Antiviral Composition for Oral Care

Abstract

Viral infection of the oral mucosa (the lining of the oral cavity) is a common feature of many respiratory viruses that is central to pathogenesis and spread. Despite this, few anti-viral oral hygiene products exist. The present invention is a composition of a zinc salt and hinokitiol to be used as an anti-viral agent in oral care products. The composition is extremely low risk for adverse effects and irritation, and as such can be used continuously and frequently as both a preventative measure and a treatment. Oral care products in which this composition may be used include, but are not limited to toothpaste, mouth rinse and gargling solution. The composition inhibits viral replication in the oral cavity through interacting with the replication machinery of the viruses.

Claims

1-36. (canceled)

37. A composition for use in oral care comprising at least one water soluble zinc salt and a zinc ionophore selected from one or more of hinokitiol, quercetin, epigallocatechin, and zincophorin or a salt thereof.

38. The composition as claimed in claim 37, wherein the composition contains at least one zinc salt, or two or more zinc salts; or wherein the at least one water soluble zinc salt is selected from one or more of zinc chloride, zinc myristate, zinc citrate, zinc nitrate, or zinc sulfate, zinc chlorate, zinc phosphate, zinc molybdate, zinc chromate, zinc bromide and zinc iodide.

39. The composition as claimed in claim 37, wherein: the composition comprises a therapeutically effective amount of at least one water soluble zinc salt and a therapeutically effective amount of one or more of hinokitiol, quercetin, epigallocatechin, and zincophorin; the zinc ionophore comprises hinokitiol or a salt thereof; or the composition comprises hinokitiol.

40. The composition as claimed in claim 37, wherein the composition comprises a mouth rinse, a toothpaste, a gargling liquid, a mouth wash, a throat lozenge, a nasal spray, a topical oral mucosa treatment composition, a topical nasal mucosa treatment, an inhaler or a puffer, or a composition for treating the oro-pharynx.

41. The composition as claimed in claim 37, wherein the composition comprises zinc present in an amount of 0.1 wt %, calculated as zinc chloride equivalent, and hinokitiol is present in an amount of from 0.01 to 0.2 wt %.

42. The composition as claimed in claim 37, wherein: the composition comprises zinc present in an amount of 0.1 wt %, calculated as zinc chloride equivalent, and hinokitiol present in an amount of from 0.3 to 1.0 wt %, and the composition is used as a treatment for treating a viral infection and the oral care composition comprises a mouth wash or a gargling liquid, a throat lozenge, a topical oral mucosa treatment composition or a topical nasal mucosa treatment or an inhaler or a puffer or a treatment for the oro-pharynx; or the composition comprises a toothpaste comprising zinc present in an amount of from 0.75 to 1.0 wt %, calculated as zinc chloride equivalent, and hinokitiol present in an amount of from 0.01 to 1.0 wt %.

43. The composition as claimed in claim 37, wherein the composition comprises an aqueous composition; or wherein the composition comprises an emulsion or a dispersion, wherein the emulsion is an oil-in-water emulsion.

44. The composition as claimed in claim 37, wherein the composition comprises one or more sweeteners.

45. The composition as claimed in claim 44, wherein: the one or more sweeteners are present in an amount of up to 75 wt %, or up to 50 wt %, or up to 25 wt %, or up to 20 wt %, or up to 15 wt %; the one or more sweeteners comprise one or more of sorbitol, glycerin, inositol, saccharine or sodium saccharine; or the composition comprises sorbitol in an amount of from 5-10 wt %, xylitol in an amount of from 1-5 wt %, and glycerin in an amount of from 1-5 wt %.

46. The composition as claimed in claim 37, further comprising: one or more flavor components or flavor masking agents, one or more preservatives or one or more biocides, or one or more gelling agents or gels.

47. The composition as claimed in claim 37, wherein the composition comprises an oil-in-water emulsion or a dispersion comprising an oil phase dispersed in an aqueous phase, the oil phase comprising less than 10 wt %, or less than 7.2 wt % of the overall composition.

48. The composition as claimed in claim 47, wherein the composition also comprises a surfactant.

49. The composition as claimed in claim 48, wherein the surfactant is present in an amount of up to 5 wt %, or up to 2 wt %, or from 0.1 to 1 wt %.

50. The composition as claimed in claim 37, further comprising plant extracts with natural anti-inflammatory, antiseptic or antibacterial action; or breath fresheners or ingredients that mask or treat bad breath.

51. A method for treating a viral infection or preventing a viral infection or lowering risk of viral infection or reducing viral load in a patient, by treating the patient with a composition as claimed in claim 37.

