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