Oral compositions containing methocinnamox
AssigneeBoard of Regents, The University of Texas System
InventorCharles Patrick FRANCE
Life of this patent
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Abstract
Disclosed herein are orally administrable compositions including MCAM. The compositions are useful for treating and preventing opioid use disorder. The compositions and methods are also useful for treating alcohol use disorder, and other disorders associated with endogenous opioid production.
Claims65
An orally administrable composition comprising methocinnamox, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.
The composition according to any preceding claim, wherein the methocinnamox is methocinnamox HCl, methocinnamox malate, methocinnamox maleate, or
- methocinnamox lactate.
The composition according to any preceding claim, wherein the methocinnamox is methocinnamox maleate.
The composition according to any preceding claim, wherein the composition comprising methocinnamox, or a pharmaceutically acceptable salt thereof in an amount of 0.5-500 mg, 0.5-250 mg, 0.5-100 mg, 0.5-50 mg, 0.5-25 mg, 0.5-20 mg, 0.5-15 mg, 0.5-10 mg, 0.5-5 mg, 0.5-2.5 mg, 1-2.5 mg, 1-5 mg, 1-10 mg, 2.5-7.5 mg, 5-15 mg, 10-20 mg, 15-25 mg, 20-30 mg, 25-50 mg, 25-75 mg, 50-100 mg, 100-250 mg, or 250-500 mg, wherein the amount is measured as the free base equivalent.
The composition according to any preceding claim, comprising methocinnamox, or a pharmaceutically acceptable salt, as an aqueous solution or dispersion.
The composition according to any preceding claim, wherein at least one pharmaceutically acceptable excipient has a melting point above 40° C.
The composition according to any preceding claim, wherein the methocinnamox, or pharmaceutically acceptable salt thereof, has an average particle size of less than 200 μm, less than 150 μm, less than 100 μm, less than 50 μm, less than 25 μm, less than 10 μm, less than 5 μm, or less than 2 μm.
The composition according to any preceding claim, wherein the composition further comprises at least one additional opioid receptor modulator.
The composition according to any preceding claim, wherein the additional opioid receptor modulator is naltrexone, naloxone, nalmefene, diprenorphine, nalorphine, nalorphine dinicotinate, levallorphan, samidorphan, nalodiene, buprenorphine, dezocine, eptazocine, butorphanol, levorphanol, nalbuphine, pentazocine, phenazocine, cyprodime, naltrindole, norbinaltorphimine, salts thereof, or a combination thereof.
The composition according to any preceding claim, wherein the additional opioid receptor modulator is naltrexone HCl.
The composition according to any preceding claim, wherein the composition comprises at least one additional opioid receptor modulator in an amount of 0.5-100 mg, 0.5-50 mg, 0.5-25 mg, 0.5-20 mg, 0.5-15 mg, 0.5-10 mg, 0.5-5 mg, 0.5-2.5 mg, 1-2.5 mg, 1-5 mg, 1-10 mg, 2.5-7.5 mg, 5-15 mg, 10-20 mg, 15-25 mg, 20-30 mg, 25-50 mg, 25-75 mg, or 50-100 mg, wherein the amount is measured as the free base equivalent.
The composition according to any preceding claim, wherein the composition comprises naltrexone HCl in an among from 25-75 mg, wherein the amount is measured as the free base equivalent.
A method of treating an opioid use disorder, comprising orally administering the composition according to any preceding claim to a subject in need thereof.
The method according to any preceding claim, wherein the method is for treating or preventing opioid dependence.
The method according to any preceding claim, wherein the method is for reducing or preventing opioid withdrawal symptoms.
The method according to any preceding claim, wherein the method is for reducing opioid cravings.
The method according to any preceding claim, wherein the method is for treating or preventing opioid overdose.
The method according to any preceding claim, wherein the method is for treating or preventing opioid-associated respiratory depression.
The method according to any preceding claim, wherein the method is for reducing or preventing renarconization in a patient being treated for opioid overdose.
