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Compositions and methods for treating nocturnal acid breakthrough and other related disorders

a technology of nocturnal acid breakthrough and other disorders, applied in the field of compositions of pharmaceutical compositions, can solve the problems of adverse side effects, relatively expensive modes of hsub>2/sub>antagonists such as ranitidine and cimetidine, and treatment is not very effective in ameliorating the disorders themselves or their symptoms

Inactive Publication Date: 2008-11-06
UNIVERSITY OF MISSOURI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, many such available treatments are not very effective in ameliorating the disorders themselves or their symptoms; additionally, many produce adverse side effects including, among others, constipation, diarrhea, and thrombocytopenia.
Moreover, H2 antagonists such as ranitidine and cimetidine are relatively costly modes of therapy generally requiring multiple daily doses to produce some control of acid secretion.
In addition, tolerance to H2 antagonists increases with continued use thus prohibiting clinical utility in chronic dosing settings.
Unfortunately, most commercially available PPIs are unstable at neutral or acidic pH and undergo decomposition in gastrointestinal fluid upon oral administration, thereby resulting in loss of therapeutic activity.
An undesirable consequence of such enteric coating is that therapeutic onset time is significantly delayed by comparison with non-enteric coated dosage forms.
Such prolonged time to therapeutic onset is particularly undesirable for patients in need of rapid relief from one or more of the above described disorders or symptoms.
Unfortunately, it is recognized that commercially available enteric coated proton pump inhibitors fail to adequately control nighttime gastric acid secretion and nighttime GERD symptoms in many patients, regardless of when administered.

Method used

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  • Compositions and methods for treating nocturnal acid breakthrough and other related disorders
  • Compositions and methods for treating nocturnal acid breakthrough and other related disorders
  • Compositions and methods for treating nocturnal acid breakthrough and other related disorders

Examples

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Effect test

example 1

[0139]Enteric coated pantoprazole and an immediate release omeprazole formulation were compared in a clinical study. Thirty-two patients with nocturnal GERD symptoms were enrolled in a crossover trial; subjects were provided 40 mg of enteric coated pantoprazole (Protonix®) given at 2200 hours (bedtime) on Day 1 and prior to dinner on Days 2-6 or 40 mg of a non-enteric coated omeprazole suspension (Zegerid™) given at 2200 hours on Days 1-6. On Day 7, both PPIs were given 1 hour prior to breakfast and at 2200 hours. Continuous 24-hour gastric pH monitoring (Medtronic) was performed on Days 1, 6, and 7. Median gastric pH, percent of time gastric pH was less than 4, and the proportion of patients with “nocturnal acid breakthrough” (NAB) (>1 hr of continuous pH<4) were determined for the nighttime period (2200-0600 hours).

[0140]Nighttime median gastric pH on Day 6 is shown below. For this 8-hr period, median time that pH was >4 was greater for Zegerid™ (55%) than for Protonix® (27%) (p4 ...

example 2

[0141]Seventeen healthy subjects were enrolled in an open-label trial. Single 20-mg doses of Zegerid™ suspension (Santarus, San Diego) were given 1 hr prior to breakfast (qAM) for 7 days. On Day 8, the 20-mg suspension was given b.i.d.: at 0830 hrs (1 hr prior to a standardized high-fat breakfast) and at 2200 hrs (bedtime). On Days 7 and 8, standardized lunch and dinner were given at 1300 and 1800 hrs. Gastric pH was continuously monitored (Medtronic) for 24 hrs following the morning doses on Days 7 and 8. The percent time pH was >4 was assessed for the 8-hr nighttime period (2200-0600 hrs) and for the 24-hr period following the morning dose. The proportion of subjects with “nocturnal acid breakthrough” (NAB) (>1 hr of continuous pH<4) was assessed for the 8-hr nighttime period.

[0142]After the bedtime dose, Zegerid™ 20 mg abruptly raised the gastric pH and sustained this effect for approximately 8 hrs. The median % time pH was >4 was greater for b.i.d dosing (87%) than for qAM dosin...

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Abstract

The present invention relates to, inter alia, pharmaceutical compositions comprising an acid labile proton pump inhibitor and a buffering agent; to methods for manufacture of such compositions, and to use of such compositions in treating and preventing diseases and / or disorders.

Description

FIELD OF THE INVENTION[0001]The present invention relates to, inter alia, pharmaceutical compositions comprising an acid labile proton pump inhibitor and a buffering agent; to methods for manufacture of such compositions, and to use of such compositions in treating and preventing diseases and disorders including but not limited to nocturnal acid breakthrough and nighttime heartburn.BACKGROUND OF THE INVENTION[0002]Gastrointestinal disorders such as active duodenal ulcers, gastric ulcers, gastroesophageal reflux disease (GERD), nocturnal acid breakthrough, severe erosive esophagitis, poorly responsive symptomatic GERD, and pathological hypersecretory conditions such as Zollinger Ellison syndrome represent a major health concern impacting millions of people globally. In fact, it is estimated that as many as 60 million Americans alone experience acid reflux at least once a month, while approximately 19 million Americans suffer from GERD.[0003]In the past, the above-described (and other...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/4439A61P1/04
CPCA61K31/4439A61K31/4745A61P1/04
Inventor PHILLIPS, JEFFREY OWEN
Owner UNIVERSITY OF MISSOURI