucosa.
  • the anti-inflammtory agents may reduce, treat, and
  • the methods may involve the administration of a pharmaceutical composition comprising a targeted (e.g., a targeted anti-viral and/or targeted anti-bacterial, etc.) component to the mucosa (e.g., nasal and/or throat, etc.) of a patient in need thereof.
  • a targeted e.g., a targeted anti-viral and/or targeted anti-bacterial, etc.
  • the pharmaceutical compositions may comprise a targeted component and a non-targeted anti-microbial.
  • the pharmaceutical compositions may comprise a targeted component and an anti-inflammatory.
  • the pharmaceutical compositions may comprise a targeted component, an antiinflammatory, and a general anti-microbial.
  • the pharmaceutical composition may comprise a non-targeted anti-microbial. In some embodiments, the pharmaceutical composition may comprise an anti-inflammatory. In some embodiments, the pharmaceutical composition is in the form of a nasal spray. In some embodiments, the pharmaceutical composition is in the form of a tablet, capsule, or lozenge. In some embodiments, the pharmaceutical composition is in the form of an oral spray.
  • the pharmaceutical product may comprise:
  • a pump mechanism capable of expelling said nasal spray composition through said orifice in appropriate sized aerosolized droplets; capable of coating the nasal mucosa of a user;
  • nasal spray composition comprises: a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial; and
  • the nasal spray may further comprise a non-targeted anti-microbial and/or an anti-inflammatory.
  • the pharmaceutical composition is in the form of an oral spray.
  • Pharmaceutical products for oral administration are provided.
  • the pharmaceutical product may comprise:
  • a pump mechanism capable of expelling said oral spray composition through said orifice in appropriate sized aerosolized droplets; capable of coating the oral mucosa (e.g., mucosa of the throat, mucosa of the mouth, etc.) of a user;
  • said oral spray composition comprises: a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial; and
  • the oral spray may further comprise a non-targeted anti-microbial and/or an anti-inflammatory.
  • FIG. 1A is a column graph illustrating the measured TEER values for each experimental MucilAirTM media group exposed to the indicated components following inoculation with coronavirus.
  • FIG. IB is a column graph illustrating the measured TEER values for each experimental MucilAirTM media group exposed to the indicated components following inoculation with influenza. "***" and “**” represent highly significant results as shown in Tables 3-8. Error bars represent one standard deviation of the mean.
  • FIG. 2A is a column graph illustrating the measured cytotoxicity derived from LDH release for each experimental MucilAirTM media group exposed to the indicated components following inoculation with coronavirus.
  • FIG. 2A is a column graph illustrating the measured cytotoxicity derived from LDH release for each experimental MucilAirTM media group exposed to the indicated components following inoculation with influenza. "*" represents a highly significant result as shown in Tables 9-14. Error bars represent one standard deviation of the mean.
  • FIG. 3A is a column graph representing the number of fluorescent viral objects measured in MucilAirTM media groups exposed to the indicated components following inoculation with influenza.
  • FIG. 3B is a column graph representing the total area of fluorescent viral objects measured in MucilAirTM media groups exposed to the indicated components following inoculation with influenza. Error bars represent one standard deviation of the mean.
  • analog is meant a molecule that is not identical, but has analogous functional or structural features.
  • a polypeptide analog retains the biological activity of a corresponding naturally- occurring polypeptide, while having certain biochemical modifications that enhance the analog's function relative to a naturally occurring polypeptide. Such biochemical modifications could increase the analog's protease resistance, membrane permeability, or half-life, without altering, for example, ligand binding.
  • An analog may include an unnatural amino acid.
  • An analog may include any fragment of a described polypeptide which retains the functionality of the described polypeptide (e.g., a virus is able to bind to the fragment of the polypeptide, etc.).
  • any agent disclosed herein may include analogs of that agent (e.g., a peptide may include analogs thereof, etc.).
  • an "effective amount,” “therapeutically effective amount” or “pharmaceutically effective amount” as used herein, refer to an amount that is sufficient to prevent or treat a disorder (e.g., a respiratory infection, a viral infection, a bacterial infection, etc.). In some embodiments, the result is a reduction in and/or alleviation of the signs, symptoms, or causes of a disorder, or any other desired alteration of a biological system.
  • an "effective amount" for therapeutic benefit may be the amount of the composition comprising an agent as disclosed herein required to provide a clinically significant decrease in a disease/disorder (e.g. a respiratory infection, etc.).
  • an “effective amount” or therapeutically effective amount of an agent or combination of agents of the disclosure may also be that amount or dose that is effective to substantially shrink or eliminate an infection, or prevent its occurrence.
  • An appropriate “effective” amount in any individual case is determined using any suitable technique, (e.g., a dose escalation study, etc.) and will depend on the judgment of the practitioner.
  • An “effective” amount may be an amount suitable to increase barrier function of mucosa (e.g., as measured by TEER, etc.).
  • an “effective” amount may be the amount of both necessary to achieve an increase in barrier function as compared to an otherwise identical formulation comprising either component alone. Suitable dosage ranges are readily determinable by to one skilled in the art.
  • Targeted component it is meant one or more active ingredients which have an effect or a mode of action which is specific for one or more particular pathogens (e.g., bacteria, virion, virus, etc.).
  • the targeted component comprises proteins which mimic the receptor recognition function of one or more virions and/or bacteria.
  • non-targeted anti-microbial it is meant one or more active ingredients having an anti-microbial effect which acts through a mode of action that is not targeted to specific pathogens.
  • receptor recognition function it is meant the mechanism by which pathogens recognize cells for infection.
  • the receptor recognition function involves cellular proteins, or macromolecules, enzymes, or compounds (e.g., gangliosides, hexasaccharides of gangliosides, sialic acids including 3 '-sialyllactose and 6'-sialyllactose, proteoglycans, phosphatidylcholines, lactoferrin, integrins, etc.) by which virions will bind to prior to entry of a cell.
  • cellular proteins, macromolecules, or compounds which mimic those used by pathogens for infection may be targeted by pathogens for competitive binding and reduced infection.
  • nucleic acid as in a nucleic acid for delivery to a cell is understood by its usual meaning in the art.
  • the term includes deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in the form of an oligonucleotide messenger RNA, anti-sense, plasmid DNA, parts of a plasmid DNA, genetic material derived from a virus, and the like.
  • Polynucleotides include nucleic acids of at least two monomers.
  • “Pharmaceutically acceptable excipient” and “pharmaceutically acceptable carrier” refer to a substance that aids the administration of an active agent to and absorption by a subject and can be included in the compositions of the present invention without causing a significant adverse toxicological effect on the patient.
  • Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline solutions, lactated Ringer's, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, salt solutions (such as Ringer's solution), alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethycellulose, polyvinyl pyrrolidine, and colors, and the like.
  • Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and/or aromatic substances and the like that do not deleteriously react with the compounds of the invention.
  • auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and/or aromatic substances and the like that do not deleteriously react with the compounds of the invention.
  • auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and/or aromatic substances and the like that do not deleteriously react with the compounds of the invention.
  • auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents
  • the term "pharmaceutically effective regimen” refers to a systematic plan for the administration of one or more therapeutic agents, which includes aspects such as type of therapeutic agent, therapeutic agent concentrations, and any changes therein made during the course of the drug administration, which when administered is capable of (e.g., is effective in, etc.) treating and/or preventing an infection. Such considerations depend on the judgment of the practitioner and are readily determinable by one skilled in the art.
  • any of the active agents described herein may be in the form of a "prodrug.”
  • “Prodrug” as used herein refers to a compound that, after administration, is metabolized or otherwise converted to a biologically active or more active compound (or drug) with respect to at least one property.
  • a prodrug, relative to the drug is modified chemically in a manner that renders it, relative to the drug, less active or inactive, but the chemical modification is such that the corresponding drug is generated by metabolic or other biological processes after the prodrug is administered.
  • a prodrug may have, relative to the active drug, altered metabolic stability or transport characteristics, fewer side effects or lower toxicity, or improved flavor.
  • a prodrug may be synthesized using reactants other than the corresponding drug.
  • prodrug of an active agent may be in the form of an in vivo hydrolysable ester of the specified active agent.
  • subject refers to any organism that is capable of experiencing a respiratory infection.
  • organisms include, but are not limited to, human, dog, cat, horse, cow, sheep, goat, mouse, rat, guinea pig, monkey, bird, primate, non-human primate, avian, reptiles, etc.
  • a subject "suffering from” or “suspected of suffering from” a specific disease, condition, or syndrome has a sufficient number of risk factors or presents with a sufficient number or combination of signs or symptoms of the disease, condition, or syndrome such that a competent individual would diagnose or suspect that the subject was suffering from the disease, condition, or syndrome.
  • Methods for identification of subjects suffering from or suspected of suffering from respiratory infection is within the ability of those in the art.
  • Subjects suffering from, and suspected of suffering from, a specific disease, condition, or syndrome are not necessarily two distinct groups.
  • the phrase "individual in need thereof or "patient in need thereof or “subject in need thereof” denotes an individual having a disease or condition (e.g., a respiratory infection, etc.).
  • the individual in need thereof is a patient that is infected with influenza virus, rhinovirus, parainfluenza virus, coronavirus, enterovirus, adenovirus, coxsackievirus, and/or Streptococcus pyogenes.
  • Non-limiting examples include humans, other mammals, bovines, rats, mice, dogs, monkeys, goat, sheep, cows, deer, and other non-mammalian animals including birds and reptiles.
  • the individual in need thereof is human.
  • treatment refers to obtaining a desired pharmacologic and/or physiologic effect.
  • the effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof and/or may be therapeutic in terms of a partial or complete cure for a disease and/or adverse effect attributable to the disease.
  • prevent or “prophylaxis” as used herein, includes delaying the onset of or progression of a disease or physiological manifestation of disease.
  • treat includes reducing, diminishing, eliminating, ameliorating, forestalling, slowing the progression of, and/or delaying the onset of a given disease or physiological manifestation thereof.
  • marshmallow extract is listed herein as an "anti-microbial,” but it is also known to be a potent anti-inflammatory, and capable of mimicking the rheological properties of mucous.
  • lactoferrin e.g., apolactoferrin, etc.
  • lactoferrin is listed herein as an "anti-microbial,” but it is also known to be a potent anti-inflammatory.
  • the density of any forms of the invention may be between 0.8 g/rriL and 1.2 g/rriL, for example between 0.9 g/rriL and 1.1 g/rriL or between 0.95 g/rriL and 1.05 g/rriL.
  • Ranges provided herein are understood to be shorthand for all of the values within the range including the limits of the range.
  • a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50, as well as all intervening decimal values between the aforementioned integers such as, for example, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, and 1.9.
  • a nested sub-range of an exemplary range of 1 to 50 may comprise 1 to 10, 1 to 20, 1 to 30, and 1 to 40 in one direction, or 50 to 40, 50 to 30, 50 to 20, and 50 to 10 in the other direction.
  • Any therapeutic agents, compositions, or methods provided herein can be combined with one or more of any of the other therapeutic agents, compositions, and methods provided herein. It will be understood that derivatives such as esters, and prodrugs that retain the functionality of the base compound are contemplated.
  • the present disclosure provides compositions and methods for preventing and treating infections.
  • the present disclosure features methods and compositions for enhancing the filtering capabilities of mucosa (e.g., oral, nasal, etc.) and protecting against pathogens by enhancing the health of membranes and filtering capabilities of mucous.
  • the disclosure features antimicrobial, antiviral, and antifungal compositions that prevent and treat respiratory infections caused by bacteria, viruses, and fungi, including influenza viruses and rhino viruses (e.g. viruses that cause the flu and common cold, respectively).
  • compositions including antimicrobial, antiviral, and/or antifungal functionalities may be used to enhance the health and filtering capabilities of oral and/or nasal membranes and protect against airborne pathogens. In so doing, they must also maintain the physiological health of the membranes such as by maintaining a healthy pH and osmolarity and encouraging the propagation of healthy microflora.
  • the present disclosure relates to an antimicrobial and anti-fungal filtering composition formulated for topical application to the proximal anterior nares or the inner anterior nasal membrane, where it may also coat nasal hairs and enhance the filtering capabilities of the nose.
  • the present disclosure provides a topically applied filtering composition for application that does not adversely affect the chemical properties of the respiratory membranes or mucosa (and enhances its natural filtering capabilities) and that will specifically target and protect against several disease causing microorganisms.
  • the present disclosure also provides for methods of enhancing the natural filtration properties of the respiratory membranes and reducing the number of microorganisms (e.g., virions, bacteria, etc.), allergens, and odorants which enter the body (e.g., pass through the mucosa surface) or proliferate along the mucosal membranes.
  • this method includes application of a topical or inhaled, or ingested solution of antimicrobial, antiviral, anti-fungal, and/or odor-neutralizing composition to the mouth, the throat, the opening of the nostrils, the nasal epithelial inside the nostrils, and/or the nasal hairs.
  • the antimicrobial, antiviral, and anti-fungal solution may be in gel, lotion, lozenge, vapor, or aerosol forms and may have a combination of active ingredients intended to bolster the natural filtration capabilities of the nose in a base medium that allows the active ingredients to be well tolerated, in their active forms, while preventing them from having undesirable effects.
  • the compositions herein may also mimic the chemical properties of natural healthy mucous or saliva such as, for example, pH and osmolality.
  • the techniques disclosed herein may administer targeted antimicrobials in pharmaceutical compositions which also maintain the specific physiological and chemical properties of the upper respiratory membranes or mucous such as, for example, their pH and osmolarity.
  • the methods of treating respiratory infection disclosed herein do not comprise non-targeted, indiscriminate antimicrobials to the upper respiratory membranes that may contain alcohol, peroxide, or other harsh ingredients.
  • the only harsh ingredients are peroxides.
  • these harsh ingredients change the pH or osmolarity of the upper respiratory membranes and negatively impact microflora.
  • the pharmaceutical composition comprises less than 10% harsh ingredients (e.g., alcohol, peroxide, etc.) by weight of the composition or less than 5% harsh ingredients by weight of the composition or less than 1% harsh ingredients by weight of the composition or less than 0.1% harsh ingredients by weight of the composition or less than 0.01% harsh ingredients by weight of the composition.
  • harsh ingredients e.g., alcohol, peroxide, etc.
  • application of the pharmaceutical composition to an upper respiratory (e.g., oral, nasal, etc.) membrane will alter the pH of the membrane and/or mucous by less than 20% or less than 10% or less than 5% or less than 1% or less than 0.1% of the pH prior to application.
  • application of the pharmaceutical composition to an upper respiratory membrane will alter the osmolarity of the membrane and/or mucous by less than 20% or less than 10% or less than 5% or less than 1% or less than 0.1%.
  • compositions with a targeted antiviral component will comprise a peptide and/or macromolecule implicated in the receptor recognition function of a virus.
  • the peptide or macromolecule may mimic the amino acid sequence of receptors to which virus bind prior to cell entry.
  • the macromolecule may be in the extracellular or intercellular domain and used by one or more virions to identify and bind to cells for infection.
  • pharmaceutical compositions with a targeted antibacterial component may comprise a peptide or macromolecule or compound that that which bacteria bind to for infection.
  • the targeted anti-bacterial component will comprise modulators of cellular functions which specific bacterium use to evade the immune response.
  • the targeted component of the pharmaceutical compositions may comprise targeted antiviral agents which virions selected from influenza virus, parainfluenza virus, enterovirus, coronavirus, adenovirus, or coxsackievirus may use for entry in the cell.
  • targeted antiviral agents which virions selected from influenza virus, parainfluenza virus, enterovirus, coronavirus, adenovirus, or coxsackievirus may use for entry in the cell.
  • the targeted component may comprise peptides, macromolecules, enzymes and/or compounds which the virus may bind to.
  • the virus is from the picarnoviridae family (e.g., rhinovirus, enterovirus, coxsackievirus, etc.)
  • the targeted component of the pharmaceutical composition may target influenza and comprise sialic acids and derivatives thereof (e.g., 3'-sialyllactose, 6'-sialyllactose, etc.) and/or quercetin and isoforms thereof (e.g., isoquercetin, etc.).
  • the targeted component of the pharmaceutical composition may target parainfluenza and comprise sialic acids (e.g., 3'-sialyllactose, 6'-sialyllactose, etc.).
  • the targeted component of the pharmaceutical composition may target coronavirus and comprise sialic acids (e.g., 3'-sialyllactose, 6'-sialyllactose, etc.).
  • the targeted component of the pharmaceutical composition may target coronavirus and comprise angiotensin-converting enzyme 2 ("ACE2"), dipeptidyl peptidase-4 ("DPP4") and/or the soluble form present in the respiratory tract, adiponectin (“APN”), and/or sialic acids (e.g., 3'-sialyllactose, 6'-sialyllactose, etc.).
  • ACE2 angiotensin-converting enzyme 2
  • DPP4 dipeptidyl peptidase-4
  • API adiponectin
  • sialic acids e.g., 3'-sialyllactose, 6'-sialyllactose, etc.
  • the targeted component of the pharmaceutical composition may target adenovirus and comprise membrane cofactor protein encoded by the CD46 gene ("CD46"), coxsackievirus and adenovirus receptor protein ("CAR"), desmoglein-2, sialic acids (e.g., 3'-sialyllactose, 6'-sialyllactose, etc.), GDla ganglioside and/or its branched hexasaccharides, ganglioside la, heparin sulfate and/or proteoglycans thereof, factor X of the coagulation cascade, dipalmitoyl phosphatidylcholine, lactoferrin (e.g., apol
  • Exemplary proteins and/or macromolecules used in the adenovirus receptor recognition function may be found in Wulfrum N. et al, Cellular Microbiology 15(2013): 53-62, hereby incorporated by reference in its entirety.
  • the targeted component of the pharmaceutical composition may target enterovirus and comprise human scavenger receptor class B ("SCARB2," also known as lysosomal integral membrane protein ⁇ or LIMP-2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycan, heparin sulfate and/or proteoglycans thereof, annexin II ("Anx2”), and/or intercellular adhesion molecule-5 (“ICAM-5").
  • SCARB2 human scavenger receptor class B
  • PSGL-1 P-selectin glycoprotein ligand-1
  • PSGL-1 P-selectin glycoprotein ligand-1
  • sialylated glycan sialylated glycan
  • heparin sulfate and/or proteoglycans thereof annexin II
  • IAM-5" intercellular adhesion molecule-5
  • Exemplary proteins and/or macromolecules used in the enterovirus receptor recognition function may
  • the targeted component of the pharmaceutical composition may target enterovirus E71 and comprise SCARB2.
  • the targeted component of the pharmaceutical composition may target enterovirus EV-D68 and comprise ICAM-5.
  • the targeted component of the pharmaceutical composition may target coxsackievirus (e.g. , coxsackievirus A, coxsackievirus B, etc.) and comprise integrin ⁇ , integrin ⁇ 3, ICAM-1, and/or CAR.
  • the targeted component of the pharmaceutical composition may target coxsackievirus A (e.g., A9, A21, etc.) and comprise integrin ⁇ , integrin ⁇ 3 and/or ICAM-1.
  • the targeted component of the pharmaceutical composition may target coxsackievirus B and comprise CAR.
  • the targeted component of the pharmaceutical composition may target infections from the genus Streptococci (e.g. , Streptococcus pyogenes, etc.) and comprise a C5a peptidase inhibitor, anti-leukoproteinase, and/or secretory leukocyte protease inhibitor.
  • the formulations may comprise more than one targeted component such that the techniques herein are able to protect against more than one pathogen or irritant at the simultaneously. Since the specific identity of a disease or allergy causing microorganism is often unknown at the time of initial exposure to a subject, such formulations may be used prior to identification of the specific pathogen causing infection.
  • the targeted component comprises CD46 (e.g. , soluble CD46, etc.).
  • the targeted component comprises CAR (e.g. , soluble CAR, etc.).
  • each active in the targeted component in whatever form (e.g. , fragments of any described peptide, macromolecules or derivatives thereof, etc.), be capable of binding the targeted virions. Accordingly, any of the described peptides or macromolecules above may be in a soluble form.
  • the targeted component is present in an amount effective to reduce infection. Persons of ordinary skill are able to determine the amount of the targeted component and/or each active in the targeted component suitable to reduce viral infection.
  • the targeted component (or any agent within the targeted component) may comprise from about 0.0001 mg/mL to about 100 mg/mL (e.g., about 0.001 to about 50 mg/mL or about 0.01 to about 10 mg/mL, or about 0.0001 mg/mL to about 1 mg/mL, or about 1 mg/mL to about 10 mg/mL, or about 0.0001 mg/mL to about 0.001 mg/mL, or about 0.001 mg/mL to about 0.01 mg/mL, or about 0.01 mg/mL to about 0.1 mg/mL, or about 0.1 mg/mL to about 1 mg/mL, or about 1 mg/mL to about 10 mg/mL, etc.).
  • about 0.0001 mg/mL to about 100 mg/mL e.g., about 0.001 to about 50 mg/mL or about 0.01 to about 10 mg/mL, or about 0.0001 mg/mL to about 1 mg/mL, or about 1 mg/mL to about 10 mg/
  • the targeted component may comprise from about 0.000001% to about 10% by weight of the composition (e.g. , about 0.00001% to about 5% by weight of the composition or about 0.0001% to about 1% by weight of the composition, or about 0.00001% to about 0.01% by weight of the composition, or about 1% to about 10% by weight of the composition, or about 0.00001% to about 0.0001% by weight of the composition, or about 0.0001% to about 0.001% by weight of the composition, or about 0.0001% to about 0.001% by weight of the composition, or about 0.001% to about 0.01% by weight of the composition, or about 0.01% to about 0.1% by weight of the composition, or about 0.1% to about 1% by weight of the composition, or about 1% to about 10% by weight of the composition, etc.).
  • the composition e.g. , about 0.00001% to about 5% by weight of the composition or about 0.0001% to about 1% by weight of the composition, or about 0.00001% to about 0.01% by weight of the composition, or about
  • the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the targeted component may comprise APN (e.g. soluble APN etc.).
