A pilot study confirmed the feasibility and safety of neuroprotectant RK-4 intracalvariosseous(ICO) injection in patients with malignant middle cerebral artery infarction (mMCAI), showing a trend in improving 90-day functional scores compared to conventional treatment. The aim of this trial is to investigate the feasibility and safety of neuroprotective agent RK-4 injection using intracalvariosseous injection device in patients with acute large hemispheric infarction (LHI) who has contraindications of reperfusion therapy or have got poor reperfusion therapy outcomes.