# US 11,077,194 B2 · Nitric oxide releasing pharmaceutical compositions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,194 B2 - Document ID: US11077194B2 - Status: Granted - Kind: B2 - Application number: 14/381,370 - Filed: 2013-02-28 - Published: 2015-01-22 - Granted: 2021-08-03 - Earliest claimed: 2012-03-14 - Assignees: Novan, Inc. - Applicants: Novan, Inc. - Inventors: Ryan Doxey - Web page: https://patentgrep.com/patent/US11077194B2 ## CPC - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - 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)} - A61K 33/00: Medicinal preparations containing inorganic active ingredients - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - A61K 47/26: 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 - A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) - A61K 47/38: Cellulose; Derivatives thereof - A61K 47/44: 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) - A61L 26/0004: {containing inorganic materials} - A61L 26/0019: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds} - A61L 26/0061: {Use of materials characterised by their function or physical properties} - A61L 26/0066: {Medicaments; Biocides} - A61L 26/0095: {Composite materials, i.e. containing one material dispersed in a matrix of the same or different material} - A61P 17/00: Drugs for dermatological disorders - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61L 2300/114: Nitric oxide, i.e. NO - A61L 2300/22: Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention generally relates to nitric oxide releasing pharmaceutical compositions and methods of using the same. ## Claims ### Claim 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. ### Claim 2 (depends on 1) The NO-releasing pharmaceutical composition of claim 1, wherein the amphiphilic compound has a hydrophilic-lipophilic balance (HLB) value of 12 to 20. ### Claim 3 (depends on 1) The NO-releasing pharmaceutical composition of claim 1, wherein the amphiphilic compound absorbs moisture and does not substantially absorb vaporous moisture. ### Claim 4 (depends on 1) The NO-releasing pharmaceutical composition of claim 1, wherein the hydrophobic base comprises at least one of mineral oil and a hydrophobic polymer. ### Claim 5 (depends on 1) 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. ### Claim 6 (depends on 5) The NO-releasing pharmaceutical composition of claim 5, wherein the cosolvent comprises a fatty acid ester. ### Claim 7 (depends on 1) 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. ### Claim 8 (depends on 7) The NO-releasing pharmaceutical composition of claim 7, wherein the humectant comprises a polyhydric alcohol. ### Claim 9 (depends on 1) 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. ### Claim 10 (depends on 1) 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. ### Claim 11 (depends on 1) The NO-releasing pharmaceutical composition of claim 1, wherein the NO-releasing pharmaceutical composition is an ointment. ### Claim 12 (depends on 1) 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. ### Claim 13 (depends on 1) The NO-releasing pharmaceutical composition of claim 1, wherein the hydrophobic base comprises a hydrophobic hydrocarbon polymer and mineral oil. ### Claim 14 (depends on 1) The NO-releasing pharmaceutical composition of claim 1, wherein the amphiphilic compound comprises a PEG-6-caprylic/capric glyceride. ### Claim 15 (depends on 1) The NO-releasing pharmaceutical composition of claim 1, wherein the hydrophobic base comprises a polysiloxane. ### Claim 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. ### Claim 17 (depends on 16) The pharmaceutical composition of claim 16, wherein water is present in the composition at a concentration of less than about 2%. ### Claim 18 (depends on 16) The pharmaceutical composition of claim 16, wherein the amphiphilic compound comprises a PEG-6-caprylic/capric glyceride. ### Claim 19 (depends on 16) 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. ### Claim 20 (depends on 16) 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. ### Claim 21 (depends on 1) 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. ### Claim 22 (depends on 21) 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.