@article{GastSchuelerWolffetal.2017,
  author    = {Gast, Klaus and Sch{\"u}ler, Anja and Wolff, Martin and Thalhammer, Anja and Berchtold, Harald and Nagel, Norbert and Lenherr, Gudrun and Hauck, Gerrit and Seckler, Robert},
  title     = {Rapid-acting and human insulins},
  series = {Pharmaceutical research},
  volume    = {34},
  journal   = {Pharmaceutical research},
  number    = {795},
  publisher = {Springer},
  address   = {New York},
  issn      = {0724-8741},
  doi       = {10.1007/s11095-017-2233-0},
  pages     = {2270 -- 2286},
  year      = {2017},
  abstract  = {Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions. Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism. Glulisine forms compact hexamers in formulation even in the absence of Zn2+. Upon severe dilution, these rapidly dissociate into monomers in less than 10 s. In contrast, in formulations of lispro and aspart, the presence of Zn2+ and phenolic compounds is essential for formation of compact R6 hexamers. These slowly dissociate in times ranging from seconds to one hour depending on the concentration of phenolic additives. The disadvantage of the long dissociation times of lispro and aspart can be diminished by a rapid depletion of the concentration of phenolic additives independent of the insulin dilution. This is especially important in conditions similar to those after subcutaneous injection, where only minor dilution of the insulins occurs. Knowledge of the diverging dissociation mechanisms of lispro and aspart compared to glulisine will be helpful for optimizing formulation conditions of rapid-acting insulins.},
  language  = {en}
}
@misc{GastSchuelerWolffetal.2017,
  author    = {Gast, Klaus and Sch{\"u}ler, Anja and Wolff, Martin and Thalhammer, Anja and Berchtold, Harald and Nagel, Norbert and Lenherr, Gudrun and Hauck, Gerrit and Seckler, Robert},
  title     = {Rapid-acting and human insulins},
  series = {Postprints der Universit{\"a}t Potsdam Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam Mathematisch-Naturwissenschaftliche Reihe},
  number    = {795},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43157},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431572},
  pages     = {2270 -- 2286},
  year      = {2017},
  abstract  = {Purpose: Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions. Methods: Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism. Results: Glulisine forms compact hexamers in formulation even in the absence of Zn2+. Upon severe dilution, these rapidly dissociate into monomers in less than 10 s. In contrast, in formulations of lispro and aspart, the presence of Zn2+ and phenolic compounds is essential for formation of compact R6 hexamers. These slowly dissociate in times ranging from seconds to one hour depending on the concentration of phenolic additives. The disadvantage of the long dissociation times of lispro and aspart can be diminished by a rapid depletion of the concentration of phenolic additives independent of the insulin dilution. This is especially important in conditions similar to those after subcutaneous injection, where only minor dilution of the insulins occurs. Conclusion: Knowledge of the diverging dissociation mechanisms of lispro and aspart compared to glulisine will be helpful for optimizing formulation conditions of rapid-acting insulins.},
  language  = {en}
}