Hormones as biotech-drugs: Human insulin and insulin analogues

Biotech-drugs or biopharmaceuticals are proteins or nucleic acids, which have been produced by living organisms as a result of biotechnology. Three decades after the beginning steps, they make a third part of all new drugs appearing each year at the world market. The era of animal source insulins has passed away and human recombinant DNA insulin and insulin analogues, as biopharmaceutics of the first and second generations, respectively, are the cornerstone of the diabetes mellitus current therapy. All insulin preparations are divided into three groups: 1) short - and rapid-acting insulins; 2) intermediate-acting insulins and 3) long-acting insulins. Short-acting human insulins and rapid-acting analogous insulin lispro, aspart and glulisine are available in form of solution for injections. In order to achieve the intermediate duration of action, human insulin is co-crystallized with protamine (insulin isophane suspensions) or human insulins and rapid-acting analogues are prepared as mixtures of isophane insulin suspension and monomer soluble form in fixed-ratios (75/25, 70/30, 50/50). The currently available long-acting insulins are analogues insulin glargine and insulin detemir, whereas use of amorphous and crystalline insulin zinc suspensions (lente and ultralente insulins) for prolonged action is now very rare, because of insufficiently favorable pharmacokinetics. Similarly, inhalation administration of insulin, although introduced into clinical practice, did not show the expected benefits in comparison to the conventional parenteral use.