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Treatment of circadian rhythm disorders

a technology for circadian rhythm and disorders, applied in the field of circadian rhythm disorders, can solve the problems of abnormal night sleep patterns, difficulty in staying awake during the day, and the inability of the master body clock to be reset daily and maintain entrainment to a 24-hour day

Inactive Publication Date: 2017-10-26
VANDA PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent is about the discovery that the daily dose of tasimelteon can be adjusted upward or downward depending on whether the patient is being treated with a CYP3A4 inducer or inhibitor. This allows for better control over the medication and can improve its effectiveness and safety.

Problems solved by technology

Inability to detect this light signal, as occurs in most totally blind individuals, leads to the inability of the master body clock to be reset daily and maintain entrainment to a 24-hour day.
Individuals with Non-24 have abnormal night sleep patterns, accompanied by difficulty staying awake during the day.
Non-24 leads to significant impairment, with chronic effects impacting the social and occupational functioning of these individuals.
In addition to problems sleeping at the desired time, individuals with Non-24 experience excessive daytime sleepiness that often results in daytime napping.
As time progresses, the internal circadian rhythms of these individuals becomes 180 degrees out of synchrony with the 24 h day-night cycle, which gradually makes sleeping at night virtually impossible, and leads to extreme sleepiness during daytime hours.
However, the alignment between the internal circadian rhythm and the 24-hour day-night cycle is only temporary.
In addition to cyclical nighttime sleep and daytime sleepiness problems, this condition can cause deleterious daily shifts in body temperature and hormone secretion, may cause metabolic disruption and is sometimes associated with depressive symptoms and mood disorders.

Method used

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  • Treatment of circadian rhythm disorders
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Examples

Experimental program
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Embodiment Construction

[0020]Tasimelteon has the chemical name: trans-N-[[2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1yl]methyl]propanamide, has the structure of Formula I:

and is disclosed in U.S. Pat. No. 5,856,529 and in US 20090105333, both of which are incorporated herein by reference as though fully set forth.

[0021]Tasimelteon is a white to off-white powder with a melting point of about 78° C. (DSC) and is very soluble or freely soluble in 95% ethanol, methanol, acetonitrile, ethyl acetate, isopropanol, polyethylene glycols (PEG-300 and PEG-400), and only slightly soluble in water. The native pH of a saturated solution of tasimelteon in water is 8.5 and its aqueous solubility is practically unaffected by pH. Tasimelteon has 2-4 times greater affinity for MT2R relative to MT1R. Ifs affinity (Ki) for MT1R is 0.3 to 0.4 and for MT2R, 0.1 to 0.2. Tasimelteon is useful in the practice of this invention because it is a melatonin agonist that has been demonstrated, among other activities, to entrain patients s...

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PUM

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Abstract

Embodiments of the invention relate to the use of a melatonin agonist in the treatment of free running circadian rhythms in patients, including light perception impaired patients, e.g., blind patients, and to methods of measuring circadian rhythm.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation U.S. patent application Ser. No. 14 / 510,321, filed 9 Oct. 2014, which is a continuation of then co-pending International Patent Application No. PCT / US13 / 76311, filed 18 Dec. 2013, which in turn claims the benefit of then co-pending U.S. Provisional Patent Application No. 61 / 903,354, filed 12 Nov. 2013, each of which is hereby incorporated herein as though fully set forth.FIELD OF THE INVENTION[0002]Embodiments of the invention relate generally to the field of circadian rhythm disorders (CRDs) and, more particularly, to the entrainment of circadian rhythms in persons afflicted with Non-24 Hour Disorder (Non-24).BACKGROUND OF THE INVENTION[0003]The master body clock controls the timing of many aspects of physiology, behavior and metabolism that show daily rhythms, including the sleep-wake cycles, body temperature, alertness and performance, metabolic rhythms and certain hormones which exhibit circadian var...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/343A61K45/06A61K31/496A61K31/31A61K31/277G06F19/00A61K31/15
CPCA61K45/06A61K31/31A61K31/343A61K31/15G06F19/322A61K31/277A61K31/496G01N33/493G01N33/50G01N33/68G01N33/74G01N2333/575G01N2800/2864Y02A90/10G16H10/60G01N30/72A61P43/00G01N30/88A61K2300/00
Inventor DRESSMAN, MARLENE MICHELLEFEENEY, JOHN JOSEPHLICAMELE, LOUIS WILLIAMPOLYMEROPOULOS, MIHAEL H.
Owner VANDA PHARMA INC
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