IP Library Granted Patent US 11,166,980
Granted Patent B2
US 11,166,980 · App. 16/091,167 · Granted Nov 9, 2021

Compositions, systems, kits, and methods for treating an infection

Inventors: Ryan Doxey (Raleigh, NC); Nathan Stasko (Chapel Hill, NC); Megan Martin (Cary, NC)
Assignee: Novan, Inc.
A61K33/00A61K9/0014A61K9/06A61K31/80A61K47/10A61K47/34A61K47/6903A61K47/6923
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Quick Facts
Patent No.
US 11,166,980
App. No.
16/091,167
Granted
Nov 9, 2021
Kind
B2
Abstract

Provided herein are compositions, systems, kits, and methods for treating a viral, bacterial, protozoan, and/or fungal (e.g., onychomycosis and/or Tinea pedis ) infection.

Claims (53)

1. An admixture comprising:

a hydrogel comprising:

a thickening agent present in an amount of about 0.1% to about 25% by weight of the hydrogel,

water present in an amount of about 50% to about 95% by weight of the hydrogel, and

a buffering agent present in an amount of about 5% to about 20% by weight of the hydrogel; and

an anhydrous gel comprising

a nitric oxide-releasing active pharmaceutical ingredient (API), wherein the nitric oxide-releasing API comprises a diazeniumdiolate-functionalized polysiloxane macromolecule,

a viscosity increasing agent present in an amount of about 0.1% to about 10% by weight of the anhydrous gel, wherein the viscosity increasing agent comprises a silicone elastomer,

a silicone emollient present in an amount of about 10% to about 30% by weight of the anhydrous gel,

a humectant present in an amount of about 10% to about 30% by weight of the anhydrous gel,

a C1-C4 alcohol present in an amount of about 1% to about 20% by weight of the anhydrous gel, and

a glycol ether present in an amount of about 20% to about 40% by weight of the anhydrous gel.

2. The admixture of claim 1 , wherein the anhydrous gel comprises at least two different viscosity increasing agents.

3. The admixture of claim 1 , wherein the nitric oxide-releasing API is present in the composition in an amount of about 0.1% to about 50% by weight of the composition.

4. The admixture of claim 1 , wherein the nitric oxide releasing compound comprises a NO-releasing co-condensed silica particle.

5. The admixture of claim 1 , wherein the viscosity increasing agent further comprises cellulose, derivatized cellulose, hydroxypropylcellulose, alginate, metallic stearates, hydrophobic and/or hydrophilic fumed silica, and any combination thereof.

6. The admixture of claim 1 , wherein the silicone emollient is selected from cyclomethicone, dimethicone, simethicone, C26-28 alkyl dimethicone, C26-28 alkyl methicone, polyphenylsisquioxane, trimethylsiloxysilicate and crosspolymers of cyclopentasiloxane and dimethicone/vinyltrimethylsiloxysilicate, and any combination thereof.

7. The admixture of claim 1 , wherein the humectant is a C1-C10 monoalkylene glycol.

8. A method of treating and/or preventing a viral, bacterial, protozoan, and/or fungal infection in and/or on a subject, the method comprising:

administering the admixture of claim 1 to the subject, thereby treating and/or preventing the viral, bacterial, protozoan, and/or fungal infection in and/or on the subject.

9. A method of treating and/or preventing a viral, bacterial, protozoan, and/or fungal infection in and/or on a subject, the method comprising:

administering the admixture of claim 1 to the subject, wherein the composition delivers a total amount of NO of at least about 50 or 100 nmol of NO/mg of the composition at about 1, 3, 5, 10, 20, 30, 40, 50, or 60 minute(s) after an initial time point as measured by in vitro release, thereby treating and/or preventing the viral, bacterial, protozoan, and/or fungal infection in and/or on the subject.

