COMPOSITIONS AND METHODS FOR TREATING CORONAVIRUS

Abstract

Oral formulations include anti-viral agents. These oral formulations are manufactured in various permutations such as a chewing gum or lozenge which incorporate anti-viral agents for protecting an individuals body from viruses.

Claims

1. A composition comprising: an active ingredient, a sugar alcohol, a blend of sugar alcohols, a sweetener, flavorings, a gum base, or combinations thereof.

2. The composition of claim 1, wherein the active ingredient is an anti-viral agent or an angiotensin-converting enzyme (ACE) inhibitor.

3. The composition of claim 1, wherein the composition further comprises a cannabinoid or derivatives thereof.

4. The composition of claim 1, wherein the anti-viral agent comprises: chitosan, zinc, potassium iodide, chlorhexidine, cetylpyridinium chloride, fucoidan, giloy, quinine, povidone-iodine, hydrogen peroxide, carbamide peroxide, plant proteins, cyclodextrin, Citrox, essential oils, angiotensin-converting enzyme (ACE) inhibitors, or in combinations thereof.

5. The composition of claim 2, wherein the ACE inhibitors comprise: benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril or combinations thereof.

6. The composition of claim 2, wherein the anti-viral agent comprises from about 1.0% to about 10.0% by weight, based on the total weight of the composition.

7. The composition of claim 3, wherein the cannabinoid or derivatives thereof comprise from about 1.0% to about 10.0% by weight, based on the total weight of the composition.

8. The composition of claim 1, wherein the composition, based on the total weight of the composition, comprises: about 40% to about 80% by weight of a sugar alcohol or a blend of sugar alcohols, or a sweetener or a combination thereof; about 20.0% to about 30.0% by weight of a gum base; about 1% to about 10% by weight of an anti-viral agent or combination of anti-viral agents, about 2% to about 15% by weight of a flavoring in liquid or powder form; about 1% to about 5% by weight of tableting lubricants and powder flow agents; about 0.2% to about 0.6% by weight of intensive sweeteners; or combinations thereof.

9. A composition comprising: sugar alcohol or a blend of sugar alcohols, a flavoring(s), an active agent(s), tableting lubricants, powder flow agents, intensive sweeteners or combinations thereof.

10. The composition of claim 9, wherein the blend of sugar alcohols comprise one or more of: sorbitol, isomalt, xylitol, maltitol, mannitol or erythritol.

11. The composition of claim 9, wherein the active agent(s) comprise at least one of: an anti-viral agent, derivatives thereof or combinations thereof.

12. The composition of claim 9, wherein the active agents based on the total weight of the composition, comprise about 1.0% to about 10.0% by weight.

13. The composition of claim 9, wherein the flavoring is in a liquid and/or powder form.

14. The composition of claim 9, wherein the flavoring, based on the total weight of the composition, comprise about 2.0% to about 12.0% by weight.

15. The composition of claim 9, wherein the sugar alcohol or a blend of sugar alcohols based on the total weight of the composition, comprise about 70.0% to about 90.0% by weight.

16. The composition of claim 9, wherein the tableting lubricants and powder flow agents, based on the total weight of the composition, comprise about 1.5% to about 5.0% by weight.

17. The composition of claim 9, wherein the active ingredient is an anti-viral agent or an angiotensin-converting enzyme (ACE) inhibitor.

18. The composition of claim 9, wherein the anti-viral agent comprises from about 1.0% to about 10.0% by weight, based on the total weight of the composition.

19. The composition of claim 9, wherein the composition further comprises a cannabinoid or derivatives thereof.

20. The composition of claim 19, wherein the cannabinoid or derivatives thereof comprise from about 1.0% to about 10.0% by weight, based on the total weight of the composition.

21. A composition comprising: a gum base, a sugar alcohol, a blend of sugar alcohols, sweeteners, a bulk filler, an anti-viral agent or combination of anti-viral agents, flavorings, tableting lubricants, powder flow agents or combinations thereof.

