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Stroke recovery

A hydroxylamine derivative, hydroxyl technology, applied in the field of hydroxylamine derivatives for the treatment of stroke, can solve problems such as limited therapeutic application

Inactive Publication Date: 2009-12-09
塞特雷克斯公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the low likelihood of achieving such a treatment in such a short period of time, unless the stroke victim is already under medical supervision, current therapies of this type are of limited use

Method used

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Experimental program
Comparison scheme
Effect test

Embodiment approach

[0062] The present invention relates to a method of treating stroke comprising administering an effective amount of one or more of certain hydroxylamine derivatives to a patient in need thereof, i.e. a patient diagnosed as having suffered from stroke, exhibiting stroke-related Patients with relevant symptoms or surrogate indicators and / or suspected stroke. Hydroxylamine derivatives useful in the practice of this method include those previously described in the following patent documents:

U.S. Patent No. 5,147,879; U.S. Patent No. 6,143,741; U.S. Patent No. 6,653,326;

U.S. Patent No. 6,649,628; U.S. Patent No. 6,384,029; U.S. Patent No. 5,328,906;

U.S. Patent No. 5,296,606; U.S. Patent No. 5,919,796; U.S. Patent No. 6,002,002

US Patent No. 6,180,787; US Patent No. 6,384,029; and US Patent Publication No. 2005 / 0043295, all of which are incorporated herein by reference.

[0063] In one embodiment, the method comprises the step of administering N-[2-hydroxy-3-(1-piperidinyl...

Embodiment 1

[0178] The aim of this study was to evaluate the efficacy of amoclorol and exenadine in enhancing neurorehabilitation in a rat model of permanent middle cerebral artery occlusion (MCAO). Permanent MCAO is well accepted and considered the standard animal model for studying the clinical aspects of stroke. (Stroke.1999; 30:2752-2758.)

[0179] Forty male Sprague Dawley rats, each weighing 300-400 g, were caged and manipulated for behavioral assessment for 7 days prior to surgery for acclimatization purposes. These rats were placed under anesthesia according to the modified Tamura model Surgery was performed to create a partial cerebral infarction by permanently occluding the proximal right middle cerebral artery (MCA). Briefly, using the N 2 O:O 2 Rats were anesthetized with 2-3% halothane in a (2:1) mixture and treated with N 2 O:O 2 Anesthesia was maintained with 1-1.5% halothane in a (2:1) mixture. The temporalis muscle is divided in half and reentranted through the inci...

Embodiment 2

Example 2. Functional rehabilitation after MCA occlusion administered with amoclorol in rats - dose study.

[0193] Fifty male Sprague Dawley rats, each weighing 300-400 g, were operated under anesthesia as described in Example 1 herein to cause MCA occlusion, and the rats were divided into 5 groups of 10 animals each. Each group was given p.o. amochlorohydrin, starting one day after occlusion, at 25 mg / kg / d, 50 mg / kg / d, 100 mg / kg / d or 200 mg / kg / d, once a day for 35 days. One group was the control group, given vehicle only.

[0194] Animals were evaluated pre-surgery (day-1) and then every 7 days (7, 14, 21, and 28 days) after surgery by the forelimb and hindlimb placement test and the body swing test, as described in Example 1 herein. out rating.

[0195] On day 35 after MCAO, rats in the control and highest dose groups were sacrificed and their brains were evaluated as in Example 1. Rats in other groups were sacrificed and their brains excised and flash frozen for further ...

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Abstract

The present invention provides methods of treating stroke comprising administering an effective amount of one or more of certain hydroxylamine derivatives to a subject in need thereof. The invention also provides pharmaceutical compositions comprising a certain hydroxylamine derivative or a pharmaceutically acceptable salt thereof, optionally in combination with one or more additional therapeutic agents. In certain compositions, the additional therapeutic agent is a second hydroxylamine derivative or a pharmaceutically acceptable salt thereof.

Description

Background of the invention [0001] Stroke is a medical emergency that affects approximately 700,000 people each year in the United States alone. A stroke is caused by the sudden loss of blood supply to a part of the brain, often followed by natural or medically intervened reperfusion. Since both hypoxia with loss of blood supply and reoxygenation with reperfusion can cause death and / or damage to brain tissue in the affected area, often resulting in permanent and temporary paralysis or weakness of one half of the body, causing vision loss or difficulty speaking, problems with thinking, awareness, attention, learning, judgment, and memory, emotional problems, and not uncommonly, death. [0002] Strokes are divided into two main types: ischemic strokes, which account for more than 85% of all stroke events, and hemorrhagic strokes, which account for the remaining events. In an ischemic stroke, a blood vessel supplying oxygen to a part of the brain becomes blocked either by a clo...

Claims

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Application Information

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IPC IPC(8): A61K31/4545A61K31/5395A61P25/28
Inventor J·R·巴伯
Owner 塞特雷克斯公司
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