Methods and compositions for supporting renal health
Inventors
Weimbs, Thomas • Torres, Jacob • Thangaraju, Muthusamy
Assignees
Augusta University • Augusta University Research Institute Inc • University of California, San Diego
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Publication Number
US-11013705-B2
Publication Date
2021-05-25
Expiration Date
Abstract
Compositions and methods for supporting health, especially renal health, comprising ketonic agents that recapitulate beneficial effects of ketosis by exogenously administered agents. The agents include BHB, analogs thereof, and GPR109A agonists. The agents may further include crystal precipitation inhibitors which synergistically improve treatment of certain renal conditions. The agents may be used in dietary supplements and therapeutic compositions for the treatment of cystic kidney diseases such as polycystic kidney disease, ciliopathies, and other conditions.
Core Innovation
The document describes ketonic compositions comprising beta-hydroxybutyrate (BHB), BHB analogs, BHB precursors, and/or GPR109A agonists for supporting renal health, with a particular focus on treating polycystic kidney disease such as autosomal dominant polycystic kidney disease. It frames the approach as a ketosis-mimic concept, using exogenous BHB-related agents to recapitulate aspects of ketosis and thereby address renal pathology. The document further describes ketonic compositions and their classes, including free acids and salts, precursors, esters, polymers, prodrugs, and enantiomer mixtures.
The document emphasizes receptor-mediated rationale centered on GPR109A (HCA2/niacin receptor) activation by ketonic compositions that include a GPR109A agonist. It describes that GPR109A-related activation is used to support the intended therapeutic effect for kidney conditions. The document associates this mechanism with experimental evidence that includes GPR109A knockout approaches and receptor-relevant readouts.
The document also describes combination concepts that include crystal precipitation inhibitors, especially citrate and citrate analogs, to address kidney stone and crystal-related drivers relevant to renal disease. It describes synergy between ketonic compositions and crystal precipitation inhibitors, including combination products such as single bi-functional BHB-citrate esters, and lists additional modulators including other calcium-oxalate/uric-acid crystal modulators. The described therapeutic compositions and delivery formats include dietary supplements and therapeutic compositions with oral delivery emphasis.
Claims Coverage
The independent claim covers methods of treating polycystic kidney disease using a therapeutically effective amount of a ketonic composition comprising BHB, a BHB analog, or a GPR109A agonist. The provided excerpt includes one independent claim family member: clm-00001, with dependent coverage adding specific ketonic components and co-administration features.
Ketonic composition treatment of polycystic kidney disease
Administering to the subject a therapeutically effective amount of a therapeutic composition comprising a ketonic composition, wherein the ketonic composition comprises BHB, a BHB analog, or a GPR109A agonist.
Raising blood BHB to a treatment threshold
Administering the ketonic composition comprising BHB or a BHB analog in a therapeutically effective amount sufficient to raise the subject’s blood BHB to at least 0.250 mMol per liter of blood.
BHB analog defined as an ester of BHB
Characterizing that the BHB analog is an ester of BHB.
BHB precursor includes 1,3-butanediol
Specifying that the precursor of BHB includes 1,3-butanediol.
Co-administration with a crystal precipitation inhibitor for in vivo crystal inhibition
Including a ketonic composition containing BHB that is co-administered with a crystal precipitation inhibitor in an amount sufficient to inhibit in vivo crystal formation.
Crystal precipitation inhibitor selected from a defined group
Specifying that the crystal precipitation inhibitor is selected from citric-acid-based compounds and related derivatives, urine alkanizing agents, carbonate/bicarbonate salts, xanthine oxidase inhibitor-related agents and drugs, and a calcium chelator.
The claims center on treating polycystic kidney disease by administering a therapeutically effective amount of a ketonic composition containing BHB, BHB analogs, and/or a GPR109A agonist, with dependent features directed to blood BHB threshold, defined BHB analog and precursor forms, and co-administration with a crystal precipitation inhibitor for in vivo crystal inhibition.
Stated Advantages
Documented Applications
No documented applications found
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