NPH insulin

Neutral Protamine Hagedorn was created in 1946 when Nordisk formulated "isophane" porcine insulin by adding Neutral Protamine Hagedorn or NPH.

This is a suspension of crystalline zinc insulin combined with the positively charged polypeptide, protamine. It has an intermediate duration of action, longer than that of regular insulin, but shorter than ultralente.

History
Hans Christian Hagedorn (1888-1971) and August Krogh (1874-1949) obtained the rights for insulin from Banting and Best in Toronto. In 1923 they formed Nordisk Insulinlaboratorium, and in 1926 with August Kongsted he obtained a Danish Royal Charters as a non-profit foundation.

In 1936 Hagedorn and B. Norman Jensen discovered that the effects of injected insulin could be prolonged by the addition of protamine obtained from the "milt" or semen of river trout. The insulin would be added to the protamine, but the solution would have to be brought to pH 7 for injection. Canada later produced ZPI insulin, a mixture of zinc, protamine and porcine insulin. This mixture only needed to be shaken before injection.

In 1946 Nordisk was able to form crystals of protamine and insulin and marketed it in 1950 as NPH insulin. NPH insulin has the advantage that it can be mixed with an insulin that has a faster onset to complement its longer lasting action.

Eventually all animal insulins were replaced by human recombinant insulin. Human insulin is also complexed with NPH.

Timeline

 * 1926 Nordisk receives Danish charter to produce insulin
 * 1936 Hagedorn discovers that adding protamine to insulin prolongs the effect of insulin
 * 1936 Canadians D.M. Scott and A.M. Fisher formulate zinc insulin mixture and license to Novo
 * 1946 Nordisk crystallizes a protamine and insulin mixture
 * 1950 Nordisk markets NPH insulin
 * 1953 Nordisk markets "Lente" zinc insulin mixtures