RAPID ACTING AND LONG ACTING INSULIN COMBINATION FORMULATIONS

摘要

? combined rapid ueting-long acting insulin formulation has been developed wherein the pll of the rapid acting insulin is adjusted so that the long acting giargine remains soluble when they are mixed together, tn the preferred embodiment, this injectable basal bolus insulin, is administered before breakfast, prm ides adequate bolus insulin levels to cover the meal, does not produce hypogly cemia alter tbc meal and provides, adequate basal insulin for 24 hours. Lunch and dinner can be covered by two bolus injections of a fast acting, or a rapid acting or a v ery rapid acting insulin. As a result, a patieni using intensive insulin iherap) should only inject three, rather than four, times a day. Fxperiments have been performed to demonstrate the importance of the addition of specific acids to hexameric insulin to enhance speed and amount of absorption and preserve bioactivity follow ing dissociation into the mopomerie form by addition of a chelator such as KDT?. As.shown by the examples, the preferred acids are aspartie. malcic, succinic, glutamic and citric acid. l hese are added in addition to a chelator, preferably ethylenedianimetctraacctic acid (IiDTA). i he results show that the citric acid formulation was more effective ut dropping Ih e blood glucose rapidly than the identical rapid acting formulation prepared with I ICI in swine. Charge masking by the polyacid appears to be responsible for rapid insulin absorption, I7DTA ?/as not effective when used with adipic acid, oxalic acid or 1 ICI at hastening the absorption of insulin, These results confirm the results seen in clinical subjects and patients with diabetes treated w ith the rapid acÍna insulin in combination with citric acid and FJDT?.