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

Patent metadata

Field	Value
Publication number	US-12403087-B2
Application number	US-202318340177-A
Country	US
Kind code	B2
Filing date	Jun 23, 2023
Priority date	Jul 11, 2014
Publication date	Sep 2, 2025
Grant date	Sep 2, 2025

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 delivery system comprising a composition comprising a nitric oxide (NO)-releasing active pharmaceutical ingredient,
wherein 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 the NO-releasing active pharmaceutical ingredient is present in the composition in an amount of 0.01% to 30% by weight of the composition,
wherein the composition stores and/or releases nitric oxide in an amount of about 0.05% to about 10% by weight of the composition, wherein the delivery system releases nitric oxide in a cumulative amount of at least about 90 nmol of NO/mg of the delivery system at 4 hours after administration, as measured by real time in vitro release testing, and
wherein the delivery system is in the form of a ring, suppository, and/or sponge.

2. The delivery system of claim 1 , further comprising a substrate, and wherein the composition is provided in and/or on the substrate.

3. The delivery system of claim 1 , wherein the delivery system is configured to contact the composition to the skin and/or nail of a subject.

4. The delivery system of claim 1 , wherein the nitric oxide-releasing active pharmaceutical ingredient comprises a nitric oxide-releasing compound including a diazeniumdiolate functional group.

5. The delivery system of claim 4 , wherein the nitric oxide releasing compound comprises a NO-releasing co-condensed silica particle.

6. The delivery system of claim 1 , wherein the composition has a pH of about 5 to about 11.

7. The delivery system of claim 1 , wherein the delivery system administers nitric oxide in an amount sufficient to induce apoptosis in virally infected cells.

8. The delivery system of claim 1 , wherein the delivery system administers nitric oxide in an amount sufficient to reduce or eliminate viral replication with less than about 50% host cell cytotoxicity.

9. A delivery system comprising a nitric oxide-releasing active pharmaceutical ingredient,
wherein the nitric oxide-releasing active pharmaceutical ingredient is a diazeniumdiolate-functionalized macromolecule and is present in the delivery system in an amount of 0.01% to 30% by weight of the delivery system,
wherein the delivery system releases nitric oxide in a cumulative amount of at least about 90 nmol of NO/mg of the delivery system at 4 hours after administration, as measured by real time in vitro release testing, and
wherein the delivery system comprises a ring, suppository, and/or sponge that is configured to administer nitric oxide to a cell of a subject.

10. The delivery system of claim 9 , further comprising a substrate, and wherein the nitric oxide-releasing active pharmaceutical ingredient is in and/or on the substrate.

11. The delivery system of claim 9 , wherein the delivery system is configured to contact the nitric oxide-releasing active pharmaceutical ingredient to the skin and/or nail of a subject.

12. The delivery system of claim 9 , wherein the nitric oxide releasing compound comprises a NO-releasing co-condensed silica particle.

13. The delivery system of claim 9 , wherein the delivery system administers nitric oxide in an amount sufficient to induce apoptosis in virally infected cells.

14. The delivery system of claim 9 , wherein the delivery system administers nitric oxide in an amount sufficient to reduce or eliminate viral replication with less than about 50% host cell cytotoxicity.

15. A method of administering nitric oxide to a subject, the method comprising:
contacting a delivery system to the skin and/or nail of the subject, wherein the delivery system comprises a ring, suppository, and/or sponge and comprises a nitric oxide-releasing active pharmaceutical ingredient,
wherein the nitric oxide-releasing active pharmaceutical ingredient is a diazeniumdiolate-functionalized macromolecule and is present in the delivery system in an amount of 0.01% to 30% by weight of the delivery system, and
wherein the delivery system releases nitric oxide in a cumulative amount of at least about 90 nmol of NO/mg of the delivery system at 4 hours after administration, as measured by real time in vitro release testing, thereby administering nitric oxide to the subject.

16. The method of claim 15 , wherein the delivery system further comprises a substrate and the nitric oxide-releasing active pharmaceutical ingredient is in and/or on the substrate.

17. The method of claim 15 , wherein the delivery system is configured for delivery to a body cavity of a subject.

18. The method of claim 15 , wherein the nitric oxide releasing compound comprises a NO-releasing co-condensed silica particle.

19. The method of claim 15 , wherein the delivery system is configured to administer nitric oxide to the skin and/or nail of the subject.

20. The method of claim 15 , wherein the delivery system administers nitric oxide in an amount sufficient to reduce or eliminate viral replication in the virally infected cell with less than about 50% host cell cytotoxicity.

21. The delivery system of claim 1 , wherein the NO-releasing compound comprises diazeniumdiolated co-condensed silica particles comprising a co-condensed silica network comprising methylaminopropyl trimethoxysilane (MAP3) and tetraethyl orthosilicate (TEOS).

22. The delivery system of claim 1 , wherein the NO-releasing compound comprises diazeniumdiolated co-condensed silica particles comprising a co-condensed silica network comprising methylaminopropyl trimethoxysilane (MAP3) and tetramethyl orthosilicate (TMOS).

23. The delivery system of claim 1 , wherein the NO-releasing compound comprises diazeniumdiolated co-condensed silica particles comprising a co-condensed silica network comprising N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (AEAP3) and tetraethyl orthosilicate (TEOS).

24. The delivery system of claim 1 , wherein the NO-releasing compound comprises diazeniumdiolated co-condensed silica particles comprising a co-condensed silica network comprising N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (AEAP3) and tetramethyl orthosilicate (TMOS).

Assignees

• Ligand Pharm Inc

Inventors

• Mchale Kimberly
• Doxey Ryan
• Stasko Nathan

Classifications

• A61K31/675

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

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · 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

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title