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4-methylpyrazole formulations for inhibiting ethanol intolerance

a technology of ethanol intolerance and formulation, applied in the direction of antinoxious agents, drug compositions, biocides, etc., can solve the problems of ineffective treatment of another the dose of 4-mp found to be helpful in treating one genetic subpopulation of alcohol intolerance persons may not be equally helpful, and the effect of reducing the likelihood or risk of a subj

Inactive Publication Date: 2011-03-03
HORIZON ORPHAN LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013]In another aspect, methods are provided for reducing a likelihood or risk in a subject with reduced or absent aldehyde dehydrogenase subtype 2 (ALDH2) for a disease or disorder caused by exposure to acetaldehyde. In certain embodiments, the acetaldehyde is a product of ethanol consumption by the subject. In certain embodiments, the subject with reduced or absent ALDH2 activity is homozygous for alcohol dehydrogenase subtype 2*1 (ADH2*1 / ADH2*1) or is heterozygous for alcohol dehydrogenase subtypes 2*1 and 2*2 (ADH2*1 / ADH2*2). In certain embodiments, the subject with reduced or absent ALDH2 activity is homozygous for alcohol dehydrogenase subtype 2*2 (ADH2*2 / ADH2*2).
[0015]In yet other aspects, methods are provided for reducing a likelihood or risk in a subject for a disease or disorder caused by exposure to acetaldehyde comprising administering to a subject in need thereof an amount of a 4-MP, or a physiologically acceptable salt of 4-MP, effective to increase catabolism of acetaldehyde in the subject, thereby reducing the likelihood or risk for the disease or disorder. In certain embodiments, the acetaldehyde is a product of ethanol consumption.

Problems solved by technology

However, such administration has not been shown to be consistently helpful for all alcohol intolerant persons.
Accordingly, a dose of 4-MP found to be helpful to treat one genetic subpopulation of alcohol intolerance persons may not be equally helpful, or may even be ineffective, to treat another genetic subpopulation of alcohol intolerance persons.

Method used

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  • 4-methylpyrazole formulations for inhibiting ethanol intolerance
  • 4-methylpyrazole formulations for inhibiting ethanol intolerance
  • 4-methylpyrazole formulations for inhibiting ethanol intolerance

Examples

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Embodiment Construction

[0062]Provided herein are methods, compositions and formulations useful for reducing or ameliorating the severity of, or preventing, an adverse physiological symptom associated with acetaldehyde accumulation accompanying ethanol consumption in a subject with reduced or absent aldehyde dehydrogenase subtype 2 activity. The subject may express specific polymorphisms of the aldehyde dehydrogenase subtype 2 (ALDH2) gene and the alcohol dehydrogenase subtype 2 (ADH2) gene. For example, the subject may be a carrier of the variant ALDH2*2 allele of the ALDH2 gene, and may further be a carrier of the variant ADH2*2 allele of the ADH2 gene, as described herein.

[0063]As explained below, the methods provided comprise the administration of 4-MP or a physiologically acceptable salt of 4-MP. Without intending to be bound by any particular theory or mechanism, it is believed that 4-MP acts to inhibit alcohol dehydrogenase (ADH) to reduce the accumulation of acetaldehyde production that results fro...

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Abstract

Provided herein are methods, compositions and formulations to prevent or ameliorate ethanol intolerance, reduce or ameliorate symptoms associated with acetaldehyde accumulation accompanying ethanol consumption, or reduce the risk of diseases or disorders caused by acetaldehyde accumulation, comprising administering 4-MP, or physiologically acceptable salts thereof, to subjects with reduced or absent aldehyde dehydrogenase subtype 2 (ALDH2) activity.

Description

1. RELATED APPLICATIONS[0001]This application is a continuation-in-part of U.S. patent application Ser. No. 10 / 591,735, filed Jul. 23, 2007, which is a 35 U.S.C. §371 U.S. National Stage Entry of International Patent Application No. PCT / US05 / 07273, filed Mar. 3, 2005, which claims the benefit of U.S. Provisional Application No. 60 / 642,007, filed Jan. 6, 2005, and U.S. Provisional Application No. 60 / 550,261, filed Mar. 3, 2004, all of which applications are herein incorporated by reference in their entireties. This application also claims the benefit of U.S. Provisional Application No. 61 / 185,884, filed Jun. 10, 2009, which application is herein incorporated by reference in its entirety.2. TECHNICAL FIELD[0002]Provided herein are methods, compositions and formulations to prevent or ameliorate ethanol intolerance, reduce or ameliorate symptoms associated with acetaldehyde accumulation, for example, accompanying ethanol consumption, or reduce the risk of diseases or disorders caused by...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/415A61P39/00A61P1/00A61P35/00A61P25/28A61P9/12A61P25/16
CPCA61K31/415A61P1/00A61P9/12A61P25/16A61P25/28A61P35/00A61P39/00
Inventor DALEY, THOMAS E.SQUIERS, ELIZABETH C.YU, KIN-HUNG PEONY
Owner HORIZON ORPHAN LLC
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