(51) International Patent Classification: (81) Designated States (Unless
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( (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 8/20 (2006.01) A 6IK 9/08 (2006.01) kind of national protection av ailable) . AE, AG, AL, AM, A61K 8/27 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, PCT/US20 19/038746 HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (22) International Filing Date: KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY,MA, MD, ME, 24 June 2019 (24.06.2019) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 62/689,366 25 June 2018 (25.06.2018) US kind of regional protection available) . ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (71) Applicant: TRIUMPH PHARMACEUTICALS INC. UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, [US/US]; 123 12 Olive Boulevard, St. Louis, Missouri TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 63 141 (US). EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (72) Inventor: BURCH, Andrew Leslie; 44 Auburndale Drive, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, St. Louis, Minnesota 63 141 (US). TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). (74) Agent: RAKERS, Leanne M.; HARNESS, DICKEY & PIERCE, P.L.C., 7700 Bonhomme Ave., Suite 400, St. Louis, Missouri 63 105 (US). (54) Title: METHODS OF INHIBITING MICROBIAL INFECTIONS USING ZINC-CONTAINING COMPOSITIONS FIG. 1 (57) Abstract: Methods of inhibiting and/or reducing the occurrences and/or duration of microbial infections, such as rhinovirus and influenza infections, are provided herein. The methods comprise delivering an oral composition comprising at least one Eh-raising compound and at least one zinc compound to a subject. [Continued on next page] Declarations under Rule 4.17: as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(H)) as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(iii)) Published: with international search report (Art. 21(3)) with amended claims (Art. 19(1)) METHODS OF INHIBITING MICROBIAL INFECTIONS USING ZINC-CONTAINING COMPOSITIONS FIELD [0001] The present disclosure relates generally to methods for inhibiting and/or reducing the occurrence and/or duration of a microbial infection, such as a rhinovirus or influenza infection. The methods comprise delivering an oral composition comprising at least one Eh-raising compound and at least one zinc compound to a subject. BACKGROUND [0002] The body hosts a diverse array of microflora, including bacteria, fungi, and viruses. Most of these microbes reside at body surfaces which are in direct contact with the environment, such as the skin, respiratory tract and mucosal surfaces, including the oral cavity (Duerkop, et a , Nature Immunology. 2013). The microbes can cause an infection, for example, when the oral surface is compromised, allowing a microbe to enter the body, or when there is a shift in the relative populations of the various microbes which reside in the oral cavity. [0003] Microbes may induce many oral diseases, and the oral cavity can be a point of entry for various pathogens. New methods are needed to reduce the opportunity for microbes to infect a subject or reduce the duration of an infection. Such methods would promote the health and well being of the subject. SUMMARY [0004] It has been found that oral compositions comprising a first component comprising an Eh-raising compound and a second component comprising at least one zinc compound are effective for inhibiting a microbial infection. Therefore, methods for inhibiting a microbial infection, reducing the occurrence or number of microbial infections suffered by a subject, and/or shortening the duration of a microbial infection are provided herein. The methods may comprise delivering an oral composition as described herein to an oral cavity in a subject. The subject may be a human or a non-human animal. Systems and kits containing an oral composition as described herein are also provided. [0005] Other embodiments, including particular aspects of the embodiments summarized above, will be evident from the following detailed description. The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS [0006] The figures described herein are for illustrative purposes only of selected embodiments and not all possible implementations. The figures are not intended to limit the scope of the present disclosure. [0007] FIG. l is a table displaying results of the study conducted in Example 37 herein on visit 2 [0008] FIG. 2 is a table displaying results of the study conducted in Example 37 on visit 3 . [0009] FIG. 3 is a table