  • the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the targeted component may comprise desmoglein 2.
  • the targeted component may comprise sialic acid.
  • the targeted component may comprise ganglioside la. In some embodiments, the targeted component may comprise heparan sulfate and proteoglycans thereof. In some embodiments, the targeted component may comprise coagulation factor X. In some embodiments, the targeted component may comprise dipalmitoyl phosphatidylcholine. In some embodiments, the targeted component may comprise lactoferrin. In some embodiments, the targeted component may comprise Av integrins. In some embodiments, the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.). In some embodiments, the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.).
  • SCAR B2 e.g. soluble SCAR B2 etc.
  • PSGL-1 e.g. soluble PSGL-1 etc.
  • the targeted component may comprise sialylated glycan. In some embodiments, the targeted component may comprise heparan sulfate and proteoglycans thereof. In some embodiments, the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.). In some embodiments, the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non-targeted component may comprise mucins. In some embodiments, the non-targeted component may comprise SLPI. In some embodiments, the non- targeted component may comprise glycyrrhizin. In some embodiments, the non-targeted component may comprise b-microseminoprotein.
  • the non-targeted component may comprise statherin. In some embodiments, the non-targeted component may comprise plant mucilage. In some embodiments, the non-targeted component may comprise marshmallow extract. In some embodiments, the non-targeted component may comprise glycyrrhizin. In some embodiments, the non-targeted component may comprise calendula extract. In some embodiments, the non-targeted component may comprise citrus peel extract. In some embodiments, the non-targeted component may comprise honey extract. In some embodiments, the non-targeted component may comprise rosemary extract. In some embodiments, the non-targeted component may comprise myrrh extract. In some embodiments, the non- targeted component may comprise Helichrysum extract.
  • the non-targeted component may comprise arrowroot extract. In some embodiments, the non-targeted component may comprise neem oil. In some embodiments, the non-targeted component may comprise vitamin C. In some embodiments, the non-targeted component may comprise vitamin E. In some embodiments, the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.).
  • the non-targeted component may comprise mucins and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non- targeted component may comprise SLPI and the targeted component may comprise sialic acid (e.g. 3 ' and 6' sialyllactose).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise sialic acid (e.g.
  • the non-targeted component may comprise statherin and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise sialic acid (e.g. 3 ' and 6' sialyllactose).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise sialic acid (e.g. 3 ' and 6' sialyllactose).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non- targeted component may comprise citrus peel extract and the targeted component may comprise sialic acid (e.g. 3 ' and 6' sialyllactose).
  • the non-targeted component may comprise honey extract and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise sialic acid (e.g. 3 ' and 6' sialyllactose).
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise sialic acid (e.g. 3 ' and 6' sialyllactose).
  • the non-targeted component may comprise Helichrysum extract and the targeted component may comprise sialic acid (e.g. 3 ' and 6' sialyllactose).
  • the non-targeted component may comprise arrowroot extract and the targeted component may comprise sialic acid (e.g. 3 ' and 6' sialyllactose).
  • the non-targeted component may comprise neem oil and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non-targeted component may comprise vitamin C and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non-targeted component may comprise vitamin E and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise sialic acid (e.g. 3' and 6' sialyllactose).
  • the non-targeted component may comprise mucins and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise SLPI and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise statherin and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non- targeted component may comprise plant mucilage and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.). In some embodiments, the non-targeted component may comprise citrus peel extract and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.). In some embodiments, the non-targeted component may comprise honey extract and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.). In some embodiments, the non-targeted component may comprise rosemary extract and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.). In some embodiments, the non- targeted component may comprise myrrh extract and the targeted component may comprise ACE2 (e.g.
  • the non-targeted component may comprise Helichrysum extract and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.). In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.). In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.). In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise vitamin E and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise ACE2 (e.g. soluble ACE2 etc.).
  • the non-targeted component may comprise mucins and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise SLPI and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise statherin and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non- targeted component may comprise plant mucilage and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise honey extract and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise DPP4 (e.g.
  • the non-targeted component may comprise Helichrysum extract and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.). In some embodiments, the non- targeted component may comprise arrowroot extract and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.). In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.). In some embodiments, the non- targeted component may comprise vitamin C and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise vitamin E and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non- targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise DPP4 (e.g. soluble DPP4 etc.).
  • the non-targeted component may comprise mucins and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise SLPI and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise statherin and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non- targeted component may comprise glycyrrhizin and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise APN (e.g.
  • the non- targeted component may comprise citrus peel extract and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise honey extract and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non- targeted component may comprise rosemary extract and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non- targeted component may comprise Helichrysum extract and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise arrowroot extract and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise neem oil and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise vitamin C and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non- targeted component may comprise vitamin E and the targeted component may comprise APN (e.g. soluble APN etc.).
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise APN (e.g.
  • the non-targeted component may comprise mucins and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise SLPI and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise statherin and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non- targeted component may comprise plant mucilage and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise CD46 (e.g.
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise honey extract and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise Helichrysum extract and the targeted component may comprise CD46 (e.g.
  • the non- targeted component may comprise arrowroot extract and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise neem oil and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non- targeted component may comprise vitamin C and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise vitamin E and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non- targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise CD46 (e.g. soluble CD46 etc.).
  • the non-targeted component may comprise mucins and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise SLPI and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise statherin and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non- targeted component may comprise glycyrrhizin and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise CAR (e.g.
  • the non- targeted component may comprise citrus peel extract and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise honey extract and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non- targeted component may comprise rosemary extract and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non- targeted component may comprise Helichrysum extract and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise arrowroot extract and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise neem oil and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise vitamin C and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non- targeted component may comprise vitamin E and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise CAR (e.g. soluble CAR etc.).
  • the non-targeted component may comprise mucins and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise SLPI and the targeted component may comprise desmoglein 2.
  • the non- targeted component may comprise glycyrrhizin and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise statherin and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise calendula extract and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise honey extract and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise desmoglein 2.
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise desmoglein 2. In some embodiments, the non-targeted component may comprise Helichrysum extract and the targeted component may comprise desmoglein 2. In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise desmoglein 2. In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise desmoglein 2. In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise desmoglein 2. In some embodiments, the non-targeted component may comprise vitamin E and the targeted component may comprise desmoglein 2. In some embodiments, the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise desmoglein 2.
  • grapefruit extract e.g. grapefruit seed extract etc.
  • the non-targeted component may comprise mucins and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise SLPI and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise statherin and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise sialic acid.
  • the non- targeted component may comprise calendula extract and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise honey extract and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise sialic acid.
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise sialic acid. In some embodiments, the non-targeted component may comprise Helichrysum extract and the targeted component may comprise sialic acid. In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise sialic acid. In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise sialic acid. In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise sialic acid. In some embodiments, the non-targeted component may comprise vitamin E and the targeted component may comprise sialic acid. In some embodiments, the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise sialic acid.
  • grapefruit extract e.g. grapefruit seed extract etc.
  • the non-targeted component may comprise mucins and the targeted component may comprise ganglioside la.
  • the non-targeted component may comprise SLPI and the targeted component may comprise ganglioside la.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise ganglioside la.
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise ganglioside la.
  • the non-targeted component may comprise statherin and the targeted component may comprise ganglioside la.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise marshmallow extract and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise glycyrrhizin and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise calendula extract and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise citrus peel extract and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise honey extract and the targeted component may comprise ganglioside la.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise myrrh extract and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise Helichrysum extract and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise ganglioside la. In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise ganglioside la.
  • the non-targeted component may comprise vitamin E and the targeted component may comprise ganglioside la.
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise ganglioside la.
  • the non-targeted component may comprise mucins and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise SLPI and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise statherin and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise glycyrrhizin and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise calendula extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise honey extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise Helichrysum extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise arrowroot extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise neem oil and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise vitamin C and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise vitamin E and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise mucins and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise SLPI and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise b- microseminoprotein and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise statherin and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise calendula extract and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise honey extract and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise coagulation factor X. In some embodiments, the non-targeted component may comprise myrrh extract and the targeted component may comprise coagulation factor X. In some embodiments, the non-targeted component may comprise Helichrysum extract and the targeted component may comprise coagulation factor X. In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise coagulation factor X. In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise coagulation factor X. In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise vitamin E and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise coagulation factor X.
  • the non-targeted component may comprise mucins and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise SLPI and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non- targeted component may comprise b-microseminoprotein and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise statherin and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non- targeted component may comprise calendula extract and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise honey extract and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise Helichrysum extract and the targeted component may comprise dipalmitoyl phosphatidylcholine. In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise dipalmitoyl phosphatidylcholine. In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise dipalmitoyl phosphatidylcholine. In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise vitamin E and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise dipalmitoyl phosphatidylcholine.
  • the non-targeted component may comprise mucins and the targeted component may comprise lactoferrin.
  • the non-targeted component may comprise SLPI and the targeted component may comprise lactoferrin.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise lactoferrin.
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise lactoferrin.
  • the non-targeted component may comprise statherin and the targeted component may comprise lactoferrin.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise lactoferrin. In some embodiments, the non-targeted component may comprise marshmallow extract and the targeted component may comprise lactoferrin. In some embodiments, the non-targeted component may comprise glycyrrhizin and the targeted component may comprise lactoferrin. In some embodiments, the non- targeted component may comprise calendula extract and the targeted component may comprise lactoferrin. In some embodiments, the non-targeted component may comprise citrus peel extract and the targeted component may comprise lactoferrin. In some embodiments, the non-targeted component may comprise honey extract and the targeted component may comprise lactoferrin.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise lactoferrin. In some embodiments, the non-targeted component may comprise myrrh extract and the targeted component may comprise lactoferrin. In some embodiments, the non-targeted component may comprise Helichrysum extract and the targeted component may comprise lactoferrin. In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise lactoferrin. In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise lactoferrin. In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise lactoferrin.
  • the non-targeted component may comprise vitamin E and the targeted component may comprise lactoferrin.
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise lactoferrin.
  • the non-targeted component may comprise mucins and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise SLPI and the targeted component may comprise Av integrins.
  • the non- targeted component may comprise glycyrrhizin and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise statherin and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise calendula extract and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise Av integrins.
  • the non- targeted component may comprise honey extract and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise Av integrins. In some embodiments, the non-targeted component may comprise myrrh extract and the targeted component may comprise Av integrins. In some embodiments, the non-targeted component may comprise Helichrysum extract and the targeted component may comprise Av integrins. In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise Av integrins. In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise Av integrins. In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise vitamin E and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise Av integrins.
  • the non-targeted component may comprise mucins and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non- targeted component may comprise SLPI and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non- targeted component may comprise statherin and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non- targeted component may comprise glycyrrhizin and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.). In some embodiments, the non-targeted component may comprise citrus peel extract and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.). In some embodiments, the non- targeted component may comprise honey extract and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.). In some embodiments, the non-targeted component may comprise rosemary extract and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non- targeted component may comprise Helichrysum extract and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise arrowroot extract and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise neem oil and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non- targeted component may comprise vitamin C and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise vitamin E and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise SCAR B2 (e.g. soluble SCAR B2 etc.).
  • the non-targeted component may comprise mucins and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.).
  • the non-targeted component may comprise SLPI and the targeted component may comprise PSGL-1 (e.g. soluble PSGL- 1 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.).
  • the non-targeted component may comprise statherin and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.). In some embodiments, the non-targeted component may comprise plant mucilage and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.). In some embodiments, the non-targeted component may comprise marshmallow extract and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.). In some embodiments, the non-targeted component may comprise glycyrrhizin and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise PSGL-1 (e.g. soluble PSGL- 1 etc.). In some embodiments, the non-targeted component may comprise citrus peel extract and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.). In some embodiments, the non- targeted component may comprise honey extract and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.). In some embodiments, the non-targeted component may comprise rosemary extract and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.). In some embodiments, the non-targeted component may comprise myrrh extract and the targeted component may comprise PSGL-1 (e.g.
  • the non-targeted component may comprise Helichrysum extract and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.). In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.). In some embodiments, the non- targeted component may comprise neem oil and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.). In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.).
  • the non-targeted component may comprise vitamin E and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.).
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise PSGL-1 (e.g. soluble PSGL-1 etc.).
  • the non-targeted component may comprise mucins and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise SLPI and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise b- microseminoprotein and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise statherin and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise calendula extract and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise honey extract and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise Helichrysum extract and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise arrowroot extract and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise neem oil and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise vitamin C and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise vitamin E and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise sialylated glycan.
  • the non-targeted component may comprise mucins and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise SLPI and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise statherin and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise plant mucilage and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise glycyrrhizin and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise calendula extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise citrus peel extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise honey extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise rosemary extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise myrrh extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise Helichrysum extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise arrowroot extract and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise neem oil and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non- targeted component may comprise vitamin C and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise vitamin E and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise heparan sulfate and proteoglycans thereof.
  • the non-targeted component may comprise mucins and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise SLPI and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise statherin and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non- targeted component may comprise plant mucilage and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise marshmallow extract and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.). In some embodiments, the non-targeted component may comprise citrus peel extract and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.). In some embodiments, the non-targeted component may comprise honey extract and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.). In some embodiments, the non-targeted component may comprise rosemary extract and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.). In some embodiments, the non-targeted component may comprise myrrh extract and the targeted component may comprise Anx2 (e.g.
  • the non-targeted component may comprise Helichrysum extract and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.). In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.). In some embodiments, the non-targeted component may comprise neem oil and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.). In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise vitamin E and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise Anx2 (e.g. soluble Anx2 etc.).
  • the non-targeted component may comprise mucins and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.).
  • the non-targeted component may comprise SLPI and the targeted component may comprise ICAM-5 (e.g. soluble ICAM- 5 etc.).
  • the non-targeted component may comprise glycyrrhizin and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.).
  • the non-targeted component may comprise b-microseminoprotein and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.).
  • the non-targeted component may comprise statherin and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non-targeted component may comprise plant mucilage and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non-targeted component may comprise marshmallow extract and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non-targeted component may comprise glycyrrhizin and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.).
  • the non-targeted component may comprise calendula extract and the targeted component may comprise ICAM-5 (e.g. soluble ICAM- 5 etc.). In some embodiments, the non-targeted component may comprise citrus peel extract and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non- targeted component may comprise honey extract and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non-targeted component may comprise rosemary extract and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non-targeted component may comprise myrrh extract and the targeted component may comprise ICAM-5 (e.g.
  • the non-targeted component may comprise Helichrysum extract and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non-targeted component may comprise arrowroot extract and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non- targeted component may comprise neem oil and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.). In some embodiments, the non-targeted component may comprise vitamin C and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.).
  • the non-targeted component may comprise vitamin E and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.).
  • the non-targeted component may comprise grapefruit extract (e.g. grapefruit seed extract etc.) and the targeted component may comprise ICAM-5 (e.g. soluble ICAM-5 etc.).
  • the pharmaceutical compositions provide a therapeutic effect useful in the treatment or prophylaxis of viral and/or bacterial infection.
  • the pharmaceutical composition may reduce the copy number of said virions in mucosa (e.g., epithelia).
  • the pharmaceutical composition may increase the barrier function in mucosa as compared to an otherwise identical composition comprising either the targeted or the non-targeted components alone. Increases in barrier function may be measured, for example as shown in the examples.
  • the targeted antiviral component and said non-targeted anti-microbial are present in an amount to increase the barrier function of epithelia as compared to an otherwise identical composition comprising either component alone.
  • the formulations may comprise more than one targeted component such that the techniques herein are able to protect against more than one pathogen or irritant at the simultaneously. Since the specific identity of a disease or allergy causing microorganism is often unknown at the time of initial exposure to a subject, such formulations may be used prior to identification of the specific pathogen causing infection.
  • the pharmaceutical compositions may further comprise a non-targeted antimicrobial portion which provides therapeutic benefit to a wide variety of pathogens.
  • the non-targeted anti-microbial portion may help to strengthen the innate immune system.
  • the non-targeted anti-microbial portion may help to remove or prevent pathogens (or pathgens bound by the targeted component) from the surface of mucosa.
  • the non-targeted antimicrobial comprise mucins, lactoferrin (e.g. , apolactoferrin, etc.), lysozyme, SLPI, ⁇ -microseminoprotein, sPLA2, and/or statherin.
  • the non-targeted anti-microbial comprises plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extracts, rosemary extracts, myrhh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, a grapefruit seed extract, and combinations thereof, zinc peroxide (ZnC ), copper, and silver, zinc, zinc compounds, silver, silver compounds, copper, copper compounds, and combinations thereof.
  • the targeted and/or non-targeted anti-microbial may derived from nasal secretions used for providing anti-microbial and filtering capabilities of the mucosa.
  • the targeted and/or non-targeted antimicrobial is derived from saliva secretions used for providing anti-microbial and filtering capabilities of the mucosa. Suitable secretions include those disclosed in Cole, A, et al, Infection and Immunity 67 (1999): 3267-75, hereby incorporated by reference in its entirety.
  • the non- targeted anti-microbial may comprise defensins (e.g.
  • BPI bacteriocidal/permeability increasing protein
  • PEP parotid secretory protein
  • PUNC proteins of palate lung and nasal epithelial clone family
  • amylase e.g. , a-amylase, etc.
  • cy statins e.g., cy statin A, cystatin B, cystatin C, cystatin D, cystatin S, cystatin SA, cystatin SN, etc.
  • proline rich peptides e.g.
  • the pharmaceutical composition comprises slatherin, marshmallow extract, mucins, lysozyme, lactoferrin, and combinations thereof.
  • the pharmaceutical composition comprises lysozyme and lactoferrin.
  • the pharmaceutical composition comprises lysozyme, lactoferrin, and mucins.
  • the pharmaceutical composition comprises marshmallow extract and mucins.
  • the pharmaceutical composition comprises marshmallow extract, mucins, lysozyme and lactoferrin (e.g. , apolactoferrin, etc.).
  • the pharmaceutical composition comprises glycyrrhizin and sialic acid.
  • the non-targeted component is present in the pharmaceutical composition in a similar amount as is typically secreted by mucosa.
  • the non-targeted component may comprise from about 0.0001 mg/mL to about 100 mg/mL (or any agent within the targeted component) may comprise from about 0.0001 mg/mL to about 100 mg/mL (e.g., about 0.001 to about 50 mg/mL or about 0.01 to about 10 mg/mL, or about 0.0001 mg/mL to about 1 mg/mL, or about 1 mg/mL to about 10 mg/mL, or about 0.0001 mg/mL to about 0.001 mg/mL, or about 0.001 mg/mL to about 0.01 mg/mL, or about 0.01 mg/mL to about 0.1 mg/mL, or about 0.1 mg/mL to about 1 mg/mL, or about 1 mg/mL to about 10 mg/mL, etc.).
  • the non-targeted component may comprise from about 0.000001% to about 10% by weight of the composition (e.g., about 0.00001% to about 5% by weight of the composition or about 0.0001% to about 1% by weight of the composition, or about 0.00001% to about 0.01% by weight of the composition, or about 1% to about 10% by weight of the composition, or about 0.00001% to about 0.0001% by weight of the composition, or about 0.0001% to about 0.001% by weight of the composition, or about 0.0001% to about 0.001% by weight of the composition, or about 0.0001% to about 0.001% by weight of the composition, or about 0.001% to about 0.01% by weight of the composition, or about 0.01% to about 0.1% by weight of the composition, or about 0.1% to about 1% by weight of the composition, or about 1% to about 10% by weight of the composition, etc.).
  • the composition e.g., about 0.00001% to about 5% by weight of the composition or about 0.0001% to about 1% by weight of the composition, or
  • compositions may be present in an amount to mimic the rheology of mucous.
  • the pharmaceutical compositions are capable of mimic the rheological parameters of the mucous secreted from that mucosa (e.g. , oral and/or nasal mucosa, etc.).
  • Administered formulations with similar rheological parameters to mucous may several beneficial effects for the formulations.
  • the residence time for various pathogens may be increased prior to contact with the surface of the membranes resulting in increased targeted binding and/or anti-microbial effect and/or the barrier function of the mucous in combination with the pharmaceutical composition may be increased.
  • Rheological parameters are described in, for example, Lai, S. et al. , Adv. Drug. Deliv. Rev. 61 (2009): 86-100, hereby incorporated by reference in its entirety.
  • the pharmaceutical compositions have non-Newtonian rheology in formulation and following administration to mucosa (e.g., the administered formulation may be an non-Newtonian gel, etc.).
  • the pharmaceutical composition may have a Viscosity of between about 10 "3 and about 10 2 Pa.s (e.g., between about 10 "3 Pa.s and 10 "2 Pa.s, between about 10 "2 Pa.s and 10 "1 Pa.s, between about 10 "1 Pa.s and 1 Pa.s, between about 1 Pa.s and 10 Pa.s, between about 10 Pa.s and 10 2 Pa.s, etc.) at a shear rate of 10 Hz at 25 °C.
  • Various agents may be used to mimic the rheology of mucous.
  • the pharmaceutical composition may comprise one or more agents selected from mucins, plant mucilage, marshmallow extract, lysozyme, and/or lactoferrin (e.g., apolactoferrin, etc.) in amounts capable of mimicking the rheology of mucous.
  • the pharmaceutical compositions may comprise mucins.
  • the pharmaceutical compositions may comprise plant mucilage.
  • the pharmaceutical compositions may comprise mucins and plant mucilage.
  • the pharmaceutical compositions may comprise mucins and marshmallow extract.
  • the pharmaceutical composition may comprise plant mucilage and marshmallow extract.
  • the pharmaceutical composition may comprise mucins, marshmallow extract, and plant mucilage.