22. The composition of claim 21, wherein the composition, based on the total weight of the composition, comprises: about 10% to about 80% by weight of a sugar alcohol, blend of sugar alcohols, sweetener, about 5% to about 50% by weight of bulk filler, about 1% to about 10% by weight of an anti-viral agent or combination of anti-viral agents, about 0.1% to about 10% by weight of a flavor powder, about 0.1% to about 10% by weight of tableting lubricants and powder flow agents, or combinations thereof.

23. The composition of claim 21, wherein the composition, based on the total weight of the composition, comprises: about 55% to about 70% by weight of a sugar, a sugar blend, sugar alcohol, blend of sugar alcohols, sweetener, about 5% to about 40% by weight of bulk filler, about 1% to about 10% by weight of an anti-viral agent or combination of anti-viral agents, about 0.1% to about 5% by weight of a flavor powder, about 0.1% to about 5% by weight of tableting lubricants and powder flow agents, or combinations thereof.

24. The composition of claim 21, wherein the sugar or sugar blend comprise dextrose, sucrose, fructose, glucose or combinations thereof.

25. The composition of claim 23, wherein the sugar alcohol or sugar alcohol blend comprise: sorbitol, isomalt, xylitol, maltitol, mannitol, erythritol or combinations thereof.

26. The composition of claim 23, wherein the sweetener comprises stevia, sucralose, monk fruit, honey or agave nectar.

27. The composition of claim 21, wherein the tablet flow agent comprises magnesium stearate.

28. The composition of claim 21, wherein a bulk filler comprises microcrystalline cellulose (MCC), bamboo fibers, or combinations thereof.

29. A composition consisting of: a sugar, a sugar blend, sugar alcohol, a blend of sugar alcohols, sweeteners, a bulk filler, an anti-viral agent or combination of anti-viral agents, flavorings, tableting lubricants, powder flow agents and combinations thereof.

30. The composition of claim 29, wherein the composition, based on the total weight of the composition, consists of: about 55% to about 70% by weight of a sugar, a sugar blend, sugar alcohol, blend of sugar alcohols, sweetener, about 5% to about 40% by weight of bulk filler, about 1% to about 10% by weight of an anti-viral agent or combination of anti-viral agents, about 0.1% to about 5% by weight of a flavor powder, about 0.1% to about 5% by weight of tableting lubricants and/or powder flow agents, and combinations thereof.

31. The composition of claim 29, wherein the composition further comprises a cannabinoid or derivatives thereof.

32. The composition of claim 31, wherein the cannabinoid or derivatives thereof comprise from about 1.0% to about 10.0% by weight, based on the total weight of the composition.

33. A method of preventing or treating diseases or disorders associated with viruses in a subject, comprising: administering to the subject a composition comprising: an anti-viral agent or combination of anti-viral agents, sugar alcohol, a blend of sugar alcohols, a gum base, or combinations thereof.

34. The method of claim 33, wherein the composition, based on the total weight of the composition, comprises: about 10% to about 80% by weight of a sugar, sugar blend, sugar alcohol, or a blend of sugar alcohols, about 5% to about 80% of a gum base.

35. The method of claim 33, further comprising: flavoring, tableting lubricants and powder flow agents, intensive sweeteners, sugar substitutes or combinations thereof.

36. The method of claim 33, wherein the composition, based on the total weight of the composition, further comprises: about 1% to about 20% by weight of flavoring, about 0.1% to about 10% by weight of tableting lubricants and powder flow agents, about 0.01% to about 2% by weight of intensive sweeteners.

37. The method of claim 33, wherein the sugar or sugar blend comprise dextrose, sucrose, fructose, glucose or combinations thereof.

38. A method of preventing or treating diseases or disorders associated with viruses in a subject, comprising: administering to a subject in need thereof, a gum-based composition for chewing, the composition comprising, based on the total weight of the composition: about 10% to about 80% by weight of a sugar, sugar blend, sugar alcohol, or a blend of sugar alcohols, about 5% to about 80% of a gum base, about 1% to about 10% by weight of an anti-viral agent or combination of anti-viral agents, about 1% to about 20% by weight of flavoring, about 0.1% to about 10% by weight of tableting lubricants and powder flow agents, about 0.01% to about 2% by weight of intensive sweeteners, or combinations thereof.

