# US 10,307,437 B2 · Methods for treatment of vascular endothelial dysfunction using nicotinamide mononucleotide > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,307,437 B2 - Document ID: US10307437B2 - Status: Granted - Kind: B2 - Application number: 15/126,548 - Filed: 2015-03-24 - Published: 2017-03-30 - Granted: 2019-06-04 - Earliest claimed: 2014-03-24 - Assignees: The Regents of the University of Colorado, a body corporate - Applicants: The Regents of the University of Colorado, a Body Corporate - Inventors: Douglas R. Seals; Lindsey Gano; Natalie Poliektor - Web page: https://patentgrep.com/patent/US10307437B2 ## CPC - A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom - A61P 39/00: General protective or antinoxious agents - 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 This invention is about the compositions and methods for assessing and treating vascular endothelial dysfunction. Various aspects provide a method for treatment of vascular endothelial dysfunction, comprising administering a composition comprising nicotinamide mononucleotide and a pharmaceutical excipient to a subject. In one embodiment the dose is administered to subjects in response to the indicator. In another embodiment the dose is administered chronically to subjects. ## Claims ### Claim 1 A method for treatment of vascular endothelial dysfunction, comprising: determining an indicator of vascular endothelial dysfunction in a subject, wherein the indicator is selected from a group consisting of: endothelium-dependent dilation; artery stiffness; and aortic pulse wave velocity; and administering a daily dose of a composition comprising nicotinamide mononucleotide and a pharmaceutical excipient, wherein the composition comprises from about 1 mg to about 25 mg of nicotinamide mononucleotide per kg body weight per day and wherein the composition is administered chronically to said subject in response to the indicator. ### Claim 2 (depends on 1) The method of claim 1, further comprising determining a subsequent effect on vascular endothelial dysfunction in the subject. ### Claim 3 (depends on 1) The method of claim 1, wherein the endothelium-dependent dilation is associated with increased superoxide production. ### Claim 4 (depends on 1) The method of claim 1, wherein the endothelium-dependent dilation is associated with decreased SIRT1 expression. ### Claim 5 (depends on 1) The method of claim 1, wherein extent of endothelium-dependent dilation and/or artery stiffness is decreased in response to administration of the composition comprising nicotinamide mononucleotide. ### Claim 6 (depends on 5) The method of claim 5, wherein the decrease in the extent of endothelium-dependent dilation further comprises a decrease in superoxide production and an increase in nitric oxide bioavailability. ### Claim 7 (depends on 5) The method of claim 5, wherein the decrease in the extent of endothelium-dependent dilation further comprises an increase in SIRT1 protein expression and activity. ### Claim 8 (depends on 1) The method of claim 1, wherein the composition is administered over a period of time of about 30 days, about 3 months, about 6 months, about 12 months, about 18 months, about 2 years, about 5 years, about 7 years, about 10 years, about 15 years, about 20 years, about 25 years, about 30 years, about 35 years, about 40 years, or continued therapy over the lifetime of the subject. ### Claim 9 (depends on 1) The method of claim 1, wherein the composition comprises about 18 mg of nicotinamide mononucleotide per kg body weight per day. ### Claim 10 A method of decreasing the extent of endothelium-dependent dilation and/or arterial stiffness in a subject, comprising: determining the extent of endothelium-dependent dilation and/or arterial stiffness in a subject, wherein the indicator is selected from a group consisting of: endothelium-dependent dilation; artery stiffness; and aortic pulse wave velocity; and administering a daily dose of a composition comprising nicotinamide mononucleotide and a pharmaceutical excipient wherein the composition comprises from about 1 mg to about 25 mg of nicotinamide mononucleotide per kg body weight per day and wherein the composition is administered chronically to said subject. ### Claim 11 (depends on 10) The method of claim 10, wherein a decrease in the extent of endothelium-dependent dilation and/or arterial stiffness is associated with an increase in bioavailability of nicotinamide adenine dinucleotide (NAD+). ### Claim 12 (depends on 11) The method of claim 11, wherein a decrease in the extent of endothelium-dependent dilation and/or arterial stiffness further comprises a decrease in superoxide production, an increase in bioavailability of nitric oxide, and/or an increase in SIRT1 protein expression and activity. ### Claim 13 (depends on 10) The method of claim 10, wherein the composition comprises about 18 mg of nicotinamide mononucleotide per kg body weight per day. ### Claim 14 A method for modulating endothelium-dependent dilation and/or arterial stiffness in a subject, comprising: administering a daily dose of a composition comprising nicotinamide mononucleotide and a pharmaceutical excipient wherein the composition comprises from about 1 mg to about 25 mg of nicotinamide mononucleotide per kg body weight per day and wherein the composition is administered chronically to said subject. ### Claim 15 (depends on 14) The method of claim 14, wherein the extent of endothelium-dependent dilation is associated with increased superoxide production. ### Claim 16 (depends on 14) The method of claim 14, wherein the extent of endothelium-dependent dilation is associated with decreased SIRT1 expression. ### Claim 17 (depends on 14) The method of claim 14, wherein the extent of endothelium-dependent dilation and/or artery stiffness is decreased in response to administration of the composition comprising nicotinamide mononucleotide. ### Claim 18 (depends on 14) The method of claim 14, wherein the extent of endothelium-dependent dilation further comprises a decrease in superoxide production and an increase in nitric oxide bioavailability. ### Claim 19 (depends on 14) The method of claim 14, wherein the extent of endothelium-dependent dilation further comprises an increase in SIRT1 protein expression and activity. ### Claim 20 (depends on 14) The method of claim 14, wherein the composition is administered over a period of time of about 30 days, about 3 months, about 6 months, about 12 months, about 18 months, about 2 years, about 5 years, about 7 years, about 10 years, about 15 years, about 20 years, about 25 years, about 30 years, about 35 years, about 40 years, or continued therapy over the lifetime of the subject. ### Claim 21 (depends on 14) The method of claim 14, wherein the composition comprises about 18 mg of nicotinamide mononucleotide per kg body weight per day.