A recently published patent application of Cell and Molecular Tissue Engineering LLC (WO2017180708) discloses a method of lowering the concentrations of preservatives and fibrils in a liquid insulin composition, replacing phenol or m-cresol with cyclodextrins.
Despite their demonstrated clinical benefits, currently insulin infusion sets are only approved for in vivo usage for only 3 days. Even with this limited approved lifespan, a substantial portion of sets fail to meet this recommended lifespan during practical use. Nevertheless Continuous Subcutaneous Insulin Infusion (CSII) therapy represents the most advanced form of insulin delivery technology currently available and administers more precise amounts of insulin in a programmable format as compared to traditional injection methods, which provides increased flexibility and enhanced quality of life for the user. To achieve effective glucostasis using an artificial pancreas, a combination of a highly accurate continuous glucose monitor (CGM) and reliable continuous subcutaneous insulin infusion (CSII) is required. Although CGM performance and lifespan has significantly improved over the last decade, CSII with a current lifespan of 3 days or less has not. As such the current approved usage lifespans for commercial CGM and CSII devices is highly mismatched with in vivo durations of 10+ days vs. 3d, respectively.
The high occurance of inflammation and scarring at insulin infusion sites in patients with diabetes is well known (i.e. 25-42 %) particularly in pediatric populations whereas infection at insulin infusion sites is also frequently seen.
The inventors postulate that current insulin excipients (phenol/m-cresol) are tissue toxic, therefore, it is important to consider alternatives and it was highlighted that cyclodextrins have been shown to be more effective than current phenol based excipients in stabilizing insulin in vitro. The feasibility of a method was also discussed for removing anti-microbial agents from a liquid insulin composition comprising incorporating an ion exchange resin and cyclodextrin polymers and/or beads into the infusion set. A liquid insulin formulation comprising cyclodextrins and/or cyclodextrin polymers as anti-microbial agents is also described.