  • the pharmaceutical compositions may further comprise an anti-inflammatory agent.
  • the anti-inflammatory agents will mitigate the type 2 immune response. Without wishing to be bound by theory, lowering specific inflammatory responses may prevent mucous hypersecretion and maintain barrier integrity. Accordingly, the pharmaceutical compositions may comprise any inhibitor of inflammatory pathways.
  • ICAM inhibitors e.g., CDl la, ezrin (EZR), CD18, glycyrrhetinic acid, pyrrolidinedithiocarbamate, etc.
  • NFKB inhibitors e.g., (heterocyclic thiazole, lipoic acid, efalizumab, 4-[(4- Methylphenyl)thio]thieno[2,3- c]pyridine-2-carboxamide, silibinin, stilbenes, (+)-epigalloylcatechin-gallate [(+)-EGCG], etc.
  • cytokine inhibitors TSLP inhibitors IL-25 inhibitors, IL-33 inhibitors, IL-1 inhibitors
  • TNF inhibitors e.g., TNF- ⁇ inhibitors, TNF- ⁇ inhibitors, etc.
  • quercetin and isoforms thereof e.g., isoquercetin, etc.
  • non steroidal anti -inflammatory
  • compositions of the invention may include one or more of a glucocorticosteroid and/or an antihistamine (e.g., an HI antagonist, etc.).
  • the anti-inflammatory may provide anti-allergenic effects.
  • pharmaceutical compositions comprising anti-inflammatory agents may be used for the treatment and/or preventions of allergic effects.
  • the targeted component and non-targeted antimicrobial are delivered to the surface of mucosa without permeation within the mucosa.
  • the anti-inflammatory may permeate the mucosa to provide therapeutic benefit. Persons of ordinary skill are able to determine the amount anti-inflammatory necessary to achieve therapeutic benefit.
  • the anti- inflammatory may comprise from about 0.0001 mg/mL to about 100 mg/mL (or any agent within the targeted component) may comprise from about 0.0001 mg/mL to about 100 mg/mL (e.g., about 0.001 to about 50 mg/mL or about 0.01 to about 10 mg/mL, or about 0.0001 mg/mL to about 1 mg/mL, or about 1 mg/mL to about 10 mg/mL, or about 0.0001 mg/mL to about 0.001 mg/mL, or about 0.001 mg/mL to about 0.01 mg/mL, or about 0.01 mg/mL to about 0.1 mg/mL, or about 0.1 mg/mL to about 1 mg/mL, or about 1 mg/mL to about 10 mg/mL, etc.).
  • the anti-inflammatory component may comprise from about 0.000001% to about 10% by weight of the composition (e.g., about 0.00001% to about 5% by weight of the composition or about 0.0001% to about 1% by weight of the composition, or about 0.00001% to about 0.01% by weight of the composition, or about 1% to about 10% by weight of the composition, or about 0.00001% to about 0.0001% by weight of the composition, or about 0.0001% to about 0.001% by weight of the composition, or about 0.0001% to about 0.001% by weight of the composition, or about 0.001% to about 0.01% by weight of the composition, or about 0.01% to about 0.1% by weight of the composition, or about 0.1% to about 1% by weight of the composition, or about 1% to about 10% by weight of the composition, etc.).
  • the targeted component e.g., targeted anti-viral and/or targeted antibacterial, etc.
  • non-targeted anti-microbial, and anti-inflammatory may be used alone in the pharmaceutical composition.
  • synergistic effects e.g., non-additive decrease of infection, reduction in infection progression, maintaining or increasing mucosal strength, non-impairment of barrier function, etc.
  • the targeted component and non-targeted anti-microbial component may provide a synergistic effect.
  • the targeted component and anti-inflammatory may provide a synergistic effect.
  • the targeted component and non-targeted anti-microbial component may provide a synergistic effect.
  • the composition may comprise one or more antimicrobial or antiviral compounds dispersed in a carrier, and typically, but not necessarily, a liquid carrier.
  • the liquid carrier is ideally, but not necessarily, of suitable rheology to be sprayed as an aerosol or fine mist.
  • the composition may comprise one or more ingredients selected from the group consisting of an emollient, an occlusive, a humectant, a carrier, an excipient, an emulsifier, and an essential oil.
  • excipients, carriers and/or diluents should be compatible with the human mucosa and epithelium, and should not cause excessive drying or irritation to the mucosa or epithelium.
  • the excipients should also account for the fact that water will tend to evaporate at body temperature and as such a secondary solvent may be included to aid in maintaining the soluble components in solution.
  • the carrier may include a polyol, such as a C2-C8 polyol, including without limitation, glycerin, propylene glycol, 1,3 -propane diol, butylene glycol, 1,4- butane diol, erythritol, threitol, arabitol, xylitol, mannitol, sorbitol, pentylene glycol, hexylene glycol, caprylyl glycol, hydrogenated starch hydrolysates, isomalt, maltitol, and the like.
  • a polyol such as a C2-C8 polyol, including without limitation, glycerin, propylene glycol, 1,3 -propane diol, butylene glycol, 1,4- butane diol
  • compositions may comprise an amount of an alcohol, such as ethanol, provided it is in an amount that does not irritate or dry the mucosa or any drying or irritation which may occur is offset by other ingredients.
  • the compositions are free of alcohol (e.g. , ethanol, etc.).
  • the carrier is an aqueous carrier including from about 1-95% or from about 5-50% or from about 10-40% or from about 15-35% or from about 20-30% 1,3 -propanediol, on a (v/v), (w/v), or (w/w) basis.
  • the composition may have a kinematic viscosity ranging from about 1-1,500 or from about 5-1,000 or from about 10-750 or from about 20-500 centiStokes (mm 2 /s).
  • the compositions may have a Newtonian or non-Newtonian rheology.
  • the compositions may be, for example, shear thinning and/or thixotropic, such that they readily flow through a spray nozzle and form a mist of suitable droplet size on shearing, but thicken in situ to form a film on the mucosa which is resistant to clearance from the nasal and/or oral cavity such that the active remain on the mucosa for a time sufficient to neutralize pathogens in contact with the mucosa.
  • the composition will be of suitable viscosity to possess a residence time on the mucosa of the nasal and/or oral cavities of at least 1 minute, more preferably, at least 5, 10, 15, 20, 25, or 30 minutes following application.
  • the composition should be semi -permeable in order to permit virions and other pathogens to penetrate the film and come into contact with the active ingredients, while possessing a sufficient barrier function to inhibit evaporation of water and volatile solvents in order to maintain the actives in solution.
  • the pharmaceutical compositions according to the invention may be in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • the carrier of the pharmaceutical composition may be selected to provide residence time of the composition on the nasal and/or oral mucosa of at least 1 minute, or at least 5 minutes, or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes following application.
  • the composition for application to the nasal and/or oral mucosa comprises one or more antiviral and/or antimicrobial agents dispersed in a liquid carrier comprising from about 1-99% (v/v) water or from about 60-90% (v/v) water and from about 10-40% (or from 20-30%) (v/v) of a polyol.
  • the pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) 1,3 -propanediol.
  • the composition may be capable of being sprayed or ingested onto the mucosa, and is adapted to remain on the mucosa for at least 5 minutes (or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes) following application without substantially irritating or drying the mucosa.
  • the antimicrobial compositions herein may incorporate the targeted and non-targeted components with a base mixture comprising one or more of water, polyols, emollients, occlusives, humectants, emulsifiers, preservatives, thickeners and suspending agents, pH adjusters, isotonicity agents, and essential oils.
  • This base mixture may allow the active ingredients to remain at or near the site of application for at least 30 minutes (e.g. 30-60 minutes, 1-2 hours, 2-4 hours, 4-8 hours, 8-12 hours, 12-24 hours, 1-2 days, 2-7 days, a week or more) before being absorbed.
  • the pharmaceutical composition remaining at the site of application may have similar pH and osmolarity to mucous. Moreover, the pharmaceutical composition may not clog pores of the mucosa. The length of time required for absorption of the pharmaceutical composition may be determined by the saccharine test or other similar tests.
  • Pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, olive oil, gel (e.g., hydrogel, etc.), castor oil, and the like.
  • Saline is a preferred carrier when the pharmaceutical composition is administered intravenously.
  • Saline solutions and aqueous dextrose and glycerol solutions may also be employed as liquid carriers, particularly for injectable solutions.
  • the pharmaceutically acceptable carrier may be selected to provide a specified residence time in the mucosa of a subject.
  • the "residence time" of the inventive compositions on the mucosa represent average residence times from studies involving multiple applications (intranasal and/or oral) using a sample of multiple individuals sufficient to approximate the population at large.
  • at least 25% (and preferably, at least 30%, or at least 40% or at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 90%) by weight of the initially applied active ingredients remain on the mucosa after the specified duration of time.
  • the pharmaceutically acceptable carrier at 25°C has the Hansen Solubility Parameters of energy from dispersion (5d), energy from dipolar intermolecular force between molecules ( ⁇ ⁇ ), energy from hydrogen bonds (5h) of between about 15 and about 18, about 12 and about 15, about 21 and about 25, respectively.
  • the pharmaceutically acceptable carrier may be aqueous.
  • the pharmaceutically acceptable carrier is free of mercurial preservatives.
  • the solvent may be 1,2- propanediol, 1,3 -propanediol and a variety of aqueous carriers can be used, e.g. buffered water, 0.9 percent saline, buffered aqueous-ethanol solutions and the like. Combinations of any of these carriers are within the scope of the invention.
  • These compositions can be sterilized by conventional, well-known sterilization techniques, or can be sterile filtered. The resulting solutions can be packaged for use as is or mixed as an adjuvant to another medication.
  • a composition can contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions, such as pH adjusting and buffering agents, tonicity adjusting agents, taste modifiers, sweeteners, wetting agents and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oleate, etc.
  • the pharmaceutically acceptable carrier is a mixture of water and a polyol.
  • the pharmaceutically acceptable carrier is a mixture of water and propanediol (e.g. 1,2-propenediol, 1,3-propanediol, etc.).
  • the pharmaceutical composition is a mixture of water and glycerin.
  • the pharmaceutically acceptable carrier may be about 1% - about 35% (e.g. about 5% - about 30%, etc.) aqueous solution of propanediol or glycerin by weight of the aqueous carrier.
  • Some pharmaceutically acceptable carriers include 20% aqueous solution of 1,3-propanediol, 20% aqueous solution of glycerin, 10% aqueous solution of 1,3-propanediol, 10% aqueous solution of glycerin, 20% aqueous solution of 1,3-propanediol with 1% sunflower oil and 5% polysorbate 80, 20% aqueous solution of glycerin with 1% sunflower oil and 5% polysorbate 80, 10% aqueous solution of 1,3-propanediol with 1% sunflower oil and 5% polysorbate 80, 10% aqueous solution of glycerin with 1% sunflower oil and 5% polysorbate 80, 10% aqueous solution of glycerin with 1% sunflower
  • the Versaflex V-175 polymeric emulsifier system with 3% sunflower oil the Versaflex V-175 polymeric emulsifier system with 3% sunflower oil and about 5 to about 30% propanediol or glycerin
  • the Versaflex V-175 emulsifier system with 3% acetylated monoglyceride the Versaflex V-175 emulsifier system with 3% acetylated monoglyceride and about 5 to about 30% propanediol or glycerin.
  • Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol, and the like.
  • the composition if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. These compositions can take the form of solutions, suspensions, emulsion, tablets, pills, capsules, powders, sustained-release formulations and the like.
  • Oral formulation can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc.
  • suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences” by E. W. Martin, the contents of which are hereby incorporated by reference in its entirety.
  • Such compositions will generally contain a therapeutically effective amount of the therapeutic agent and/or the immunotherapeutic agent, in purified form, together with a suitable amount of carrier so as to provide the form for proper administration to the patient.
  • the formulation should suit the mode of administration.
  • an exemplary composition may further include the following additional base (e.g., carrier, etc.) ingredients either alone or in combination: a polyol, a humectant (such as but not limited to glycerin, aloe vera, or butylene glycol), an emollient (such as but not limited to shea butter, castor oil, coconut oil, caprylic acid, butyl stearate, or triglyceride), an occlusive substance (such as but not limited to petroleum jelly, dimethicone, lanolin, cocoa butter, shea butter, beeswax, plant butters, or carnauba wax).
  • additional base e.g., carrier, etc.
  • the addition and exact concentrations of these ingredients may be optimized to achieve a barrier function that does not clog pores, keeps active ingredients in their bioactive conformations and in place for at least 30 minutes, maintains osmolarity and pH similar to physiological mucus, is tolerable and effective when applied.
  • any excipient or additive may be included in an amount sufficient to serve its intended functional purpose without harming or irritating the respiratory tissues. Unless otherwise indicated, all excipients may be present in an amount from about 0.000001% or 0.01% to about 1, 5, 10, or 25% by weight of the composition.
  • the carrier may be any pharmaceutically acceptable diluent and may be solid at room temperature or liquid at room temperature.
  • Suitable carriers include water, alcohol (e.g., ethanol, etc.), Propylene glycol, isopropanol, propanediol, glycerin, benzyl alcohol, isostearyl isosterate, caprylic/capric triglyceride, oleyl oleate, tocopherol acetate, decyl cocoate, squalene, span 40, coco-caprylate/caprate, span 80, tocopherol, osstearic acid, oleyl erucate, span 20, glyceryl isostearate, and caprylic/capric triglyceride.
  • alcohol e.g., ethanol, etc.
  • Propylene glycol isopropanol
  • propanediol propanediol
  • glycerin glycerin
  • benzyl alcohol isostearyl isosterate
  • caprylic/capric triglyceride e.g.,
  • the carrier may be, for example, in the form of an aqueous solution, a water in oil emulsion, or an oil in water emulsion.
  • the emulsion carrier will typically comprise from 0.0001% to about 10% by weight of an emulsifier suitable to stabilize the emulsion.
  • the composition is intended for oral use and may include one or more of the following ingredients: glucose syrup, soy lecithin, alginates, sucralose, com syrup, gelatin, erythritol, lecithin, plant mucins, carrageenan, chicory root extract, malitol, and stevia.
  • the excipients should not interfere with the biological activity of the actives and should be compatible in solution with the actives.
  • the excipients should also not penetrate the epithelia (respiratory membranes). Accordingly, it is desirable to have a higher solubility of the actives in the base composition to maintain them in solution and prevent penetration of the actives into the epithelia.
  • the excipients may serve to maintain moisture in the mucosa and the compositional film thereon, such that the active ingredients do not precipitate from solution.
  • the carrier will comprise water, and a secondary solvent of lower volatility than the water in which the actives are also soluble.
  • the carrier and excipients are selected such that they have a polarity that is closer to the polarity of the active ingredients than to the polarity of the epithelia.
  • the secondary solvent may serve to keep the actives soluble after water has evaporated. In oral formulations, loss of moisture is less important and it may be desirable to select excipients so as to retard the dissolution of the composition in the saliva.
  • the pH of the formulation may be adjusted with pharmaceutically acceptable acids, bases, or buffers to enhance the stability of the formulated compound or its delivery form.
  • the pharmaceutical carriers may be in the form of a sterile liquid preparation, for example, as a sterile aqueous or oleaginous suspension.
  • acceptable vehicles and solvents that may be employed are mannitol, water, Ringer's solution and isotonic sodium chloride solution.
  • the composition may include odor-neutralizing compounds such as, but not limited to activated charcoal or sodium bicarbonate.
  • the composition may have adhesive properties and be specifically formulated to keep active ingredients and antimicrobials/antivirals on the surface of the upper respiratory epithelium for an extended period of time.
  • the compositions herein may include substances of low volatility, or occlusive substances such as, for example, polyols, shea butter, or other plant butters, coconut oil, beeswax, and bioadhesive substances such as mucilage, or alginates.
  • formulations described herein and their active ingredients are intended to be well tolerated, exert beneficial effect on ciliary function, have good dispensing properties, a high degree of adhesion, and maintain the chemical properties of the mucosa.
  • ingredients are balanced to create synergistic effects.
  • one or more of the active ingredients of the targeted component may target undesirable microorganisms and viruses specifically.
  • Many airborne pathogens such as rhinoviruses and influenza gain entry into upper respiratory epithelial cells, mucosa, or cells of the lower respiratory tract through specific cell surface targets.
  • ICAM-1 Intracellular Adhesion Molecule- 1 as one such target for most rhinoviruses and another for influenza (Abraham and Colonno 1984).
  • ICAM-1 is an intercellular adhesion molecule expressed on the cell surface of nasal epithelial cells, as well as cells of the lower respiratory tract. The N-terminal domain of ICAM-1 is recognized by receptors on certain rhinovirus capsids.
  • Influenza viruses Upon binding ICAM-1, the virus sheds its capsid and is transported into the cell where it initiates infection and an inflammatory response by the host.
  • Influenza viruses exhibit a similar mechanism of infection: in humans, hemagglutinin (HA) on viral surfaces bind sialic acid attached to galactose (e.g. by an alpha 2,6 linkage (6'-sialyllactose) or by an alpha 2,3 linkage (3'-sialyllactose), etc.), on the host cell membrane of erythrocytes and cells of the upper respiratory tract.
  • HA hemagglutinin
  • the receptor-binding SI subunit of coronavirus spike proteins contains two distinctive domains, the N-terminal domain (Sl-NTD) and the C-terminal domain (Sl-CTD), both of which can function as receptor-binding domains (RBDs).
  • Sl-NTDs and Sl-CTDs from three major coronavirus genera recognize at least four protein receptors and three sugar receptors and demonstrate a complex receptor recognition pattern.
  • highly similar coronavirus Sl-CTDs within the same genus can recognize different receptors
  • very different coronavirus Sl-CTDs from different genera can recognize the same receptor.
  • coronavirus Sl-NTDs can recognize either protein or sugar receptors.
  • the composition may also include odor-neutralizing compounds such as activated charcoal or sodium bicarbonate alone or in combination. Other odor-neutralizing compounds are contemplated for inclusion in the composition.
  • Suitable therapeutic agents include, but are not limited to, pharmaceutical drugs or compounds (i.e., small molecule drugs), therapeutic antibodies, therapeutic proteins or biologies (e.g., hormone therapies, etc.), and nucleic acid molecules (e.g., interfering RNA, siRNAs, etc.).
  • the therapeutic agent may be an agent shown to have targeted or untargeted antimicrobial properties against infectious organisms.
  • the therapeutic agent is an existing market-approved pharmaceutical drug or other market-approved composition for treating infection using a conventional approach.
  • the pharmaceutical compositions may further comprise an antibody or stimulate the antibody response to infection.
  • nasal secretions contain immunoglobulins offering antibody mediated defense and research indicates a majority is the secretory form of IgA (slgA).
  • slgA antibodies prevent microbial attachment and the absorption of molecular antigens including potential allergens.
  • Certain bacteria produce IgA proteases, by cleaving IgA, these enzymes may interfere with the barrier function of these antibodies. Research indicates that cleavage of IgA may result in atopic disease.
  • Other antibodies most commonly found in nasal secretions and which may serve protective functions are IgG and IgM (Kirkeby et al 2000). By augmenting the amounts of these antibodies, the present disclosure may protect against undesirable irritants or pathogens.
  • Therapeutic antibodies contemplated by the present disclosure may include any isotype (IgA, IgG, IgE, IgM, or IgD) of an anti-microbial or antiviral antibody or immune-active fragment or derivative thereof.
  • Such fragments may include, for example, single-chain variable fragments (scFv), antigen-binding fragment (Fab), crystallizable fragment (Fc) modified to contain an antigen or epitope binding region, and domain antibodies.
  • Derivatized versions of therapeutic antibodies may include, for example, diabodies, nanobodies, bispecific antibodies, and virtually any antibody-derived structure which contains or is engineered to contain an appropriate and effective antigen binding site.
  • preventing or treating respiratory disease may be effected using a nucleic acid molecule that targets a specified "target gene" that has a role in infection.
  • the effect of the nucleic acid molecule on the target gene may include gene silencing, mRNA destruction, or inhibited transcription, or the like, such that the level of expression and/or conversion of the target gene to an operable encoded polypeptide are substantially regulated (up or down) such that the infection is inhibited and/or destroyed by the agent.
  • target gene refers to nucleic acid sequences (e.g., genomic DNAs or mRNAs, etc.) encoding a target protein, peptide, or polypeptide, or that encode for or are regulatory nucleic acids (e.g., a "target gene” for purpose of the instant disclosure can also be a miRNA or miRNA-encoding gene sequence, etc.) which have a role in infection.
  • a target gene for purpose of the instant disclosure can also be a miRNA or miRNA-encoding gene sequence, etc.
  • target gene is also meant to include isoforms, mutants, polymorphisms, and splice variants of target genes.
  • interfering RNA can be assembled from two separate oligonucleotides, where one strand is the sense strand and the other is the antisense strand, wherein the antisense and sense strands are self- complementary (i.e., each strand comprises a nucleotide sequence that is complementary to nucleotide sequence in the other strand; such as where the antisense strand and sense strand form a duplex or double stranded structure); the antisense strand comprises nucleotide sequence that is complementary to a nucleotide sequence in a target nucleic acid molecule or a portion thereof and the sense strand comprises nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof.
  • interfering RNA may be assembled from a single oligonucleotide, where the self- complementary sense and antisense regions are linked by means of nucleic acid based or non-nucleic acid-based linker(s).
  • the interfering RNA may be a polynucleotide with a duplex, asymmetric duplex, hairpin or asymmetric hairpin secondary structure, having self- complementary sense and antisense regions, wherein the antisense region comprises a nucleotide sequence that is complementary to nucleotide sequence in a separate target nucleic acid molecule or a portion thereof and the sense region having nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof.
  • the interfering RNA can be a circular single- stranded polynucleotide having two or more loop structures and a stem comprising self- complementary sense and antisense regions, wherein the antisense region comprises nucleotide sequence that is complementary to nucleotide sequence in a target nucleic acid molecule or a portion thereof and the sense region having nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof, and wherein the circular polynucleotide can be processed either in vivo or in vitro to generate an active siRNA molecule capable of mediating RNA interference.
