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3-hydroxybutyrate alone or in combination for use in the treatment of critical care treatment

A technology of hydroxybutyric acid and sodium hydroxybutyrate, which is applied in the direction of drug combination, anhydride/acid/halide active ingredients, medical preparations containing active ingredients, etc.

Active Publication Date: 2019-09-17
UNIVERSITE CATHOLIQUE DE LOUVAIN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, despite significant advances in the past decades in understanding critical illness including sepsis, severe sepsis, severe sepsis with septic shock, critical illness myopathy, and critical illness polyneuropathy, There are still no effective treatments to treat these conditions or alleviate the symptoms associated with them, such as ICUAW

Method used

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  • 3-hydroxybutyrate alone or in combination for use in the treatment of critical care treatment
  • 3-hydroxybutyrate alone or in combination for use in the treatment of critical care treatment
  • 3-hydroxybutyrate alone or in combination for use in the treatment of critical care treatment

Examples

Experimental program
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Effect test

Embodiment 1

[0127] Example 1: Mouse Study - Body Composition

[0128] We hypothesized that during critical illness, fat mobilized from excess adipose tissue could provide energy to vital organs more efficiently than exogenous macronutrients and that this might prevent lean tissue atrophy. We tested this hypothesis in a mouse model of central venous catheterization in cecal ligation and puncture (CLP)-induced septic critical illness and in human studies. The effects of 5 days of critical illness on body weight and body composition, muscle atrophy, and weakness were compared in lean and premorbidly obese mice, under fasted and parenterally fed states, respectively. In addition, in matched lean and overweight / obese critically ill patients, we compared markers of muscle atrophy in muscle biopsies of the two muscle groups (vastus lateralis and rectus abdominis) MRC) total score quantifies muscle strength.

[0129] Before CLP, the body weight of obese mice was significantly higher than that o...

Embodiment 2

[0131] Example 2: Mouse studies - markers of skeletal muscle atrophy and autophagy

[0132] We investigated whether less activation of the atrophy pathway could explain the maintenance of muscle mass and muscle fiber size observed in obese CLP mice. Muscle protein content tended to be reduced in lean fed CLP mice compared to lean healthy control mice (83.9 μg / mg±8.3 μg / mg vs 55.1 μg / mg±10.1 μg / mg, p=0.06), and was Decreased in lean fasted CLP mice (50.4 μg / mg±11.1 μg / mg compared to lean healthy controls, p=0.01). In contrast, obese CLP mice maintained their muscle protein content (108.1 μg / mg±20.8 μg / mg vs. 76.1 μg / mg±14.8 μg / mg in fed CLP mice, p=0.8; and fasted CLP was less Rat 63.5 μg / mg±6.6 μg / mg, p=0.1). Gene expression of markers of the ubiquitin-proteasome system, Fbxo32 and Trim63, was upregulated in lean and obese CLP mice (Fig. 3a-b). Fasted lean CLP mice showed a further increase in the expression of Fbxo32 and Trim63 (Fig. 3a-b). The activity of the proteolytic...

Embodiment 3

[0135] Example 3: Mouse Study - Ectopic Triglyceride Content

[0136] To determine whether effects on lipid content might contribute to the maintenance of muscle mass in obese CLP mice, muscle triglyceride content was quantified. While healthy lean and obese mice had comparable muscle triglyceride content, muscle triglyceride content was reduced in lean CLP mice independent of nutrient intake (Fig. 4a). In contrast, muscle triglyceride content was maintained in fed and fasted obese CLP mice (Fig. 4a). In addition, muscle mass of the tibialis anterior muscle was significantly correlated with muscle triglyceride content (R=0.498, p=0.0002).

[0137] We then investigated whether a similar effect existed in the liver. Healthy lean and obese mice had comparable hepatic triglyceride content (Fig. 4b), confirming the absence of potentially adverse features of morbid obesity-associated hepatic steatosis. Hepatic triglyceride content was reduced in lean CLP mice regardless of nutrie...

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Abstract

This invention relates generally to methods and compositions for the treatment or prevention of critical illness myopathy and critical illness polyneuropathy and of critical illness myopathy and critical illness polyneuropathy caused by critical illnesses including sepsis, severe sepsis, severe sepsis with septic shock, and particularly to the use of a combination of parenteral or enteral feeding with a 3-hydroxybutyrate.

Description

technical field [0001] The present invention generally relates to therapeutic methods and compositions for the amelioration or prevention of sepsis, severe sepsis, severe sepsis with septic shock, critical illness myopathy and critical illness polyneuropathy, and in particular Use involving parenteral or enteral feeding in combination with a carboxylic acid. Background technique [0002] Critical illness is defined as any acute medical condition requiring vital organ support or imminent death. Whether triggered by sepsis, severe sepsis, septic shock, trauma, major surgery, or other critical illness, patients may have critical illness myopathy and / or critical illness polyneuropathy, which is known as Clinical manifestations of intensive care unit (ICU) acquired weakness (ICUAW) (Kress JP, Hall JB 2014NEJM 370(17):1626-35). The prevalence of ICUAW varies according to the study population, but up to 80% of ICU patients appear to suffer from muscle wasting and / or muscle weakne...

Claims

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Application Information

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IPC IPC(8): A61K31/22A61K31/195A61K31/198A61K31/7004A61K31/7016A61K31/702A61K31/715A61P43/00A61K31/23A61K31/232
CPCA61K31/195A61K31/198A61K31/22A61K31/23A61K31/232A61K31/7004A61K31/7016A61K31/702A61K31/715A61P21/00A61P25/00A61P3/02A61P31/00A61P31/04A61P43/00A61K2300/00A61K31/19A61K9/0029
Inventor 克洛伊·古森斯莱斯·朗古谢格里特·范登伯格伊尔瑟·范胡蕾比克
Owner UNIVERSITE CATHOLIQUE DE LOUVAIN
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