National Institutes of Health, a Component of the US Dept. of Health & Human Services

Tdeltas Limited

Oxford University Innovation Limited

Isis Innovation Limited

Isis Innovation Limited Xford

Kieran Clarke

Richard Lewis Veech

Brianna Stubbs

Michael Todd King

Jeremy Robertson

M Todd King

Peter Hespel

Andrew James Murray

Michaela Scheuermann-Freestone

Todd King

Michael T King

Peter Cox

The subject disclosure provides compositions for reducing serum cholesterol and/or triglyceride levels in subjects. These compositions can comprise racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol or R-1,3 butandiol alone and can be, optionally, administered in conjunction with a low fat diet to a subject. Alternatively, compositions comprising racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol, R-1,3 butandiol or combinations thereof can be formulated as nutritional supplements (also referred to as nutritional compositions) or incorporated into therapeutic compositions containing a) anti-hypertensive agents; b) anti-inflammatory agents; c) glucose lowering agents; or d) anti-lipemic agents) which are administered to a subject, optionally in combination with a low fat diet, in order to cause a reduction or lowering of: serum cholesterol levels; triglyceride levels; serum glucose levels, serum homocysteine levels, inflammatory proteins (e.g., C reactive protein) and/or hypertension in treated subjects. Alternatively, compositions disclosed herein can be administered alone, or in combination with other therapeutic agents to prevent or reverse vascular disease.

Ketone bodies and ketone body esters as blood lipid lowering agents

The present invention provides a compound for use in reducing liver fat in a subject, wherein the compound is selected from: (i) (R)-3-hydroxybutyrate; (ii) an ester of (R)-3-hydroxybutyrate; and (iii) an oligomer obtainable by polymerising (R)-3-hydroxybutyrate moieties; or a pharmaceutically acceptable salt or solvate thereof. The compound is particularly useful in subjects suffering from a fatty liver. The compound can be used to treat non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH) or non-alcoholic fatty liver (NAFL).

3-hydroxybutyrate compounds for use in reducing liver fat

A method of protecting animal tissue particularly skin, from damage caused by radiation exposure, by contacting the tissue with a ketone ester, a method of protecting skin, reducing the deterioration of skin or maintaining or improving the properties of skin by applying topically to the skin a ketone body comprising (R)-3-hydroxybutyrate moieties is disclosed. A ketone body comprising (R)-3-hydroxybutyrate moieties, especially enantiomerically enriched R-1,3-hydroxybutyl-(R)-3-hydroxybutyrate, for such uses is also provided.

Compound for use in protecting skin

The present invention provides a method of suppressing hunger by lowering plasma ghrelin levels comprising administration of a compound to a human or animal body, wherein the compound is selected from:

Hunger suppression

The present invention provides a compound for use in preventing or treating overtraining in a subject, wherein the compound is selected from (i) (R)-3-hydroxybutyrate; (ii) an ester of (R)-3-hydroxybutyrate; and (iii) an oligomer obtainable by oligomerising (R)-3-hydroxybutyrate moieties; or a pharmaceutically acceptable salt or solvate thereof.

Compounds for use in preventing or treating athlete overtraining

The present invention provides a compound for use in treating cancer cachexia in a subject, wherein the compound is of general formula I: (I) or a pharmaceutically acceptable salt or solvate thereof; wherein —Ris a C-Calkyl group, which alkyl group carries up to five —ORsubstituents, wherein Rrepresents hydrogen, or C-Calkyl or wherein —ORrepresents a (R)-3-hydroxybutyrate moiety; or —Ris a moiety derived from an alcohol HORI, wherein said alcohol is a sugar. Typically, the invention also provides treatment of the conditions associated with cachexia, such as muscle wasting.