  • therapeutic nucleic acid molecules may be delivered in a delivery vehicle, such as a lipid vesicle or other polymer carrier material known in the art.
  • a delivery vehicle such as a lipid vesicle or other polymer carrier material known in the art.
  • additional lipid- based carrier systems (which may be prepared with at least one modified cationic lipid of the disclosure) suitable for use in the present disclosure include lipoplexes (see, e.g., U.S. Patent Publication No. 20030203865; and Zhang et al, J. Control Release, 100: 165-180 (2004)), pH-sensitive lipoplexes (see, e.g., U.S. Patent Publication No.
  • liposomes containing lipids derivatized with releasable hydrophilic polymers see, e.g., U.S. Patent Publication No. 2003/0031704
  • lipid-entrapped nucleic acid see, e.g., PCT Publication Nos. WO 03/057190 and WO 03/059322
  • lipid-encapsulated nucleic acid see, e.g., U.S. Patent Publication No. 2003/0129221; and U.S. Pat. No. 5,756,122
  • other liposomal compositions see, e.g., U.S. Patent Publication Nos. 2003/0035829 and 2003/0072794; and U.S.
  • any of the agents of the disclosure including pharmaceutical drugs, biologies, and therapeutic antibodies, may also be delivered via the above described carrier systems. All carrier systems may further be modified with a targeting moiety or the like in order to facilitate delivery of the composition to a site of infection in the respiratory airways.
  • the disclosure employs one or more immunotherapeutic agents that may further enhance the infection clearing effects imparted by the use of the targeted component, non- targeted anti-microbial and/or anti-inflammatory.
  • the immunotherapeutic agent may be delivered after the effects of the antimicrobial agent has set in, but the disclosure is not limited to this concept.
  • the disclosure contemplates any administration regimen involving multiple agents so long as the therapeutic benefits attributable to each of the agents may occur. It is also contemplated within the scope of the disclosure that administration of the one or more immunotherapeutic agents may have immunostimulatory activity that provides prophylaxis against further recurrence of an infection. This immunostimulatory effect may be achieved when the agent is given intranasally, orally, or systemically.
  • an immunotherapeutic agent is a treatment that aims to use an individual's own immune system to fight infection or disease. This may be accomplished by boosting the individual's own immune system or to provide supplemental pieces of an otherwise defective or deficient immune system.
  • Immunotherapy is a form of biological therapy that can be used in the present disclosure to supplement and/or enhance the effects of treating with the therapeutic agent.
  • immunotherapy There are generally two recognized forms of immunotherapy, which are referred to as active immunotherapies and passive immunotherapies.
  • Active immunotherapies stimulate the body's own immune system to fight a disease.
  • Passive immunotherapies use immune system components, such as antibodies, prepared outside the body, to enhance the body's immune response level.
  • Immunotherapies may also work by targeting certain types of cells or antigens (specific immunotherapies) or they may work by more generally stimulating the immune system (non-specific immunotherapies, or sometimes referred to as adjuvants).
  • immunotherapies contemplated by the disclosure include monoclonal antibody therapy, non-specific immunotherapies and adjuvants (substances which boost the immune response such as interleukin-2 and interferon-alpha), immunomodulating drugs (such as thalidomide and lenalidomide), and vaccines.
  • immunotherapeutic agents which may also be referred to as “immunomodulators” may include, for example, interleukins (e.g., IL-2, IL-7, or IL-12, etc.), certain other cytokines (e.g., interferons, growth colony stimulating factor (G-CSF), imiquimod, etc.), chemokines, and other types of agents, which can include antigens, epitopes, antibodies, monoclonal antibodies, or even a delivery vehicle to deliver one or more of these compounds, and may even also include recombinant immune system cells.
  • Such immunotherapeutic agents may include recombinant forms, synthetic forms, and natural preparations (see D'Alessandro, N. et al, Cancer Therapy: Differentiation, Immunomodulation and Angiogenesis, New York: Springer- Verlag, 1993 and Hegde et al, Immunotherapy 1 (2009): 691- 711).
  • the immunotherapeutic agent takes advantage of the body's innate immune system and has the effect when introduced of triggering the innate immune response against the unwanted pathogens.
  • Introduction of the immunotherapeutic agents may be achieved using any suitable approach, including by local or regional administration of the agent at, near, or within the respiratory infection.
  • the agent may also be delivered, where suitable, via gene therapy.
  • the antibody-inducing antigen may be introduced by injecting or otherwise directly administering a genetic vector or otherwise nucleic acid molecule capable of expressing the desired antigen.
  • the antigens themselves may also be directly administered into the target infected tissue.
  • the immunotherapeutic agent enhances the immunomodulatory effects of the therapeutic agent.
  • the immunotherapeutic agent further reduces the growth of the infection or further shrinks the infection.
  • the immunotherapeutic agent may be administered before, during, or after the therapeutic agent has been administered. In embodiments, the immunotherapeutic agent is administered before the first administration of the therapeutic agent. In embodiments, the immunotherapeutic agent is administered simultaneously with the first administration of the therapeutic agent. [0099] In any of the above aspects or embodiments, the therapeutic agent and the immunotherapeutic agent can be administered in a ratio of about 1 :2, 1 :4, 1 : 10, 1 :25, 1 :50, 1 : 100, 1 :200, or any ratio there between (weight ratio of therapeutic agent: immunotherapeutic agent).
  • the immunotherapeutic agent can be administered intranasally, orally, locally, regionally, or systemically (e.g. intravenously, etc.).
  • the present disclosure is directed to an antimicrobial, antiviral, anti-fungal, odor- neutralizing topical application that simulates certain chemical properties of mucous, does not impair the health or integrity of the mucosal (e.g., oral, nasal, etc.) membranes, or adversely affect its beneficial microflora, and also serves as a filter to prevent airborne irritants and pathogens from penetrating the mucosal membranes and/or entering the lower respiratory tract.
  • the compositions herein prevent infection of the respiratory tract, while also preventing irritation and/or allergic reactions.
  • compositions herein may be isotonic to upper respiratory epithelia and mucous membranes and contain compounds with health promoting properties.
  • Beneficial microflora and certain properties of the upper respiratory membrane such as osmolarity and pH have been shown to affect the likelihood of infection.
  • medications and health conditions have been identified that make people more susceptible to respiratory infection. For example, diabetics are likely to have dry nasal membranes and suffer from fungal sinusitis. Oral contraceptives, sleep apnea machines, and allergies are also known to make the nasal membranes drier and more susceptible to infection.
  • the targeted component or any agent of the targeted component may be present in an amount from about 0.00000001% to 10% by weight of composition. More typically, one or more targeted components may be present in an amount from 0.0000001% to 0.1% by weight of the composition. More typically, one or more targeted components (e.g.
  • C5a peptidase inhibitor C5a peptidase inhibitor; anti-leukoproteinase, secretory leukocyte protease inhibitor, sialic acids (including but not limited to 3 ' and 6' sialyllactose), soluble ACE2, soluble DPP4, soluble APN, CD46, CAR, desmoglein 2, ganglioside la, heparin sulfate proteoglycan, coagulation factor X, dipalmytoyl phosphatidylcholine, lactoferrin, Av integrins, SLPI, SCAR B2, PSGL-1, sialylated glycan, heparan sulfate, Anx2, ICAM-5, integrin ⁇ , integrin ⁇ 3, ICAM-1, etc.) and combinations thereof may be present in an amount from 0.000001% to 0.01% by weight of the composition.
  • one or more targeted components may be present in an amount of about 0.00000001%, 0.0000001%, 0.000001%, 0.00001%, 0.0001%, 0.001%, 0.01%, 0.05%, 1%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, 1.0%, 1.05%, 1.1%, 1.15%, 1.2%, 1.25%, 1.3%, 1.35%, 1.4%, 1.45%, 1.5%, 1.55%, 1.6%, 1.65%, 1.7%, 1.76%, 1.8%, 1.85%, 1.9%, 1.95%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, and 10.0% by weight of composition.
  • one or more targeted components may be present from 0.2% to 1.0% by weight of composition. In some embodiments, one or more targeted components may be present from about 0.000005% to 0.05% by weight of the composition. In preferred embodiments, one or more targeted components may be present from about 0.00005% to 0.005% by weight of the composition.
  • the non-targeted antimicrobial may be present in an amount from about 0.00000001% to 10% by weight of composition. More typically, anti-microbial may be present in an amount from 0.0000001% to 0.1% by weight of the composition.
  • the non-targeted antimicrobial e.g., one or more selected from mucins, lactoferrin (e.g. , apolactoferrin, etc.), lysozyme, SLPI, ⁇ -microseminoprotein, sPLA2, and/or statherin.
  • the non-targeted antimicrobial comprises plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extracts, rosemary extracts, myrhh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, a grapefruit seed extract, and combinations thereof, zinc peroxide (ZnC ), copper, and silver, zinc, zinc compounds, silver, silver compounds, copper, copper compounds, defensins (e.g., a and/or ⁇ defenins, etc.), histatins, cathelicidins, adrenomedullin, bacteriocidal/permeability increasing protein ("BPI”) and BPI-like proteins such as parotid secretory protein ("PSP”), proteins of palate lung and nasal epithelial clone family (“PLUNC”) including both short type and long type, amylase (e.g.
  • cystatins e.g. , cystatin A, cystatin B, cystatin C, cystatin D, cystatin S, cystatin SA, cystatin SN, etc.
  • proline rich peptides mucins (e.g., MUC7, MUC5b, etc.), peroxidases (e.g. , lactoperoxidase, myeloperoxidase, etc.), slatherin, and/or salivary agglutinin, etc.) may be present in an amount from 0.000001% to 0.01% by weight of the composition.
  • one or more targeted components may be present in an amount of about 0.00000001%, 0.0000001%, 0.000001%, 0.00001%, 0.0001%, 0.001%, 0.01%, 0.05%, 1%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, 1.0%, 1.05%, 1.1%, 1.15%, 1.2%, 1.25%, 1.3%, 1.35%, 1.4%, 1.45%, 1.5%, 1.55%, 1.6%, 1.65%, 1.7%, 1.76%, 1.8%, 1.85%, 1.9%, 1.95%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, and 10.0% by weight of composition.
  • one or more targeted components may be present from 0.2% to 1.0% by weight of composition.
  • the non-targeted anti-microbial may be present from about 0.000005% to 0.05% by weight of the composition.
  • the non-targeted antimicrobial may be present from about 0.00005% to 0.005% by weight of the composition.
  • the anti-inflammatory may be present in an amount from about 0.00000001% to 10% by weight of composition. More typically, anti-inflammatory may be present in an amount from 0.0000001% to 0.1% by weight of the composition.
  • the anti-inflammatory e.g., one or more selected from ICAM inhibitors (e.g., CDl la, ezrin (EZR), CD18, glycyrrhetinic acid, pyrrolidinedithiocarbamate, etc.), NFKB inhibitors (e.g., (heterocyclic thiazole, lipoic acid, efalizumab, 4-[(4- Methylphenyl)thio]thieno[2,3-c]pyridine-2-carboxamide, silibinin, stilbenes, (+)- epigalloylcatechin-gallate [(+)-EGCG], etc.), TSLP inhibitors, IL-25 inhibitors, 11-33 inhibitors, II- 1 inhibitors, TNF
  • one or more targeted components may be present in an amount of about 0.00000001%, 0.0000001%, 0.000001%, 0.00001%, 0.0001%, 0.001%, 0.01%, 0.05%, 1%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, 1.0%, 1.05%, 1.1%, 1.15%, 1.2%, 1.25%, 1.3%, 1.35%, 1.4%, 1.45%, 1.5%, 1.55%, 1.6%, 1.65%, 1.7%, 1.76%, 1.8%, 1.85%, 1.9%, 1.95%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, and 10.0% by weight of composition.
  • one or more targeted components may be present from 0.2% to 1.0% by weight of composition.
  • the non-targeted anti-microbial may be present from about 0.000005% to 0.05% by weight of the composition.
  • the non- targeted anti-microbial may be present from about 0.00005% to 0.005% by weight of the composition.
  • Bio- manufacturing can utilize genetically engineered microorganisms like bacteria, fungi, animal cells, yeast, or plants (including algae). Expression in mammalian cell lines, bacteria, and yeast is often costly. One of the reasons for this is the need for purification. Algae offer several advantages to other methods in that very high levels of purification are often not required.
  • Algae or other plants are the preferred expression system of the recited proteins because recombinantly engineered algae or other plants are far more economical to grow and harvest than mammalian cells or bacteria.
  • Algae are grown for use as nutritional supplements themselves and are also used to bioengineer certain nutritional compounds for commercial production such as omega-3 fatty acids and carotenoids (Gimpel JA, Henriquez V, and Mayfield SP Frontiers in Microbiology 2015). Most metabolic engineering strategies have been geared towards enhancing commercial production of these compounds and also for using algae as biofuels.
  • algae may be optimized to produce a range of different metabolites that have certain characteristics in an efficient manner.
  • Transgenic algae have been shown to support recombinant protein expression from both the chloroplast and nuclear genomes (Rasal BA et al., Plant Biotechnology J 2010). Originally, only the nuclear genomes were used but the development of techniques required to express recombinant proteins in the chloroplast genome add versatility to the platform and make it possible to either express proteins that cannot be expressed in the nuclear genome or to express the proteins more efficiently. The majority of recombinant proteins produced today are produced mainly in bacteria, yeast (S. cervisiae), or mammalian cell culture. Other systems under development for large scale production include the yeast P. pastoris, insect cells, and other animals and plants.
  • Any viable plant or animal expression system may be used but first, those which are likely to be the most cost-efficient such as those recombinant expression systems that will not require a high degree of purification will be investigated and sought out. This will make it possible for the embodiment to be sold over the counter without the need for clinical trials. If needed, other recombinant expression systems are used that may require higher degrees of purification.
  • the method may reduce the growth of a respiratory infection, shrink the infection, or eradicate the infection.
  • the infection shrinks by 5%, 10%, 25%, 50%, 75%, 85%, 90%, 95%, or 99% or more as compared to its original size.
  • the method for prophylaxis and/or treatment of human rhinovirus infection comprises applying any of the composition described herein to the nasal and/or oral mucosa of an individual in need thereof. In some embodiments, the nasal and/or oral mucosa of individuals in need thereof has human rhinovirus in contact therewith. In some embodiments, the method for prophylaxis and/or treatment of influenza infection comprises applying any of the composition described herein to the nasal and/or oral mucosa of an individual in need thereof. In some embodiments, the nasal and/or oral mucosa of individuals in need thereof has influenza in contact therewith.
  • the method for prophylaxis and/or treatment of parainfluenza infection comprises applying any of the composition described herein to the nasal and/or oral mucosa of an individual in need thereof. In some embodiments, the nasal and/or oral mucosa of individuals in need thereof has parainfluenza in contact therewith. In some embodiments, the method for prophylaxis and/or treatment of enterovirus infection comprises applying any of the composition described herein to the nasal and/or oral mucosa of an individual in need thereof. In some embodiments, the nasal and/or oral mucosa of individuals in need thereof has enterovirus in contact therewith.
  • the method for prophylaxis and/or treatment of adenovirus infection comprises applying any of the composition described herein to the nasal and/or oral mucosa of an individual in need thereof. In some embodiments, the nasal and/or oral mucosa of individuals in need thereof has adenovirus in contact therewith. In some embodiments, the method for prophylaxis and/or treatment of coronavirus infection comprises applying any of the composition described herein to the nasal and/or oral mucosa of an individual in need thereof. In some embodiments, the nasal and/or oral mucosa of individuals in need thereof has coronavirus in contact therewith.
  • the method for prophylaxis and/or treatment of coxsackievirus infection comprises applying any of the composition described herein to the nasal and/or oral mucosa of an individual in need thereof. In some embodiments, the nasal and/or oral mucosa of individuals in need thereof has coxsackievirus in contact therewith. In some embodiments, the method for prophylaxis and/or treatment of Streptococcal pyogenes infection comprises applying any of the composition described herein to the nasal and/or oral mucosa of an individual in need thereof. In some embodiments, the nasal and/or oral mucosa of individuals in need thereof has Streptococcal pyogenes in contact therewith.
  • the invention provides for a method of prophylaxis or treatment of respiratory infection in subjects suffering from or at risk of suffering from respiratory infection comprising: determining a subject is suffering from or at risk of suffering from a respiratory infection; and administering a composition according to the invention comprising one or more antimicrobial or antiviral compounds and a base mixture comprising one or more ingredients selected from the group consisting of a carrier, an emollient, an occlusive, a humectant, an emulsifier, and an essential oil.
  • the one or more antimicrobial or antiviral compounds comprise IgA, IgG, and/or IgM.
  • the one or more antimicrobial or antiviral compounds comprise zinc peroxide (ZnC ), copper, and/or silver.
  • the compositions may be administered by any suitable route, including orally, topically, nasally, and combinations thereof.
  • the composition is administered to nasal membranes.
  • the composition is administered to oral membranes.
  • the composition is administered using a device selected from the group consisting of an atomizer, an inhaler, a nebulizer, a spray bottle, and a spray pump.
  • the composition may include a propellant or may be free of propellants.
  • the methods may involve administering the pharmaceutical composition multiple times per day.
  • the methods may involve administering the pharmaceutical composition on a first day and repeating the administration on one or more subsequent days.
  • the first day and one or more subsequent days are separated by between 1 day and about 3 weeks.
  • the pharmaceutical composition is coadministered with another therapeutic regimen. It is further contemplated within the scope of the disclosure that the pharmaceutical composition may be administered over the course of one or more cycles.
  • each active component ⁇ e.g., the targeted component, non-targeted antimicrobial, and/or anti-inflammatory) of the pharmaceutical composition may be coadministered with one another to achieve the therapeutic effect.
  • the order or sequence of administering the different agents of the disclosure e.g., antibiotics, antivirals, antifungals, or immunotherapeutic agents, may vary and is not confined to any particular sequence of administration.
  • Co-administering may also refer to the situation where two or more agents are administered to different regions of the body or via different delivery schemes, e.g., where a first agent is administered intranasally and a second agent is administered systemically, or vice versa.
  • Co-administering may also refer to two or more agents administered via the same delivery scheme, e.g., where a first agent is administered intranasally and a second agent is administered intranasally or where a first agent is administered orally and a second agent is administered orally or where a first agent is administered intranasally and a second agent is administered orally.
  • two or more agents may be coupled together to form a covalent or otherwise stable association between the two or more agents.
  • an anti-viral agent may be coupled with an anti-inflammatory agent via a covalent bond, a covalently tethered linker moiety, or non-covalently through ionic interactions or hydrogen bonding.
  • One or more agents that are coupled together retain substantially their same independent functions and characteristics. For example, the therapeutic agent when coupled to another agent may retain its same activity as if it were independent.
  • the compounds and pharmaceutical compositions can be formulated and employed in combination therapies, that is, the compounds and pharmaceutical compositions can be formulated with or administered concurrently with, prior to, or subsequent to, one or more other desired therapeutics or medical procedures.
  • the particular combination of therapies (therapeutics or procedures) to employ in a combination regimen will take into account compatibility of the desired therapeutics and/or procedures and the desired therapeutic effect to be achieved. It will also be appreciated that the therapies employed may achieve a desired effect for the same disorder, or they may achieve different effects ⁇ e.g., control of any adverse effects).
  • the antimicrobial agent can be any agent well known in the art, including, but not limited to, those described herein.
  • the present disclosure contemplates treating a broad range of respiratory diseases, including infections of all types, locations, sizes, and characteristics.
  • the methods of the disclosure are suitable for treating, for example, sinusitis, influenza, rhinovirus (the common cold), coronavirus, adenovirus, enterovirus, coxsackievirus or infection caused by Streptococcus pyogenes.
  • any type of respiratory-related infection may be treated by the present disclosure including, but not limited to, the following respiratory infections: tonsillitis, pharyngitis, laryngitis, sinusitis, otitis media, certain types of influenza, bronchitis, pneumonia, and the common cold.
  • compositions of the invention are contemplated to be useful in the prophylaxis or treatment of viral infection from any rhinovirus or enterovirus.
  • compositions of the invention are also contemplated to be suitable for prophylaxis and/or treatment of infection from any serotype of human influenza virus, including without limitation, those of the genera Influenzavirus A, Influenzavirus B, and Influenzavirus B, including the species influenza A virus (including, without limitation, serotypes H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7N3, H10N7, and H7N9 to name a few), influenza B virus, and influenza C virus.
  • influenza A virus including, without limitation, serotypes H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7N3, H10N7, and H7N9 to name a few
  • influenza B virus and influenza C virus.
  • compositions of the invention are also contemplated to be suitable for prophylaxis and/or treatment of infection from any virion species of enterovirus, including without limitation, those of the genera Enterovirus A (e.g., coxsackievirus serotypes CV-A2, CV-A3, CV-A4, CV-A5, CV-A6, CV-A7, CV-A8, CV-A10, CV-A12, CV-A14, CV- A16, enterovirus serotypes EV-A71, EV-A76, EV-A89, EV-A90, EV-A91, EV-A92, EV-A114, EV- A119, SV19, SV43, SV46 & BA13 etc.), Enterovirus B (e.g., coxsackievirus serotypes CV-B1, CV-B2, CV-B3, CV-B4, CV-B5, CV-B6, CV-A9, enterovirus serotypes EV-B69, EV-B73,
  • compositions of the invention are also contemplated to be suitable for prophylaxis and/or treatment of infection from any virion species of coronavirus, including without limitation, the species Human coronavirus HKUl, Human coronavirus OC43, Human coronavirus 229E, MERS-CoV, SARS-CoV, Pipistrellus bat coronavirus HKU5, Tylonycteris bat coronavirus HKU4, Rousettus bat coronavirus HKU9, Bat SL-CoV-WIVl, Londonl novel CoV/2012, or HCoV-EMC/2012.