52. The method as claimed in claim 51, wherein the composition comprises an oral care composition and the patient uses the oral care composition by taking it into the mouth.

53. The method as claimed in claim 52, wherein the oral care composition is gargled, or used as a toothpaste or a mouthwash or as an oral spray.

54. The method as claimed in claim 51, wherein: the composition comprises zinc present in an amount of 0.1 wt %, calculated as zinc chloride equivalent, and hinokitiol present in an amount of from 0.01 to 0.2 wt % and the method is a prophylactic method for avoiding or minimizing likelihood of a viral infection occurring; the composition comprises zinc present in an amount of 0.1 wt %, calculated as zinc chloride equivalent, and hinokitiol present in an amount of from 0.3 to 1.0 wt %, and the composition is used as a treatment for treating a viral infection of the oral mucosa or to reduce a viral load or to reduce symptoms and severity of viral infection or to prevent appearance of symptoms arising from viral infection and the oral care composition comprises a mouth wash or a gargling liquid, a throat lozenge, a topical oral mucosa treatment composition or a topical nasal mucosa treatment or an inhaler or a puffer or a treatment for the oro-pharynx; or the composition comprises a toothpaste comprising zinc present in an amount of from 0.75 to 1.0 wt %, calculated as zinc chloride equivalent, and hinokitiol present in an amount of from 0.01 to 1.0 wt % and the method comprises brushing the teeth, or inside the cheeks, or the tongue, of a patient for prophylactic or treatment of a viral infection of the oral mucosa.

55. The method as claimed in claim 51, wherein the method treats one or more selected from the following: viral infections caused by rhinoviruses; corona viruses that cause colds; severe acute respiratory syndrome and COVID-19; and influenza viruses.

56. A method for inhibiting viral replication in an oral cavity through interacting with replication machinery of one or more viruses by applying a composition as claimed in claim 37 to the oral mucosa.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0039] Various embodiments of the invention will be described with reference to the following drawings, in which:

[0040] FIG. 1 depicts an illustration of the infection and replication process of an RNA virus, such as that of influenza. Zinc ions interact with the processing of viral polyproteins and the RNA dependent RNA polymerase (RdRp), inhibiting the replication of the viral genome and proteins. However, zinc ions are normally unable to pass through the membrane, due to possessing a charge. Hinokitiol promotes the uptake of zinc ions into cells through an uncharacterized mechanism, enabling maximal effect.

DESCRIPTION OF EMBODIMENTS

[0041] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items. As used herein, the singular forms “a”, “an”, and “the” are intended to include the plural forms as well as singular forms, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising”, when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof.

[0042] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one having ordinary skill in the art to which the invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0043] In describing the invention, it will be understood that a number of techniques and steps are disclosed. Each of these has individual benefit and each can also be used in conjunction with one or more, or in some cases all, of the other disclosed techniques. Accordingly, for the sake of clarity, this description will refrain from repeating every possible combination of the individual steps in an unnecessary fashion. Nevertheless, the specifications and claims should be read with the understanding that such combinations are entirely within the scope of the invention and claims.

[0044] The present disclosure is to be considered as an exemplification of the invention, and is not intended to limit the invention to the specific embodiments illustrated by the figures or description below.

[0045] The present invention will now be described. The composition is comprised of hinokitiol and a zinc salt or zinc compounds, including but not limited to zinc chloride, zinc oxide, zinc nitrate, zinc chlorate, zinc sulfate, zinc phosphate, zinc molybdate and zinc chromate. Other zinc compounds or zinc salts may also be used. Two or more zinc compounds or zinc salts may be used. This composition may be used as an anti-viral active agent in oral care formulations. The proportions of hinokitiol and zinc are not limited, but are especially preferable in a ratio of hinokitiol to zinc of 1:3 to 10:1.

[0046] The anti-viral action of the zinc salt and hinokitiol composition occurs through multiple mechanisms of action. The present inventors have postulated that zinc ions derived from a zinc compound or a zinc salt inhibit the replication machinery of RNA viruses, and as such can help control illness and spread of the diseases. Hinokitiol strongly promotes the transport of zinc into cells, making this mode of action more effective. Common RNA viruses include the influenza, which affects at least 9 million people a year. Another RNA virus is the COVID-19, the coronavirus which has currently caused a pandemic. COVID-19 is very similar to the virus which caused severe acute respiratory syndrome (SARS). It was found that the SARS virus entered and replicated inside the oral mucosa, and then was released into saliva, facilitating its spread. A similar process has been predicted to occur with COVID-19.