39. The method of claim 38, wherein the composition is in a gum or tablet form.

40. A composition comprising: an anti-viral agent or combination of anti-viral agents, a sugar, sugar blend, sugar alcohol, a blend of sugar alcohols, a gum base, or combinations thereof.

41. The composition of claim 40, wherein the composition, based on the total weight of the composition, comprises: about 1% to about 10% by weight of an anti-viral agent or combination of anti-viral agents, about 10% to about 80% by weight of a sugar, sugar blend, sugar alcohol, or a blend of sugar alcohols, about 5% to about 80% of a gum base.

42. The composition of claim 40, further comprising: flavoring, tableting lubricants and powder flow agents, intensive sweeteners, sugar substitutes or combinations thereof.

43. The composition of claim 40, wherein the composition, based on the total weight of the composition, further comprises: about 1% to about 20% by weight of flavoring, about 0.1% to about 10% by weight of tableting lubricants and powder flow agents, about 0.01% to about 2% by weight of intensive sweeteners.

44. The composition of claim 41, wherein the sugar alcohol or sugar alcohol blend comprise: sorbitol, isomalt, xylitol, maltitol, mannitol, erythritol or combinations thereof.

45. The composition of claim 42, wherein a sugar substitute comprises stevia, sucralose, monk fruit, honey or agave nectar.

46. A composition consisting of: an anti-viral agent or combination of anti-viral agents, a sugar alcohol or a blend of sugar alcohols, tableting lubricants, powder flow agents and intensive sweeteners.

47. The composition of claim 46, wherein the composition, based on the total weight of the composition, consists of: about 70.0% to about 90.0% by weight of a sugar, sugar blend, sugar alcohol, or a blend of sugar alcohols, about 1% to about 10% by weight of an anti-viral agent or combination of anti-viral agents, about 2% to about 12% by weight of flavoring, about 1% to about 5% by weight of tableting lubricants and powder flow agents, about 0.1% to about 2% by weight of intensive sweeteners.

48. The composition of claim 47, wherein the composition further comprises a cannabinoid or derivatives thereof.

49. The composition of claim 48, wherein the cannabinoid or derivatives thereof comprise from about 1.0% to about 10.0% by weight, based on the total weight of the composition.

50. A composition consisting of: an anti-viral agent or combination of anti-viral agents, a sugar alcohol or a blend of sugar alcohols, or derivatives thereof, gum base, tableting lubricants, powder flow agents and intensive sweeteners.

51. The composition of claim 50, wherein the composition, based on the total weight of the composition, consists of: about 42.0% to about 80.0% by weight of a sugar, sugar blend, sugar alcohol, or a blend of sugar alcohols, about 20% to about 30% of a gum base, about 1% to about 10% by weight of an anti-viral agent or combination of anti-viral agents, about 2% to about 12% by weight of flavoring, about 1% to about 5% by weight of tableting lubricants and powder flow agents, about 0.2% to about 0.6% by weight of intensive sweeteners.

52. The composition of claim 50, wherein the composition further comprises a cannabinoid or derivatives thereof.

53. The composition of claim 52, wherein the cannabinoid or derivatives thereof comprise from about 1.0% to about 10.0% by weight, based on the total weight of the composition.

Description

DETAILED DESCRIPTION

[0023] Provided herein, is an innovative chewing gum that contains safe and effective active ingredients with properties that either prevent viruses from spreading throughout a person's body, or to another person. The regular use of the gums embodied herein would serve as a prophylactic solution at the main point of entry for a virus into the body before the virus can spread disease. The target population is any human being.

[0024] Specifically, Coronaviruses use the angiotensin converting enzyme (ACE-2) as the host receptor for target cell entry. The extent and distribution of ACE-2 has been associated with the clinical symptoms of coronavirus disease. ACE-2 is abundantly expressed in oral mucosa. Once firmly established in the oral cavity and replicating, Coronaviruses are: [0025] easily spread to other ACE-2 expressing epithelial cells in the lungs, intestines, kidneys, and colon with the potential for causing significant health problems which can be severe and deadly. [0026] easily expelled from the oral cavity via breathing, coughing or sneezing thus spreading the virus quickly to other people in close proximity.