  • any virion species of coronavirus including without limitation, the species Human coronavirus HKUl, Human coronavirus OC43, Human coronavirus 229E, MERS-CoV, SARS-CoV, Pipistrellus bat coronavirus HKU5, Tylonycteris bat coronavirus HKU4, Rousettus bat coronavirus HKU9, Bat SL-Co
  • compositions of the invention are also contemplated to be suitable for prophylaxis and/or treatment of infection from any virion species of adenovirus, including HAdV-1 to HAdV-5.
  • inventive compositions are contemplated to be useful in the prophylaxis or treatment of viral infection from any sialic acid-binding virus, including influenza virus, enterovirus, adenovirus and/or rotavirus.
  • sialic acid-binding virus including influenza virus, enterovirus, adenovirus and/or rotavirus.
  • compositions according to the invention are applied to the nasal and/or oral mucosa for prophylaxis or treatment of human rhinovirus, human influenza virus infection, enterovirus, adenovirus, coronavirus, coxsackievirus, infections from Streptococcus pyogenes, or combinations thereof.
  • the present disclosure may generally treat and/or prevent all forms of the above infections.
  • the method of the disclosure advantageously may treat or prevent infections arising in any part of the respiratory tract including, but not limited to, the upper respiratory tract (nose, sinuses, larynx and pharynx) and the lower respiratory tract (trachea, primary bronchi, bronchial tubes, bronchioles, and lungs).
  • Reduction of infection means a measurable decrease in growth of the infection.
  • the infection may be reduced by at least about a factor of 10 (for example 100, 1000-fold or more) or by decrease of at least about 10% (for example at least about 20, 30, 40, 50, 60, 70, 80, 90, 95, 99 or 100%) as compared to the growth measured over time prior to treatment as defined herein.
  • the reduction in infection according to the invention is ideally of a statistically significant degree as compared to otherwise identical infected tissues in the absence of the active ingredients contained the composition of the invention.
  • Full eradication of the infection may also be achieved through methods of the disclosure. Eradication refers elimination of the infection and infectious organisms. The infection is considered to be eliminated when it is no longer detectable using detection methods known in the art.
  • the amount of the pharmaceutical composition of the disclosure that will be effective in the treatment or prevention of a respiratory infection or allergy may depend on the nature of the pathogen and can be determined by standard clinical techniques, including blood tests and/or imaging techniques. In addition, in vitro assays may optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the formulation may also depend on the route of administration, and the seriousness of the infection, and should be decided according to the judgment of the practitioner and each patient's circumstances. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems. [0126] The therapeutic agents, immunotherapeutic agents, or compositions containing these agents are administered in a manner compatible with the dosage formulation, and in such amount as may be therapeutically affective, protective and immunogenic.
  • the agents and/or compositions may be administered through different routes, including, but not limited to, nasal, aerosol, topical, buccal and sublingual, oral, intradermal, subcutaneous, and parenteral.
  • parenteral as used herein includes, for example, intraocular, subcutaneous, intraperitoneal, intracutaneous, intravenous, intramuscular, intraarticular, intraarterial, intrasynovial, intrastemal, intrathecal, intralesional, and intracranial injection, or other infusion techniques.
  • administration of the therapeutic agents is delivered locally or regionally (e.g., intranasally, orally, etc.).
  • a device is used to deliver the antimicrobial composition to the respiratory tract.
  • the composition may be delivered through use of an inhaler, atomizer, nebulizer, nasal spray bottle, nasal spray pump, ventilator, compressed air tank, aerosolizer, and nasal cannula.
  • the composition can be delivered through insufflation, inhalation, oral ingestion, sublingual, and any combination thereof.
  • preparations for inhaled or aerosol delivery comprise a plurality of particles.
  • such preparations have a mean particle size of 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 microns.
  • preparations for inhaled or aerosol delivery are formulated as a dry powder.
  • preparations for inhaled or aerosol delivery are formulated as a wet powder, for example through inclusion of a wetting agent, in some embodiments, the wetting agent is selected from the group consisting of water, saline, or other liquid of physiological pH.
  • inventive compositions are administered as drops to the nasal or buccal cavity.
  • a dose may comprise a plurality of drops (e.g., 1-100, 1-50, 1-20, 1-10, 1-5, etc.).
  • the present invention relates to kit comprising a stable fixed dose, aqueous pharmaceutical composition of the present invention contained in a container for nasal and/or oral administration and a package insert containing instructions about the use of said pharmaceutical composition.
  • the container is part of a sprayer which has an actuator. When the actuator is actuated, the composition is delivered in the form of a spray.
  • the pharmaceutical composition is contained in a sprayer, and has, on deliver a spray of the composition to a human nose, a spray pattern having a longest axis of 15-75 mm, a shortest axis of 10- 65 mm, and an ellipticity of 1-2.
  • the pharmaceutical composition when delivered as a nasal and/or oral spray using a sprayer yields a specific spray pattern and spray droplet size.
  • the spray pattern can be determined by various known techniques such as with an ADSA with NSPUA set up (Innova System) and the spray droplet size distribution can be determined by various known techniques such as with a Malvern Spraytec with NSPUA set up (Innova System).
  • a commercially available laser diffraction instrument is arranged so that the nozzle is about 3 cm or 6 cm below the laser beam of the laser diffraction instrument.
  • the pump is actuated with a conventional mechanical actuator using a constant force.
  • the resulting spray of the composition crosses the laser beam.
  • Data are collected for Dio, D50, D90, SPAN, and % Volume ⁇ 10 ⁇ . The average values for each of these parameters for three sprays are calculated.
  • the aqueous nasal spray suspension can be administered as a drop or any other form suitable for topical administration.
  • the composition may also be administered using a nasal tampon or a nasal sponge.
  • the aqueous suspension is provided in the form of nasal spray wherein the suspension is administered in a single unit-dose container or multi-dose container.
  • Suitable single unit-dose containers or multi-dose containers include, but are not limited to, glass, aluminum, polypropylene or high density polyethylene, for example, high density polyethylene containers produced using a blow-fill-seal manufacturing technique.
  • the invention provides a multi dosage composition of matter, comprising: (a) a multi-unit dosage of a pharmaceutical composition of the present invention; and (b) a container comprising: (i) a squeezable chamber holding the multi dosage of the composition and having an opening wherein the dosage exits the opening when the squeezable chamber is squeezed; and (ii) a closure mechanism removably attached to the opening of the squeezable chamber.
  • the multi dosage container is made of a moldable polymer.
  • suitable polymers include, but are not limited to, polyethylene, polypropylene (PP), polystyrene (PS), nylon (Ny), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polycarbonate (PC), poly oxy methylene (POM), polysulfon (PSF), polyethersulfon (PES), polyacrylate (PAR), and polyamid (PA).
  • polymers include polyethylene, particularly medium-density polyethylene (MDPE) (or branched polyethylene) or high density polyethylene (HDPE) (or linear, polyethylene).
  • the multi dose container is made of high density polyethylene (HDPE).
  • the pharmaceutical composition is administered orally, and more particularly, as an oral spray.
  • a sweetener and flavor enhancers may also be included in the oral spray composition.
  • Sweeteners may include fructose, dextrose, sucrose or the like.
  • Non-artificial sweeteners work best with a preferred embodiment including fructose in an amount of about 8 to 15 weight percent of the oral spray composition, and preferably at about 10 weight percent of the oral composition.
  • a variety of flavorings may be used, preferably in the form of a stable extract. Alcohol containing forms of flavorings are not preferred.
  • One preferred embodiment of the oral spray composition includes a flavor enhancer, such as peppermint, for example, in an amount of about 0.5 to 2.0 weight percent of the oral spray composition, and preferably at about 1 weight percent of the oral composition.
  • a preservative may be added to the oral composition to facilitate stability of the various ingredients.
  • Any suitable preservative may be used in accordance with the present invention such as, for example, benzalkonium chloride, benzyl alcohol, and disodium EDTA.
  • the preservative includes a 50% solution of benzalkonium chloride admixed into the oral composition at a concentration of about 0.01 to 0.02 percent by weight, and preferably about 0.015 percent by weight.
  • the composition of the present invention is preferably delivered to the oral cavity through the mouth by way of a fine spray mist.
  • the method includes the steps of obtaining an oral composition in accordance with the present invention for delivery into the oral cavity.
  • the method further includes the step of applying the oral composition to the oral cavity with a spray applicator.
  • any suitable applicator may be used.
  • the applicator is available from Pfeiffer of America, 12 Roszel Road, Suite C-104, Princeton, N.J. 08540 as Item #63922. This applicator is configured to hold about 120 metered 0.25 ml doses, of the composition.
  • the composition may be delivered to an individual in any suitable dosage.
  • the oral spray applicator is configured to supply a unit dose of about 0.25 rriLs of composition to the individual each time a pump associated with the spray applicator is activated (0.25 mLs/spray).
  • the composition is delivered by applying about 4 sprays in the mouth approximately every 3 hours during waking hours until the infection symptoms have subsided.
  • Other means for delivering the nasal and/or oral spray such as inhalation via a metered dose inhaler (MDI), may also be used.
  • MDIs metered dose inhaler
  • MDI breath-actuated MDIs
  • spacer/holding chambers in combination with MDIs
  • nebulizers can include breath-actuated MDIs, spacer/holding chambers in combination with MDIs, and nebulizers.
  • MDI refers to an inhalation delivery system comprising, for example, a canister containing a mixture of an active agent and a propellant optionally with one or more excipients, a metered dose valve, an actuator, and a mouthpiece.
  • the canister is may be filled with a suspension of an active agent, such as the nasal spray composition, and a propellant, such as one or more hydrofluoroalkanes [e.g.
  • the composition is free of propellants.
  • the actuator When the actuator is depressed a metered dose of the suspension is aerosolized for inhalation. Particles comprising the active agent are propelled towards the mouthpiece where they may then be inhaled by a subject.
  • the agents and/or compositions formulated according to the present disclosure are formulated and delivered in a manner to evoke a systemic immune response.
  • the formulations are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers.
  • Formulations suitable for administration include aqueous and nonaqueous sterile solutions, which may contain anti- oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient, and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.
  • the formulations may be presented in unit-dose or multi-dose containers, for example, sealed ampoules and vials, and may be stored in a freeze- dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example, water, immediately prior to use.
  • sterile liquid carrier for example, water
  • Extemporaneous solutions and suspensions may be prepared from sterile powders, granules and tablets commonly used by one of ordinary skill in the art.
  • agents and/or compositions may be administered in different forms, including, but not limited to, gases, solutions, emulsions and suspensions, gels, foams, sprays, mists, lotions, microspheres, particles, microparticles, nanoparticles, liposomes, and the like.
  • the agents and/or compositions are administered in a manner compatible with the dosage formulation, and in such amount as may be therapeutically effective, immunogenic and protective.
  • the quantity to be administered depends on the subject to be treated, including, for example, the size of the infection and the capacity of the individual's immune system to synthesize antibodies and/or to produce a cell-mediated immune response.
  • Precise amounts of active ingredients required to be administered depend on the judgment of the practitioner. However, suitable dosage ranges are readily determinable by one skilled in the art and may be of the order of micrograms to milligrams of the active ingredient(s) per dose.
  • the dosage may also depend on the route of administration and may vary according to the size of the host.
  • the agents and/or compositions should be administered to a subject in an amount effective to stimulate a protective immune response in the subject.
  • Specific dosage and treatment regimens for any particular subject may depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health status, sex, diet, time of administration, rate of excretion, drug combination, the severity and course of the infection, condition or symptoms, the subject's disposition to the disease, condition or symptoms, method of administration, and the judgment of the treating physician. Actual dosages can be readily determined by one of ordinary skill in the art.
  • Exemplary unit dosage formulations are those containing a dose or unit, or an appropriate fraction thereof, of the administered ingredient. It should be understood that in addition to the ingredients mentioned herein, the formulations of the present disclosure may include other agents commonly used by one of ordinary skill in the art.
  • a therapeutically effective amount of the present compounds in dosage form usually ranges from slightly less than about 0.025 mg/kg/day to about 2.5 g/kg/day, preferably about 0.1 mg/kg/day to about 100 mg/kg/day of the patient or considerably more, depending upon the compound used, the condition or infection treated and the route of administration, although exceptions to this dosage range may be contemplated by the present disclosure.
  • antimicrobial/antiviral compositions according to the present disclosure may be administered intranasally in amounts ranging from about 0.5 mg/mL of dosing solution to about 50 mg/mL.
  • antimicrobial compositions according to the present disclosure may be administered intranasally in amounts ranging from about 10 mg/mL to about 30 mg/mL.
  • the dosage of the antimicrobial composition(s) may depend on the type of infection being treated, the particular compound used, the therapeutic agent, and other clinical factors and conditions of the patient. It is to be understood that the present disclosure has application for both human and veterinary use.
  • the agents and/or compositions may be administered in one or more doses as required to achieve the desired effect.
  • the agents and/or compositions may be administered in 1, 2, to 3, 4, 5, or more doses. Further, the doses may be separated by any period of time, for example hours, days, weeks, months, and years.
  • the agents and/or compositions may be formulated as liquids or dry powders, or in the form of microspheres.
  • the agents and/or compositions may be stored at temperatures of from about -100° C to about 25° C. depending on the duration of storage.
  • the agents and/or compositions may also be stored in a lyophilized state at different temperatures including room temperature.
  • the agents and/or compositions may be sterilized through conventional means known to one of ordinary skill in the art. Such means include, but are not limited to, filtration.
  • the amount of active ingredient that may be combined with carrier materials to produce a single dosage form may vary depending upon the host treated and the particular mode of administration.
  • a preparation may contain from about 0.1% to about 95% active compound (w/w), from about 20% to about 80% active compound, or from any percentage there between.
  • sterile, fixed oils are conventionally employed as a solvent or suspending medium.
  • any bland fixed oil may be employed including synthetic mono- or to diglycerides.
  • Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions.
  • These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, or carboxymethyl cellulose or similar dispersing agents which are commonly used in the formulation of pharmaceutically acceptable dosage forms such as emulsions and or suspensions.
  • the pharmaceutical composition may be administered locally as an immediate release or controlled release composition, for example by controlled dissolution and/or the diffusion of the active substance.
  • Dissolution or diffusion controlled release can be achieved by incorporating the active substance into an appropriate matrix.
  • a controlled release matrix may include one or more of shellac, beeswax, glycowax, castor wax, carnauba wax, stearyl alcohol, glyceryl monostearate, glyceryl distearate, glycerol palmitostearate, ethylcellulose, acrylic resins, dl-polylactic acid, cellulose acetate butyrate, polyvinyl chloride, polyvinyl acetate, vinyl pyrrolidone, polyethylene, polymethacrylate, methylmethacrylate, 2-hydroxymethacrylate, methacrylate hydrogels, 1,3 butylene glycol, ethylene glycol methacrylate, and/or polyethylene glycols.
  • the matrix material may also include, e.g., hydrated metylcellulose, carnauba wax and stearyl alcohol, carbopol 934, silicone, glyceryl tristearate, methyl acrylate-methyl methacrylate, polyvinyl chloride, polyethylene, and/or halogenated fluorocarbon.
  • the controlled release matrix is a hydrogel.
  • a hydrogel is a three- dimensional, hydrophilic or amphiphilic polymeric network capable of taking up large quantities of water.
  • the networks are composed of homopolymers or copolymers, which are insoluble due to the presence of covalent chemical or physical (e.g., ionic, hydrophobic interactions, entanglements, etc.) crosslinks.
  • the crosslinks provide the network structure and physical integrity.
  • Hydrogels exhibit a thermodynamic compatibility with water that allows them to swell in aqueous media.
  • the chains of the network are connected in such a fashion that pores exist and that a substantial fraction of these pores are of dimensions between 1 nm and 1000 nm.
  • the hydrogels can be prepared by crosslinking hydrophilic biopolymers or synthetic polymers.
  • Examples of the hydrogels formed from physical or chemical crosslinking of hydrophilic biopolymers include but are not limited to, hyaluronans, chitosans, alginates, collagen, dextran, pectin, carrageenan, polylysine, gelatin, agarose, (meth)acrylate-oligolactide- PEO-oligolactide-(meth)acrylate, poly(ethylene glycol) (PEO), poly(propylene glycol) (PPO), PEO-PPO-PEO copolymers (Pluronics), poly(phosphazene), poly(methacrylates), poly(N- vinylpyrrolidone), PL(G)A-PEO-PL(G)A copolymers, poly(ethylene imine), and the like.
  • the agents and/or compositions can be delivered in an exosomal delivery system.
  • Exosomes are small membrane vesicles that are released into the extracellular environment during fusion of multivesicular bodies with plasma membrane. Exosomes are secreted by various cell types including hematopoietic cells, normal epithelial cells and even some tumor cells. Exosomes are known to carry MHC class I, various costimulatory molecules and some tetraspanins. Recent studies have shown the potential of using native exosomes as immunologic stimulants.
  • the agents and/or compositions provided herein can contain nanoparticles having at least one or more agents linked thereto, e.g., linked to the surface of the nanoparticle.
  • a composition typically includes many nanoparticles with each nanoparticle having at least one or more agents linked thereto.
  • Nanoparticles can be colloidal metals.
  • a colloidal metal includes any water- insoluble metal particle or metallic compound dispersed in liquid water.
  • a colloid metal is a suspension of metal particles in aqueous solution. Any metal that can be made in colloidal form can be used, including gold, silver, copper, nickel, aluminum, zinc, calcium, platinum, palladium, and iron.
  • gold nanoparticles are used, e.g., prepared from HAuCk Nanoparticles can be any shape and can range in size from about 1 nm to about 10 nm in size, e.g., about 2 nm to about 8 nm, about 4 to about 6 nm, or about 5 nm in size.
  • Methods for making colloidal metal nanoparticles, including gold colloidal nanoparticles from HAuCU, are known to those having ordinary skill in the art. For example, the methods described herein as well as those described elsewhere ⁇ e.g., US Pat. Publication Nos. 2001/005581 ; 2003/0118657; and 2003/0053983, which are hereby incorporated by reference) are useful guidance to make nanoparticles.
  • a nanoparticle can have two, three, four, five, six, or more active agents linked to its surface. Typically, many molecules of active agents are linked to the surface of the nanoparticle at many locations. Accordingly, when a nanoparticle is described as having, for example, two active agents linked to it, the nanoparticle has two active agents, each having its own unique molecular structure, linked to its surface. In some cases, one molecule of an active agent can be linked to the nanoparticle via a single attachment site or via multiple attachment sites. An active agent can be linked directly or indirectly to a nanoparticle surface. For example, the active agent can be linked directly to the surface of a nanoparticle or indirectly through an intervening linker.
  • a linker can be an aliphatic chain including at least two carbon atoms ⁇ e.g., 3, 4, 5, 6, 7, 8, 9, 10 or more carbon atoms), and can be substituted with one or more functional groups including ketone, ether, ester, amide, alcohol, amine, urea, thiourea, sulfoxide, sulfone, sulfonamide, and disulfide to functionalities.
  • a linker can be any thiol-containing molecule. Reaction of a thiol group with the gold results in a covalent sulfide (— S— ) bond.
  • Linker design and synthesis are well known in the art.
  • the nanoparticle is linked to a targeting agent/moiety.
  • a targeting functionality can allow nanoparticles to accumulate at the target ⁇ e.g. nasal membrane) at higher concentrations than in other tissues.
  • a targeting molecule can be one member of a binding pair that exhibits affinity and specificity for a second member of a binding pair.
  • an antibody or antibody fragment therapeutic agent can target a nanoparticle to a particular region or molecule of the body ⁇ e.g., the region or molecule for which the antibody is specific) while also performing a therapeutic function.
  • a receptor or receptor fragment can target a nanoparticle to a particular region of the body, e.g. , the location of its binding pair member.
  • Other therapeutic agents such as small molecules can similarly target a nanoparticle to a receptor, protein, or other binding site having affinity for the therapeutic agent.
  • compositions of this disclosure comprise one or more additional therapeutic or prophylactic agents
  • the therapeutic/enhancing/immunotherapy agent and the additional agent should be present at dosage levels of between about 0.1 to 100%, or between about 5 to 95% of the dosage normally administered in a monotherapy regimen.
  • the additional agents may be administered separately, as part of a multiple dose regimen, from the agents of this disclosure. Alternatively, those additional agents may be part of a single dosage form, mixed together with the agents of this disclosure in a single composition.
  • the administration of the agents and/or compositions of the disclosure elicits an immune response against a pathogen.
  • the dose can be adjusted within this range based on, e.g., the subject's age, the subject's health and physical condition, the capacity of the subject's immune system to produce an immune response, the subject's body weight, the subject's sex, diet, time of administration, the degree of protection desired, and other clinical factors.
  • Those in the art can also readily address parameters such as biological half-life, bioavailability, route of administration, and toxicity when formulating the agents and/or compositions of the disclosure.
  • Embodiment 1 A pharmaceutical composition comprising:
  • a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial
  • a pharmaceutically acceptable carrier diluent and/or excipient.
  • Embodiment 2 The pharmaceutical composition according to embodiment 1, comprising a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted anti-bacterial component for bacteria selected from Streptococcus pyogenes.
  • Embodiment 3 The pharmaceutical composition according to embodiment 1, wherein said non- targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 4 The pharmaceutical composition according to embodiment 1, wherein said non- targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g. , grapefruit seed extract, etc.), or combinations thereof.
  • said non- targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil
  • Embodiment 6 The pharmaceutical composition according to any one of embodiments 1-5, wherein said targeted antiviral component and said non-targeted anti-microbial are present in an amount effective to reduce the copy number of said virions in mucosa.
  • Embodiment 7 The pharmaceutical composition according to embodiment 6, wherein said mucosa is the mucosa of the nose or the throat.
  • Embodiment 8 The pharmaceutical composition according to embodiment 1, wherein said pharmaceutical composition does not alter the pH and/or osmolarity of mucosa following application to said mucosa.
