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Publication Number
US-9827220-B2
Publication Date
2017-11-28
Expiration Date
Abstract
Granulocyte colony-stimulating factor (G-CSF; a stem cell enhancer and facilitator), DETC-MeSO (a glutamate receptor partial antagonist and anti-excitotoxicity agent), and sulindac (a potent anti-oxidant and anti-inflammatory agent) each can protect brain tissue exposed to a cerebral ischemia/reperfusion injury, and minimize the size of infarcts that develop as a result of the injury. When administered in combination, these agents are effective at protecting brain tissue and minimizing the size of an infarct resulting from the injury at much lower concentrations compared to using a single agent.
Core Innovation
The disclosed invention relates to a method of reducing the size of a brain infarct that develops in a mammalian subject in response to cerebral ischemia/reperfusion injury. The method comprises administering a N-diethylthiocarbamate sulfoxide (DETC-MeSO) agent after the cerebral ischemia/reperfusion injury in an amount effective to reduce the infarct size compared to a subject not treated by administration of a DETC-MeSO agent.
The described approach is positioned as protection of brain tissue and reduction of infarct size following cerebral ischemia/reperfusion injury using DETC-MeSO as a glutamate receptor partial antagonist to provide anti-excitotoxicity, together with related pharmaceutical uses in the context of neurology/pharmaceutical treatment. The disclosure includes discussion of multi-factor mechanisms including apoptosis and ER-stress protein modulation.
In addition to DETC-MeSO, the disclosure further encompasses administering other agents, including G-CSF and sulindac, individually and in combination, to achieve infarct reduction. The method scope also includes optional thrombolysis-treated subjects using tissue plasminogen activator, and method elements concerning injectable formulations and administration timing within 24 hours of symptom onset with repeated dosing.
Claims Coverage
The partial content identifies one independent claim directed to administering an effective amount of DETC-MeSO after cerebral ischemia/reperfusion injury, with dependent claims adding timing, repeat dosing, injectable formulation, and optional co-administered agents including G-CSF, sulindac, and tissue plasminogen activator.
Administering DETC-MeSO after cerebral ischemia/reperfusion injury to reduce brain infarct size
A method of reducing the size of a brain infarct that develops in a mammalian subject in response to a cerebral ischemia/reperfusion injury, comprising administering to the subject a N-diethylthiocarbamate sulfoxide (DETC-MeSO) agent after the cerebral ischemia/reperfusion injury in an amount effective for reducing the size of a brain infarct compared to a subject not treated by administration of a DETC-MeSO agent.
DETC-MeSO administration within 24 hours after onset of ischemic stroke symptoms
The method further specifies that the DETC-MeSO agent is administered to the subject within 24 hours after the onset of ischemic stroke symptoms.
Repeated DETC-MeSO administration at least once per day for at least 3 days
The method further specifies repeatedly administering the DETC-MeSO agent to the subject at least once per day for at least 3 days.
DETC-MeSO in a pharmaceutical composition formulated for injection
The method specifies that the DETC-MeSO agent is included in a pharmaceutical composition formulated for injection.
Administering tissue plasminogen activator after cerebral ischemia/reperfusion injury
The method specifies administering tissue plasminogen activator after the subject experiences cerebral ischemia/reperfusion injury.
Co-administering G-CSF and sulindac agents with DETC-MeSO
The method further comprises administering a G-CSF agent and a sulindac agent to the subject.
The core claim coverage is the post-injury administration of an effective amount of DETC-MeSO to reduce brain infarct size in cerebral ischemia/reperfusion injury, with refinements specifying injectable DETC-MeSO, administration within 24 hours of symptom onset, repeated administration at least once per day for at least 3 days, and optional co-administration of tissue plasminogen activator, G-CSF, and sulindac.
Stated Advantages
Reducing the size of a brain infarct that develops in a mammalian subject in response to cerebral ischemia/reperfusion injury compared to a subject not treated by administration of a DETC-MeSO agent.
Greater infarct reduction reported for combinations including DETC-MeSO with additional agents such as G-CSF and sulindac at much lower doses than single-agent use.
Documented Applications
Use in a mammalian subject with cerebral ischemia/reperfusion injury in order to reduce the size of a brain infarct.
Use in a thrombolysis-treated subject optionally using tissue plasminogen activator as part of the overall method.
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