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Mao-b inhibitors and rehabilitation

An inhibitor and disease technology, applied in the field of MAO‑B inhibitor and rehabilitation, which can solve problems such as paralysis and inability to speak

Inactive Publication Date: 2017-08-18
DART NEUROSCIENCE CAYMAN LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Small strokes can cause only minor problems, such as weakness in an arm or leg, while larger strokes can cause paralysis on one side or inability to speak

Method used

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  • Mao-b inhibitors and rehabilitation
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  • Mao-b inhibitors and rehabilitation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0364] Example 1: MAO-B Inhibitor Compositions

[0365] Tablets and capsules containing the following unit doses for oral administration can be prepared by conventional procedures well known in the art of pharmacy. Compound X is any one of the active ingredients disclosed in the present invention.

[0366] tablet 1

[0367] components mg / tablet Compound X (MAO-B inhibitor) 100 lactose 77.5 povidone 15.0 Croscarmellose Sodium 12.0 microcrystalline cellulose 92.5 Magnesium stearate 3.0 total 300

[0368] tablet 2

[0369] components mg / tablet Compound X (active ingredient) 50 microcrystalline cellulose 410.0 starch 50.0 Sodium starch glycolate 15.0 Magnesium stearate 5.0 total 530

[0370] Capsule 1

[0371] components mg / capsule Compound X (MAO-B inhibitor) 100 Colloidal silica 1.5 lactose 465.5 pregelatinized starch 120.0...

Embodiment 2

[0372] Example 2: Enhanced Cognitive and Motor Rehabilitation in a Rat TBI Model

[0373] Exemplary MAO-B inhibitors of the invention were tested for their ability to enhance rehabilitation after TBI in the well-characterized lateral flow impingement model (LFP) (Mcintosh et al., Neuroscience, 1989, 28, 233-244; Hallam et al., J. Neurotrauma 2004 , 21, 521-539).

[0374] sports rehabilitation

[0375] The Staggered Step (SS) assay is a skilled motor task suitable for evaluating the ability of compounds to enhance motor rehabilitation in the rat TBI model. (Klint et al., J. Neurotrauma 2003, 21st Annual National Neurotrauma Society Symposium, 10). It consists of an 8' long and 3.5' wide runway to which a series of 28 raised steps are attached. The steps were alternately "staggered" 0.5 cm from the midline and 25 cm between steps. Attach dark home boxes (12"xl2"xl2") to both ends of the runway. Attach high beams and speakers with white noise generators to the inside of t...

Embodiment 3

[0383] Example 3. Enhanced Motor Rehabilitation in a Rat Stroke Model

[0384] Compounds of the invention were tested for efficacy in enhancing motor recovery after stroke based on cortical ischemia and motor impairment in well-established rodent models (e.g., Boychuk et al., Neurorehabil. Neural Repair. 2011, 25, 88-97; MacDonald et al., Neurorehabil. Neural Repair. 2007, 21, 486-496). The protocol will allow a broad combination of behavioral and neurophysiological approaches to comprehensively assess the neural correlates mediating motor impairment after stroke.

[0385] To establish a baseline level of motor performance, rats are trained on one or more spontaneous locomotor forelimb tasks, which may include the following:

[0386] 1. Single pellet arrival: Animals were diet restricted (90% of initial body weight) prior to training and testing. Initially, a pre-training period was spent in a test cage in which animals were trained until they successfully retrieved 10 p...

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PUM

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Abstract

Methods of rehabilitation of neurological disorders, includes neurological deficits associated with neurotraumas, such as stroke and traumatic brain injury, and with muscle disorders, that includes administering to a subject a MAO-B inhibitor.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Serial No. 62 / 051,728 filed September 17, 2014, the disclosure of which is incorporated herein by reference in its entirety. technical field [0003] The present invention relates to methods of rehabilitating neurological disorders, including neurological deficits associated with neurological trauma such as stroke and traumatic brain injury, and to the use of MAO-B inhibitors in such methods, said inhibitors comprising Certain naphthyridine and quinolone derivatives, isoxazole derivatives and pyrazole derivatives. Background technique [0004] Monoamine oxidase (MAO) is a flavin-dependent enzyme that oxidatively deaminates monoamine neurotransmitters such as dopamine, serotonin, epinephrine, tyramine, and phenylethylamine, as well as exogenous amines found in some foods and drugs . In humans there are two subtypes of MAO, MAO-A and MAO-B, which are produced by separate genes....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P21/02A63B21/00A63B21/002
CPCA61K31/4375A61K31/454A61K31/4725A61K9/2054A61K9/4866A61K45/06A61K31/47A61K31/435A61K31/444A61P21/00A61P21/02A61P25/00A61P25/28A61P43/00A61P9/10A61K31/4535A61K9/2013A61K9/2018A61K9/2027A61K9/2059A61K9/485A61K9/4858
Inventor 蒂莫西·塔利菲利普·佩雷拉
Owner DART NEUROSCIENCE CAYMAN LTD