# US 11,077,209 B2 · Use of cerebral nitric oxide donors in the assessment of the extent of brain dysfunction following injury > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,209 B2 - Document ID: US11077209B2 - Status: Granted - Kind: B2 - Application number: 16/077,560 - Filed: 2017-02-17 - Published: 2019-01-31 - Granted: 2021-08-03 - Earliest claimed: 2016-02-19 - Assignees: Oxford University Innovation Limited - Applicants: Oxford University Innovation Limited - Inventors: Kyle Pattinson; Jon Westbrook; Matt Rowland; Payashi Garry; Martyn Ezra - Web page: https://patentgrep.com/patent/US11077209B2 ## CPC - A61K 49/0004: {Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions} - A61B 5/0042: {for the brain} - A61B 5/0075: {by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy (A61B5/0071 takes precedence)} - A61B 5/0263: {using NMR} - A61B 5/14525: {using microdialysis} - A61B 5/245: specially adapted for magnetoencephalographic [MEG] signals - A61B 5/372: Analysis of electroencephalograms - A61B 5/4064: {Evaluating the brain (for intracranial pressure A61B5/031; for cerebral blood gases A61B5/14553; using EEG A61B5/369)} - A61B 5/4848: {Monitoring or testing the effects of treatment, e.g. of medication} - A61B 6/037: {Emission tomography} - A61K 33/00: Medicinal preparations containing inorganic active ingredients - A61B 5/026: Measuring blood flow {(A61B3/1233, A61B3/1241 take precedence)} - A61B 5/14542: {for measuring blood gases (A61B5/14551 takes precedence)} - A61B 5/14553: {specially adapted for cerebral tissue} - A61B 5/374: Detecting the frequency distribution of signals, e.g. detecting delta, theta, alpha, beta or gamma waves - 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) - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) ## Abstract The invention provides a cerebral nitric oxide donor for use in a method for assessing the extent of brain dysfunction following brain injury, said method comprising contacting at least a portion of the brain of a subject with a brain injury with said cerebral nitric oxide donor and determining whether or not there is a subsequent change in one or more aspects of brain physiology, wherein the extent by which said one or more aspects of brain physiology improves is indicative of the extent of brain dysfunction. ## Claims ### Claim 1 A method for assessing the extent of, or risk of developing, delayed cerebral ischemia (DCI) following subarachnoid haemorrhage, said method comprising: (i) contacting at least a portion of the brain of a subarachnoid haemorrhage subject with a cerebral nitric oxide donor, wherein said nitric oxide donor is a nitrite salt; (ii) monitoring at least a portion of the brain of the subject with qEEG; (iii) determining whether or not there is a change in a qEEG parameter indicative of DCI within 360 minutes of said contact between the nitric oxide donor and the brain of the subject; and, (iv) assessing the subject's extent of, or risk of developing, DCI prior to the contact with the nitric oxide donor, wherein an improvement in the qEEG parameter indicative of DCI results in an assessment of a lower extent of DCI or lower risk of developing DCI, as compared to the extent of DCI or the risk of developing DCI in the brain of a subarachnoid haemorrhage subject that was contacted with the cerebral nitric oxide donor, but where the qEEG of that subject did not show an improvement in the qEEG parameter indicative of DCI. ### Claim 2 (depends on 1) The method of claim 1, wherein said monitoring comprises a monitoring step which commences within 360, 300, 240, 180, 120, 90, 75, 60, 45, 30, 15, 5 or 1 minute of, or concurrently with, contacting of the brain with the cerebral nitric oxide donor. ### Claim 3 (depends on 2) The method of claim 2, wherein the results of said monitoring are compared to the results of a monitoring step commenced no more than 360, 300, 240, 180, 120, 90, 75, 60, 45, 30, 15, 5 or 1 minute prior to contacting of the brain with the cerebral nitric oxide donor. ### Claim 4 (depends on 1) The method of claim 1, wherein said monitoring of said subsequent change in said one or more monitoring modality is essentially continuous and commences within 360, 300, 240, 180, 120, 90, 75, 60, 45, 30, 15, 5 or 1 minute before initiation of contact of the brain with the cerebral nitric oxide donor and ceases no more than 24 hrs, 18 hrs, 12 hrs, 10 hrs, 8 hrs, 6 hrs, 5 hrs, 4 hrs, 3 hrs, 2 hrs, 1 hrs or 30 minutes after contact of the brain with an effective amount of the cerebral nitric oxide donor. ### Claim 5 (depends on 1) The method of claim 1, wherein the qEEG parameter is the alpha/delta ratio and/or the relative alpha power variability and/or the relative delta power variability. ### Claim 6 A method for assessing the extent of, or risk of developing, delayed cerebral ischemia (DCI) following subarachnoid haemorrhage, said method comprising: (i) contacting at least a portion of the brain of a subarachnoid haemorrhage subject with a cerebral nitric oxide donor, wherein said nitric oxide donor is a nitrite salt; (ii) monitoring at least a portion of the brain of the subject with qEEG and measuring the alpha/delta ratio; (iii) determining whether or not there is a change in the alpha/delta ratio within 360 minutes of said contacting between the nitric oxide donor and the brain of the subject; and (iv) assessing the subject's extent of, or risk of developing, DCI prior to the contacting with the nitric oxide donor, wherein an increase in the alpha/delta ratio results in an assessment of a lower extent of DCI or lower risk of developing DCI, as compared to the extent of DCI or the risk of developing DCI in the brain of a subarachnoid haemorrhage subject that was contacted with the cerebral nitric oxide donor, but where the alpha/delta ratio did not change or decreased. ### Claim 7 (depends on 6) The method of claim 6 wherein said nitrite salt is formed from one or more nitrite anions and one or more cations selected from the alkali metals, alkaline earth metals, transition metals, ammonium and organic cations. ### Claim 8 (depends on 7) The method of claim 7 wherein said nitrite salt is selected from lithium nitrite, sodium nitrite, potassium nitrite, magnesium nitrite, and calcium nitrite, preferably sodium nitrite. ### Claim 9 (depends on 6) The method of claim 6, wherein said monitoring and measuring comprises a monitoring and measuring step which commences within 360, 300, 240, 180, 120, 90, 75, 60, 45, 30, 15, 5 or 1 minute of, or concurrently with, contacting of the brain with the cerebral nitric oxide donor. ### Claim 10 (depends on 9) The method of claim 9, wherein the results of said monitoring and measuring are compared to the results of a monitoring and measuring step commenced no more than 360, 300, 240, 180, 120, 90, 75, 60, 45, 30, 15, 5 or 1 minute prior to contact of the brain with the cerebral nitric oxide donor. ### Claim 11 (depends on 6) The method of claim 6, wherein said monitoring and measuring is essentially continuous and commences within 360, 300, 240, 180, 120, 90, 75, 60, 45, 30, 15, 5 or 1 minute before initiation of contact of the brain with the cerebral nitric oxide donor and ceases no more than 24 hrs, 18 hrs, 12 hrs, 10 hrs, 8 hrs, 6 hrs, 5 hrs, 4 hrs, 3 hrs, 2 hrs, 1 hr or 30 minutes after contact of the brain with an effective amount of the cerebral nitric oxide donor. ### Claim 12 (depends on 1) The method of claim 1 wherein said nitrite salt is formed from one or more nitrite anions and one or more cations selected from the alkali metals, alkaline earth metals, transition metals, ammonium and organic cations. ### Claim 13 (depends on 12) The method of claim 12 wherein said nitrite salt is selected from lithium nitrite, sodium nitrite, potassium nitrite, magnesium nitrite, and calcium nitrite, preferably sodium nitrite.