[0027] ACE-2 is a protein on the surface of many cell types. It is an enzyme that generates small proteins (by cutting up the larger protein angiotensinogen) that then go on to regulate functions in the cell. Using the spike-like protein on its surface, Coronaviruses bind to ACE-2 (like a key being inserted into a lock) prior to entry and infection of cells. Hence, ACE-2 acts as a cellular doorway (a receptor) for the virus (Sriam, 2021).

[0028] Chewing gum. In certain embodiments, the composition is a chewing gum which releases the active agent(s) during chewing. A suitable chewing gum base comprises one or more constituents including elastomers for elasticity, resins to act as binders and softeners, plasticizers to render the elastomer soft to ensure thorough blending of the gum base and flavors during shelf life. The method for manufacture of a chewing gum is exemplified in U.S. Pat. No. 9,744,128 issued Aug. 29, 2017, the contents of which are incorporated herein by reference, in its entirety. Briefly, the method comprises initially heating the gum base in ovens to melt the gum base to an internally measured temperature between 140-160° F. The ingredients, including the one or more active ingredients are combined in a mixer. The melted gum base is added to the mixer and cooled to produce a particulate mixture. The temperature of the gum base exceeds that of the mixer when first introduced, but as mixing continues it cools quickly to room temperature and forms rock-sized granular pieces. These granular pieces are then conditioned for a period of time which allows the granular pieces to dry slightly and complete the crystallization process. The pieces are conditioned for at least about 6 hours at a temperature not greater than about 75° F. and about 60% relative humidity. The pieces are then ground into a powder at room temperature with tableting excipients, and tableted. This process preserves the efficacy of the active ingredient or ingredients by avoiding exposure to high heat and extreme cold, mainly during milling that can otherwise degrade the active ingredient's efficacy.

[0029] In some embodiments, a composition based on a chewing gum comprises a therapeutically effective amount of an anti-viral active compound, a sugar alcohol, a blend of sugar alcohols, a gum base, or combinations thereof. In certain embodiments, a therapeutically effective amount of anti-viral agents comprises about 0.1% to about 20% by weight, based on the total weight of the composition. Examples of anti-viral active compounds include, but are not limited to, chitosan, zinc, potassium iodide, povidone iodine, chlorhexidine, cetylpyridinium chloride, fucoidan, giloy, quinine, plant enzymes, plant proteins, plant essential oils, ACE-2 inhibitors, anti-viral drug compounds, Cannabis sativa extracts from either hemp or marijuana, molnupiravir, chemokines, cytokines, immune stimulating agents, immune modulating agents, enzymes, ribavirin, protease inhibitors, helicase inhibitors, polymerase inhibitors, helicase inhibitors, neuraminidase inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, purine nucleosides, chemokine receptor antagonists, interleukins, Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, Sambucus nigra, Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale or combinations thereof.

[0030] Examples of ACE-2 inhibitors comprise: benazepril (LOTENSIN®, LOTENSIN HCT®), captopril (CAPOTEN®), enalapril (VASOTEC®), fosinopril (MONOPRIL®), lisinopril (PRINIVIL®, ZESTRIL®), moexipril (UNIVASC®), perindopril (ACEON®), quinapril (ACCUPRIL®), ramipril (ALTACE®), and trandolapril (MAVIK®).

[0031] In certain embodiments, the non-nucleoside reverse transcriptase inhibitor (NNRTI) analogs, variants or combinations thereof, comprises: etravirine, efavirenz, nevirapine, rilpivirine, delavirdine, or nevirapine. In certain embodiments, a nucleoside reverse transcriptase inhibitor (NRTI), comprises: lamivudine, zidovudine, emtricitabine, abacavir, zalcitabine, dideoxycytidine, azidothymidine, tenofovir disoproxil fumarate, didanosine (ddI EC), dideoxyinosine, stavudine, abacavir sulfate or combinations thereof.

[0032] Cannabinoids in the chewing gum composition according to embodiments may be synthetic or procured from natural source. Natural sources of cannabinoids may be from cannabis plants, hemp plants, or other organisms capable of producing cannabinoids. Organisms capable of producing cannabinoids may be genetically modified. Where cannabinoids are from natural sources, a combination of cannabinoids may be present at different concentration. The sources may be chosen such that a cannabinoid may be present as the major cannabinoid, such as CBD, CBG, or THC.

