Topical antiviral compositions, delivery systems, and methods of using the same

Patent metadata

Field	Value
Publication number	US-10736839-B2
Application number	US-201916431214-A
Country	US
Kind code	B2
Filing date	Jun 4, 2019
Priority date	Jul 11, 2014
Publication date	Aug 11, 2020
Grant date	Aug 11, 2020

Abstract

The present invention relates generally to topical antiviral compositions, delivery systems, and methods of using the same.

First claim

That which is claimed is:

1. A method of treating and/or preventing a viral infection in a subject in need thereof comprising:
administering a topical composition to the skin of a subject,
wherein the topical composition comprises a nitric oxide (NO)-releasing active pharmaceutical ingredient in an amount of about 0.5% to about 25% by weight of the topical composition and the NO-releasing active pharmaceutical ingredient is a NO-releasing compound comprising an NO donor selected from the group consisting of a diazeniumdiolate, nitrosothiol, nitrosamine, hydroxyl nitrosamine, hydroxyl amine and hydroxyurea; and
wherein the topical composition has a C max of greater than 160 pmol of NO/mg, as measured by in vitro release testing, thereby treating and/or preventing the viral infection in the subject.

2. The method of claim 1 , wherein the topical composition has a C max of greater than 175 pmol of NO/mg, as measured by in vitro release testing.

3. The method of claim 1 , wherein the topical composition has a C max of greater than 200 pmol of NO/mg, as measured by in vitro release testing.

4. The method of claim 1 , wherein the topical composition has a C max of greater than 160 pmol to about 3500 pmol of NO/mg, as measured by in vitro release testing.

5. The method of claim 1 , wherein the topical composition releases nitric oxide in an amount of about 0.05% to about 10% by weight of the topical composition, as measured by real time in vitro release testing.

6. The method of claim 1 , wherein the topical composition releases nitric oxide in a cumulative amount of about 10 nmol of NO/mg of the topical composition to 1000 nmol of NO/mg of the topical composition in a time period of 1 hour after administration of the topical composition to the skin of the subject, as measured by real time in vitro release testing.

7. The method of claim 1 , wherein the topical composition releases nitric oxide in a cumulative amount of about 90 nmol of NO/mg of the topical composition to 450 nmol of NO/mg of the topical composition in a time period of 4 hours after administration of the topical composition to the skin of the subject, as measured by real time in vitro release testing.

8. The method of any one of claim 1 , wherein the topical composition releases nitric oxide in a cumulative amount of about 180 nmol of NO/mg of the topical composition to 1000 nmol of NO/mg of the topical composition in a time period of 24 hours after administration of the topical composition to the skin of the subject, as measured by real time in vitro release testing.

9. The method of claim 1 , wherein the topical composition provides a continuous release of nitric oxide for at least about 5 hours after administration of the topical composition to the skin of the subject, as measured by real time in vitro release testing.

10. The method of claim 9 , wherein, during the continuous release of nitric oxide, the topical composition has a release of NO that, on average, is in a range of about 1 to about 500 pmol of NO/mg of the composition, as measured by real time in vitro release testing.

11. The method of claim 1 , wherein the nitric oxide-releasing active pharmaceutical ingredient releases nitric oxide in an amount of at least about 50% in about 9 minutes or more after administration of the topical composition to the skin of the subject, based on a total NO release determined at 24 hours after administration and measured by real time in vitro release testing.

12. The method of claim 1 , wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a co-condensed silica network comprising diazeniumdiolated methylaminopropyl trimethoxysilane (MAP3) and tetra methyl orthosilicate (TMOS) and/or diazeniumdiolated methylaminopropyl trimethoxysilane (MAP3) and tetraethyl orthosilicate (TEOS).

13. A method of treating and/or preventing molluscum contagiosum in a subject in need thereof comprising:
administering a topical composition to the skin of a subject,
wherein the topical composition comprises a nitric oxide (NO)-releasing active pharmaceutical ingredient in an amount of about 0.5% to about 25% by weight of the topical composition and the NO-releasing active pharmaceutical ingredient is a NO-releasing compound comprising an NO donor selected from the group consisting of a diazeniumdiolate, nitrosothiol, nitrosamine, hydroxyl nitrosamine, hydroxyl amine and hydroxyurea; and
wherein the topical composition has a C max of greater than 160 pmol of NO/mg, as measured by in vitro release testing, thereby treating and/or preventing molluscum contagiosum in the subject.

14. A method of reducing the appearance and/or size of a lesion on a subject in need thereof comprising:
administering a topical composition to the lesion on the subject,
wherein the topical composition comprises a nitric oxide (NO)-releasing active pharmaceutical ingredient in an amount of about 0.5% to about 25% by weight of the topical composition and the NO-releasing active pharmaceutical ingredient is a NO-releasing compound comprising an NO donor selected from the group consisting of a diazeniumdiolate, nitrosothiol, nitrosamine, hydroxyl nitrosamine, hydroxyl amine and hydroxyurea; and
wherein the topical composition has a C max of greater than 160 pmol of NO/mg, as measured by in vitro release testing, thereby reducing the appearance and/or size of the lesion on the subject.

15. The method of claim 14 , wherein the lesion is caused by cytomegalovirus (CMV), epstein-barr virus, varicella zoster virus (VZV), vaccinia virus, cowpox virus, monkeypox virus, herpes simplex virus (HSV), herpes zoster, human herpes virus 6 (HHV-6), human herpes virus 8 (HHV-8), papillomavirus, molluscum contagiosum, orf, variola, and/or coxsackie virus.

16. The method of claim 15 , wherein the lesion is caused by a papillomavirus.

17. The method of claim 15 , wherein the lesion is caused by herpes simplex type 1 and/or herpes simplex type 2.

18. The method of claim 15 , wherein the lesion is caused by molluscum contagiosum.

19. The method of claim 14 , wherein the lesion is a benign lesion.

20. The method of claim 14 , wherein the lesion is a malignant lesion.

Assignees

• Novan Inc

Inventors

• Mchale Kimberly
• Doxey Ryan
• Stasko Nathan

Classifications

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• A61K47/44

  Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14) · CPC title

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title

• A61K9/0014 Primary

  Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00) · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title