Use of carbamate compound for prevention, alleviation or treatment of status epilepticus
Inventors
Choi, Eun Ju • Shin, Hye Won • SHIN, Yu Jin
Assignees
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Publication Number
US-12070448-B2
Publication Date
2024-08-27
Expiration Date
Abstract
The present invention relates to a use for the purpose of preventing, alleviating, or treating status epilepticus by administering a medicament or pharmaceutical composition comprising a carbamate compound of chemical formula 1.
Core Innovation
The disclosed invention relates to using a compound of Formula 1 for preventing, alleviating, or treating status epilepticus. The compound of Formula 1 includes substituents R1 and R2 selected from specified groups and a specific relationship between A1 and A2, where one of A1 and A2 is CH and the other is N. The disclosure includes pharmaceutically acceptable salt, solvate or hydrate forms, and pharmaceutical compositions comprising the compound.
The disclosure addresses status epilepticus in patients with refractory status epilepticus and discusses second-line use as well as combinations with benzodiazepines and other anti-epileptic drugs. The target scope includes convulsive status epilepticus and non-convulsive status epilepticus across various etiologies, including stroke, metabolic derangements, CNS infections, traumatic brain injury, alcohol abuse, brain tumors, chronic cerebral infarction lesions, and low AED level.
The disclosure provides experimental support including in vitro Mg2+-low whole-cell patch-clamp seizure-like event results and in vivo pilocarpine-induced status epilepticus results in a mouse model. The results state significant reductions in seizure count and/or seizure score versus vehicle, with comparisons made versus a positive control valproate, and support administration of the compound as a therapeutically effective amount in a once-daily regimen.
Claims Coverage
The independent claim is clm-00001. The inventive features focus on the administration of a therapeutically effective amount of a Formula 1 compound, including acceptable salt, solvate or hydrate forms, for alleviating or treating status epilepticus, together with the defined substituent pattern for R1/R2 and the CH/N arrangement for A1/A2.
Therapeutically effective formula 1 administration for status epilepticus
Administering to a subject in need thereof a therapeutically effective amount of a compound of Formula 1, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for alleviating or treating status epilepticus.
Defined r1/r2 substituent selection and ch/n pattern for a1/a2
Selecting R1 and R2 independently from hydrogen, halogen, C1-C8 alkyl, halo-C1-C8 alkyl, C1-C8 thioalkoxy and C1-C8 alkoxy, and having one of A1 and A2 be CH with the other being N.
Carbamate compound instantiation of formula 1
Using as the Formula 1 compound carbamic acid (R)-1-(2-chlorophenyl)-2-tetrazol-2-yl-ethyl ester of Formula 2.
Treatment in status epilepticus associated with specified conditions or low aed level
Applying the method to status epilepticus caused by one or more specified conditions including stroke, metabolic derangements, CNS infections, traumatic brain injury, alcohol abuse, brain tumors, chronic cerebral infarction lesions, or low antiepileptic drug (AED) levels in patients with epilepsy.
Treatment of convulsive status epilepticus
Applying the method to convulsive status epilepticus.
Restricted r1/r2 selection set
Specifying that R1 and R2 are each independently selected from hydrogen, halogen, or C1-C8 alkyl groups.
The coverage centers on administration of a Formula 1 carbamate compound with defined substituent constraints for R1/R2 and a CH/N relationship for A1/A2, for alleviating or treating status epilepticus, with dependent claims narrowing the compound to a specific Formula 1 instantiation, restricting R1/R2 selection, narrowing the clinical context and convulsive status epilepticus, and further specifying dosing refinements where included in the provided claim set.
Stated Advantages
Reduces seizure count and/or seizure score versus vehicle in the pilocarpine-induced status epilepticus mouse model.
Shows statistically significant reductions versus vehicle and includes comparisons to a positive control valproate.
Documented Applications
Preventing, alleviating, or treating status epilepticus, including convulsive status epilepticus and non-convulsive status epilepticus, across specified etiologies and in refractory status epilepticus.
Second-line use and combinations with benzodiazepines and other anti-epileptic drugs are discussed in the background context.
Use supported by in vitro Mg2+-low whole-cell patch-clamp seizure-like event results.
Use supported by in vivo pilocarpine-induced status epilepticus results in a mouse model.
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