Insulin Preparations with Prolonged Effect

Schlichtkrull, J.; Pingel, M.; Hedïng, Lise G.; Brange, Jens; Jørgensen, Karsten Juhl

doi:10.1007/978-3-642-66002-3_22

Cited by 9 publications

(3 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Insulin is often administered through daily injections, which can become an inconvenience to the patient, and can be dangerous if administered incorrectly. The frequency of these injections can be reduced considerably by the use of suspensions of crystallites (Schlichtkrull, 1965;Schlichtkrull et al, 1972). Sustained release of the insulin into the blood stream is achieved if the crystallites have a narrow size distribution (Long et al, 1996;Peseta et al, 1989;Reichert et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Thermodynamics of the Hydrophobicity in Crystallization of Insulin

Bergeron

Filobelo

Galkin

et al. 2003

Biophysical Journal

View full text Add to dashboard Cite

For insight into the solvent structure around protein molecules and its role in phase transformations, we investigate the thermodynamics of crystallization of the rhombohedral form of porcine insulin crystals. We determine the temperature dependence of the solubility at varying concentration of the co-solvent acetone, Cac=0%, 5%, 10%, 15%, and 20%, and find that, as a rule, the solubility of insulin increases as temperature increases. The enthalpy of crystallization, undergoes a stepwise shift from approximately -20 kJ mol(-1) at Cac=0%, 5%, and 10% to approximately -55 kJ mol(-1) at Cac=15% and 20%. The entropy change upon crystallization is approximately 35 J mol(-1) K(-1) for the first three acetone concentrations, and drops to approximately -110 J mol(-1) K(-1) at Cac=15% and 20%. DeltaS degrees cryst>0 indicates release of solvent, mostly water, molecules structured around the hydrophobic patches on the insulin molecules' surface in the solution. As Cac increases to 15% and above, unstructured acetone molecules apparently displace the waters and their contribution to DeltaS degrees cryst is minimal. This shifts DeltaS degrees cryst to a negative value close to the value expected for tying up of one insulin molecule from the solution. The accompanying increase in DeltaH degrees cryst suggests that the water structured around the hydrophobic surface moieties has a minimal enthalpy effect, likely due to the small size of these moieties. These findings provide values of the parameters needed to better control insulin crystallization, elucidate the role of organic additives in the crystallization of proteins, and help us to understand the thermodynamics of the hydrophobicity of protein molecules and other large molecules.

show abstract

Section: Introductionmentioning

confidence: 99%

Thermodynamics of the Hydrophobicity in Crystallization of Insulin

Bergeron

Filobelo

Galkin

et al. 2003

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…This led to the development of insulin preparations with prolonged effect, described as ‘intermediate-’ and ‘long-acting’ insulin formulations (Fig. 1 ) [ 53 ]. The pharmacokinetics of currently available insulin preparations are summarized in Table 1 .…”

Section: Development Of Synthetic Human Insulinmentioning

confidence: 99%

The Evolution of Insulin Glargine and its Continuing Contribution to Diabetes Care

Hilgenfeld

Seipke

Berchtold

et al. 2014

Drugs

View full text Add to dashboard Cite

The epoch-making discovery of insulin heralded a new dawn in the management of diabetes. However, the earliest, unmodified soluble insulin preparations were limited by their short duration of action, necessitating multiple daily injections. Initial attempts to protract the duration of action of insulin involved the use of various additives, including vasoconstrictor substances, which met with limited success. The subsequent elucidation of the chemical and three-dimensional structure of insulin and its chemical synthesis and biosynthesis allowed modification of the insulin molecule itself, resulting in insulin analogs that are designed to mimic normal endogenous insulin secretion during both fasting and prandial conditions. Insulin glargine was the first once-daily, long-acting insulin analog to be introduced into clinical practice more than 10 years ago and is specifically designed to provide basal insulin requirements. It has a prolonged duration of action and no distinct insulin peak, making it suitable for once-daily administration and reducing the risk of nocturnal hypoglycemia that is seen with intermediate-acting insulins. Insulin glargine can be used in combination with prandial insulin preparations and non-insulin anti-diabetic agents according to individual requirements.Electronic supplementary materialThe online version of this article (doi:10.1007/s40265-014-0226-4) contains supplementary material, which is available to authorized users.

show abstract

“…The principle was that after injecting an acid, unbuffered solution of insulin, and the basic compound, a complex forms that is sparingly soluble at neutral reaction. One reason for the abandonment of these preparations was that their duration of action was too short (see Schlichtkrull et al, 1975).…”

Section: Rationale Of Design and Mode Of Action Of Prolonged-acting mentioning

confidence: 99%