[0033] Synthetic cannabinoids may be synthesized by methods known in the art. Synthetic cannabinoids are purer, such that only one cannabinoid may be present. A combination of cannabinoids may be provided at ratios as desired. This may be done to achieve the desired concentrations for the various synthetic cannabinoids.

[0034] In certain embodiments, cannabinoids may be provided in a solid material composed of an edible solid, such as a sugar alcohol, to prevent binding with the gum base. Other solids suitable for embedding cannabinoids are contemplated, such that cannabinoids or derivatives thereof are provided within internal voids of solid materials. Alternatively, cannabinoids or derivatives thereof may be provided in a granule embedded into the gum matrix. Cannabinoids or derivatives thereof provided in these manners may improve cannabinoid release during mastication of the chewing gum according to embodiments.

[0035] Other suitable carriers which may be combined with cannabinoids before inclusion into the gum matrix may include certain celluloses such as microcrystalline cellulose derivatives, dextran, agarose, agar, pectin, alginate, xanthan, chitosan, or starch. The combination of cannabinoids and suitable carriers may result in cannabinoids being present within internal voids of these carriers.

[0036] Providing cannabinoids by combining with a suitable carrier or by providing cannabinoids in a capsule within the gum matrix may enable controlled release of cannabinoids during chewing of the chewing gum composition.

[0037] In certain embodiments, cannabinoids or derivatives thereof may also be provided in microencapsulated or nanoencapsulated form or in freeze dried form. Microencapsulated, nanoencapsulated, or freeze-dried cannabinoids may improve the chewing gum's taste, prevent binding with the gum matrix, control cannabinoid release during mastication, and further improve bioavailability of the cannabinoids.

[0038] In the chewing gum composition according to embodiments, cannabinoids may be provided in encapsulated form. Microencapsulation or nanoencapsulation into particles may improve bioavailability profiles of cannabinoids. Encapsulation of cannabinoids may result in particles of size 20-40 nm. Microencapsulation or nanoencapsulation may be by liposomal encapsulation, such that the cannabinoids are present inside particles having lipid walls. Other encapsulation methods may be used.

[0039] In certain embodiments, freeze dried cannabinoids may be in solid form obtained from freezing cannabis oil containing cannabinoids and subliming other components, leaving a solid having a high cannabinoid concentration. Solid cannabinoids may be effectively incorporated into a chewing composition by combining with other suitable solid carriers and embedding the resulting solid as a granule within the chewing gum composition.

[0040] In other embodiments the composition comprises: about 10% to about 80% by weight based on the total weight of the composition, of a sugar, sugar blend, sugar alcohol, or a blend of sugar alcohols, and, about 5% to about 80% by weight based on the total weight of the composition, of a gum base. In certain embodiments, the composition further comprises: flavoring, tableting lubricants and powder flow agents, intensive sweeteners, sugar substitutes or combinations thereof. In certain embodiments, the composition comprises about 1% to about 20% by weight of flavoring, about 0.1% to about 10% by weight of tableting lubricants and powder flow agents, about 0.01% to about 2% by weight of intensive sweeteners and/or sugar substitutes. In embodiments, the sugar or sugar blend comprise dextrose, sucrose, fructose, glucose or combinations thereof. In other embodiments, the sugar alcohol or sugar alcohol blend comprise: sorbitol, isomalt, xylitol, maltitol, mannitol, erythritol, allulose, lactose or combinations thereof. In other embodiments, a sugar substitute comprises stevia, sucralose, monk fruit, honey or agave nectar. In certain embodiments, the chewing gum composition comprises a flavoring agent, e.g., fruity flavors, menthol flavor, eucalyptus, mint flavor, peppermint flavor, spearmint flavor, and the like. Flavorings can be in the form of flavored extracts, volatile oils, chocolate flavorings, peanut butter flavoring, cookie crumbs, crisp rice, vanilla or any commercially available flavoring. Examples of useful flavoring include, but are not limited to, pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or pure vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, walnut oil, cherry oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch or toffee.

