Compositions, methods and kits for reducing lipid levels
Inventors
Zemel, Michael • Bruckbauer, Antje
Assignees
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Publication Number
US-9895357-B2
Publication Date
2018-02-20
Expiration Date
Abstract
Compositions, methods, and kits useful for treating hyperlipidemic conditions are provided herein. Such compositions can contain synergizing amounts of nicotinic acid, nicotinamide riboside and/or nicotinic acid metabolites in combination with leucine and/or a leucine metabolite, with or without resveratrol.
Core Innovation
The invention relates to hyperlipidemia treatment compositions, methods, and kits that combine leucine and/or leucine metabolites with nicotinic acid and/or nicotinamide riboside and/or nicotinic acid metabolites. The composition includes at least 250 mg of leucine and/or at least 25 mg of one or more leucine metabolites selected from keto-isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and hydroxymethylbutyrate (HMB), together with at least 1 mg of nicotinic acid and/or nicotinamide riboside and/or nicotinic acid metabolites selected from nicotinyl CoA, nicotinuric acid, nicotinate mononucleotide, nicotinate adenine dinucleotide, and nicotinamide adenine dinucleotide.
A central aspect is that the composition is substantially free of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, valine, isoleucine and tyrosine. The disclosed approach emphasizes a substantially free amino-acid formulation combined with nicotinic acid-family components at dosing that is characterized as sub-therapeutic for lowering lipids alone. The combined use is described as producing lipid-lowering effectiveness and an outcome profile that includes improved lipid parameters.
The document further describes additional mechanistic and biological readouts, including Sirt1 activation and Sirt3 activation, AMPK activation as indicated by P-AMPK/AMPK ratio, along with fat oxidation. The described biological outcomes include reduced atherosclerotic lesion size and macrophage infiltration, including CD68, supported by in vitro and in vivo examples and human trial-style examples. The disclosed formulations optionally include additional therapeutic agents, and the kit is described with multiple dosage form and supply configurations, including unit dosage and multi-day supply concepts.
Claims Coverage
The provided claim coverage includes one independent kit claim with one inventive core feature set and narrowing dependent features.
Leucine plus nicotinic acid-family combination in a substantially free amino-acid composition
A kit comprising a composition that includes at least 250 mg of leucine and/or at least 25 mg of one or more leucine metabolites selected from keto-isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and hydroxymethylbutyrate (HMB), and at least 1 mg of nicotinic acid and/or nicotinamide riboside and/or one or more nicotinic acid metabolites selected from nicotinyl CoA, nicotinuric acid, nicotinate mononucleotide, nicotinate adenine dinucleotide, and nicotinamide adenine dinucleotide; wherein the composition is substantially free of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, valine, isoleucine and tyrosine, and the kit includes instructions.
The claim coverage centers on a kit combining a leucine/leucine-metabolite component with nicotinic acid-family components within a substantially free amino-acid composition, with dependent features narrowing quantitative ranges and specifying synergistic biological outcomes and optional additional anti-hyperlipidemic agents.
Stated Advantages
Improved lipid-lowering effectiveness, including reduced triglycerides/total cholesterol/LDL and increased HDL.
Reduced nicotinic-acid-associated cutaneous vasodilation at matched lipid-lowering effectiveness.
Synergistic biological outcomes including increased fat oxidation and Sirt1 activation, and mechanistic readouts including AMPK activation as indicated by P-AMPK/AMPK ratio.
Reduced atherosclerotic lesion size and reduced macrophage infiltration (including CD68).
Documented Applications
Hyperlipidemia treatment using the disclosed compositions and kits, with described outcomes including lipid parameter changes and cutaneous vasodilation endpoints.
Assessment of mechanistic and biological readouts including Sirt1/Sirt3 activation, AMPK activation (P-AMPK/AMPK), fat oxidation, and reduced atherosclerotic lesion size and macrophage infiltration (CD68) supported by in vitro and in vivo examples and human trial-style examples.
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