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-10716803-B2
Publication Date
2020-07-21
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 provides a method of treating oral mucositis in a subject that has been exposed to radiation by administering an effective amount of an aqueous composition comprising a solubilized compound of formula (I). The composition is described as an oral dosage form and as including pharmaceutically acceptable carriers and adjuvants, and treatment is described as reducing the severity of oral mucositis upon administration.
The disclosure concerns functionalized polyglucosamine compounds, including polyglucosamine derivatives and polyglucosamine-arginine compounds such as PAAG (poly(acetyl, arginyl) glucosamine). The compounds have variable substituents denoted as R1, with composition requirements for hydrogen and acetyl substituents and additional material-property constraints such as degree of deacetylation, functionalization percentage, polydispersity index, solubility, and aqueous solubility pH range.
The described approach is directed to oral mucositis that occurs after radiation exposure, including dirty bomb, accidental nuclear incident, and therapeutic radiation not related to the treatment of cancer. The document further associates the compounds with reduction of bacterial translocation, inhibition of bacterial adhesion, reduced mucositis scores, improved survival, and tissue-related effects in irradiated animal contexts.
Claims Coverage
The identified independent claim set covers treatment of oral mucositis in a radiation-exposed subject by administering an aqueous composition containing a solubilized compound of formula (I). The merged claim coverage includes the radiation-exposed subject, the aqueous solubilized formula (I) compound, oral administration, treatment upon administration, and dependent refinements relating to radiation source, comparative reduction, and compound constraints.
Radiation-exposed subject oral mucositis treatment with aqueous composition of formula (I)
A method of treating oral mucositis in a subject that has been exposed to radiation, comprising administering to the subject an effective amount of an aqueous composition comprising a solubilized compound of formula (I).
R1 substituent composition constraints for formula (I)
Each R1 is independently selected from hydrogen or acetyl, with percentage constraints on the substituents and a further defined substituent group as recited in the claims.
Oral administration
The composition is administered orally.
Comparative reduction versus non-administered subject
The method treats or reduces the severity of oral mucositis in a subject exposed to radiation compared with a subject not administered with the composition.
Radiation source definition excluding cancer-treatment radiation
The radiation is specified as being from a dirty bomb, accidental nuclear incident, or therapeutic radiation not related to the treatment of cancer.
Solubility pH range and molecular weight range
The compound is soluble in aqueous solution from about pH 3 to about pH 9, and the molecular weight of the compound is from 40 to 120 kDa.
Overall, the claim coverage focuses on treating radiation-associated oral mucositis via administration of an aqueous, solubilized formula (I) compound, with dependent limitations refining the radiation source, oral route, comparative efficacy, and compound properties.
Stated Advantages
Treats or reduces the severity of oral mucositis upon administration.
Reduces severity of oral mucositis as supported by the described outcomes, including reduced mucositis scores.
Reduces mortality in total-body irradiation models.
Reduces inflammatory and microbial-related measures described in the document narrative, including IL-8, TNF, bacterial adhesion, bacterial binding and invasion, and bacterial translocation.
Documented Applications
Treatment of oral mucositis in a subject exposed to radiation, including dirty bomb, accidental nuclear incident, and therapeutic radiation not related to the treatment of cancer.
Use in total-body irradiation models.
Use in dose-ranging and scheduling studies.
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