The method according to any preceding claim, wherein the method is for preventing opioid dependence in a patient receiving an opioid analgesic.
The method according to any preceding claim, wherein the method is for preventing opioid overdose in a patient receiving a medically prescribed opioid.
The method according to any preceding claim, wherein the method is for preventing an opioid-induced adverse event in a patient receiving a medically prescribed opioid.
The method according to any preceding claim, wherein the method is for preventing an opioid-induced adverse event in a patient receiving a medically prescribed opioid, wherein the opioid-induced adverse effect comprises bowel dysfunction, nausea, vomiting, somnolence, dizziness, respiratory depression, headache, dry mouth, sedation, sweats, asthenia, hypotension, dysphoria, delirium, miosis, pruritis, urticaria, urinary retention, hyperalgesia, allodynia, physical dependence, tolerance, or a combination thereof.
The method according to any preceding claim, comprising reducing and/or preventing opioid-induced hypoxia.
The method according to any preceding claim, comprising reducing and/or preventing opioid poisoning.
The method according to any preceding claim, wherein the opioid use disorder is fentanyl overdose, fentanyl analog overdose, morphine overdose, heroin overdose, oxycodone overdose, hydrocodone overdose, oxymorphone overdose, hydromorphone overdose, codeine overdose, dihydrocodeine overdose, tramadol overdose, buprenorphine overdose, methadone overdose, etorphine or a combination thereof.
The method according to any preceding claim, wherein the fentanyl analog has the structure:
- wherein
- R1 is H or C1-6alkyl, optional substituted one or more times by OH, CO2C1-6alkyl, aryl, C3-10cycloalkyl, C2-10heterocyclyl, or C1-10heteroaryl;
- R2 is C1-6alkyl, C2-4alkenyl, C3-10cycloalkyl or C1-10heteroaryl;
- wherein R2 may be substituted by aryl, OC1-6alkyl;
- R3 is H, CO2C1-6alkyl, C1-6alkyl, aryl, wherein R3 may be substituted by OC1-6alkyl;
- R4 is aryl or C1-10heteroaryl, wherein R4 substituted one or more times by F;
- R5 is in each case independently selected from C1-6alkyl, C2-4alkenyl, and F;
- and
- n is 0, 1, or 2.
The method according to any preceding claim, wherein the fentanyl analog is sufentanil, alfentanil, remifentanil, and carfentanil, furanylfentanyl, 4-fluorobutyrylfentanyl, 4-methoxyburtyrylfentanyl, acrylfentanyl, 4-chloroisobutyryfentanyl (4Cl-iBF), 4-fluoroisobutyrfentanyl (4F-iBF), tetrahydrofuranfentanyl (THF-F), cyclopentylfentanyl, AH-7921, U-47700, MT-45, AH-7921, U-47700, AH-7921, or a combination thereof.
The method according to any preceding claim, wherein the opioid use disorder is fentanyl overdose, fentanyl analog overdose, or a combination thereof.
The method according to any preceding, wherein the opioid use disorder is opioid overdose with concomitant use of alcohol, barbiturates, xylazine, benzodiazepines, cocaine, amphetamines, gamma-hydroxy butyrate, PCP, ketamine, or a combination thereof.
The method according to any preceding claim, wherein the opioid use disorder is opioid addiction.
A method for supporting opioid cessation in a subject in need thereof, comprising orally administering to the subject the composition according to any preceding claim.
A method of treating an alcohol use disorder in a subject, comprising orally administering to the subject the composition according to any preceding claim.
The method according to any preceding claim, wherein the alcohol use disorder is alcohol dependence.
The method according to any preceding claim, wherein the alcohol use disorder is alcohol detoxification.
The method according to any preceding claim, wherein the method is for reducing alcohol cravings.
The method according to any preceding claim, wherein the method is for treating or preventing alcohol overdose.
The method according to any preceding claim, wherein the method is for reducing or preventing alcohol use disorder in an at-risk patient.
The method according to any preceding claim, wherein the at-risk patient is a trauma-survivor.
