Tobramycin compound-copolymer conjugates and derivative compositions

A pharmaceutical composition 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 copolymer complexing agent forms a stable complex with the active pharmaceutical ingredient and the complexing agent detectably promotes the uptake of the active pharmaceutical ingredient by corneal cells, the retention of the active pharmaceutical ingredient by corneal cells, or both the uptake and retention of the active pharmaceutical ingredient by corneal cells, as compared to the free (noncomplexed) compound.