Efficient tobramycin compound conjugate compositions

A pharmaceutically acceptable composition for treating an infection caused by a bacteria in a mammalian eye comprising an effective amount of an ophthalmologically suitable complex, the complex comprising:

• (a) an antimicrobial active pharmaceutical ingredient comprising a structure according to the formula
• 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 (Formula I);
• and
• (b) an ophthalmologically safe copolymer complexing agent, wherein the ophthalmologically safe copolymer complexing agent forms a stable complex with the active pharmaceutical ingredient and the complexing agent detectably promotes the uptake of the composition by corneal cells, the retention of the complex by corneal cells, or both, as compared to the free (noncomplexed) compound,
• wherein administration of the composition at a daily dosing frequency of less than three times per day to an infected eye of each mammal in a population of mammals suffering from a bacterial infection of the eye, each dose comprising an amount of the active pharmaceutical ingredient, results in a therapeutic effect that is significantly similar to or improved with respect to administering a second composition consisting of tobramycin at 0.3% w/v, benzalkonium chloride at 0.01% w/v, boric acid, sodium sulfate, sodium chloride, tyloxapol, sodium hydroxide and/or sulfuric acid, and purified water to an infected eye of each mammal in a similar population of mammals suffering from the bacterial infection of the eye at a daily dosing frequency of three or more times per day, each dose of the second composition comprising the amount of the active pharmaceutical ingredient.