A method for reducing alcohol consumption in a subject, comprising orally administering to the subject the composition according to any preceding claim, in combination with at least one additional opioid receptor modulator.
A method for promoting alcohol use cessation in a subject, comprising orally administering to the subject the composition according to any preceding claim, in combination with at least one additional opioid receptor modulator.
The method according to any preceding claim, further comprising administering an alcohol dehydrogenase inhibitor, NMDA antagonist, anticonvulsant, antidepressant, other serotonergic agent, or combination thereof like.
The method according to any preceding claim, wherein the alcohol dehydrogenase inhibitor is disulfiram, the NMDA antagonist is acamprosate, the anticonvulsant is gabapentin, pregabalin, or topiramate.
The method according to any preceding claim, wherein the additional opioid receptor modulator is naltrexone, naloxone, nalmefene, diprenorphine, nalorphine, nalorphine dinicotinate, levallorphan, samidorphan, nalodiene, buprenorphine, dezocine, eptazocine, butorphanol, levorphanol, nalbuphine, pentazocine, phenazocine, cyprodime, naltrindole, norbinaltorphimine, salts thereof, or a combination thereof.
The method according to any preceding claim, wherein the additional opioid receptor modulator is naltrexone, or a pharmaceutically acceptable salt thereof.
The method according to any preceding claim, wherein the additional opioid receptor modulator is naltrexone HCl.
The method according to any preceding claim, wherein the additional opioid receptor modulator is naloxone, or a pharmaceutically acceptable salt thereof.
The method according to any preceding claim, wherein the additional opioid receptor modulator is naloxone HCl.
The method according to any preceding claim, wherein the methocinnamox and the additional opioid receptor modulators are administered in the same event dosing event.
The method according to any preceding claim, wherein the composition is administered no more than once a day, no more than once every 3 days, no more than once every 5 days, no more than once every 7 days, no more than once every 10 days, or no more than once every 14 days.
The method according to any preceding claim, wherein the methocinnamox is administered before the additional opioid receptor modulator.
The method according to any preceding claim, wherein the methocinnamox is administered after the additional opioid receptor modulator.
The method according to any preceding claim, wherein the additional opioid receptor modulator is administered enterally by oral administration, sublingual administration, buccal administration, rectal administration, or a combination thereof.
The method according to any preceding claim, wherein the additional opioid receptor modulator is administered parenterally by intramuscular injection, intravenous injection, subcutaneous injection, or a combination thereof.
The method according to any preceding claim, wherein the additional opioid receptor modulator is administered intranasally.
The method according to any preceding claim, wherein the additional opioid receptor modulator is administered by inhalation.
The method according to any preceding claim, wherein the methocinnamox and additional opioid receptor modulator are administered in the same unit dose.
A kit for the treatment of an opioid use disorder, comprising the composition according to any preceding claim.
The kit according to any preceding claim, further comprising at least one additional opioid receptor modulator.
The kit according to any preceding claim, wherein the additional opioid receptor modulator is naltrexone, naloxone, nalmefene, diprenorphine, nalorphine, nalorphine dinicotinate, levallorphan, samidorphan, nalodiene, buprenorphine, dezocine, eptazocine, butorphanol, levorphanol, nalbuphine, pentazocine, phenazocine, cyprodime, naltrindole, norbinaltorphimine, salts thereof, or a combination thereof.
The kit according to any preceding claim, wherein the additional opioid receptor modulator is naltrexone, or a pharmaceutically acceptable salt thereof.
The kit according to any preceding claim, wherein the additional opioid receptor modulator is naltrexone HCl.
The kit according to any preceding claim, wherein the additional opioid receptor modulator is naloxone, or a pharmaceutically acceptable salt thereof.
The kit according to any preceding claim, wherein the additional opioid receptor modulator is naloxone HCl.
The kit according to any preceding claim, wherein the additional opioid receptor modulator is provided as a separate unit dosage form.
Dependencies are inferred from the claim text.