[0047] Viral infection of the oral mucosa (the lining of the oral cavity) is a common feature of many respiratory viruses that is central to pathogenesis and spread. Despite this, few anti-viral oral hygiene products exist. The present invention in some embodiments is a composition of a zinc salt and hinokitiol to be used as an anti-viral agent in oral care products. The composition is extremely low risk for adverse effects and irritation, and as such can be used continuously and frequently as both a preventative measure and a treatment. Oral care products in which this composition may be used include, but are not limited to toothpaste, mouth rinse and gargling solution. The composition inhibits viral replication in the oral cavity through interacting with the replication machinery of the viruses.

EXAMPLE 1

[0048] The following composition was prepared:

TABLE-US-00001 Phase Ingredient Percentage A Aqua .sup. 50-75 A Sorbitol   5-10 B PEG-40 Hydrogenated Castor Oil .sup. 1-5 A Xylitol .sup. 1-5 A Glycerin .sup. 1-5 A Poloxamer 407 0.1-1 B Eucalyptus Globulus Leaf Oil <0.1 B Mentha Piperita Oil 0.1-1 A Sodium Citrate 0.1-1 A Inositol <0.1 A Zinc Chloride <0.1 A Sodium Saccharin 0.1-1 A O-Cymen-5-OL <0.1 B Hexetidine <0.1 A Sodium Benzoate <0.1 B Phenoxyethanol 0.1-1 A Citric Acid 0.1-1 C Hinokitiol 0.1-1

[0049] This composition was prepared by combining the Phase A ingredients and heating to 60° C. Following this, the Phase B ingredients were combined and added to phase A under high shear to form a stable emulsion. Hinokitiol can be added either to phase A, B or to the complete emulsion.

[0050] The composition of Example 1 was tested on human HeLa cells infected with the feline coronavirus. Viral titre was measured after 5 minutes and after 1 hour. A log reduction of 3 represents a 99.9% reduction in virus titre, and a log reduction of 4 represents a 99.99% reduction. The following results were obtained:

TABLE-US-00002 Log-reduction in viral Treatment, titre (feline coronavirus) Control, 0 5 Minutes with 3.25 composition of example 1 1 Hour with composition 4.00 of example 1

[0051] The above results show a dramatic reduction in the viral load by use of the composition of example 1 in a short period of time.

[0052] In the present specification and claims (if any), the word ‘comprising’ and its derivatives including ‘comprises’ and ‘comprise’ include each of the stated integers but does not exclude the inclusion of one or more further integers.

[0053] Reference throughout this specification to ‘one embodiment’ or ‘an embodiment’ means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearance of the phrases ‘in one embodiment’ or ‘in an embodiment’ in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more combinations.

[0054] In compliance with the statute, the invention has been described in language more or less specific to structural or methodical features. It is to be understood that the invention is not limited to specific features shown or described since the means herein described comprises preferred forms of putting the invention into effect. The invention is, therefore, claimed in any of its forms or modifications within the proper scope of the appended claims (if any) appropriately interpreted by those skilled in the art.

CITATION LIST

Patent Literature

[0055] Otsu, Yoshiro, Yaeno Arima, and Yoriko Nakai. 1997. “Antibacterial and Antifungal Activity Method, Therapeutic Method of Infectious Diseases and Preserving Method of Cosmetics.”—U.S. Pat. No. 5,696,169A [0056] Fukui, Atsuko and Takuya Nakatsubo. 2019. “Antiviral Agent and Throat Candy, Gargle, and Mouthwash Using the Same.”—JP2019077617A [0057] Dong, Liang, Steven Espinal, Patrick Wong, and Paul Magruder. 2007. “Antiviral Medication.”—ES2236012T3

Non Patent Literature

[0058] Krenn, B. M. et al. 2009. “Antiviral Activity of the Zinc Ionophores Pyrithione and Hinokitiol against Picornavirus Infections.” Journal of Virology 83(1):58-64. [0059] Te Velthuis, Aartjan J. W. et al. 2010. “Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity in Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture.” PLoS Pathogens 6(11):1-10. [0060] Wang, Wei Kung et al. 2004. “Detection of SARS-Associated Coronavirus in Throat Wash and Saliva in Early Diagnosis.” Emerging Infectious Diseases 10(7):1213-19

[0061] Xu, Hao et al. 2020. “High Expression of ACE2 Receptor of 2019-NCoV on the Epithelial Cells of Oral Mucosa.” International Journal of Oral Science 12(1 PG-8):8. Retrieved (https://doi.org/10.1038/s41368-020-0074-xNS-).