A neuroprotective drug in new bismuth formulation

Project of formulation development from mechanism discovery


  • Bismuth’s effects on the CNS are the first findings
  • Demonstration has done by administration of Bismuth Subnitrate/Subcitrate on human brain endothelial cell and on traumatic brain injury model
  • Confirmed effectiveness of blood-brain spinal cord barrier (BBSCB) protection and spinal cord injury repair
  • Possible to search for new compounds using our own screening system

Background & Technology

Bismuth has long been known to have antibacterial activity and has been used to treat infectious enteritis, peptic ulcers, and infections caused by Helicobacter pylori. Bismuth hypocitrate (CBS) and bismuth salicylate (BSS) have strong antibacterial activity, while bismuth nitrate and bismuth carbonate are said to have weak antibacterial activity.

Principal investigator noticed that secondary damage to the central nervous system, such as the brain and spinal cord, can be reduced by preventing disruption of the BBSCB, and while conducting exploratory research on BBSCB protective agents using an original screening system, they found that Bismuth has a BBSCB protective effect.

In this study, we elucidated the mechanism of BBSCB protection, and found that appropriate Bismuth formulation has a protective effect on BBSCB by protecting vascular endothelial cells. The effects of other known and novel compounds have also been found.


■Behavioral performance evaluation

Treadmill walking speed analysis (DigiGait) in a spinal cord injury model showed that the Bismuth group had a superior effect on improving walking function.

■Histological evaluation

Bismuth and papaverine predominantly suppressed IgG leakage in a brain transection model.

Patent status



Hokkaido University

Principal Investigator

Hokkaido University Faculty of Medicine

Specially Appointed Associate Professor Ken Kadoya


We are looking for partner companies that are interested in license or collaboration research in the following topics.

  1. Licensing, co-development and commercialization of discovered bismuth compounds
  2. Collaboration research for new drug screening or drug efficacy evaluation in CNS disorders related to BBSCB dysfunction

Product No. ON-03567b



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