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Publication Number
US-12303550-B2
Publication Date
2025-05-20
Expiration Date
Abstract
The invention relates to the use of an isolated peptide of 10 to 32 amino acid residues in length for the treatment of neural injury, wherein the isolated peptide comprises at least 10 to 22 arginine residues. The peptide may be a poly-arg sequence or an arginine-rich peptide.
Core Innovation
The invention relates to neuroprotective cationic/arginine-rich peptides comprising sequences of 10 to 32 amino acids, including poly-arginine peptides having 12 to 18 arginine residues. The peptides are described as isolated peptides and include poly-arginine peptide variants, as well as protamine and mixtures of protamine, such as protamine sulphate (Ptm1-4 mixture) and low molecular weight protamine (LMWP).
The invention addresses treating a surgery patient at risk of suffering cerebral ischemia or stroke, including neural injury scenarios such as stroke and ischemia associated with surgical procedures. The described method uses intravenous administration of a pharmaceutical composition containing an effective amount of a poly-arginine peptide having 12 to 18 arginine residues, administered 0.25 hours to 4 hours prior to the surgery.
The document additionally provides mechanistic hypotheses for neuroprotection, including reduced Ca2+ influx through interaction with NMDA/AMPA/VGCC/NCX/TRP/ASIC/mGluR, stabilization of the mitochondrial outer membrane, and inhibition of furin and calcium-dependent pathways. Experimental observations are described across in vitro excitotoxicity models, in vitro ischemia/OGD, and an in vivo rat MCAO stroke model, with reported neuroprotection associated with poly-arginine peptides and protamine.
Claims Coverage
The partial content provided includes two independent claims that define a shared inventive framework: intravenous administration before surgery of a pharmaceutical composition containing a poly-arginine peptide with 12 to 18 arginine residues and no other active pharmaceutical ingredient, within a specified pre-surgical timing window.
Pre-surgical intravenous poly-arginine neuroprotection for stroke risk
A method of treating a surgery patient at risk of suffering cerebral ischemia or stroke, comprising intravenously administering 0.25 hours to 4 hours prior to the surgery a pharmaceutical composition comprising an effective amount of a poly-arginine peptide having 12 to 18 arginine residues, wherein the pharmaceutical composition does not contain an active pharmaceutical ingredient that is not a poly-arginine peptide.
Neuron survival promotion by pre-surgical intravenous poly-arginine peptide
A method for promoting the survival of neurons and/or inhibiting neuron death from stroke in a patient scheduled for a surgery carrying a risk of stroke, comprising intravenously administering a pharmaceutical composition comprising an effective amount of a poly-arginine peptide having 12 to 18 arginine residues, wherein the pharmaceutical composition does not contain an active pharmaceutical ingredient that is not a poly-arginine peptide, and administering the pharmaceutical composition 0.25 hours to 4 hours prior to the surgery.
Across the two independent claims, the core coverage centers on intravenous pre-surgical administration of an effective amount of a poly-arginine peptide with 12 to 18 arginine residues, explicitly excluding any active pharmaceutical ingredient other than the poly-arginine peptide, and using a 0.25 to 4 hour pre-surgery timing window to address stroke/cerebral ischemia risk and associated neuron death.
Stated Advantages
Promoting the survival of neurons.
Inhibiting neuron death from stroke.
Documented Applications
Treating a surgery patient at risk of suffering cerebral ischemia or stroke.
Promoting neuron survival and/or inhibiting neuron death from stroke in a patient scheduled for surgery with a stroke risk.
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