# US 11,026,917 B2 · Antioxidative stress compositions, methods of preparing and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,026,917 B2 - Document ID: US11026917B2 - Status: Granted - Kind: B2 - Application number: 16/531,264 - Filed: 2019-08-05 - Published: 2019-11-21 - Granted: 2021-06-08 - Earliest claimed: 2016-04-20 - Applicants: John Michael Pezzuto - Inventors: John Michael Pezzuto - Web page: https://patentgrep.com/patent/US11026917B2 ## CPC - A61K 31/366: having six-membered rings, e.g. delta-lactones - A23K 20/10: Organic substances - A23K 20/179: Colouring agents, e.g. pigmenting or dyeing agents - A23K 50/40: for carnivorous animals, e.g. cats or dogs - A23K 50/42: Dry feed - A61K 31/05: Phenols {(cannabinoids A61K31/658)} - A61K 31/12: Ketones - A61K 31/352: condensed with carbocyclic rings, e.g. methantheline {(cannabinoids A61K31/658)} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 9/0056: {Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals} - 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) - A23K: FODDER ## Abstract Antioxidative stress compositions, methods of using antioxidative stress composition and methods of preparing antioxidative stress composition compositions are described. The antioxidative stress compositions may be chemopreventive and/or immunomodulatory. Resveratrol, genistein, ellagic acid, curcumin and quercetin may be included in the antioxidative stress composition compositions individually or in any combination. ## Claims ### Claim 1 A dietary supplement comprising at least three active agents selected from the group consisting of resveratrol, genistein, curcumin, quercetin, and salts thereof, wherein the at least three active agents are in an amount that provides a decrease in plasma level of IL-2 after oral or intravenous administration of the dietary supplement to a mammal for three weeks, wherein the decrease in plasma level of IL-2 is below 0.4 ng/ml, resveratrol comprises from about 1% to about 80% of the dietary supplement by weight, and the dietary supplement, after said administration, provides a serum level of resveratrol of from about 3.86 ng/ml to about 154 μg/ml. ### Claim 2 (depends on 1) The dietary supplement of claim 1, which, after said administration, provides an increase in IL-10 production in the mammal. ### Claim 3 (depends on 1) The dietary supplement of claim 1, which, after said administration, provides an increase in expression of CYBB, DUS, GSR, UCP2, and VIMP genes in the mammal. ### Claim 4 (depends on 1) The dietary supplement of claim 1, which, after said administration, provides a downregulation of ATOX1, CCL5, EPX, MPV17, PRNP and SOD3 gene in the mammal. ### Claim 5 (depends on 1) The dietary supplement of claim 1, which, after said administration, provides: (i) a serum level of trans-resveratrol-4′-sulfate of from about 8.9 ng/ml to about 355 μg/ml; (ii) a serum level of trans-resveratrol-3-sulfate of from about 84.9 ng/ml to about 3397 μg/ml; (iii) a serum level of cis-resveratrol-3-sulfate of from about 2.7 ng/ml to about 108 μg/ml; and (iv) a serum level of resveratrol sulfate total of from about 36.7 ng/ml to about 1467 μg/ml. ### Claim 6 (depends on 1) The dietary supplement of claim 1, wherein the dietary supplement comprises resveratrol or a salt thereof, genistein or a salt thereof, curcumin or a salt thereof, and quercetin or a salt thereof; resveratrol comprises from about 1% to about 80% of the dietary supplement by weight, genistein comprises from about 0.5% to about 40% of the dietary supplement by weight, curcumin comprises from about 1% to about 80% of the dietary supplement by weight, and quercetin comprises from about 1% to about 80% of the dietary supplement by weight; and the dietary supplement provides: (i) a mean serum level of resveratrol of from about 3.86 ng/ml to about 154 μg/ml; (ii) a mean serum level of resveratrol-3-O-glucuronide of from about 12.9 ng/ml to about 514 μg/ml; (iii) a mean serum level of trans-resveratrol-4′-sulfate of from about 8.9 ng/ml to about 355 μg/ml; (iv) a mean serum level of trans-resveratrol-3-sulfate of from about 84.9 ng/ml to about 3397 μg/ml; (v) a mean serum level of cis-resveratrol-3-sulfate of from about 2.7 ng/ml to about 108 μg/ml; (vi) a mean serum level of resveratrol sulfate total of from about 36.7 ng/ml to about 1467 μg/ml; (vii) a mean serum level of genistein-4′-glucuronide of from about 14 μg/ml to about 14167 μg/ml; (viii) a mean serum level of genistein-4′-glucuronide of from about 1.7 μg/ml to about 1700 μg/ml; (ix) a mean serum level of genistein sulfate of from about 54 μg/ml to about 53836 μg/ml; (x) a mean serum level of curcumin