Topical gels and methods of using the same

• US 9,526,738 B2
• Filed: 08/20/2010
• Issued: 12/27/2016
• Est. Priority Date: 08/21/2009
• Status: Active Grant

• Current Assignee: LNHC Incorporated
• Original Assignee: Novan, Inc.
• Inventors: Joshi, Pranav R., Stasko, Nathan, Bauman, Susanne
• Primary Examiner(s): YOUNG, MICAH PAUL
• Application Number:
  US13/256,928
• Publication Number:
  US 20120134951A1
• Time in Patent Office: 2,321 Days
• Field of Search: 424/401, 424/402, 424/77.2, 424484-486
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/655 Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
• CPC Class Codes: A61K 31/80 Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61K 9/0014 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 Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

Provided according to some embodiments of the invention are topical gels that may release nitric oxide. Also provided are methods of using such topical gels in the treatment of wounds and other skin ailments. The topical gels comprise diazeniutndiolate-functionalized polysiloxane macromolecules.

Claims

1. A topical composition comprising nitric oxide-releasing polysiloxane macromolecules and a hydrophobic, non-aqueous gel base, the hydrophobic, non-aqueous gel base comprising mineral oil, wherein the nitric oxide (NO) storage per gram is in a range of 100 nmol NO/g to 1 mmol NO/g of the topical composition and at least 70% of NO of the nitric oxide-releasing polysiloxane macromolecule remains in the topical composition two days after initial formulation when the topical composition is stored at room temperature.

2. The topical composition of claim 1, wherein the concentration of the nitric oxide-releasing polysiloxane macromolecules is in a range of 0.1% to 20% by weight of the topical composition.

3. The topical composition of claim 1, wherein the hydrophobic, non-aqueous gel base is a silicone gel.

4. The topical composition of claim 1, wherein the hydrophobic, non-aqueous gel base comprises petrolatum.

5. The topical composition of claim 1, wherein mineral oil is present in the topical composition at a concentration in a range of 10% to 90% by weight of the topical composition.

6. The topical composition of claim 1, wherein the hydrophobic, non-aqueous gel base comprises gel excipients and the nitric oxide-releasing polysiloxane macromolecules and gel excipients have an octanol/water partition coefficient in a range of 0.1 to 7.

7. The topical composition of claim 1, wherein the nitric oxide-releasing polysiloxane macromolecules have a hydrodynamic radius in a range of 1000 nm to 10 microns.

8. The topical composition of claim 1, wherein the nitric oxide-releasing polysiloxane macromolecules have a hydrodynamic radius in a range of 1 nm to 100 nm.

9. The topical composition of claim 1, further comprising an anti-acne agent, antimicrobial agent, benzoyl peroxide, or a corticosteroid.

17. A method of treating a wound comprising applying the topical composition of claim 1.

19. A method of treating a burn comprising applying the topical composition of claim 1.

20. A method of treating acne comprising applying the topical composition of claim 1.

22. The topical composition of claim 1, wherein at least 80% of NO of the nitric oxide-releasing polysiloxane macromolecule remains in the topical composition two days after initial formulation when the topical composition is stored at room temperature.

24. The topical composition of claim 1, wherein the topical composition comprises one or more hydrophobic components and the total concentration of the one or more hydrophobic components present in the topical composition is at least 49% by weight of the topical composition.

25. The topical composition of claim 1, wherein the topical composition comprises one or more hydrophobic components and the total concentration of the one or more hydrophobic components present in the topical composition is at least 80% by weight of the topical composition.

10. A topical composition comprising nitric oxide-releasing polysiloxane macromolecules and a hydrophilic gel base, the hydrophilic gel base comprising an alcohol, wherein the nitric oxide (NO) storage per gram is in a range of 100 nmol NO/g to 1 mmol NO/g of the topical composition and at least 70% of NO of the nitric oxide-releasing polysiloxane macromolecule remains in the topical composition two days after initial formulation when the topical composition is stored at room temperature.

11. The topical composition of claim 10, wherein the concentration of the nitric oxide-releasing polysiloxane macromolecules is in a range of 0.1% to 20% by weight of the topical composition.

12. The topical composition of claim 10, further comprising isopropyl alcohol at a concentration in a range of 60% to 90% by weight of the topical composition;

and hydroxypropyl cellulose at a concentration in a range of 0.75% to 2.5% by weight of the topical composition.

13. The topical composition of claim 10, wherein the hydrophilic gel base comprises gel excipients and the nitric oxide-releasing polysiloxane macromolecules and the gel excipients have an octanol/water partition coefficient in a range of −

2 to 0.

14. The topical composition of claim 10, wherein the nitric oxide-releasing polysiloxane macromolecules have a hydrodynamic radius in a range of 1000 nm to 10 microns.

15. The topical composition of claim 10, wherein the nitric oxide-releasing polysiloxane macromolecules have a hydrodynamic radius in a range of 1 nm to 100 nm.

16. The topical composition of claim 10, further comprising a retinoid, antimicrobial agent, benzoyl peroxide, or a corticosteroid.

18. A method of treating a wound comprising applying the topical composition of claim 10.

21. A method of treating acne comprising applying the topical composition of claim 10.

23. The topical composition of claim 10, wherein at least 80% of NO of the nitric oxide-releasing polysiloxane macromolecule remains in the topical composition two days after initial formulation when the topical composition is stored at room temperature.

26. The topical composition of claim 10, wherein the alcohol is present in the topical composition at a concentration of at least 60% by weight of the topical composition.

27. The topical composition of claim 10, wherein the alcohol is present in the topical composition at a concentration in a range of 60% to 90% by weight of the topical composition.

28. The topical composition of claim 10, wherein the alcohol is isopropyl alcohol.

29. The topical composition of claim 10, wherein the hydrophilic gel base further comprises hydroxypropyl cellulose.

30. The topical composition of claim 29, wherein the hydroxypropyl cellulose is present at a concentration in a range of 0.75% to 2.5% by weight of the composition.

31. The topical composition of claim 10, wherein the topical composition is non-aqueous.