Oligosaccharide compositions and methods of use thereof for reducing ammonia levels

A composition and oligosaccharide technology, applied in the direction of drug combination, sugar derivatives, sugar derivatives, etc., can solve problems such as ammonia accumulation

Active Publication Date: 2021-06-29
DSM营养产品有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the amount of ammonia released often exceeds the metabolic needs of these gut bacteria, which leads to the accumulation of ammonia in the gut

Method used

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  • Oligosaccharide compositions and methods of use thereof for reducing ammonia levels
  • Oligosaccharide compositions and methods of use thereof for reducing ammonia levels
  • Oligosaccharide compositions and methods of use thereof for reducing ammonia levels

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0516] Example 1. Reduction of ammonia from human feces slurries in the presence of oligosaccharide compositions

[0517] Approximately three hundred and fifty oligosaccharide compositions were tested for their ability to modulate ammonia levels in fecal slurries of healthy human subjects in vitro (also referred to as an ex vivo assay). Fecal samples and slurries were processed in an anaerobic chamber (AS-580, Anaerobe Systems) in the presence of a palladium catalyst. Prepare the oligosaccharide composition at 5% w / v in water, filter sterilize and add to a 96-well deep well microplate assay plate so that the final concentration in the assay is 0.5% or 0.05% w / v, water as A negative control is provided.

[0518] Human stool sample donations were stored at -80°C. To prepare working stocks of fecal slurries, the fecal samples were transferred to an anaerobic chamber and allowed to thaw. Fecal samples were then prepared in phosphate buffered saline (PBS) pH 7.4 (P0261, Teknova ...

Embodiment 2

[0521] Example 2: Study of selected oligosaccharide compositions in healthy human subjects

[0522] The safety and tolerability of the selected oligosaccharide compositions described in Example 1 were evaluated in healthy adults by a randomized, double-blind, placebo-controlled study (n=47) designed to measure Prebiotic activity in the presence of a high protein diet. To maximize tolerance, the dose will be titrated in four phases, starting with 9 g twice daily with food for four days to 36 g twice daily for six days; subjects are allowed to decrease the dose as tolerated (dose step down).

[0523] The gut (eg, via food fermentation by enterobacteria and glutaminase activity by enterocytes) contributes significant amounts of ammonia to human metabolism. According to some estimates, as much as 70% of the excess ammonia in hyperammonemic subjects can accumulate in the gastrointestinal tract (US Patent No. 9,487,764). In the gut, ammonia is produced by microbial urease and ami...

Embodiment 3

[0532] Example 3: Reduction of ammonia levels in ex vivo assays of fecal samples from patients with urea cycle disorders (UCD)

[0533] An ex vivo assay was performed to assess the ability of human fecal populations collected from urea cycle disorder (UCD) patients to utilize selected oligosaccharide compositions (as described in Example 1) and reduce ammonia production or increase its consumption. From 12 patients (Patient 1 to Patient 12, Figure 3A ) to collect stool samples.

[0534]Human stool sample donations were stored at -80°C. To prepare working stocks, the fecal samples were transferred to an anaerobic chamber and allowed to thaw. Each stool sample was prepared at 20% w / v in phosphate buffered saline (PBS) pH 7.4 (P0261, Teknova Inc., Hollister, CA), 15% glycerol and stored at -80°C. Centrifuge the 20% w / v fecal slurry + 15% glycerol at 2,000 x g, remove the supernatant, and suspend the pellet in 900 mg / L NaCl, 26 mg / L Calcium Chloride Dihydrate, 20 mg / L Magnesiu...

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Abstract

Aspects of the disclosure relate to oligosaccharide compositions and methods of making the same. Also provided are methods of using oligosaccharide compositions as microbiome metabolic therapies for reducing ammonia levels and for the treatment of hyperammonemia-related diseases (e.g., urea cycle disorders and hepatic encephalopathy).

Description

[0001] related application [0002] This application claims U.S. Provisional Application 62 / 720,924, filed August 21, 2018, entitled "Oligosaccharide Compositions and Methods of Use Therefor for Reducing Ammonia Levels"; U.S. Provisional Application 62 / 755,461, filed November 8, 2018, entitled "Oligosaccharide Compositions and Methods of Using the Same for Reducing Ammonia Levels" Provisional Application 62 / 757,723; the benefit of the filing date of U.S. Provisional Application 62 / 845,295, filed May 8, 2019, entitled "Oligosaccharide Compositions and Methods of Use Therefor for Lowering Ammonia Levels," the contents of each Incorporated herein in its entirety by reference. technical field [0003] The present disclosure relates to oligosaccharide compositions and uses thereof. Background technique [0004] The gut microbiome is about one hundred trillion (1x10 14 ) ecosystem of microbial cells, which can be seen as vital organs of the human body, responsible for functions...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/00C08L5/02
CPCC07H3/06C07H3/04C07H1/00C08L5/02A23L33/125A23L33/21A23L33/40A61P3/00A23V2002/00C08L5/00
Inventor C.M.刘J.M.杰里迈亚A.里奥博米罗夫M.赫克特
Owner DSM营养产品有限责任公司
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