# US 10,864,184 B1 · Metabolic therapy for wound healing > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,864,184 B1 - Document ID: US10864184B1 - Status: Granted - Kind: B1 - Application number: 14/554,172 - Filed: 2014-11-26 - Granted: 2020-12-15 - Earliest claimed: 2013-11-27 - Assignees: University of South Florida - Applicants: University of South Florida - Inventors: Dominic Paul D'Agostino; Shannon Kesl - Web page: https://patentgrep.com/patent/US10864184B1 ## CPC - A61K 31/231: having one or two double bonds - A61K 31/047: having two or more hydroxy groups, e.g. sorbitol - A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) - 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 31/22: of acyclic acids, e.g. pravastatin - A61K 36/889: Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto - A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like - 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 Ketone supplementation, such as through use of precursors of beta-hydroxybutyrate (BHB) and acetoacetate (AcAc), increased blood levels of ketone bodies, increases blood flow and wound closure in ischemic young and aged fisher rats significantly earlier compared to standard diet in aged rats. In vitro experiments with ketone bodies demonstrate decreased mitochondrial and cytosolic ROS in young and aged primary human dermal fibroblasts (PHDF). Ketone bodies increased migration in young and aged PHDFs. ## Claims ### Claim 1 A method of improving wound healing, comprising: orally, intragastrically, intraarterially, or intravenously administering at least one ketone source to a patient, in need thereof wherein the at least one ketone source includes 1,3-butanediol and is administered to obtain ketosis in the patient; wherein the patient has a wound, and wherein the patient is fed ad libitum and is not on a ketogenic diet. ### Claim 2 (depends on 1) The method of claim 1, wherein the at least one ketone source further comprises beta-hydroxybutyrate precursor, acetoacetate, acetoacetate precursor, or at least one medium chain triglycerides or beta-hydroxybutyrate mineral salt. ### Claim 3 (depends on 2) The method of claim 2, wherein the beta-hydroxybutyrate precursor is a beta-hydroxybutyrate salt. ### Claim 4 (depends on 3) The method of claim 3, wherein the beta-hydroxybutyrate salt is sodium beta-hydroxybutyrate, arginine beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxybutyrate, magnesium beta-hydroxybutyrate, lithium beta-hydroxybutyrate, lysine beta-hydroxybutyrate, histidine beta-hydroxybutyrate, ornithine beta-hydroxybutyrate, creatine beta-hydroxybutyrate, agmatine beta-hydroxybutyrate, citrulline beta-hydroxybutyrate, beta-hydroxy butyrate sodium salt, beta-hydroxy butyrate potassium salt, beta-hydroxy butyrate calcium salt, beta-hydroxy butyrate magnesium salt, or a combination thereof. ### Claim 5 (depends on 4) The method of claim 4, wherein the at least one ketone source is a racemic DL-beta hydroxybutyrate precursor or a single isomer R-beta hydroxybutyrate precursor. ### Claim 6 (depends on 2) The method of claim 2, wherein the β-hydroxybutyrate precursor is ethyl acetoacetate or ethyl beta-hydroxybutyrate. ### Claim 7 (depends on 2) The method of claim 2, wherein the β-hydroxybutyrate precursor is administered at between 2 grams and 50 grams. ### Claim 8 (depends on 1) The method of claim 1, wherein the at least one ketone source is administered at about 1 g/kg/day to about 10 g/kg/day. ### Claim 9 (depends on 2) The method of claim 2, wherein the at least one medium chain triglyceride is coconut oil, coconut milk powder, fractionated coconut oil, palm oil, palm kernel oil, caprylic acid, isolated hexanoic acid, isolated octanoic acid, isolated decanoic acid, esterified ester derivatives thereof, ethoxylated derivatives thereof, enone-ylated derivatives thereof, aldehyde derivatives thereof, monoglyceride derivatives thereof, diglyceride derivatives thereof, and triglyceride derivatives thereof, salt derivatives thereof, or a combination thereof. ### Claim 10 (depends on 9) The method of claim 9, wherein the at least one medium chain triglyceride is optionally administered at between 5 grams and 50 grams. ### Claim 11 A method of reducing or treating redox stress in wound repair, comprising: orally, intragastrically, intraarterially, or intravenously administering at least one ketone source to a patient, in need thereof wherein the at least one ketone source includes 1,3-butanediol and is administered to obtain ketosis in the patient; wherein the patient has a wound, and wherein the patient is fed ad libitum and is not on a ketogenic diet. ### Claim 12 (depends on 11) The method of claim 11, wherein the ketone source further comprises beta-hydroxybutyrate precursor, acetoacetate, acetoacetate precursor, or at least one medium chain triglycerides or beta-hydroxybutyrate mineral salt. ### Claim 13 (depends on 12) The method of claim 12, wherein the beta-hydroxybutyrate precursor is a beta-hydroxybutyrate salt. ### Claim 14 (depends on 13) The method of claim 13, wherein the beta-hydroxybutyrate salt is sodium beta-hydroxybutyrate, arginine beta-hydroxybutyrate, potassium beta-hydroxybutyrate, calcium beta-hydroxy butyrate, magnesium beta-hydroxybutyrate, lithium beta-hydroxybutyrate, lysine beta-hydroxybutyrate, histidine beta-hydroxybutyrate, ornithine beta-hydroxybutyrate, creatine beta-hydroxybutyrate, agmatine beta-hydroxybutyrate, citrulline beta-hydroxybutyrate, beta-hydroxy butyrate sodium salt, beta-hydroxy butyrate potassium salt, beta-hydroxy butyrate calcium salt, beta-hydroxy butyrate magnesium salt, or a combination thereof. ### Claim 15 (depends on 11) The method of claim 11, wherein the ketone source further comprises a racemic DL-beta hydroxybutyrate precursor or a single isomer R-beta hydroxybutyrate precursor. ### Claim 16 (depends on 12) The method of claim 12, wherein the β-hydroxybutyrate precursor is ethyl acetoacetate, or ethyl beta-hydroxybutyrate. ### Claim 17 (depends on 12) The method of claim 12, wherein the β-hydroxybutyrate precursor is administered at between 2 grams and 50 grams. ### Claim 18 (depends on 11) The method of claim 11, wherein the ketone source is administered at about 1 g/kg/day to about 10 g/kg/day. ### Claim 19 (depends on 12) The method of claim 12, wherein the at least one medium chain triglyceride is coconut oil, coconut milk powder, fractionated coconut oil, palm oil, palm kernel oil, caprilic acid, isolated hexanoic acid, isolated octanoic acid, isolated decanoic acid, esterified ester derivatives thereof, ethoxylated derivatives thereof, enone-ylated derivatives thereof, aldehyde derivatives thereof, monoglyceride derivatives thereof, diglyceride derivatives thereof, and triglyceride derivatives thereof, salt derivatives thereof, or a combination thereof. ### Claim 20 (depends on 12) The method of claim 12, wherein the at least one medium chain triglyceride is optionally administered at between 5 grams and 50 grams.