[0041] An elastomeric base is normally present in the chewing gum composition in an amount of about 25 to about 85% by weight, based on the total weight of the chewing gum composition.

[0042] Other suitable carriers which may be combined with the anti-viral agents before inclusion into the gum matrix may include certain celluloses such as microcrystalline cellulose derivatives, dextran, agarose, agar, pectin, alginate, xanthan, chitosan, tri-calcium phosphate, inulin, calcium carbonate or starch.

[0043] Lozenges. In another embodiment, the composition is a lozenge which releases the active agent(s) over a period of time, e.g., from about 3 minutes or more, once it is in the subject's mouth. The lozenges are formulated to administer a dose of about 1 to 500 mg of the active agent per application directly to the oral mucosa inside the mouth.

[0044] Accordingly, in certain embodiments, a composition for a lozenge comprises a sugar, a sugar blend, sugar alcohol, a blend of sugar alcohols, sweeteners, a bulk filler, and/or derivatives thereof, flavorings, tableting lubricants, powder flow agents or combinations thereof. In certain embodiments, the composition comprises, based on the total weight of the composition: about 10% to about 80% by weight of a sugar, a sugar blend, sugar alcohol, blend of sugar alcohols, sweetener, about 5% to about 50% by weight of bulk filler, about 0.1% to about 10% by weight of a flavor powder, about 0.1% to about 10% by weight of tableting lubricants and powder flow agents, or combinations thereof.

[0045] In one embodiment, the composition, based on the total weight of the composition, comprises: about 55% to about 70% by weight of a sugar, a sugar blend, sugar alcohol, blend of sugar alcohols, sweetener, about 5% to about 40% by weight of bulk filler, about 0.1% to about 5% by weight of a flavor powder, about 0.1% to about 5% by weight of tableting lubricants and powder flow agents, or combinations thereof. In certain embodiments, the sugar or sugar blend comprise dextrose, sucrose, fructose, glucose or combinations thereof. In other embodiments, the sugar alcohol or sugar alcohol blend comprise: sorbitol, isomalt, xylitol, maltitol, mannitol, erythritol or combinations thereof and the sweetener comprises stevia, sucralose, monk fruit, honey or agave nectar.

[0046] In one embodiment, the tablet flow agent comprises magnesium stearate.

[0047] In other embodiments, a bulk filler comprises microcrystalline cellulose (MCC), bamboo fibers, tri-calcium phosphate, inulin, calcium carbonate or combinations thereof. In order to manufacture a slower versus fast-dissolving lozenge or tablet, the proportion of the bulk fillers are increased or decreased relative to the other constituents to alter the dissolution rate of the lozenge, i.e., fast-dissolving, slow dissolving etc. The bulk fillers absorb moisture quickly which creates the dissolution. Suitable fillers include celluloses and cellulose derivatives including microcrystalline cellulose, hydroxypropylcellulose and sodium carboxymethylcellulose, lactose, starches including potato starch and corn starch, carbohydrates including a cellulose derivative, e.g., hemicellulose. The cellulose derivative may be of natural origin, e.g., dextran, agarose, agar, pectin, alginate, xanthan, chitosan, starch. The cellulose derivative may also be of synthetic or semi-synthetic origin. In certain embodiments, a bulk filler comprises microcrystalline cellulose (MCC), bamboo fibers, or combinations thereof. The bulk fillers are present in the composition from about 5% to about 50% by weight of bulk filler, based on total weight of the composition. Specific examples of a suitable microcrystalline cellulose is microcrystalline cellulose comprising: AVICEL™ grades PH-100, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-302, VIVACEL™ grades 101, 102, 12, 20 and EMOCEL™ grades 50M and 90M, and the like, and mixtures thereof.

[0048] Flavors, coloring agents, spices, and the like can be incorporated into the product. Flavorings can be in the form of flavored extracts, volatile oils, chocolate flavorings, peanut butter flavoring, cookie crumbs, crisp rice, vanilla or any commercially available flavoring. Examples of useful flavoring include, but are not limited to, pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or pure vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, walnut oil, cherry oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch or toffee.

