Nitric oxide releasing pharmaceutical compositions

Patent metadata

Field	Value
Publication number	US-11077194-B2
Application number	US-201314381370-A
Country	US
Kind code	B2
Filing date	Feb 28, 2013
Priority date	Mar 14, 2012
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

The present invention generally relates to nitric oxide releasing pharmaceutical compositions and methods of using the same.

First claim

That which is claimed is:

1. A nitric oxide (NO)-releasing pharmaceutical composition, the NO-releasing pharmaceutical composition comprising:
a hydrophobic base present in the NO-releasing pharmaceutical composition at a concentration from about 35% to about 90% by weight of the NO-releasing pharmaceutical composition;
an amphiphilic compound present in the NO-releasing pharmaceutical composition at a concentration from about 1% to about 30% by weight of the NO-releasing pharmaceutical composition, wherein the amphiphilic compound is a polyethylene glycol (PEG) caprylic/capric glyceride;
water at a concentration of less than about 2% by weight of the NO-releasing pharmaceutical composition; and
an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient consists of diazeniumdiolate-functionalized polysiloxane macromolecules that are NO-releasing co-condensed silica particles.

2. The NO-releasing pharmaceutical composition of claim 1 , wherein the amphiphilic compound has a hydrophilic-lipophilic balance (HLB) value of 12 to 20.

3. The NO-releasing pharmaceutical composition of claim 1 , wherein the amphiphilic compound absorbs moisture and does not substantially absorb vaporous moisture.

4. The NO-releasing pharmaceutical composition of claim 1 , wherein the hydrophobic base comprises at least one of mineral oil and a hydrophobic polymer.

5. The NO-releasing pharmaceutical composition of claim 1 , further comprising a cosolvent and the cosolvent is present in the NO-releasing pharmaceutical composition at a concentration from about 1% to about 30% by weight of the NO-releasing pharmaceutical composition.

6. The NO-releasing pharmaceutical composition of claim 5 , wherein the cosolvent comprises a fatty acid ester.

7. The NO-releasing pharmaceutical composition of claim 1 , further comprising a humectant and the humectant is present in the NO-releasing pharmaceutical composition at a concentration from about 1% to about 25% by weight of the NO-releasing pharmaceutical composition.

8. The NO-releasing pharmaceutical composition of claim 7 , wherein the humectant comprises a polyhydric alcohol.

9. The NO-releasing pharmaceutical composition of claim 1 , wherein the diazeniumdiolate-functionalized polysiloxane macromolecules are present in the composition at a concentration of up to about 70% by weight of the NO-releasing pharmaceutical composition.

10. The NO-releasing pharmaceutical composition of claim 1 , wherein the co-condensed silica particles have a mean particle size of less than about 10 μm.

11. The NO-releasing pharmaceutical composition of claim 1 , wherein the NO-releasing pharmaceutical composition is an ointment.

12. The NO-releasing pharmaceutical composition of claim 1 , wherein the amphiphilic compound is present in the NO-releasing pharmaceutical composition at a concentration from about 1% to less than 5% by weight of the NO-releasing pharmaceutical composition.

13. The NO-releasing pharmaceutical composition of claim 1 , wherein the hydrophobic base comprises a hydrophobic hydrocarbon polymer and mineral oil.

14. The NO-releasing pharmaceutical composition of claim 1 , wherein the amphiphilic compound comprises a PEG-6-caprylic/capric glyceride.

15. The NO-releasing pharmaceutical composition of claim 1 , wherein the hydrophobic base comprises a polysiloxane.

16. A pharmaceutical composition for topical delivery of nitric oxide, the composition comprising:
an active pharmaceutical ingredient;
a hydrophobic base comprising:
a first hydrophobic base present in the composition at a concentration from 35% to 80% by weight of the composition, wherein the first hydrophobic base comprises a hydrophobic hydrocarbon polymer; and
a second hydrophobic base present in the composition at a concentration from 1% to 20% by weight of the composition, wherein the second hydrophobic base is mineral oil; and

an amphiphilic compound present in the composition at a concentration from 1% to 20% by weight of the composition, wherein the amphiphilic compound is a polyethylene glycol (PEG) caprylic/capric glyceride;
wherein the active pharmaceutical ingredient consists of diazeniumdiolate-functionalized polysiloxane macromolecules that are nitric oxide (NO)-releasing co-condensed silica particles and the diazeniumdiolate-functionalized polysiloxane macromolecules are present in the composition at a concentration of up to 35% by weight of the composition, and
wherein the composition has a NO content in a range of 0.27% to 3.30% by weight of the composition.

17. The pharmaceutical composition of claim 16 , wherein water is present in the composition at a concentration of less than about 2%.

18. The pharmaceutical composition of claim 16 , wherein the amphiphilic compound comprises a PEG-6-caprylic/capric glyceride.

19. The pharmaceutical composition of claim 16 , wherein mineral oil is present in the composition at a concentration from 1% to 9% by weight of the composition, and the PEG caprylic/capric glyceride is present in the composition at a concentration from about 1% to less than 5% by weight of the composition.

20. The pharmaceutical composition of claim 16 , wherein mineral oil is present in the composition at a concentration from 10% to 20% by weight of the composition, and the PEG caprylic/capric glyceride is present in the composition at a concentration from about 1% to less than 5% by weight of the composition.

21. A method of treating the skin of a subject, the method comprising topically administering the NO-releasing pharmaceutical composition of claim 1 in an amount effective to treat the skin of a subject.

22. The method of claim 21 , further comprising contacting water to the pharmaceutical composition before, after, and/or during the step of topically administering the composition.

Assignees

• Novan Inc

Inventors

• Doxey Ryan

Classifications

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61L2300/22

  Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes · CPC title

• A61L26/0061

  Use of materials characterised by their function or physical properties · CPC title

• A61K9/0014

  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 title

• A61L26/0095

  Composite materials, i.e. containing one material dispersed in a matrix of the same or different material · CPC title