displaying results of the study conducted in Example 37 on visit 4 . [0010] FIG. 4 is a table displaying results of the study conducted in Example 37 on visit 5. DETAILED DESCRIPTION [0011] In various aspects of the invention, oral compositions comprising a first component comprising an Eh-raising compound and a second component comprising a zinc compound are provided. Also provided are methods for inhibiting a microbial infection, reducing the number or occurrence of microbial infections suffered by a subject, and shortening the duration of a microbial infection comprising administration of said oral composition to the oral cavity of the subject. I. Definitions [0012] As used herein, the term “oral composition” is intended to include various embodiments of compositions that are useful for all aspects of oral hygiene including, but not limited to, inhibiting a microbial infection, reducing the number of microbial infections in an individual, shortening the duration of a microbial infection, preventing and/or treating oral disease, maintaining oral health, reducing or eliminating bad breath (oral malodor), whitening teeth, preventing gum deterioration, and/or preventing tooth decay. More particularly, the oral composition facilitates preventing oral microbes from reducing the oxidation-reduction potential (Eh) of an oral cavity and, at the same time, increasing the existing oxidation-reduction potential to a level, wherein an oral environment is created that is not conducive to microbes in the oral cavity. Further, the oral composition can be used for inhibiting the formation of sulfur- containing anions, reducing gingivitis, reducing the formation of dental caries, reducing canker sores, inhibiting plaque formation, and/or reducing plaque and tartar (calculus) formation. [0013] As used herein, the term “Eh-raising” is defined as a compound capable of directly or indirectly raising the Eh of the oral cavity. [0014] As used herein, the term “zinc compound” is defined as a compound capable of providing freely available zinc ions. Without being bound by theory, it is believed that the freely available zinc ions are capable of inhibiting a decrease of the Eh in the oral cavity. ETnbound zinc ions are freely available, and therefore have a greater reaction with Eh-lowering enzymes within the oral cavity than bound zinc ions. Moreover, zinc ions have been shown to possess antimicrobial properties, as it disrupts the cellular machinery of the microbe. These freely available zinc ions may also inhibit the breakdown of cysteine or cystine from saliva, mucosal tissues, and/or foods by oral bacteria. As such, oral bacteria are prevented from lowering the existing Eh within the oral cavity. [0015] As used herein, the term “microbe” or “microbial” is defined as a microorganism, such as a bacterium, a fungus (including yeast), and a virus. Non-limiting examples of bacteria include Gram positive bacteria, such as Actinomyces (e.g., A . meyeri and A . viscous), Bacillus (e.g., B . cereus, B . subtilis), Escherichia (e.g., E . coli), Staphylococcus (e.g., S. aureus, including methicillin-resistant S. aureus (MRSA)), Streptococcus (e.g., S. gordonii, S. mutans); and Gram negative bacteria, such as Aggregatibacter (e.g., A . actinomycetemocitans), Campylobacter (e.g., C . rectus), Eikenella (e.g., E . corrodens), Fusobacterium (e.g., F. nucleatum), Moraxella (e.g., M . catarrhalis), Porphyromonas (e.g., P. gingivalis), Prevotella (e.g., P. intermedia, P. melaninogenica, P. nigrescens), Pseudomonas (e.g., P. aeruginosa), Solobacterium, (e.g., S. moorei), and Viellonella (e.g., V. atypica, V. dispar). [0016] Non-limiting examples of fungus include yeast, such as Candida (e.g., C . albicans), Capnocytophaga (e.g., C . gingivalis), Streptomyces (e.g., S. cervisiae). [0017] Non-limiting examples of viruses include influenza virus, coronavirus, coxsackievirus, foot-and-mouth virus, herpes virus (including herpes simplex virus (HSV)), mengovirus, nidovirus, parainfluenza virus, picomavirus, respiratory syncytial virus (RSV), and rhinovirus. In a particular embodiment, the virus is a rhinovirus. [0018] As used herein, the term “microbial infection” is defined as the invasion and growth of a microbe on or in an individual’s body where said microbe does not normally grow when the individual is healthy. Also encompassed by “microbial infection” is when the microbe grows to a greater degree on or in the body of an individual (e.g., the population of the microbe is larger) when compared to the microbe’s population at the same body location when the individual is healthy.