# US 10,500,318 B1 · Dosing regimens for treating hypoxia-associated tissue damage > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,318 B1 - Document ID: US10500318B1 - Status: Granted - Kind: B1 - Application number: 16/027,080 - Filed: 2018-07-03 - Granted: 2019-12-10 - Earliest claimed: 2018-07-03 - Assignees: Temple Therapeutics, Inc. - Applicants: Temple Therapeutics BV - Inventors: Lynne M. Robertson - Web page: https://patentgrep.com/patent/US10500318B1 ## CPC - A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)} - 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 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 38/05: Dipeptides - A61L 31/047: {Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046} - A61L 31/145: {Hydrogels or hydrocolloids} - A61L 31/148: {Materials at least partially resorbable by the body} - A61L 2300/214: Amino acids - A61L 2300/25: Peptides having up to 20 amino acids in a defined sequence - A61L 2300/412: Tissue-regenerating or healing or proliferative agents - A61L 2300/424: Anti-adhesion agents - 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) - 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) ## Abstract Described herein are methods for the treatment of hypoxia-associated tissue damage in subjects. More particularly, the methods relate to treating hypoxia-associated tissue damage in a subject during a surgical procedure with a therapeutically effective amount of a glutamine source comprising glutamine, a dipeptide comprising glutamine, or a glutamine amino ester conjugate according to particular dosing regimens. Specifically, the methods concern a dosing scheme comprising dosing a subject during a surgical procedure with a glutamine source wherein the first dose is administered to the subject within about 30 minutes following an initial surgical incision made during the surgical procedure, one or more additional doses of the glutamine source is administered at fixed intervals of time after the first dose, and one or more doses is administered just prior to closure of all surgical incisions. ## Claims ### Claim 1 A method of treating or preventing tissue adhesions in a subject that is undergoing a surgical procedure, the method comprising topically administering to the subject during the surgical procedure a therapeutically effective amount of a glutamine source comprising glutamine, a dipeptide comprising glutamine, or a glutamine amino ester conjugate to a tissue that is subject to adhesion formation, wherein a first dose of the glutamine source is administered within about 30 minutes to about 60 minutes after an initial surgical incision during the surgical procedure, one or more additional doses of the glutamine source is administered at fixed intervals of time after the first dose, and one or more doses is administered just prior to closure of the surgical incision. ### Claim 2 (depends on 1) The method of claim 1, wherein the first dose of the glutamine source is administered within about 30 minutes after the initial surgical incision. ### Claim 3 (depends on 1) The method of claim 1, wherein the first dose of the glutamine source is administered within about 60 minutes after the initial surgical incision. ### Claim 4 (depends on 3) The method of claim 3, wherein the fixed interval of time is about 15 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 90 minutes, or about 120 minutes after the first dose. ### Claim 5 (depends on 4) The method of claim 4, wherein the fixed interval of time is about 30 minutes after the first dose. ### Claim 6 (depends on 1) The method of claim 1, wherein the surgical procedure affects the abdominal cavity of the subject. ### Claim 7 (depends on 1) The method of claim 1, wherein the surgical procedure affects the thoracic cavity of the subject. ### Claim 8 (depends on 1) The method of claim 1, wherein the surgical procedure affects the head, neck, or spine of the subject. ### Claim 9 (depends on 1) The method of claim 1, wherein the surgical procedure affects one or more limbs of the subject. ### Claim 10 (depends on 1) The method of claim 1, wherein the glutamine source is L-glutamine. ### Claim 11 A method of treating or preventing hypoxia-associated tissue damage in a subject that is undergoing a surgical procedure, the method comprising topically administering to the subject during the surgical procedure a therapeutically effective amount of a glutamine source comprising glutamine, a dipeptide comprising glutamine, or a glutamine amino ester conjugate to a tissue subject to hypoxia-associated tissue damage, wherein a first dose of the glutamine source is administered within about 30 minutes to about 60 minutes after an initial surgical incision during the surgical procedure, one or more additional doses of the glutamine source is administered at fixed intervals of time after the first dose, and one or more doses is administered just prior to closure of the surgical incision. ### Claim 12 (depends on 11) The method of claim 11, wherein the first dose of the glutamine source is administered within about 30 minutes after the initial surgical incision. ### Claim 13 (depends on 11) The method of claim 11, wherein the first dose of the glutamine source is administered within about 60 minutes after the initial surgical incision. ### Claim 14 (depends on 13) The method of claim 13, wherein the fixed interval of time is about 15 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 90 minutes, or about 120 minutes after the first dose. ### Claim 15 (depends on 14) The method of claim 14, wherein the fixed interval of time is about 30 minutes after the first dose. ### Claim 16 (depends on 11) The method of claim 11, wherein the surgical procedure affects the abdominal cavity of the subject. ### Claim 17 (depends on 11) The method of claim 11, wherein the surgical procedure affects the thoracic cavity of the subject. ### Claim 18 (depends on 11) The method of claim 11, wherein the surgical procedure affects the head, neck, or spine of the subject. ### Claim 19 (depends on 11) The method of claim 11, wherein the surgical procedure affects one or more limbs of the subject. ### Claim 20 (depends on 11) The method of claim 11, wherein the glutamine source is L-glutamine. ### Claim 21 A method for reducing HIF-1α in hypoxia-associated damaged tissue in a subject that is undergoing a surgical procedure, the method comprising topically administering to the subject during the surgical procedure a therapeutically effective amount of a glutamine source comprising glutamine, a dipeptide comprising glutamine, or a glutamine amino ester conjugate to the damaged tissue, wherein a first dose of the glutamine source is administered within about 30 minutes to about 60 minutes after an initial surgical incision during the surgical procedure, one or more additional doses of the glutamine source is administered at fixed intervals of time after the first dose, and one or more doses is administered just prior to closure of the surgical incision. ### Claim 22 (depends on 21) The method of claim 21, wherein the first dose of the glutamine source is administered within about 30 minutes after the initial surgical incision. ### Claim 23 (depends on 21) The method of claim 21, wherein the first dose of the glutamine source is administered within about 60 minutes after the initial surgical incision. ### Claim 24 (depends on 21) The method of claim 21, wherein the fixed interval of time is about 15 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 90 minutes, or about 120 minutes. ### Claim 25 (depends on 21) The method of claim 21, wherein the fixed interval of time is about 30 minutes.