Synergistic nutritional compositions for promoting axonal regeneration
Inventors
SAMANT, Rajaram • Tongra, Rajendra Prasad
Assignees
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Publication Number
US-11311565-B2
Publication Date
2022-04-26
Expiration Date
Abstract
The invention disclosed herein relates to a novel synergistic nutritional composition for promoting axonal regeneration. Particularly, the present invention provides potent nutritional composition comprising synergistic exogenous blend of agmatine (decarboxylated L-arginine) and inosine monophosphate (IMP) and salts thereof, which are present in a weight ratio of 1:0.05 to 1:2 along with pharmaceutically acceptable excipients. The instant synergistic nutritional composition is useful for treating diseases or disorders related to traumatic injury in the central nervous system such as brain or spinal cord injury, optic nerve lesions.
Core Innovation
The invention relates to a synergistic nutritional composition for promoting axonal regeneration. The composition comprises a therapeutically effective exogenous combination of a crystalline form of an inosine monophosphate salt and an agmatine salt, formulated with pharmaceutically acceptable excipients for oral administration.
The problem addressed is the promotion of axonal regeneration after central nervous system injuries, including brain and spinal cord trauma and optic nerve lesions. The disclosure attributes therapeutic intent to improving outcomes associated with axonal degeneration by targeting cellular injury pathways and tissue microenvironment factors implicated in oligodendrocyte damage and impaired neural repair.
The composition is described as combining multiple mechanistic actions. Agmatine is described as an iNOS inhibitor that suppresses iNOS/NO-mediated oligodendrocyte damage, supports metallothionein metal-binding/plasticity to reduce ionic zinc neurotoxicity, and modulates microglia/macrophage activity, while inosine monophosphate is described as inhibiting complement MAC formation to limit C5b-9 deposition, activating Mst3b for axon outgrowth, and increasing serum uric acid to scavenge peroxynitrite/free radicals.
The disclosure further characterizes the composition by crystalline salt forms, including agmatine sulphate and inosine monophosphate disodium salt hydrate, and weight-ratio concepts for the agmatine salt and inosine monophosphate salt. It links efficacy biomarkers and outcomes, including plasticity proteins (GAP-43, BDNF, NGF, NTF3), CNS ionic zinc reduction, limb movement improvement, and neuron sprouting and re-wiring characterized by axon crossing on a denervated side.
Claims Coverage
The partial content identifies one independent claim. Across the dependent claims, the inventive features are refined by specifying crystalline salt forms, a weight ratio range, an oral formulation, and quantitative outcome thresholds linked to biological markers and axonal crossing, as well as narrowing to a defined set of axonal degeneration disorders.
Orally administered crystalline inosine monophosphate-agmatine synergistic nutritional composition for axonal regeneration
A synergistic nutritional composition for promoting axonal regeneration comprising a therapeutically effective exogenous combination of a crystalline form of an inosine monophosphate salt and an agmatine salt, along with pharmaceutically acceptable excipients, formulated for oral administration.
Specified weight ratio of inosine monophosphate salt to agmatine salt
The inosine monophosphate salt and the agmatine salt are present in a weight ratio of 1:0.4 to 1:0.8.
Crystalline inosine monophosphate disodium salt hydrate form
The inosine monophosphate salt is a white crystalline inosine monophosphate disodium salt hydrate.
Crystalline agmatine sulphate inclusion range by weight
White crystalline agmatine sulphate is included at 10% to 55% by weight of the total composition.
CNS ionic zinc reduction threshold
A synergistic nutritional composition that reduces CNS ionic zinc concentration by more than 98%.
Neuron sprouting and re-wiring outcome defined by subject and axon-crossing criteria
A synergistic nutritional composition producing neuron sprouting and re-wiring effects in more than 83% of subjects, characterized by 1000 axons crossing the denervated side.
Treatment application to a specified set of axonal degeneration disorders
Treating an axonal degeneration disorder selected from a specified list including spinal cord injury, head and spinal cord trauma, traumatic brain injury, multiple sclerosis, Alzheimer's disease, Parkinson's disease, and other enumerated neurological and systemic conditions.
Overall, the claim coverage centers on an orally administered synergistic nutritional composition combining crystalline inosine monophosphate salt and agmatine salt at a defined weight ratio, with dependent claims further specifying crystalline salt forms and quantitative biological and functional outcomes and narrowing the treatment to enumerated axonal degeneration disorders.
Stated Advantages
Promotes axonal regeneration after central nervous system injuries.
Suppresses iNOS/NO-mediated oligodendrocyte damage.
Supports metallothionein-associated plasticity to reduce ionic zinc neurotoxicity.
Inhibits complement MAC formation to limit C5b-9 deposition.
Activates Mst3b for axon outgrowth.
Increases serum uric acid to scavenge peroxynitrite/free radicals.
Modulates microglia/macrophage activity.
Reduces CNS ionic zinc concentration by more than 98%.
Produces neuron sprouting and re-wiring effects in more than 83% of subjects with neuron sprouting characterized by axon crossing criteria.
Improves limb movement.
Documented Applications
Promotion of axonal regeneration in central nervous system injury contexts including brain and spinal cord trauma.
Promotion of axonal regeneration in optic nerve lesions.
Treatment application to axonal degeneration disorders including spinal cord injury (SCI), head and spinal cord trauma, traumatic brain injury, multiple sclerosis, Alzheimer's disease, Parkinson's disease, and other enumerated neurological and systemic diseases listed in the dependent claim summary.
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