Methods of treating oral mucositis
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.
1. 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 and the superoxide dismutase mimetic is administered prior to or simultaneous with the mammal receiving a chemotherapy treatment, and wherein the superoxide dismutase mimetic is a compound represented by the formula:
wherein
W is an unsubstituted pyridino moiety;
U and V are trans-cvclohexanvl fused rings;
R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 are each independently selected from the group consisting of hydrogen, alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, and aralkyl radicals and radicals attached to the α-carbon or α-amino acids,
M is Mn 2+ or Mn 3+ ;
and X, Y and Z are independently selected from the group consisting of halide, oxo, aquo, hydroxo, alcohol, phenol, dioxyqen, peroxo, hydroperoxo, alkylperoxo, arylperoxo, ammonia, alkylamino, arylamino, heterocycloalkyl amino, heterocycloaryl amino, amine oxides, hydrazine, alkyl hydrazine, aryl hydrazine, nitric oxide, cyanide, cyanate, thiocyanate, isocyanate, isothiocyanate, alkyl nitrile, aryl nitrile, alkyl isonitrile, aryl isonitrile, nitrate, nitrite, azido, alkyl sulfonic acid, aryl sulfonic acid, alkyl sulfoxide, aryl sulfoxide, alkyl aryl sulfoxide, alkyl sulfenic acid, aryl sulfenic acid, alkyl sulfinic acid, aryl sulfinic acid, alkyl thiol carboxylic acid, aryl thiol carboxylic acid, alkyl thiol thiocarboxylic acid, aryl thiol thiocarboxylic acid, alkyl carboxylic acid, aryl carboxylic acid, urea, alkyl urea, aryl urea, alkyl aryl urea, thiourea, alkyl thiourea, aryl thiourea, alkyl aryl thiourea, sulfate, sulfite, bisulfate, bisulfite, thiosulfate, thiosulfite, hydrosulfite, alkyl phosphine, aryl phosphine, alkyl phosphine oxide, aryl phosphine oxide, alkyl aryl phosphine oxide, alkyl phosphine sulfide, aryl phosphine sulfide, alkyl aryl phosphine sulfide, alkyl phosphonic acid, aryl phosphonic acid, alkyl phosphinic acid, aryl phosphinic acid, alkyl phosphinous acid, aryl phosphinous acid, phosphate, thiophosphate, phosphite, pyrophosphite, triphosphate, hydrogen phosphate, dihydroqen phosphate, alkyl quanidino, aryl quanidino, alkyl aryl quanidino, alkyl carbamate, aryl carbamate, alkyl aryl carbamate, alkyl thiocarbamate, aryl thiocarbamate, alkylaryl thiocarbamate, alkyl dithiocarbamate, aryl dithiocarbamate, alkylaryl dithiocarbamate, bicarbonate, carbonate, perchlorate, chlorate, chlorite, hypochlorite, perbromate, bromate, bromite, hypobromite, tetrahalomanganate, tetrafluoroborate, hexafluoroantimonate, hypophosphite, iodate, periodate, metaborate, tetraaryl borate, tetra alkyl borate, tartrate, salicylate, succinate, citrate, ascorbate, saccharinate, amino acid, hydroxamic acid, thiotosylate, and anions of ion exchange resins, or the corresponding anions thereof;
or X, Y and Z are independently selected from the group consisting of charge-neutralizing anions which are derived from any monodentate or polydentate coordinating ligand and a ligand system and the corresponding anion thereof;
or X, Y and Z are independently attached to one or more of R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 ;
and n is an integer from 0 to 3.
2. A method in accordance with claim 1 , wherein M is Mn 2+ .
3. A method in accordance with claim 1 , wherein R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 are each hydrogen.
4. A method of treating an oral mucositis in accordance with claim 1 , wherein the superoxide dismutase mimetic is a compound represented by the formula:
5. A method of lessening the severity of oral mucositis in accordance with claim 1 , wherein the mammal is a human patient in need thereof.
6. A method of lessening the severity of mucositis in accordance with claim 1 , wherein the administering occurs prior to the subject receiving the chemotherapy treatment.
7. A method of lessening the severity of oral mucositis in accordance with claim 1 , wherein the administering occurs simultaneous with the subject receiving the cancer treatment.
8. A method of lessening the severity of oral mucositis in accordance with claim 1 , wherein the chemotherapy treatment further comprises administration of a chemotherapeutic agent selected from the group consisting of all-trans retinoic acid, azacitidine, azathioprine, bleomycin, capecitabine, chlorambucil, cyclophosphamide, cytarabine, daunorubicin, docetaxel, doxifluridine, doxorubicin, epirubicin, epothilone, etoposide, fluorouracil, gemcitabine, hydroxyurea, idarubicin, imatinib, mechlorethamine, mercaptopurine, methotrexate, mitoxantrone, paclitaxel, pemetrexed, teniposide, tiguanine, valrubicin, vinblastine, vincristine, vindesine, and vinorelbine.
9. A method in accordance with claim 6 , wherein the superoxide dismutase mimetic is administered on the day before or the day of, but prior to the chemotherapy treatment.
10. A method in accordance with claim 6 , wherein the superoxide dismutase mimetic is administered prior to but not after the chemotherapy treatment.