Compositions and methods for increasing energy metabolism
Inventors
Zemel, Michael • Bruckbauer, Antje • Baggett, Brooke
Assignees
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Publication Number
US-9943517-B2
Publication Date
2018-04-17
Expiration Date
Abstract
Compositions and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss, or increasing Sirt1, Sirt3, or AMPK activity are provided herein. Such compositions comprise a combination of a PDE 5 inhibitor, such as sildenafil or icariin, and resveratrol, and a branched amino acid such as leucine, or its metabolite.
Core Innovation
The invention relates to compositions comprising a synergistically effective amount of a phosphodiesterase 5 (PDE 5) inhibitor and at least 500 mg of leucine and/or at least 200 mg of a leucine metabolite, wherein the PDE 5 inhibitor comprises sildenafil. The disclosed approach targets enhanced energy metabolism and mitochondrial biogenesis and fatty-acid oxidation via sirtuin-pathway output, with stated pathway output including Sirt1/Sirt3/AMPK and PGC1-b1.
The document describes synergistic combinations using a PDE 5 inhibitor, including sildenafil and icariin, together with leucine and/or leucine metabolites, notably beta-hydroxymethylbutyrate (HMB), and also keto-isocaproic acid (KIC). The invention includes embodiments employing additional co-ingredients such as resveratrol and optional vitamin B6, and it provides concepts for preferred formulations and kit concepts while associating the combinations with measured cellular and in vivo readouts.
The problem addressed is the need to improve energy metabolism and mitochondrial biogenesis and fatty-acid oxidation, including effects associated with glucose utilization and insulin sensitivity, as described by the document's background framing. The invention further addresses outcomes related to nitric oxide production, mitochondrial biomass, and metabolic improvements in disease-relevant models, including reductions in liver mass and C-reactive protein (CRP) as described.
Claims Coverage
The independent claim identified is clm-00001. The inventive features focus on synergy between a PDE 5 inhibitor and leucine/leucine metabolites and specific quantitative thresholds for the leucine and leucine metabolite components, with sildenafil specified as a PDE 5 inhibitor comprising component.
Synergistic PDE 5 inhibitor and leucine/leucine metabolite composition
A composition comprising a synergistically effective amount of a phosphodiesterase 5 (PDE 5) inhibitor and at least 500 mg of leucine and/or at least 200 mg of a leucine metabolite.
Sildenafil as the PDE 5 inhibitor
The PDE 5 inhibitor comprises sildenafil.
Quantitative leucine threshold
At least 500 mg of leucine is present in the composition.
Quantitative leucine metabolite threshold
At least 200 mg of a leucine metabolite is present in the composition.
HMB as a specified leucine metabolite option
A leucine metabolite comprises beta-hydroxymethylbutyrate (HMB) and is present at at least 200 mg.
Overall claim coverage in the provided independent claim centers on a synergistic composition combining a PDE 5 inhibitor, specifically sildenafil, with leucine and/or a leucine metabolite using the stated quantitative thresholds. Dependent claim refinements further specify selected embodiments such as using HMB as the leucine metabolite and including additional agents like resveratrol and sub-therapeutic anti-diabetic agents.
Stated Advantages
Improves energy metabolism and mitochondrial biogenesis and fatty-acid oxidation, as associated with the stated sirtuin-pathway output (Sirt1/Sirt3/AMPK and PGC1-b1) and measured readouts.
Improves glucose utilization and glucose-related outcomes, including post-prandial/fasting glycemia and insulin tolerance/insulin sensitivity metrics (including HOMA-IR and glucose tolerance test AUC, as described in the provided summary).
Increases nitric oxide production and improves mitochondrial biomass, as described by the document's measured readouts.
Reduces liver mass and C-reactive protein (CRP), as described for diet-induced obese mouse outcomes in the provided summary.
Documented Applications
Use of the PDE 5 inhibitor plus leucine/leucine metabolite combinations to improve metabolic outcomes in cellular and in vivo settings, including diet-induced obese mice, with effects on post-prandial/fasting glycemia, insulin tolerance/HOMA-IR, liver mass, and CRP as described.
Use of the claimed combinations in cellular contexts including C2C12 myotubes and 3T3-L1 adipocytes, as indicated by the document's measured readouts and model list in the provided summary.
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