Abstract: A composition of a long-acting enzyme comprises the enzyme in a formulation comprising a buffer and an additive selected from the group consisting of tranexamic acid, ?-aminocaproic acid, and analogs of L-lysine other than tranexamic acid and ?-aminocaproic acid, combinations thereof, and mixtures thereof. The composition can further comprise another additive selected from the group consisting of L-lysine, L-arginine, L-ornithine (or its pharmaceutically acceptable salts; e.g., L-ornithine hydrochloride), ?-aminobutyric acid, 5-aminovaleric acid, 7-aminoheptanoic acid, glycylglycine, triglycine, N-?-acetyl-L-arginine, betaine, sarcosine, gelatin, HSA, streptokinase, tPA, uPA, non-ionic surfactants, glycerin, D-sorbitol, combinations thereof, and mixtures thereof. A method for prolonging the activity of an autodegradable enzyme comprises storing the enzyme after manufacture at a low pH, and reconstituting the acidified enzyme before use with a solution containing at least one of such additives.