[0049] Other formulations. The active agents may further be formulated with acceptable excipients and/or carriers for oral consumption. The carrier may be a liquid, gel, gelcap, capsule, powder, solid tablet (coated or non-coated), tea, or the like. Suitable excipient and/or carriers include maltodextrin, calcium carbonate, dicalcium phosphate, tricalcium phosphate, microcrystalline cellulose, dextrose, rice flour, magnesium stearate, stearic acid, croscarmellose sodium, sodium starch glycolate, crospovidone, sucrose, vegetable gums, lactose, methylcellulose, povidone, carboxymethylcellulose, corn starch, and the like (including mixtures thereof). Preferred carriers further include calcium carbonate, magnesium stearate, maltodextrin, and mixtures thereof. The various ingredients and the excipient and/or carrier are mixed and formed into the desired form using conventional techniques. The tablet or capsule of the present invention may be coated with an enteric coating that dissolves at a pH of about 6.0 to 7.0. A suitable enteric coating that dissolves in the small intestine but not in the stomach is cellulose acetate phthalate. Further details on techniques for formulation for and administration may be found in the latest edition of Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, Pa.). Such formulations may preferably comprise from about 1 mg to 500 mg of the concentrate. Where the formulation is an oral delivery vehicle such as a capsule or tablet, the oral delivery vehicle may comprise from about 1 to 250 mg of the concentrate, 10 to 200 mg of the concentrate to 10 to 100 mg of the concentrate. A daily dosage may comprise 1, 2, 3, 4 or 5 of the oral delivery vehicles.

[0050] In other embodiments, the active agents are provided as a powder or liquid suitable for adding by the consumer to a food or beverage. For example, in some embodiments, the concentrate can be administered to an individual in the form of a powder, for instance to be used by mixing into a beverage, or by stirring into a semi-solid food such as a pudding, topping, sauce, puree, cooked cereal, or salad dressing, for instance, or by otherwise adding to a food.

[0051] In other embodiments, the compositions comprising one or more additional bioactive agents, phytonutrients, or nutraceutical agents to provide a dietary supplement. For example, the dietary supplement of the present invention may also contain optional ingredients including, for example, herbs, vitamins, minerals, enhancers, colorants, sweeteners, flavorants, inert ingredients, and the like. For example, the dietary supplement of the present invention may contain one or more of the following: ascorbates (ascorbic acid, mineral ascorbate salts, rose hips, acerola, and the like), dehydroepiandosterone (DHEA), Fo-Ti or Ho Shu Wu (herb common to traditional Asian treatments), Cat's Claw (ancient herbal ingredient), green tea (polyphenols), inositol, kelp, dulse, bioflavinoids, maltodextrin, nettles, niacin, niacinamide, rosemary, selenium, silica (silicon dioxide, silica gel, horsetail, shavegrass, and the like), spirulina, zinc, and the like. Such optional ingredients may be either naturally occurring or concentrated forms. Nutraceutical agents are natural, bioactive chemical compounds that have health promoting, disease preventing or medicinal properties. Examples of nutraceutical agents that may be combined with the concentrates of the present invention include, but are not limited to, resveratrol, fucoidan, Allium cepa, Allium sativum, Aloe vera, Angelica Species, Naturally Occurring Antioxidants, Aspergillus oryzae, barley grass, Bromelain, Carnitine, carotenoids and flavonoids, Catechin, Centella asiatica (Gotu kola), Coenzyme Q10, Chinese Prepared Medicines, Coleus forskohlii, Commiphora mukul, Conjugated Linoleic Acids (CLAs), Crataegus oxyacantha (Hawthorne), Curcuma longa (Turmeric), Echinacea Species (Purple Coneflower), Eleutherococcus senticosus (Siberian Ginseng), Ephedra Species, Dietary Fish Oil, Genistein, Ginkgo biloba, Glycyrrhiza (Licorice), Hypericum perforatum (St. John's Wort), Hydrastis (Goldenseal) and other Berberine-containing plants, Lactobacillus, Lobelia (Indian Tobacco), Melaleuca alternifolia, Menaquinone, Mentha piperita, n-glycolylneuraminic acid (NGNA), Panax ginseng, Pancreatic Enzymes, Piper mythisticum, Procyanidolic Oligomers, Pygeum africanum, Quercetin, Sarsaparilla species, Serenoa repens (Saw palmetto, Sabal serrulata), Silybum marianum (Milk Thistle), Rosemary/Lemon balm, Selenite, Tabebuia avellanedae (LaPacho), Taraxacum officinale, Tanacetum parthenium (Feverfew), Taxol, Uva ursi (Bearberry), Vaccinium myrtillus (Blueberry), Valerian officinalis, Viscum album (Mistletoe), Vitamin A, Beta-Carotene and other carotenoids, and Zingiber officinale (Ginger).

