Hydroxybutyrate ester and medical use thereof
Inventors
Clarke, Kieran • Veech, Richard Lewis
Assignees
ISIS LNNOVATION Ltd • Oxford University Innovation Ltd • US Department of Health and Human Services
Publication Number
US-8642654-B2
Publication Date
2014-02-04
Expiration Date
2031-02-18
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Abstract
A compound which is 3-hydroxybutyl 3-hydroxybutyrate enantiomerically enriched with respect to (3R)-hydroxybutyl (3R)-hydroxybutyrate of formula (I) is an effective and palatable precursor to the ketone body (3R)-hydroxybutyrate and may therefore be used to treat a condition which is caused by, exacerbated by or associated with elevated plasma levels of free fatty acids in a human or animal subject, for instance a condition where weight loss or weight gain is implicated, or to promote alertness or improve cognitive function, or to treat, prevent or reduce the effects of neurodegeneration, free radical toxicity, hypoxic conditions or hyperglycaemia.
Core Innovation
The invention relates to 3-hydroxybutyl 3-hydroxybutyrate enantiomerically enriched with respect to the (3R)-hydroxybutyl (3R)-hydroxybutyrate isomer, which is an effective and palatable precursor to the ketone body (3R)-hydroxybutyrate. This compound can be administered orally and increases blood levels of (3R)-hydroxybutyrate, thus providing a favorable pharmacokinetic profile with rapid and sustained release of the ketone body.
The compound reduces plasma levels of free fatty acids and can be used in treating conditions caused by or associated with elevated plasma free fatty acids. It acts on appetite centers in the brain to increase anorexigenic neuropeptides and metabolites associated with decreased appetite, thereby being useful to treat or prevent obesity, promote weight loss, maintain a healthy weight, or decrease fat to lean muscle ratio. It also increases brain metabolic efficiency, promoting improved cognitive function and treating or reducing neurodegeneration.
The problem solved by the invention arises from the impracticality and potential dangers in direct administration of ketone bodies such as (R)-3-hydroxybutyrate or acetoacetate, which can cause acidosis or sodium overload. Prior art disclosed ketone derivatives that raise blood ketone levels but they were often unpalatable or had unfavorable pharmacokinetics. The invention provides a compound that is both palatable and has advantageous in vivo conversion, overcoming these issues.
Claims Coverage
The patent discloses four main inventive features covered by independent claims, relating to the composition, its types, and medical uses.
Ingestible composition comprising a specific enantiomerically enriched compound
An ingestible composition comprising 3-hydroxybutyl 3-hydroxybutyrate enantiomerically enriched with respect to (3R)-hydroxybutyl (3R)-hydroxybutyrate.
Varied composition formulations
The composition can be formulated as a food product, beverage, drink, food supplement, dietary supplement, functional food, nutraceutical, or medicament.
Treatment of conditions related to elevated plasma free fatty acids
A method of treating conditions caused by, exacerbated by, or associated with elevated plasma free fatty acids in humans or animals by administering the enantiomerically enriched compound composition.
Treatment of appetite and weight conditions
A method of suppressing appetite, treating obesity, promoting weight loss, maintaining healthy weight, or decreasing fat to lean muscle ratio by administering the enantiomerically enriched compound composition.
These inventive features collectively cover the defined compound in various ingestible formulations and its therapeutic uses to reduce free fatty acids and treat related conditions including metabolic and weight-related disorders.
Stated Advantages
The (3R,3R') enantiomer is palatable and less bitter tasting, making it suitable for oral administration compared to other ketone bodies.
The compound is cleaved in vivo to provide immediate and sustained release of (3R)-hydroxybutyrate, offering a favorable pharmacokinetic profile.
Administration reduces plasma levels of free fatty acids and affects appetite centers to increase anorexigenic neuropeptides and metabolites, promoting weight loss and improved body composition.
The compound increases brain metabolic efficiency, thereby promoting improved cognitive function and potentially treating or reducing neurodegeneration.
Documented Applications
Treatment of conditions caused by, exacerbated by, or associated with elevated plasma levels of free fatty acids in humans or animals.
Suppression of appetite, treatment of obesity, promotion of weight loss, maintenance of healthy weight, or decrease of fat to lean muscle ratio in subjects.
Treatment of muscle impairment or muscle fatigue, including in conditions such as myalgic encephalopathy or chronic fatigue syndrome.
Treatment, prevention or reduction of effects of neurodegeneration, free radical toxicity, hypoxic conditions, or hyperglycaemia.
Use as dietary supplements, food products, beverages, functional foods, nutraceuticals, or medicaments containing the compound of the invention.
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