Compounds for use in cancer cachexia

The present invention provides a method of suppressing hunger by lowering plasma ghrelin levels comprising administration of a compound to a human or animal body, wherein the compound is selected from: (i) (R)-3-hydroxybutyrate; (ii) an ester of (R)-3-hydroxybutyrate; and (iii) an oligomer of (R)-3-hydroxybutyrate moieties; or a pharmaceutically acceptable salt or solvate thereof. The invention also provides a method of administering such a compound in a dosage effective to reduce hunger in order that a cosmetically beneficial loss or maintenance of body weight occurs, wherein in the method, plasma ghrelin levels are lowered. The aforementioned compound is also provided for use in a method of treatment of the human or animal body wherein the compound is administered and hunger is suppressed by lowering of plasma ghrelin levels. The compound is particularly useful for subjects having conditions associated with overeating, such as overweight, obese, severely obese patients or diabetic patients.

Method of treatment

An organoleptically acceptable composition containing a ketone body or a ketone body precursor including a hydroxybutyrate ester and a flavouring is provided and gives improved palatability and user adherence to the intended dose regime. The flavouring may be a bitter flavouring and the composition may further contain an adsorbent for the ketone such that on ingestion, the bitterness of the composition may be masked. The composition may be in the form of a solid, gel or liquid and provides increased blood ketone levels and may be used in therapy or in treating muscle impairment or fatigue.

Nutritional composition

Embodiments of the present invention are directed to processes for the production of (R)-3-hydroxybutyl (R)-3-hydroxybyrate. Poly (R)-3-hydroxybyrate is transesterified with an alcohol, to form a first ester portion and a second ester portion. The first ester portion is reduced to the diol to form a diol portion and the diol portion is reacted with the second ester portion to produce (R)-3-hydroxybutyl (R)-3-hydroxybyrate.

Process for producing (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

The subject disclosure provides compositions for reducing serum cholesterol and/or triglyceride levels in subjects. These compositions can comprise racemic &#x3b2;-hydroxybutyrate or D-&#x3b2;-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic &#x3b2;-hydroxybutyrate or D-&#x3b2;-hydroxybutyrate, esters of D-&#x3b2;-hydroxybutyrate, oligomers of D-&#x3b2;-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol or R-1,3 butandiol alone and can be, optionally, administered in conjunction with a low fat diet to a subject. Alternatively, compositions comprising racemic &#x3b2;-hydroxybutyrate or D-&#x3b2;-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic &#x3b2;-hydroxybutyrate or D-&#x3b2;-hydroxybutyrate, esters of D-&#x3b2;-hydroxybutyrate, oligomers of D-&#x3b2;-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol, R-1,3 butandiol or combinations thereof can be formulated as nutritional supplements (also referred to as nutritional compositions) or incorporated into therapeutic compositions containing a) anti-hypertensive agents; b) anti-inflammatory agents; c) glucose lowering agents; or d) anti-lipemic agents) which are administered to a subject, optionally in combination with a low fat diet, in order to cause a reduction or lowering of: serum cholesterol levels; triglyceride levels; serum glucose levels, serum homocysteine levels, inflammatory proteins (e.g., C reactive protein) and/or hypertension in treated subjects. Alternatively, compositions disclosed herein can be administered alone, or in combination with other therapeutic agents to prevent or reverse vascular disease.

Described herein is the surprising discovery that ketone bodies protect cell and tissues from ionizing radiation. Based on this finding, methods of protecting animal tissue and cells from damage caused by radiation exposure are disclosed which include, contacting the tissue with a therapeutically effective amount of an agent including at least one ketone ester, thereby protecting the tissue from radiation damage. Ketone esters can be used to minimize, reduce and/or prevent tissue damage following intentional and accidental radiation exposure, as well as increasing the therapeutic efficacy of radiation therapies by protecting non-target tissue from incidental radiation damage.

Ketone bodies to protect tissues from damage by ionizing radiation

Novel compounds and compositions containing (R)-3-hydroxybutyrate derivatives are disclosed. The compounds and compositions can be used as nutritional supplements to increase physical performance and as therapeutics to ameliorate symptoms of medical conditions, particularly neurological conditions, such as Alzheimer's and similar conditions. Novel methods for making R-3-hydroxybutyrate derivatives also are disclosed. Exemplary methods employ a supercritical solvent, such as supercritical carbon dioxide, and employ a lipase catalyzed esterification or transesterification reaction to produce the (R)-3-hydroxybutyrate derivatives.

Growing community of inventors

Oxford, United Kingdom

Kieran Clarke