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Treatment of epilepsy

a technology for epilepsy and pharmaceutical compositions, applied in the field of pharmaceutical compositions for treating epilepsy, can solve the problems of significantly affecting the daily life of patients, poorer quality of life, and current asds that fail to control the seizures of 30% of patients

Inactive Publication Date: 2020-06-11
KATHOLIEKE UNIV LEUVEN +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes compounds and methods for their use in treating seizures and epilepsy. The compounds are isoquinoline derivatives that have been found to have anticonvulsant properties. The invention also includes methods for synthesizing these compounds and pharmaceutical compositions containing them. The technical effects of the invention include the development of new compounds that can be used to treat seizures and epilepsy, as well as methods for their synthesis and pharmaceutical compositions.

Problems solved by technology

Despite considerable efforts, current ASDs fail to control the seizures of 30% of patients due to drug-resistance [Dalic & Cook (2016) Neuropsychiatr Dis Treat 12, 2605-2616.].
Uncontrolled epilepsy can result in a poorer quality of life because of physical, psychological, cognitive, social, and occupational problems [Golyala, A., and Kwan, P.
Moreover, first-line ASDs are associated with important adverse effects that can significantly impact daily life and are a main cause of treatment failure [Dalic & Cook (2016) Neuropsychiatr Dis Treat 12, 2605-2616; Moshe et al.

Method used

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Experimental program
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example 1

[0113]1.1. Chemical Experimental Procedures

[0114]Ultra-high performance liquid chromatography-diode array detection-quadrupole time of flight mass spectrometry (UHPLC-DAD-QTOFMS) was performed on an Agilent Infinity 1290 UHPLC system (Agilent Technologies, Santa Clara, Calif., USA) equipped with a diode array detector (DAD). Separation was achieved on an Agilent Poroshell 120 phenyl-hexyl column (2.1×150 mm, 2.7 μm) with a flow of 0.35 mL / min at 60° C. using a linear gradient 10% acetonitrile (MeCN) in Milli-Q water buffered with 20 mM formic acid (FA) increased to 100% in 15 min staying there for 2 min, returned to 10% in 0.1 min and kept there for 3 min before the following run. MeCN was LC-MS grade. MS detection was done on an Agilent 6550 iFunnel QTOF MS equipped with Agilent Dual Jet Stream electrospray ion source with the drying gas temperature of 160° C. and gas flow of 13 L / min and sheath gas temperature of 300° C. and flow of 16 L / min. Capillary voltage was set to 4000 V an...

example 2

-Based Antiseizure Drug Discovery

[0151]2009 marine NPs, i.e., extracts and pre-fractionated fractions, provided by the different PharmaSea partners, were screened for neuroactivity at a concentration of 100 μg / mL (2 hours incubation time) using the zebrafish PMR assay. The PMR was described by a behavioral fingerprint of 16 pseudo Z-scores that represent the embryonic motion over a 30 second recording period using the first and third quantile (Q1 and Q3) for each of the 8 time periods. A neuroactive hit was defined as a marine NP that modified the PMR such that its behavioral fingerprint contained at least one pseudo Z-score with an absolute value equal to or exceeding 5. Each PMR-assay was followed by visual evaluation of the embryos under a light microscope to assess toxicity of treatment. Only 109 marine NPs were observed to cause toxicity. All other treatments did not induce toxicity under the test conditions, whereof 332 were neuroactive and 1568 samples were inactive. The 332 ...

example 3

ty-Guided Identification of Active Compounds

[0153]To identify the active constituents of SK0107 that are responsible for its antiseizure activity bioactivity-guided purification was performed of Aspergillus insuetus IBT 28443. In the crude extract of Aspergillus insuetus dereplication using ultra-high performance liquid chromatography-diode array detection-quadrupole time of flight mass spectrometry (UHPLC-DAD-QTOFMS) tentatively identified an abundant presence of the sesterterpenoids, ophiobolins (inactive, data not shown). Before any large scale cultivation, small scale extracts were prepared of the fungus cultivated individually on CYA, YES and OAT media, as the tested bioactive extract was of the combined cultivation on both CYA and YES media. This was done in hope of finding a medium where the production of ophiobolins was reduced and other compounds presented in a higher concentration than the original crude extract. CYA medium was chosen based on the activity of fractions fro...

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Abstract

The present invention discloses isoquinolines and 1H-2-Benzopyranes and their use in the treatment and prevention in epilepsy and other seizures. The present invention further discloses methods to screen isoquinoline- and 1H-2-Benzopyran-like molecules as pharmaceutically active compounds.

Description

FIELD OF THE INVENTION[0001]The present invention provides a pharmaceutical composition for treating epilepsy.BACKGROUND OF THE INVENTION[0002]Epilepsy is among the most common severe neurological conditions, affecting more than 70 million people worldwide [Sander (2003) Curr Opin Neurol 16, 165-170; Ngugi et al. (2010) Epilepsia 51, 883-890; Singh and Trevick (2016) Neurol Clin 34, 837-847]. It is characterized by an enduring predisposition of the brain to generate epileptic seizures, with neurobiologic, cognitive, psychological, and social consequences [Fisher et al. (2005) Epilepsia 46, 470-472.]. The treatment of epilepsy consists mostly of pharmacotherapy with antiseizure drugs (ASDs) to control seizures [Golyala & Kwan (2017) Seizure 44, 147-156.]. Despite considerable efforts, current ASDs fail to control the seizures of 30% of patients due to drug-resistance [Dalic & Cook (2016) Neuropsychiatr Dis Treat 12, 2605-2616.]. Uncontrolled epilepsy can result in a poorer quality of...

Claims

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Application Information

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IPC IPC(8): A61K31/4741A61K31/496A61K31/353A61P25/08
CPCA61K31/4741A61P25/08A61K31/353A61K31/496A61K31/352A61K36/06A61K2300/00
Inventor COPMANS, DANIËLLECRAWFORDDE WITTE, PETERESGUERRA, CAMILAKILDGAARD, SARAOSTENFELD LARSEN, THOMASNY, ANNELII
Owner KATHOLIEKE UNIV LEUVEN