Methods for treatment or prevention of damage resulting from radiation, trauma or shock
Inventors
Baker, Shenda M. • Wiesmann, William P.
Assignees
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Publication Number
US-11975018-B2
Publication Date
2024-05-07
Expiration Date
Abstract
Described herein are methods of treating a subject that has been or will be exposed to radiation, trauma or shock, the method comprising identifying a subject that has been or will be exposed to radiation, and treating the subject with a compound that treats, reduces the severity or delays the onset of sepsis or reduces the likelihood of mortality in a subject upon administration of a therapeutically effective amount the compound to the subject.
Core Innovation
The invention relates to polyglucosamine compounds, including chitosan and derivatized chitosan, and compounds such as PAAG, defined as compounds of Formula (I). The compounds have an integer n between 20 and 6000 and R1 substituents independently selected from hydrogen and acetyl, with compositional constraints that at least 25% of R1 substituents are H and at least 1% and at least 2% of R1 substituents are acetyl.
The invention additionally ties the functionalized polyglucosamine composition to molecular weight ranges, aqueous solubility across pH, degree of deacetylation and functionalization, and polydispersity index. Variant embodiments are described for different functionalized polyglucosamine derivatives, while targeting specific characteristics including degree of deacetylation (DDA), functionalization percentage, polydispersity index (PDI), and molecular weight ranges.
The disclosed methods administer a therapeutically effective amount of the Formula (I) compound to a subject exposed to radiation, trauma, or shock that results in gastrointestinal (GI) damage. The methods are directed to treating, reducing the severity of, or delaying the onset of sepsis, and/or reducing the likelihood of mortality in the subject, and to reducing permeability of the gastrointestinal tract after exposure to radiation, trauma, or shock.
The permeability is described as a result of shock, trauma, or exposure to infection in the GI, and the administered Formula (I) compound reduces gastrointestinal permeability. The stated outcomes include GI damage-related endpoints such as mucositis, inflammation, bacterial translocation, and biomarkers including IL-8, pro-calcitonin (PCT), and citrulline.
Claims Coverage
The independent claims are directed to three therapeutic methods using Formula (I) functionalized polyglucosamine in subjects exposed to radiation, trauma, or shock with GI damage. The main inventive features comprise the Formula (I) compound definition with n and R1 composition thresholds, together with the claimed GI-focused treatment effects for sepsis-related outcomes or GI permeability reduction.
Functionalized polyglucosamine of Formula (I) for post-exposure GI damage treatment
A method of treating a subject identified as having been exposed to radiation, trauma, or shock that results in gastrointestinal (GI) damage by administering a therapeutically effective amount of a compound of Formula (I) in which n is an integer between 20 and 6000 and each R1 is independently selected for each occurrence from hydrogen and acetyl, with at least 25% of R1 substituents being H, at least 1% of R1 substituents being acetyl, and at least 2% of R1 substituents being acetyl-containing substituents, wherein upon administration the compound treats, reduces the severity, or delays the onset of sepsis or reduces the likelihood of mortality in the subject.
Reducing gastrointestinal permeability using Formula (I) after radiation, trauma, or shock exposure
A method of reducing permeability of the gastrointestinal tract of a subject identified as having been exposed to radiation, trauma, or shock by administering a therapeutically effective amount of a compound of Formula (I) in which n is an integer between 20 and 6000 and each R1 is independently selected for each occurrence from hydrogen and acetyl, with at least 25% of R1 substituents being H, at least 1% of R1 substituents being acetyl, and at least 2% of R1 substituents being acetyl-containing substituents, wherein upon administration the compound reduces permeability of the gastrointestinal tract of a subject.
GI permeability caused by shock, trauma, or infection exposure
The method of reducing gastrointestinal permeability, wherein the permeability is a result of shock, trauma, or exposure to infection in the GI.
The claim set centers on administering a therapeutically effective amount of a functionalized polyglucosamine compound defined by Formula (I), with constraints on n and R1 substituent composition. The independent claims cover treating or delaying sepsis and/or reducing mortality likelihood in radiation, trauma, or shock subjects with GI damage, and reducing gastrointestinal permeability in such subjects, including permeability resulting from shock, trauma, or infection exposure in the GI.
Stated Advantages
Treats, reduces the severity of, or delays the onset of sepsis after administration.
Reduces the likelihood of mortality in the subject after administration.
Reduces permeability of the gastrointestinal tract after administration.
Documented Applications
Methods of treating a subject identified as having been exposed to radiation, trauma, or shock where the exposure results in gastrointestinal (GI) damage, with sepsis and/or mortality-likelihood outcomes.
Methods of reducing permeability of the gastrointestinal tract in a subject identified as having been exposed to radiation, trauma, or shock.
Application context includes GI permeability resulting from shock, trauma, or exposure to infection in the GI.
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