FIELD: pharmaceuticals.
SUBSTANCE: invention relates to a method of reducing the incidence, heaviness and / or duration of mucositis in the oral cavity in a subject who has been exposed to a damaging amount of radiation or chemotherapeutic agents, comprising administering to the patient an effective amount of peptide comprising an amino acid sequence of up to 7 amino acids, and this peptide comprises the amino acid sequence X1X2X3P (SEQ ID NO: 56), wherein: X1 is R; X2 is I or V, where X2 can be N-methylated; X3 is I or V, where X3 can be N-methylated; P is proline; wherein SEQ ID NO: 56 if the first four amino acids at the N-terminus of the peptide, or a pharmaceutical salt, ester or amide thereof and a pharmaceuticaily-acceptable carrier, diluent, or excipient; carrier, diluent or excipient; or a peptide comprising the amino acid sequence selected from the group consisting SEQ ID NO: 5, 7, 10, 14, 17, 18, 22, 23, 24, 27, 28, 31, 34, 35, 63, 64, 66–69, 72, 76, 77, 90 and 92, or a pharmaceutical salt, ester or amide thereof and a pharmaceuticaily-acceptable carrier, diluent or excipient. Preclinical data obtained in models of chemotherapy-induced mucositis, radiation-induced mucositis, neutropenic infection and colitis, indicate oral mucositis is a promising indication for Innate Defense Regulator (IDR) peptides.
EFFECT: preclinical efficacy results obtained with IDRs in mouse and hamster models of mucositis, indicate that dosing every third day should be able to cover the mucositis "window" with seven to fourteen doses, depending on the duration of chemotherapy or radiation exposure; IDRs have also shown efficacy in mouse models of chemotherapy-induced oral and gastrointestinal mucositis, consistent with the response of the innate immune response to chemotherapy and / or radiation damage; IDRs are also effective at reducing bacterial burden and improve survival in the presence or absence of antibiotic treatment in various murine infection models.
8 cl, 19 dwg, 2 tbl, 1 ex
