Claims for Patent: 10,322,081

Summary for Patent: 10,322,081

Title:	Topical antiviral compositions and methods of using the same
Abstract:	The present invention relates generally to topical antiviral compositions and methods of using the same.
Inventor(s):	McHale Kimberly, Doxey Ryan, Stasko Nathan
Assignee:	Novan, Inc.
Application Number:	US15324332
Patent Claims:	1. A method of treating and/or preventing a viral infection in skin of a subject in need thereof comprising:administering a topical composition to a surface of virally infected skin of a subject,wherein the topical composition comprises a nitric oxide-releasing active pharmaceutical ingredient that releases nitric oxide to the skin of the subject,wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a NO-releasing co-condensed silica particle including a diazeniumdiolate functional group,wherein the topical composition releases nitric oxide in a cumulative amount of at least about 90 nmol of NO/mg of the composition at 4 hours after administration, as measured by real time in vitro release testing, andwherein the topical composition maintains a real time concentration of nitric oxide of at least about 25 pmol of NO/mg of the composition for at least 30 minutes after administration, as measured by real time in vitro release testing, thereby treating and/or preventing the viral infection in the skin of the subject.2. The method of claim 1 , wherein the topical composition maintains a real time concentration of nitric oxide of at least about 6 pmol of NO/mg of the composition for at least 2 hours after administration claim 1 , as measured by real time in vitro release testing.3. The method of claim 1 , wherein the topical composition maintains a real time concentration of nitric oxide of at least about 5 pmol of NO/mg of the composition for at least 4 hours after administration claim 1 , as measured by real time in vitro release testing.4. The method of claim 1 , wherein the topical composition has a maximum concentration of nitric oxide in a range of about 12 pmol of NO/mg of the composition to about 3500 pmol of NO/mg of the composition claim 1 , as measured by real time in vitro release testing.5. The method of claim 1 , wherein the topical composition releases nitric oxide in a cumulative amount of about 300 nmol of NO/mg of the composition to about 1000 nmol of NO/mg of the composition at 24 hours after administration claim 1 , as measured by real time in vitro release testing.6. The method of claim 1 , wherein the topical composition has a half life in a range of about 9 minutes to about 420 minutes claim 1 , as measured by real time in vitro release testing.7. A method of treating and/or preventing a viral infection in skin of a subject in need thereof comprising:administering a topical composition to a surface of virally infected skin of a subject,wherein the topical composition comprises a nitric oxide-releasing active pharmaceutical ingredient that releases nitric oxide to the skin of the subject,wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a NO-releasing co-condensed silica particle including a diazeniumdiolate functional group,{'sup': '2', 'wherein the topical composition maintains a real time concentration of nitric oxide of at least about 300 pmol of NO/cmover a time period of at least 30 minutes after administration of the composition to the skin of the subject, as measured by real time in vitro release testing, and'}{'sup': 2', '2, 'wherein the topical composition releases nitric oxide in a cumulative amount of about 1300 nmol of NO/cmto about 14,000 nmol of NO/cmin a time period of about 4 hours after administration of the composition to the skin of the subject, as measured by real time in vitro release testing, thereby treating and/or preventing the viral infection in the skin of the subject.'}8. The method of claim 7 , wherein the topical composition maintains a real time concentration of nitric oxide of at least about 74 pmol of NO/cmover a time period of at least 4 hours after administration of the composition to the skin of the subject claim 7 , as measured by real time in vitro release testing.9. The method of claim 7 , wherein the topical composition releases nitric oxide in a cumulative amount of about 4500 nmol of NO/cmto about 14000 nmol of NO/cmin a time period of about 24 hours after administration of the composition to the skin of the subject claim 7 , as measured by real time in vitro release testing.10. The method of claim 7 , wherein claim 7 , after administration of the topical composition to the skin of the subject claim 7 , the topical composition has a real time concentration of at least 50 pmol of NO/cmat 1 hour after administration claim 7 , at least 40 pmol of NO/cmat 2 hours after administration claim 7 , at least 25 pmol of NO/cmat 3 hours after administration claim 7 , and/or at least 20 pmol of NO/cmat 4 hours after administration claim 7 , as measured by real time in vitro release testing.11. The method of claim 1 , wherein the topical composition does not comprise acidified nitrite.12. The method of claim 1 , wherein the viral infection is caused by cytomegalovirus (CMV) claim 1 , epstein-barr virus claim 1 , varicella zoster virus (VZV) claim 1 , vaccinia virus claim 1 , cowpox virus claim 1 , monkeypox virus claim 1 , herpes simplex virus (HSV) claim 1 , herpes zoster claim 1 , human herpes virus 6 (HHV-6) claim 1 , human herpes virus 8 (HHV-8) claim 1 , papillomavirus claim 1 , molluscum contagiosum claim 1 , orf claim 1 , variola claim 1 , and/or coxsackie virus.13. The method of claim 1 , wherein the viral infection is caused by a papillomavirus.14. The method of claim 1 , wherein the viral infection is caused by herpes simplex type 1 and/or herpes simplex type 2.15. The method of claim 1 , wherein the method prevents and/or reduces the appearance and/or size of a benign lesion.16. The method of claim 1 , wherein the method prevents and/or reduces the appearance and/or size of a malignant lesion.17. The method of claim 1 , wherein the subject is a human.18. The method of claim 1 , wherein the administering step comprises applying the topical composition to virally infected skin of the subject claim 1 , wherein the virally infected skin comprises a wart claim 1 , sore claim 1 , papilloma claim 1 , blister claim 1 , and/or rash.19. The method of claim 1 , wherein the topical composition has a pH in a range of about 5 to about 8.20. The method of claim 1 , wherein the topical composition comprises:a first viscosity increasing agent;at least one polyhydric alcohol;at least one buffer;a second viscosity increasing agent;at least one organic solvent;at least one humectant;at least one active pharmaceutical ingredient; andwater.21. The method of claim 1 , wherein the topical composition comprises two compositions that are mixed together prior to and/or during the administering step.22. The method of claim 1 , wherein a treatment effective and/or a prevention effective amount of nitric oxide is administered to the basal layer and/or basement membrane of the subject's epithelium.23. The method of claim 1 , wherein nitric oxide in an amount of about 1×10M to about 1×10M is administered to the basal layer and/or basement membrane of the subject's epithelium.24. The method of claim 1 , wherein nitric oxide is administered in an amount sufficient to induce apoptosis in virally infected cells.25. The method of claim 1 , wherein the topical composition has a Cof greater than 160 pmol of NO/mg claim 1 , as measured by in vitro release testing.26. The method of claim 1 , wherein the topical composition has a Cof about 160 pmol of NO/mg to about 3500 pmol of NO/mg claim 1 , as measured by in vitro release testing.27. The method of claim 1 , wherein the nitric oxide-releasing active pharmaceutical ingredient is present in the topical composition in an amount of about 0.5% to about 25% by weight of the topical composition.28. The method of claim 1 , wherein the topical composition stores and/or releases nitric oxide in an amount of about 0.05% to about 10% by weight of the composition.29. The method of claim 1 , wherein the topical composition releases nitric oxide in a cumulative amount of about 90 nmol of NO/mg to about 1000 nmol of NO/mg of the composition at 4 hours after administration claim 1 , as measured by real time in vitro release testing.30. The method of claim 1 , wherein the topical composition maintains a real time concentration of nitric oxide of at least about 7 pmol of NO/mg of the composition for at least 1 hour after administration claim 1 , as measured by real time in vitro release testing.31. The method of claim 7 , wherein the topical composition maintains a real time concentration of nitric oxide of at least about 104 pmol of NO/cmover a time period of at least 1 hour after administration of the composition to the skin of the subject claim 7 , as measured by real time in vitro release testing.32. The method of claim 7 , wherein the topical composition maintains a real time concentration of nitric oxide of at least about 89 pmol of NO/cmover a time period of at least 2 hours after administration of the composition to the skin of the subject claim 7 , as measured by real time in vitro release testing.33. A method of treating and/or preventing a viral infection in skin of a subject in need thereof comprising:administering a topical composition to a surface of virally infected skin of a subject,wherein the topical composition comprises a nitric oxide-releasing active pharmaceutical ingredient that releases nitric oxide to the skin of the subject,wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a NO-releasing compound including a diazeniumdiolate functional group, and a first viscosity increasing agent;', 'at least one polyhydric alcohol;', 'at least one buffer;', 'a second viscosity increasing agent;', 'at least one organic solvent;', 'at least one humectant;', 'at least one active pharmaceutical ingredient; and', 'water, and, 'wherein the topical composition compriseswherein the topical composition releases nitric oxide in a cumulative amount of at least about 90 nmol of NO/mg of the composition at 4 hours after administration, as measured by real time in vitro release testing, thereby treating and/or preventing the viral infection in the skin of the subject.