  • Embodiment 9 The pharmaceutical composition according to embodiment 8, wherein said mucosa is the mucosa of the nose, throat, and/or mouth.
  • Embodiment 101731 Embodiment 10.
  • Embodiment 11 The pharmaceutical composition according to embodiment 1, wherein said composition is in the form of a nasal spray.
  • Embodiment 12 The pharmaceutical composition according to embodiment 1, wherein said compositions is in the form of an oral spray.
  • Embodiment 13 The pharmaceutical composition according to embodiment 1, wherein said pharmaceutically acceptable carrier is adapted to provide residence time of said composition on the nasal and/or oral mucosa of at least 1 minute, or at least 5 minutes, or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes.
  • Embodiment 14 The pharmaceutical composition according to embodiment 1, wherein said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g., 1,3- propanediol, etc.).
  • said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g., 1,3- propanediol, etc.).
  • Embodiment 15 The pharmaceutical composition according to embodiment 1, wherein said antiviral component is capable of binding to said virions via the receptor recognition mechanism of said virions.
  • Embodiment 16 The pharmaceutical composition according to embodiment 1, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 19 The pharmaceutical composition according to embodiment 1, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition and said non-targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 20 The pharmaceutical composition according to embodiment 1, wherein said targeted anti-bacterial component comprises from about 0.000001-10% by weight of said composition and said non-targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 21 The pharmaceutical composition according to embodiment 1, wherein said targeted anti-bacterial component comprises from about 0.000001-10% by weight of said composition, said targeted anti-viral component comprises from about 0.000001-10% by weight of said composition, and said non-targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 22 The pharmaceutical composition according to embodiment 1 or 2, wherein said virions comprise coronavirus, influenza, and/or parainfluenza.
  • Embodiment 23 The pharmaceutical composition according to embodiment 22, wherein said targeted antiviral component for coronavirus, influenza, and/or parainfluenza comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 24 The pharmaceutical composition according to embodiment 22, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 25 The pharmaceutical composition according to embodiment 22, wherein said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof.
  • said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, ne
  • Embodiment 27 The pharmaceutical composition according to embodiment 22, wherein said targeted antiviral component comprises sialic acid ⁇ e.g., 3' and 6' sialyllactose), ACE2 ⁇ e.g., soluble ACE2, etc.), DPP4 ⁇ e.g., soluble DPP4, etc.), APN ⁇ e.g., soluble APN, etc.).
  • sialic acid ⁇ e.g., 3' and 6' sialyllactose
  • ACE2 ⁇ e.g., soluble ACE2, etc.
  • DPP4 ⁇ e.g., soluble DPP4, etc.
  • APN ⁇ e.g., soluble APN, etc.
  • Embodiment 28 The pharmaceutical composition according to embodiment 27, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 29 The pharmaceutical composition according to embodiment 27, wherein said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof.
  • said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, ne
  • Embodiment 31 The pharmaceutical composition according to embodiment 27, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 32 The pharmaceutical composition according to embodiment 27, wherein said composition is in the form of a nasal spray.
  • Embodiment 33 The pharmaceutical composition according to embodiment 1 or 2, wherein said virions comprise adenovirus.
  • Embodiment 34 The pharmaceutical composition according to embodiment 33, wherein said targeted antiviral component for adenovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 35 The pharmaceutical composition according to embodiment 33, wherein said targeted antiviral component comprises CD46 ⁇ e.g., soluble CD46, etc.), CAR ⁇ e.g., soluble CAR, etc.), desmoglein 2, sialic acid, ganglioside la, heparan sulfate and proteoglycans thereof, coagulation factor X, dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins.
  • CD46 ⁇ e.g., soluble CD46, etc.
  • CAR ⁇ e.g., soluble CAR, etc.
  • desmoglein 2 sialic acid
  • ganglioside la heparan sulfate and proteoglycans thereof
  • coagulation factor X dipalmitoyl phosphatidylcholine
  • lactoferrin lactoferrin
  • Av integrins integrins
  • Embodiment 36 The pharmaceutical composition according to embodiment 35, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 37 The pharmaceutical composition according to embodiment 35, wherein said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g. , grapefruit seed extract, etc.), or combinations thereof.
  • said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract,
  • Embodiment 39 The pharmaceutical composition according to embodiment 35, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 40 The pharmaceutical composition according to embodiment 35, wherein said composition is in the form of a nasal spray.
  • Embodiment 41 The pharmaceutical composition according to embodiment 1, wherein said virions comprise enterovirus ⁇ e.g. , E71 or EV-D68).
  • Embodiment 42 The pharmaceutical composition according to embodiment 41, wherein said targeted antiviral component for enterovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 43 The pharmaceutical composition according to embodiment 41, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 44 The pharmaceutical composition according to embodiment 41, wherein said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g. , grapefruit seed extract, etc.), or combinations thereof.
  • said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract,
  • Embodiment 46 The pharmaceutical composition according to embodiment 41, wherein said targeted antiviral component comprises SCAR B2 ⁇ e.g., soluble SCAR B2, etc.), PSGL-1 ⁇ e.g. , soluble PSGL-1, etc.), sialylated glycan, heparan sulfate and proteoglycans thereof, Anx2 (e.g. , soluble Anx2, etc.), or ICAM-5 (e.g. , soluble ICAM-5, etc.).
  • SCAR B2 ⁇ e.g., soluble SCAR B2, etc.
  • PSGL-1 ⁇ e.g. , soluble PSGL-1, etc.
  • sialylated glycan heparan sulfate and proteoglycans thereof
  • Anx2 e.g. , soluble Anx2, etc.
  • ICAM-5 e.g. , soluble ICAM-5, etc.
  • Embodiment 47 The pharmaceutical composition according to embodiment 46, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 49 The pharmaceutical composition according to embodiment 46, wherein said composition comprises a non-targeted anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract (e.g., grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • a non-targeted anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myr
  • Embodiment 50 The pharmaceutical composition according to embodiment 46, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • composition according to embodiment 46 wherein said composition is in the form of a nasal spray.
  • Embodiment 52 The pharmaceutical composition according to embodiment 46, wherein said composition is in the form of an oral spray.
  • Embodiment 53 The pharmaceutical composition according to embodiment 1, wherein said virions comprise coxsackievirus (e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.).
  • coxsackievirus e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.
  • Embodiment 54 The pharmaceutical composition according to embodiment 53, wherein said targeted antiviral component for coxsackievirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 55 The pharmaceutical composition according to embodiment 53, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • compositions comprising a non-targeted anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract (e.g., grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • a non-targeted anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract
  • Embodiment 58 The pharmaceutical composition according to embodiment 53, wherein said targeted antiviral component comprises integrin ⁇ , ⁇ 3, ICAM-1 (e.g., soluble ICAM-1, etc.), or CAR (e.g., soluble CAR, etc.).
  • ICAM-1 e.g., soluble ICAM-1, etc.
  • CAR e.g., soluble CAR, etc.
  • Embodiment 59 The pharmaceutical composition according to embodiment 58, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 61 The pharmaceutical composition according to embodiment 58, wherein said composition comprises a non-targeted anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract (e.g., grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • a non-targeted anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract,
  • Embodiment 62 The pharmaceutical composition according to embodiment 58, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 63 The pharmaceutical composition according to embodiment 58, wherein said composition is in the form of a nasal spray.
  • Embodiment 64 The pharmaceutical composition according to embodiment 1, wherein said anti -bacterial is capable of killing or inhibiting growth of bacteria from the genus Streptococcus.
  • Embodiment 65 The pharmaceutical composition according to embodiment 64, wherein said anti-bacterial is capable of killing or inhibiting growth of Streptococcus pyogenes.
  • Embodiment 66 The pharmaceutical composition according to embodiment 65, wherein said targeted antibacterial component for Streptococcus pyogenes comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 67 The pharmaceutical composition according to embodiment 65, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 68 The pharmaceutical composition according to embodiment 65, wherein said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof.
  • said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract,
  • Embodiment 70 The pharmaceutical composition according to embodiment 64, wherein said anti-bacterial is a C5a peptidase inhibitor, an anti-leukoproteinase, or a secretory leukocyte protease inhibitor.
  • Embodiment 71 The pharmaceutical composition according to embodiment 70, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 72 The pharmaceutical composition according to embodiment 70, wherein said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof.
  • said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, n
  • Embodiment 74 The pharmaceutical composition according to embodiment 70, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 75 The pharmaceutical composition according to embodiment 70, wherein said composition is in the form of a nasal spray.
  • a pharmaceutical composition comprising:
  • a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial
  • Embodiment 77 The pharmaceutical composition according to embodiment 76, comprising a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted antibacterial component for bacteria selected from Streptococcus pyogenes.
  • a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted antibacterial component for bacteria selected from Streptococcus pyogenes.
  • Embodiment 78 The pharmaceutical composition according to embodiment 76, wherein said targeted antiviral component and said non-targeted anti-inflammatory are present in an amount effective to reduce the copy number of said virions in mucosa.
  • Embodiment 79 The pharmaceutical composition according to embodiment 78, wherein said mucosa is the mucosa of the nose or the throat. f 0237 ⁇ Embodiment 80. The pharmaceutical composition according to embodiment 76, wherein said pharmaceutical composition does not alter the pH and/or osmolarity of mucosa following application to said mucosa.
  • Embodiment 81 The pharmaceutical composition according to embodiment 80, wherein said mucosa is the mucosa of the nose or the throat.
  • Embodiment 82 The pharmaceutical composition according to embodiment 76, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 83 The pharmaceutical composition according to embodiment 76, wherein said composition is in the form of a nasal spray.
  • Embodiment 84 The pharmaceutical composition according to embodiment 76, wherein said pharmaceutically acceptable carrier is adapted to provide residence time of said composition on the nasal and/or oral mucosa of at least 1 minute, or at least 5 minutes, or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes.
  • Embodiment 85 The pharmaceutical composition according to embodiment 76, wherein said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g. , 1,3- propanediol, etc.).
  • said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g. , 1,3- propanediol, etc.).
  • Embodiment 86 The pharmaceutical composition according to embodiment 76, wherein said composition comprises an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 87 The pharmaceutical composition according to embodiment 76, further comprising an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract (e.g., grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrow
  • Embodiment 88 The pharmaceutical composition according to embodiment 76, wherein said antiviral component is capable of binding to said virus via the receptor recognition mechanism of said virus.
  • Embodiment 89 The pharmaceutical composition according to embodiment 76, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 90 The pharmaceutical composition according to embodiment 76, wherein said targeted anti-bacterial component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 91 The pharmaceutical composition according to embodiment 76, wherein said anti-inflammatory comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 92 The pharmaceutical composition according to embodiment 76, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition, said targeted anti-bacterial component comprises from about 0.000001-10% by weight of said composition, and said anti-inflammatory comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 93 The pharmaceutical composition according to embodiment 76, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition, said targeted anti-bacterial component comprises from about 0.000001-10% by weight of said composition, and said anti-inflammatory comprises from about 0.000001-10% by weight of said composition, and said composition further comprises a non-targeted antimicrobial in an amount from about from about 0.000001-10% by weight of said composition.
  • Embodiment 94 The pharmaceutical composition according to embodiment 76 or 88, wherein said virions comprise coronavirus, influenza, or parainfluenza.
  • Embodiment 95 The pharmaceutical composition according to embodiment 94, wherein said targeted antiviral component for coronavirus, influenza, and/or parainfluenza comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 96 The pharmaceutical composition according to embodiment 94, wherein said composition comprises an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 97 The pharmaceutical composition according to embodiment 94, further comprising an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g. , grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract,
  • Embodiment 98 The pharmaceutical composition according to embodiment 94, wherein said targeted antiviral component comprises sialic acid ⁇ e.g. , 3' and 6' sialyllactose), ACE2 ⁇ e.g., soluble ACE2, etc.), DPP4 ⁇ e.g. , soluble DPP4, etc.), APN ⁇ e.g. , soluble APN, etc.).
  • sialic acid ⁇ e.g. , 3' and 6' sialyllactose
  • ACE2 ⁇ e.g., soluble ACE2, etc.
  • DPP4 ⁇ e.g. , soluble DPP4, etc.
  • APN ⁇ e.g. , soluble APN, etc.
  • Embodiment 99 The pharmaceutical composition according to embodiment 98, wherein said composition comprises an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 100 The pharmaceutical composition according to embodiment 98, further comprising an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g. , grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract,
  • Embodiment 101 The pharmaceutical composition according to embodiment 98, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 102 The pharmaceutical composition according to embodiment 98, wherein said composition is in the form of a nasal spray.
  • Embodiment 103 The pharmaceutical composition according to embodiment 76, wherein said virions comprise adenovirus.
  • Embodiment 104 The pharmaceutical composition according to embodiment 103, wherein said targeted antiviral component for adenovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 105 The pharmaceutical composition according to embodiment 103, wherein said composition comprises an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 106 The pharmaceutical composition according to embodiment 103, further comprising an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g. , grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract,
  • Embodiment 107 The pharmaceutical composition according to embodiment 103, wherein said targeted antiviral component comprises CD46 ⁇ e.g. , soluble CD46, etc.), CAR ⁇ e.g. , soluble CAR, etc.), desmoglein 2, sialic acid, ganglioside la, heparan sulfate and proteoglycans thereof, coagulation factor X, dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins.
  • CD46 ⁇ e.g. , soluble CD46, etc.
  • CAR ⁇ e.g. , soluble CAR, etc.
  • desmoglein 2 sialic acid
  • ganglioside la heparan sulfate and proteoglycans thereof
  • coagulation factor X dipalmitoyl phosphatidylcholine
  • lactoferrin lactoferrin
  • Av integrins integrins
  • Embodiment 108 The pharmaceutical composition according to embodiment 103, wherein said composition comprises an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 109 The pharmaceutical composition according to embodiment 103, further comprising an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g. , grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract,
  • Embodiment 110 The pharmaceutical composition according to embodiment 103, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 111 The pharmaceutical composition according to embodiment 103, wherein said composition is in the form of a nasal spray.
  • Embodiment 112. The pharmaceutical composition according to embodiment 103, wherein said virions comprise enterovirus ⁇ e.g. , E71 or EV-D68).
  • Embodiment 113. The pharmaceutical composition according to embodiment 112, wherein said targeted antiviral component for enterovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 114 The pharmaceutical composition according to embodiment 112, wherein said composition comprises an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 115 The pharmaceutical composition according to embodiment 112, further comprising an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrow
  • Embodiment 116 The pharmaceutical composition according to embodiment 112, wherein said targeted antiviral component comprises SCAR B2 ⁇ e.g., soluble SCAR B2, etc.), PSGL-1 ⁇ e.g., soluble PSGL-1, etc.), sialylated glycan, heparan sulfate and proteoglycans thereof, Anx2 ⁇ e.g., soluble Anx2, etc.), or ICAM- 5 ⁇ e.g., soluble ICAM-5, etc.).
  • SCAR B2 ⁇ e.g., soluble SCAR B2, etc.
  • PSGL-1 ⁇ e.g., soluble PSGL-1, etc.
  • sialylated glycan sialylated glycan, heparan sulfate and proteoglycans thereof
  • Anx2 ⁇ e.g., soluble Anx2, etc.
  • ICAM- 5 ⁇ e.g., soluble ICAM-5, etc.
  • Embodiment 117 The pharmaceutical composition according to embodiment 112, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 118 The pharmaceutical composition according to embodiment 112, wherein said composition is in the form of a nasal spray.
  • Embodiment 119 The pharmaceutical composition according to embodiment 76, wherein said virions comprise coxsackievirus ⁇ e.g., coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.).
  • coxsackievirus ⁇ e.g., coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.
  • Embodiment 120 The pharmaceutical composition according to embodiment 119, wherein said composition comprises an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 121 The pharmaceutical composition according to embodiment 119, further comprising an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract (e.g. , grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract,
  • Embodiment 122 The pharmaceutical composition according to embodiment 119, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 123 The pharmaceutical composition according to embodiment 119, wherein said composition is in the form of a nasal spray.
  • Embodiment 124 The pharmaceutical composition according to embodiment 116, wherein said targeted antiviral component comprises integrin ⁇ , ⁇ 3, ICAM-1 (e.g., soluble ICAM-1, etc.), or CAR (e.g., soluble CAR, etc.).
  • ICAM-1 e.g., soluble ICAM-1, etc.
  • CAR e.g., soluble CAR, etc.
  • Embodiment 125 The pharmaceutical composition according to embodiment 76, wherein said anti -bacterial is effective killing or inhibiting growth of bacteria from the genus Streptococcus.
  • Embodiment 126 The pharmaceutical composition according to embodiment 125, wherein said anti-bacterial is capable of killing or inhibiting growth of Streptococcus pyogenes.
  • Embodiment 127 The pharmaceutical composition according to embodiment 126, wherein said targeted antibacterial component for Streptococcus pyogenes comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 128 The pharmaceutical composition according to embodiment 33, wherein said anti-bacterial is a C5a peptidase inhibitor, an anti-leukoproteinase, or a secretory leukocyte protease inhibitor.
  • Embodiment 129 The pharmaceutical composition according to embodiment 128, wherein said composition comprises an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL- 25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 130 The pharmaceutical composition according to embodiment 128, further comprising an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract (e.g. , grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • an anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot
  • Embodiment 131 The pharmaceutical composition according to embodiment 128, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 132 The pharmaceutical composition according to embodiment 128, wherein said composition is in the form of a nasal spray.
  • a pharmaceutical product comprising:
  • a pump mechanism capable of expelling said nasal spray composition through said orifice in appropriate sized aerosolized droplets; capable of coating the nasal mucosa of a user;
  • nasal spray composition comprises:
  • a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial
  • a pharmaceutically acceptable carrier diluent and/or excipient.
  • Embodiment 134 The pharmaceutical product according to embodiment 133, comprising a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted anti-bacterial component for bacteria selected from Streptococcus pyogenes.
  • a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted anti-bacterial component for bacteria selected from Streptococcus pyogenes.
  • Embodiment 135. The pharmaceutical product according to embodiment 133, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 136 The pharmaceutical product according to embodiment 133, wherein said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof.
  • said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract,
  • Embodiment 138 The pharmaceutical product according to embodiment 133, wherein said targeted antiviral component and said non-targeted anti-microbial are present in an amount effective to reduce the copy number of said virions in nasal mucosa.
  • Embodiment 139 The pharmaceutical product according to embodiment 133, wherein said pharmaceutical composition does not alter the pH and/or osmolarity of nasal mucosa following application to said mucosa.
  • Embodiment 140 The pharmaceutical product according to embodiment 133, wherein said pharmaceutically acceptable carrier is adapted to provide residence time of said composition on the nasal mucosa of at least 1 minute, or at least 5 minutes, or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes.
  • Embodiment 141 The pharmaceutical product according to embodiment 133, wherein said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g., 1,3- propanediol, etc.).
  • said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g., 1,3- propanediol, etc.).
  • Embodiment 142 The pharmaceutical product according to embodiment 133, wherein said antiviral component is capable of binding to said virus via the receptor recognition mechanism of said virus.
  • Embodiment 143 The pharmaceutical product according to embodiment 133, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 144 The pharmaceutical product according to embodiment 133, wherein said targeted anti-bacterial component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 145 The pharmaceutical product according to embodiment 133, wherein said non-targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 146 The pharmaceutical product according to embodiment 133, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition and said non-targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 147 The pharmaceutical product according to embodiment 133, wherein said targeted anti -bacterial component comprises from about 0.000001-10% by weight of said composition and said non-targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 148 The pharmaceutical product according to embodiment 133, wherein said targeted anti -bacterial component comprises from about 0.000001-10% by weight of said composition, said targeted anti-viral component comprises from about 0.000001-10% by weight of said composition, and said non-targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • j 0 12] Embodiment 149.
  • the pharmaceutical product according to embodiment 133, wherein said virions comprise coronavirus, influenza, or parainfluenza.
  • Embodiment 150 The pharmaceutical product according to embodiment 149, wherein said targeted antiviral component for coronavirus, influenza, and/or parainfluenza comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 151 The pharmaceutical product according to embodiment 133, wherein said targeted antiviral component comprises sialic acid (e.g., 3' and 6' sialyllactose), ACE2 (e.g., soluble ACE2, etc.), DPP4 (e.g., soluble DPP4, etc.), APN (e.g., soluble APN, etc.).
  • sialic acid e.g., 3' and 6' sialyllactose
  • ACE2 e.g., soluble ACE2, etc.
  • DPP4 e.g., soluble DPP4, etc.
  • APN e.g., soluble APN, etc.
  • Embodiment 152 The pharmaceutical product according to embodiment 133, wherein said virions comprise adenovirus.
  • Embodiment 153 The pharmaceutical product according to embodiment 152, wherein said targeted antiviral component for adenovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 154 The pharmaceutical product according to embodiment 133, wherein said targeted antiviral component comprises CD46 (e.g., soluble CD46, etc.), CAR (e.g., soluble CAR, etc.), desmoglein 2, sialic acid, ganglioside la, heparan sulfate and proteoglycans thereof, coagulation factor X, dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins.
  • CD46 e.g., soluble CD46, etc.
  • CAR e.g., soluble CAR, etc.
  • desmoglein 2 sialic acid
  • ganglioside la e.g., heparan sulfate and proteoglycans thereof
  • coagulation factor X dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins.
  • Embodiment 155 The pharmaceutical product according to embodiment 133, wherein said virions comprise enterovirus (e.g., E71 or EV-D68).
  • enterovirus e.g., E71 or EV-D68.
  • Embodiment 156 The pharmaceutical product according to embodiment 155, wherein said targeted antiviral component for enterovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 157 The pharmaceutical product according to embodiment 133, wherein said targeted antiviral component comprises SCAR B2 (e.g., soluble SCAR B2, etc.), PSGL-1 (e.g., soluble PSGL-1, etc.), sialylated glycan, heparan sulfate and proteoglycans thereof, Anx2 (e.g., soluble Anx2, etc.), or ICAM-5 (e.g., soluble ICAM-5, etc.).
