GB2510407A — Aqueous suspensions of kallikrein inhibitors for parenteral administration

USPTO Abstract

An aqueous suspension for parenteral administration comprises a protease inhibitor, preferably a kallikrein inhibitor. Preferably the kallikrein inhibitor is a benzylamine derivative of formula (I) wherein R1 is selected from H, alkyl, -COalkyl, -COaryl, -COheteroaryl, -CO2heteroaryl, -CO2alkyl, -(CH2)aOH, -(CH2)bCOOR10, -(CH2)cCONH2, -SO2alkyl and SO2aryl; R2 is selected from H and alkyl; R3 is selected from H, alkyl, -(CH2)daryl, -(CH2)cheretoaryl, -(CH2)fcycloalkyl, -(CH2)gheterocycloalkyl, -CH(cycloalkyl)2 and CH(heterocycloalkyl)2; R4 and R6 are independently selected from H and alkyl; R5 is selected from H, alkyl, alkoxy and OH; or R4 and R5 together with the atoms to which they are attached, may join to form a 5- or 6-membered azacycloalkyl; R7 and R8 are independently selected from H, alkyl, alkoxy, CN and halo; R9 is aryl or heteroaryl; R10 is H or alkyl; a, b, c, d, e, f and g are independently 1, 2 or 3; and *1 and *2 denote chiral centres. Preferably the composition comprises N-[(R)-1-[(S)-1-(4-aminomethyl-benzylcarbamoyl)-2-phenyl-ethylcarbamoyl]-2-(4-ethoxy-phenyl)ethyl]-benzamide. Preferably the parenteral administration is intravenous or intravitreous for the treatment of retinal vascular permeability associated with diabetic retinopathy or diabetic macular oedema.