ULTRA-CONCENTRATED RAPID-ACTING INSULIN ANALOGUE FORMULATIONS

摘要

A pharmaceutical formulation comprises insulin having a variant insulin B-chain polypeptide containing an ortho-monofluoro-Phenylalanine substitution at position B24 in combination with a substitution of an amino acid containing an acidic side chain at position B10, allowing the insulin to be present at a concentration of between 0.6 mM and 3.0 mM. The formulation may optionally be devoid of zinc. Amino-acid substitutions at one or more of positions B3, B28, and B29 may additionally be present. The variant B-chain polypeptide may be a portion of a proinsulin analogue or single-chain insulin analogue. The insulin analogue may be an analogue of a mammalian insulin, such as human insulin. A method of lowering the blood sugar of a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to the patient.

主权项

1. A pharmaceutical formulation comprising insulin having a variant insulin B-chain polypeptide containing an ortho-monofluoro-Phenylalanine substitution at position B24 in relation to the sequence of human insulin, in combination with a substitution of an amino acid containing an acidic side chain at position B10 in relation to the sequence of human insulin selected from Aspartic Acid and Glutamic Acid, wherein the insulin is present at a concentration of between 0.6 mM and 3.0 mM.