Gamma-hydroxybutyrate delivering compounds and processes for making and using them
Inventors
Bera, Sanjib • Guenther, Sven • Smith, Adam • Mickle, Travis
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12251445-B2
Publication Date
2025-03-18
Expiration Date
Abstract
Disclosed are one or more compounds comprising chemically modified gamma-hydroxybutyrate (GHB), 2-hydroxytetrahydrofuran, and/or 1,4-butanediol, and salts of such compounds (GHB delivering compounds and salts thereof). Also disclosed are compositions comprising at least one GHB delivering compound, or a salt thereof, methods of making such compounds, and methods of using such GHB delivering compounds and compositions. Methods of treatment using the compounds are also disclosed.
Core Innovation
The disclosure relates to GHB delivering compounds and pharmaceutically acceptable salts, including GHB-delivering conjugates, ether prodrugs, and chemically modified GHB-related moieties. The structures include GHB, 2-hydroxytetrahydrofuran (2-OH-THF), 1,4-butanediol (BD), O-(2-THF)-GHB, 4-hydroxybutyl O-(2-THF)-GHB, O-(2-THF)-BD, ascorbate tetrakis-O-(2-THF) ether, a carboxylate carbonate derivative, and amino-acid/peptide-conjugated and multiply-conjugated derivatives.
The disclosure also describes 3CPr carbamate derivatives and related substituted forms, including sulfonyl, phosphoryl/phosphate, sulfamate, phenylsulfonyl, and 2-THF adduct forms, together with multiple salt forms. The scope further includes ligand groups denoted by L, M, R/R1, Z, Y1/Y2, and M in Formula V, with ligand variants such as phosphate, sulfate/sulfamate, oxoacids, amino acids and peptides, as well as pharmaceutically acceptable salts.
The disclosed compositions are used for preventing or treating sleep disorders or sleep syndrome in a subject by administering therapeutically effective amounts of the GHB delivering compounds. The document describes oral administration and hydrolysis-triggered release with fast, controlled, or sustained release profiles, and includes sleep disorders associated with degenerative neurological diseases, including Parkinson’s disease, primary parkinsonism, paralysis agitans, and idiopathic parkinsonism.
Claims Coverage
The provided claim content covers selected GHB-delivering compounds or pharmaceutically acceptable salts, compositions containing enumerated salt forms, methods of preventing or treating sleep disorders by administration, dosing about one to two times per day, and kit embodiments with specified unit dosage forms and instructions for use. In total, the claim family centers on 6 inventive features.
Selected compound or pharmaceutically acceptable salt
A compound selected from the disclosed group, or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition with enumerated pharmaceutically acceptable salts
A pharmaceutical composition containing the compound or a pharmaceutically acceptable salt, where the salt is selected from a listed group of specific salt forms and mixtures thereof.
Preventing or treating sleep disorder or sleep syndrome by administration
A method for preventing or treating a sleep disorder or sleep syndrome by administering the composition to a subject who needs it.
Sleep disorder tied to degenerative neurological disease
The sleep disorder is a symptom of and/or a side effect of treatment for Parkinson’s disease, primary parkinsonism, paralysis agitans, or idiopathic parkinsonism.
Dosing regimen of about one to two times per day
The composition is administered according to a dosing regimen about one to two times per day.
Kit with therapeutically effective amount and specified unit dosage forms
A kit that includes a therapeutically effective amount of the compound or pharmaceutically acceptable salt in a unit dosage form selected from specified oral and other dosage formats, together with instructions for use.
Overall, the claims focus on selected GHB-delivering compounds or pharmaceutically acceptable salts, compositions with enumerated salt options, therapeutic administration for sleep disorders or sleep syndrome, disease-associated sleep disorder limitations, dosing frequency about one to two times per day, and kits with specified unit dosage forms and instructions.
Stated Advantages
Oral administration.
Hydrolysis-triggered release of GHB/GHB precursors.
Potential fast, controlled and/or sustained release profiles.
Lower molar dosing versus NaGHB.
Improved bioavailability and brain uptake.
Reduced side effects.
Reduced substance abuse risk.
Documented Applications
Preventing or treating sleep disorders or sleep syndrome by administering compositions containing the GHB-delivering compounds and pharmaceutically acceptable salts.
Treating sleep disorders associated with degenerative neurological diseases, including Parkinson’s disease, primary parkinsonism, paralysis agitans, and idiopathic parkinsonism.
Use directed to central hypersomnolence disorders, obstructive sleep apnea, and shift work disorder.
Pharmacokinetic evaluation in rats, including oral administration results and comparison versus sodium oxybate (NaGHB).
Kit use providing a therapeutically effective amount in specified unit dosage forms together with instructions for use.
Interested in licensing this patent?