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US 2022/0054518 A1Published application
Tobramycin compound conjugate formulations
AssigneeSomerset Therapuetics, LLC
InventorsMandar V. Shah, Veerappan Subramanian, Ilango Subramanian
Life of this patent
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Abstract
Disclosed herein are compositions comprising tobramycin or a tobramycin derivative that exhibit improvements in permeation of corneal cells, retention in corneal cells, or both. Such compositions can comprise tobramycin or tobramycin derivative(s) complexed to an agent which facilitates improved permeation of corneal cells, retention in corneal cells, or both. The invention also relates to a process of preparing such compositions.
Claims32
A pharmaceutically acceptable composition for treating an infection caused by an infective agent 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);
- (b) a lipophilic and amphoteric complexing agent, wherein the lipophilic and amphoteric 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;
- (c) means for adjusting the tonicity of the composition;
- and
- (d) means for adjusting the pH of the composition.
6 more elements
A pharmaceutically acceptable composition for treating an infection caused by an infective agent 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);
- (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;
- (c) means for adjusting the tonicity of the composition;
- and
- (d) means for adjusting the pH of the composition.
6 more elements
Dependencies are inferred from the claim text.