Prolonged insulin zinc

Insulin-zinc suspension suspension of insulin, generated by crystallization with zinc, formulated in this way in order to prolong its duration of action... 

K. Hallas-Moller, K. Petersen, and J. Schlichtkrull. Crystalline and amorphous insulin-zinc compounds with prolonged action. Science 116 394—398, 1952. 

Intcrmcdiale- and limg-acliiig insulins. These have a duration of action between 16 and 33 hours. Scmilentc is a suspension of amorphous insulin zinc. i.enie is a mixture of amorphous insulin zinc (.30%) and insulin zinc crystals (TO ). the latter prolonging the dumtion of this preparation. 

It has been shown that, if zinc is present, the hypoglycemic action of protamine-insulin or spermine-insulin compounds (which are more effective than pure insulin) is greatly prolonged. Insulin preparations contain zinc as a micro-constituent. 

Insulin preparations that are commercially available differ in their relative onset of action, maximal activity, and duration of action. Conjugation of the insulin molecule with either zinc or protamine, or both, will convert the normally rapidly absorbed parenterally administered insulin to a preparation with a more prolonged duration of action. The various formulations of insulin are usually classified as short acting (0.5 to 14 h), intermediate acting (1 to 28 h), and long acting (4 to 36 h). The duration of action can vary, however, depending on injection volume, injection site, and blood flow at the site of administration. 

Lente insulin is a mixture of 30% semilente (an amorphous precipitate of insulin with zinc ions in acetate buffer that has a relatively rapid onset of action) with 70% ultralente insulin (a poorly soluble crystal of zinc insulin that has a delayed onset and prolonged duration of action). These two components provide a combination of relatively rapid absorption with sustained long action, making lente insulin a useful therapeutic agent. As with regular insulin, the time of onset, time to peak, and duration of action are dose-dependent. 

An important consideration to the pharmacologist is the useful lifetime of a drug in the body. Protein hormones have been modified chemically to lower their rate of removal from the bloodstream, prolong the effect of the injected hormone, and thus reduce the required frequency of administration. The modification of animal insulin by coupling to protamine-zinc is probably the best-known example. Others are the studies by Marshall on the possibility of lengthening the lifetime in the bloodstream of injected proteins by supplying them as dextran conjugates... 

Medication can be delivered via the eye in the form of eyedrops or in an ocular device. Sodium or zinc insulin was incorporated into a Gelfoam sponge-based device. An in vitro dissolution test indicated that the release of insulin from the device was proportional to the flow rate of the dissolution medium. An in vivo dissolution experiment provided support for the hypothesis that there was a direct relationship between the prolonged pharmacological response to insulin and its release from the device. The ocular device with or without the aid of an enhancer was placed in the eye of rabbits as an ocular insert and produced a uniform blood glucose-lowering effect of 60% over 8h. The blood glucose... 

Most diabetics in the UK are now treated with human insulin. Insulin is administered by subcutaneous injection aiul its rate of (thxi/fption ciin be prolonged by mcri ci.iing ilw /Mriicle size (i.e. crystals slowier ihan amorphous) or by complexinsi the insulin with zinc or protamine. 

Insulin forms a salt with protamines that is less soluble and more prolonged in action than the free hormone, and this therapeutic effect may be extended by traces of zinc (p. 23). 

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