Cytokine modulation
Inventors
Green, Colin Richard • MUGISHO, Odunayo Omolola Boluwarin • Duft, Bradford James
Assignees
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Publication Number
US-11344603-B2
Publication Date
2022-05-31
Expiration Date
Abstract
The inventions relate to the use of hemichannel blockers to modulate cytokine levels in a subject, including the angiogenic cytokine, VEGF, and their production, secretion and/or release, and to the use of hemichannel blockers to reduce or level cytokine activity, including in conditions characterized in whole or in part by angiogenesis and/or vessel leak.
Core Innovation
The invention relates to modulating cytokine activity in a human subject by administering a benzoylamino benzopyran connexin 43 hemichannel blocker according to Formula I in an amount effective to reduce cytokine levels and/or activities. The cytokines explicitly include interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1), and vascular endothelial growth factor (VEGF).
The invention is directed to treating a disease, disorder, or condition characterized at least in part by abnormal, elevated, dysregulated, undesired, unwanted or detrimental levels or activities of one or more of the specified cytokines. The connexin 43 hemichannel blocker is administered to reduce the levels and/or activities of the cytokine or cytokines in the subject, and hemichannel opening is linked to amplification of cytokine feedback loops and to cytokine production, secretion, and/or release.
The document further identifies named connexin hemichannel blockers and drug examples, including Xiflam (tonabersat) and Peptagon. It describes inflammatory cytokine effects on IL-6, IL-8, MCP-1, and sICAM-1, as well as angiogenic effects on VEGF, particularly in settings involving angiogenesis and/or vessel leak.
Claims Coverage
Two independent claims are provided. Across the independent claims, the coverage centers on administering benzoylamino benzopyran connexin 43 hemichannel blockers according to Formula I to reduce levels and/or activities of selected cytokines in methods for modulating cytokine activity and for treating cytokine-dysregulation-associated disease, disorder, or condition.
Connexin 43 hemichannel blocker dosing to reduce cytokine activity
Administering to a human subject an amount of a benzoylamino benzopyran connexin 43 hemichannel blocker effective to reduce cytokine levels and/or activities, with the blocker being a compound according to Formula I.
Target cytokine set for modulation
Reducing cytokine levels and/or activities where the cytokine is selected from interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1), and vascular endothelial growth factor (VEGF).
Treatment of cytokine-dysregulated disease by connexin 43 hemichannel blockade
Treating a subject having a disease, disorder or condition characterized at least in part by abnormal, elevated, dysregulated, undesired, unwanted or detrimental levels or activities of one or more cytokines selected from IL-6, IL-8, MCP-1, sICAM-1 and VEGF, by administering an effective amount of a benzoylamino benzopyran connexin 43 hemichannel blocker according to Formula I to reduce the levels and/or activities of the cytokine or cytokines.
The independent claim set covers administering a benzoylamino benzopyran connexin 43 hemichannel blocker according to Formula I to reduce levels and/or activities of IL-6, IL-8, MCP-1, sICAM-1 and/or VEGF. One independent claim focuses on modulating cytokine activity in a human subject, and the other focuses on treating cytokine-dysregulation-associated disease, disorder, or condition using the same connexin 43 hemichannel blockade concept.
Stated Advantages
Reduce cytokine levels and/or activities in a human subject.
Reduce abnormal, elevated, dysregulated, undesired, unwanted or detrimental cytokine levels or activities in a subject having a related disease, disorder or condition.
Documented Applications
A pharmaceutical delivery/combination embodiment for hemichannel blockers, including connexin 43 hemichannel blockers such as Xiflam and Peptagon, using sustained-release, liposomal, particle-based, and systemic administration routes.
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