  • SCAR B2 e.g., soluble SCAR B2, etc.
  • PSGL-1 e.g., soluble PSGL-1, etc.
  • sialylated glycan e.g., heparan sulfate and proteoglycans thereof
  • Anx2 e.g., soluble Anx2, etc.
  • ICAM-5 e.g., soluble ICAM-5, etc.
  • Embodiment 158 The pharmaceutical product according to embodiment 133, wherein said virions comprise coxsackievirus (e.g., coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.).
  • said targeted antiviral component comprises integrin ⁇ , ⁇ 3, ICAM-1 (e.g., soluble ICAM-1, etc.), or CAR (e.g., soluble CAR, etc.).
  • Embodiment 160 The pharmaceutical product according to embodiment 133, wherein said anti -bacterial is capable of killing or inhibiting growth of bacteria from the genus Streptococcus.
  • Embodiment 161 The pharmaceutical product according to embodiment 133, wherein said bacteria is capable of killing or inhibiting growth of Streptococcus pyogenes.
  • Embodiment 162 The pharmaceutical composition according to embodiment 161, wherein said targeted antibacterial component for Streptococcus pyogenes comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 163 The pharmaceutical product according to embodiment 133, wherein said anti-bacterial is a C5a peptidase inhibitor, an anti-leukoproteinase, or a secretory leukocyte protease inhibitor.
  • a pharmaceutical product comprising:
  • a pump mechanism capable of expelling said nasal spray composition through said orifice in appropriate sized aerosolized droplets; capable of coating the nasal mucosa of a user;
  • nasal spray composition comprises:
  • a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial
  • a pharmaceutically acceptable carrier diluent and/or excipient.
  • Embodiment 165 The pharmaceutical product according to embodiment 164, comprising a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted anti-bacterial component for bacteria selected from Streptococcus pyogenes. 10336] Embodiment 166.
  • the pharmaceutical product according to embodiment 164, further comprising a non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, or combinations thereof.
  • Embodiment 167 The pharmaceutical product according to embodiment 164 further comprising a non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof.
  • a non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot
  • Embodiment 168 The pharmaceutical product according to embodiment 164, further comprising a non-targeted anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • a non-targeted anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, my
  • Embodiment 169 The pharmaceutical product according to embodiment 164, wherein said anti-inflammatory is selected from ICAM inhibitors, TSLP inhibitors, IL-25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 170 The pharmaceutical product according to embodiment 164, wherein said pharmaceutical composition does not alter the pH and/or osmolarity of nasal mucosa following application to said mucosa.
  • Embodiment 171 The pharmaceutical product according to embodiment 164, wherein said pharmaceutically acceptable carrier is adapted to provide residence time of said composition on the nasal mucosa of at least 1 minute, or at least 5 minutes, or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes.
  • Embodiment 172 The pharmaceutical product according to embodiment 164, wherein said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol ⁇ e.g. , 1,3- propanediol, etc.).
  • said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol ⁇ e.g. , 1,3- propanediol, etc.).
  • Embodiment 173 The pharmaceutical product according to embodiment 164, wherein said antiviral component is capable of binding to said virus via the receptor recognition mechanism of said virus.
  • Embodiment 174 The pharmaceutical product according to embodiment 164, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 175. The pharmaceutical product according to embodiment 164, wherein said targeted anti-bacterial component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 176 The pharmaceutical product according to embodiment 164, wherein said anti-inflammatory comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 177 The pharmaceutical product according to embodiment 164, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition, said targeted anti -bacterial component comprises from about 0.000001-10% by weight of said composition, and said anti-inflammatory comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 178 The pharmaceutical product according to embodiment 164, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition, said targeted anti -bacterial component comprises from about 0.000001-10% by weight of said composition, and said anti-inflammatory comprises from about 0.000001-10% by weight of said composition, and said composition further comprises a non-targeted antimicrobial in an amount from about from about 0.000001-10% by weight of said composition.
  • Embodiment 179 The pharmaceutical product according to embodiment 164, wherein said virions comprise coronavirus, influenza, and/or parainfluenza.
  • Embodiment 180 The pharmaceutical product according to embodiment 179, wherein said targeted antiviral component for coronavirus, influenza, and/or parainfluenza comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 181 The pharmaceutical product according to embodiment 164, wherein said targeted antiviral component comprises sialic acid (e.g., 3' and 6' sialyllactose), ACE2 (e.g., soluble ACE2, etc.), DPP4 (e.g., soluble DPP4, etc.), APN (e.g., soluble APN, etc.).
  • sialic acid e.g., 3' and 6' sialyllactose
  • ACE2 e.g., soluble ACE2, etc.
  • DPP4 e.g., soluble DPP4, etc.
  • APN e.g., soluble APN, etc.
  • Embodiment 182 The pharmaceutical product according to embodiment 164, wherein said virions comprise adenovirus.
  • the pharmaceutical product according to embodiment 182, wherein said targeted antiviral component for adenovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 184 The pharmaceutical product according to embodiment 164, wherein said targeted antiviral component comprises CD46 (e.g. , soluble CD46, etc.), CAR (e.g. , soluble CAR, etc.), desmoglein 2, sialic acid, ganglioside la, heparan sulfate and proteoglycans thereof, coagulation factor X, dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins.
  • CD46 e.g. , soluble CD46, etc.
  • CAR e.g. , soluble CAR, etc.
  • desmoglein 2 sialic acid
  • ganglioside la e.g. , heparan sulfate and proteoglycans thereof
  • coagulation factor X dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins.
  • Embodiment 185 The pharmaceutical product according to embodiment 164, wherein said virions comprise enterovirus (e.g., E71 or EV-D68).
  • enterovirus e.g., E71 or EV-D68.
  • Embodiment 186 The pharmaceutical product according to embodiment 185, wherein said targeted antiviral component for enterovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 187 The pharmaceutical product according to embodiment 164, wherein said targeted antiviral component comprises SCAR B2 (e.g. , soluble SCAR B2, etc.), PSGL-1 (e.g., soluble PSGL-1, etc.), sialylated glycan, heparan sulfate and proteoglycans thereof, Anx2 (e.g., soluble Anx2, etc.), or ICAM-5 (e.g., soluble ICAM-5, etc.).
  • SCAR B2 e.g. , soluble SCAR B2, etc.
  • PSGL-1 e.g., soluble PSGL-1, etc.
  • sialylated glycan e.g., heparan sulfate and proteoglycans thereof
  • Anx2 e.g., soluble Anx2, etc.
  • ICAM-5 e.g., soluble ICAM-5, etc.
  • Embodiment 188 The pharmaceutical product according to embodiment 164, wherein said virions comprise coxsackievirus (e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.).
  • coxsackievirus e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.
  • Embodiment 189 The pharmaceutical product according to embodiment 188, wherein said targeted antiviral component for coxsackievirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 190 The pharmaceutical product according to embodiment 164, wherein said targeted antiviral component comprises integrin ⁇ 6, ⁇ 3, ICAM-1 (e.g., soluble ICAM-1, etc.), or CAR (e.g. , soluble CAR, etc.).
  • said targeted antiviral component comprises integrin ⁇ 6, ⁇ 3, ICAM-1 (e.g., soluble ICAM-1, etc.), or CAR (e.g. , soluble CAR, etc.).
  • Embodiment 191 The pharmaceutical product according to embodiment 191, wherein said anti -bacterial is capable of killing or inhibiting growth of bacteria from the genus Streptococcus.
  • Embodiment 192 The pharmaceutical product according to embodiment 164, wherein said anti-bacterial is capable of killing or inhibiting growth of Streptococcus pyogenes.
  • Embodiment 193. The pharmaceutical product according to embodiment 192, wherein said targeted antibacterial component for Streptococcus pyogenes comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 194 The pharmaceutical product according to embodiment 164, wherein said anti-bacterial is a C5a peptidase inhibitor, an anti-leukoproteinase, or a secretory leukocyte protease inhibitor.
  • Embodiment 195 A method for prophylaxis and/or treatment of infection in a user, comprising applying to the mucosa of said user a pharmaceutical composition comprising:
  • a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial
  • a pharmaceutically acceptable carrier diluent and/or excipient.
  • Embodiment 196 comprising a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted anti-bacterial component for bacteria selected from Streptococcus pyogenes.
  • a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted anti-bacterial component for bacteria selected from Streptococcus pyogenes.
  • Embodiment 197 The method according to embodiment 195, wherein said non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, or combinations thereof.
  • a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, or combinations thereof.
  • Embodiment 198 The method according to embodiment 195, wherein said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof.
  • said non-targeted anti-microbial is selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract,
  • Embodiment 199 The method according to embodiment 195, wherein said composition comprises a non-targeted anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g., grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • Embodiment 200 The method according to embodiment 195, wherein said targeted antiviral component and said non-targeted anti-microbial are present in an amount effective to reduce the copy number of said virions in mucosa.
  • Embodiment 201 The method according to embodiment 195, wherein said mucosa is the mucosa of the nose or the throat.
  • Embodiment 202 The method according to embodiment 195, wherein said pharmaceutical composition does not alter the pH and/or osmolarity of mucosa following application to said mucosa.
  • Embodiment 203 The method according to embodiment 195, wherein said mucosa is the mucosa of the nose or the throat.
  • Embodiment 204 The method according to embodiment 195, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 205 The method according to embodiment 195, wherein said composition is in the form of a nasal spray.
  • Embodiment 206 The method according to embodiment 195, wherein said pharmaceutically acceptable carrier is adapted to provide residence time of said composition on said mucosa of at least 1 minute, or at least 5 minutes, or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes.
  • Embodiment 207 The method according to embodiment 195, wherein said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g., 1,3- propanediol, etc.).
  • said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g., 1,3- propanediol, etc.).
  • Embodiment 208 The method according to embodiment 195, wherein said antiviral component is capable of binding to said virus via the receptor recognition mechanism of said virus.
  • Embodiment 209 The method according to embodiment 195, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 210 The method according to embodiment 195, wherein said targeted antibacterial component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 211 The method according to embodiment 195, wherein said non-targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 212 The method according to embodiment 195, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition and said non- targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 213 The method according to embodiment 195, wherein said targeted antibacterial component comprises from about 0.000001-10% by weight of said composition and said non- targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 214 The method according to embodiment 195, wherein said targeted antibacterial component comprises from about 0.000001-10% by weight of said composition, said targeted anti -viral component comprises from about 0.000001-10% by weight of said composition, and said non- targeted antimicrobial comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 215. The method according to embodiment 195, wherein said virions comprise coronavirus, influenza, or parainfluenza.
  • Embodiment 216 The method according to embodiment 215, wherein said targeted antiviral component for coronavirus, influenza, and/or parainfluenza comprises from about 0.000001- 10% by weight of said composition.
  • non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, or combinations thereof.
  • non-targeted anti-microbial comprises a naturally derived anti-microbial selected from mucins, SLPI, glycyrrhizin, b- microseminoprotein, statherin, or combinations thereof.
  • Embodiment 219. The method according to embodiment 195, wherein said virions comprise adenovirus.
  • Embodiment 220 The method according to embodiment 219, wherein said targeted antiviral component for adenovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 221. The method according to embodiment 195, wherein said targeted antiviral component comprises CD46 (e.g., soluble CD46, etc.), CAR (e.g., soluble CAR, etc.), desmoglein 2, sialic acid, ganglioside la, heparan sulfate and proteoglycans thereof, coagulation factor X, dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins. 10395] Embodiment 222. The method according to embodiment 195, wherein said virions comprise enterovirus (e.g. , E71 or EV-D68).
  • enterovirus e.g. , E71 or EV-D68
  • Embodiment 224 The method according to embodiment 195, wherein said targeted antiviral component comprises SCAR B2 (e.g. , soluble SCAR B2, etc.), PSGL-1 (e.g. , soluble PSGL-1, etc.), sialylated glycan, heparan sulfate and proteoglycans thereof, Anx2 (e.g. , soluble Anx2, etc.), or ICAM-5 (e.g. , soluble ICAM-5, etc.).
  • SCAR B2 e.g. , soluble SCAR B2, etc.
  • PSGL-1 e.g. , soluble PSGL-1, etc.
  • sialylated glycan e.g. , soluble PSGL-1, etc.
  • sialylated glycan e.g. , soluble PSGL-1, etc.
  • sialylated glycan e.g. , soluble PSGL-1, etc.
  • Embodiment 225 The method according to embodiment 195, wherein said virions comprise coxsackievirus (e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.).
  • coxsackievirus e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.
  • Embodiment 226 The method according to embodiment 225, wherein said targeted antiviral component for coxsackievirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 227 The method according to embodiment 195, wherein said targeted antiviral component comprises integrin ⁇ , ⁇ 3, ICAM-1 (e.g. , soluble ICAM-1, etc.), or CAR (e.g. , soluble CAR, etc.).
  • ICAM-1 e.g. , soluble ICAM-1, etc.
  • CAR e.g. , soluble CAR, etc.
  • Embodiment 228 The method according to embodiment 195, wherein said composition is in the form of a nasal spray.
  • Embodiment 229. The method according to embodiment 195, wherein said anti-bacterial is capable of killing or inhibiting growth of bacteria from the genus Streptococcus.
  • Embodiment 231 The method according to embodiment 230, wherein said targeted antibacterial component for Streptococcus pyogenes comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 232 The method according to embodiment 195, wherein said anti-bacterial is a C5a peptidase inhibitor, an anti-leukoproteinase, or a secretory leukocyte protease inhibitor.
  • Embodiment 233 A method for prophylaxis and/or treatment of infection in a user, comprising applying to the mucosa of said user a pharmaceutical composition comprising: 10407] (1) a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial; and
  • Embodiment 234 comprising a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted anti-bacterial component for bacteria selected from Streptococcus pyogenes.
  • a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted anti-bacterial component for bacteria selected from Streptococcus pyogenes.
  • Embodiment 236 The method according to embodiment 233, wherein said mucosa is the mucosa of the nose or the throat.
  • Embodiment 237 The method according to embodiment 233, wherein said pharmaceutical composition does not alter the pH and/or osmolarity of mucosa following application to said mucosa.
  • Embodiment 238 The method according to embodiment 233, wherein said mucosa is the mucosa of the nose or the throat.
  • composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 240 The method according to embodiment 233, wherein said composition is in the form of a nasal spray.
  • Embodiment 241 The method according to embodiment 195, wherein said pharmaceutically acceptable carrier is adapted to provide residence time of said composition on said mucosa of at least 1 minute, or at least 5 minutes, or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes.
  • Embodiment 242 The method according to embodiment 195, wherein said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol ⁇ e.g. , 1,3- propanediol, etc.).
  • said composition comprises an anti-inflammatory selected from ICAM inhibitors, TSLP inhibitors, IL-25 inhibitors, 11-33 inhibitors, IL-1 inhibitors, TNF inhibitors and NSAIDs.
  • Embodiment 244 The method according to embodiment 233, further comprising an antimicrobial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot extract, neem oil, vitamin C, vitamin E, grapefruit extract ⁇ e.g. , grapefruit seed extract, etc.), or combinations thereof, zinc, zinc peroxide, copper, silver, or combinations thereof.
  • an antimicrobial selected from mucins, SLPI, glycyrrhizin, b-microseminoprotein, statherin, plant mucilage, marshmallow extract, glycyrrhizin, calendula extract, citrus peel extract, honey extract, rosemary extract, myrrh extract, Helichrysum extract, arrowroot
  • Embodiment 245. The method according to embodiment 233, wherein said antiviral component is capable of binding to said virus via the receptor recognition mechanism of said virus.
  • Embodiment 246 The method according to embodiment 233, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 248 The method according to embodiment 233, wherein said antiinflammatory comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 249. The method according to embodiment 233, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition, said targeted anti -bacterial component comprises from about 0.000001-10% by weight of said composition, and said anti-inflammatory comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 250 The method according to embodiment 233, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition, said targeted anti -bacterial component comprises from about 0.000001-10% by weight of said composition, and said anti-inflammatory comprises from about 0.000001-10% by weight of said composition, and said composition further comprises a non-targeted antimicrobial in an amount from about from about 0.000001-10% by weight of said composition.
  • Embodiment 251 The method according to embodiment 233, wherein said virions comprise coronavirus, influenza or parainfluenza. 10428] Embodiment 252.
  • said targeted antiviral component comprises sialic acid (e.g. , 3 ' and 6' sialyllactose), ACE2 (e.g. , soluble ACE2, etc.), DPP4 (e.g., soluble DPP4, etc.), APN (e.g. , soluble APN, etc.).
  • sialic acid e.g. , 3 ' and 6' sialyllactose
  • ACE2 e.g. , soluble ACE2, etc.
  • DPP4 e.g., soluble DPP4, etc.
  • APN e.g. , soluble APN, etc.
  • Embodiment 253 The method according to embodiment 233, wherein said virions comprise adenovirus.
  • Embodiment 254 The method according to embodiment 253, wherein said targeted antiviral component for adenovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 255 The method according to embodiment 233, wherein said targeted antiviral component comprises CD46 (e.g. , soluble CD46, etc.), CAR (e.g. , soluble CAR, etc.), desmoglein 2, sialic acid, ganglioside la, heparan sulfate and proteoglycans thereof, coagulation factor X, dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins.
  • CD46 e.g. , soluble CD46, etc.
  • CAR e.g. , soluble CAR, etc.
  • desmoglein 2 sialic acid
  • ganglioside la e.g. , heparan sulfate and proteoglycans thereof
  • coagulation factor X dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins.
  • Embodiment 256 The method according to embodiment 233, wherein said virions comprise enterovirus (e.g. , E71 or EV-D68).
  • enterovirus e.g. , E71 or EV-D68.
  • Embodiment 257 The method according to embodiment 256, wherein said targeted antiviral component for enterovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 258 Embodiment 258.
  • said targeted antiviral component comprises SCAR B2 (e.g. , soluble SCAR B2, etc.), PSGL-1 (e.g. , soluble PSGL-1, etc.), sialylated glycan, heparan sulfate and proteoglycans thereof, Anx2 (e.g. , soluble Anx2, etc.), or ICAM-5 (e.g. , soluble ICAM-5, etc.).
  • SCAR B2 e.g. , soluble SCAR B2, etc.
  • PSGL-1 e.g. , soluble PSGL-1, etc.
  • sialylated glycan e.g. , heparan sulfate and proteoglycans thereof
  • Anx2 e.g. , soluble Anx2, etc.
  • ICAM-5 e.g. , soluble ICAM-5, etc.
  • Embodiment 259. The method according to embodiment 233, wherein said virions comprise coxsackievirus (e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.).
  • coxsackievirus e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.
  • Embodiment 260 The method according to embodiment 259, wherein said targeted antiviral component for coxsackievirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 261 The method according to embodiment 233, wherein said targeted antiviral component comprises integrin ⁇ 6, ⁇ 3, ICAM-1 (e.g. , soluble ICAM-1, etc.), or CAR (e.g. , soluble CAR, etc.).
  • said targeted antiviral component comprises integrin ⁇ 6, ⁇ 3, ICAM-1 (e.g. , soluble ICAM-1, etc.), or CAR (e.g. , soluble CAR, etc.).
  • Embodiment 262 The method according to embodiment 233, wherein said anti-bacterial is capable of killing or inhibiting growth of bacteria from the genus Streptococcus.
  • Embodiment 263. The method according to embodiment 233, wherein said anti-bacterial is capable of killing or inhibiting growth of bacteria is Streptococcus pyogenes.
  • Embodiment 264 The method according to embodiment 263, wherein said targeted antibacterial component for Streptococcus pyogenes comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 265. The method according to embodiment 233, wherein said antibacterial is a C5a peptidase inhibitor, an anti-leukoproteinase, or a secretory leukocyte protease inhibitor.
  • Embodiment 266 A pharmaceutical composition comprising:
  • a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial
  • a pharmaceutically acceptable carrier diluent and/or excipient.
  • Embodiment 267 The pharmaceutical composition according to embodiment 266, comprising a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted antibacterial component for bacteria selected from Streptococcus pyogenes.
  • a targeted antiviral component for virions selected from influenza, parainfluenza, rhinovirus, enterovirus, coronavirus, adenovirus, coxsackievirus, and combinations thereof and/or a targeted antibacterial component for bacteria selected from Streptococcus pyogenes.
  • Embodiment 268 The pharmaceutical composition according to embodiment 266, wherein said targeted antiviral component and said non-targeted anti-microbial are present in an amount capable to reduce the copy number of said virions in mucosa.
  • Embodiment 269. The pharmaceutical composition according to embodiment 268, wherein said mucosa is the mucosa of the nose, mouth, and/or throat.
  • Embodiment 270 The pharmaceutical composition according to embodiment 266, wherein said pharmaceutical composition does not alter the pH and/or osmolarity of mucosa following application to said mucosa.
  • Embodiment 271 The pharmaceutical composition according to embodiment 270, wherein said mucosa is the mucosa of the nose, throat, and/or mouth.
  • Embodiment 272 The pharmaceutical composition according to embodiment 266, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge. (0451 j Embodiment 273. The pharmaceutical composition according to embodiment 266, wherein said composition is in the form of a nasal spray.
  • Embodiment 274 The pharmaceutical composition according to embodiment 266, wherein said compositions is in the form of an oral spray.
  • Embodiment 275 The pharmaceutical composition according to embodiment 266, wherein said pharmaceutically acceptable carrier is adapted to provide residence time of said composition on the nasal and/or oral mucosa of at least 1 minute, or at least 5 minutes, or at least 10 minutes, or at least 15 minutes, or at least 20 minutes, or at least 25 minutes, or at least 30 minutes.
  • Embodiment 276 The pharmaceutical composition according to embodiment 266, wherein said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g., 1,3- propanediol, etc.).
