Methods of treating oral mucositis
Inventors
Rothstein, David M. • Murphy, Chris • Wong, Vivien • Kazo, Glenn
Assignees
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Publication Number
US-10610533-B2
Publication Date
2020-04-07
Expiration Date
Abstract
Methods and kits for treating oral mucositis are disclosed. The treatment comprises administering to a patient in need thereof a Reactive Oxygen Species scavenger in a pharmaceutically acceptable formulation.
Core Innovation
The invention relates to treating oral mucositis in a mammal afflicted with cancer by parenterally administering a superoxide dismutase mimetic. The method lessens the severity of oral mucositis by providing a reactive oxygen species scavenger in a pharmaceutical delivery format, and the superoxide dismutase mimetic includes non-proteinaceous superoxide dismutase mimetic pentaaza-macrocyclic complexes such as M40403.
The superoxide dismutase mimetic is defined by a structural formula including a macrocycle with a transition-metal center M and variable substituents. In the disclosed compounds, W is an unsubstituted pyridino moiety, U and V are trans-cyclohexanyl fused rings, M is Mn2+ or Mn3+, and X, Y and Z are independently selected from halide, oxo, aquo, hydroxo, alcohol, phenol, dioxygen, peroxo, hydroperoxo, and related anions or charge-neutralizing anions.
The method includes administering the superoxide dismutase mimetic prior to or simultaneous with the mammal receiving chemotherapy treatment. The disclosure also includes pharmaceutical kit concepts in which the reactive oxygen species scavenger is combined with a chemotherapeutic and, in some instances, an additional ROS scavenger such as amifostine or N-acetylcysteine.
Claims Coverage
The provided independent claims cover parenteral administration of a specifically defined superoxide dismutase mimetic to lessen the severity of oral mucositis in a cancer-afflicted mammal, with administration prior to or simultaneous with chemotherapy. Three inventive features are present, centered on the treatment objective, the timing relative to chemotherapy, and the structural formula definition of the mimetic.
Parenteral administration to lessen oral mucositis severity in cancer patients
A method comprising parenterally administering a superoxide dismutase mimetic to a mammal to lessen the severity of an oral mucositis, wherein the mammal is afflicted with cancer.
Prior to or simultaneous with chemotherapy administration
The superoxide dismutase mimetic is administered prior to or simultaneous with the mammal receiving a chemotherapy treatment.
Pentaaza-macrocyclic superoxide dismutase mimetic formula with W/U/V/M/X-Y-Z definitions
The superoxide dismutase mimetic is a compound represented by a structural formula wherein W is an unsubstituted pyridino moiety; U and V are trans-cyclohexanyl fused rings; M is Mn2+ or Mn3+; and X, Y and Z are independently selected from halide, oxo, aquo, hydroxo, alcohol, phenol, dioxygen, peroxo, hydroperoxo, and related anions or charge-neutralizing anions, with n being an integer from 0 to 3.
The inventive coverage is directed to parenteral use of a pentaaza-macrocyclic superoxide dismutase mimetic defined by W/U/V/M and extensive X-Y-Z selection rules, administered prior to or simultaneous with chemotherapy to lessen the severity of oral mucositis in a cancer-afflicted mammal.
Stated Advantages
Lessen the severity of oral mucositis in a mammal afflicted with cancer.
Toxicity and body weight effects are reported for certain dosing schedules in the hamster model, including reversal of weight loss after cessation of a shorter dosing schedule.
Documented Applications
Treatment of oral mucositis associated with cancer therapy, including in the context of chemotherapy treatment.
Hamster oral mucositis studies using an acute radiation model to evaluate systemic and topical effects of M40403 relative to vehicle control and to report mucositis scores, progression over days, and associated toxicity and weight effects.
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