The present invention relates to polyethylene glycol (PEG) modified protein drugs, and a PEGylated tissue kallikrein, a preparation method and use thereof are disclosed. The tissue kallikrein has a sequence as shown in SEQ ID No. 1 or SEQ ID No. 2, and the tissue kallikrein may be natural or recombinant. The PEG has a molecular weight of 20 to 40 kDa, and is conjugated to the N-terminal primary amino of the tissue kallikrein. In addition to the advantages of significantly extended half-life, significantly reduced immunogenicity and stable and uniform structure, the biological activity of the PEGylated KLK1 provided in the present invention is improved to a higher extent, which is more significant in the treatment of cerebral apoplexy and diabetic nephropathy in particular.

Provided are dosage forms of one or more tissue kallikrein-1 (KLK1) polypeptides which have a total KLK1 polypeptide dosage of about 0.1 g/kg to about 10.0 g/kg, including subcutaneous and intravenous dosage forms. Also provided are related devices and methods of use thereof, for example, for treating ischemic and hemorrhagic conditions.

Provided are methods and compositions for using tissue kallikrein-1 (KLK1) to treat or prevent pregnancy disorders such as fetal growth restriction (FGR) and preeclampsia.

Provided are pharmaceutical compositions, kits, and methods for the clinical use of tissue kallikrein-1 (KLK1) polypeptides in polyolefin-containing intravenous (IV) systems, including polyolefin IV bags.

Provided are dosage forms of one or more tissue kallikrein-1 (KLK1) polypeptides which have a total KLK1 polypeptide dosage of about 0.1 g/kg to about 10.0 g/kg, including subcutaneous and intravenous dosage forms. Also provided are related devices and methods of use thereof, for example, for treating ischemic and hemorrhagic conditions.