glucuronide of from about 6.25 ng/ml to about 250 μg/ml; and (xi) a mean serum level of quercetin of from about 0.2 ng/ml to about 8000 μg/ml, based on oral administration of the dietary supplement to a group of eight mammals. ### Claim 7 (depends on 1) The dietary supplement of claim 1, further comprising flour. ### Claim 8 (depends on 1) The dietary supplement of claim 1, further comprising beef bouillon cubes. ### Claim 9 (depends on 6) The dietary supplement of claim 6, wherein the mammal is a dog. ### Claim 10 (depends on 1) The dietary supplement of claim 1, which is in a form of a tablet. ### Claim 11 A dietary supplement comprising resveratrol or a salt thereof, genistein or a salt thereof, curcumin or a salt thereof, and quercetin or a salt thereof in an amount that provides (i) an increase in expression of CYBB, DUS, GSR, UCP2, and VIMP genes, (ii) a downregulation of ATOX1, CCL5, EPX, MPV17, PRNP and SOD3 gene, after administration of the dietary supplement to a mammal for three weeks, and (iii) a decrease in plasma level of IL-2, wherein the decrease in plasma level of IL-2 is below 0.4 ng/ml resveratrol comprises from about 1% to about 80% of the dietary supplement by weight, genistein comprises from about 0.5% to about 40% of the dietary supplement by weight, curcumin comprises from about 1% to about 80% of the dietary supplement by weight, and quercetin comprises from about 1% to about 80% of the dietary supplement by weight, and the dietary supplement provides (i) a mean serum level of resveratrol of from about 3.86 ng/ml to about 154 μg/ml; (ii) a mean serum level of resveratrol-3-O-glucuronide of from about 12.9 ng/ml to about 514 μg/ml; (iii) a mean serum level of trans-resveratrol-4′-sulfate of from about 8.9 ng/ml to about 355 μg/ml; (iv) a mean serum level of trans-resveratrol-3-sulfate of from about 84.9 ng/ml to about 3397 μg/ml; (v) a mean serum level of cis-resveratrol-3-sulfate of from about 2.7 ng/ml to about 108 μg/ml; (vi) a mean serum level of resveratrol sulfate total of from about 36.7 ng/ml to about 1467 μg/ml; (vii) a mean serum level of genistein-4′-glucuronide of from about 14 μg/ml to about 14167 μg/ml; (viii) a mean serum level of genistein-4′-glucuronide of from about 1.7 μg/ml to about 1700 μg/ml; (ix) a mean serum level of genistein sulfate of from about 54 μg/ml to about 53836 μg/ml; (x) a mean serum level of curcumin glucuronide of from about 6.25 ng/ml to about 250 μg/ml; and (xi) a mean serum level of quercetin of from about 0.2 ng/ml to about 8000 μg/ml, based on oral administration of the dietary supplement to a group of eight mammals. ### Claim 12 (depends on 11) The dietary supplement of claim 11, wherein the mammal is a dog. ### Claim 13 (depends on 11) The dietary supplement of claim 11, further comprising beef bouillon cubes. ### Claim 14 (depends on 11) The dietary supplement of claim 11, further comprising flour. ### Claim 15 A dietary supplement comprising resveratrol or a salt thereof, genistein or a salt thereof, curcumin or a salt thereof, and quercetin or a salt thereof in an amount that provides (i) a decrease in plasma level of IL-2, (ii) an increase in plasma level of IFN-γ and (iii) a decrease in plasma level of IL-2, after oral or intravenous administration of the dietary supplement to the mammal for three weeks, wherein the decrease in plasma level of IL-2 is below 0.4 ng/ml, and after said administration, the dietary supplement provides (i) a mean serum level of resveratrol of from about 3.86 ng/ml to about 154 μg/ml; (ii) a mean serum level of resveratrol-3-O-glucuronide of from about 12.9 ng/ml to about 514 μg/ml; (iii) a mean serum level of trans-resveratrol-4′-sulfate of from about 8.9 ng/ml to about 355 μg/ml; (iv) a mean serum level of trans-Resveratrol-3-sulfate of from about 84.9 ng/ml to about 3397 μg/ml; (v) a mean serum level of cis-resveratrol-3-sulfate of from about 2.7 ng/ml to about 108 μg/ml; (vi) a mean serum level of resveratrol sulfate total of from about 36.7 ng/ml to about 1467 μg/ml; (vii) a mean serum level of genistein-4′-glucuronide of from about 14 μg/ml to about 14167 μg/ml; (viii) a mean serum level of genistein-4′-glucuronide of from about 1.7 μg/ml to about 1700 μg/ml; (ix) a mean serum level of genistein sulfate of from about 54 μg/ml to about 53836 μg/ml; (x) a mean serum level of curcumin glucuronide of from about 6.25 ng/ml to about 250 μg/ml; and (xi) a mean serum level of quercetin of from about 0.2 ng/ml to about 8000 μg/ml, based on oral administration of the dietary supplement to a group of eight mammals. ### Claim 16 (depends on 15) The dietary supplement of claim 15, which is a dog biscuit.