  • said pharmaceutically acceptable carrier is an aqueous solution comprising from about 5-50% (v/v), or from about 10-40% (v/v), or from about 15-35% (v/v), or from about 20-30% (v/v) polyol (e.g., 1,3- propanediol, etc.).
  • Embodiment 277 The pharmaceutical composition according to embodiment 266, wherein said antiviral component is capable of binding to said virions via the receptor recognition mechanism of said virions.
  • Embodiment 278 The pharmaceutical composition according to embodiment 266, wherein said targeted antiviral component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 279. The pharmaceutical composition according to embodiment 266, wherein said targeted anti-bacterial component comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 280 The pharmaceutical composition according to embodiment 266, wherein said virions comprise coronavirus, influenza, and/or parainfluenza.
  • Embodiment 281 The pharmaceutical composition according to embodiment 266, wherein said targeted antiviral component comprises sialic acid (e.g., 3' and 6' sialyllactose), quercetin and isoforms thereof, ACE2 (e.g., soluble ACE2, etc.), DPP4 (e.g., soluble DPP4, etc.), APN (e.g., soluble APN, etc.).
  • sialic acid e.g., 3' and 6' sialyllactose
  • quercetin e.g., quercetin and isoforms thereof
  • ACE2 e.g., soluble ACE2, etc.
  • DPP4 e.g., soluble DPP4, etc.
  • APN e.g., soluble APN, etc.
  • Embodiment 282 The pharmaceutical composition according to embodiment 266, wherein said composition is in the form of a nasal spray, nasal drops, oral spray, oral rinse, or lozenge.
  • Embodiment 283 The pharmaceutical composition according to embodiment 266, wherein said composition is in the form of a nasal spray.
  • Embodiment 284. The pharmaceutical composition according to embodiment 266, wherein said virions comprise adenovirus.
  • Embodiment 285. The pharmaceutical composition according to embodiment 33, wherein said targeted antiviral component for adenovirus comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 286 The pharmaceutical composition according to embodiment 266, wherein said targeted antiviral component comprises CD46 (e.g. , soluble CD46, etc.), CAR (e.g. , soluble CAR, etc.), desmoglein 2, sialic acid, ganglioside la, heparan sulfate and proteoglycans thereof, coagulation factor X, dipalmitoyl phosphatidylcholine, lactoferrin, or Av integrins.
  • CD46 e.g. , soluble CD46, etc.
  • CAR e.g. , soluble CAR, etc.
  • desmoglein 2 sialic acid
  • ganglioside la e.g. , heparan sulfate and proteoglycans thereof
  • coagulation factor X dipalmitoyl phosphatidylcholine
  • lactoferrin e.g. adylcholine
  • Embodiment 287 The pharmaceutical composition according to embodiment 266, wherein said virions comprise enterovirus (e.g. , E71 or EV-D68).
  • enterovirus e.g. , E71 or EV-D68.
  • Embodiment 288 The pharmaceutical composition according to embodiment 266, wherein said targeted antiviral component comprises SCAR B2 (e.g., soluble SCAR B2, etc.), PSGL-1 (e.g. , soluble PSGL-1, etc.), sialylated glycan, heparan sulfate and proteoglycans thereof, Anx2 (e.g. , soluble Anx2, etc.), or ICAM-5 (e.g. , soluble ICAM-5, etc.).
  • SCAR B2 e.g., soluble SCAR B2, etc.
  • PSGL-1 e.g. , soluble PSGL-1, etc.
  • sialylated glycan e.g. , heparan sulfate and proteoglycans thereof
  • Anx2 e.g. , soluble Anx2, etc.
  • ICAM-5 e.g. , soluble ICAM-5, etc.
  • Embodiment 289. The pharmaceutical composition according to embodiment 266, wherein said virions comprise coxsackievirus (e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.).
  • coxsackievirus e.g. , coxsackievirus A, coxsackievirus A9 cocksackie virus B, etc.
  • Embodiment 290 The pharmaceutical composition according to embodiment 266, wherein said anti -bacterial is capable of killing or inhibiting growth of bacteria from the genus Streptococcus.
  • Embodiment 291 The pharmaceutical composition according to embodiment 266, wherein said anti-bacterial is capable of killing or inhibiting growth of Streptococcus pyogenes.
  • Embodiment 292 The pharmaceutical composition according to embodiment 266, wherein said targeted antibacterial component for Streptococcus pyogenes comprises from about 0.000001-10% by weight of said composition.
  • Embodiment 293. A pharmaceutical composition comprising: (0472 j a non-targeted anti-mi crobial; and
  • a pharmaceutically acceptable carrier diluent and/or excipient.
  • a pharmaceutical composition comprising: 10475] an anti-inflammatory; and
  • a pharmaceutically acceptable carrier diluent and/or excipient.
  • Embodiment 295. A method for the treatment and/or prophylaxis of a respiratory infection to a patient in need thereof comprising administering a pharmaceutical to the upper respiratory mucosa; wherein said pharmaceutical composition comprises:
  • a targeted antiviral component comprising one or more active agents capable of binding to virions and/or a targeted anti-bacterial
  • Embodiment 296 A method for the treatment and/or prophylaxis of a respiratory infection to a patient in need thereof comprising administering a pharmaceutical to the upper respiratory mucosa; wherein said pharmaceutical composition comprises a non-targeted anti-microbial; and a pharmaceutically acceptable carrier, diluent and/or excipient.
  • Embodiment 297 A method for the treatment and/or prophylaxis of a respiratory infection to a patient in need thereof comprising administering a pharmaceutical to the upper respiratory mucosa; wherein said pharmaceutical composition comprises an anti-inflammatory; and a pharmaceutically acceptable carrier, diluent and/or excipient.
  • Example 1 Administration of antimicrobial compositions in non-human subjects to prevent infection
  • compositions comprising a targeted component, together with a non-targeted anti-microbial and/or an anti-inflammatory are administered intranasally to a group of healthy, uninfected mice selected for age, gender and weight.
  • mice are inoculated nasally with varying doses of respiratory pathogens (e.g., rhinovirus, adenovirus, enterovirus, coxsackievirus, Streptococcus pyogenes, coronavirus, etc.).
  • respiratory pathogens e.g., rhinovirus, adenovirus, enterovirus, coxsackievirus, Streptococcus pyogenes, coronavirus, etc.
  • samples are extracted from the mice and analyzed for microbial infection. Lack of infection indicates the pharmaceutical composition prevents the airborne pathogens from infecting the mice.
  • the pharmaceutical composition enhances the filtering capabilities of the nasal membrane and protects against the airborne pathogens.
  • a group of healthy, uninfected mice selected for age, gender and weight are inoculated nasally with varying doses of respiratory pathogens (influenza, rhinovirus, bacteria, and fungi).
  • respiratory pathogens influenza, rhinovirus, bacteria, and fungi
  • varying pharmaceutical compositions comprising a targeted component, together with a non-targeted anti-microbial and/or an anti-inflammatory are administered intranasally to the infected mice.
  • samples are extracted from the mice and analyzed for microbial infection. Lack of infection indicates the antimicrobial composition treats the respiratory infections within the mice.
  • the pharmaceutical compositions enhance the filtering capabilities of the nasal membrane and treats the infection caused by airborne pathogens.
  • Example 3 Administration of antimicrobial compositions in human subjects to treat infection
  • a group of human subjects presenting without pre-existing viral or bacterial infections are selected for treatment and their baseline blood drawn to screen for markers of respiratory infection.
  • a pharmaceutical compositions comprising a targeted component, together with a non-targeted antimicrobial and/or an anti-inflammatory (as in Examples 1 and 2) are administered intranasally to the subjects. After a suitable period of time to allow the compositions to take effect, subjects are exposed to pathogens (e.g., rhinovirus, adenovirus, enterovirus, coxsackievirus, Streptococcus pyogenes, coronavirus, etc.).
  • pathogens e.g., rhinovirus, adenovirus, enterovirus, coxsackievirus, Streptococcus pyogenes, coronavirus, etc.
  • Example 4 Measurements on full differentiated 3D cell model of human airway epithelia inoculated with virus
  • MucilAirTM is a reconstituted human 3D tissue from airways and lung surgical pieces, fully differentiated, pseudostratified in vitro epithelium.
  • MucilAirTM-Pool is of nasal origin and reconstituted with a mixture of cells isolated from 14 different donors. Cultured at the air- liquid interface, the model displays high trans-epithelial electrical resistance, cilia beating as well as mucus production, demonstrating the full functionality of the epithelial tissue.
  • compositions were formulated with various active components (some targeted and some nontargeted) and added to MucilAirTM in the concentrations as shown in Table 2. Table 2 also specifies which virus(es) each composition was measured against. Each composition was prepared in a buffered saline solution vehicle (0.9% NaCl, 1.25 mM CaCb, 10 mM HEPES).
  • the sialic acid is a mix of 3' and 6' sialyllactose from Carbosynth in a (50:50 ratio) concentration of lOmg/ml final.
  • the formulation was prepared by dissolving the solid mixture in sterile water. 20 ⁇ was added to vehicle to the indicated concentration and added to the apical portion of MucilAirTM.
  • 10493 j SLPI is a recombinant human secretory leukocyte protease inhibitor from Origene Technologies Inc. 11 ⁇ of stock solution (concentration of 20 ⁇ g/400 ⁇ ) was added directly to a 20 ⁇ vehicle to the indicated concentrations and added to the apical portion of MucilAirTM.
  • Aminopeptidase N (recombinant human) combined 100 ⁇ at 0.1 ⁇ g/ul from Millipore Sigma and 2 vials of 46 ⁇ at 0.5 ug/ul from RnD Biosystems to result in a final concentration of 206 ⁇ g/ml, which was added 8 ⁇ vehicle for 20 ⁇ apical MucilAirTM application resulting in a final concentration of 100 ⁇ g/ml added to the apical portion of MucilAirTM.
  • the MucilAirTM were inoculated with HCoV 229e (coronavirus) or HlNl (influenza) on the apical surface of the epithelia (MucilAirTM Pool). Inserts were prepared with either HCoV 229E at 1.2* 10 8 genome copies/insert or HlNl at 1.11 x lO 6 copies/insert in 50 ⁇ on the apical surface of the epithelia. The components were applied to the media at the indicated concentrations apically prior to virus inoculation, again at 45 minutes post-inoculation ("PI") for HlNl, at 2 hours PI for HCoV, and after 24 hours PI for both viral conditions. For the coronavirus study, MucilAirTM were kept at 35°C. For the influenza study, MucilAirTM were kept at 37°C.
  • TEER Trans Epithelial Electric resistance
  • TEER transepithelial electrical resistance
  • TEER is a dynamic parameter that reflects the state of epithelia and the barrier function which can be affected by several factors. For example, if holes were present or if cellular junction were broken, the TEER values would be generally below 100 ⁇ cm 2 . In contrast, when epithelia are not damaged, the TEER values are typically above 200 ⁇ cm 2 . A notable decrease of the TEER values (but > 100 ⁇ cm 2 ) generally reflects an activation of the ion channels. A drastic increase of the TEER value reflects a blockage of the ion channel activity or a destruction of the ciliated cells.
  • TEER (Q.cm 2 ) (resistance value ( ⁇ ) - 100 ( ⁇ )) x 0.33 (cm 2 ). TEER measurements were taken at 48 hours PI.
  • Tables 6-9 show the ANOVA values and comparisons calculated for HlNl experiments.
  • TEER epithelia exposed to SLPI+glycerhizzin condition in the coronavirus study increased compared to positive control.
  • TEER changes after SLPI alone or glycyrhizzin alone administration were less significant compared to positive control.
  • glcycyrhizzin and SLPI together are more protective to the integrity of the mucus membranes. Accordingly, these two components are more protective against infection since they strengthen the mucosal barrier function than either component when used alone.
  • TEER results on the H1N1 experiments showed increases in epithelial resistance of combinations indicating that combined formulations are protective of the mucus membrane.
  • Lactate dehydrogenase is a stable cytoplasmic enzyme that is rapidly released into the culture medium upon rupture of the plasma membrane.
  • the basal media of each condition was collected at 24 hours and 48 hours PI.
  • Controls include a "High Control”, a “Low Control” and a "Background Control.” High Controls were prepared by incubating the apical side of one MucilAirTM insert with 50 ⁇ of 2% Triton X-100 for 3h at 37°C.
  • the Low Controls were generated by collecting basal media from untreated cells as spontaneous LDH release of the models. Background Controls are constituted of fresh MucilAirTM media.
  • a percentage below 5% reflects a physiological release of LDH in the medium.
  • LDH measurements were taken at 24 and 48 hours pi. The results are shown in FIGS. 2 A (coronavirus) and 2B (HlNl).
  • drug formulations do not increase LDH release in the 3D models.
  • Epithelia administered the combination of sialic acid and glycyrrhizin were less toxic than glycyrrhizin alone.
  • the SLPI and glycyrrhizin combination do not show increased cytotoxicity, while glycyrrhizin alone appeared to have increased cytotoxicity in the influenza inoculated model.
  • HlNl nucleoprotein binding to cell nuclei were measured by immunofluorescence microscopy.
  • Influenza virus nucleoprotein (NP) is a critical factor in the viral infectious cycle in switching influenza virus RNA synthesis from transcription mode to replication mode an is known to bind in the nucleus of infected cells.
  • An antibody to HlNl nucleoprotein (abl28193) was used to stain MucilAirTM inserts at the conclusion of the viral incubation. This antibody specifically stains nuclei of HlNl infected cells in an expected circular pattern (York et al 2014 J Virol. 2014 Nov; 88(22): 13284-13299, hereby incorporated by reference in its entirety). The staining of positive and negative control membranes were compared.
  • the inserts were then rinsed 3 times with cold PBS and then permeabilized with 0.1% triton X in PBS for 10 minutes.
  • the tissues were again rinsed 3 times with PBS and blocked with 3% normal donkey serum and 0.2% Tween 20 ("blocking solution") in PBS overnight at 4°C.
  • blocking solution 3% normal donkey serum and 0.2% Tween 20
  • membranes were incubated with NP antibody in new blocking solution at a concentration of 1/200 2 hours at room temperature. Following this, the membranes were rinsed 3 times for 15 min in PBS followed by incubation with secondary antibody (donkey anti-mouse conjugated with Alexa488, A21202 Invitrogen) at a concentration of 1/2000 in blocking buffer for 1 hour at room temperature.
  • the membranes were then rinsed 3 times with PBS and mounted on microscope slides with Prolong anti-fade mounting media containing 4',6-diamidino-2-phenylindole (DAPI).
  • DAPI Prolong anti-fade mounting media containing 4',6-diamidino-2-phenylindole
  • Three inserts for each group were applied to the same microscope slide in different locations on the slide. Images to measure the fluorescence were taken by focusing near the center of each insert on the supporting slide and maintaining imaging parameters such as gain the same.
  • a Nikon Eclipse Ts2R-FL inverted fluorescence microscope with a 20 ⁇ objective CFI Achro Flat Field 20x / 0.40 / 3.90 LWD
  • a monochromatic camera (16 bit Monochrome Camera (USB-3)
  • the microscope was equipped with Nikon Elements Documentation Software including Camera Driver and a 385 nm Internal LED module with AT Sputter Ex375/28 for DAPI fluorescence detection and a Dm415, Em460/50 for Alexa 488 fluorescence.
  • the 20 ⁇ objective described was used for all analysis images. Images were obtained and analyzed using NIS Elements software. Automated object counting was used to compare fluorescent intensities of viral particles labeled with Alexa 488 using the appropriate LED and specific filter sets on the microscope using the object count function in the NIS Elements software.
  • An intensity threshold was set for detection at grey level intensities of between 15082 and 65,000 (the grey threshold). Therefore, any pixel above at or above a grey level intensity of 15082 would be captured and counted. Adjacent pixels with intensities within the threshold are identified as single objects. The circularity of the objects are measured as well as their fluorescent intensity and area (in ⁇ 2 ) as converted from pixels.
  • Fluorescent objects with a circularity of at least 0.87 were counted as fluorescence viral particles as analyzed with the automated counting software. Total area of all fluorescent particles were compared across conditions as well the total number of objects.
  • FIG. 3 A shows the number of fluorescent viral particles in MucilAirTM exposed to different components. Tables 9-11 comprise the results of ANOVA analysis with Kruskal-Wallis test and comparisons for the measured number of fluorescent viral particles measurements.
  • FIG. 3B illustrates the total area of influenza viral particles taken from the same images.
  • Tables 12-14 comprise the results of ANOVA analysis with Kruskal-Wallis test and comparisons for the measured number of total area measurements.
  • MucilAirTM exposed to sialic acid and glycyrrhizin resulted in lower numbers of virions (and total area of virions) as compared to positive control.

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Abstract

La présente invention concerne des méthodes et des compositions destinées à améliorer la capacité des membranes respiratoires à filtrer des agents pathogènes en suspension dans l'air et à protéger un sujet contre des infections respiratoires qui résultent de l'inhalation ou de l'ingestion de tels agents pathogènes. En particulier, l'invention concerne des compositions antimicrobiennes qui préviennent et traitent des infections respiratoires causées par des bactéries, des champignons et des virus.
PCT/US2018/048985 2017-08-30 2018-08-30 Compositions et méthodes de protection contre des agents pathogènes et irritants Ceased WO2019046664A1 (fr)

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CN111529685A (zh) * 2020-04-21 2020-08-14 厦门诺康得生物科技有限公司 抗呼吸道病毒感染的鼻腔喷雾制剂
CN112972389A (zh) * 2021-01-21 2021-06-18 中山大学附属第五医院 甘草酸纳米颗粒的合成及其在新型冠状病毒肺炎中的联合治疗应用
JP2021138619A (ja) * 2020-03-02 2021-09-16 フマキラー株式会社 抗コロナウイルス剤
WO2021191800A1 (fr) * 2020-03-23 2021-09-30 Kerecis Ag Solutions antimicrobiennes et leurs méthodes d'utilisation dans le traitement ou la prévention d'infections
WO2021209652A1 (fr) * 2020-04-16 2021-10-21 Dermopartners,S.L. Nouvelle composition destinée à être utilisée dans le traitement et la prévention d'infections par la covid19 et autres coronavirus
CN113521099A (zh) * 2021-09-10 2021-10-22 吉林大学第一医院 锌离子在抗肠道病毒ev-d68中的应用
US20220041660A1 (en) * 2020-08-06 2022-02-10 University Of Delaware Compositions and methods for sequestering viral particles in respiratory tract
EP3928785A4 (fr) * 2020-04-27 2022-05-18 Guangzhou Century Clinical Research Co., Ltd Médicament et aliment pour la prévention ou le traitement du covid-19, et application de ceux-ci
IT202100022172A1 (it) * 2021-08-23 2023-02-23 Natural Acad S R L Composizione liquida medicale per somministrazione aerea
CN115734783A (zh) * 2020-05-28 2023-03-03 玛希敦大学 一种能够抑制冠状病毒复制的药物组合物
RU2800117C1 (ru) * 2022-09-13 2023-07-18 Федеральное государственное бюджетное учреждение науки Государственный научный центр Российской Федерации - Институт медико-биологических проблем Российской академии наук (ГНЦ РФ - ИМБП РАН) Искусственный назальный секрет
EP4337242A4 (fr) * 2021-05-12 2025-05-14 The Trustees of the University of Pennsylvania Compositions et procédés de réduction de la charge d'un virus ou d'un micro-organisme dans la cavité buccale

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WO2004024919A1 (fr) * 2002-09-13 2004-03-25 Replicor, Inc. Oligonucleotides antiviraux non complementaires de sequence
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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021138619A (ja) * 2020-03-02 2021-09-16 フマキラー株式会社 抗コロナウイルス剤
US12478583B2 (en) 2020-03-23 2025-11-25 Kerecis Ag Antimicrobial solutions and methods of using the same in the treatment or prevention of infections
WO2021191800A1 (fr) * 2020-03-23 2021-09-30 Kerecis Ag Solutions antimicrobiennes et leurs méthodes d'utilisation dans le traitement ou la prévention d'infections
WO2021209652A1 (fr) * 2020-04-16 2021-10-21 Dermopartners,S.L. Nouvelle composition destinée à être utilisée dans le traitement et la prévention d'infections par la covid19 et autres coronavirus
CN111529685A (zh) * 2020-04-21 2020-08-14 厦门诺康得生物科技有限公司 抗呼吸道病毒感染的鼻腔喷雾制剂
EP3928785A4 (fr) * 2020-04-27 2022-05-18 Guangzhou Century Clinical Research Co., Ltd Médicament et aliment pour la prévention ou le traitement du covid-19, et application de ceux-ci
CN115734783A (zh) * 2020-05-28 2023-03-03 玛希敦大学 一种能够抑制冠状病毒复制的药物组合物
US20220041660A1 (en) * 2020-08-06 2022-02-10 University Of Delaware Compositions and methods for sequestering viral particles in respiratory tract
CN112972389A (zh) * 2021-01-21 2021-06-18 中山大学附属第五医院 甘草酸纳米颗粒的合成及其在新型冠状病毒肺炎中的联合治疗应用
EP4337242A4 (fr) * 2021-05-12 2025-05-14 The Trustees of the University of Pennsylvania Compositions et procédés de réduction de la charge d'un virus ou d'un micro-organisme dans la cavité buccale
IT202100022172A1 (it) * 2021-08-23 2023-02-23 Natural Acad S R L Composizione liquida medicale per somministrazione aerea
WO2023026121A1 (fr) * 2021-08-23 2023-03-02 Natural Academy S.R.L. Composition liquide médicale pour administration aérienne
CN113521099A (zh) * 2021-09-10 2021-10-22 吉林大学第一医院 锌离子在抗肠道病毒ev-d68中的应用
RU2800117C1 (ru) * 2022-09-13 2023-07-18 Федеральное государственное бюджетное учреждение науки Государственный научный центр Российской Федерации - Институт медико-биологических проблем Российской академии наук (ГНЦ РФ - ИМБП РАН) Искусственный назальный секрет

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