# US 2016/0256381 A9 · Treatment of erectile dysfunction and other indications > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2016/0256381 A9 - Document ID: US20160256381A9 - Status: Published application - Kind: A9 - Application number: 13/977,461 - Filed: 2011-12-29 - Published: 2016-09-08 - Earliest claimed: 2010-12-29 - Assignees: Strategic Science & Technologies, LLC - Inventors: Eric T. Fossel - Web page: https://patentgrep.com/patent/US20160256381A9 ## CPC - A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) - 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 9/0034: {Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} - A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) - A61K 31/495: having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) - A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 47/02: Inorganic compounds - A61K 47/06: Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite - 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 47/16: containing nitrogen, {e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates} - A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame} - A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones - 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 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 15/10: for impotence - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention generally relates to the transdermal delivery of various compounds. In some aspects, transdermal delivery may be facilitated by the use of a hostile biophysical environment. One set of embodiments provides a composition for topical delivery comprising a phosphodiesterase type 5 inhibitor and/or a salt thereof, and optionally, a hostile biophysical environment and/or a nitric oxide donor. In some cases, the composition may be stabilized using a combination of a stabilization polymer (such as xanthan gum, KELTROL® BT and/or KELTROL® RD), propylene glycol, and a polysorbate surfactant such as Polysorbate 20, which combination unexpectedly provides temperature stability to the composition, e.g., at elevated temperatures such as at least 40° C. (at least about 104° F.), as compared to compositions lacking one or more of these. ## Claims ### Claim 1 A composition for topical delivery to the skin of a subject, the composition comprising: a nitric oxide donor comprising L-arginine and/or L-arginine hydrochloride; a hostile biophysical environment comprising an ionic salt; a stabilization polymer comprising xanthan gum; propylene glycol; a polysorbate surfactant comprising Polysorbate 20; and a phosphodiesterase type 5 inhibitor and/or a salt thereof. ### Claim 2 (canceled) ### Claim 3 (depends on 1) The composition of claim 1, wherein the composition is stable when exposed to a temperature of 40° C. for at least about 4 weeks. ### Claim at position 4 4-5. (canceled) ### Claim 6 (depends on 1) The composition of claim 1, wherein the composition is a cream. ### Claim at position 6 7-8. (canceled) ### Claim 9 (depends on 1) The composition of claim 1, wherein the composition is contained within a transdermal patch. ### Claim at position 8 10-12. (canceled) ### Claim 13 (depends on 1) The composition of claim 1, wherein the nitric oxide donor is present at a concentration of at least about 0.5% by weight of the composition. ### Claim at position 10 14-17. (canceled) ### Claim 18 (depends on 1) The composition of claim 1, wherein the ionic salt is present at a concentration of at least about 5% by weight of the composition. ### Claim at position 12 19-20. (canceled) ### Claim 21 (depends on 1) The composition of claim 1, wherein the hostile biophysical environment comprises one or more salts selected from the group consisting of sodium chloride, choline chloride, magnesium chloride, and calcium chloride. ### Claim at position 14 22-24. (canceled) ### Claim 25 (depends on 1) The composition of claim 1, wherein the hostile biophysical environment has an ionic strength of at least about 0.25 M. ### Claim 26 (depends on 1) The composition of claim 1, wherein the hostile biophysical environment has an ionic strength of at least about 1 M. ### Claim at position 17 27-31. (canceled) ### Claim 32 (depends on 1) The composition of claim 1, wherein the composition further comprises a package containing the nitric oxide donor, the package being selected from the group consisting of liposomes, emulsions of collagen, collagen peptides and combinations thereof. ### Claim at position 19 33-37. (canceled) ### Claim 38 (depends on 1) The composition of claim 1, wherein the stabilization polymer is present at a concentration of at least about 0.5% by weight of the composition. ### Claim 39 (canceled) ### Claim 40 (depends on 1) The composition of claim 1, wherein the propylene glycol is present at a concentration of at least about 1% by weight of the composition. ### Claim at position 23 41-43. (canceled) ### Claim 44 (depends on 1) The composition of claim 1, wherein the polysorbate surfactant is present at a concentration of at least about 1% by weight of the composition. ### Claim at position 25 45-52. (canceled) ### Claim 53 (depends on 1) The composition of claim 1, wherein the phosphodiesterase type 5 inhibitor is avanafil. ### Claim 54 (depends on 1) The composition of claim 1, wherein the phosphodiesterase type 5 inhibitor is lodenafil. ### Claim 55 (depends on 1) The composition of claim 1, wherein the phosphodiesterase type 5 inhibitor is mirodenafil. ### Claim 56 (depends on 1) The composition of claim 1, wherein the phosphodiesterase type 5 inhibitor is sildenafil. ### Claim 57 (depends on 1) The composition of claim 1, wherein the phosphodiesterase type 5 inhibitor is tadalafil. ### Claim 58 (depends on 1) The composition of claim 1, wherein the phosphodiesterase type 5 inhibitor is vardenafil. ### Claim 59 (depends on 1) The composition of claim 1, wherein the phosphodiesterase type 5 inhibitor is udenafil. ### Claim 60 (depends on 1) The composition of claim 1, wherein the phosphodiesterase type 5 inhibitor is acetildenafil. ### Claim 61 (depends on 1) The composition of claim 1, wherein the phosphodiesterase type 5 inhibitor is thiomethisosildenafil. ### Claim 62 (depends on 1) The composition of claim 1, wherein the a phosphodiesterase type 5 inhibitor and/or salt thereof is present at a concentration of at least about 0.1% by weight of the composition. ### Claim at position 36 63-65. (canceled) ### Claim 66 (depends on 1) A method, comprising applying the composition of claim 1 to a subject. ### Claim at position 38 67-169. (canceled) ### Claim 170 (depends on 1) The composition of claim 1, wherein the hostile biophysical environment is capable of driving the phosphodiesterase type 5 inhibitor and/or salt thereof through stratum corneum. ### Claim 171 (depends on 1) The composition of claim 1, wherein the composition has a pH of between about 5 and about 9. ### Claim 172 A composition for topical delivery to the skin of a subject, wherein at least about 80% by weight of the composition comprises: water; at least one chloride salt; a nitric oxide donor; a stabilization polymer; propylene glycol; a polysorbate surfactant; and a phosphodiesterase type 5 inhibitor and/or a salt thereof. ### Claim 173 (depends on 172) The composition of claim 172, wherein the composition further comprises glyceryl stearate. ### Claim 174 (depends on 172) The composition of claim 172, wherein the composition further comprises cetyl alcohol. ### Claim 175 (depends on 172) The composition of claim 172, wherein the composition further comprises squalane. ### Claim 176 (depends on 172) The composition of claim 172, wherein the composition further comprises isopropyl myristate. ### Claim 177 (depends on 172) The composition of claim 172, wherein the composition further comprises oleic acid. ### Claim 178 (depends on 172) The composition of claim 172, wherein the water is present at a concentration of at least about 35% by weight of the composition. ### Claim 179 (depends on 172) The composition of claim 172, wherein the water is present at a concentration of at least about 40% by weight of the composition. ### Claim 180 (depends on 172) The composition of claim 172, wherein the composition has a pH of between about 5 and about 8.5. ### Claim 181 A composition for topical delivery to the skin of a subject, the composition consisting essentially of: water; sodium chloride; a nitric oxide donor; glyceryl stearate; cetyl alcohol; magnesium chloride; squalane; a stabilization polymer; isopropyl myristate; oleic acid; propylene glycol; a polysorbate surfactant; and a phosphodiesterase type 5 inhibitor and/or a salt thereof. ### Claim 182 A composition for topical delivery to the skin of a subject, the composition comprising each of the following compounds at concentrations of no more than ±20% of the stated concentrations: water at a concentration of about 35% to about 55% by weight; sodium chloride at a concentration of about 2.5% to about 15% by weight; a nitric oxide donor at a concentration of about 2.5% to about 15% by weight; glyceryl stearate at a concentration of about 4% to about 10% by weight; cetyl alcohol at a concentration of about 4% to about 10% by weight; magnesium chloride at a concentration of about 0.1% to about 5% by weight; squalane at a concentration of about 1% to about 8% by weight; a polysorbate surfactant at a concentration of about 0.2% to about 2% by weight; isopropyl myristate at a concentration of about 0.1% to about 5% by weight; oleic acid at a concentration of about 0.1% to about 5% by weight; propylene glycol at a concentration of about 1% to about 10% by weight; a stabilization polymer at a concentration of about 1% to about 10% by weight; and a phosphodiesterase type 5 inhibitor and/or a salt thereof at a concentration of about 1% to about 10% by weight.