# US 10,369,103 B2 · Neuroprotective liposome compositions and methods for treatment of stroke > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,369,103 B2 - Document ID: US10369103B2 - Status: Granted - Kind: B2 - Application number: 14/420,429 - Filed: 2013-08-09 - Published: 2015-08-06 - Granted: 2019-08-06 - Earliest claimed: 2012-08-10 - Assignees: Board of Regents, The University of Texas System - Applicants: The Board of Regents of the University of Texas System - Inventors: Shao-Ling Huang; Melvin E. Klegerman; Yong-Jian Geng; Hyunggun Kim; David D. McPherson - Web page: https://patentgrep.com/patent/US10369103B2 ## CPC - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 33/00: Medicinal preparations containing inorganic active ingredients - A61K 41/0028: {Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds} - A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors - A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - 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 Methods for the treatment of stroke, such as stroke of undetermined origin, by administration of xenon (Xe)-loaded liposome compositions are provided. In some aspects, Xe is encapsulated in echogenic liposomes and release of Xe can be enhanced by application of ultrasound stimulation. Compositions for use in treating stroke, such as liposomes loaded with Xe or Xe in combination with H2 or H2S, are also provided. ## Claims ### Claim 1 A method of treating stroke in a subject who has been determined to have hemorrhagic stroke as a result of an intracranial aneurysm or subarachnoid hemorrhage comprising administering an effective amount of a composition comprising xenon-loaded echogenic liposomes to the subject, wherein the composition reduces infarct size in the treated subject. ### Claim 2 (depends on 1) The method of claim 1, wherein the subject has not been determined to have a thrombotic stroke. ### Claim 3 (depends on 1) The method of claim 1, wherein the composition is administered intravenously, intra-arterially, intracranially, via intravenous infusion or via intra-arterial infusion. ### Claim 4 (depends on 1) The method of claim 1, further comprising applying ultrasound stimulation to the subject in an amount effective to promote gas release from the liposomes. ### Claim 5 (depends on 4) The method of claim 4, wherein the ultrasound stimulation is applied with an ultrasound probe or a cervical collar ultrasound device. ### Claim 6 (depends on 4) The method of claim 4, wherein the ultrasound stimulation is applied to the neck or head of the subject. ### Claim 7 (depends on 4) The method of claim 4, wherein the ultrasound stimulation is applied at a frequency of about 1 to 8 MHz and with a mechanical index of between about 0.1 and 1.4. ### Claim 8 (depends on 1) The method of claim 1, wherein the administration is within 6, 4, 3, 2 or 1 hours of stroke onset. ### Claim 9 (depends on 1) The method of claim 1, wherein the subject is human. ### Claim 10 (depends on 1) The method of claim 1, wherein the composition is administered to the subject a second time. ### Claim 11 (depends on 1) The method of claim 1, further comprising administering a second therapeutic agent to the subject. ### Claim 12 (depends on 1) The method of claim 1, wherein administering the composition comprises suspending lyophilized liposomes in a solution and administering the solution to the subject. ### Claim 13 (depends on 1) The method of claim 1, wherein administering the composition comprises thawing a frozen liposome suspension and administering the suspension to the subject. ### Claim 14 (depends on 1) The method of claim 1, wherein the composition further comprises a cryoprotectant. ### Claim 15 (depends on 14) The method of claim 14, wherein the cryoprotectant is mannitol. ### Claim 16 (depends on 1) The method of claim 1, wherein the xenon-loaded echogenic liposomes comprise a phosphatidylcholine (PC), a phosphoethanolamine (PE), polyethylene glycol (PEG), a phosphatidylglycerol (PG) or a phosphatidylserine (PS) or cholesterol. ### Claim 17 (depends on 16) The method of claim 16, wherein the xenon-loaded echogenic liposomes were produced by a pressure-freeze or lyophilization method and comprise: (i) phosphatidylcholine; (ii) a PEGylated lipid; (iii) cholesterol; and (iv) phosphatidylglycerol or phosphatidylserine, and wherein the composition comprises a cryoprotectant. ### Claim 18 (depends on 1) The method of claim 1, wherein the xenon-loaded echogenic liposomes comprise a negatively charged lipid. ### Claim 19 (depends on 1) The method of claim 1, wherein the liposomes have an average size of 0.4 to 10 microns. ### Claim 20 (depends on 1) The method of claim 1, wherein the xenon-loaded echogenic liposomes are administered to the subject in a unit dose of between about 0.6 and 3.0 mg/kg. ### Claim 21 (depends on 1) The method of claim 1, wherein the administration is after reperfusion. ### Claim 22 (depends on 1) The method of claim 1, wherein the composition is administered to the subject a second time and a third time. ### Claim 23 (depends on 22) The method of claim 22, wherein the composition is administered to the subject a second time, a third time and a fourth time. ### Claim 24 (depends on 1) The method claim 1, wherein the composition is administered a second time within 4-6 hours of the first administration. ### Claim 25 (depends on 1) The method claim 1, wherein the composition is administered a second time less than about 2, 3, 4, 5, 6, 7 or 8 hours after the first administration.