[0052] In some embodiments, the dietary supplements further comprise vitamins and minerals including, but not limited to, calcium phosphate or acetate, tribasic; potassium phosphate, dibasic; magnesium sulfate or oxide; salt (sodium chloride); potassium chloride or acetate; ascorbic acid; ferric orthophosphate; niacinamide; zinc sulfate or oxide; calcium pantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxine hydrochloride; thiamin mononitrate; folic acid; biotin; chromium chloride or picolonate; potassium iodide; sodium selenate; sodium molybdate; phylloquinone; vitamin D3; cyanocobalamin; sodium selenite; copper sulfate; vitamin A; vitamin C; inositol; potassium iodide. Suitable dosages for vitamins and minerals may be obtained, for example, by consulting the U.S. RDA guidelines.

[0053] Manufacture

[0054] The various compositions embodied herein can be manufactured using known methods.

[0055] The manufacturing of the various compositions utilizes methods of tablet compression incorporating ingredients in powder forms. The method for manufacturing the chewing gum combines the powdered ingredients with gum bases into a mixture that is then milled into a powder with a certain particle size. The powdered gum composition is compressed into a tablet using tablet presses. The method for manufacturing lozenges combines the powdered ingredients into a mixture that is then compressed into a tablet using tablet presses. The chewing gum may be compressed into either a single layer, a bi-layer or a tri-layer tablet.

[0056] Effective Doses

[0057] Effective doses of the compositions of the present invention, for the treatment of the above-described diseases, vary depending upon many different factors, including means of administration, physiological state of the patient, whether the patient is human or an animal, other medications administered, and whether treatment is prophylactic or therapeutic. Usually, the patient is a human.

[0058] The compositions can be administered on multiple occasions, wherein intervals between single dosages can be as-needed, hourly, daily, weekly, monthly, or yearly. Dosage and frequency may vary depending on the half-life of the compounds of the invention. In therapeutic applications, a relatively high dosage at relatively short intervals is sometimes required until progression of the disease is reduced or terminated, and sometimes until the patient shows partial or complete amelioration of symptoms of the disease. Thereafter, the patient can be administered a prophylactic regime.

[0059] For any active agent used in the methods of the invention, the therapeutically effective amount or dose can be estimated initially from activity assays in cell cultures and/or animals.

[0060] The pharmaceutical compositions may be sterilized and/or contain adjuvants, such as preserving, stabilizing, wetting or emulsifying agents, solution promoters, salts for regulating the osmotic pressure and/or buffers. In addition, they may also contain other therapeutically valuable substances. The compositions are prepared according to conventional mixing, granulating, or coating methods, and typically contain about 0.1% to 75%, preferably about 1% to 50%, of the active ingredient.

[0061] While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not limitation. Numerous changes to the disclosed embodiments can be made in accordance with the disclosure herein without departing from the spirit or scope of the invention. Thus, the breadth and scope of the present invention should not be limited by any of the above-described embodiments.

[0062] All publications and patent documents cited in this application are incorporated by reference for all purposes to the same extent as if each individual publication or patent document were so individually denoted. By their citation of various references in this document, applicants do not admit any particular reference is “prior art” to their invention.

REFERENCES

[0063] 1. Mythily Srinivasan, Susan L Zunt, Lawrence I Goldblatt; Oral epithelial expression of angiotensin converting enzyme-2: Implications for COVID-19 diagnosis and prognosis, bioRxiv 2020.06.22.165035 [0064] 2. Krishna Sriam, Paul Insel, Rohit Loomba; What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? The experts explain, TheConversation.com, 2021.