10. A method of increasing the release of nitric oxide from an anhydrous gel comprising a diazeniumdiolate functional group, the method comprising:

contacting the anhydrous gel with a hydrogel to provide an admixture; and

applying the admixture to the skin of a subject,

wherein the anhydrous gel comprises

a nitric oxide-releasing active pharmaceutical ingredient (API), wherein the nitric oxide-releasing API comprises a diazeniumdiolate-functionalized polysiloxane macromolecule,

a viscosity increasing agent present in an amount of about 0.1% to about 10% by weight of the anhydrous gel, wherein the viscosity increasing agent comprises a silicone elastomer, a silicone elastomer blend, and any combination thereof,

a silicone emollient present in an amount of about 10% to about 30% by weight of the anhydrous gel,

a humectant present in an amount of about 10% to about 30% by weight of the anhydrous gel,

a C1-C4 alcohol present in an amount of about 1% to about 20% by weight of the anhydrous gel, and

a glycol ether present in an amount of about 20% to about 40% by weight of the anhydrous gel; and

wherein the hydrogel comprises

a thickening agent present in an amount of about 0.1% to about 25% by weight of the hydrogel;

water present in an amount of about 50% to about 95% by weight of the hydrogel, and

a buffering agent present in an amount of about 5% to about 20% by weight of the hydrogel.

11. The admixture of claim 1 , wherein the hydrogel further comprises a second thickening agent that is selected from the group consisting of a carboxypolymethylene, a polyacrylic polymer and/or copolymer, a cellulose ether, a methacrylate, a polyvinylpyrollidone, a cross-linked polyvinyl pyrrolidone, a copolymer of methyl vinyl ether and maleic anhydride, a polyvinylpyrrolidone-vinyl acetate copolymer, polyvinylalcohol, polyethylene oxide, polyethylene glycol, polyvinylalkyl ether-maleic acid copolymer, a carboxy vinyl polymer, a polysaccharide, a gum, and any combination thereof.

12. The admixture of claim 1 , wherein the admixture stores and/or releases nitric oxide in an amount of about 0.15% to about 20% by weight of the anhydrous gel.

13. The admixture of claim 1 , wherein the admixture stores and/or releases about 0.1 μmol to about 7 μmol of nitric oxide per mg of the diazeniumdiolate-functionalized polysiloxane macromolecule.

14. The admixture of claim 1 , wherein the composition delivers a total amount of NO of at least about 50 or 100 nmol of NO/mg of the composition at about 1, 3, 5, 10, 20, 30, 40, 50, or 60 minute(s) after an initial time point as measured by in vitro release.

15. A kit comprising:

a hydrogel comprising:

a thickening agent present in an amount of about 0.1% to about 25% by weight of the hydrogel,

water present in an amount of about 50% to about 95% by weight of the hydrogel, and

a buffering agent present in an amount of about 5% to about 20% by weight of the hydrogel; and

an anhydrous gel comprising

a nitric oxide-releasing active pharmaceutical ingredient (API), wherein the nitric oxide-releasing API comprises a diazeniumdiolate-functionalized polysiloxane macromolecule,

a viscosity increasing agent present in an amount of about 0.1% to about 10% by weight of the anhydrous gel, wherein the viscosity increasing agent comprises a silicone elastomer, silicone elastomer blend, and any combination thereof,

a silicone emollient present in an amount of about 10% to about 30% by weight of the anhydrous gel,

a humectant present in an amount of about 10% to about 30% by weight of the anhydrous gel,

a C1-C4 alcohol present in an amount of about 1% to about 20% by weight of the anhydrous gel, and

a glycol ether present in an amount of about 20% to about 40% by weight of the anhydrous gel.

16. The admixture of claim 1 , wherein the hydrogel has a pH in a range of about 3 to about 5.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2025
From: LNHC, INC.
To: LIGAND PHARMACEUTICALS INCORPORATED
Reel/Frame 071481/0040 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 18, 2024
From: NOVAN, INC.
To: LNHC, INC.
Reel/Frame 066350/0942 →
SECURITY INTEREST Recorded Oct 18, 2023
From: CYDEX PHARMACEUTICALS, INC.; LIGAND PHARMACEUTICALS INCORPORATED; METABASIS THERAPEUTICS, INC.; PFENEX INC.
To: CITIBANK, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 065271/0025 →