Effect of succinylated gelatin conjugated soybean trypsin inhibitor (SBTI.) against hypotension and septic shock

Chikako Kinoshita, Takaaki Akaike, Hiroshi Maeda, Chikako Kinoshita, Young Hee Shin

Research output: Contribution to journalArticlepeer-review

Abstract

Plasma kallikrein is a protease that releases bradykinin from high-molecular-weight kininogen in plasma. Bradykinin is thought to be involved in the pathogenesis of septic shock. Soybean trypsin inhibitor (SBTI, Kunitz type) is a potent inhibitor against plasma kallikrein. However, half-life (T1/2) of SBTI in the circulating blood is too short after iv injection because of its small molecular size (Mr 21, 000), and hence the therapeutic application is limited. To enhance therapeutic value of SBTI, we conjugated SBTI with succinylated gelatin (suc-gel-SBTI), which exhibits about 6 times longer plasma T1/2 and about 4 times larger AUC. We report here improved therapeutic effect against septic shock in rats and guinea pigs by treatment with suc-gel-SBTI. The conjugate prevented hypotension together with production of bradykinin in blood induced by Pseudomonas elastase and lipopolysaccharide from E. coli much more effectively and for a longer time period than that with the native SBTI. In conclusion, the therapeutic efficacy of SBTI is much improved by its polymer conjugation due to the better pharmacokinetics than the native SBTI.

Original languageEnglish
Pages (from-to)335-338
Number of pages4
JournalDrug Delivery System
Volume12
Issue number5
DOIs
Publication statusPublished - 1997
Externally publishedYes

Keywords

  • Pseudomonas elastase
  • hypotension
  • lipopolysaccharide
  • septic shock
  • soybean trypsin inhibitor

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Effect of succinylated gelatin conjugated soybean trypsin inhibitor (SBTI.) against hypotension and septic shock'. Together they form a unique fingerprint.

Cite this