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AssigneeShire LLC
InventorsRandal J. Kirk, Suma Krishnan, James Scott Moncrief
Estimating the term…
The invention generally relates to compositions and methods with covalently bound compounds, such as controlled substances covalently attached to a chemical moiety, and opioid antagonists or covalently bound opioid antagonists to enhance analgesic potency and/or attenuate one or more adverse effects of covalently bound compounds, including adverse side effect(s) in humans such as nausea, vomiting, dizziness, headache, sedation (somnolence), physical dependence or pruritis. This invention relates to compositions and methods for selectively enhancing the analgesic potency of a covalently bound compound and simultaneously attenuating anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects associated with the administration of a covalently bound compound. The methods of the invention comprise administering to a subject an analgesic or sub-analgesic amount of a covalently bound compound and an amount of excitatory opioid receptor antagonist such as naltrexone or nalmefene effective to enhance the analgesic potency of a covalently bound compound and attenuate the anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects of covalently bound compound. The invention also relates to the addition of covalently-bound opioid antagonists to the compositions containing covalently bound compounds such that if the compositions are subjected to manipulation by illicit chemists, the opioid antagonist is released effectively reducing or eliminating the euphoric effect of the covalently bound compounds.
A composition for oral administration comprising (1) an analgesic or sub-analgesic amount of an opioid agonist conjugate comprising an opioid agonist covalently bound to an amino acid or peptide, and (2) an effective amount of an opioid antagonist conjugate to reduce the euphoric effect of the opioid agonist conjugate, wherein the opioid antagonist conjugate is an opioid antagonist covalently bound to an amino acid or peptide.
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A composition comprising (1) an analgesic or sub-analgesic amount of a G-protein coupled receptor (GPCR) agonist conjugate comprising a GPCR agonist covalently bound to an amino acid or peptide, wherein the GPCR agonist conjugate does not promote endocytosis and resensitization of the targeted GPCR and (2) an effective amount of an opioid agonist conjugate comprising a mu opioid receptor agonist covalently bound to an amino acid or peptide, wherein the mu opioid receptor agonist promotes the endocytosis of the GPCR.
A composition comprising (1) an analgesic or sub-analgesic amount of an opioid agonist conjugate comprising an opioid agonist that targets a G-protein coupled receptor (GPCR) covalently bound to a single amino acid or peptide and (2) racemic methadone, wherein the opioid agonist does not promote endocytosis and resensitization of the targeted GPCR and the methadone reduces or prevents constipation.
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A composition comprising (1) an analgesic or sub-analgesic amount of an agonist conjugate comprising an agonist that targets a G-protein coupled receptor (GPCR) covalently bound to a single amino acid or peptide, wherein the agonist does not promote endocytosis and resensitization of the targeted GPCR, (2) a mu opioid receptor agonist conjugate comprising a mu opioid receptor agonist covalently bound to a single amino acid or peptide, and (3) an opioid antagonist compound comprising an opioid antagonist covalently bound to a single amino acid or peptide, wherein the mu opioid receptor agonist compound promotes the endocytosis of the GPCR, the mu opioid receptor agonist compound reduces, prevents or delays the development of tolerance to and/or physical dependence on particular drugs that target GPCRs and the opioid antagonist compound is present in an amount sufficient to prevent the euphoric effect of the covalently bound agonist and the covalently bound mu opioid receptor agonist.
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Dependencies are inferred from the claim text.