Methods of treating eye disease with tobramycin-related compositions

A method of treating an infection caused by an infective agent in a mammalian eye comprising administering to the eye an ophthalmologically suitable pharmaceutical formulation, which formulation comprises a complexed compound, the complexed compound comprising:

• (a) an effective amount of an antibacterial active pharmaceutical ingredient comprising a compound having a structure identified as Formula I below:
• wherein (1) R1 is —CH—NH2 (i.e., Me-NH2) or an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkylalkyl, an optionally substituted heterocyclyl, an optionally substituted heterocyclylalkyl, an optionally substituted heteroaryl, or an optionally substituted heteroarylalkyl;
• (2) R4, R6, R8, and R9 are —NH2 or an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkylalkyl, an optionally substituted heterocyclyl, an optionally substituted heterocyclylalkyl, an optionally substituted heteroaryl, or an optionally substituted heteroarylalkyl;
• (3) R2 is -Me-OH or an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkylalkyl, an optionally substituted heterocyclyl, an optionally substituted heterocyclylalkyl, an optionally substituted heteroaryl, or an optionally substituted heteroarylalkyl;
• and (4) R3, R5, R7 and R10 are —OH or an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkylalkyl, an optionally substituted heterocyclyl, an optionally substituted heterocyclylalkyl, an optionally substituted heteroaryl, or an optionally substituted heteroarylalkyl, and
• (b) histidine which forms a complex with the antibacterial active pharmaceutical ingredient, and,
• wherein the histidine detectably increases the uptake of the antibacterial active pharmaceutical ingredient by corneal cells, the retention of the antibacterial active pharmaceutical ingredient by corneal cells, or both, as compared to the noncomplexed (free) antibacterial active pharmaceutical ingredient and wherein the antibacterial active pharmaceutical ingredient and the histidine are not covalently bound to one another.