Insulin formulations – a review

In the history of insulin therapy some milestones are present. In 1921, the young physician Frederick Banting (1881-1941) and the forth year medical student Charles Best (1899-1978), working in the laboratory of Prof. McLeod in the Toronto University, found the final link in a series of studies begun in 1916 by other researchers that guessed the pancreas secretetion of substance, already named “insulin”, capable to decrease blood glucose concentrations. The young researchers isolated this pancreas extract that “cured” hyperglycemia in diabetic dogs1-2 and in 1922 they successfully administered it for the first time to a 14-year-old diabetic patient, Leonard Thompson3. In 1923, the company Lilly began marketing animal insulin. In 1928, the hormone was identified to be a protein. Since the insulin of Banting and Best could not function for more than 6 h, much research went into finding ways of prolonging action. In 1936, Hagedorn noted that addition of a basic protein, such as protamine, to the insulin preparation, kept the hormone in suspension at the injection site, delaying absorption and prolonging its action4. In 1946, the first insulin “Isophane NPH” (Neutral Protamine Hagedorn), obtained combining insulin and protamine in stoichiometric quantities (hence the term isophane from the Greek equal and manifest) at neutral pH, was marketed5. In 1952, the first Lente insulin, retarded with zinc and without protamine, was produced in Denmark6. In 1955, Sanger determined the exact formula of bovine insulin7. The sixties saw the development of a radioimmunoassay for insulin8. In the seventies, production of mono-component insulins, obtained by ion exchange chromatography and of monopeak ones, separated by Sephadex G50 column, began. High performance chromatography made it possible to isolate an insulin 99% pure from proinsulin and other islet hormones9. European Review for Medical and Pharmacological Sciences