Compositions and methods for stimulating ventilatory and/or respiratory drive

{
  "publication_number": "US12083089B2",
  "country": "US",
  "kind": "B2",
  "title": "Compositions and methods for stimulating ventilatory and/or respiratory drive",
  "abstract": "A method of attenuating opioid induced ventilatory and/or respiratory depression and/or augmenting opioid induced analgesia in a subject in need thereof includes administering to the subject a therapeutically effective amount of a composition comprising a cystine ester or an adduct, a pharmaceutically acceptable salt, a tautomer, or a solvate thereof.",
  "claims": [
    "1. A method of attenuating opioid induced ventilatory and/or respiratory depression and/or augmenting opioid induced analgesia in a subject in need thereof, the method comprising: administering to the subject an opioid in combination with a therapeutically effective amount of a composition comprising a cystine ester or an adduct, a pharmaceutically acceptable salt, a tautomer, or a solvate thereof.",
    "2. The method of claim 1, wherein the therapeutically effective amount is an amount effective to stimulate the ventilatory and/or respiratory drive of the subject and/or augment opioid induced analgesia.",
    "3. The method of claim 1, wherein the cystine ester has the formula: where R 1 and R 2 are the same or different and are selected from the group consisting of H, unsubstituted or substituted C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, C 3 -C 20 aryl, heterocycloalkenyl containing from 5-6 ring atoms, heteroaryl, and heterocyclyl containing from 5-14 ring atoms, wherein at least one of R 1 and R 2 is not a H; or an adduct, a pharmaceutically acceptable salt, a tautomer, or a solvate thereof.",
    "4. The method of claim 3, wherein R 1 and R 2 are independently H or an unsubstituted or substituted C 1 -C 24 alkyl, wherein at least one of R 1 and R 2 is not a H.",
    "5. The method of claim 3, wherein R 1 and R 2 are independently selected from the group consisting of H, methyl, ethyl, propyl, and butyl, wherein at least one of R 1 and R 2 is not a H.",
    "6. The method of claim 1, wherein the cystine ester is a cystine dialkyl ester.",
    "7. The method of claim 6, wherein the cystine dialkyl ester is a D-cystine dialkyl ester or an adduct, a pharmaceutically acceptable salt, a tautomer, or a solvate thereof.",
    "8. The method of claim 6, wherein the cystine dialkyl ester is selected from the group consisting of cystine dimethyl ester, cystine diethyl ester, combinations thereof, or an adduct, a pharmaceutically acceptable salt, a tautomer, or a solvate thereof.",
    "9. The method of claim 6 wherein the cystine dialkyl ester is D-cystine dimethyl ester or an adduct, a pharmaceutically acceptable salt, a tautomer, or a solvate thereof.",
    "10. The method of claim 1, wherein the opioid comprises at least one of alfentanil, buprenorphine, butorphanol, carfentanil, codeine, diamorphine, dextromoramide, dezocine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, meptazinol, methadone, morphine, nalbuphine, nalorphine, opium, oxycodone, oxymorphone, pentazocine, propoxyphene, remifentanil, sufentanil, tapentadol, and tramadol, and pharmaceutically acceptable salts thereof.",
    "11. The method of claim 1, wherein opioid administration elicits disturbances in ventilatory parameters, ABG chemistry, and A-a gradient while causing sedation and analgesia.",
    "12. The method of claim 11, wherein the therapeutically effective amount of the composition administered to the subject is the amount effective to elicit sustained reversal of opioid elicited disturbances in ventilatory parameters, ABG chemistry, and A-a gradient while augmenting opioid induced sedation and/or analgesia.",
    "13. The method of claim 1, wherein the composition is administered to the subject systemically.",
    "14. The method of claim 1, wherein the opioid is administered systemically by intravenous infusion.",
    "15. The method of claim 1, wherein the composition is administered concurrently with opioid administration and/or up to about 120 minutes before or after initiation of opioid administration.",
    "16. The method of claim 1, wherein the opioid comprises morphine and/or fentanyl."
  ],
  "description_excerpt": "Embodiments described herein relate to compositions and methods of stimulating ventilatory and/or respiratory drive in a subject in need thereof, and particularly relates to compositions and methods of treating breathing diseases and/or disorders associated with impaired ventilatory and/or respiratory drive.\n\nNormal control of breathing is a complex process that involves the body's interpretation and response to chemical stimuli, such as carbon dioxide, pH and oxygen levels in blood, tissues and the brain. Breathing control is also affected by wakefulness (i.e., whether the patient is awake or sleeping). Within the brain medulla there are respiratory control centers that interpret the various signals that affect respiration and issue commands to muscles that perform the work of breathing. Key muscle groups are located in the abdomen, diaphragm, larynx, pharynx and thorax. Sensors located centrally and peripherally provide input to the brain's central respiration control areas that enable response to changing oxygen requirements.\n\nNormal respiratory rhythm is maintained primarily by the body's rapid response to changes in carbon dioxide levels (CO 2). Increased CO 2 levels signal the body to increase breathing rate and depth resulting in higher oxygen levels and subsequent lower CO 2 levels. Conversely, low CO 2 levels can result in periods of apnea (no breathing) since the stimulation to breathe is absent. This is what happens when a person hyperventilates. Additionally, low blood oxygen levels stimulate respiratory drive, and this mechanism can become the primary driver in patients with chronically high PCO 2 levels.",
  "cpc": [
    "A61K 31/225",
    "A61K 2300/00",
    "A61K 31/24",
    "A61K 31/485",
    "A61K 45/06",
    "A61K 9/0019"
  ],
  "ipc": [
    "A61K 31/225",
    "A61K 45/06",
    "A61K 9/00"
  ],
  "assignees": [
    "Case Western Reserve University"
  ],
  "inventors": [
    "Benjamin M. Gaston",
    "Stephen J. Lewis"
  ],
  "filing_date": "2022-05-11",
  "publication_date": "2024-09-10",
  "grant_date": "2024-09-10",
  "priority_date": "2015-01-13",
  "application_number": "US-202217742040-A",
  "family_id": "83006730",
  "cited_by_count": 1,
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}